High density lipoprotein heterogeneity & function among Indians with coronary artery disease.

Background & objectives: Impaired high density lipoprotein (HDL) functionality has been shown to be associated with cardiovascular disease risk. The study was aimed to identify the alterations in HDL function [antioxidative activity (AOA)] and subfraction distribution between acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) individuals and analysing the accuracy of HDL parameters to discriminate between the groups. Methods: HDL subfraction distribution analysis was performed in 200 coronary artery disease patients (ACS and SCAD) and 60 control individuals using dextran sulphate, heparin and manganese chloride precipitation method. In terms of HDL function, AOA was evaluated by dihydrorhodamine-based fluorescent cell-free assay and paraoxonase (PON1) enzyme paraoxonase and arylesterase activity. Results: We found that higher AOA [odds ratio (95% confidence interval {CI})]: 0.09 (0.02-0.44), P<0.01 for SCAD; 0.008 (0.001-0.07), P<0.001 for ACS and higher PON1 activity [0.22 (0.8-0.59), P<0.01 for SCAD; 0.16 (0.06-0.4), P<0.001 for ACS] were associated with a lower odds of developing coronary artery disease (CAD). AOA of apoB-depleted serum was significantly correlated with HDL2-C/HDL3-C (HDL-cholesterol) ratio in controls (r=-0.31, P=0.01) and ACS (r=-0.18, P=0.04). It was observed that AOA and HDL subfraction distribution together could discriminate between the two groups of CAD with an accuracy of 72.8 per cent (P=0.004). Interpretation & conclusions: Impaired AOA and altered subfraction distribution of HDL may be responsible for its diminished anti-athero protective activity and can discriminate between the two groups of CAD individuals.

Determinants of high-density lipoprotein (HDL) functions beyond proteome in Asian Indians: exploring the fatty acid profile of HDL phospholipids.

Impaired high-density lipoprotein (HDL) functions are associated with development of coronary artery disease. In this study, we explored the quantitative differences in HDL (i.e. HDL proteome and fatty acid profile of HDL phospholipids) underlying the functional deficits associated with acute coronary syndrome (ACS). The relationship between HDL function and composition was assessed in 65 consecutive ACS patients and 40 healthy controls. Cholesterol efflux capacity (CEC) of HDL and lecithin cholesterol acyl transferase (LCAT) activity were significantly lower in patients with ACS compared to controls. In HDL proteome analysis, HDL isolated from ACS individuals was enriched in apolipoprotein C2 (inhibitor of LCAT), apolipoprotein C4 and serum amyloid A proteins and was deficient in apolipoprotein A-I and A-II. The fatty acid profile of HDL phospholipids analyzed using gas chromatography showed significantly lower percentages of stearic acid (17.4 ± 2.4 vs 15.8 ± 2.8, p = 0.004) and omega-3 fatty acids [eicosapentaenoic acid (1.0 (0.6-1.4) vs 0.7 (0.4-1.0), p = 0.009) and docosahexaenoic acid (1.5 ± 0.7 vs 1.3 ± 0.5, p = 0.03)] in ACS patients compared to controls. Lower percentages of these fatty acids in HDL were associated with higher odds of developing ACS. Our results suggest that distinct phospholipid fatty acid profiles found in HDL from ACS patients could be one of the contributing factors to the deranged HDL functions in these patients apart from the protein content and the inflammatory conditions.

Standardisation and application of a novel multiplex assay for estimating micronutrient status and inflammatory markers in women of Sauria Paharia and Santhal tribes of Jharkhand.

This study aimed to document the method standardisation and assessment of micronutrient and inflammatory markers in women from indigenous tribal communities of Jharkhand using a low-volume, high-throughput assay. This cross-sectional study was done among women of the reproductive age group from Sauria Paharia and Santhal tribal households (HH) in selected villages. Capillary blood samples were collected from the women during a HH survey to estimate ferritin, soluble transferrin receptor, retinol binding protein 4 and inflammatory biomarkers, C-reactive protein (CRP) and α-1-acid glycoprotein (AGP) using a multiplex assay. Vitamin D and Hb were estimated using an LC-MS technique and cyanmethaemoglobin method, respectively. A multiplex Luminex-based method was developed and standardised. The assay was used to estimate biomarkers in samples from 413 women (178 and 235 from Sauria Paharia and Santhal tribes, respectively). Over 51 % of women had raised CRP or AGP levels. Fe status was significantly better in Sauria Paharia compared with the Santhal women. Anaemia prevalence was 72 % among Santhal women. The proportion of women with Fe deficiency increased after adjusting for inflammation. The overall prevalence of vitamin A deficiency and insufficiency was 25 and 34 %, respectively, with similar prevalence in both tribes. All Santhal women had sufficient vitamin D levels, while 25 and 20 % of Sauria Paharia women had insufficient and deficient vitamin D levels, respectively. Our low-volume, high-throughput multiplex assays may provide a feasible approach for assessing nutritional biomarkers in nutritionally vulnerable hard-to-reach communities.

The effect of Bacillus coagulans Unique IS-2 supplementation on plasma amino acid levels and muscle strength in resistance trained males consuming whey protein: a double-blind, placebo-controlled study.

PURPOSE: The aim of the present study was to assess the effect of Bacillus coagulans Unique IS-2 supplementation on absorption and utilization of protein in resistance-trained males. METHODS: In this double blind, placebo-control trial, resistance-trained males (21.08 ± 2.84 years) were randomized to consume, either 20 g of whey protein powder {80% whey protein concentrate (WPC80), amounting to 15.4 g protein} with 2 billion CFU Bacillus coagulans Unique IS-2 (supplemental group) or 20 g of whey protein powder and lactose instead of Bacillus coagulans (placebo group) once daily for 60 days with a controlled resistance exercise protocol. The whey protein concentrate (WPC-80) given to both groups had a lactose content of 6.8%. Plasma-free amino acids (PFAAs) were determined at baseline, at 30 and 60 days of supplementation. Muscle strength, hypertrophy, VO2 max, and body composition, and other biochemical parameters were assessed at baseline and end line. RESULTS: A positive effect of probiotic Bacillus coagulans Unique IS-2 supplementation was observed on protein absorption as evidenced by an increase in total PFAA by + 16.1% (p = 0.004). Branched chain amino acids (BCAA) comprising isoleucine (p = 0.016), leucine (p = 0.001), and valine (p = 0.002) were increased by + 33.1% in ITT analysis as compared to placebo after 60 days. At 30 days an increase in isoleucine by + 35% (p = 0.113), leucine by + 43% (p = 0.032), and valine by + 32% (p = 0.017) was observed in ITT analysis. Probiotic effect was shown on exercise performance as evidenced by an increase in one RM of leg press and vertical jump power by + 16.61% (p = 0.024) and + 7.86% (p = 0.007), respectively. CONCLUSION: Significantly increased absorption of BCAA with supplementation of B. coagulans Unique IS-2 along with whey protein and improvement in leg press and vertical jump power was noted indicating the positive effect of the probiotic on muscle power in the lower body. TRIAL REGISTRATION NUMBER: CTRI/2017/03/008117; Date:16.03.2017.

Endothelial colony forming cells' tetrahydrobiopterin level in coronary artery disease patients and its association with circulating endothelial progenitor cells.

Endothelial colony forming cells (ECFCs) participate in neovascularization. Endothelial nitric oxide synthase (eNOS) derived NO· helps in homing of endothelial progenitor cells (EPCs) at the site of vascular injury. The enzyme cofactor tetrahydrobiopterin (BH4) stabilizes the catalytic active state of eNOS. Association of intracellular ECFCs biopterins and ratio of reduced to oxidized biopterin (BH4:BH2) with circulatory EPCs and ECFCs functionality have not been studied. We investigated ECFCs biopterin levels and its association with circulatory EPCs as well as ECFCs proliferative potential in terms of day of appearance in culture. Circulatory EPCs were enumerated by flowcytometry in 53 coronary artery disease (CAD) patients and 42 controls. ECFCs were cultured, characterized, and biopterin levels assessed by high performance liquid chromatography. Appearance of ECFCs' colony and their number were recorded. Circulatory EPCs were significantly lower in CAD and ECFCs appeared in 56% and 33% of CAD and control subjects, respectively. Intracellular BH4 and BH4:BH2 were significantly reduced in CAD. BH4:BH2 was positively correlated with circulatory EPCs (p = 0.01), and negatively with day of appearance of ECFCs (p = 0.04). Circulatory EPCs negatively correlated with ECFCs appearance (p = 0.02). These findings suggest the role of biopterins in maintaining circulatory EPCs and functional integrity of ECFCs.

Agroforestry diversity, indigenous food consumption and nutritional outcomes in Sauria Paharia tribal women of Jharkhand, India.

Like several indigenous populations, Sauria Paharias, a vulnerable indigenous tribal group residing in a biodiverse environment of Jharkhand, India, have high levels of undernutrition. We assessed agroforestry and dietary diversity, food consumption especially indigenous food (IF) intake and nutritional status of Sauria Paharia women through a cross-sectional study conducted in 18 villages of Godda district, Jharkhand. Household level information was elicited through household surveys including a dietary survey and a food frequency questionnaire. Twenty-four-hour dietary recalls (24 HDR) and anthropometric assessments were taken on one randomly selected woman per household. An index, Food Accessed Diversity Index (FADI) created to measure agroforestry diversity, showed a low mean score of 0.21 ± 0.15 and range: 0, 0.85. Fifty-nine percent of women consumed any IF during 24 HDR. Median minimum dietary diversity score for women (MDD-W) was 3 (acceptable score ≥5). More than 96% of women had intakes below estimated average requirements for all nutrients studied (energy; vitamins A, C, thiamine, riboflavin, niacin, pyridoxine; folate; iron; calcium and zinc) except protein; 41% women were underweight. IF consumption was independently associated with calcium and vitamin A intake. Decision trees developed for micronutrient consumption at different levels of MDD-W score and IF consumption scenarios revealed 1.3 to 2.9 times higher consumption of micronutrients among women with MDD-W ≥ 3 or 4. Strategies like agricultural extension programmes promoting indigenous varieties and nutrition education for increasing dietary diversity with IFs have potential to address undernutrition in Sauria Paharia women.

HDL functions and their interaction in patients with ST elevation myocardial infarction: a case control study.

BACKGROUND: Recent studies emphasize the importance of HDL function over HDL cholesterol measurement, as an important risk for cardiovascular diseases (CVD). We compared the HDL function of patients with acute coronary syndrome (ACS) and healthy controls. METHODS: We measured cholesterol efflux capacity of HDL using THP-1 macrophages labelled with fluorescently tagged (BODIPY) cholesterol. PON1 activities toward paraoxon and phenyl acetate were assessed by spectrophotometric methods. RESULTS: We recruited 150 ACS patients and 110 controls. The HDL function of all patients during acute phase and at six month follow-up was measured. The mean age of the patients and controls was 51.7 and 43.6 years respectively. The mean HDL cholesterol/apolipoprotein A-I levels (ratio) of patients during acute phase, follow-up and of controls were 40.2 mg/dl/ 112.5 mg/dl (ratio = 0.36), 38.3 mg/dl/ 127.2 mg/dl (ratio = 0.30) and 45.4 mg/dl/ 142.1 mg/dl (ratio = 0.32) respectively. The cholesterol efflux capacity (CEC) of HDL was positively correlated with apolipoprotein A-I levels during acute phase (r = 0.19, p = 0.019), follow-up (r = 0.26, p = 0.007) and of controls (r = 0.3, p = 0.0012) but not with HDL-C levels (acute phase: r = 0.07, p = 0.47; follow-up: r = 0.1, p = 0.2; control: r = 0.02, p = 0.82). Higher levels of cholesterol efflux capacity, PON1 activity and apolipoprotein A-I were associated with lower odds of development of ACS. We also observed that low CEC is associated with higher odds of having ACS if PON1 activity of HDL is also low and vice versa. CONCLUSION: ACS is associated with reduced HDL functions which improves at follow-up. The predicted probability of ACS depends upon individual HDL functions and the interactions between them.

Innovative matrix for applying a food systems approach for developing interventions to address nutrient deficiencies in indigenous communities in India: a study protocol.

BACKGROUND: Indigenous communities retain knowledge of the land and food resources rooted in historical continuity within their region of residence. Food systems research can be leveraged to identify strategies to encourage sustainable use of complex multi-species agroforestry systems by indigenous communities contributing to nutritional needs while simultaneously preserving the ecosystems and their benefits to society. Till date, the analyses of food systems have predominantly focused on high income countries often overlooking the alternatives (dietary and production) that would be most relevant to low and middle income countries (LMIC). Thus, innovative methodological approaches are needed to comprehensively characterize diverse food systems in LMICs with special reference to indigenous communities. DESIGN: This protocol paper describes a food systems approach that will be employed to understand diverse and dynamic food systems of vulnerable tribal communities of Jharkhand, India and leverage their agroforestry systems to improve dietary diversity, nutrition status and address food security. Four tribal groups namely Santhal, Ho, Munda and Sauria Paharia of Godda, West Singhbhum and Khunti districts of Jharkhand would be studied. This will be an exploratory cross-sectional study design, along with a longitudinal component to capture seasonality in dietary intake and agricultural diversity. A mixed methods approach will be used based on a conceptual framework on drivers of food systems, food supply chain, food environment (both wild & cultivated, and market food environments), as well as consumer behaviour and maternal and child health outcomes in tribal communities. The quantitative surveys will be conducted on socio-economic, demographic profile of households, their availability of, access to and utilization of food environment and nutritional status of reproductive age group women and children under 5 years. Qualitative enquiries will examine barriers and facilitators to increase sustainable production, procurement and consumption of indigenous foods. The final outcome would be development of interventions to promote indigenous food consumption. DISCUSSION: By utilizing a combination of value chain analysis and 'Optifoods linear programming software' that will use above information on indigenous community, dietary intake, nutritional status and food environment, evidence based interventions promoting indigenous food systems aimed at addressing food and nutritional security of tribal communities will be developed.

Elevated mitochondrial DNA copy numbers in pediatric acute lymphoblastic leukemia: A potential biomarker for predicting inferior survival.

BACKGROUND: Studies on mitochondrial DNA copy number reveal an increase or decrease in copy number that appears to be cancer specific, but data on acute lymphoblastic leukemia have been inconsistent regarding the significance of changes in mitochondrial DNA copies. The purpose of this pilot study was to analyze mitochondrial DNA copy number and mitochondrial DNA integrity. PROCEDURE: Copy number and mitochondrial deletion ratios were estimated in the bone marrow of 51 patients and peripheral blood of 30 healthy controls using quantitative real-time PCR. The copy number values were correlated with prognostic markers in patients. RESULTS: Significantly increased mitochondrial DNA copy number (P-value < 0.0001) and increased mitochondrial deletion ratios (P-value = 0.0018) were observed in patients compared with controls. The copy numbers were significantly decreased in patients after chemotherapy (P-value = 0.0232). Patients with higher copy numbers exhibited significantly inferior survival than patients with lower copy numbers (for event-free survival, P-value = 0.04 and overall survival, P-value = 0.1175). CONCLUSIONS: Significant decreases in mitochondrial DNA copy number with therapy indicates that copy number could be evaluated as a potential marker for therapeutic efficacy and a higher mitochondrial DNA copy number could be a poor prognostic marker.

Contribution of indigenous foods towards nutrient intakes and nutritional status of women in the Santhal tribal community of Jharkhand, India.

OBJECTIVE: The indigenous food environment, dietary intake and nutritional status of women in the Santhal tribal community of Jharkhand were assessed. Contribution of indigenous foods to nutritional status and nutrient intakes was explored. DESIGN: Exploratory cross-sectional study with a longitudinal dietary intake assessment component. Household and dietary surveys were conducted to elicit information on socio-economic and demographic profile and food consumption patterns at household level. A 24 h dietary recall for two consecutive days (repeat surveys in two more seasons) and anthropometric assessments were carried out on one woman per household. SETTING: Households (n 151) with at least one woman of reproductive age in four villages of Godda district of Jharkhand, India. SUBJECTS: Women aged 15-49 years. RESULTS: Almost all households owned agricultural land and grew fruits and vegetables in backyards for household consumption. A wide variety of indigenous foods were reported but dietary recalls revealed low intake. Women consumed adequate energy and protein but micronutrient intake was inadequate (less than 66 % of recommended) in the majority (more than 50 %) for Ca, Fe, vitamin B2, folate and vitamin B12. Women consuming indigenous foods in the past 2 d had significantly higher intakes of Ca (P=0·008) and Fe (P=0·010) than those who did not. Varying degrees of underweight were observed in 50 % of women with no significant association between underweight and consumption of indigenous foods. CONCLUSIONS: Promotion of preferential cultivation of nutrient-dense indigenous food sources and effective nutrition education on their importance may facilitate better micronutrient intakes among women in Santhal community of Jharkhand.

The need for multisectoral food chain approaches to reduce trans fat consumption in India.

BACKGROUND: The World Health Organization (WHO) recommends virtually eliminating trans fat from the global food supply. Although several high-income countries have successfully reduced trans fat levels in foods, low- and middle-income countries such as India face additional challenges to its removal from the food supply. This study provides a systems analysis of the Indian food chain to assess intervention options for reducing trans fat intake in low-income consumers. METHODS: Data were collected at the manufacturer, retailer and consumer levels. Qualitative interviews were conducted with vanaspati manufacturers (n = 13) and local food vendors (n = 44). Laboratory analyses (n = 39) of street foods/snacks sold by the vendors were also conducted. Trans fat and snack intakes were also examined in low-income consumers in two rural villages (n = 260) and an urban slum (n = 261). RESULTS: Manufacturers of vanaspati described reducing trans fat levels as feasible but identified challenges in using healthier oils. The fat content of sampled oils from street vendors contained high levels of saturated fat (24.7-69.3 % of total fat) and trans fat (0.1-29.9 % of total fat). Households were consuming snacks high in trans fat as part of daily diets (31 % village and 84.3 % of slum households) and 4 % of rural and 13 % of urban households exceeded WHO recommendations for trans fat intakes. CONCLUSIONS: A multisectoral food chain approach to reducing trans fat is needed in India and likely in other low- and middle-income countries worldwide. This will require investment in development of competitively priced bakery shortenings and economic incentives for manufacturing foods using healthier oils. Increased production of healthier oils will also be required alongside these investments, which will become increasingly important as more and more countries begin investing in palm oil production.

Ante natal care (ANC) utilization, dietary practices and nutritional outcomes in pregnant and recently delivered women in urban slums of Delhi, India: an exploratory cross-sectional study.

BACKGROUND: Antenatal Care (ANC) is one of the crucial factors in ensuring healthy outcomes in women and newborns. Nutrition education and counselling is an integral part of ANC that influences maternal and child health outcomes. A cross sectional study was conducted in Pregnant Women (PW) and mothers who had delivered in the past three months; Recently Delivered Women (RDW) in urban slums of North-east district of Delhi, India, to explore ANC utilization, dietary practices and nutritional outcomes. METHODS: A household survey was conducted in three urban slums to identify PW and RDW. Socio-economic and demographic profile, various components of ANC received including nutrition counselling, dietary intake and nutritional outcomes based on anthropometric indices and anaemia status were assessed. Socio-demographic characteristics, nutrient intake and nutritional status were compared between those who availed ANC versus those who did not using logistic regression. Descriptive summary for services and counselling received; dietary and nutrient intake during ANC were presented. RESULTS: Almost 80% (274 out of 344) women received some form of ANC but the package was inadequate. Determinants for non-utilization of ANC were poverty, literacy, migration, duration of stay in the locality and high parity. Counselling on nutrition was reported by a fourth of the population. Nutrient intake showed suboptimal consumption of protein and micronutrients like iron, calcium, vitamin A, vitamin C, thiamine, riboflavin niacin, zinc and vitamin B12 by more than half of women. A high prevalence of anaemia among PW (85%) and RDW (97.1%) was observed. There was no difference in micronutrient intake and anaemia prevalence among women who received ANC versus who did not. CONCLUSIONS: Pregnant women living in urban poor settlements have poor nutritional status. This may be improved by strengthening the nutrition counselling component of ANC which was inadequate in the ANC package received. Empowering community based health workers in providing effective nutrition counselling should be explored given the overburdened public health system.

Traditional Knowledge and Nutritive Value of Indigenous Foods in the Oraon Tribal Community of Jharkhand: An Exploratory Cross-sectional Study.

Traditional knowledge and nutritional value of indigenous foods of the Oraon tribal community in Jharkhand, India was explored. Focus group discussions were conducted with adult members to identify commonly consumed indigenous foods. Taxonomic classification and quantitative estimation of nutritive value were conducted in laboratories or utilized data from Indian food composition database. More than 130 varieties of indigenous foods were identified, many of which were rich sources of micronutrients like calcium, iron, vitamin A, and folic acid. Some were reported having medicinal properties. Utilization and ease of assimilation of indigenous foods into routine diets can be leveraged to address malnutrition in tribal communities.

Adipocyte ABCA1 expression analysis using flow cytometry.

Adipocyte characterization and assessing membrane proteins using flow cytometry has been proven to be challenging as adipocytes are fragile, especially in subjects with high BMI. We overcame these challenges through a protocol optimizing tissue digestion time by reducing intermediate steps to minimize adipocyte friction and breakage. We avoided requirement for specialized instrument configuration and used a modified gating strategy to prevent inclusion of lipid droplets during analysis. Up to 90% of the cell population were available in the gating area. We checked the expression level of ABCA1, a membrane protein reaffirming adipocyte selection. In summary, this protocol requires lesser tissue sample improving feasibility and cost efficiency. Thus, our flow cytometry method is an improvement for studying adipocyte membrane characteristics.

Role of miR-128-3p and miR-195-5p as biomarkers of coronary artery disease in Indians: a pilot study.

Coronary artery disease (CAD) imposes a significant economic burden in developing countries like India. Timely diagnosis and treatment should be prioritized to mitigate the disease. Current diagnostic tools being invasive and less specific raise the need to develop less invasive and more reliable molecular biomarkers. MicroRNAs (miRNAs) are an emerging class of molecules that can serve as a potential source of non-invasive biomarkers for CAD. The objective of this study was to determine the potential of circulatory miRNAs as diagnostic biomarkers in CAD. In this study, we have reported two microRNAs, miR-128-3p and miR-195-5p in the serum of CAD patients in Indian Population. A total of 124 subjects were recruited which included 89 angiographically proven CAD patients and 35 control subjects. Our results show a significant decrease in the levels of miR-128-3p in CAD patients while there were no significant changes in the levels of miR-195-5p. Further bioinformatics analysis revealed the potential role of miR-128-3p in cholesterol homeostasis. Altered homeostasis due to cholesterol accumulation in macrophages is the driving force behind formation of foam cells which in turn accelerates the progression of CAD. Here, we have shown that miR-128-3p increases cholesterol levels in macrophages by decreasing cholesterol efflux in-vitro.

Reformulating partially hydrogenated vegetable oils to maximise health gains in India: is it feasible and will it meet consumer demand?

BACKGROUND: The consumption of partially hydrogenated vegetable oils (PHVOs) high in trans fat is associated with an increased risk of cardiovascular disease and other non-communicable diseases. In response to high intakes of PHVOs, the Indian government has proposed regulation to set limits on the amount of trans fat permissible in PHVOs. Global recommendations are to replace PHVOs with polyunsaturated fatty acids (PUFAs) in order to optimise health benefits; however, little is known about the practicalities of implementation in low-income settings. The aim of this study was to examine the technical and economic feasibility of reducing trans fat in PHVOs and reformulating it using healthier fats. METHODS: Thirteen semi-structured interviews were conducted with manufacturers and technical experts of PHVOs in India. Data were open-coded and organised according to key themes. RESULTS: Interviewees indicated that reformulating PHVOs was both economically and technically feasible provided that trans fat regulation takes account of the food technology challenges associated with product reformulation. However, there will be challenges in maintaining the physical properties that consumers prefer while reducing the trans fat in PHVOs. The availability of input oils was not seen to be a problem because of the low cost and high availability of imported palm oil, which was the input oil of choice for industry. Most interviewees were not concerned about the potential increase in saturated fat associated with increased use of palm oil and were not planning to use PUFAs in product reformulation. Interviewees indicated that many smaller manufacturers would not have sufficient capacity to reformulate products to reduce trans fat. CONCLUSIONS: Reformulating PHVOs to reduce trans fat in India is feasible; however, a collision course exists where the public health goal to replace PHVOs with PUFA are opposed to the goals of industry to produce a cheap alternative product that meets consumer preferences. Ensuring that product reformulation is done in a way that maximises health benefits will require shifts in knowledge and subsequent demand of products, decreased reliance on palm oil, investment in research and development and increased capacity for smaller manufacturers.

Expression analysis of MMP14: Key enzyme action in modulating visceral adipose tissue plasticity in patients with obesity.

Compromised adipose tissue plasticity is a hallmark finding of obesity orchestrated by the intricate interplay between various extracellular matrix components. Collagen6 (COL6) is well characterized in obese visceral adipose tissue (VAT), not much is known about MMP14 which is hypothesized to be the key player in matrix reorganization. Subjects with obesity (BMI ≥40; n = 50) aged 18-60 years undergoing bariatric surgery and their age-matched controls (BMI < 25; n = 30) were included. MMP14, Col6A3 and Tissue inhibitor of metalloproteinase 2 (TIMP2) mRNA expression was assessed in VAT and their serum levels along with endotrophin were estimated in both groups preoperatively and post-operatively in the obese group. The results were analysed statistically and correlated with anthropometric and glycaemic parameters, namely fasting glucose and insulin, HbA1c, HOMA-IR, HOMA-ß and QUICKI. Circulating levels as well as mRNA expression profiling revealed significant differences between the individuals with and without obesity (p < .05), more so in individuals with diabetes and obesity (p < .05). Follow-up serum analysis revealed significantly raised MMP14 (p < .001), with decreased Col6A3, endotrophin and TIMP2 levels (p < .01, p < .001 and p < .01, respectively). A rise in serum MMP14 protein, simultaneous with post-surgical weight loss and decreased serum levels of associated extracellular matrix (ECM) remodellers, suggests its crucial role in modulating obesity-associated ECM fibrosis and pliability of VAT.

Contribution of natural food environments to nutritional intake and biomarker status: insights from the women of indigenous santhal communities of Jharkhand, India.

BACKGROUND: Many indigenous communities reside in biodiverse environments replete with natural food sources but show ​poor access and utilization. METHODS: To understand the links between indigenous food access, dietary intakes, and biomarkers, we conducted a cross-sectional study among women of the Santhal Community (n = 211) from 17 villages in the Godda district of Jharkhand, India. Survey methods included household surveys, dietary intake assessment (24 HDR) and micronutrient and inflammatory biomarkers' estimation. RESULTS: The diversity in access to foods from different natural sources expressed as Food access diversity index was low. This led to poor consumption and thus a low Minimum Dietary Diversity. The mean nutrient intake was less than the estimated average requirement for all nutrients. Women with higher dietary diversity scores had higher nutrient intakes. Thiamine and calcium intakes were significantly higher in women consuming indigenous foods than non-consumers. One-fourth of the women had elevated levels of inflammatory biomarkers. The prevalence of iron deficiency was approximately 70%. Vitamin A insufficiency (measured as retinol-binding protein) was observed in around 33.6% women, while 28.4% were deficient. Household access to natural food sources was associated with specific biomarkers. The access to kitchen garden (baari) was positively associated with retinol-binding protein levels and negatively with inflammatory biomarkers, while access to ponds was positively associated with ferritin levels. CONCLUSION: The findings highlight the role of access to diverse natural foods resources, including indigenous foods, for improving nutrition security in indigenous communities. Nutrition and health programs promoting indigenous food sources should include the assessment of biomarkers for effective monitoring and surveillance.

Mitochondrial gene expression signature predicts prognosis of pediatric acute myeloid leukemia patients.

Introduction: Gene expression profile of mitochondrial-related genes is not well deciphered in pediatric acute myeloid leukaemia (AML). We aimed to identify mitochondria-related differentially expressed genes (DEGs) in pediatric AML with their prognostic significance. Methods: Children with de novo AML were included prospectively between July 2016-December 2019. Transcriptomic profiling was done for a subset of samples, stratified by mtDNA copy number. Top mitochondria-related DEGs were identified and validated by real-time PCR. A prognostic gene signature risk score was formulated using DEGs independently predictive of overall survival (OS) in multivariable analysis. Predictive ability of the risk score was estimated along with external validation in The Tumor Genome Atlas (TCGA) AML dataset. Results: In 143 children with AML, twenty mitochondria-related DEGs were selected for validation, of which 16 were found to be significantly dysregulated. Upregulation of SDHC (p<0.001), CLIC1 (p=0.013) and downregulation of SLC25A29 (p<0.001) were independently predictive of inferior OS, and included for developing prognostic risk score. The risk score model was independently predictive of survival over and above ELN risk categorization (Harrell's c-index: 0.675). High-risk patients (risk score above median) had significantly inferior OS (p<0.001) and event free survival (p<0.001); they were associated with poor-risk cytogenetics (p=0.021), ELN intermediate/poor risk group (p=0.016), absence of RUNX1-RUNX1T1 (p=0.027), and not attaining remission (p=0.016). On external validation, the risk score also predicted OS (p=0.019) in TCGA dataset. Discussion: We identified and validated mitochondria-related DEGs with prognostic impact in pediatric AML and also developed a novel 3-gene based externally validated gene signature predictive of survival.

Augmenting the Angiogenic Profile and Functionality of Cord Blood Endothelial Colony-Forming Cells by Indirect Priming with Bone-Marrow-Derived Mesenchymal Stromal Cells.

Cellular therapy has shown promise as a strategy for the functional restoration of ischemic tissues through promoting vasculogenesis. Therapy with endothelial progenitor cells (EPCs) has shown encouraging results in preclinical studies, but the limited engraftment, inefficient migration, and poor survival of patrolling endothelial progenitor cells at the injured site hinder its clinical utilization. These limitations can, to some extent, be overcome by co-culturing EPCs with mesenchymal stem cells (MSCs). Studies on the improvement in functional capacity of late EPCs, also referred to as endothelial colony-forming cells (ECFCs), when cultured with MSCs have mostly focused on the angiogenic potential, although migration, adhesion, and proliferation potential also determine effective physiological vasculogenesis. Alteration in angiogenic proteins with co-culturing has also not been studied. We co-cultured ECFCs with MSCs via both direct and indirect means, and studied the impact of the resultant contact-mediated and paracrine-mediated impact of MSCs over ECFCs, respectively, on the functional aspects and the angiogenic protein signature of ECFCs. Both directly and indirectly primed ECFCs significantly restored the adhesion and vasculogenic potential of impaired ECFCs, whereas indirectly primed ECFCs showed better proliferation and migratory potential than directly primed ECFCs. Additionally, indirectly primed ECFCs, in their angiogenesis proteomic signature, showed alleviated inflammation, along with the balanced expression of various growth factors and regulators of angiogenesis.