Nanobiotix 2019 Q4 and Annual Revenues – BioSpace

NANOBIOTIX (Paris:NANO) (Euronext : NANO ISIN : FR0011341205 the Company), a late clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, today announced its unaudited annual revenues for Q4 and the unaudited revenues for the year ended December 31, 2019.

2019 Revenues

In K

Twelve months Ended

December 31st, 2019

Twelve months Ended

December 31st, 2018




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Revenue for Q4 2019

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Q4 2019

Q3 2019

Q2 2019

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Activity and results

Nanobiotixs revenue for the fourth quarter amounted to approximatively 20k.

Most of the revenues generated by the Company during this period result from the recharge of costs related to our license and collaboration agreement with PharmaEngine.

Overall, Nanobiotixs annual revenue in 2019 amounted to approximatively 68k.

The amount of cash and cash equivalent as of December 31st, 2019 amounted to 35 094k. This amount does not include the research tax credit related to 2018, normally expected in Q4 which was received in February 2020.

In November 2019, Nanobiotix announced promising results from a pre-clinical immuno-oncology study of NBTXR3 at the 2019 Annual Meeting of the Society for Immunotherapy of Cancer (SITC). In the study, conducted at The University of Texas MD Anderson Cancer Center, researchers studied NBTXR3 activated by radiation therapy in combination with anti-PD-1 treatment in immunocompetent mice. Combination treatment that included NBTXR3 and anti-PD-1 increased local control of the irradiated tumor, generated a marked abscopal effect, decreased the number of spontaneous lung metastases, and significantly increased survival when compared to other treatments in the study, including anti-PD-1 combined with radiation therapy alone. The results indicated that the combination treatment has the potential to achieve an equivalent abscopal effect at a lower dose of radiation.

The study also included an in vivo RadScopal model in which a second tumor received a low dose of radiation while the first tumor received a full dose. In this model, researchers evaluated NBTXR3 activated by radiation therapy combined with anti-PD-1 and anti-CTLA-4 treatment. In the study, combination treatment triggered better local control, along with significant increases in abscopal effect and survival, when compared to all other tested combinations. Several complete responses were observed in the second tumor of the group that received the NBTXR3 combination, while none were observed in the other groups. Nanobiotix believes these results could pave the way for the use of NBTXR3 to improve treatment outcomes for immunooncology patients, including checkpoint inhibitor non-responders.

On December 16th 2019, Nanobiotix received the French 2019 Prix Galien award for Most Innovative MedTech. This award recognizes outstanding biomedical and medical technology product achievements that improve the human condition.

2020 Financial agenda

Nanobiotix plans to announce its financial and operating results as follows:

About NANOBIOTIX: http://www.nanobiotix.com

Incorporated in 2003, Nanobiotix is a leading, clinical-stage nanomedicine company pioneering new approaches to significantly change patient outcomes by bringing nanophysics to the heart of the cell.

The Nanobiotix philosophy is rooted in designing pioneering, physical-based approaches to bring highly effective and generalized solutions to address unmet medical needs and challenges.

Nanobiotixs first-in-class, proprietary lead technology, NBTXR3, aims to expand radiotherapy benefits for millions of cancer patients. Nanobiotixs Immuno-Oncology program has the potential to bring a new dimension to cancer immunotherapies.

Nanobiotix is listed on the regulated market of Euronext in Paris (Euronext: NANO / ISIN: FR0011341205; Bloomberg: NANO: FP). The Companys headquarters are in Paris, France with a U.S. affiliate in Cambridge, MA, and European affiliates in Spain and Germany. The Company also possesses an affiliate, Curadigm, located in Paris, France and Cambridge, MA in the U.S.


This press release contains certain forward-looking statements concerning Nanobiotix and its business, including its prospects and product candidate development. Such forward-looking statements are based on assumptions that Nanobiotix considers to be reasonable. However, there can be no assurance that the estimates contained in such forward-looking statements will be verified, which estimates are subject to numerous risks including the risks set forth in the reference document of Nanobiotix registered with the French Financial Markets Authority (Autorit des Marchs Financiers) under number R.19-018 on April 30, 2019 (a copy of which is available on http://www.nanobiotix.com) and to the development of economic conditions, financial markets and the markets in which Nanobiotix operates. The forward-looking statements contained in this press release are also subject to risks not yet known to Nanobiotix or not currently considered material by Nanobiotix. The occurrence of all or part of such risks could cause actual results, financial conditions, performance or achievements of Nanobiotix to be materially different from such forward-looking statements.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200228005446/en/

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Nanobiotix 2019 Q4 and Annual Revenues - BioSpace

Dying Of Flu, College Student Used Cellphone To Call 911. He Died When Police Couldn’t Find His Location. – Kaiser Health News

Location technology is "kind of a coin toss." The FCC has given carriers until 2021 to make sure transmission locations are within 50 yards 80% of the time. Public health news is on USPS work-related injuries, a biomedical research contest, suicide-crisis centers, prostate cancer, a lucky fall, perinatal stroke, birthing plans, disparity in birth outcomes, medical clowns, chocolate's appeal, friendship and health, childhood prosthetics, and healthy beverages, as well.

The Washington Post:College Student Yeming Shen Died Of Flu In Troy, N.Y., After 911 Couldnt Track His Location.Yeming Shen called 911 on Feb. 10. He was alone in his Troy, N.Y., apartment, dying of the flu. But the garbled call was unintelligible to the operators, and police couldnt pinpoint the phones location. For 45 minutes after Shen called 911, five police officers, three firefighters and a police dog searched in vain for the student. All they had was a general area encompassing two apartment buildings. They eventually gave up without finding Shen. Six hours later, the Rensselaer Polytechnic Institute students roommate discovered his body, the Times Union first reported. (Kornfield, 2/22)

ProPublica:The Postal Service Fired Thousands Of Workers For Getting Injured While Delivering And Processing Your MailOne night in 2009, Madelaine Sattlefield lifted an 80-pound tray of letters carefully sorted by Missouri ZIP code. She had done this task thousands of times in nine years, but on this night, her arm seared with pain and went limp by her side. The tray crashed and sent envelopes cascading around her. She could barely move but immediately worried about what an injury might mean for her job. Anxiety had kicked in. I was like, what are they going to say, what are they going to do? Sattlefield said. (Jameel, 2/24)

Stat:Here Are The Contenders For STAT Madness 2020ADNA microscope. A gene therapy for bubble boy disease. The restoration of cellular activity in pig brains four hours after death. Nano-robots that might clean teeth better than flossing. These are just some of the 64 important discoveries and inventions included in this years STAT Madness, a bracket-style competition to honor the best biomedical research published in 2019. (2/24)

Stateline:As Suicide Rates Climb, Crisis Centers ExpandNationwide, most people picked up by police for a misdemeanor while in a psychiatric crisis are taken directly to a hospital emergency department, where they typically are held for hours or days, often involuntarily confined, according to emergency department surveys. Many are charged and held in jail with no mental health professional to talk to and no access to psychiatric medicines. The same goes for people with drug addiction. In the past five years, thats become a rarity in Arizona. As in other parts of the country, Arizonas crisis centers are open 24 hours, seven days a week, and everyone is accepted, regardless of whether they have health insurance. (Vestal, 2/24)

The New York Times:Debating The Value Of PSA Prostate ScreeningWeve long been schooled on the lifesaving value of early detection of a potentially deadly cancer. So when a simple blood test was introduced in 1994 that could detect the possible presence of prostate cancer, the second leading cause of cancer deaths among American men, its not hard to understand why it quickly became hugely popular. (Brody, 2/24)

The Washington Post:Synovial Chondromatosis: A Hard Fall Unmasked This Unusual And Painful ConditionIf she hadnt tripped over her neighbors dog, causing her to miss the step down into a sunken living room where she landed squarely on her left hip, Lynda Holland still might not know what was wrong. Holland scrambled to her feet, shaken and grateful she hadnt been injured: Her puffy down coat had cushioned her fall onto the hardwood floor. Then she realized the pain that had dominated her life for the previous six years had suddenly diminished. (Boodman, 2/22)

The Washington Post:Perinatal Stroke: Some Infants In Utero Lose Blood Supply To Their Brains, Causing Physical Or Cognitive Problems Later. New Therapies May Help.Nicole Dodds first noticed her son, Rowan, was having trouble using the right side of his body when he was about 6 months old. Babies typically use both hands to pick up toys and lift their chest off the floor at that age, but Rowan was mostly using his left arm and hand, keeping his right hand balled in a fist. That started a string of doctor visits. Around Rowans first birthday, doctors did an MRI and diagnosed his one-sided weakness as hemiplegia, probably caused by a stroke he sustained in utero. This surprised Dodds, since as far as she knew shed had a totally normal pregnancy and birth. (Witman, 2/22)

NBC News:She Wanted A 'Freebirth' With No Doctors. Online Groups Convinced Her It Would Be OK.For women who havent gone into labor by 42 weeks, just about every medical and birth professional recommends induction a jump-start to labor from medicines that ripen the cervix or contract the uterus. But Judith, an artist and freethinker who believes in all that hippy jazz, had a different kind of birth plan one that dismissed medical recommendations and relied on nature and intuition, that rejected a sterile hospital for a warm pool in her own home and that avoided doctors and midwives. Instead, Judith wanted to be with only her husband and her closest friend, a plan known as freebirth, or unassisted birth, by the tiny subculture of women who practice it. (Zadrozny, 2/21)

GMA:Stunning Photos Of Black Women Raises Awareness About Disparity In Birth OutcomesIt was about five years ago when Dallas-Fort Worth photographer Elaine Baca photographed her first birth. Until then, she had been primarily working weddings... According to the Centers for Disease Control and Prevention, the risk of pregnancy-related deaths for black women is 3 to 4 times higher than those of white women."It's important for people to see and understand that black women and babies who are dying in childbirth are not just statistics put out by the CDC," Baca told "GMA." (Brown, 2/24)

The Washington Post:Clowns Can Help Treatment In HospitalsMedicine is serious business. But for a growing number of patients, a trip to the hospital may include a laugh with a clown. Medical clowns health-care workers who dress up and act like clowns to help make medical procedures and hospital stays less stressful can be found around the world. The growing field relies on the age-old performance art of clowning to help lift the strain that can pervade the treatment of all-too-serious health concerns. (Blakemore, 2/22)

NBC News:Why Chocolate Is So Addicting And How To Tap Into The Health BenefitsThough chocolate is typically divided into three categories: dark, milk and white, the latter two really should just be called highly-processed interpretations of chocolate, because thats basically what they are. And its the processed sugars, salts and fats that make these varieties so tasty which is also what makes them so addictive. (Spector, 2/23)

CNN:Want To Lose More Weight? Intensive Therapy From Dietitians Can Help Older Adults, Study FindsOlder adults may have better success at losing weight if they do it with the help of intensive behavioral therapy from dietitians, a new study suggests. Intensive behavioral therapy for obesity, or IBTO, is a customized treatment that helps people change their eating and exercise behaviors through a series of one-on-one counseling sessions. (Rogers, 2/21)

NPR:How Good Friends Are Good For Your HealthLydia Denworth wants you to make more time for your friends. We don't fully appreciate our friendships, says the science writer and author of the new book Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond. If we did, we'd take cultivating those intimate bonds as seriously as working out or eating well. Because, she writes, a new field of science is revealing that social connections play a vital role in our health. (Renken, 2/22)

The Washington Post:Children Who Need Prosthetics Can Quickly Outgrow Them And Insurers Are Reluctant To Pay For Running Legs. Nonprofits Are Helping Out.Faith Trznadel was born without a tibia bone, and when she was 10months old, doctors had to amputate her lower leg. The hardest part is the staring, the snickering, said Faiths mother, Sheila Trznadel, about how other people treated her daughter. One message to get across to people is its okay to ask questions. ... Its better to ask questions than just stare. [Its] getting rid of that stigma. (Furby, 2/23)

The New York Times:Milk And Juice Are Not As Needed As You Might ThinkIs there such a thing as a healthful beverage? In truth, theres not much of a health case to drink any beverage other than water after the age of 2 despite the marketing and advertising you might have seen on the benefits of things like dairy milk, plant-based milks, juices and more. (Carroll, 2/24)

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Dying Of Flu, College Student Used Cellphone To Call 911. He Died When Police Couldn't Find His Location. - Kaiser Health News

Clene Nanomedicine Announces First Patient Dosed in the RESCUE-ALS Clinical Trial for the Treatment of Amyotrophic Lateral Sclerosis (ALS) with Lead…

SALT LAKE CITY, Jan. 21, 2020 /PRNewswire/ --Clene Nanomedicine, Inc., a clinical-stage biopharmaceutical company, today announcedits Australian subsidiary had completed enrollment and dosing of the first participant in the Phase 2 RESCUE-ALS study with its lead nanocatalytic therapy, CNM-Au8, for the treatment of Amyotrophic Lateral Sclerosis (ALS). The RESCUE-ALS study is substantially funded by FightMND.

"The objective of the randomized, double-blind RESCUE-ALS study is to demonstrate that improvements in brain bioenergetic cellular support in early symptomatic ALS patients treated with CNM-Au8 will help preserve motor neurons survival and function. The primary endpoint is the mean change in the average difference between active treatment and placebo from baseline through week 36 for the Motor Unit Number Index (MUNIX) score, which quantitatively reflects the loss of motor neurons in ALSthe primary cause of clinical progression in ALS," said Robert Glanzman, MD, FAAN, Clene's Chief Medical Officer.

"We are excited to advance CNM-Au8 clinically into this Phase 2 study for ALS patients," said Rob Etherington, President and CEO of Clene. "As neurodegenerative diseases such as ALS have very few treatment options, this study will prove whether CNM-Au8 may be an effective disease-modifying treatment for people with ALS."

"We are very excited to partner with Clene on the Phase 2 study in ALS, RESCUE-ALS," said Professor Steve Vucic, Director of Neurophysiology, Department of Neurology, at Sydney Medical School, Westmead Hospital. "CNM-Au8 offers an innovative approach of potentially treating neurodegenerative diseases, such as ALS, for which there are no effective treatments at present. We are hopeful that CNM-Au8 will be an effective therapy in the future and this trial will go a long way in addressing this question."


RESCUE-ALS is Phase 2 multi-center randomized, double-blind, parallel group, placebo-controlled study examining the efficacy, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in participants who are newly symptomatic ALS (within 24-months of screening or 12-months from diagnosis) and with a clinically probable or possible or definite ALS diagnosis. Enrolled subjects will be randomized 1:1 to receive either active treatment with CNM-Au8 30 mg or placebo in addition to their current standard of care. Participants will receive their randomized oral treatment daily over 36 consecutive weeks during the Treatment Period. The treatment is taken by mouth once daily first thing every morning. The objective of this study is to assess bioenergetic catalysis with CNM-Au8 to slow disease progression in patients with ALS.

About CNM-Au8

CNM-Au8 is a concentrated, aqueous suspension of clean-surfaced faceted nanocrystalline gold (Au) that acts catalytically to support important intracellular biological reactions. CNM-Au8 consists solely of gold atoms organized into faceted, geometrical crystals held in suspension in sodium bicarbonate buffered, pharmaceutical grade water. CNM-Au8 has demonstrated safety in Phase 1 studies in healthy volunteersand both remyelination and neuroprotection effects in multiple preclinical models. Preclinical data presented at scientific congresses demonstrated that treatment with CNM-Au8 in neuronal cultures improved survival of neurons, protected neurite networks, decreased intracellular levels of reactive oxygen species, and improved mitochondrial capacity in response to cellular stress, induced by multiple disease-relevant neurotoxins. Oral treatment with CNM-Au8 improved functional behaviors in a rodent models of ALS, multiple sclerosis, and Parkinson's disease versus vehicle (placebo). CNM-Au8 has received regulatory approval to proceed to clinical studies for the treatment of remyelination failure in patients with multiple sclerosis and neuroprotection in patients with amyotrophic lateral sclerosis(ALS) and Parkinson's disease.

About Amyotrophic Lateral Sclerosis (ALS)

ALS is a universally fatal neurodegenerative disorder that results in loss of motor neurons in the cerebral cortex, brain stem, and spinal cord. ALS, also known as Lou Gehrig's disease, leads to the death of the neurons controlling voluntary muscles resulting in weakness, muscle atrophy, and progressive paralysis. ALS affects more than 15,000 patients in the United States and is the most prevalent adult-onset progressive motor neuron disease.

About Clene

Clene Nanomedicine, Inc. is a privately-held, clinical-stage biopharmaceutical company, focused on the development of unique therapeutics for neurodegenerative diseases. Clene has innovated a novel nanotechnology drug platform for the development of a new class of orally-administered neurotherapeutic drugs. Founded in 2013, the company is based in Salt Lake City, Utah with R&D and manufacturing operations located in North East, Maryland. For more information, please visit http://www.clene.com.

About FightMND

FightMND is a not-for-profit registered charity, founded in 2014. It was established to raise the awareness of Motor Neurone Disease (MND) in Australia, to increase funding for research to find an effective treatment and cure and to provide care equipment for MND patients. We have a clear objective to a have a world free from MND.

FightMND is Australia's largest independent MND foundation focused on funding large- scale, collaborative research and clinical trials. The generous donations contributed by everyday Australians, right across the country, has enabled FightMND to raise and commit millions to cure and care initiatives.

Investor ContactKaitlyn BroscoThe Ruth Group646-536-7032 kbrosco@theruthgroup.com

Media Contact Kirsten ThomasThe Ruth Group508-280-6592 kthomas@theruthgroup.com

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SOURCE Clene Nanomedicine, Inc.

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Clene Nanomedicine Announces First Patient Dosed in the RESCUE-ALS Clinical Trial for the Treatment of Amyotrophic Lateral Sclerosis (ALS) with Lead...

Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form N | IJN – Dove Medical Press

Xiaoyi Zhang, 1, 2 Yixin Zhang, 1, 2 Yaonan Wang, 1, 2 Jianhui Wu, 1, 2 Haiyan Chen, 1, 2 Ming Zhao, 13 Shiqi Peng 1, 2

1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, Peoples Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, Peoples Republic of China; 3Beijing Laboratory of Biomedical Materials and Key Laboratory of Biomedical Materials of Natural Macromolecules, Department of Biomaterials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100026, Peoples Republic of China

Correspondence: Shiqi Peng; Ming ZhaoDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, No. 10, Youanmenwaixitoutiao, Fengtai District, Beijing 100069, Peoples Republic of ChinaTel +86 10 8391 1528; +86 10 8391 1535Fax +86 10 8391 1528; +86 10 8391 1533Email sqpeng@bjmu.edu.cn; maozhao@126.com

Background: 1-(4-isopropylphenyl)--carboline-3-carboxylic acid (ICCA) was modified by Trp-Phe-Phe to form 1-(4-isopropylphenyl)--carboline-3-carbonyl-Trp-Phe-Phe (ICCA-WFF).Purpose: The object of preparing ICCA-WFF was to enhance the in vivo efficacy of ICCA, to explore the possible targeting action, and to visualize the nano-feature.Methods: The advantages of ICCA-WFF over ICCA were demonstrated by a series of in vivo assays, such as anti-tumor assay, anti-arterial thrombosis assay, anti-venous thrombosis assay, P-selectin expression assay, and GPIIb/IIIa expression assay. The nano-features of ICCA-WFF were visualized by TEM, SEM and AFM images. The thrombus targeting and tumor-targeting actions were evidenced by FT-MS spectrum analysis.Results: The minimal effective dose of ICCA-WFF slowing tumor growth and inhibiting thrombosis was 10-fold lower than that of ICCA. ICCA-WFF, but not ICCA, formed nano-particles capable of safe delivery in blood circulation. In vivo ICCA-WFF, but not ICCA, can target thrombus and tumor. In thrombus and tumor, ICCA-WFF released Trp-Phe-Phe and/or ICCA.Conclusion: Modifying ICCA with Trp-Phe-Phe successfully enhanced the anti-tumor activity, improved the anti-thrombotic action, formed nano-particles, targeted tumor tissue and thrombus, and provided an oligopeptide modification strategy for heterocyclic compounds.

Keywords: ICCA, modification, Trp-Phe-Phe, anti-tumor, thrombus targeting, release, toxicity, nano-species

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form N | IJN - Dove Medical Press

Healthcare Nanotechnology (Nanomedicine) Market Share, Size, Future Demand, Global Research, Top Leading Player, Emerging Trends and Forecast to 2015 …

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Animal Feed Antioxidant Market Size and Forecast

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Healthcare Nanotechnology (Nanomedicine) Market Share, Size, Future Demand, Global Research, Top Leading Player, Emerging Trends and Forecast to 2015 ...

Biomedical Applications of Zeolitic Nanoparticles, with an Emphasis on | IJN – Dove Medical Press

Hossein Derakhshankhah, 1, 2,* Samira Jafari, 1, 2,* Sajad Sarvari, 3 Ebrahim Barzegari, 4 Faezeh Moakedi, 5 Milad Ghorbani, 6 Behrang Shiri Varnamkhasti, 1 Mehdi Jaymand, 7 Zhila Izadi, 1, 8 Lobat Tayebi 9

1Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Zistmavad Pharmed Co., Tehran, Iran; 3Department of Pharmaceutical and Pharmacological Science, School of Medicine, West Virginia University, Morgantown, WV, USA; 4Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 5Department of Biochemistry and Molecular Biology, School of Medicine, West Virginia University, Morgantown, WV, USA; 6Department of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran; 7Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 8Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 9Marquette University School of Dentistry, Milwaukee, WI 53201, USA

*These authors contributed equally to this work

Correspondence: Zhila Izadi; Lobat Tayebi Email izadi_zh@razi.tums.ac.ir; lobat.tayebi@marquette.edu

Abstract: The advent of porous materials, in particular zeolitic nanoparticles, has opened up unprecedented putative research avenues in nanomedicine. Zeolites with intracrystal mesopores are low framework density aluminosilicates possessing a regular porous structure along with intricate channels. Their unique physiochemical as well as physiological parameters necessitate a comprehensive overview on their classifications, fabrication platforms, cellular/macromolecular interactions, and eventually their prospective biomedical applications through illustrating the challenges and opportunities in different integrative medical and pharmaceutical fields. More particularly, an update on recent advances in zeolite-accommodated drug delivery and the prevalent challenges regarding these molecular sieves is to be presented. In conclusion, strategies to accelerate the translation of these porous materials from bench to bedside along with common overlooked physiological and pharmacological factors of zeolite nanoparticles are discussed and debated. Furthermore, for zeolite nanoparticles, it is a matter of crucial importance, in terms of biosafety and nanotoxicology, to appreciate the zeolite-bio interface once the zeolite nanoparticles are exposed to the bio-macromolecules in biological media. We specifically shed light on interactions of zeolite nanoparticles with fibrinogen and amyloid beta which had been comprehensively investigated in our recent reports. Given the significance of zeolite nanoparticles interactions with serum or interstitial proteins conferring them new biological identity, the preliminary approaches for deeper understanding of administration, distribution, metabolism and excretion of zeolite nanoparticles are elucidated.

Keywords: zeolite, mesoporous, nanostructure, biosafety, biomedical applications

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Biomedical Applications of Zeolitic Nanoparticles, with an Emphasis on | IJN - Dove Medical Press

Nanocarriers for Stroke Therapy: Advances and Obstacles in Translating | IJN – Dove Medical Press

Syed Abdullah Alkaff, 1 Krishna Radhakrishnan, 1 Anu Maashaa Nedumaran, 1 Ping Liao, 2 Bertrand Czarny 1, 3

1School of Materials Science and Engineering, Nanyang Technological University 639798, Singapore; 2Calcium Signalling Laboratory, National Neuroscience Institute 308433, Singapore; 3Lee Kong Chian School of Medicine, Nanyang Technological University 639798, Singapore

Correspondence: Bertrand CzarnySchool of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Ave, Block N4.1, #02-17 639798, SingaporeTel +65 67904613Email bczarny@ntu.edu.sg

Abstract: The technology of drug delivery systems (DDS) has expanded into many applications, such as for treating neurological disorders. Nanoparticle DDS offer a unique strategy for targeted transport and improved outcomes of therapeutics. Stroke is likely to benefit from the emergence of this technology though clinical breakthroughs are yet to manifest. This review explores the recent advances in this field and provides insight on the trends, prospects and challenges of translating this technology to clinical application. Carriers of diverse material compositions are presented, with special focus on the surface properties and emphasis on the similarities and inconsistencies among in vivo experimental paradigms. Research attention is scattered among various nanoparticle DDS and various routes of drug administration, which expresses the lack of consistency among studies. Analysis of current literature reveals lipid- and polymer-based DDS as forerunners of DDS for stroke; however, cell membrane-derived vesicles (CMVs) possess the competitive edge due to their innate biocompatibility and superior efficacy. Conversely, inorganic and carbon-based DDS offer different functionalities as well as varied capacity for loading but suffer mainly from poor safety and general lack of investigation in this area. This review supports the existing literature by systematizing presently available data and accounting for the differences in drugs of choice, carrier types, animal models, intervention strategies and outcome parameters.

Keywords: nanoparticle, drug delivery system, stroke, animal model, nano medicine, therapeutics

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Nanocarriers for Stroke Therapy: Advances and Obstacles in Translating | IJN - Dove Medical Press

Advancells Group & IFC Concluded their 3-Day Workshop on Regenerative Medicine – Business Wire India

The key-note speaker of the workshop was Dr. Rita Bakshi, founder and chairperson of International Fertility Centre, the oldest fertility clinic and one of the most renowned IVF clinics in India, one of the organizers of the event. Participants also had a privilege to listen to Dr. Sachin Kadam, CTO, Advancells and gain hands-on experience in the preparation of PRP; Liposuction method; and Bone Marrow aspiration. All these techniques were talked about at length and demonstrated in the form of manual & kit-based models to help the candidates gain exposure.

Dr. Punit Prabha, Head of Clinical Research and Dr. Shradha Singh Gautam, Head of Lab Operations at Advancells successfully set the base of stem cell biology for the participants who were experts in gynecology field, stem cell research and pain specialist. With the help of detailed analysis of Application of PRP for Skin rejuvenation; Preparation of Micro-fragmented Adipose Tissue and Nano Fat & SVF (Stromal Vascular Fraction) from Adipose Tissue; and Cell Culturing and Expansion in a Laboratory, applicants understood the application of stem cells in aesthetics, cosmetology, and anti-aging.

Vipul Jain, Founder & CEO of Advancells Group said, Educating young scientists about stem cells is important for us. With this workshop we wanted to discuss and share the challenges and lessons we have learned in our journey of curing our customers. We wanted to establish more concrete knowledge base in the presence of subject matter experts and help our attendees in more possible ways. We are hopeful to have successfully achieved what we claimed with this workshop.

Given the resounding success of the Sub-Specialty Training in Application of Regenerative Medicine (S.T.A.R. 2020), its hoped that the future events shall offer even greater wisdom to the participants by helping them improve and the lead the community into the age of greater awareness.

About Advancells Group

Advancells is leading the field of stem cell therapies in India and abroad, with representative offices in Bangladesh and Australia. The company provides arrangements for stem cell banking and protocols for partner doctors and hospitals which they can use for treating the patients using regenerative medicine. With a GMP compliant research and processing center that works on different cell lines from various sources such as Bone Marrow, Adipose Tissue, Dental Pulp, Blood, Cord Tissue etc. Advancells also intends to file a patent for this processing technology soon.

For more information, visit https://www.advancells.com/

About International Fertility Centre

IFC is Indias leading fertility center under the leadership and guidance of Dr. Rita Bakshi. She along with her solid team of experienced doctors have create a network of 10+ IVF clinics located in India and Nepal. Their services include In-vitro Fertilization (IVF), Intrauterine Insemination (IUI), Intracytoplasmic Injection (ICSI), Egg Donation, Surrogacy, Blastocyst, Assisted Hatching, Hysteroscopy, Laparoscopy and much more.

For more information, visit https://www.internationalfertilitycentre.com/

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Advancells Group & IFC Concluded their 3-Day Workshop on Regenerative Medicine - Business Wire India

I asked Tanzanians about studying in China: here’s what they said – The Conversation Africa

Over the past three decades, China has turned into a major study-abroad hotspot for thousands of African students. In 2018 it hosted over 60,000 African students, making it the second most popular destination for African students abroad, after France. It is even ahead of the US and UK.

This trend can, in part, be explained by Chinas growing provision of scholarships and also by the Chinese governments human resource and education capacity building schemes, such as the African talents programme, which target the continent.

Driving this relationship is Chinas desire for international diplomacy and to improve the international ranking of Chinese universities. Chinese institutions also want to improve the mobility of Chinese students and academics into Africa and have African scholars lecture in China.

One African country with a long history of education cooperation with China is Tanzania. This dates back to 1962. A major component of this relation is scholarships.

As part of my research interest in Chinas role towards technological capacity building in Tanzania, I wanted to know how useful these scholarships were for Tanzanian students. I did a study with 85 Tanzanians who had academic training in China, provided by the Chinese government. I also got inputs from 13 stakeholders, including Chinese and Tanzanian administrators of the scholarship scheme.

I found that, the study group was generally positive about the knowledge and skills they received through classroom sessions and practical and laboratory activities. They also brought back equipment (like multimedia projectors) and technical literature which would benefit them and others back home.

But there were some challenges too. These included cross-cultural barriers and language related communication problems. Another factor was that Tanzania sometimes didnt have the capacity to use some of the advanced Chinese technologies, such as nano science, taught in the courses.

More must be done to improve the relevance of training courses for African students in China. For this to happen, Chinese trainers need to become more acquainted with Tanzanias, and more largely Africas, developmental and technical situation.

In 2014, about 1,400 Tanzanians attended various training courses in China, including scholarship recipients funded by the Chinese or Tanzanian government. The figure reached 3,520 in 2016.

My study focused on the two scholarship schemes that attract the largest number of applicants for short and long education programs in China.

Just over 60% of the studys participants had attended academic training programmes that lasted at least one year. The rest attended short training courses. For those in academia, 45% were pursing a Bachelors degree, 38% a Masters and 17% were at the PhD level.

I used both interviews and surveys to assess what the students thought about the relevance and quality of the courses.

Students were generally positive when it came to the quality of the programmes, particularly when they were asked to compare the courses to similar ones they encountered at Tanzanian institutions.

The greatest gains they found were access to electronic and physical learning resources, specifically literature and equipment which are limited or too expensive in Tanzania. Chinese scholarship awards were also considered to be more prestigious than local accolades.

The students and trainees also highlighted some challenges.

For example, participants of the short seminars described the training using phrases such as; more of a tour, serves the demonstration of Chinas economic achievements or a series of unrelated lectures.

Some recipients were suspicious of the Chinese motives for the training. Many believed the awards were meant to favour Chinese more than Tanzanian interests.

The language barrier came out as the leading challenge facing the majority of the surveyed trainees. 67% of respondents were trained in English, 19% in Mandarin with English translations and the remaining 14% attended the courses in Mandarin language.

Language barriers prevented classroom communication, socio-cultural interactions and also the acquisition of basic services while they stayed in China.

For those in long term academia, a major challenge they faced was access to English learning resources. Medical trainees had the added challenge of having to interact with patients during clinical sessions.

For their part, the Tanzanian governments scholarship administrators were happy with their engagement in the awarding process. They did say that more could be done in granting them access to completion records.

Meanwhile, the Chinese officials said that Chinese universities improved their global ranking because of programmes like these.

Other than communication, there were other socio-cultural differences that the students found challenging. These included the different type of food and racism particularly for those trained in smaller, less multicultural Chinese cities. These challenges led to students feeling isolated, homesick and lonely particularly amongst the longer-term candidates.

Finally, while the students were impressed by Chinas advanced technological capabilities, some found they couldnt use their new skills at home because of technology gaps. For instance, a medicine alumni used a diagnostic kit that he found very efficient during his training in China. However, the government hospital where he works was only able to get them three years after his return.

I propose that collaborative research and exchange programmes be designed between Chinese and Tanzanian academic institutions. This would make them more relevant. And as China continues to invest in businesses in Tanzania, it could ensure graduates have the right training for the jobs being created.

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I asked Tanzanians about studying in China: here's what they said - The Conversation Africa

Nanomedicine: Nanotechnology, Biology and Medicine …

The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine.

Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results...

The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine.

Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.

Nanomedicine: NBM journal publishes articles on artificial cells, regenerative medicine, gene therapy, infectious disease, nanotechnology, nanobiotechnology, nanomedicine, stem cell and tissue engineering.

Sub-categories include synthesis, bioavailability, and biodistribution of nanomedicines; delivery, pharmacodynamics, and pharmacokinetics of nanomedicines; imaging; diagnostics; improved therapeutics; innovative biomaterials; interactions of nanomaterials with cells, tissues, and living organisms; public health; toxicology; theranostics; point of care monitoring; nutrition; nanomedical devices; prosthetics; biomimetics; and bioinformatics.

Article formats include Rapid Communications, Original Articles, Reviews, Perspectives, Technical and Commercialization Notes, and Letters to the Editor. We invite authors to submit original manuscripts in these categories.

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Nanomedicine: Nanotechnology, Biology and Medicine ...

Nanomedicine | medicine | Britannica

Nanomedicine, branch of medicine that seeks to apply nanotechnologythat is, the manipulation and manufacture of materials and devices that are smaller than 1 nanometre [0.0000001 cm] in sizeto the prevention of disease and to imaging, diagnosis, monitoring, treatment, repair, and regeneration of biological systems.

Although nanomedicine remains in its early stages, a number of nanomedical applications have been developed. Research thus far has focused on the development of biosensors to aid in diagnostics and vehicles to administer vaccines, medications, and genetic therapy, including the development of nanocapsules to aid in cancer treatment.

An offshoot of nanotechnology, nanomedicine is an emerging field and had garnered interest as a site for global research and development, which gives the field academic and commercial legitimacy. Funding for nanomedicine research comes both from public and private sources, and the leading investors are the United States, the United Kingdom, Germany, and Japan. In terms of the volume of nanomedicine research, these countries are joined by China, France, India, Brazil, Russia, and India.

Working at the molecular-size scale, nanomedicine is animated with promises of the seamless integration of biology and technology, the eradication of disease through personalized medicine, targeted drug delivery, regenerative medicine, as well as nanomachinery that can substitute portions of cells. Although many of these visions may not come to fruition, some nanomedicine applications have become reality, with the potential to radically transform the practice of medicine, as well as current understandings of the health, disease, and biologyissues that are of vital importance for contemporary societies. The fields global market share totalled some $78 billion dollars in 2012, driven by technological advancements. By the end of the decade, the market is expected to grow to nearly $200 billion.

Nanomedicine derives much of its rhetorical, technological, and scientific strength from the scale on which it operates (1 to 100 nanometers), the size of molecules and biochemical functions. The term nanomedicine emerged in 1999, the year when American scientist Robert A. Freitas Jr. published Nanomedicine: Basic Capabilities, the first of two volumes he dedicated to the subject.

Extending American scientist K. Eric Drexlers vision of molecular assemblers with respect to nanotechnology, nanomedicine was depicted as facilitating the creation of nanobot devices (nanoscale-sized automatons) that would navigate the human body searching for and clearing disease. Although much of this compelling imagery still remains unrealized, it underscores the underlying vision of doctors being able to search and destroy diseased cells, or of nanomachines that substitute biological parts, which still drives portrayals of the field. Such illustrations remain integral to the field, being used by scientists, funding agencies, and the media alike.

Attesting to the fields actuality are numerous dedicated scientific and industry-oriented conferences, peer-reviewed scientific journals, professional societies, and a growing number of companies. However, nanomedicines identity, scope, and goals are a matter of controversy. In 2006, for instance, the prestigious journal Nature Materials discussed the ongoing struggle of policy makers to understand if nanomedicine is a rhetorical issue or a solution to a real problem. This ambivalence is reflected in the numerous definitions of nanomedicine that can be found in scientific literature, that range from complicated drugs to the above mentioned nanobots. Despite the lack of a shared definition, there is a general agreement that nanomedicine entails the application of nanotechnology in medicine and that it will profoundly impact medical practice.

A further topic of debate is nanomedicines genealogy, in particular its connections to molecular medicine and nanotechnology. The case of nanotechnology is exemplary: on one hand, its potentialin terms of science but also in regard to funding and recognitionis often mobilized by nanomedicine proponents; on the other, there is an attempt to distance nanomedicine from nanotechnology, for fear of being damaged by the perceived hype that surrounds it. The push is then for nanomedicine to emerge not as a subdiscipline of nanotechnology but as a parallel field.

Although nanomedicine research and development is actively pursued in numerous countries, the United States, the EU (particularly Germany), and Japan have made significant contributions from the fields outset. This is reflected both in the number of articles published and in that of patents filed, both of which have grown exponentially since 2004. By 2012, however, nanomedicine research in China grew with respect to publications in the field, and the country ranked second only to the United States in the number of research articles published.

In 2004, two U.S. funding agenciesthe National Institutes of Health and the National Cancer Instituteidentified nanomedicine as a priority research area allocating $144 million and $80 million, respectively, to its study. In the EU meanwhile, public granting institutions did not formally recognize nanomedicine as a field, providing instead funding for research that falls under the headers of nanotechnology and health. Such lack of coordination had been the target of critiques by the European Science Foundation (ESF), warning that it would result in lost medical benefits. In spite of this, the EU ranked first in number of nanomedicine articles published and in 2007 the Seventh Framework Programme (FP7) allocated 250 million to nanomedicine research. Such work has also been heavily funded by the private sector. A study led by the European Science and Technology Observatory found that over 200 European companies were researching and developing nanomedicine applications, many of which were coordinating their efforts.

Much of nanomedicine research is application oriented, emphasizing methods to transfer it from the laboratory to the bedside. In 2005 the ESF pointed to four main subfields in nanomedicine research: analytical tools and nanoimaging, nanomaterials and nanodevices, novel therapeutics and drug delivery systems, and clinical, regulatory, and toxicological issues. Research in analytical tools and nanoimaging seeks to develop noninvasive, reliable, cheap, and highly sensitive tools for in vivo diagnosis and visualization. The ultimate goal is to create fully functional mobile sensors that can be remotely controlled to conduct in vivo, real-time analysis. Research on nanomaterials and nanodevices aims to improve the biocompatibility and mechanical properties of biomaterials used in medicine, so as to create safer implants, substitute damaged cell parts, or stimulate cell growth for tissue engineering and regeneration, to name a few. Work in novel therapeutics and drug delivery systems strives to develop and design nanoparticles and nanostructures that are noninvasive and can target specific diseases, as well as cross biological barriers. Allied with very precise means for diagnosis, these drug delivery systems would enable equally precise site-specific therapeutics and fewer side effects. The area of drug delivery accounts for a large portion of nanomedicines scientific publications.

Finally, the subfield of clinical, regulatory, and toxicological issues lumps together research that examines the field as a whole. Questions of safety and toxicology are prevalent, an issue that is all the more important given that nanomedicine entails introducing newly engineered nanoscale particles, materials, and devices into the human body. Regulatory issues revolve around the management of this newness, with some defending the need for new regulation, and others the ability of systems to deal with it. This subfield should also include other research by social scientists and humanists, namely on the ethics of nanomedicine.

Combined, these subfields build a case for preventive medicine and personalized medicine. Building upon genomics, personalized medicine envisions the possibility of individually tailored diagnostics and therapeutics. Preventive medicine takes this notion further, conjuring the possibility of treating a disease before it manifests itself. If realized, such shifts would have radical impacts on understandings of health, embodiment, and personhood. Questions remain concerning the cost and accessibility of nanomedicine and also about the consequences of diagnostics based on risk propensity or that lack a cure.


Medicine, the practice concerned with the maintenance of health and the prevention, alleviation, or cure of disease. The


Nanotechnology, the manipulation and manufacture of materials and devices on the scale of atoms or small groups of atoms. The nanoscale is typically measured in nanometres, or billionths of a metre (nanos, the Greek word for dwarf, being the source of the prefix), and materials built at this scale often


Disease, any harmful deviation from the normal structural or functional state of an organism, generally associated with certain signs and symptoms and differing in nature from physical injury. A diseased organism commonly exhibits signs or symptoms indicative of its abnormal state. Thus, the normal condition of an organism must be

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Nanomedicine | medicine | Britannica

The Future Of Nano Medicine

Nanomedicine, refers to highly specific medical intervention at the molecular level for curing disease or repairing damaged tissues. Though in its infancy, could we be looking at the future of medicine? Early clinical trials certainly look promising.How Nanomedicine Works

- Nanomedicine works by injecting nanoparticles into the body- Can be used to:- Deliver medicine- Find and treat disease- Repair damaged cells

One human hair is approximately 80,000 nanometers wideApplications of Nanomedicine

- Drug Delivery- Using nanotechnology to deliver medicine, diabetic rats kept stable blood sugar levels for 10 days after injection- Cancer Diagnosis and Treatment- Using microRNA from a patient's blood plasma and nanotechnology:- Medical professionals can determine if lung cancer is present- Begin treatment the same day- Using Nano-Therm therapy to overheat brain cancer cells helps to destroy them- In clinical trials, those with recurrent glioblastoma survived a median of 13 months- More than double the survival rate of those not receiving Nano-Therm therapyNanotechnology is already commonly used in sunscreen and to make tennis balls more bouncy

- Flu Testing- Today's flu tests are:- Time consuming- Inaccurate- Nanomedicine gold flu testing provides:- Instant results- Immediate treatment cycle to avoid spreading to others- commercial nanotech testing no more than 5 years away- Cell Feedback- Nanomedicine can be used to test cell's response to drugs offering new drug testing methods- Provides instant feedback to how cells respond to medicine- Can save years and millions of dollars on testing and clinical trials- Can improve current medications

In a 1956, Arthur C. Clarke first envisioned the concept of nanotechnology in a short story, The Next TenantsAdvantages of Nanomedicine

- Faster diagnosis of many ailments- More precise treatments of conditions such as cancer- Repair tissue deep within the body- Target only diseased organs, lessening the need for drugsSources

- https://commonfund.nih.gov/nanomedicine/overview.aspx- http://www.understandingnano.com/medicine.html- http://pubs.acs.org/doi/abs/10.1021/nn400630x- http://www.nature.com/nnano/journal/v6/n10/full/nnano.2011.147.html- http://www.dana.org/news/features/detail_bw.aspx?id=35592- http://pubs.rsc.org/en/Content/ArticleLanding/2011/AN/C1AN15303J- http://onlinelibrary.wiley.com/doi/10.1002/smll.201001642/abstract- http://www.clinam.org/benefits.html

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The Future Of Nano Medicine

New Approaches in Breast Cancer Therapy Through Green Nanotechnology a | IJN – Dove Medical Press

Menka Khoobchandani, 1, 2 Kavita K Katti, 1, 2 Alice Raphael Karikachery, 1, 2 Velaphi C Thipe, 1, 2 Deepak Srisrimal, 3 Darsha Kumar Dhurvas Mohandoss, 3 Rashmi Dhurvas Darshakumar, 3 Chintamani M Joshi, 3 Kattesh V Katti 1, 2, 4

1Department of Radiology, University of Missouri, Columbia, MO 65212, USA; 2Institute of Green Nanotechnology, University of Missouri, Columbia, MO 65212, USA; 3Dhanvantari Nano Ayushadi Pvt Ltd, Chennai 600017, India; 4Department of Physics, Department of Pharmacology, Department of Biological Engineering, University of Missouri Research Reactor (MURR), University of Missouri, Columbia, MO 65212, USA

Correspondence: Kattesh V KattiDepartment of Radiology, University of Missouri, One Hospital Drive, Columbia, MO 65212 USATel +1 573 882-5656Email KattiK@health.missouri.edu

Purpose: The overarching objective of this investigation was to investigate the intervention of green nanotechnology to transform the ancient holistic Ayurvedic medicine scientifically credible through reproducible formulations and rigorous pre-clinical/clinical evaluations.Methods: We provide, herein, full details: (i) on the discovery and full characterization of gold nanoparticles-based Nano Swarna Bhasma (henceforth referred to as NSB drug); (ii) In vitro anti-tumor properties of NSB drug in breast tumor cells; (iii) pre-clinical therapeutic efficacy studies of NSB drug in breast tumor bearing SCID mice through oral delivery protocols and (iv) first results of clinical translation, from mice to human breast cancer patients, through pilot human clinical trials, conducted according to the Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy (abbreviated as AYUSH) regulatory guidelines of the Government of India in metastatic breast cancer patients.Results: The preclinical in vitro and in vivo investigations, in breast tumor bearing mice, established unequivocally that the NSB Nano-Ayurvedic medicine-gold nanoparticles-based drug is highly effective in controlling the growth of breast tumors in a dose dependent fashion in vivo. These encouraging pre-clinical results prompted us to seek permission from the Indian Governments holistic medicine approval authority, AYUSH, for conducting clinical trials in human patients. Patients treated with the NSB drug capsules along with the standard of care treatment (Arm B) exhibited 100% clinical benefits when compared to patients in the treatment Arm A, thus indicating the tremendous clinical benefits of NSB drug in adjuvant therapy.Conclusion: We have succeeded in clinically translating, from mice to humans, in using proprietary combinations of gold nanoparticles and phytochemicals to develop the Nano-Ayurvedic drug: Nano Swarna Bhasma (NSB), through innovative green nanotechnology, for treating human metastatic breast cancer patients.

Keywords: gold nanoparticles, mangiferin, mango peel, Nano Swarna Bhasma, NSB, triple negative breast tumor, pilot clinical

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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New Approaches in Breast Cancer Therapy Through Green Nanotechnology a | IJN - Dove Medical Press

A New Old Therapy – The UCSB Current

The fight against drug-resistant pathogens remains an intense one. While the Centers for Disease Controls (CDC) 2019 biggest threats report reveals an overall decrease in drug-resistant microbe-related deaths as compared to its previous report (2013) the agency also cautions that new forms of drug-resistant pathogens are still emerging.

Meanwhile, the options for treating infections by these germs are diminishing, confirming doctors and scientists worries about the end of the age of antibiotics.

We knew it was going to be a problem early on, said UC Santa Barbara chemistry and biochemistry professor Irene Chen. Basically as soon as penicillin was discovered, a few years later it was reported that there was a resistant organism. Thanks to factors such as horizontal gene transfer and rapid reproduction, organisms such as Gram-negative bacteria are able to evolve faster than we can produce antibiotics to control them.

So Chen and her research group are seeking alternatives to antibiotics, in a growing effort to head off the tide of incurable bacterial infections. In their work, the group has turned to bacteriophages, a naturally occurring group of viruses that colonize on bacteria.

Thats their natural function, really, to grow on and kill bacteria, said Chen, author of a paper that appears in the Proceedings of the National Academy of Sciences. By taking advantage of the bacteriophages ability to home in on specific bacteria without damaging the rest of the microbiome, the researchers were able to use a combination of gold nanorods and near-infrared light to destroy even multidrug-resistant bacteria without antibiotics.

Phage therapy isnt new, Chen said. In fact, it has been used in the former Soviet Union and Europe for about a century, though they are seen largely as last-resort alternatives to antibiotics. Among the unresolved issues of phage therapy is the incomplete characterization of the phages biology a biology that could allow for unintended consequences due to the phages own rapid evolution and reproduction, as well as potential toxins the viruses may carry. Another issue is the all-or-nothing aspect of phage therapy, Chen added.

Its difficult to analyze the effect of a phage treatment, she said. You might see it completely work or you might see it completely fail, but you dont have the kind of dose response you want.

To surmount these challenges, the Chen lab developed a method of controlled phage therapy.

What we did was to conjugate the phages to gold nanorods, she explained. These phanorods were applied to bacteria on in-vitro cultures of mammalian cells and then exposed to near-infrared light.

Conjugated to phages,gold nanorods find their target: a bacterial cell wall


When these nanorods are photo-excited, they translate the energy from light to heat, Chen said, and that creates very high local temperatures.

The heat is enough to kill the bacteria, and it also kills the phages, preventing any unwanted further evolutions. The result is a guided missile of targeted phage therapy that also allows for dosage control. The lab found success in destroying E. coli, P. aeruginosa and V. cholerae human pathogens that cause acute symptoms if left unchecked. They also were able to successfully destroy X. campestris, a bacteria that causes rot in plants.

In a collaboration with UC Santa Barbara mechanical engineer Beth Pruitt, the lab determined that while the heat successfully destroyed bacteria and phage, more than 80% of the mammalian cell culture underneath the bacteria biofilm survived.

Bacteria under fire: Green bacteria are alive, while the red ones are dead


This issue of whether it damages mammalian tissues is very important, Chen said. Work in nanotechnology and nanomedicine treating bacterial infections indicates that when its non-targeted, it really does burden the surrounding tissues.

The lab plans to investigate other possible phages to counter other bacteria, possibly engineering a photothermal method that could treat multiple bacterial infections.

Research on this study was conducted also by UCSB postdoctoral fellow Huan Peng (lead author), Raymond E. Borg and Liam P. Dow.

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A New Old Therapy - The UCSB Current

Controlled phage therapy hints at future alternative to antibiotics – New Atlas

Phages, viruses that thrive by infecting bacteria, have long been mooted as a potential replacement for antibiotics. But where antibiotics pose the problem of the bacteria they target mutating into dangerous resistant strains, phages pose risks due to their own fast-paced evolution, though those risks are poorly understood.

But new research suggests it may be possible to mitigate those risks. Left to nature, particular phages are able to seek out and destroy particular types of bacteria. But here its only the seeking that the researchers are interested in, using the phages to deliver a payload of gold nanorods which, with the help of light, destroy both the target bacteria and their phages at once. If youll forgive the grim analogy, you can think of the phage as the guidance system and the nanorods the warhead of this particular antibacterial guided missile.

What we did was to conjugate the phages to gold nanorods, UC Santa Barbaras Irene Chen explains in a press release. If you thought conjugation was something that happened only to verbs, dont panic: it can also simply mean to join or couple. When these nanorods are photo-excited, they translate the energy from light to heat, and that creates very high local temperatures.

The so-called phanorod combinations of nanorods and phages were added to in-vitro cultures of mammal cells with an added bacteria biofilm. They were then exposed to light in near-infrared wavelengths to cause the all-important photo-excitement. The resulting heat kills both the bacteria and the phage.

In experiments, the phanorods successfully destroyed the potent human pathogens E. coli, P. aeruginosa and V. cholerae. Its important to note that the phanorods also destroyed 20 percent of the mammal cells in the culture, which the research categorizes as a low rate of damage.

This issue of whether it damages mammalian tissues is very important, Chen explains. Work in nanotechnology and nanomedicine treating bacterial infections indicates that when its non-targeted, it really does burden the surrounding tissues.

As well as the unpredictable nature of unchecked phage evolution, there are other issues with their historical use. They can potentially carry toxins, and its hard to gauge the success of the treatment. You might see it completely work or you might see it completely fail, but you dont have the kind of dose response you want, Chen explains. But this new controlled approach to phage therapy could potentially mitigate these issues as well.

The teams research will go on to look at more phages to target more types of bacteria, as well as exploring photothermal methods to treat several bacterial infections at once. However, the work is very much at the research stage, and theres no suggestion of clinical use at this stage.

The teams research was published Monday in Proceedings of the National Academy of Sciences. Its free to read online.

Sources: UC Santa Barbara, Proceedings of the National Academy of Sciences

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Controlled phage therapy hints at future alternative to antibiotics - New Atlas

Most engineered nanoparticles enter tumours through cells not between them, U of T researchers find – News@UofT

University of Toronto researchers have discovered that an active rather than passive process dictates which nanoparticles enter solid tumours, upending decades of thinking in the field of cancer nanomedicine and pointing toward more effective nanotherapies.

The prevailing theory in cancer nanomedicine an approach that enables more targeted therapies than standard chemotherapy has been that nanoparticles mainly diffuse passively into tumours through tiny gaps between cells in the endothelium, which lines the inner wall of blood vessels that support tumour growth.

The researchers previously showed thatless than one per centof nanoparticle-based drugs typically reach their tumour targets. In the current study, they found that among nanoparticles that do penetrate tumours, more than 95 per cent pass through endothelial cells not between gaps among those cells.

Our work challenges long-held dogma in the field and suggests a completely new theory, saysAbdullah Syed, a co-lead author on the study and post-doctoral researcher in the lab ofWarren Chan, a professor at theInstitute of Biomaterials and Biomedical Engineeringand theDonnelly Centre for Cellular and Biomolecular Research.

We saw many nanoparticles enter the endothelial cells from blood vessels and exit into the tumour in various conditions. Endothelial cells appear to be crucial gatekeepers in the nanoparticle transport process.

The findings were recently published in thejournalNature Materials.

From left to right: U of T researchers Jessica Ngai, Shrey Sindhwani, Abdullah Syed and Benjamin Kingston (photo by Qin Dai)

Syed compares nanoparticles to people trying to get into popular restaurants on a busy night. Some restaurants dont require a reservation, while others have bouncers who check if patrons made reservations, he says. The bouncers are a lot more common than researchers thought, and most places only accept patrons with a reservation.

The researchers established that passive diffusion was not the mechanism of entry with multiple lines of evidence. They took over 400 images of tissue samples from animal modelsand saw few endothelial gaps relative to nanoparticles. They observed the same trend using 3D fluorescent imaging and live-animal imaging.

Similarly, they found few gaps between endothelial cells in samples from human cancer patients.

The group then devised an animal model that completely stopped the transportation of nanoparticles through endothelial cells. This allowed them to isolate the contribution of passive transport via gaps between endothelial cells, which proved to be miniscule.

The researchers posit several active mechanisms by which endothelial cells might transport nanoparticles into tumours, including binding mechanisms, intra-endothelial channels and as-yet undiscovered processes all of which they are investigating.

Meanwhile, the results have major implications for nanoparticle-based therapeutics.

These findings will change the way we think about delivering drugs to tumours using nanoparticles, saysShrey Sindhwani, also a co-lead author on the paper and an MD/PhD student in the Chan lab. A better understanding of the nanoparticle transport phenomenon will help researchers design more effective therapies.

The research included collaborators from U of Ts department of physics in the Faculty of Arts & Science, Cold Spring Harbor Laboratory In New York and the University of Ottawa. The study was funded by the Canada Research Chairs Program, Canadian Cancer Society, Natural Sciences and Engineering Research Council of Canadaand the Canadian Institutes of Health Research.

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Most engineered nanoparticles enter tumours through cells not between them, U of T researchers find - News@UofT

Canterbury father and son’s invention will revolutionise medical treatment – Stuff.co.nz

A typical father and son project might mean restoring a classic car or completing a home renovation, but this Christchurch pair have set their sights a little higher. LEE KENNY reports.

Phil and Anthony Butlerhave utilised cutting-edge technologyused in the hunt for the Higgs Boson to invent the world's first 3-D colour X-ray.

Phil is a professor at University of Canterbury and a Fellow of New Zealand Institute of Physics, while Anthony is a clinical radiologist and a professor at University of Otago.

Together they have created the MARS scanner, which will one day replace many of the functions of the X-ray, positron emission tomography (PET) scans and magnetic resonance imaging (MRI).


Phil and Anthony Butler work on an arm scanner at MARS' Christchurch laboratory.

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The non-invasive technique will enable doctors to see colour images from inside the body, allowing them to make a more accurate diagnosis when treating everything from a broken bone to heart disease.

Phil, 72, first thought about the concept while he was atCERN (European Organization for Nuclear Research) in 2002.

Scientists working on the Large Hadron Collider used high-tech Medipix detectors to track particles and it was theorisedthey could also be used to detect X-ray photons.

Anthony joined CERN in 2005 and it was while the Butlerswere on a family holiday in Croatia that they decided to put the theory to the test.


A 3-D image of Phil Butler's wrist taken by the MARS scanner in 2018.

They founded MARS Bioimaging in 2007 and today their 50-strong team consists of physicists, radiologists, mathematicians, biologists, engineers and computer scientists.

The company is part owned by University of Canterbury where it is based and has close ties to Otago Medical School.

Anthony, 44, explains the machine works by shining X-rays through the body and measuring the tissue composition before a computer reconstructs the information into a high-resolution 3-D colour image.

"The underlying process is often called spectral photon counting we measure the X-ray beam one photon at a time, which means we need to have very fast electronics to do this."

He says they have been looking at several medical applications for the scanners, across a range of clinical disciplines.


Professor Phil Butler is the chief executive of MARS Bioimaging but still takes a hands-on role.

"We've been working with orthopedic surgeons looking at fracture healing, cardiologists looking at the causes of heart disease and stroke, cancer specialists looking whether we can look at cell lines and the way they progress and we've looked at infectious diseases.

"That covers a large chunk of medicine and I expect we'll see [the scanners]hit the clinics at different times.

"It's going to be routine within a few years for a lot of point-of-care stuff."

The primary difference between the MARS scanner and other techniques is the level of detailed information it can record.

Anthony says the work is so cutting edge that components had to be built from scratch.

Dean Mouhtaropoulos

The MARS scanner was inspired by technology used at CERN, the World's Largest Particle Physics Laboratory.

"We did computer simulations to work out what we should be doing, then we had to come up with the designs, then manufacture it."

Dipanjan Pan, professor in chemical and biological engineering and radiology at University of Maryland Baltimore County, is an expert in nanomedicine and molecular imaging.

He collaborated with the MARS team for several years and says the3-D scanner has the potential to "dramatically change the ambiguity often found in black and white conventional CT imaging".

"Looking through MARS's proprietary photon counting CT 'magic lenses', you are visualising in colour the future of various biological processes as it merges with the present," he says.

"Their powerful reconstruction technique is astounding."

The technology has a range of uses from security and engineeringto physics and astronomy.


The traditional 2-D X-ray is good at showing solid objects like bones.

But the Butlers are focused on clinical applications and in July 2018 Phil became the first person to be scanned, with images generated of his wrist and ankle.

The next stage will be clinical trials next year when orthopaedic and rheumatology patients from Christchurch will bescanned.

Phil saysthe breakthrough is comparable to the first X-ray images in 1895 and the first low-resolution Computed Tomography (CT) in 1972.

"It's a major step. We went from 2-D to 3-D, now we're going from black and white to colour.

"The other thing that makes ours different from pretty much any other clinical system is we've got very high-resolution, basically 10 times the resolution of any other comparable technology."

Dr Diana Siew, associate director at MedTech Centre of Research Excellence at Auckland Bioengineering Institute, said the MARS X-ray scanner is a "game changer in medical diagnostics" because "it visualises what is happening in the body in a way that has not been achieved before".

"Different components of the body like fat, calcium, water and disease biomarkers show-up on the X-ray images in different colours, thus allowing a fuller and more accurate picture of a patient's condition," she says.


The new MRI scanner at Palmerston North Hospital had to be slotted through a hole in the wall when it was installed in April 2019.

"From a research perspective, this is exciting as it could underpin new understanding of disease onset and progression and be used to determine the efficacy of treatments.

"The MARS technology is a world's first and it is so exciting that it is happening in NZ."

As well as heralding a quantum leap in imaging capability, Anthony says the MARS technology will improve health treatment for Kiwis, as not everywhere has access to PET or MRI scanners.

"About half the people in rural New Zealand don't get appropriate cancer treatment, not because the country can't afford it but because the cancer centres are in large hospitals, the same is true for imaging," he says.

"If you are on the West Coast you cannot get a PET scan, you have to come over to Christchurch.


MRI scanners can record incredible detail but they are large and not widely available.

"So those access issues, we beat most of them because we use X-rays and they are very easy to have in a local practice, every dentist has got one."

Phil added: "One of the design goals for this system is to make it as easy to operate as a dentist's X-ray".

As well as the high cost of PET and MRI scanners, Anthony says there are other practicalities that make them less accessible.

"MRI requires rooms with big machines, you have to have liquid helium cooling it down, you can't put someone in with a pacemaker, certain vascular clips can't go in there [or] hip replacements," he says.

"With PET you have similar things, you have radioisotopes. In New Zealand we have one cyclotron in Wellington producing radioisotopes and they have to be flown around the country, so if it's a windy day in Wellington, no PET imaging can happen in the country."


A 3-D image of Phil Butler's ankle, scanned in 2018.

MARS is operated from a secure area of University of Canterbury and as well as full-time staff, research is carried out by 15 PhD candidates.

Phil is in no doubt that a key component of the project's success is that it's based in Canterbury.

"If you look at the electronics or mechanical engineering skills of Christchurch, we can build anything," he says.

"We've got the skills to do it but the people also know each other, whereas if you go to a big city of several million, they can do it but they can't talk to their allied disciplines.

"That goes back to the farming industries, where people had to build their own machines and those skills of being able to build anything are all part of that."

Anthony agrees.

"If you go to really large research institutes they can be really skilled but they tend to have big silos. In New Zealand we tend not to operate that way.

Don Scott/Stuff

The Butlers, pictured here in 2010, examine coloured Iodine and Barium infused tissue.

"I think we're the sweet-spot in terms of size, where there's enough skill around that there's experts but we're not so big that we can't talk to each other."

Almost 15 years since the father and son team decided to embark on the research, they have made huge advances but there is still work to be done.

"If you look at where we were in 2006 or 2007 we were able to measure four colours but we had to do them one after the other, not simultaneously," Anthony says.

"We scanned the abdomen of a mouse, a pretty small object, and it [took] a day to image it and a month to do all the data reconstruction to get a picture to look at."

Day-to-day, Anthony is the company's chief medical officer and scientific lead.

Phil is the chief executive but, but according to Anthony, he still "does a lot of the technical work".

Working with family members can bring its challenges but Anthony says one of the advantages of partnering with his dad is the "innate trust" they have.

"It's actually a real pleasure," he says.

"I'm quite lucky, I didn't start working with him until I was in my early 30s, which meant I'd done all of my qualifications, established my own life.

"He had done many things himself and been pro-vice chancellor of the university and wanted to get more into practical applications so we founded this project together and that's been really nice.

"You're always going to have problems in any relationship but the fact that it's a family member gives you structure where you can actually work through problems and solve them and know that you're on the same team."

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Canterbury father and son's invention will revolutionise medical treatment - Stuff.co.nz

Rewind 2019: A Look Back at Significant Developments in Indian Science This Year – The Weather Channel

Representational image: A young science enthusiast peering at the sky using a telescope

Chandrayaan-2 may have dominated popular imagination during 2019 despite the Vikram Lander failing to soft-land on the lunar surface, but the year was marked by several significant developments by Indian scientists in fields ranging from nanotechnology to climate change.

The run-up to the lunar mission with planned landing of the lander-cum-rover, the launch campaign, the journey to the lunar orbit and the landing sequence all attracted national and international attention. The year ended in triumph for citizen science when Chennai-based software engineer, Shanmuga Subramanian, discovered debris of Vikram on the lunar surface using publicly available high-resolution images of the landing site. This development comes close to a rise in citizen science initiatives in the country.

Staying with space and astronomy, star of an exoplanet was named after Indian physicist, Bibha Chowdhury. During the year, Indian software engineers got readied software that will run the Thirty Meter Telescope (TMT), which is slated to be the worlds largest ground-based telescope operating at optical and infrared wavelengths. Details about TMT and other international Big Science projects in which India is participating were on display in a roving exhibition called Vigyan Samagam which attracted huge crowds.

Climate change: Responding to climate change impacts being seen in the Himalayan region, Indian scientists developed a common framework for assessment of climate change vulnerability in all the states in the region, using an index based on socio-economic factors, demographic and health status, sensitivity of agricultural production, forest-dependent livelihoods, and access to information, services and infrastructure. This knowledge will now be applied to develop a countrywide map of climate vulnerability.

Scientists from the Indian Institute of Tropical Meteorology (IITM) found a link between warming of the Indo-Pacific Ocean and changing rainfall patterns in many parts of the globe, including India. The warming pools of the Indo-Pacific Ocean are expanding, and this, in turn, is altering a major weather phenomenon known as the Madden Julian Oscillation (MJO). The warming of Indo-Pacific Ocean is occurring due to man-made emissions. Another group from the Indian Institute of Science warned that as many as 55 percent of glaciers in the Satluj basin may disappear by 2050. and 97 percent by 2090, under extreme climate change scenario. Using ice thickness of glaciers as the basis, scientists also estimated that glaciers in the Hindu Kush Himalayas might contain 27% less ice than previously suggested.

Eco-friendly technologies: The year saw progress towards development of less polluting crackers, with the Council of Scientific and Industrial Research (CSIR) releasing first set of green crackers. A national centre to pursue R&D in clean coal technologies was also opened in Bangalore. Eight teams of innovators from different parts of the world were selected for an international competition to develop more efficient and climate-friendly cooling solutions for residential buildings. The team will get seed money to translate their ideas into prototypes. The final winner of the Global Climate Prize will be announced in November 2020.

Representational image: Microscopic bacteria

Indian genomic data: In an important development, Delhi-based Institute of Genomics and Integrative Biology (IGIB) and Hyderabad-based Centre for Cellular and Molecular Biology (CCMB) completed whole genome sequencing of 1008 Indian individuals representing diverse ethnic groups in the country. The data will act as baseline information for developing various applications in predictive and preventive medicine.

Scientists from CCMB also found underlying genetic factors for infertility among Indian men. This knowledge could help in developing a genetic test for male infertility in near future. As part of genetic studies to trace the origins of population groups in the Indian sub-continent, it had been seen that sizeable population group of Mundas in central and northeast India shares genetic ancestry with Southeast Asian populations as well. A study revealed how and when this admixture between Mundas and Southeast Asian populations took place.

The Department of Biotechnology (DBT) launched a new human atlas initiative called Manav to develop a unified database of molecular network of all the tissues in the human body, and to derive a holistic picture of the working of human body. This mega project will collate and integrate molecular information on human tissues and organs that currently lies hidden in research articles in an unstructured and disorganized form.

Developments in gene editing: Indian scientists developed a new variant of currently popular gene editing tool, CRISPR-Cas9, and showed that it can increase precision in editing genome while avoiding unintended changes in DNA. The researchers showed that this type of gene editing can be used to correct sickle cell anemia, a genetic blood disorder. The experiments were done in human-derived cells from patients of sickle cell anemia, according to findings published in Proceedings of the National Academy of Sciences (PNAS).

New nano materials: Continuing their work in nano science and technology in 2019, scientists at the Mumbai-based Tata Institute of Fundamental Research (TIFR) used gold nanoparticles, and by rearranging size and gaps between them, developed a new material with unique properties like capacity to absorb light and carbon dioxide. Gold does not have these properties, and therefore, the new material has been named black gold, dye to its black appearance.

Boosting rice productivity: Scientists at the National Institute of Plant Genome Research (NIPGR) identified a gene involved in regulating the size of rice grain. The new development represents a new approach towards developing rice varieties that produce bigger and consequently heavier grains. Scientists from the Bose Institute came up with a new salt-tolerant transgenic rice plant by over-expressing a gene from a wild rice called Porteresia coarctata into the commonly used IR 64 indica rice variety.

Other important developments during the year included a new plan to establish a museum for marine archaeology at Lothal, a new satellite-based weather information service for deep sea fishers, grand challenge for cancer research to develop affordable cancer diagnostics and treatment, a white paper on e-cigarettes that led to its ban in India, and new initiative to boost malaria research in the country.

(This article was originally published on India Science Wire.)

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Rewind 2019: A Look Back at Significant Developments in Indian Science This Year - The Weather Channel

Electroplating method makes conductive nanostraws for injecting into and sampling from cells – Chemical & Engineering News

Credit: ACS Appl. Mater. Interfaces

An array of platinum nanostraws can be used to deliver molecules to cells or sample their contents.

Hollow nanosized needles, or nanostraws, are a promising tool for opening up tiny, temporary holes in cell membranes to deliver molecules or sample a cells contents. Nanostraws could also deliver gene editors into cells for immunotherapy, cutting the need to use costly viruses for the job. But making nanostraws requires expensive manufacturing equipment in a clean room facility, and using nanostraws often requires applying a high voltage in order to open up the cell membrane. Now, researchers have developed a more affordable fabrication approach that can be done in an ordinary lab. Whats more, the new nanostraws are conductive, thus lowering the amount of voltage needed to levels less likely to damage cells (ACS Appl. Mater. Interfaces 2019, DOI: 10.1021/acsami.9b15619).

Researchers made earlier iterations of nanostraws with atomic layer deposition (ALD), which grows thin films of materials such as metal oxides one layer of atoms at a time. In their new approach, Xi Xie of Sun Yat-Sen University and colleagues replaced ALD with electroplating, a simple process which uses an electrical potential to deposit ions in a solution onto a surface.

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They first sputtered a thin layer of gold on the bottom surface of a polycarbonate template containing an array of pores in order to make a conductive base layer. Then they electroplated platinum, gold, or the conductive polymer poly(3,4-ethylenedioxythiophene)three common materials used in electrophysiology studiesfrom the top. The materials lined the pores of the template, creating the hollow nanostraws. The team then used mechanical polishing and oxygen plasma etching to remove the polycarbonate template, revealing an array of vertical nanostraws, each a few hundred nanometers in diameter. According to Xie, their method can work with templates of various pore sizes or pore densities, or with other plating materials.

Ciro Chiappini, a nanomedicine researcher at Kings College London, says this study is a needed and significant step toward developing affordable nanostraws.

Using a representative platinum nanostraw array, Xie and colleagues demonstrated that they could deliver a fluorescent dye into cultured human cells and extract intracellular materials to examine how the levels of an enzyme changed over time.

The conductivity of the new nanostraws allowed the researchers to open tiny pores in the cell membrane by applying a voltage of only 35 V, a safer range for cells compared with 1020 V needed when using nonconductive nanostraws.

These straws could make cellular treatments such as CAR-T therapy faster, safer, and cheaper, says Nicholas A. Melosh, a materials scientist at Stanford University who has done nanostraw research. Typical immunotherapy delivers therapy to a patients immune cells using viruses, which is costly and carries the risk of dangerous immune responses once the cells are put back into the patient, he says. Nanostraws could potentially deliver the necessary therapies to cells without the need for viruses.

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Electroplating method makes conductive nanostraws for injecting into and sampling from cells - Chemical & Engineering News

Protein-Protected Metal Nanoclusters That Behave Like Natural Enzymes – Advanced Science News




Metal nanoclusters, made up of several to one hundred metal atoms (e.g., Au, Ag, Cu, Pt), are a novel class of intermediate between metal atoms and nanoparticles. As their size (<2 nm) borders on the Fermi wavelength of electrons, metal nanoclusters possess strong photoluminescence in comparison with large metal nanoparticles (>2 nm). This, combined with tunable fluorescence emissions, high photostability, good quantum yields and facile synthesis, make them excellent fluorescent labels for biomedical applications.

However, the reduction of metal ions in liquid solution during synthesis usually causes large nanoparticles rather than small metal nanocluster formation because of their tendency to aggregate. In light of this, proteins whose thiol, amino, and carboxyl groups have a strong affinity for metal atoms are typically used to stabilize metal nanoclusters to protect them from aggregationthese proctected clusters are commonly called protein-protected metal nanoclusters.

Protein-protected metal nanoclusters have excellent biocompatibility and have received considerable attention as a luminescent probe in a number of fields such as biosensing, bioimaging, and imaging-guided therapy. However, apart from unique optical properties, protein-protected metal nanoclusters also possess interesting biological properties such as enzyme-like activity similar to that of natural enzymes; until recently, this has been an overlooked quality that is starting to shine in basic research and practical applications.

Nanozymes is a new termed used to refer to nanomaterials with intrinsic enzyme-like activity. Since professor Yan and coworkers first discovered that nanoparticleswhich are traditionally assumed to be inertpossessed intrinsic enzyme-like activity, a substantial amount of work has focused on further developing and harnessing the advantageous properties of nanozymes, which include high catalytic ability, high stability, and low cost. Nowadays, more than 540 kinds of nanomaterials, which possess intrinsic enzymatic activity, have been reported from 350 laboratories in 30 countries and have been used in biological analysis, environmental treatment, as antibacterial agents, cancer therapy, and antioxidation therapy.

In a recent study published in WIREs Nanomedicine and Nanobiotechnology, Professor Xiyun Yan and Kelong Fan explore the newly developing field of biologically active protein-protected metal nanoclusters, namely those that possess peroxidase, oxidase, and catalase activities, and are consequently used for biological analysis and environmental treatment.

An intriguing example of this is bovine serum albumin-protected gold (Au) nanoclusters, which exhibit peroxidase enzymatic activity to catalyze the oxidation of colored organic substrates, which is currently carried out using natural peroxidases. This method showed an advantage over the natural peroxidase-based methods because bovine serum albumin-protected Au nanoclusters exhibited higher robustness and retained enzymatic activity over a wide range of pH and temperatures. In another example, lysozyme-protected platinum (Pt) nanoclusters exhibit oxidase enzymatic activity which has been applied to the oxidative degradation of pollutants, such as methylene blue in lake water.

The proteins themselves not only provide protection and stabilization during synthesis, but can also provide a myriad of other functions to the nanoclusters. Proteins have been shown to enable in vivo applications because of their enhanced biocompatibility. In fact, a protease-responsive sensor for in vivo disease monitoring was designed by utilizing the peroxidase activity of peptide-protected Au nanoclusters and their ultra-small size dependent tumor accumulation and renal clearance properties.

The sensor was developed using peptides which are the substrates/targets of disease related proteases as protective ligands to synthesis the Au nanoclusters nanozymes, which were then conjugated to a carrier. After reaching the site of disease, the sensor was disassembled in response to the dysregulated protease and the liberated Au nanoclusters were filtered through the kidneys and into urine to produce a rapid and sensitive colorimetric readout of diseases state. By employing different enzymatic substrate as protective ligands for Au nanoclusters, this modular approach could enable the rapid detection of a diverse range of diseases with dysregulated protease activities such as cancer, inflammation, and thrombosis.

These findings have extended the horizon of protein-protected metal nanoclusters properties as well as their application in various fields, says Kelong Fan. Furthermore, in the field of nanozymes, protein-protected metal nanoclusters have emerged as an outstanding new addition. Due to their ultra-small size (<2 nm), they usually have higher catalytic activity, more suitable size for in vivo application, better biocompatibility and photoluminescence in comparison with large size nanozymes. We think that ultra-small nanozymes based on protein-protected MNCs are on the verge of attracting great interest across various disciplines and will stimulate research in the fields of nanotechnology and biology.

Despite the advantages and advancedprogress in the development of protein-protected metal nanoclusters asultra-small nanozymes, there are still some challenges that need to be addressedin future work.

First, most researchers still only rely on bovine serum albumin as both the reducing agent and stabilizer. Since we know that protein-protected metal nanoclusters may retain the bioactivity of the protein ligand, it is necessary to explore methods for synthesizing other new protein-protected metal nanoclusters, which will widen the diagnostic and therapeutic applications of protein-protected metal nanoclusters nanozymes.

Second, there are six types of catalytic reactions in nature: oxidoreductases, transferases, hydrolases, isomerases, ligases, and lyases. Thus far, although many protein-protected metal nanoclusters have demonstrated enzyme activities they all are oxidoreductase-like activities such as peroxidase, oxidase, and catalase. Therefore, there is a ample room to develop other types of nanozymes based on protein-protected metal nanoclusters. In this regard, more understanding of the structures and catalytic mechanisms of protein-protected metal nanoclusters is required in addition to the deeper understanding on natural enzymes themselves.

Third, a considerable number of reports have suggested that ultra-small nanozymes based on protein-protected metal nanoclusters are promising tools for biological analysis. However, little is known about the therapeutic function of these ultra-small clusters in vivo despite their advantages of suitable size and good biocompatibility. It is well known that peroxidase, oxidase, and catalase are main enzymes in biological systems involved in the maintenance of redox homeostasis. Thus, more attention should be paid to the usage of these ultra-small nanozymes based on protein-protected metal nanoclusters as bio-catalysts in various human diseases involved in redox dysregulation such as cancer, inflammation, cardiovascular diseases. It is also possible to employ the products of redox nanozymes to treat other diseases, for example, use the toxic hydroxyl radicals produced by peroxidase nanozymes to treat bacterial infection.

Overall, there is still much room for future research and application of ultra-small nanozymes based on protein-protected metal nanoclusters. It is expected that the enzyme-like activity of protein-protected metal nanoclusters will certainly attract broader interests across various disciplines and stimulate research in the fields of nanotechnology and biology, making these emerging ultra-small nanozymes become novel multifunctional nanomaterials for a number of biomedical applications.

Kindly contributed by the authors.

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Protein-Protected Metal Nanoclusters That Behave Like Natural Enzymes - Advanced Science News