Saturday, July 25, 2020

New pancreas from OLD is it like the Alladins New lamps for Old lamps ?

Because human islet transplantation is limited by the scarcity of donors and graft failure within a few years, efforts have recently concentrated on the use of stem cells to replace the deficient -cells. Currently, embryonic stem cells and induced pluripotent stem cells achieve high levels of -cell differentiation, but their clinical use is still hampered by ethical issues and/or the risk of developing tumors after transplantation. Pancreatic epithelial cells (duct, acinar, or-cells) represent an appealing alternative to stem cells because they demonstrate -cell differentiation capacities. Yet translation of such capacity to human cells after significant in vitro expansion has yet to be achieved. Besides providing new-cells, cell therapy also has to address the question on how to protect the transplanted cells from destruction by the immune system via either allo- or autoimmunity. Encouraging developments have been made in encapsulation and immunomodulation techniques, but many challenges still remain.

Friday, July 24, 2020

What if a single injection could lower blood levels of cholesterol and triglycerides — for a lifetime?

What if a single injection could lower blood levels of cholesterol and triglycerides — for a lifetime?

In the first gene-editing experiment of its kind, scientists have disabled two genes in monkeys that raise the risk for heart disease. Humans carry the genes as well, and the experiment has raised hopes that a leading killer may one day be tamed.

“This could be the cure for heart disease,” said Dr. Michael Davidson, director of the Lipid Clinic at the University of Chicago Pritzker School of Medicine, who was not involved in the research.

But it will be years before human trials can begin, and gene-editing technology so far has a mixed tracked record. It is much too early to know whether the strategy will be safe and effective in humans; even the monkeys must be monitored for side effects or other treatment failures for some time to come.

The results were presented on Saturday at the annual meeting of the International Society for Stem Cell Research, this year held virtually with about 3,700 attendees around the world. The scientists are writing up their findings, which have not yet been peer-reviewed or published.

The researchers set out to block two genes: PCSK9, which helps regulate levels of LDL cholesterol; and ANGPTL3, part of the system regulating triglyceride, a type of blood fat. Both genes are active in the liver, which is where cholesterol and triglycerides are produced. People who inherit mutations that destroyed the genes’ function do not get heart disease.

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People with increased blood levels of triglycerides and LDL cholesterol have dramatically greater risks of heart disease, heart attacks and strokes, the leading causes of death in most of the developed world. Drug companies already have developed and are marketing two so-called PCSK9 inhibitors that markedly lower LDL cholesterol, but they are expensive and must be injected every few weeks.

Researchers at Verve Therapeutics, led by Dr. Sekar Kathiresan, the chief executive, decided to edit the genes instead. The medicine they developed consists of two pieces of RNA — a gene editor and a tiny guide that directs the editor to a single sequence of 23 letters of human DNA among the genome’s 3.25 billion so-called base pairs.

The RNA is shrouded in tiny lipid spheres to protect the medicine from being instantly degraded in the blood. The lipid spheres travel directly to the liver where they are ingested by liver cells. The contents of the spheres are released, and once the editor lands on its target, it changes a single letter of the sequence to another — like a pencil erasing one letter and writing in another.

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Not only did the system work in 13 monkeys, the researchers reported, but it appeared that every liver cell was edited. After gene editing, the monkeys’ LDL levels dropped by 59 percent within two weeks. The ANGPTL3 gene editing led to a 64 percent decline in triglyceride levels.

One danger of gene editing is the process may result in modification of DNA that scientists are not expecting. “You will never be able to have no off-target effects,” warned Dr. Deepak Srivastava, president of the Gladstone Institutes in San Francisco.

In treating a condition as common as heart disease, he added, even an uncommon side effect can mean many patients are affected. So far, however, the researchers say that they have not seen any inadvertent editing of other genes.

Another question is how long the effect on cholesterol and triglyceride levels will last, Dr. Davidson said. “We hope it will be one-and-done, but we have to validate that with clinical trials,” he said.

Jennifer Doudna, a biochemist of the University of California, Berkeley, and a discoverer of Crispr, the revolutionary gene editing system, said: “In principle, Verve’s approach could be better because it’s a one-time treatment.”

But it is much too soon to say if it will be safe and long-lasting, she added.

If the strategy does work in humans, its greatest impact may be in poorer countries that cannot afford expensive injections for people at high risk of heart disease, said Dr. Daniel Rader, chairman of the department of genetics at the University of Pennsylvania and a member of Verve’s scientific advisory board.

Dr. Kathiresan, of Verve, noted that half of all first heart attacks end in sudden death, making it imperative to protect those at high risk.

Dr. Kathiresan began the research at the Massachusetts General Hospital and the Broad Institute, where he and his colleagues found a collection of genes that increase risk of heart attack at a relatively young age, as well as eight genes that, when mutated, decrease risk.

Those protective genes, he reasoned, could be targets for gene editing if there were a way to alter them in people. Gene editing is only now succeeding, and so far its successes have been in rare diseases.

Other investigators and companies have tried editing genes in mice to prevent heart disease, with some success, but primates are a much more difficult challenge.

Dr. Kathiresan said that to his knowledge, his study is the first to use the pencil-and-eraser type gene editing in primates for a very common disease. Verve licensed the technology, called base editing, from Beam Therapeutics.

If all goes well, Dr. Kathiresan hopes in a few years to begin treating people who have had heart attacks and still have perilously high cholesterol. For them, the risk of another heart attack is so high that the possible benefit may far outweigh the risks of the treatment.

Heart disease generally occurs only after decades of high cholesterol levels, Dr. Davidson noted. By age 50, people most likely to have a heart attack already have a significant accumulation of plaque in their arteries.

But if the PCSK9 gene could be knocked out in 20-year-olds, he said, “there would be no heart disease in their future.”

Liberal regulatory environments for regenerative medicine.

Liberal regulatory environments for regenerative medicine.

"First they ignore you, then they laugh at you, then they fight you, then you win” 

"And, my friends, in this story you have a history of this entire movement. First they ignore you. Then they ridicule you. And then they attack you and want to burn you. And then they build monuments to you. And that, is what is going to happen to the Amalgamated Clothing Workers of America."

the same thing will happen to my proposal for  embryonic myometrial stem cell transplantation.


India should try and follow JAPAN!

Liberalize Stem cell therapies !


The government of Prime Minister Shinzo Abe decided to establish one of the world’s more liberal regulatory environments for regenerative medicine.

But it isn’t only Japanese companies that are in a rush to commercialize stem-cell treatments. The country is becoming a magnet for scientists and entrepreneurs from around the world who are seeking a rapid route to commercializing products and therapies .

Japan’s attractiveness to regenerative-medicine entrepreneurs is prompting other countries to look closely at its regulatory changes. There is undoubtedly a competition under way, and unless something is done, it risks becoming a race to the bottom.

Supporters of Japan’s laws justify the fast-track approvals system by arguing that more conventional regulations would drive clinics underground, and regulators would constantly have to work to catch up — as is the case for the US Food and Drug Administration. Japan’s solution, they argue, means that companies are compelled to operate in the public eye, which is itself a form of transparency, because clinics are visible and not hidden.

Moreover, the law requires stem cells to be processed in high-quality, certified cell-processing centres, and treatments to pass through an independent ethical-review board — there are 100 of these. An official in Japan’s Ministry of Health, Labour and Welfare told Nature that double-blind clinical trials are expensive, and that there are ethical issues involved in giving placebos to people with illnesses.

It is possible that some of these justifications have a degree of merit, but there’s still no denying that the majority of commercially available stem-cell therapies have not been tested in more rigorous phased clinical trials.


Japan should put the brakes on stem-cell sales
That leads to a second concern. As with all medical therapies, people regard government approval for stem-cell clinics as reassurance that treatments they offer are both safe and viable. Unless people have read the text of the law, they will not know that stem-cell products and therapies have a low barrier to regulatory approval. One doctor told Nature that, from a patient’s perspective, an approval is an approval, and “everything else is just details”.

Japan’s dilemma is a global one. Every government can see a pot of gold at the end of the stem-cell rainbow, but countries know that these riches cannot come at the expense of increased risks to patient safety.

Regulators in the United States, who have also struggled with these issues, are adhering to the international regulatory consensus for medical therapies, and seem to be getting the upper hand in their battles against treatments that have not been rigorously tested.

If we had a way of manufacturing young cartilage for your weight-bearing joints,

If we had a way of manufacturing young cartilage for your weight-bearing joints, your knee and your hip, that would be absolutely fantastic. The number one complaint in an aging population is the pain of osteoarthritis, and it’s really as simple as a tire wearing out on an automobile. The cartilage wears out, you get bone on bone, and that’s very painful. So if we could just put that cartilage back, like putting a new tire on, we would already solve the number one complaint of an aging population. Well, pluripotent stem cells allow us to make young cells of every kind on an industrial scale. And we now know how to make them so that your immune system would not reject them. So that’d be off-the-shelf products for all people. We can envision fixing that problem.

Ready to order red blood cells

Ready to order red blood cells red blood cell production from stem cell

The existing transfusion system is expensive to maintain and vulnerable to potentially major disruptions that could be caused by the emergence of novel pathogens or social upheaval. Historical analysis of emergency responses after major natural or man-made disasters suggests that short-term blood needs in such circumstances are relatively small and can be fulfilled by locally available supplies [5]. Rather, the most threatening scenarios involve long-term disruption of the supply chain caused, for instance, by a major pandemic that would decrease the ability of the population to donate blood for an extended period of time [6]. Generally, supply problems and transient shortages are expected to worsen over the next 20 to 30 years because of current demographic trends in the Western world, with an increasing proportion of older people needing transfusion therapy and much smaller proportion of younger donors

Methods to immortalize hematopoietic cells with erythroid potential have been developed in chicken and mouse over the last 20 years. These extensive studies have shown that immortalization of erythroblasts can be achieved by manipulating the expression of transcription factors, tumor suppressors, and nuclear receptors. In addition to the factors mentioned above, vErb-a (THRA), v-Erb-b, and Raf, as well as several other genes, have been shown to have the potential to contribute to immortalization of erythroid precursors [32–36]. Some of the cell lines created with these factors have retained the capacity to differentiate and enucleate. These animal studies provide a strong theoretical basis for the engineering of human erythroid cell lines that could be developed into highly scalable precursors for cRBC production. Importantly, this approach might be safe because cRBCs are not oncogenic since they are enucleated and remain fully functional after irradiation. The use of transformed cells to produce cRBCs is therefore not a safety issue since contaminating precursors could be eliminated. However, whether fully functional cRBCs could be derived in large quantities from a transformed cell line remains to be demonstrated. Hiroyama and colleagues have established a method to derive an immortalized hematopoietic line from mouse embryonic stem (ES) cells without the use of transgenic oncogenes by simply growing ES cells in the presence of stroma and hematopoietic cytokines [37, 38]. Three of the cell lines produced retained the capacity to form enucleated RBCs upon induction of differentiation [37, 38].

Thursday, July 23, 2020

My eyes well up intears when I look at this picture of my Almamater. Osmania General Hospital.


 Hagia sophia the Building  presently a museum and  now going to be back  o being a mosque was built in 537 







Osmania general Hospital was built in 1910  
see the difference in maintenance and the dilapidated state.
 We all are in some way responsible for not bothering about our heritage .
 let us all cry for it's restoration  and  take it up  on a war footing in spite of Covid 19 

Tuesday, July 21, 2020

What's Going Wrong? The enforcement of the PCPNDT Act, 2003

What's Going Wrong? The enforcement of the PCPNDT Act, 2003, which prohibits sex determination tests on the foetus (leading to abortion in many cases if it is found to be a female), has been far from satisfactory. The main reasons for this have been:

 1. poor supervision of genetic and ultrasound clinics 
2. unethical and illegal practices by concerned doctors/ radiologists rampant misuse of technology 
3. fast increase in the number of ultrasound clinics over the 
4. years poor implementation of the PCPNDT Act
5. failure of genetics centres to generate any records of 
6. illegal sex determination: there are no complainants and no evidence. Unfortunately, like many other acts, this act also faces implementation problems, 
7. no effective monitoring mechanism
8. no proper knowledge of the law and procedures
 8. no standardisation in practices, record keeping, etc. 
9. problems of under-reporting and false reporting 
10. problems of under-reporting and false reporting
11. failure to report critical records, as a result of which no proofs/evidence is available to authorities to take action