miRNA and leptin signaling in metabolic diseases and at extreme environments.

The burden of growing concern about the dysregulation of metabolic processes arises due to complex interplay between environment and nutrition that has great impact on genetics and epigenetics of an individual. Thereby, any abnormality at the level of food intake regulating hormones may contribute to the development of metabolic diseases in any age group due to malnutrition, overweight, changing lifestyle, and exposure to extreme environments such as heat stress (HS), cold stress, or high altitude (HA). Hormones such as leptin, adiponectin, ghrelin, and cholecystokinin regulate appetite and satiety to maintain energy homeostasis. Leptin, an adipokine and a pleiotropic hormone, play major role in regulating the food intake, energy gain and energy expenditure. Using in silico approach, we have identified the major genes (LEP, LEPR, JAK2, STAT3, NPY, POMC, IRS1, SOCS3) that play crucial role in leptin signaling pathway. Further, eight miRNAs (hsa-miR-204-5p, hsa-miR-211-5p, hsa-miR-30, hsa-miR-3163, hsa-miR-33a-3p, hsa-miR-548, hsa-miR-561-3p, hsa-miR-7856-5p) from TargetScan 8.0 database were screened out that commonly target these genes. The role of these miRNAs should be explored as they might play vital role in regulating the appetite, energy metabolism, metabolic diseases (obesity, type 2 diabetes, cardiovascular diseases, inflammation), and to combat extreme environments. The miRNAs regulating leptin signaling and appetite may be useful for developing novel therapeutics for metabolic diseases.

Ionic reverberation modulates the cellular fate of CD8+tissue resident memory T cells (TRMs) in patients with renal cell carcinoma: A novel mechanism.

In metastatic renal cell carcinoma (mRCC), existing treatments including checkpoint inhibitors are failed to cure and/or prevent recurrence of the disease. Therefore, in-depth understanding of tumor tissue resident memory T cells (TRMs) dysfunction are necessitated to enrich efficacy of immunotherapies and increasing disease free survival in treated patients. In patients, we observed dysregulation of K+, Ca2+, Na2+ and Zn2+ ion channels leads to excess infiltration of their respective ions in tumor TRMs, thus ionic gradients are disturbed and cells became hyperpolarized. Moreover, overloaded intramitochondrial calcium caused mitochondrial depolarization and trigger apoptosis of tumor TRMs. Decreased prevalence of activated tumor TRMs reflected our observations. Furthermore, disruptions in ionic concentrations impaired the functional activities and/or suppressed anti-tumor action of circulating and tumor TRMs in RCC. Collectively, these findings revealed novel mechanism behind dysfunctionality of tumor TRMs. Implicating enrichment of activated TRMs within tumor would be beneficial for better management of RCC patients.

Optimal Cut-Off Values for Body Mass Index and Fat Mass Index Based on Age in Physically Active Males Using Receiver Operating Characteristic Curve.

This study aims to redefine obesity cut-off points for body mass index (BMI) and fat mass index (FMI) according to the different age groups of physically active males. Healthy physically active volunteers (N = 1442) aged 18-57 years (y), with a mean BMI = 22.7 ± 2.8 kg/m2, and mean FMI = 4.3 ± 1.7 kg/m2 were recruited from various fitness centers. BMI was calculated and individuals were categorized according to the Asia-Pacific BMI criterion of ≤22.9 kg/m2 and the previous WHO-guided BMI criterion of ≤24.9 kg/m2. FMI was also calculated for the study participants with a cut-off of 6.6 kg/m2. Redefining of BMI and FMI cut-off values was carried out based on different age groups categorized with a difference of 10 y and 5 y using the receiver operating characteristic (ROC) curve and Youden's index. For the entire study population, BMI redefined cut-off points for overweight and obesity were 23.7 kg/m2 and 24.5 kg/m2, respectively, while FMI redefined cut-off points for overweight and obesity were 4.6 kg/m2 and 5.7 kg/m2, respectively. With 10 y of age group difference, a constant BMI and FMI values were observed, while with 5 y of age group difference, a constant increase in the BMI cut-offs was observed as the age group increased, i.e., from 23.3 kg/m2 in 20-24 y to 26.6 kg/m2 in ≥45 y and a similar trend was seen in FMI cut-offs. To conclude, our study suggests that age-dependent BMI and FMI cut-off points may provide appropriate measurements for physically active males as the age group increases.

KCMF1 regulates autophagy and ion channels' function in renal cell carcinoma: a future therapeutic target.

INTRODUCTION: In RCC, systematic procedures such as surgery, chemo-radiation therapy, and application of target-based inhibitors increase the risk of several comorbidities such as chronic kidney disease, hemorrhage, and cardiac arrest that may increase the mortality rate. Even though immune-based checkpoint inhibitor therapies have an overall good response rate, it is restricted to only 30-40% of patients. Hence, an in-depth study of tumor pathophysiology in RCC is needed to identify the new therapeutic target. In RCC, persisted hypoxia is an essential phenomenon for tumor growth and progression. KCMF1 is a newly identified ubiquitin ligase whose domain interacts with destabilized proteins and reprogrammed the ubiquitin coding for lysosome-mediated degradation and autophagy under hypoxic conditions/oxidative stress and maintaining cellular homeostasis. But in RCC, the functional role of KCMF1 remains undefined to date. METHOD: We determined KCMF1 and its associated proteins RAD6 and UBR4 expression and their co-localization using confocal microscopy in tumor and non-tumor tissues samples. Further, immunofluorescence staining was performed to determine autophagy (LC3B, p62), hypoxia-inducible factor (HIF-1A) and ion channel markers (Kv1.3, KCNN4) in RCC patients (n-10). Inductively coupled plasma mass spectrophotometry (ICPMS) was performed to estimate the concentration of potassium (K+), sodium (Na+) and Zinc (zn2+) in tumor and non-tumor cells of RCC patients (n-20). Lastly, images were analyzed using ZEN3.1, and ImageJ software. RESULT AND CONCLUSION: We observed a discrepancy in the formation of ubiquitin ligase, autophagosome via KCMF1, and ionic concentration in tumor cells, which might be one of the possible factors for cancer evolution. KCMF1-associated ubiquitin ligase system could be considered as a novel therapeutic target for RCC in the future.

Insight into the role of myokines and myogenic regulatory factors under hypobaric hypoxia induced skeletal muscle loss.

BACKGROUND: The present study aimed to analyse the role of myokines and the regeneration capacity of skeletal muscle during chronic hypobaric hypoxia (CHH). METHODS: Male Sprague-Dawley rats were exposed to hypobaric hypoxia (HH) for 1d, 3d and 7d. RESULTS: Exposure to HH enhanced the levels of decorin, irisin, IL-6 and IL-15 till 3 days of hypoxia and on 7 day of exposure, no significant changes were observed in relation to control. A significant upregulation in myostatin, activated protein kinase, SMAD3, SMAD4, FOXO-1, MURF-1 expression was observed with prolonged HH exposure as compared to normoxic control. Further, myogenesis-related markers, PAX-7, Cyclin D1 and myogenin were downregulated during CHH exposure in comparison to control. Energy metabolism regulators such as Sirtuin 1, proliferator-activated receptor gamma coactivator-1α and GLUT-4, were also increased on 1-d HH exposure that showed a declining trend on CHH exposure. CONCLUSIONS: These results indicated the impairment in the levels of myokines and myogenesis during prolonged hypoxia. CHH exposure enhanced the levels of myostatin and reduced the regeneration or repair capacity of the skeletal muscles. Myokine levels could be a predictive biomarker for evaluating skeletal muscle performance and loss at high altitudes.

Endogenous dipeptide-carnosine supplementation ameliorates hypobaric hypoxia-induced skeletal muscle loss via attenuating endoplasmic reticulum stress response and maintaining proteostasis.

High altitude is an environmental stress that is accompanied with numerous adverse biological responses, including skeletal muscle weakness and muscle protein loss. Skeletal muscle wasting is an important clinical problem, progressing to critical illness, associated with increased morbidity and mortality. The present study explores the protective efficacy of endogenous dipeptide, carnosine (CAR), supplementation in ameliorating skeletal muscle protein loss under hypobaric hypoxia (HH). Male Sprague-Dawley rats (n = 5) were randomly divided into control group, HH-exposed group (3 days HH exposure equivalent to 7,620 m), and HH-exposed rats supplemented with carnosine (3 days; 150 mg/kg b.w, orally) (HH + CAR). HH-exposed rats supplemented with CAR ameliorated HH-induced oxidative protein damage, lipid peroxidation, and maintained pro-inflammatory cytokines levels. HH-associated muscle protein degradative pathways, including calpain, ubiquitination, endoplasmic reticulum stress, autophagy, and apoptosis were also regulated in carnosine-supplemented rats. Further, the muscle damage marker, the levels of serum creatine phosphokinase were also reduced in HH + CAR co-supplemented rats which proved the protective efficacy of CAR against hypobaric hypoxia-induced muscle protein loss. Altogether, CAR supplementation ameliorated HH-induced skeletal muscle protein loss via performing multifaceted ways, mainly by maintaining redox homeostasis and proteostasis in skeletal muscle.

Multipotent antioxidant and antitoxicant potentiality of an indigenous probiotic Bifidobacterium sp. MKK4.

Probiotic bacteria are now becoming an effective natural medicine for alleviating many non-communicable lifestyle-related diseases. The present study was conducted to evaluate the antioxidant and antitoxicant properties of a foodborne probiotic Bifidobacterium sp. MKK4 and its rice fermented beverage. The extracts of culture broth, whole cells, fermented beverage, and it's heat-inactivated counterparts subjected to in vitro antioxidant/antiradical assays by DPPH, ABTS, and FRAP analysis. Except for heat-inactivated states, all samples exhibited strong antioxidant activity. In the experimental rat model, both Bifidobacterium sp. MKK4 and its rice fermented beverage significantly prevented arsenic toxicity by inducing a higher level of superoxide dismutase (SOD), catalase (CAT), reduced glutathione and preventing lipid peroxidation (LPO) and DNA fragmentation, and transmembrane mitochondrial potential. Besides, the organism supported systematic protection by improving the level of serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase, lactate dehydrogenase, C-reactive protein, urea, creatinine, and uric acid. The inherent antioxidant nature of the isolate can be exploited as an ingredient in functional food and an effective antidote against arsenic toxicity.

Emerging role of MyomiRs as biomarkers and therapeutic targets in skeletal muscle diseases.

Several chronic diseases lead to skeletal muscle loss and a decline in physical performance. MicroRNAs (miRNAs) are small, noncoding RNAs, which have exhibited their role in the development and diseased state of the skeletal muscle. miRNA regulates gene expression by binding to the 3' untranslated region of its target mRNA. Due to the robust stability in biological fluids, miRNAs are ideal candidate as biomarker. These miRNAs provide a novel avenue in strengthening our awareness and knowledge about the factors governing skeletal muscle functions such as development, growth, metabolism, differentiation, and cell proliferation. It also helps in understanding the therapeutic strategies in improving or conserving skeletal muscle health. This review outlines the evidence regarding the present knowledge on the role miRNA as a potential biomarker in skeletal muscle diseases and their exploration might be a unique and potential therapeutic strategy for various skeletal muscle disorders.

Diet and redox state in maintaining skeletal muscle health and performance at high altitude.

High altitude exposure leads to compromised physical performance with considerable weight loss. The major stressor at high altitude is hypobaric hypoxia which leads to disturbance in redox homeostasis. Oxidative stress is a well-known trigger for many high altitude illnesses and regulates several key signaling pathways under stressful conditions. Altered redox homeostasis is considered the prime culprit of high altitude linked skeletal muscle atrophy. Hypobaric hypoxia disturbs redox homeostasis through increased RONS production and compromised antioxidant system. Increased RONS disturbs the cellular homeostasis via multiple ways such as inflammation generation, altered protein anabolic pathways, redox remodeling of RyR1 that contributed to dysregulated calcium homeostasis, enhanced protein degradation pathways via activation calcium-regulated protein, calpain, and apoptosis. Ultimately, all the cellular signaling pathways aggregately result in skeletal muscle atrophy. Dietary supplementation of phytochemicals could become a safe and effective intervention to ameliorate skeletal muscle atrophy and enhance the physical performance of the personnel who are staying at high altitude regions. The present evidence-based review explores few dietary supplementations which regulate several signaling mechanisms and ameliorate hypobaric hypoxia induced muscle atrophy and enhances physical performance. However, a clinical research trial is required to establish proof-of-concept.

Deciphering Biochemical and Molecular Signatures Associated with Obesity in Context of Metabolic Health.

This study aims to identify the clinical and genetic markers related to the two uncommon nutritional statuses-metabolically unhealthy normal-weight (MUNW) and metabolically healthy overweight/obese (MHOW) individuals in the physically active individuals. Physically active male volunteers (n = 120) were recruited, and plasma samples were analyzed for the clinical parameters. Triglycerides, HDL-Cholesterol, LDL-cholesterol, total cholesterol, C-reactive protein, and insulin resistance were considered as markers of metabolic syndrome. The subjects were classified as 'healthy' (0 metabolic abnormalities) or 'unhealthy' (≥1 metabolic abnormalities) in their respective BMI group with a cut-off at 24.9 kg/m2. Analysis of biochemical variables was done using enzyme linked immunosorbent assay (ELISA) kits with further confirmation using western blot analysis. The microarray was conducted, followed by quantitative real-time PCR to identify and analyze differentially expressed genes (DEGs). The MHOW group constituted 12.6%, while the MUNW group constituted 32.4% of the total study population. Pro-inflammatory markers like interleukin-6, tumor necrosis factor (TNF)-α, and ferritin were increased in metabolically unhealthy groups in comparison to metabolically healthy groups. Gene expression profiling of MUNW and MHOW individuals resulted in differential expression of 7470 and 5864 genes, respectively. The gene ontology (GO) biological pathway analysis showed significant enrichment of the 'JAK/STAT signaling pathway' in MUNW and 'The information-processing pathway at the IFN-ß enhancer' pathway in MHOW. The G6PC3 gene has genetically emerged as a new distinct gene showing its involvement in insulin resistance. Biochemical, as well as genetic analysis, revealed that MUNW and MHOW are the transition state between healthy and obese individuals with simply having fewer metabolic abnormalities. Moreover, it is possible that the state of obesity is a biological adaptation to cope up with the unhealthy parameters.

Coronavirus Disease 2019 (COVID-19): Research, Clinical Knowledge, and Preventive Measures.

In early December 2019, a novel coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) commenced in Wuhan, China, and WHO declared the outbreak a pandemic and Public Health Emergency of International Concern. An ample number of clinical trials with multiple drugs is underway to overcome the current perilous condition. Still, the situation is alarming with no therapeutic measure in our hand at present. Keeping the present scenario in mind, this review comprises the research, clinical knowledge, and repurposed herbals with regard to COVID-19. Preventive measures such as yoga, nasal breathing, and herbal administration could also provide protection and beneficial effects against coronavirus. Innumerable clinical trials are ongoing to manage COVID-19 and the drugs were selected on the basis of life cycle of coronavirus. The selection of herbals was done on the basis of the previous reported pharmacological activities and docking study. The results concluded that garlic, liquorice, and Ashwagandha have a potential against SARS-CoV-2, which was further proved via a docking study and their reported biological functions. The very well-known fact "prevention is always better than cure" is applied to overcome with coronavirus infection. It is expected that following the preventive measures could impede or lessen the adverse effect of SARS-CoV-2.

Evaluation of nutrient profile, biochemical composition and anti-gastric ulcer potentialities of khambir, a leavened flat bread.

Khambir is a leavened staple food among the native highlanders of Western Himalaya. It is prepared by sourdough fermentation of wheat flour with yeast (YAK) or buttermilk (BAK). Both types of bread were rich in carbohydrate, protein, dietary fiber, containing less fat and gluten, and enriched with lactic acid, vitamins, and minerals. The in vitro digestibility test showed a slow glucose-controlled release potential of khambir that reflected improved content of rapidly digestible starch, slowly digestible starch, resistant starch, and predicted glycemic index. The changes of crystallinity to amorphous structures of starch, content of protein and fatty acid, and accumulation of 17 major metabolites were evaluated through FTIR and GC-MS. The extracts of khambir alleviated cold-induced gastric ulcers in the animal model as it exhibited histoprotective and anti-inflammatory activities. This study demonstrated that the traditional leavened bread khambir is nutritious and can alleviate gastric lesions related to acute mountain sickness.

Ursolic acid ameliorates hypobaric hypoxia-induced skeletal muscle protein loss via upregulating Akt pathway: An experimental study using rat model.

Hypobaric hypoxic stress leads to oxidative stress, inflammation, and disturbance in protein turnover rate. Aggregately, this imbalance in redox homeostasis is responsible for skeletal muscle protein loss and a decline in physical performance. Hence, an urgent medical need is required to ameliorate skeletal muscle protein loss. The present study investigated the efficacy of ursolic acid (UA), a pentacyclic triterpene acid to ameliorate hypobaric hypoxia (HH)-induced muscle protein loss. UA is a naturally occurring pentacyclic triterpene acid present in several edible herbs and fruits such as apples. It contains skeletal muscle hypertrophy activity; still its potential against HH-induced muscle protein loss is unexplored. To address this issue, an in vivo study was planned to examine the beneficial effect of UA supplementation on HH-induced skeletal muscle loss. Male Sprague Dawley rats were exposed to HH with and without UA supplementation (20 mg/kg; oral) for 3 continuous days. The results described the beneficial role of UA as supplementation of UA with HH exposure attenuated reactive oxygen species production and oxidative protein damage, which indicate the potent antioxidant activity. Furthermore, UA supplementation enhanced Akt, pAkt, and p70S6kinase activity (Akt pathway) and lowered the pro-inflammatory cytokines in HH exposed rats. UA has potent antioxidant and anti-inflammatory activity, and it enhanced the protein content via upregulation of Akt pathway-related proteins against HH exposure. These three biological activities of UA make it a novel candidate for amelioration of HH-induced skeletal muscle damage and protein loss.

Redox modification of ryanodine receptor contributes to impaired Ca2+ homeostasis and exacerbates muscle atrophy under high altitude.

At extreme altitude, prolonged and severe hypoxia menaces human function and survival, and also associated with profound loss of muscle mass which results into a debilitating critical illness of skeletal muscle atrophy. Hypobaric hypoxia altered redox homeostasis and impaired calcium ion handling in skeletal muscles. Dysregulated Ca2+ homeostasis and activated calpain is the prime stressor in high altitude hypoxia while the reason for subsequent abnormal release of pathological Ca2+ into cytoplasm is largely unexplored. The present study identified the redox remodeling in the Ca2+ release channel, Ryanodine Receptor (RyR1) owing to its hypernitrosylation state in skeletal muscles in chronic hypobaric hypoxia exposed rats. RyR1-hypernitrosylation decreases the binding of FKBP12/calstabin-1 and other complexes from the channel, causing "leakiness" in RyR1 ion-channel. A strong RyR1 stabilizer, S107 enhanced binding affinity of FKBP12 with hypernitrosylated RyR1, reduced Sarco(endo)plasmic reticulum (SR) Ca2+ leak and improved muscle strength and function under chronic hypoxia. Administration of S107 inhibited the skeletal muscle damage, maintained ultrastructure of sarcomere and sarcolemmal integrity. Histological analysis proved the increase in cross-sectional area of myofibers. Further, the number of apoptotic cells was also reduced by S107 treatment. Conclusively, we proposed that the redox remodeling of RyR1 (hypernitrosylated-RyR1) might be responsible for dysregulated Ca2+ homeostasis which consequently impaired muscle strength and function in response to chronic hypoxic stress. Reduced SR Ca2+ leak and enhanced binding affinity of FKBP12 may provide a novel therapeutic avenue in ameliorating skeletal muscle atrophy at high altitude.

Sensory acceptability of value added cookies incorporated with Tinospora cordifolia (TC) stem powder; improvement in nutritional properties and antioxidant potential.

Tinospora cordifolia (TC) is regarded nature's treasure as it is salutary in various ways to the human health in ayurvedic and vedic scriptures. The TC stem creeping on neem tree (Azadirachta indica) are considered best for medicinal use. Present study was carried out to develop functional food as cookies by incorporating the TC stem powder. Functional cookies were prepared by incorporating 2%, 4%, 8%, 10% and 12% of TC stem powder and admissibility was decided on the basis of sensory evaluation to get the optimized cookies (TCC). Further physical parameters (L*, a* and b* color value and spread ratio) were analyzed. TC, TCC and control cookies without TC were evaluated for nutritional composition and antioxidant potential [antioxidant assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing power (FRAP) and nitric oxide (NO), total polyphenolic content and total flavonoid content]. Results showed that with increase in TC addition from 0 to 12% in cookies there was decreases in the sensory parameters and maximum admissible concentration was up to 8% of TC, hence optimized at this level. Incorporation of TC in cookies resulted in increase in b* value, protein, moisture, total ash, iron, copper, zinc and antioxidant potential, whereas the fat content decreases. Developed cookies proved to be better than standard control cookies with respect to functional properties.

Tanshinone IIA pretreatment promotes cell survival in human lung epithelial cells under hypoxia via AP-1-Nrf2 transcription factor.

Activator protein-1 (AP-1) plays a decisive role in cell proliferation, apoptosis, and inflammation under hypoxia; thus, AP-1 subunits or dimers could be modulated for a desired phenomenon in a cell using a suitable compound of therapeutic potential. Herein, we used Tanshinone-IIA as an AP-1 (subunits) modulator, and the purpose of the study was to investigate the signaling mechanism exhibited by Tan-IIA in facilitating tolerance to hypoxia. A549 cells were pretreated with Tan-IIA and exposed to hypoxia for 6, 12, 24, and 48 h. Biochemical and molecular parameters were assessed in order to trace the signaling pathway. Tan-IIA attenuated hypoxia-induced oxidative stress by modulating the expression of AP-1 subunits (via. MAPK) and Nrf2 transcription factor, which in turn were responsible for maintaining the higher levels of antioxidant enzymes and genes (HO). Tan-IIA increased the cell survival. This could be attributed to an increased NO level via iNOS gene and activated JNK, ERK pathway that induced c-jun/c-fos, c-jun/fosB, junD/c-fos, and junD/fosB heterodimers. This in turn leads to the cell cycle progression by activating cyclins (D and B). This was further confirmed by the lower levels of p53 and their downstream genes (p16, p21, p27). In addition, Tan-IIA decreased pro-inflammatory cytokine levels by inhibiting the formation of junB/fra-1 heterodimer regulated by p38. Tan-IIA increased cell survival to hypoxia by maintaining the higher levels of cellular iNOS, HO-1, jun-D, c-jun, fos B via Nrf2-AP-1.

Study of Metal-Metal Interactions and Their Biomarkers Using an Intestinal Human Cell Line.

From the time of dietary intake to their utilization, the number of important interactions occurs among mineral elements, which can affect their bioavailability because of similarity in physicochemical properties and common absorptive pathways. However, the studies that have analyzed the interactions among copper, iron, and zinc have conflicting results and need further exploration. HT-29 cells grown to confluence in 6-well plates were incubated with increasing concentrations (0 to 200 µM) of Cu, Fe, and Zn for 3 and 6 h for uptake studies. Interaction studies involved measuring the uptake of metal in the presence of 0:1-4:1 ratio of the other metal for 3 h using atomic absorption spectrophotometer. The concentration of metal biomarkers and cytokines was also measured in the cell lysate following extracellular supplementation. The presence of 50 µM Zn significantly decreased (P < 0.05) cellular Cu uptake in HT-29 cells at 0.5:1 Cu:Zn ratio and also the cellular Fe uptake at the ratios 0.5:1, 2:1, and 4:1 Fe:Zn. The presence of 50 µM Fe significantly (P < 0.05) decreased cellular Cu uptake at the ratios 1:1, 2:1, and 4:1 Cu:Fe. The concentration of metallothionein responded significantly (P < 0.05) to changes in extracellular Zn concentration (supplementation and depletion). There was a decrease in concentration of IL-1ß and TNF-α (P < 0.05) with an increasing extracellular concentration of Cu and Fe. The results of the study indicated that the presence of one mineral in the diet and multi mineral supplement may influence the bioavailability of the other mineral. Copper and iron may find application in promoting gut health.

High altitude mediated skeletal muscle atrophy: Protective role of curcumin.

Chronic hypobaric hypoxia induced muscle atrophy results in decreased physical performance at high altitude. Curcumin has been shown to have muscle sparing effects under cachectic conditions. However, the protective effects of curcumin under chronic hypobaric hypoxia have not been studied till now. Therefore, the present study aims at evaluating the effects of curcumin administration on muscle atrophy under chronic hypobaric hypoxia. Male Sprague Dawley rats were divided into four groups: Control (C)-normoxia exposed, Control Treated (CT)-normoxia exposed and administered with curcumin at a dose of 100 mg/kg body weight for 14 days, Hypoxia (H)-exposed to hypobaric hypoxia for 14 days and Hypoxia Treated (HT)-exposed to hypobaric hypoxia and administered with curcumin for 14 days. Oxidative stress, muscle protein degradation, proteolytic pathways, myosin heavy chain (MHC), CPK activity and muscle histology were performed in gastrocnemius muscle samples of the exposed rats. In addition, fatigue time on treadmill running was also evaluated to observe the effects of curcumin administration on physical performance of the rats. As previously shown, hypobaric hypoxia increased muscle protein degradation via upregulated calpain and ubiquitin-proteolytic pathways. An enhanced oxidative stress has been linked to upregulation of these pathways under hypoxic conditions. Curcumin administration resulted in reduced oxidative stress as well as reduced activity of the proteolytic pathways in HT group as compared to H group thereby resulting in reduced muscle protein degradation under hypobaric hypoxia. Histology of rat muscle revealed an increased number of muscle fibres in HT as compared to H group. Thus, increased number of muscle fibres and decreased muscle proteolysis following curcumin administration, lead to enhanced muscle mass under hypobaric hypoxia resulting in improved physical performance of the rats.

Effect of physical activity and age on plasma copper, zinc, iron, and magnesium concentration in physically active healthy males.

OBJECTIVES: The concentration of nutritionally important minerals in circulation is under tight homeostatic control, however, physical activity and aging influence their body stores and nutritional requirement. The aim of this study was to evaluate the effect of both physical activity and age on plasma concentrations of copper, zinc, iron, and magnesium. METHODS: Stratified cluster sampling was used for selection of study participants (N = 360) belonging to three physical activity groups: sedentary, moderately active, and highly active on the basis of their physical activity levels as 1.53, 1.8, and 2.3, respectively. They were also divided into six different age groups (18-20, 21-25, 26-30, 31-35, 36-40, and 41-45 y). We assessed nutritional status by determining their body composition using bioelectrical impedance method and measuring intake levels. Fasting blood samples were taken to separate plasma for analysis of copper, zinc, magnesium, and iron. RESULTS: There was a major difference (P < 0.001) in the mean value of plasma copper, zinc, magnesium, and iron for the three activity groups. The plasma copper and iron concentrations were higher in the moderately active group (copper: 1.59 ± 0.05 mg/L, iron: 0.79 ± 0.22 mg/L) whereas zinc concentration was higher in the sedentary group (2.37 ± 0.29 mg/L). Both the highly and moderately active groups had higher plasma magnesium levels compared with the sedentary group. Plasma copper, zinc, magnesium, and iron levels also were influenced by age in a different pattern with respect to physical activity. CONCLUSION: Physical activity-related energy expenditure and age play a remarkable role in deciphering the plasma mineral levels in the healthy individuals.

Prevalence and risk factors associated with the presence of Soil-Transmitted Helminths in children studying in Municipal Corporation of Delhi Schools of Delhi, India.

To determine the type, prevalence, intensity and the potential risk factors for helminths infection harboured by primary school aged children from selected schools of Delhi, India. Stool samples collected from 347 boys and girls studying in grades I-IV (aged 5-15 years) were examined by the semi-quantitative Kato-Katz method for presence of eggs of soil-transmitted helminths. Questionnaire data on the potential risk factors, associated variables and consequences of infection were categorized as individual, household, hygiene/sanitation related and behavioural factors. Associations between infection and these factors were assessed by multiple logistic regressions. The overall prevalence of infection with any of the helminths was 29.7 %. The prevalence of single infection with Ascaris lumbricoides was 8.1 % while that of hookworm and Trichuris trichiura was 3.7 % each. Strongest predictors for the helminths presence were never deworming (OR = 1.76; 95 % CI: 1.05, 2.95), no facility for defection (OR = 4.31; 95 % CI: 1.22, 15.22), using left hand for cleaning anal region (OR = 2.01; 95 % CI: 1.18, 3.43) and not reporting pain in stomach (OR = 1.93; 95 % CI: 1.14, 3.26). Though the infection intensities were low, we highlighted some of the potential risk factors that increase the susceptibility to these infections. Periodic deworming along with improvement in hygiene and sanitation practices through concerted efforts, not only from the school infrastructure but also the community at large, will help prevent helminths transmission and reinfection.