Monday, 22 October 2018

Injectable Gel May Deliver Islet Cells for Type 1 Diabetes: Study

IIT-Guwahati researchers developed an injectable gel using silk proteins to deliver insulin-producing cells needed to address type-1 diabetes.

By Ratneshwar Thakur Published in India Science Wire

(Left to Right) Dr. Biman B. Mandal And Dr. Manishekhar Kumar

Researchers at the Indian Institute of Technology, Guwahati have developed an injectable gel using silk proteins to deliver insulin-producing cells needed to address type1 diabetes.
The gel has been tested in rats. Normally islets in the pancreas are surrounded by the extracellular matrix which provides structural and biochemical support to cells. The components of this matrix bind to transmembrane proteins on the islet surface to facilitate cell to cell connection, proliferation and insulin secretion.
Previous studies had suggested hydrogels have potential to deliver islets as they contain high water content and mimic hydrophilic content of extracellular matrix. However, use of harsh chemicals in making gels makes them unsuitable to deliver cells or bioactive molecules.
To address this problem, researchers used mixture of two silk proteins (mulberry Bombyx mori and non-mulberry Antheraea assama) which leads to self-gelation. Insulin-producing islet cells were harvested from rats and encapsulated in the hydrogel. The hydrogel was loaded with immunosuppressive drugs to prevent immune rejection. It was then injected under the skin of rats.
“The islet delivery matrix could be easily injected in a minimally invasive manner while maintaining islet cell viability and glucose-responsive insulin production at the transplantation site. The hydrogel could be highly affordable as raw materials for making the hydrogel are abundantly available,” said Dr. Biman B. Mandal, who led the research.
The development, he said, is promising as it may help type 1 diabetes patients to get rid of frequent insulin injections in future.
The research team included Manishekhar Kumar, Prerak Gupta, Sohenii Bhattacharjee and Biman B. Mandal (IIT- Guwahati); AND Samit K. Nandi (West Bengal University of Animal and Fishery Sciences, Kolkata). The study results have been published in journal Biomaterials.

Journal Reference:

Friday, 19 October 2018

This Gel Can Protect Farmers From Toxic Pesticides

Indian farmers usually do not wear any protective gear while spraying chemicals in farms. This exposes them to harmful toxins contained in pesticides, causing severe health impacts and even death in extreme cases. Indian scientists now develop a protective gel to address this problem. 

By Dinesh C Sharma Published in India Science Wire
(Members of the research team at InStem, Bangalore)

Indian farmers usually do not wear any protective gear while spraying chemicals in fields. This exposes them to harmful toxics contained in pesticides, causing severe health impacts and even death in extreme cases. Indian scientists have now developed a protective gel to address this problem.

The gel can be applied on skin and can break down toxic chemicals in pesticides, insecticides and fungicides including the most hazardous and widely used organo phosphorous compounds. The gel deactivates these chemicals, preventing them from going deep into the skin and organs like the brain and the lungs. It has been found to be effective in tests done in rats and researchers hope to soon test it in humans.

Exposure to chemicals contained in pesticides interferes with an enzyme called acetylcholinesterase (AChE) which is present in the nervous system and is critical for neuromuscular functions. When its functioning is disrupted by chemical pesticides entering the body through the skin, it can cause neurotoxicity, cognitive dysfunction and even death in severe cases. 

When the gel was applied on rats and they were exposed to a lethal dose of pesticide MPT, it did not lead to any change in their AChE level, showing it could prevent penetration of the pesticide into the skin.

The gel, named poly-Oxime, has been prepared by researchers at the Institute for Stem Cell Science and Regenerative Medicine (InStem), Bangalore from a nucleophilic polymer. In lab studies, rats treated with poly-Oxime gel survived pesticide treatment, whereas rats with no gel or sham gel showed symptoms of poisoning or died. The results of the study were reported in journal Science Advances on Thursday.

The gel does not act like a physical barrier, but it acts like a catalyst to deactivate organophosphate. An oxime could hydrolyze multiple organophosphate molecules, one after another. And it can do so at temperatures ranging from 20 to 40 degrees, and even after long exposure to ultraviolet light. 

“Our data suggests that a thin layer of poly-Oxime gel can hydrolyze organo-phosphates on the skin; therefore, it can prevent AChE inhibition quantitatively in blood and in all internal organs such as brain, lung, liver, and heart,” the study notes. It has also been found that the catalytic gel can work against a range of commonly used commercial pesticides, insecticides, and fungicides.

“At present, we are conducting extensive safety studies in animals which will be completed in four months. Subsequently we plan a pilot study in humans to demonstrate efficacy of the gel,” Praveen Kumar Vemula, a senior member of the research team, told India Science Wire.

As the next logical step, the research group plans to develop an active mask to deactivate pesticides since the gel now developed does not provide any protection from inhalation of pesticide vapours, according to Vemula.

In order to understand the problem of toxicity caused by pesticides, researchers interacted with several farmers and their families. While many of them said they experienced pain right after spraying pesticides, they had no access to protective means. Farmers, according to researchers, showed willingness to adopt any low-cost topical methods that can prevent pesticide exposure.

The research team included Ketan Thorat, Subhashini Pandey, Sandeep Chandrashekharappa, Nikitha Vavilthota, Ankita A. Hiwale, Purna Shah, Sneha Sreekumar, Shubhangi Upadhyay, Tenzin Phuntsok, Manohar Mahato, Kiran K. Mudnakudu-Nagaraju, Omprakash Sunnapu and Praveen K. Vemula.

Tuesday, 16 October 2018

Scientists Find Why Long Chain Lipids Accumulate Inside Brain In PHARC Disorder

Study will help to better understand the pathology of PHARC and it might enable development of much-needed biomarkers, very long chain lipids, for better diagnostics.

(Research team at IISER Pune)

PHARC is a rare genetic human neurological disorder caused by mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. 

Recent studies have shown that mice without ABHD12, murine model of PHARC, show increased concentrations of lyso-phosphatidylserine (lyso-PS) lipids in brains. Now Indian researchers, using mice model, have found the biochemical explanation for such very long chain lipids accumulation in the brain.

Dr. Siddhesh S. Kamat’s team at Indian Institute of Science Education and Research (IISER), Pune - have shown that the enzyme ABHD12 has a strong substrate preference for very long chain lipids which contains ≥ C22 atoms. 

Researchers found the location of this enzyme (ABHD12) in the membrane of the endoplasmic reticulum, a cellular compartment, where virtually, all of the very long chain lipids are biosynthesized. The results of this study were published in ‘The Journal of Biological Chemistry.’

“We first chemically synthesized a library of lipid substrates ranging from fatty acids C10 – C24 with different degrees of un-saturations. Next, we performed enzyme kinetics studies for this lipid library against recombinant human, and endogenous mouse brain ABHD12, and found in both cases that there is a preference for very long chain lipids,” said  Dr. Siddhesh S. Kamat.

“Our study will help to better understand the pathology of PHARC and it might enable development of much-needed biomarkers (very long chain lipids) for better diagnostics for this condition,” he added.

“This work is a classic illustration of the value of a biochemical approach in understanding what a clinically important protein actually does in cells. This biochemical characterization reveals a very broad substrate choice for this important protein, and also explains how cells can maintain an appropriate balance of long-chain lipid substrates. This can now be used to identify activators or inhibitors of this enzyme,” commented Dr. Sunil Laxman from InStem, Bangalore, who was not associated with this study.

The research team included Alaumy Joshi, Minhaj Shaikh, Shubham Singh, Abinaya Rajendran, Amol Mhetre and Siddhesh S. Kamat from IISER Pune. This study was supported by Wellcome Trust DBT India Alliance and DST-FIST infrastructure development grant.

Journal Reference:

Monday, 1 October 2018

Scientists Open New Avenue To Study Head Muscle Dystrophy

The study, done in mice and human stem cells, may help in future to test drugs developed for treating muscular dystrophies involving head muscles.

                                                     Dr. Ramkumar Sambasivan with his research team at inSTEM

Indian researchers have identified the mechanism by which muscles above the neck, known as head muscles, are formed during development of the embryo in the womb.

The study, done in mice and human stem cells, may help in future to test drugs developed for treating muscular dystrophies involving head muscles.

Till now scientists had only known about the way muscles below the neck develop in the embryo. The new study has found that the process is different for the development of head muscles. It was observed that formation of head muscles was triggered by inhibition of two pathways called Wnt/beta-catenin and Nodal pathways, while muscles below neck require switching on of two different pathways (Wnt and Fgf).

“We found that muscles in the head, such as jaw and facial muscles, have fundamentally different developmental program when compared to that of muscles below neck. We have shown this by mutating two genes in mice embryos,” explained Dr. Ramkumar Sambasivan, study leader and Scientist at the Institute for Stem Cell Biology and Regenerative Medicine (InStem), Bangalore.

“We observed that in the mutant mice embryos, muscle development below neck fails completely. The head muscle development, however, surprisingly, appeared completely normal. These findings provided evidence that the two muscle groups have distinct paths of development,” he added. 

“The study has traced an evolutionary process that allowed emergence of head in vertebrates and identifies mechanistic cues that might be involved in the process. This information can be used to streamline therapy for muscular disorders affecting distinct parts of the body, rather than a ‘one therapy fits all muscles’ approach,” commented Dr. Suchitra Gopinath of Translational Health Science and Technology Institute (THSTI), Faridabad, who was not part of this study.

Sam J. Mathew, Assistant Professor at Regional Centre for Biotechnology (RCB), Faridabad, said, “This work raises interesting possibilities to find new treatment strategies for patients who have weakness and dysfunction of the head muscles.”

The research team included Nitya Nandkishore (InStem and SASTRA University, Thanjavur), Bhakti Vyas (InStem and Manipal Academy of Higher Education, Manipal), Alok Javali (InStem and NCBS), Subho Ghosh and Dr. Sambasivan (InStem). 

The results have been published in journal DevelopmentThe study was supported by Department of Biotechnology.

Journal Reference: