Occupational and Environmental Exposure Influences the Inflammatory (Pro-and Anti-) Status in Benign Prostate Hyperplasia and Prostate Carcinoma Patients: A Retrospective Analysis.

Multiple diseases and disorders are connected with occupational and environmental exposure risk. It is also well-established that chemicals and chemical mixtures have an influence on the immune cells of humans. This is an important field of research that has been pursued extensively in relation to autoimmune illnesses, allergy/asthma, and lung cancer, but Prostate Carcinoma has received rare reports. Chronic chemical exposure is known to produce inflammation, which is one of the most prominent characteristics of all malignancies. Changes in the ratio of pro-inflammatory to anti-inflammatory molecules are thought to be a key factor in the emergence of inflammation. Prostate gland cells express the pro-inflammatory cytokine interleukin-18 (IL-18), which is a major facilitator of immunological responses. Conversely, interleukin-10 (IL-10) is an anti-inflammatory cytokine that is linked to immune responses and inhibits the development of an inflammatory environment. Our goal is to investigate the inflammatory status of IL-18 (pro-) and IL-10 (anti-) in a variety of occupationally exposed populations in patients with Benign Prostate Hyperplasia (BPH) and patients with Prostate Carcinoma. The present study was conducted with 664 subjects, comprising 285 Prostate Carcinoma patients, 94 BPH patients and 285 controls. The subjects of BPH and Prostate Carcinoma were screened and confirmed on the basis of Prostate Serum Antigen (PSA) and pathological biopsy. All subjects were categorized as per their occupational exposure into various groups. The pro-inflammatory and anti-inflammatory Interleukins (IL-18 and IL-10) and serum PSA levels were analysed by using corresponding quantitative ELISA kits. The results showed that as compared to control participants, the serum PSA levels were higher in the Prostate Carcinoma and BPH groups. When mean levels of IL-18 were compared between various occupational groups, Tanners (tanning industry), Agriculture, and Ordnance workers had significantly higher levels (P < 0.05) of IL-18 than sedentary workers. The pro-inflammatory cytokine (IL-18) levels were also found to be aggravated in Prostate Carcinoma compared to BPH and controls. According to the findings of the current study, the levels of inflammatory cytokines (IL-18 and IL-10) in various occupational groups of BPH, Prostate Carcinoma, and controls were altered. Long-term occupational exposure may have a negative influence on inflammation levels and the immune system; therefore, preventative measures should be explored for improved health.

Association of Serum Adipsin Level with Insulin Resistance and Inflammatory Markers in Newly Diagnosed Type two Diabetes Mellitus Patients.

Adipsin is an anti-inflammatory adipokines and its altered level was seen in obesity and type II DM. Our study investigated the clinical significance of serum adipsin levels as a risk marker for type 2 diabetes and its relationships with insulin resistance and various adipo-cytokines. The study included 110 treatment-naïve T2DM cases and 100 controls of similar age and gender from northern India. Clinical, biochemical, and anthropometric characteristics were all profiled. Serum adipo-cytokines were measured using ELISA methods. Adipsin was significantly inversely correlated with body mass index (BMI), waist circumference, fasting plasma glucose, glycated haemoglobin (HbA1C), total cholesterol (TC), triglyceride (TG), homeostasis model assessment-estimated insulin resistance (HOMA-IR), tumour necrosis factor- α (TNF-α) and interleulin-6 (IL-6) and positively correlated with high-density lipoprotein cholesterol (HDL-C) and homeostasis model assessment of ß-cell function (HOMA-B) (P < 0.05). T2DM occurrence decreased with increasing concentration of adipsin with an odds ratio (OR) of 0.68 (95% CI = 0.58-0.79), P < 0.001. The area under curve (95% CI) for adipsin was 0.70 (0.63 to 0.76) with P < 0.001. The best cutoff value for adipsin to predict T2DM was < 5.50 µg/ml with 47.27% sensitivity and 82.00% specificity. FPG and WC were both independent predictors of serum adipsin levels. Our findings showed that high adipsin levels reduced the likelihood of T2DM and emerged as a potential risk marker in the prediction of T2DM.

Therapeutic spectrum of piperine for clinical practice: a scoping review.

Translation of traditional knowledge of herbs into a viable product for clinical use is still an uphill task. Piperine, a pungent alkaloid molecule derived from Piper nigrum and Piper longum possesses diverse pharmacological effects. Traditionally, pepper is used for arthritis, bronchitis, gastritis, diarrhea, snake bite, menstrual pain, fever, and bacterial infections, etc. The anti-inflammatory, antioxidant and immunomodulatory actions of piperine are the possible mechanisms behind its therapeutic potential. Various in-silico and experimental studies have shown piperine as a possible promising molecule in coronavirus disease (COVID-19), ebola, and dengue due to its immunomodulatory and antiviral activities. The other important clinical applications of piperine are due to its bio enhancing effect on drugs, by modulating, absorption in the gastrointestinal tract, altering activities of transporters like p-glycoprotein substrates, and modulating drug metabolism by altering the expression of cytochrome P450 or UDP-glucuronosyltransferase enzymes. Piperine attracted clinicians in treating patients with arthritis, metabolic syndrome, diabetes, skin infections, gastric and liver disorders. This review focused on systematic, evidence-based insight into the use of piperine in clinical settings and mechanistic details behind its therapeutic actions. Also, highlights a number of clinical trials of piperine at various stages exploring its clinical application in cancer, neurological, respiratory, and viral disease, etc.

Assesement of serum Sfrp5/Wnt-5a level and its utility in the risk stratification of treatment naïve patients with metabolic syndrome.

Our study focused on investigating the clinical significance of serum Sfrp5/Wnt-5a levels as a risk marker in metabolic syndrome (MetS). The study involved a total of 107 treatment-naive MetS cases and 100 controls with similar age and sex belonging to northern India. The profiling of clinical, biochemical, and anthropometric variables was done. ELISA methods were employed for serum cytokine estimation. Serum Sfrp5 was inversely correlated with BMI, WC, SBP, DBP, FPG, TG, fasting insulin level, and HOMA-IR in both males and females. The best cutoff value for Sfrp5 to predict MetS in males was ≤40.48 ng/ml (sensitivity 53.70% and specificity 90.48%), while in female, it was ≤66.67 ng/ml (sensitivity 98.11% and specificity 34.48%). MetS occurrence decreased with increasing concentration of Sfrp5 with an odds ratio (OR) of 0.95 (95% CI = 0.92-0.98, P < .001) in male and 0.93 (95% CI = 0.91-0.97, P < .001) in female. Quartile analysis revealed that odds of MetS significantly decreased in quartile 4 vs. 1, 0.06 (95% CI = 0.01-0.25), P = .001 and 0.13 (95% CI = 0.04-0.44), P = .001, respectively, in male and female. The inverse association of serum concentration of Sfrp5 with MetS might have a useful addition to the available risk marker as well as a therapeutic target for MetS.

No Association Between a Genetic Variant of FOXO3 and Risk of Type 2 Diabetes Mellitus in the Elderly Population of North India.

Aging can be considered an evolutionary process that is modulated by various genetic and biochemical processes. Therefore the genetic variants may interplay a role in human longevity as well as age related illness. Forkhead Box O (FOXO) gene is one of the major defensive genes that are known for ameliorating lifespan. FOXO proteins act as nuclear transcription factors that facilitate the action of insulin or insulin-like growth factor (IGF-1) in various physiological processes. The rationale of our study is to find out association between genetic variant rs2253310 of FOXO3 and risk of Type 2 Diabetes Mellitus (T2DM) in elderly population. This case control study involved 172 age sex matched elderly subjects while patients were recruited as per IDF criteria. Clinical, biochemical, ELISA methods were employed for assesement of clinical samples while Taqman method was used for genotyping analysis. Our results revealed that there was no significant difference in genotypic and allelic frequencies for the tested SNP (p > 0.05) between elderly T2DM patients and controls. The SNP rs2253310 was not associated with risk of T2DM in any genetic model. Also no association was found among the studied group between FOXO3 variant and HOMA-IR, HOMA-B index and Fasting plasma glucose. Serum level of inflammatory markers like CRP and TNF-α was significantly higher in patients but its not associated with SNP rs2253310. Our study concluded that, this intronic longevity-associated variant rs2253310 in FOXO3 is not associated with type 2 diabetes in geriatric patients of northern India.

Anti-diabetic Effect of Emblica-officinalis (Amla) Against Arsenic Induced Metabolic Disorder in Mice.

Chronic exposure to arsenic through drinking water and occupational exposure has been found to be associated with the diabetic symptoms. Earlier, we reported that arsenic induced enhanced oxidative stress, inflammation, dislipidemia and hepatotoxicity in mice have been protected by treatment with Emblica officinalis (amla). The present study has therefore been focused to investigate the efficacy of amla in mitigation of arsenic induced hyperglycemia in mice. Arsenic exposure (3 mg/kg b.w./day for 30 days) in mice altered glucose homeostasis and significantly decreases hepatic glucose regulatory enzyme, glucokinase (43%), glucose-6 phosphate dehydrogenase (38%), malic enzyme (60%) and significantly increases the level of glucose-6 phosphates (65%), phosphoenolpyruvate carboxykinase (43%), lactate, (59%) Na+ (6.8%) Cl- (10.4%), anion gap (13.9%) and pancreatic (IL-1ß, TNF-α) inflammation markers (52%, 53%) as compared to controls. Arsenic exposure also significantly decreased serum insulin (44%) and c-peptide protein (38%) in mice as compared to controls. Co-administration of arsenic and amla (500 mg/kg b.w./day for 30 days) balanced blood sugar level, hepatic glucose regulatory enzyme (glucokinase, glucose-6 phosphate dehydrogenase, malic enzyme (68%, 37%, 45%) and significantly decreases glucose-6 phosphatase (25%), phosphoenolpyruvate carboxykinase (22%), blood ion concentration and also lactate, Na+, Cl- and anion gap (20%, 4.6%, 6.7%, 5.2%), pancreatic (IL-1ß, TNF-α) inflammation marker (21%, 24%) and significantly increased the serum insulin (57%) and c-peptide protein (31%) as compared to those treated with arsenic alone. Results of the present study suggests that the hypoglycemic and antioxidant property of amla could be responsible for its protective efficacy in arsenic induced hyperglycemia.

Assessment of drug prescribing pattern using world health organization indicators in a tertiary care teaching hospital.

This cross-sectional study was carried out to assess drug prescribing pattern at a tertiary care teaching medical institute. One thousand prescriptions were randomly collected and analyzed using the world health organization prescribing indicators. The average number of drugs per prescription was 2.91. The percentage of drugs prescribed by generic name, from the essential drug list (National) and as fixed dose combinations (FDCs) was 10.05%, 22.57%, and 49.22%, respectively. The total percentage of encounters with antibiotics, injectables, and FDCs was 19.70%, 2.20%, and 73.60%, respectively. The most common group of drug prescribed was gastrointestinal tract drugs (26.38%) followed by Vitamins and Minerals (23.12%), cardiovascular system drugs (11.56%) and antimicrobials (9.63%). The prescribing practices were not appropriate as they consist of polypharmacy, lesser prescription by generic name, and overprescription of FDCs. There is a need for improvement in the standards of prescribing patterns in many aspects.

Determination of Cd, Cr, Pb and Ni contents among Parkinson's disease individuals: a case-control study.

BACKGROUND: Various uses of metals in industries, including the domestic sphere, agriculture, medicine and technology, have led to their wide distribution in the environment. These result in raising concerns over their potential effects on human health and the environment. Because of their high degree of toxicity, Cd, Cr and Pb are some of the priority metals that are of public health significance. The levels of Cd, Cr, Pb and Ni were measured in Parkinson's disease (PD) patients. METHODS: Blood samples were collected from 40 patients and 40 healthy controls, and stored at -80 °C until assayed. Atomic absorption spectrophotometry was used to determine the levels of metals. RESULTS: The level of Pb was significantly decreased in patients than in controls. However, the difference in the level of Ni between patients and controls failed to reach significance. Cr was not detectable in patients, but it was measurable in 12 controls (controls = 0.056-2.397 µg/ml). Similarly, Cd was not detectable in patients, but it was measurable in all the controls (controls = 0.004-1.268 µg/ml). Pb was the only metal that was found in all study participants (PD = 0.012-2.758 µg/ml and controls = 0.779-9.840 µg/ml). Ni could be measured only in six patients and in all the controls (PD = 0.154-0.754 µg/ml and controls = 0.034-1.691 µg/ml). CONCLUSION: Patients exhibited significantly decreased levels of Pb than in controls. However, Cd, Cr and Ni were too low to be measured among the patients. This indicates that these metals might play a probable role in PD.

Diseases and Molecular Diagnostics: A Step Closer to Precision Medicine.

The current advent of molecular technologies together with a multidisciplinary interplay of several fields led to the development of genomics, which concentrates on the detection of pathogenic events at the genome level. The structural and functional genomics approaches have now pinpointed the technical challenge in the exploration of disease-related genes and the recognition of their structural alterations or elucidation of gene function. Various promising technologies and diagnostic applications of structural genomics are currently preparing a large database of disease-genes, genetic alterations etc., by mutation scanning and DNA chip technology. Further the functional genomics also exploring the expression genetics (hybridization-, PCR- and sequence-based technologies), two-hybrid technology, next generation sequencing with Bioinformatics and computational biology. Advances in microarray "chip" technology as microarrays have allowed the parallel analysis of gene expression patterns of thousands of genes simultaneously. Sequence information collected from the genomes of many individuals is leading to the rapid discovery of single nucleotide polymorphisms or SNPs. Further advances of genetic engineering have also revolutionized immunoassay biotechnology via engineering of antibody-encoding genes and the phage display technology. The Biotechnology plays an important role in the development of diagnostic assays in response to an outbreak or critical disease response need. However, there is also need to pinpoint various obstacles and issues related to the commercialization and widespread dispersal of genetic knowledge derived from the exploitation of the biotechnology industry and the development and marketing of diagnostic services. Implementation of genetic criteria for patient selection and individual assessment of the risks and benefits of treatment emerges as a major challenge to the pharmaceutical industry. Thus this field is revolutionizing current era and further it may open new vistas in the field of disease management.

Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis.

BACKGROUND: Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population. MATERIALS AND METHODS: This cross-sectional study carried out in northern part of India. The study subjects of similar ethnicity were recruited according to International Diabetes Federation (IDF) criteria for MS, while chronic PD was diagnosed on the basis of packet depth and clinical attachment level. ELISA method was employed to assess cytokine level. All subjects were divided in four groups Gr A (MS + PD), B (MS), C (PD), and a control Gr D. RESULTS: The serum and salivary tumor necrosis factor alpha (TNF-α) level in Gr A, B, and C was significantly higher than Gr D (P < 0.05). Serum interleukin-10 (IL-10) level in Gr A, B, and C was lower than Gr D (P < 0.05), but this difference was not significant between Gr C and Gr D. Serum IL-10 level in Gr A was significantly lower than Gr C (P < 0.05). Salivary IL-10 level was not significantly altered in any group. CONCLUSIONS: Proinflammatory marker TNF-α has correlation with clinical parameters in patients of MS having PD. The study suggests level of salivary TNF-α may be utilized as a surrogate marker of MS and PD.

Curcuma longa extract reduces inflammatory and oxidative stress biomarkers in osteoarthritis of knee: a four-month, double-blind, randomized, placebo-controlled trial.

BACKGROUND AND PURPOSE: Curcuma longa L. (CL), an Indian herb, has been used to treat many disorders because of its wide spectrum of pharmacological activities. It has been shown to exhibit anti-oxidant and anti-inflammatory properties, and is being used as herbal remedy since ancient times. Osteoarthritis of knee (KOA) is a chronic painful disorder in which prolong use of non-steroidal anti-inflammatory drugs (NSAIDs) or steroids may result into many serious side effects; hence, there is a need to develop herbal drugs, having good analgesia without side effects. Therefore, we planned to evaluate the efficacy of CL in KOA. METHODS: The study was designed as a randomized, double-blind, placebo-controlled trial in patients of KOA. After obtaining ethical clearance and written informed consent, a total of 160 patients of KOA were randomly enrolled into two groups to receive either CL extract or placebo along with the standard drug regimen. The patients were assessed on day 0, day 60, and day 120. On the days of their visit, the clinical prognosis was assessed by visual analog scale (VAS) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis index. On these days, the radiographs were also taken for Kellgren and Lawrence grading and blood samples were collected for assessing the changes in levels of IL-1ß and biomarkers of oxidative stress, such as reactive oxygen species and malondialdehyde (MDA). RESULTS: Over all significant improvement was observed in the patients of CL extract group as compared to placebo group. Clinically, the VAS and WOMAC scores became better, and simultaneously, the levels of biomarkers, viz., IL-1ß, ROS, and MDA, were also significantly (p < 0.05) improved. CONCLUSION: It may be concluded that on chronic administration, CL suppresses inflammation and brings clinical improvement in patients of KOA, which may be observed by decreased level of IL-1ß and VAS/WOMAC scores, respectively. At the same time, CL decreases the oxidative stress also.

Functional genetic variability at promoters of pro-(IL-18) and anti-(IL-10) inflammatory affects their mRNA expression and survival in prostate carcinoma patients: Five year follow-up study.

BACKGROUND: Inflammation is an important hallmark of all cancers. The net inflammatory response is determined by a delicate balance between pro- and anti-inflammatory cytokines, which, in turn, is determined by the genetic make-up. The present study investigates the role of variations in the promoter regions of IL-18 and IL-10 (anti-inflammatory) cytokines on mRNA expressions and survival in prostate cancer (PCa) patients. METHODS: The study was conducted on 584 volunteer males (291 patients of PCa, between 40-80 years of age. Genetic variants were studied by using RFLP and confirmed by probe based method. Expressions of mRNA were evaluated by real-time PCR (Roche light cycler 480). Relative mRNA and fold change gene expressions were analyzed by ([1/2] (ΔCt) ) and (2(-ΔΔCt) ) methods, respectively, and 5 year follow-ups were evaluated by Log-rank (Mantel-Cox) test with Log-rank test for trends. RESULTS: IL-18 mRNA expression was significantly elevated in GG genotypes (at -137) of PCa with relative mRNA expression of 13.95, that is, 8.48 folds higher (P < 0.05) than controls; and showed a significant median survival of 1243 days. The CC genotypes of IL-10 at both loci (-819 T/C and -592C/A) showed 3.63 and 3.52 higher relative mRNA expressions than controls, but poor survival of 984 and 1052 days than TT of 1359 days and AA of 1371 days. CONCLUSIONS: Genetic variants of pro-inflammatory IL-18 which showed higher relative mRNA expressions have better survival. Genetic variants of anti-inflammatory IL-10 with higher relative mRNA expression showed decreased chances of survival.

Genetic variability at promoters of IL-18 (pro-) and IL-10 (anti-) inflammatory gene affects susceptibility and their circulating serum levels: An explorative study of prostate cancer patients in North Indian populations.

Inflammation is an important hallmark of all types of cancers with a well-established role in carcinogenesis. The net inflammatory response is determined by the balance between pro- and anti-inflammatory cytokines, the levels of which may be affected by the genetic make-up. Interleukin (IL)-18, a pro-inflammatory cytokine expressed by various cells including those of the prostate, is a key mediator of anti-cancer immune response. IL-10, an anti-inflammatory cytokine associated with tumour malignancy, causes escape from immune surveillance. This study hypothesizes that genetic variants of IL-18 (-607 C/A and -137 G/T) and IL-10 (-819 C/T and -592 C/A) may influence the circulating levels of these interleukins, thereby generating susceptibility risk to prostate cancer. The study was conducted on 676 subjects (controls and patients of prostate cancer (PCa): 291 each; and 94 patients with benign prostate hypertrophy (BPH)). Genotyping was performed by PCR-RFLP and Real-Time PCR probe-based method. Circulating interleukin levels were obtained by ELISA. Circulating IL-18 levels were significantly elevated in cancer and BPH patients carrying GG genotypes for -137 of IL-18. The trend of circulating IL-18 levels was GG>GC>CC, observed in all groups. The -137 genetic variants of IL-18 significantly associated with PCa risk were GC, CC, and GC+CC, compared to GG (OR: 1.71, 95% CI: 1.20-2.46; OR: 3.35, 95% CI: 2.03-5.53; and OR: 2.05, 95% CI: 1.46-2.87, respectively). A significant association of AA and CA+AA against CC genotype was observed at -607 locus of IL-18 (OR: 0.46, 95%CI: 0.29-0.72; OR: 0.61, 95% CI: 0.41-0.90, respectively). Significantly elevated levels of IL-10 were observed with TT (wild) genotype at -819 of IL-10, compared to the CC (homozygous mutant) genotype in all three groups of subjects. However, no significant association was found between IL-10 promoter genotypes and PCa risk. We conclude that genetic variants of IL-18 and IL-10 promoters influence the circulating levels of these interleukins. Variations at -137 and -607 loci of IL-18 are associated with susceptibility to PCa.

Evaluation of peripheral matrix metalloproteinase-1 in Parkinson's disease: a case-control study.

BACKGROUND: Several types of proteinases are implicated in extracellular matrix (ECM) degradation, but the major enzymes are considered to be matrix metalloproteinases (MMPs). Matrix metalloproteinase-1 (MMP-1) is a major proteinase of the MMP family. MMP-1 is critical for modeling and remodeling of the extracellular matrix. In the present study, we evaluated circulating level of MMP-1 in Parkinson's disease (PD) patients and controls. METHOD: Enzyme linked immunosorbent assay (ELISA) was used to determine the serum level of MMP-1 in Parkinson's patients and matched healthy controls. RESULTS: The mean age of Parkinson's patients (65%) and controls (62.5%) were 55.80 ± 9.69 and 54.05 ± 8.71 years respectively, with similar male/female ratio between patients and controls. The MMP-1 level was (p = 0.005) significantly lower in Parkinson's patients (2380.32 ± 2245.27 pg/ml) as compared to controls (4453.07 ± 3321.01 pg/ml). Poor correlation was found between MMP-1 level and disease duration (r = 0.36, p = 0.02), however it was statistically significant. CONCLUSION: Significantly lower level of serum MMP-1 was found in PD patients in comparison to controls. This difference in MMP-1 level was more prominent in females.

Arsenic-Induced Hepatic Toxicity and Its Attenuation by Fruit Extract of Emblica officinalis (Amla) in Mice.

Arsenic a metalloid and environmental contaminated has been found to be associated with public health problems in the affected areas. It is naturally occurred in groundwater and its accumulation in plant and animals leads to toxicity in several tissues most notably hepatic organ. Arsenic exposures (3 mg/kg body weight/day for 30 days) in mice exhibited increased arsenic and Zn levels in hepatocytes associated with enhanced oxidative stress in hepatocytes while there were no significantly changes were observed in Cu level. An increase in the lipid peroxidation and decrease in the levels of reduced glutathione and activity of superoxide dismutase, catalase, and glutathione peroxidase were observed in arsenic treated mice as compared to controls. Arsenic exposure in mice also caused a significant change in serum biomarkers in the SGOT, SGPT and creatinine as compared to the controls. There were no significant changes in the serum levels of total protein in these mice. Co-administration of arsenic and fruit extract of amla (500 mg/kg body weight/day for 30 days) caused a significant reduction of arsenic transference associated with significantly decreases hepatic arsenic levels and balanced the antioxidant enzyme and levels of serum hepatic enzymes like SGOT and SGPT. The results of the present study clearly demonstrate the antioxidant property of amla that could be responsible for its protective efficacy in arsenic induced hepatic toxicity.

Efficacy of crude extract of Emblica officinalis (amla) in arsenic-induced oxidative damage and apoptosis in splenocytes of mice.

INTRODUCTION: Arsenic, an environmental contaminant naturally occurred in groundwater and has been found to be associated with immune-related health problems in humans. OBJECTIVE: In view of increasing risk of arsenic exposure due to occupational and non-occupational settings, the present study has been focused to investigate the protective efficacy of amla against arsenic-induced spleenomegaly in mice. RESULTS: Arsenic exposures (3 mg/kg body weight p.o for 30 days) in mice caused an increase production of ROS (76%), lipid peroxidation (84%) and decrease in the levels of superoxide dismutase (53%) and catalase (54%) in spleen as compared to controls. Arsenic exposure to mice also caused a significant increase in caspases-3 activity (2.8 fold) and decreases cell viability (44%), mitochondrial membrane potential (47%) linked with apoptosis assessed by the cell cycle analysis (subG1-28.72%) and annexin V/PI binding in spleen as compared to controls. Simultaneous treatment of arsenic and amla (500 mg/kg body weight p.o for 30 days) in mice decreased the levels of lipid peroxidation (33%), ROS production (24%), activity of caspase-3 (1.4 fold), apoptosis (subG1 12.72%) and increased cell viability (63%), levels superoxide dismutase (80%), catalase (77%) and mitochondrial membrane potential (66%) as compared to mice treated with arsenic alone. CONCLUSIONS: Results of the present study indicate that the effect of arsenic is mainly due to the depletion of glutathione in liver associated with enhanced oxidative stress that has been found to be protected following simultaneous treatment of arsenic and amla.

Significance of impaired serum gelatinases activities in metabolic syndrome.

INTRODUCTION: A consortium of metabolic risk factors accelerate the onset of diabetes, heart disease, stroke, and certain cancers. Proteolytic enzymes like matrix metalloproteinases (MMP) are regulated by a group of endogenous proteins called tissue inhibitors of metalloproteinases (TIMP). These TIMPs binds to active and alternate sites of activated MMPs and facilitate regulation. Impaired expression of MMPs may have a significant contribution in the pathogenesis of many tissues-destructive processes like tumor progression and cardiovascular and metabolic disorders. MATERIALS AND METHODS: This case control study lays stress on the possible role of impaired levels of circulating MMP-2 and 9 in metabolic syndrome (MetS). The age, sex-matched 388 subjects with 190 newly diagnosed patients, and 198 healthy controls were recruited. To screen the patients with MetS, biochemical analysis of patients for impaired glucose level, hypertension, body mass index (BMI), and lipid profile was performed. The circulating level of MMP-2 and -9 in serum was analyzed by enzyme-linked immunosorbent assay (ELISA) in all patients and control. RESULTS: All metabolic risk factors were statistically significant (P < 0.01) in patients against control group. The serum MMP-2 and -9 level was significantly higher (P < 0.001) in patients having MetS as compared with control group. CONCLUSIONS: Similar trend was observed in gender wise analysis of serum MMP level. Higher MMP level alteration observed in male patients as compared with female patients.

Immunomodulatory role of Emblica officinalis in arsenic induced oxidative damage and apoptosis in thymocytes of mice.

BACKGROUND: Arsenic is widely distributed in the environment and has been found to be associated with the various health related problems including skin lesions, cancer, cardiovascular and immunological disorders. The fruit extract of Emblica officinalis (amla) has been shown to have anti-oxidative and immunomodulatory properties. In view of increasing health risk of arsenic, the present study has been carried out to investigate the protective effect of amla against arsenic induced oxidative stress and apoptosis in thymocytes of mice. METHODS: Mice were exposed to arsenic (sodium arsenite 3 mg/kg body weight p.o.) or amla (500 mg/kg body weight p.o.) or simultaneously with arsenic and amla for 28 days. The antioxidant enzyme assays were carried out using spectrophotometer and generation of ROS, apoptotic parameters, change in cell cycle were carried out using flow cytometer following the standard protocols. RESULTS: Arsenic exposure to mice caused a significant increase in the lipid peroxidation, ROS production and decreased cell viability, levels of reduced glutathione, the activity of superoxide dismutase, catalase, cytochrome c oxidase and mitochondrial membrane potential in the thymus as compared to controls. Increased activity of caspase-3 linked with apoptosis assessed by the cell cycle analysis and annexin V/PI binding was also observed in mice exposed to arsenic as compared to controls. Co-treatment with arsenic and amla decreased the levels of lipid peroxidation, ROS production, activity of caspase-3, apoptosis and increased cell viability, levels of antioxidant enzymes, cytochrome c oxidase and mitochondrial membrane potential as compared to mice treated with arsenic alone. CONCLUSIONS: The results of the present study exhibits that arsenic induced oxidative stress and apoptosis significantly protected by co-treatment with amla that could be due to its strong antioxidant potential.

Tobacco exposure may enhance inflammation in prostate carcinoma patients: an explorative study in north Indian population.

Prostate cancer is responsible for major deaths globally after lung cancer. However, etiology of prostate cancer is still unknown. Individual risk and incidence of prostate cancer may result from the interaction of genetic susceptibility with exposure to environmental factors such as infectious agents, tobacco, occupational exposure, dietary carcinogens, and/or hormonal imbalances leading to injury of the prostate and to the development of chronic inflammation. About 30% of all human cancers are caused by tobacco smoking and inhaled pollutants. Inflammation is now regarded as an important hallmark of cancer. The present study has been aimed to explore the pro-inflammatory levels in prostate carcinoma patients by examining the serum levels of novel cytokine interleukin-18 (IL-18) expression in tobacco exposed population. A total of 578 (n = 284 biopsy proven prostate cancer patients, n = 294 controls with and without tobacco exposed population) were recruited. Serum IL-18 (Interleukin-18) level was done by ELISA. The IL-18 levels between cancer patients and controls within same mode tobacco exposure as tobacco smoking (overall) showed significant difference (P < 0.0001) and further we compared within stratified group, it significantly differ (P < 0.0001) in bidi and cigarette smoking than control non users. Furthermore, IL-18 levels in tobacco chewers (overall) with gutkha and khaini chewers showed significant difference (P < 0.01) than controls non users. Moreover, the IL-18 levels between cancer patients and controls with in of combined mode chewers smokers and alcohol (CSA), smokers with alcohol showed significant difference (P < 0.01) than controls. The IL-18 levels also differed significantly (P < 0.05) with smokers and chewers in higher stages of III and IV, and showed non significant with in lower stages. Tobacco exposure enhance the inflammation in prostate carcinoma patients in stratified group as it have been represented as a risk factors in various cancers, but this study provide further its role that seems to influence inflammation especially in prostate carcinoma.

Evaluation of the Effect of FOXO3 rs13217795 Genotype and Minor Allele (C) on Clinical Chemistry and Genetic Risk of Diabetes Among the Elderly Individuals from Northern India.

The forkhead box O family (FOXO) is expressed ubiquitously in a spatio-temporal manner and plays a key role in cellular metabolism, senescence, and aging. Genetic mutations in FOXO lead to metabolic diseases and cancer, and affect the longevity of individuals. Our study investigated how the genetic risk of type 2 diabetes mellitus (T2DM) altered due to an intronic variant rs13217795 of the longevity-associated FOXO3 gene in the geriatric population of North India. Genotypic characteristics of rs13217795 were determined among 347 age sex-matched (177 diabetic cases, 170 healthy controls) elderly individuals by TaqMan SNP assays after clinical assessment. Clinical chemistry and circulating cytokines level were assessed by biochemical and immunoassays. Genotype frequencies were not significantly (p = 0.526) different between cases and controls. The minor allele (C) frequency in diabetic cases and controls was 0.47 and 0.49, respectively (OR = 0.94, 95% CI = 0.69-1.26, p > 0.05). The minor allele was associated with lower fasting plasma glucose (FPG), fasting insulin, HOMA-IR, CRP, TNF-α, and IL-6 (p < 0.05). The homozygous minor allele carriers showed significantly lower levels of FPG, HOMA-IR, and TNF-α in T2DM patients. The minor allele (C) of intronic polymorphism in FOXO3 (rs13217795: T/C) confers the protective role characterized by its association with a decrease in glycemic and insulin resistance and proinflammatory markers.