Stem Cell Therapy in Diabetic Polyneuropathy: Recent Advancements and Future Directions.

Diabetic polyneuropathy (DPN) is the most frequent, although neglected, complication of long-term diabetes. Nearly 30% of hospitalized and 20% of community-dwelling patients with diabetes suffer from DPN; the incidence rate is approximately 2% annually. To date, there has been no curable therapy for DPN. Under these circumstances, cell therapy may be a vital candidate for the treatment of DPN. The epidemiology, classification, and treatment options for DPN are disclosed in the current review. Cell-based therapies using bone marrow-derived cells, embryonic stem cells, pluripotent stem cells, endothelial progenitor cells, mesenchymal stem cells, or dental pulp stem cells are our primary concern, which may be a useful treatment option to ease or to stop the progression of DPN. The importance of cryotherapies for treating DPN has been observed in several studies. These findings may help for the future researchers to establish more focused, accurate, effective, alternative, and safe therapy to reduce DPN. Cell-based therapy might be a permanent solution in the treatment and management of diabetes-induced neuropathy.

The Role of Mineral Deficiencies in Insulin Resistance and Obesity.

Minerals are critical for maintaining overall health. These tiny chemical compounds are responsible for enzymatic activation, maintaining healthy teeth and bones, regulating energy metabolism, enhancing immunity, and aiding muscle and brain function. However, mineral deficiency in the form of inadequate or under nourished intake affects millions of people throughout the world, with well-documented adverse health consequences of malnutrition. Conversely, mineral deficiency may also be a risk factor for Insulin Resistance (IR) and obesity. This review focuses on another, more "less discussed" form of malnutrition, namely mineral deficiency and its contribution to metabolic disorders. At the cellular level, minerals maintain not only molecular communication but also trigger several key biochemical pathways. Disturbances in these processes due to mineral insufficiency may gradually lead to metabolic disorders such as insulin resistance, pre-diabetes, and central obesity, which might lead to renal failure, cardiac arrest, hepatic carcinoma, and various neurodegenerative diseases. Here we discuss the burden of disease promoted by mineral deficiencies and the medical, social, and economic consequences. Mineral deficiency-mediated IR and obesity have a considerable negative impact on individual well-being, physical consideration, and economic productivity. We discuss possible molecular mechanisms of mineral deficiency that may lead to IR and obesity and suggest strategies to counter these metabolic disorders. To protect mankind from mineral nutrient deficiencies, the key is to take a variety of foods in reasonable quantities, such as organic and pasture-raised eggs, low fat dairy, and grass-fed and finished meats, insecticide, and pesticide-free vegetables and fruits.

Preventive Role of Resveratrol Against Inflammatory Cytokines and Related Diseases.

BACKGROUND: Immunity is the ultimate barrier between foreign stimuli and a host cell. Unwanted immune responses can threaten the host cells and may eventually damage a vital organ. Overproduction of inflammatory cytokines may also lead to autoimmune diseases. Inflammatory cells and pro-inflammatory cytokines can eventually progress to renal, cardiac, brain, hepatic, pancreatic and ocular inflammation that can result in severe damage in the long run. Evidence also suggests that inflammation may lead to atherosclerosis, Alzheimer's, hypertension, stroke, cysts and cancers. METHODS: This study was designed to correlate the possible molecular mechanisms for inflammatory diseases and prevent biochemical changes owing to inflammatory cytokines by using Resveratrol. Therefore, we searched and accumulated very recent literature on inflammatory disorders and Resveratrol. We scoured PubMed, Scopus, Science Direct, PLoS One and Google Scholar to gather papers and related information. RESULTS: Reports show that inflammatory diseases are very complex, as multiple cascade systems are involved; therefore, they are quite difficult to cure. However, our literature search also correlates some possible molecular interactions by which inflammation can be prevented. We noticed that Resveratrol is a potent lead component and has multiple activities against harmful inflammatory cytokines and related microRNA. Our study also suggests that the anti-inflammatory properties of Resveratrol have been highly studied on animal models, cell lines and human subjects and proven to be very effective in reducing inflammatory cell production and pro-inflammatory cytokine accumulation. Our tables and figures also demonstrate recent findings and possible preventive activities to minimize inflammatory diseases. CONCLUSION: This study would outline the role of harmful inflammatory cytokines as well as how they accelerate pathophysiology and progress to an inflammatory disorder. Therefore, this study might show a potential therapeutic value of using Resveratrol by health professionals in preventing inflammatory disorders.

Angiotensin-converting enzyme inhibitor prevents oxidative stress, inflammation, and fibrosis in carbon tetrachloride-treated rat liver.

Hepatic fibrosis is a common feature of chronic liver injury, and the involvement of angiotensin II in such process has been studied earlier. We hypothesized that anti-angiotensin II agents may be effective in preventing hepatic fibrosis. In this study, Long Evans female rats were used and divided into four groups such as Group-I, Control; Group-II, Control + ramipril; Group-III, CCl4; and Group-IV, CCl4 + ramipril. Group II and IV are treated with ramipril for 14 d. At the end of treatment, the livers were removed, and the level of hepatic marker enzymes (aspartate aminotransferase, Alanine aminotransferase, and alkaline phosphatase), nitric oxide, advanced protein oxidation product , catalase activity, and lipid peroxidation were determined. The degree of fibrosis was evaluated through histopathological staining with Sirius red and trichrome milligan staining. Carbon-tetrachloride (CCl4) administration in rats developed hepatic dysfunction and raised the hepatic marker enzymes activities significantly. CCl4 administration in rats also produced oxidative stress, inflammation, and fibrosis in liver. Furthermore, angiotensinogen-inhibitor ramipril normalized the hepatic enzymes activities and improved the antioxidant enzyme catalase activity. Moreover, ramipril treatment ameliorated lipid peroxidation and hepatic inflammation in CCl4-treated rats. Ramipril treatment also significantly reduced hepatic fibrosis in CCl4-administered rats. In conclusion, our investigation suggests that the antifibrotic effect of ramipril may be attributed to inhibition of angiotensin-II mediated oxidative stress and inflammation in liver CCl4-administered rats.

DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart and kidney in two kidney and one clip (2K1C) rats.

BACKGROUND: Hyperglycemia and insulin resistance often develop cardiovascular and nephrological dysfunction in diabetic patients. Sitagliptin is used to treat diabetes and showed potential benefit in lowering increased blood glucose level in diabetes. This investigation reports the effect of sitagliptin treatment on oxidative stress in kidney and heart of 2K1C rats. METHODS: Male Long Evans rats underwent unilateral surgical stenosis of the renal artery [2-kidney-1-clip (2K1C) method]. These animals entered a 4-weeks dosing period with sitagliptin. Blood and urine sampling and organ harvesting were finally performed. Blood plasma, heart, kidney tissues and urine were tested for the assessment of inflammation and oxidative stress in kidney and heart of 2K1C rats after 4 weeks of surgery. RESULTS: 2K1C rats showed cardiac hypertrophy, increased left ventricular wet weight compared to sham which was not significantly altered by sitagliptin treatment. Uric acid and creatinin concentrations were also increased in 2K1C rats. Sitagliptin significantly prevented the elevation of uric acid and creatinin concentration in plasma and urine in this rat model. Oxidative stress markers in plasma such as malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) concentrations were increased in the 2K1C rats as compared to sham-operated animals. Increased concentrations of these oxidative stress markers were also normalized by sitagliptin treatment. 2K1C rats also showed increased level of uric acid and creatinine both in plasma and urine; which are also reduced to normal level in sitagliptin treated rats. Moreover, 2K1C surgery initiated inflammatory cell infiltration, increased MPO activity and fibrosis in both heart and kidneys which were further ameliorated by sitagliptin treatment. CONCLUSION: Our study suggests that sitagliptin treatment in 2K1C rats prevented inflammation and fibrosis of heart and kidney by ameliorating elevated oxidative stress in heart and kidney tissues.

Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4) Treated Rats.

Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (-)-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4) treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA), nitric oxide, advanced protein oxidation products level (APOP), and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level) and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.