Resveratrol Mitigates Bisphenol A-Induced Metabolic Disruptions: Insights from Experimental Studies.

The aim of this study was to investigate the disruptions of metabolic pathways induced by bisphenol A (BPA) and explore the potential therapeutic intervention provided by resveratrol (RSV) in mitigating these disruptions through the modulation of biochemical pathways. Wistar albino rats were divided into three groups: group 1 served as the control, group 2 received 70 mg/Kg of BPA, and group 3 received 70 mg/kg of BPA along with 100 mg/Kg of RSV. After the treatment period, various biomarkers and gene expressions were measured to assess the effects of BPA and the potential protective effects of RSV. The results revealed that BPA exposure significantly increased the serum levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines such as TNF-α and IL-6. Concurrently, BPA exposure led to a reduction in the levels of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as GLUT4 and HDL cholesterol. However, the administration of RSV along with BPA significantly ameliorated these alterations in the biomarker levels induced through BPA exposure. RSV treatment effectively reduced the elevated levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines, while increasing the levels of antioxidant enzymes, GLUT4, and HDL cholesterol. Furthermore, BPA exposure suppressed the mRNA expression of glucokinase (GCK), insulin-like growth factor 1 (IGF-1), and glucose transporter 2 (GLUT2) and up-regulated the mRNA expression of uncoupling protein 2 (UCP2), which are all critical biomarkers involved in glucose metabolism and insulin regulation. In contrast, RSV treatment effectively restored the altered mRNA expressions of these biomarkers, indicating its potential to modulate transcriptional pathways and restore normal metabolic function. In conclusion, the findings of this study strongly suggest that RSV holds promise as a therapeutic intervention for BPA-induced metabolic disorders. By mitigating the disruptions in various metabolic pathways and modulating gene expressions related to glucose metabolism and insulin regulation, RSV shows potential in restoring normal metabolic function and counteracting the adverse effects induced by BPA exposure. However, further research is necessary to fully understand the underlying mechanisms and optimize the dosage and duration of RSV treatment for maximum therapeutic benefits.

Genetic mutations of APOEε4 carriers in cardiovascular patients lead to the development of insulin resistance and risk of Alzheimer's disease.

Type 2 diabetes mellitus and Alzheimer's disease (AD), both are chronic and progressive diseases. Many cardiovascular and genetic risk factors are considered responsible for the development of AD and diabetes mellitus (DM). Genetic risk factor such as apolipoprotein E (APOE) plays a critical role in the progression of AD. Specifically, APOEε4 is genetically the strongest isoform associated with neuronal insulin deficiency, altered lipid homeostasis, and metabolism, decreased glucose uptake, impaired gray matter volume, and cerebrovascular functions. In this article, we have summarized the mechanisms of cardiovascular disturbances associated with AD and DM, impact of amyloid-ß aggregation, and neurofibrillary tangles formation in AD. Moreover, cardiovascular risk factors leading to insulin resistance (IR) and amyloid-ß aggregation are highlighted along with the effects of APOE risk alleles on cerebral, lipid, and cholesterol metabolism leading to CVD-mediated IR. Correspondingly, the contribution of IR, genetic and cardiovascular risk factors in amyloid-ß aggregation, which may lead to the late onset of AD and DM, has been also discussed. In short, IR is related to significantly lower cerebral glucose metabolism, which sequentially forecasts poorer memory performance. Hence, there will be more chances for neural glucose intolerance and impairment of cognitive function in cardiac patients, particularly APOEε4 carriers having IR. Hence, this review provides a better understanding of the corresponding crosstalk among different pathways. This will help to investigate the rational application of preventive measures against IR and cognitive dysfunction, specifically in APOEε4 carriers' cardio-metabolic patients.

Versatile role of sirtuins in metabolic disorders: From modulation of mitochondrial function to therapeutic interventions.

Sirtuins (SIRT1-7) are distinct histone deacetylases (HDACs) whose activity is determined by cellular metabolic status andnicotinamide adenine dinucleotide (NAD+ ) levels. HDACs of class III are the members of the SIRT's protein family. SIRTs are the enzymes that modulate mitochondrial activity and energy metabolism. SIRTs have been linked to a number of clinical and physiological operations, such as energy responses to low-calorie availability, aging, stress resistance, inflammation, and apoptosis. Mammalian SIRT2 orthologs have been identified as SIRT1-7 that are found in several subcellular sections, including the cytoplasm (SIRT1, 2), mitochondrial matrix (SIRT3, 4, 5), and the core (SIRT1, 2, 6, 7). For their deacetylase or ADP-ribosyl transferase action, all SIRTs require NAD+ and are linked to cellular energy levels. Evolutionarily, SIRT1 is related to yeast's SIRT2 as well as received primary attention in the circulatory system. An endogenous protein, SIRT1 is involved in the development of heart failure and plays a key role in cell death and survival. SIRT2 downregulation protects against ischemic-reperfusion damage. Increase in human longevity is caused by an increase in SIRT3 expression. Cardiomyocytes are also protected by SIRT3 from oxidative damage and aging, as well as suppressing cardiac hypertrophy. SIRT4 and SIRT5 perform their roles in the heart. SIRT6 has also been linked to a reduction in heart hypertrophy. SIRT7 is known to be involved in the regulation of stress responses and apoptosis in the heart.

Exposure of Environmental Contaminants and Development of Neurological Disorders.

In this era of technology, neurological disorders are the most prevalent disorders in growing population. Alzheimer's and Parkinson's diseases are the most common neurological disorders which are manifested by any abnormality in the structure and functions of neurons present in brain and spinal cord. Exposure to environmental pollution is a serious issue which is associated with high morbidity and mortality rate in the worldwide. Air pollutants are the major contributors to induce the inflammation in lungs and brain which ultimately impairs the normal functioning of CNS. Air pollution persuades CNS pathology by inducing the oxidative stress, activation of microglial cells, neuroinflammation and alteration in permeability of blood brain barrier. Similarly, exposure of heavy metals also exhibits the major and long-lasting effects on brain and causes cognitive dysfunction. Likewise, pesticides have also major influence on the etiology of neurological disorders. Pesticides such as paraquat and rotenone are involved in the pathogenesis of Parkinson's disease. Treatment strategy for environmental pollutants-induced neurological disorders is a challenging task because conventional therapeutics are effective but do not have optimum therapeutic efficacy against such type of disorders. This article addresses how the environmental pollutants are involved in the pathogenesis of neurological disorders and treatment strategies to reduce the occurrence of neurological disorders.

Therapeutic interventions of remdesivir in diabetic and nondiabetic COVID-19 patients: A prospective observational study conducted on Pakistani population.

We aimed to investigate the interventions of remdesivir in both diabetic and nondiabetic individuals who were suffering from a severe infection of novel coronavirus disease (COVID-19). In this study, we aimed to explore the relationship between therapeutic effectiveness of remdesivir and complications of diabetes mellitus by observing the recovery period among diabetic and nondiabetic patients associated with COVID-19 infection. A total of 850 COVID-19 patients were recruited for this study, out of which 48% were diabetic and 52% were nondiabetics. The results of this study indicated that nondiabetic individuals administered with remdesivir recovered from COVID-19 within 10 days showing a 95% confidence interval (p < 0.01), while the diabetic individuals recovered in 15 days. Nondiabetic patients administered with remdesivir exhibited higher chances of clinical improvement at 15th day than those who were associated with diabetes. Remdesivir administration improved the levels of various biochemical parameters, such as C-reactive protein, lactate dehydrogenase, d-Dimer, and ferritin both in diabetic and nondiabetic patients. However, a significant improvement (p < 0.01) was seen in the level of biochemical parameters among nondiabetic patients as compared to that of diabetic patients administered with remdesivir treatment. In the end, it was concluded that remdesivir could be considered as a possible therapeutic agent in the treatment of COVID-19 both in diabetic and nondiabetic situations. However, diabetic patients showed a delayed recovery as compared with that of nondiabetic patients, in which the recovery rate was high.

The composite alliance of FTO locus with obesity-related genetic variants.

Obesity has become a genuine global pandemic due to lifestyle and environmental modifications, and is associated with chronic lethal comorbidities. Various environmental factors such as lack of physical activity due to modernization and higher intake of energy-rich diets are primary obesogenic factors in pathogenesis of obesity. Genome-wide association study has identified the crucial role of FTO (fat mass and obesity) in human obesity. A bunch of SNPs in the first intron of FTO has been identified and subsequently correlated to body mass index and body composition. Findings of in silico, in vitro, and in vivo studies have manifested the robust role of FTO in regulation of energy expenditure and food consumption. Numerous studies have highlighted the mechanistic pathways behind the concomitant functions of FTO in adipogenesis and body size. Current investigation has also revealed the link of FTO neighbouring genes i.e., RPGRIP1L, IRX3 and IRX5 and epigenetic factors with obesity phenotypes. The motive behind this review is to cite the consequences of FTO on obesity vulnerability.

Prevalence of contamination of aflatoxin M1 in milk: a retrospective analysis of studies conducted in Pakistan.

Aflatoxins, produced by multiple fungal species, are present in several kinds of food items and animal feed. Several studies conducted in Pakistan have reported the presence of aflatoxin M1 (AFM1) in milk. Hence, owing to the public health concern and absence of general statistics regarding the prevalence of AFM1 contamination, current study was aimed to investigate the prevalence of AFM1 in milk in Pakistan. For this study, various databases were searched from 2007 to 2020. A random effect model was applied for analytical purpose and heterogeneity of selected studies was investigated with an I2 index. Comprehensive meta-analysis (version 3) was used for analysis of data. According to the results, prevalence of AFM1 in milk was 84.4% (95% CI 75.0-90.7%). Regarding the heterogeneity based on meta-regression, it has been observed that there was a significant difference between the effect of year of study and sample size with prevalence of AFM1 in animal milk. These results suggest that AFM1 contamination in animal milk is high in Pakistan. Hence, continuous monitoring of AFM1 in animal milk requires utmost attention from the respective food and drug regulatory authorities of Pakistan so that the strict actions and preventive measures should be taken to prevent the prevalence of exposure of AFM1 in animal milk.

Inhibition of Hepatitis B Virus with the Help of CRISPR/Cas9 Technology.

Hepatitis B infection caused by hepatitis B virus (HBV) is a serious health issue worldwide. Existing therapeutic strategies hardly eradicate HBV infections, and they fail to attain complete cure. Advanced treatment strategies are urgently needed to successfully terminate further spread of HBV infection and eliminate hidden reservoirs of virus. Recently, a novel RNA-guided gene editing tool, known as the clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9) system, has been established. It facilitates site-specific mutagenesis and reveals a new way to develop applicable techniques for disease treatment, such as extermination of infectious agents like HBV This study highlights the current developments in CRISPR/Cas9 technology and its importance for target-specific inhibition of HBV genome. Benefits, challenges, feasible solutions, and proposed guidelines for forthcoming study in CRISPR/Cas9 are described to highlight the possible cures of and treatments for chronic HBV infection.

Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes.

Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) is a leading cause of deaths due to metabolic disorders in recent years. Molecular mechanisms involved in the initiation and development of IR and T2DM are multiples. The major factors include mitochondrial dysfunction which may cause incomplete fatty acid oxidation (FAO). Oleic acid upregulates the expression of genes causing FAO by deacetylation of PGC1α by PKA-dependent activation of SIRT1-PGC1α complex. Another potent factor for the development of IR and T2DM is endothelial dysfunction as damaged endothelium causes increased release of inflammatory mediators such as TNF-α, IL-6, IL-1ß, sVCAM, sICAM, E-selectin and other proinflammatory cytokines. While, on the other hand, oleic acid has the ability to regulate E-selectin, and sICAM expression. Rest of the risk factors may include inflammation, ß-cell dysfunction, oxidative stress, hormonal imbalance, apoptosis, and enzyme dysregulation. Here, we have highlighted how oleic acid regulates underlying causatives factors and hence, keeps surpassing effect in prevention and treatment of IR and T2DM. However, the percentage contribution of these factors in combating IR and ultimately averting T2DM is still debatable. Thus, because of its exceptional protective effect, it can be considered as an improved therapeutic agent in prophylaxis and/or treatment of IR and T2DM.

Diabetes-associated infections: development of antimicrobial resistance and possible treatment strategies.

Diabetes mellitus is associated with various types of infections notably skin, mucous membrane, soft tissue, urinary tract, respiratory tract and surgical and/or hospital-associated infections. The reason behind this frequent association with infections is an immunocompromised state of diabetic patient because uncontrolled hyperglycemia impairs overall immunity of diabetic patient via involvement of various mechanistic pathways that lead to the diabetic patient as immunocompromised. There are specific microbes that are associated with each type of infection and their presence indicates specific type of infections. For instance, E. coli and Klebsiella are the most common causative pathogens responsible for the development of urinary tract infections. Diabetic-foot infections commonly occur in diabetic patients. In this article, we have mainly focused on the association of diabetes mellitus with various types of bacterial infections and the pattern of resistance against antimicrobial agents that are frequently used for the treatment of diabetes-associated infections. Moreover, we have also summarized the possible treatment strategies against diabetes-associated infections.

Gut Microbiota and Metabolic Disorders: Advances in Therapeutic Interventions.

Human gut microbiota consist of numerous microorganisms, but the most abundant species are Bacteroides and Firmicutes. Each human possesses a specific gut microbiota, which can be altered by diet, antibiotics, lifestyle, and genetic background. Gut microbiota perform vital functions, but in this article, we aimed to elaborate the effects of modified composition of microbiota on host metabolism. Ligands for G protein coupled receptors (GPCRs) are short-chain fatty acids (SCFAs) located on endocrine glands, epithelial cells, and adipocytes. SCFAs are produced in the distal gut by bacterial fermentation of nondigestible polysaccharides; they induce the various beneficial effects including decrease serum glucose level, insulin resistance, as well as inflammation; and they increase glucagon-like peptide-1 (GLP-1) secretion. Fasting-induced adipose factor (FIAF) is suppressed by gut microbiota and results in the increased storage of fatty acids in the adipose tissues and liver. An increased lipopolysaccharide level due to altered gut microflora cause the initiation of inflammation associated with type 2 diabetes mellitus (T2DM). Intestinal dysbiosis and metabolic endotoxemia are considered key mechanisms that seem to be associated with the development of T2DM and obesity. Therapeutic interventions that can be used for the treatment of diabetes include metformin, dietary modulation, probiotics, prebiotics, fecal microbiota transplantation and bariatric surgery.

Assessment of heavy metals by ICP-OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes.

Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.

Biochemical investigation of rs1801282 variations in PPAR-γ gene and its correlation with risk factors of diabetes mellitus in coronary artery disease.

We aimed to investigate the association of single nucleotide polymorphism of Pro/Ala (rs1801282) in peroxisome proliferator-activated receptor-gamma (PPAR-γ) gene with risk factors of diabetes mellitus (DM) in cardiovascular disease (CVD) patients. We recruited 244 participants from Faisalabad Institute of Cardiology and Department of Cardiology, Sargodha District Head Quarter Teaching Hospital, Pakistan. Out of 244 participants, 144 cases were CVD patients and 100 were healthy controls. CVD patients were further divided into 111 coronary artery disease (CAD) and 33 cardiomyopathy (CMP) patients. Assessment of variant specific polymorphism/mutation of Pro/Pro and Pro/Ala genotypes was done through amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Further, serum biomarkers were measured to investigate the association among risk factors of DM and Pro/Ala polymorphism in PPAR-γ gene. About 31.5% Pro/Ala genotype was found in CVD patients out of which 22.5% were CAD patients and 9% were CMP patients. As a result, obesity, hypertension and smoking (35%, 23%, 21%, respectively) were observed to be the most critical risk factors accompanying Pro/Ala mutation in PPAR-γ particularly in CAD patients as compared to that in CMP patients. A similar pattern of association was observed among the elevated levels of glucose, cholesterol, triglyceride and ALT with Pro/Ala mutation in CAD patients. Further, CAD patients using ACE inhibitors (18%) and ß-blockers (13%) were found to be the carriers of Pro/Ala genotype and also showed significant increase in glucose level. This study suggests that hyperglycaemia in CAD patients particularly obese, smokers and hypertensives having Pro/Ala polymorphism in PPAR-γ gene are at high risk of developing DM as clearly observed by hyperglycaemia in CAD patients.

Review: Importance of vitamin D in cancer management.

Vitamin D is essential element for growth and development of bones. The receptor of the metabolite of vitamin D known as "nuclear calcitriol" have been identified in tissues and is responsible for playing a wide range of biological processes. Calcidiol [25(OH) D3] corresponds to the storage space and the chief flowing metabolite of vitamin D3. Calcitriol 1-α-25-dihydroxycholecalciferol is formed in the kidney. Deficiency of vitamin D and lack of sun exposure has been found to cause unceasing illnesses together with various lethal cancers. At cellular level the mechanism of anticancer action of vitamin D has not been entirely implicated. For the setting off and regulation of particular genes, calcitriol-VDR-RXR complex attach to definite DNA fragments called as vitamin D response elements (VDREs). After binding with VDR, calcitriol performs its function by regulating the function of over and above 60 genes providing direction for antiproliferative, prodifferentiating and antimetastatic effects on cells to result in antiangiogenic property. Vitamin D deficiency is evaluated as level of calcidiol less than 20ng/mL, shortage to the level of 21-29 ng/mL, and adequacy level is 30ng/mL.

Taxifolin prevents postprandial hyperglycemia by regulating the activity of α-amylase: Evidence from an in vivo and in silico studies.

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.

Stem Cell Therapy and Type 1 Diabetes Mellitus: Treatment Strategies and Future Perspectives.

Type 1 diabetes mellitus (T1DM) is classified as an autoimmune disease which progressively results in the depletion of insulin-secreting ß-cells. Consequently, the insulin secretion stops leading to hyperglycemic situations within the body. Under severe conditions, it also causes multi-organ diabetes-associated dysfunctionalities notably hypercoagulability, neuropathy, nephropathy, retinopathy, and sometimes organ failures. The prevalence of this disease has been noticed about 3% that has highlighted the serious concerns for healthcare professionals around the globe. For the treatment of this disease, the cell therapy is considered as an important therapeutic approach for the replacement of damaged ß-cells. However, the development of autoantibodies unfortunately reduces their effectiveness with the passage of time and finally with the recurrence of diabetes mellitus. The development of new techniques for extraction and transplantation of islets failed to support this approach due to the issues related to major surgery and lifelong dependence on immunosuppression. For T1DM, such cells are supposed to produce, store, and supply insulin to maintain glucose homeostasis. The urgent need of much-anticipated substitute for insulin-secreting ß-cells directed the researchers to focus on stem cells (SCs) to produce insulin-secreting ß-cells. For being more specific and targeted therapeutic approaches, SC-based strategies opened up the new horizons to cure T1DM. This cell-based therapy aimed to produce functional insulin-secreting ß-cells to cure diabetes on forever basis. The intrinsic regenerative potential along with immunomodulatory abilities of SCs highlights the therapeutic potential of SC-based strategies. In this article, we have comprehensively highlighted the role of SCs to treat diabetes mellitus.

Biochemical investigation of association of arsenic exposure with risk factors of diabetes mellitus in Pakistani population and its validation in animal model.

Arsenic is one of the naturally occurring heavy metal that has been reported to cause damaging effects on different body organs. This study was aimed to determine the arsenic level in different water sources and investigate the effect of arsenic exposure on risk factors of diabetes mellitus (DM) in human participants and experimental animals. We recruited 150 participants to investigate the arsenic exposure in their urine and from drinking water. We found that males contained significantly higher (P < 0.001) concentrations of urinary arsenic as compared with that of their female counterparts. Similarly, urinary arsenic concentration was high and showed significant association in the age of ≥ 60 years (P < 0.05), illiterate (P < 0.001), smokers (P < 0.0001), and diabetic (P < 0.0001) participants. Moreover, urinary arsenic exposure was also associated with higher levels of fasting (P < 0.001) and random blood glucose (P < 0.001), HbA1c (P < 0.001), AST, ALT, MDA, IL-6, CRP, blood urea nitrogen, and creatinine in arsenic-exposed diabetics as compared with that of unexposed diabetics. Further, we also exposed the white albino rats with arsenic in drinking water for 30 days and their blood glucose was measured at 15th and 30th days of treatment that was significantly higher (P < 0.001) in arsenic-exposed animals as compared with that of unexposed animals. Similarly, arsenic-exposed animals failed to tolerate exogenously administered glucose (P < 0.001) as compared with that of unexposed animals. Likewise, insulin and glutathione concentrations were also significantly decreased (P < 0.001) in arsenic-exposed animals as compared with that of unexposed animals. The alterations in normal values of glucose, insulin, and glutathione exhibited the damaging effects of arsenic exposure in experimental rats. This study showed that arsenic exposed to human beings and animals through drinking water resulted in the disruption of pancreatic ß-cell functioning that provoked the risk factor for development of DM. This study also suggested that long-term arsenic exposure induces hyperglycemia, inflammation, and oxidative stress that may lead to the onset of development of DM.

Tumor Necrosis Factor-Alpha: Role in Development of Insulin Resistance and Pathogenesis of Type 2 Diabetes Mellitus.

Pathogenesis of type 2 diabetes mellitus (T2DM) and development of insulin resistance are characterized by multi-stimuli factors notably glucolipotoxicity, generation of reactive oxygen species (ROS), epigenetic factors, activation of various transcriptional mediated pathways along with the augmented levels of various pro-inflammatory cytokines. Among the various pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) is one the most important pro-inflammatory mediator that is critically involved in the development of insulin resistance and pathogenesis of T2DM. TNF-α is mainly produced in adipocytes and/or peripheral tissues, and induces tissue-specific inflammation through the involvement of generation of ROS and activation of various transcriptional mediated pathways. The raised level of TNF-α induces insulin resistance in adipocytes and peripheral tissues by impairing the insulin signaling through serine phosphorylation that leads to the development of T2DM. Anti-TNF-α treatment strategies have been developed to reduce the incidence of insulin resistance and development of T2DM. In this article, we have briefly described how TNF-α plays crucial role to induce insulin resistance and pathogenesis of T2DM. To block the inflammatory responses by blocking TNF-α and TNF-α signaling may be an effective strategy for the treatment of insulin resistance and T2DM. J. Cell. Biochem. 119: 105-110, 2018. © 2017 Wiley Periodicals, Inc.

Leptin: A new therapeutic target for treatment of diabetes mellitus.

Leptin is an endogenous protein having 167 amino acids and is derived from adipocytes. It has tertiary structure that resembles with that of the pro-inflammatory cytokines family. The fundamental role of leptin is to maintain the energy homeostasis with the aid of its counter hormone called ghrelin, known as the "hunger hormone." Small quantities of leptin are also present in various tissues like ovary, placenta, pituitary gland, mammary gland, skeletal muscle, stomach, and lymphoid tissue. Expression of leptin is strongly associated with various inflammatory responses and immune system, and plays crucial role in the pathophysiology of obesity and development of diabetes mellitus (DM) and insulin resistance. The metabolic action of leptin is equally important as that of insulin in the pathophysiology of obesity and DM. Thereby, this review article tends to discuss the diverse and complicated role of leptin in the pathogenesis of DM. Furthermore, this article will highlight the signifying role of leptin as a therapeutic target by indicating the targeted treatment of DM through the appropriate understanding of advanced therapeutic approaches using leptin as a treatment strategy for DM.

Prevalence of exposure of heavy metals and their impact on health consequences.

Even in the current era of growing technology, the concentration of heavy metals present in drinking water is still not within the recommended limits as set by the regulatory authorities in different countries of the world. Drinking water contaminated with heavy metals namely; arsenic, cadmium, nickel, mercury, chromium, zinc, and lead is becoming a major health concern for public and health care professionals. Occupational exposure to heavy metals is known to occur by the utilization of these metals in various industrial processes and/or contents including color pigments and alloys. However, the predominant source resulting in measurable human exposure to heavy metals is the consumption of contaminated drinking water and the resulting health issues may include cardiovascular disorders, neuronal damage, renal injuries, and risk of cancer and diabetes. The general mechanism involved in heavy metal-induced toxicity is recognized to be the production of reactive oxygen species resulting oxidative damage and health related adverse effects. Thus utilization of heavy metal-contaminated water is resulting in high morbidity and mortality rates all over the world. Thereby, feeling the need to raise the concerns about contribution of different heavy metals in various health related issues, this article has discussed the global contamination of drinking water with heavy metals to assess the health hazards associated with consumption of heavy metal-contaminated water. A relationship between exposure limits and ultimate responses produced as well as the major organs affected have been reviewed. Acute and chronic poisoning symptoms and mechanisms responsible for such toxicities have also been discussed.