Pancreatic stem cells can regenerate beta cells and respond to glucose

Progenitor cells within human pancreas were stimulated and developed into beta cells, which are responsive to glucose. These significant findings were published in the journal Cell Reports, which paved the way for developing regenerative cell therapies, which is an important breakthrough for type 1 diabetic patients. This addresses a major challenge that blocks the way for discovering a complete cure for type 1 diabetes.

Pancreas harbors 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 were able to identify the exact anatomic location of stem cells. They validated their proliferative ability to transform into beta cells, which were responsive to glucose.

An in-depth study of pancreatic stem cells was used to tap into an endogenous cell supply ‘bank’ of beta cells, which were used for regeneration purposes. In the future, these stem cells could be used for therapeutic applications of people living with type 1 diabetes.. In our previous findings, BMP-7 was used to stimulate growth and induce stem cells to transform into functional islets.

In previous studies, it was reported that bone morphogenetic protein 7 (BMP-7), which is a naturally occurring growth factor, could be used for clinical applications and to stimulate progenitor-like cells within non-endocrine pancreatic tissue of humans.

In a recent study, researchers further demonstrated that stem cells responding to BMP-7 would reside within ductal and glandular network of pancreas. Pancreatic cells are characterized by the expression of PDX1 and ALK3. The protein PDX1 is required for the development of beta cells, whereas ALK3 is a cell surface receptor associated with regeneration of multiple tissues.

With the help of “molecular fishing” techniques, researchers could selectively extract cells that expressed PDX1 and ALK3. These cells were grown in a dish, and they proliferated in the presence 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, insulin-producing cells of pancreas were destroyed by the immune system. Patients had to manage their blood glucose levels 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 they received infusions of donor cells; however, enough cells are not there to treat millions of patients with type 1 diabetes.

Presently, research studies have primarily focused on creating more pancreatic cells, which can be transplanted from sources like 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 of pancreas transplantation or other insulin-producing cells. 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.

 

Risks and benefits of phase I trials in pediatric cancer patients

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 published in a systematic review and meta-analysis in PLOS Medicine. In phase I clinical trials, the safety and dosage of anti-cancer drugs was determined.

According to national and international regulations, limits on permissible risk were determined with respect to minors. Researchers systematically scoured pediatric phase I cancer studies, which were published between 2004 and 2015. They identified 170 studies that included 4,604 patients. They determined objective response rates and graded intensities as follows: 3, 4, or 5 (fatal). These caused adverse reactions 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 solid tumors (3.17, 95% CI 2.62 to 3.72) was significantly greater than that for hematological malignancies (27.90, 95% CI 20.53 to 35.27).

The overall rate of fatal grade 5 adverse events 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 drug-related adverse events per person. The adverse events and response rates were similar to those observed in adults that participated in phase I cancer trials.

This study has following limitations: heterogeneous types of cancer and treatment in included trials, reliance on only published data, and low-quality or incomplete reports of some clinical trial outcomes.

The data was coupled with careful ethical analysis, providing an empirical basis for further discussions on therapeutic status of phase I clinical trials in pediatric cancer patients. They provided evidence for refining risk/benefit in phase I trials and for identifying studies, which present greater challenges that meet standards of acceptable risk in children.

 

Correlation between obesity and gut bacteria

A new link exists between gut bacteria and obesity according to a latest research study conducted at Lund University in Sweden. In this research study, it was found that certain amino acids, which were present in our blood, were associated with both obesity and composition of gut microbiome. The significance of gut bacteria is not completely understood till date.

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 an important role in maintaining the overall health of patients.

Gut microbiota governs the metabolism of humans, and it is linked to obesity, type 2 diabetes, and cardiovascular diseases. Previous studies have reported that the occurrence of different metabolites, i.e. small molecules or metabolic residues, varies in the bloodstream of people with these diseases.

The main aim of this new study was to identify metabolites in blood, which were linked with obesity (high body mass index, BMI). These studies had to determine whether these metabolites would affect the composition of bacterial flora in stool samples.

Researchers analyzed blood plasma and stool samples of 674 participants. They identified 19 different metabolites, which were linked with the BMI of person. There was a strong connection between obesity and following chemical compounds: glutamate and BCAA (branched-chain and aromatic amino acids).

Obesity-related metabolites were strongly linked with four different intestinal bacteria: blautia, dorea and ruminococcus in Lachnospiraceae family, and SHA98. The differences between BMI were largely associated with differences in glutamate levels and BCAA. There were interactions between metabolites and gut bacteria, but these interactions were not dependent on each other.

Glutamate is the strongest risk factor for obesity. This finding was compliant with the findings of previous studies. Moreover, BCAA predicts the onset of type 2 diabetes and cardiovascular diseases in near future.

Future studies have focused on how composition of gut bacteria could be modified, reducing the risk of obesity, metabolic diseases, and cardiovascular diseases. A proper understanding of a healthy normal gut flora is required to determine the factors that affect bacterial composition. Large population studies and intervention studies must be conducted for this purpose.

 

Calcium linked with progression of Parkinson’s disease

Excess calcium levels in brain cells lead to the formation of toxic clusters, which is a major warning sign of Parkinson’s disease. Researchers have found that calcium mediates the interaction between small membranous structures, which are present within nerve endings and are important for signaling neurons in human brain.

Alpha-synuclein is a protein associated with the development of Parkinson’s disease. When calcium or alpha-synuclein is present in excess levels, a chain reaction is triggered and it leads to the death of brain cells.

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

Among several neurodegenerative diseases, Parkinson’s disease is the most common one that is caused under following conditions: naturally occurring proteins transform into wrongly shaped molecules, and they stick with other proteins.

They eventually form a thin structure that resembles a filament, and they are known as amyloid fibrils. Amyloid deposits of aggregated alpha-synuclein, which are also known as Lewy bodies, are warning signs of Parkinson’s disease.

The exact role of alpha-synuclein in the cell has not been understood till date. The exact role and function of alpha-synuclein is not understood till date. Alpha-synuclein is implicated in various processes, which govern smooth flow of chemical signals in human brain and flow of molecules in and out of nerve endings; however, the exact behavior of these molecules remains unclear till date.

The protein alpha-synuclein has a very small structure, and its functional capacity depends on its interaction with other proteins or structures. It is difficult to study these protein structures.

The behavior of alpha-synuclein can be determined within cells with the help of super-resolution microscopy techniques. 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 with synaptic vesicles at multiple points and vesicles could come into contact with each other. This indicates how alpha-synuclein is used to chemically transmit information across nerve cells.

Calcium influences the pathways of alpha-synuclein protein, which interacts with synaptic vesicles. The protein alpha-synuclein acts like a calcium sensor. In the presence of calcium, there is a change in the structure of protein alpha-synuclein and its interaction with environment. This is likely to be very important for the normal functioning of protein alpha-synuclein.

A fine balance exists between calcium and the protein alpha-synuclein in cell. Whenever there is too much of one or the other, the balance would be tipped and aggregation would begin. This leads to the development of Parkinson’s disease.

The imbalance was caused by genetically doubling the amount of alpha-synuclein, which is a protein used for duplication of genes. This is an age-related slowing mechanism involved in the breakdown of excess protein.

By increasing the level of calcium in neurons, the secretion of the protein alpha-synuclein sensitive to Parkinson’s disease can be controlled. Calcium buffering capacity is lacking in these neurons.

By understanding the role of alpha-synuclein in physiological or pathological processes, new treatments for Parkinson’s disease can be developed strategically. Calcium levels were blocked with the development of novel drug candidates, which are used in pathogenesis of heart diseases and they can also combat Parkinson’s disease.

 

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.