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Pancreatic stem cells can regenerate beta cells and respond to glucose

Within the human pancreas, scientists stimulated progenitor cells and developed them into beta cells that were responsive to glucose. These findings were published in the journal Cell Reports, which paved the way for developing novel cell therapies, which is an important breakthrough for type 1 diabetic patients. This addresses a major obstacle that blocks the way for discovering a complete cure for type 1 diabetes.

Pancreas contains progenitor cells and has the potential of regenerating islets. This hypothesis has been established since many decades, but it has not been proven conclusively. Scientists identified the exact location of stem cells anatomically. They validated their proliferative ability to transform into beta cells, which were responsive to glucose.

A detailed study of stem cells was conducted in the human pancreas, and the results were used to tap into the cell supply ‘bank’ of beta cells. These events occurred endogenously and were used for regeneration purposes. In the years to come, these stem cells could be used for therapeutic applications of type 1 diabetic patients..

In earlier studies, it was found that the bone morphogenetic protein 7 (BMP-7) could be used for clinical applications and to stimulate cells that resemble progenitors. These cells occur within the non-endocrine sections of the human pancreatic tissue. In previous studies, it was reported that BMP-7 is used to stimulate growth and to induce the transformation of stem cells into functional islets.

In a recent study, researchers further demonstrated that stem cells responding to BMP-7 reside within the network of ducts and glands of the human pancreas. Moreover, the expression of PDX1 and ALK3 is used to characterize these cells of the human pancreas. The protein PDX1 is required for the development of beta cells, whereas ALK3 is a receptor of cell surfaces and is used to regenerate several tissues.

With the help of “molecular fishing” techniques, researchers could selectively extract cells that expressed PDX1 and ALK3. A petri-dish was used to grow the cell culture, and they proliferated due to the expression of BMP-7. These cells were later differentiated into beta cells. The combined results of this study were used to develop regenerative cell therapies for both type 1 and type 2 diabetes patients.

In patients with type 1 diabetes, the cells that produce insulin in the pancreas are attacked and sabotaged by the immune system. Patients had to control their glucose levels in the blood with a daily regimen of insulin therapy. In patients with type 2 diabetes, insulin was produced to some extent but beta cells became dysfunctional over a period of time.

With islet transplantation, some type 1 diabetes patients could live without insulin injections. This is because donor cells were infused into these patients; however, enough cells are not there to treat several patients with type 1 diabetes.

Presently, research studies have primarily focused on synthesizing many pancreatic cells, which can be transplanted from embryonic (hESc), pluripotent (hPSc) and adult stem cells, and porcine (pig) islets. It would be better to regenerate insulin-producing cells in patients, which prevents the need to completely transplant donor tissue and eliminate roadblocks to other immune-related disorders.

Regenerative medicine strategies must be developed to restore insulin production in native pancreas. This would replace the need for pancreas transplantation or other cells that produce insulin. In patients with type 1 diabetes, autoimmunity abrogation must be stopped in order to prevent the destruction of immune system and newly produced insulin cells. For this purpose, efforts were made to converge immune tolerance induction that did not require anti-rejection drugs for a long period of time.

 

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The risks and advantages of phase I clinical trial in kids with cancer

On an average, one out of ten children with pediatric phase I cancer improve after being treated for the illness. But one out of fifty children succumb to drug-related complications. This was mentioned in a meta-analysis review published in PLOS Medicine. In phase I clinical trials, researchers determined how safe was the prescribed dosage of drugs used to fight cancer.

According to the guidelines of regulatory authorities in the US, limits on permissible risk were determined with respect to minors. Researchers systematically scoured the phase I clinical trials of pediatric patients, which were published from 2004 to 2015. They found that there were 170 studies related to pediatric cancer and they included a total of 4,604 patients. They objectively determined the rate of response by pediatric patients, and they graded their intensities as follows: 3, 4, or 5 (fatal). These events had led to an adverse reaction of drugs.

Among all clinical trials, the overall response rate was 10.29% (95% CI 8.33 to 12.25). The overall response rate for tumors in the solid state (3.17, 95% CI 2.62 to 3.72) was significantly greater than that for malignancies that occurred hematologically (27.90, 95% CI 20.53 to 35.27).

The overall rate of  adverse events of the grade 5 type was 2.09% (95% CI 1.45 to 2.72). An average response rate of 1.32 was reported for grades 3 and 4, which were adverse events related to drugs administered to each person. The response rates and adverse events were similar to those observed in adults that participated in the phase I clinical trials of cancer patients.

This study has following limitations: we evaluated cancers of the heterogeneous type and investigated the treatment provided in the included clinical trials; we relied on only published data. We also included the outcomes of clinical trials that were of low-quality or had incomplete reports.

The data was carefully combined with the findings of ethical analysis, providing an empirical platform for further investigation on the therapeutic value of phase 1 clinical trials in pediatric cancer patients. They provided evidences for improving the risk/advantages of phase I clinical trials and for identifying studies, which impose greater challenges for complying with the  standards of tolerable risk in children.

 

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A correlation between obesity and gut bacteria

According to a latest research study conducted at Sweden’s Lund University, there exists a connection between obesity and the bacteria found in the gut. The researchers found that specific amino acids, which were present in the human blood, were associated with obesity and the composition of gut bacteria. However, researchers have not yet been able to completely decipher the functions of gut bacteria in the human body.

Many research studies have been conducted on animals, but the findings of these studies may not be applicable to human beings. Gut flora of a healthy person may not necessarily be compatible with another person.Several research studies have reported that gut microbiota plays a significant role in maintaining the overall health of humans.

Gut microbiota governs the metabolism of humans, and it is associated with obesity,  diabetes mellitus, and cardiovascular diseases. Several researchers have proved that the concentration of small molecules or similar metabolites is different in the bloodstream of people with metabolic diseases.

The main aim of this research study was to determine which metabolites of the human blood are associated with obesity, especially in people with high BMI. These studies had to determine whether the bacterial composition of stool samples would be affected by these metabolites.

Researchers collected samples of plasma and stool from 674 participants. They identified the 19 metabolites that were linked to the BMI of an obese person. There was a strong connection between obesity and the following chemical compounds: glutamate and BCAA (branched-chain and aromatic amino acids).

The metabolites that were strongly linked to obesity were also found to be associated with four species of intestinal bacteria: blautia, dorea and ruminococcus in Lachnospiraceae family, and SHA98. The differences between the BMI of obese participants was largely related to the differences in the concentration of glutamate and BCAA. There were interactions between the gut bacteria and metabolites, but these interactions were not dependent on each other.

Glutamate is the most risky factor that triggers obesity in humans. This finding was compliant with the findings of previous studies. Moreover, BCAA predicts the onset of diabetes mellitus and cardiovascular diseases in near future.

Future studies have focused on how to modify the gut bacteria’s composition as this would minimize the risk of developing obesity, cardiovascular disorders, and metabolic diseases.

We need to have a proper understanding of the healthy flora in the gut of normal humans. This will further help us in determining the factors that affect the composition of gut bacteria. Therefore, population studies and intervention studies must be conducted on a large scale.

 

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Calcium linked with progression of Parkinson’s disease

In the cells of the human brain, toxic clusters may be formed by the excess deposition of calcium. The clusters are a major warning sign of Parkinson’s disease. At the University of Cambridge, researchers have discovered how calcium acts an intermediary between small membranous structures that interact with each other. These structures are present within nerve endings and regulate the signaling of neurons in the human brain.

The researchers found that a protein named alpha-synuclein is strongly related to the development of Parkinson’s disease. When the concentration of calcium or alpha-synuclein becomes abnormal in the human brain, a chain reaction is triggered and many brain cells die immediately.

In the scientific journal Nature, latest research studies present the vivid pathogenesis of Parkinson’s disease. In the UK, one out of every 350 adults  has Parkinson’s disease. As per global estimates, 145,000 are estimated to have developed this disease, which remains incurable till date.

Parkinson’s disease is one of the most common neurodegenerative disease, which is caused under the following conditions: proteins that occur naturally get transformed into wrongly shaped molecules, and they stick with the remaining proteins.

They eventually form a thin structure that resembles a filament, and they are known as amyloid fibrils. These deposits of amyloid are basically aggregated forms of alpha-synuclein. They are also known as Lewy bodies. The appearance of Lewy bodies is considered to be one of the warning signs of Parkinson’s disease.

The exact role and function of alpha-synuclein in brain cells has not been understood till date. Alpha-synuclein is found to be play a pivotal role in various biological processes, ensuring that the chemical signals flow smoothly into the human brain and the molecules move in and out of the nerve endings; however, the exact behavior of these protein remains unclear till date.

The structure of the protein alpha-synuclein is very small, and its functional capacity depends on its interaction with other protein molecules or structures. Therefore, it is very difficult to investigate these protein structures.

The behavior of alpha-synuclein can be determined within brain cells by using the technique of super-resolution microscopy. For this purpose, researchers isolated synaptic vesicles that form a part of nerve cells, which store neurotransmitters and send signals to different nerve cells.

The release of neurotransmitters in neurons depends on the concentration of calcium levels. Calcium levels can increase in nerve cells, such as in neuronal signaling processes.

The protein alpha-synuclein would bind at multiple points of synaptic vesicles, and these vesicles could come into contact with each other. This indicates how alpha-synuclein ensures that information flows across nerve cells through the chemical transmission pathway.

Calcium regulates the pathways of alpha-synuclein protein, which has an interaction with synaptic vesicles. The protein alpha-synuclein acts like a calcium sensor. Owing to calcium, the structure of protein alpha-synuclein and its interaction with environment changes drastically. This seems to be very essential for the normal functioning of the protein alpha-synuclein.

Both calcium and the protein alpha-synuclein seem to  be perfectly balanced in the brain cells. Whenever the concentration of these exceeds normal levels, there is an imbalance and this leads to the process of aggregation. This leads to the development of Parkinson’s disease.

In this study, the researchers created an imbalance by genetically doubling the concentration of alpha-synuclein, which is a protein used for the duplication of genes. This slowing mechanism is related to ageing process, and excess protein molecules undergo a breakdown due to this process.

By increasing calcium levels in neurons, the researchers controlled the secretion of the protein alpha-synuclein. This protein is sensitive to the development of Parkinson’s disease. In these neurons, calcium does not really act as a buffer.

Scientists need to understand what role does alpha-synuclein play in various physiological or pathological processes. This will help them in developing new treatment methods for Parkinson’s disease can be developed strategically. Calcium levels can be blocked with the development of novel drug candidates, which are used in the pathogenesis of heart diseases. Moreover, they can also combat Parkinson’s disease.

 

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The onset of type 1 diabetes may be prevented with existing drug

According to researchers at the University of Colorado, a drug used to treat high blood pressure may also be used as a preventive medication for type 1 diabetes. This study was published in the Journal of Clinical Investigation.  This seems to be an important breakthrough to combat type 1 diabetes. In the clinical investigating laboratory, this discovery was path-breaking on mice and humans with the aid of supercomputers.

In pregnant woman and children, the drug methyldopa was used to treat high blood pressure for the past 50 years. This drug was included in the list of essential drugs at the World Health Organization (WHO).

Many drugs may be used to treat a single condition; however, the path-breaking discovery was completely unrelated to current use of medication. The risk of developing type 1 diabetes increases manifold with the molecule D8, with about 60 percent people with type 1 diabetes being diagnosed with this molecule. Scientists believe that the onset of heart disease could be prevented if the molecule D8 can be blocked specifically.

Every allopathic medication has side-effects. Excessive consumption of acetaminophen can cause damage to liver. Every small molecule approved by FDA was taken into consideration and analyzed with a supercomputer to identify whether the linkage between HLA and DQ8 existed. Each drug exhibited more than thousand orientations. We identified the ones that were associated with DQ8 molecule.

Thousands of drugs were analyzed with a supercomputer. The drug methyldopa was found to block DQ8. Nevertheless, the immune function of remaining cells was not compromised in this case like the way other immunosuppressant drugs. These research studies were conducted over a period of 10 years, but the efficacy was proved in mice and in 20 patients who were diagnosed with type 1 diabetes.

These patients participated in the clinical trial that was conducted at the School of Medicine, University of Colorado. With this discovery, prediction of type 1 diabetes is possible. The ultimate aim of this study was either to delay or to prevent the onset of type 1 diabetes among the people who were at risk of developing diabetes.

The drug used to prevent type 1 diabetes can be administered orally, at least three times a day. The strategy of blocking the expression of a specific molecule can also be used to combat other diseases.This study showed significant improvement in people suffering from diabetes and other autoimmune diseases.

The same approach can also be used to treat other autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis, systemic lupus, etc. To verify the implications of this disease, a larger clinical trial would be conducted at the National Institutes of Health in spring season. A very significant development would be the prevention of type 1 diabetes in people at risk of developing the illness.