Unveiling the Compositional Analysis of Green Coffee Beans with and without Silver Skin.

BACKGROUND: Green Coffee Bean (GCB) is covered with silver skin that is shed as a by-product of the roasting process. For the first time, a comparative study was conducted to differentiate the compositional analysis of green coffee beans with silver skin and without silver skin. OBJECTIVE: The study aims comparatively assessing nutritional, anti-nutritional and fatty acids composition of green coffee beans with silver skin and without silver skin. The present study is also intended to find out various organic compounds of green coffee beans. METHODS: The proximate analysis was used to study nutritional composition. Mineral analysis was assessed by atomic absorption spectroscopy. The antinutrients like phytic acid and tannin were assessed by UV-visible spectroscopy whereas volumetric and gravimetric analysis was used to determine oxalates and alkaloids. Gas chromatography and Fourier Transform Infra-Red spectroscopy were used for studying fatty acids and organic compounds, respectively. RESULTS: Protein content was significantly (p<0.05) high in green coffee beans with silver skin, indicating 15% higher protein. Macro mineral content was also found significantly (p<0.05 and p<0.01) high in green coffee beans with silver skin, whereby 5.11% higher Phosphorus and 24.12% higher Calcium content was observed. However, iron content was 68.10% lower in green coffee beans with silver skin which might be due to its higher tannin content. Trace minerals zinc and copper were also found to contain 57.18% to 18.11% higher concentrations respectively in silver skin. Anti-nutritional analysis revealed the content of phytic acid and tannin as 161 and 77.29 mg/100g, respectively in green coffee beans with silver skin. The percentages of oxalates and alkaloids were found to be 0.64 and 14.30. These anti-nutritional compounds were significantly (p<0.05 and p<0.01) higher from green coffee beans without silver skin. Green coffee beans have been found with an utmost number of saturated fatty acids having palmitic acid as the most abundant. The unsaturated part is mainly composed of linoleic and oleic acid. Chlorogenic acid isomers and caffeine were the organic compounds detected through Fourier transform infrared spectroscopy. CONCLUSION: These findings reveal the presence of both nutritional and anti-nutritional components in Coffee silver skin, with significantly higher levels of anti-nutritional factors in green coffee with silver skin, emphasizing the need for caution in the consumption of green coffee and utilization of coffee silver skin as a valuable bioresource.

HLA-DR3 mediated CD4 T cell response against GAD65 in type 1 diabetes patients.

AIM: We planned this study to identify diabetogenic glutamic acid decarboxylase (GAD65) peptides possibly responsible for human leucocyte antigen (HLA)-DR3/DQ2-mediated activation of GAD65-specific CD4 T cells in type 1 diabetes (T1D). METHODS: Top 30 GAD65 peptides, found to strongly bind in silico with HLA-DR3/DQ2 molecules, were selected and grouped into four pools. The peptides were used to stimulate CD4 T cells of study subjects in 16-h peripheral blood mononuclear cell culture. CD4 T cells' stimulation in terms of interferon-gamma (IFN-γ), interleukin (IL)-17, tumor necrosis factor-alpha (TNF-α), and IL-10 expression was analyzed using flow cytometry. RESULTS: Although all four GAD65 peptide pools (PP1-4) resulted in significantly higher expression of IFN-γ by CD4 T cells (p = .003, p < .0001, p = .026, and p = .002, respectively), only pool 2 showed significant increase in IL-17 expression (p < .0001) in T1D patients vs healthy controls. Interpeptide group comparison for immunogenicity revealed significantly higher IFN-γ and IL-17 expressions and significantly lower IL-10 expression for PP2 compared to other groups (p < .0001, p = .02, and p = .04, respectively) in patients but not in controls. Further, group 2 peptides resulted in significant increase in CD4 T cells' expression of IFN-γ and IL-17 (p = .002 for both) and significant decrease in IL-10 (p = .04) in HLA-DRB1*03-DQA1*05-DQB1*02+ patients vs HLA-DRB1*03-DQA1*05-DQB1*02+ controls. The CD4 T cells' expression of IL-17 was significantly higher (p = .03) in recently diagnosed vs long-standing HLA-DRB1*03-DQA1*05-DQB1*02+ T1D patients. CONCLUSION: GAD65 peptides, particularly those belonging to PP2, induced CD4 T cells to express IFN-γ and IL-17 cytokines in T1D patients, suggesting that group 2 peptides possibly presented by HLA-DR3 molecule to CD4 T cells shift immune balance toward inflammatory phenotype in patients.

Antiviral and ROS scavenging potential of Carica papaya Linn and Psidium guajava leaves extract against HIV-1 infection.

Antiretroviral therapy is the only treatment option for HIV-infected patients; however, it has certain drawbacks in terms of developing multiple toxic side effects. Thus, there is a continuous need to explore safe and efficacious anti-retroviral agents. Carica papaya Linn and Psidium guajava are known for their various biological activities. In this study, we characterized the bioactive fractions of methanolic leaves extract from both plants using the High-resolution electrospray ionization mass spectrometry (HR-ESI-MS) technique, followed by the investigation of their potential as anti-HIV-1 and antioxidant agents through in vitro mechanistic assays. The anti-HIV-1 activity was examined in TZM-bl cells through luciferase gene assay against two different clades of HIV-1 strains, whereas the intracellular ROS generation was analyzed by Fluorescence-Activated Cell Sorting. Additionally, the mechanisms of action of these phyto-extracts were determined through the Time-of-addition assay. The characterization of Carica papaya Linn and Psidium guajava leaves extract through HR-ESI-MS fragmentation showed high enrichment of various alkaloids, glycosides, lipids, phenolic compounds, terpenes, and fatty acids like bioactive constituents. Both the phyto-extracts were found to be less toxic and exhibited potent antiviral activity against HIV-1 strains. Furthermore, the phyto-extracts also showed a decreased intracellular ROS in HIV-1 infected cells due to their high antioxidant potential. Overall, our study suggests the anti-HIV-1 potential of Carica papaya Linn and Psidium guajava leaves extract due to the synergistic action of multiple bioactive constituents.

Therapies for Type 1 Diabetes: Is a Cure Possible?

The current standard method for type 1 diabetes (T1D) management majorly focuses on controlling blood glucose levels with exogeneous insulin administration. Recent developments have focused on finding ways to predict and prevent the development of T1D, as well as finding a curative therapy for T1D. Such developments include ß-cell replacement therapy by islet transplantation, non-insulin adjunct therapy, gene and stem cell-based therapies, immunotherapy, and automated treatment with an artificial pancreas. In recent years, non-traditional alternative therapy has also become a popular treatment option for T1D. This review discusses the various therapeutic options for T1D currently under various stages of development, the challenges associated with the present strategies, and their potential to eventually change the way T1D is treated.

Effect of Encapsulated Ferrous Sulphate Fortified Salt on Hemoglobin Levels in Anemic Rats.

(1) Background: Iron deficiency anemia is a significant nutritional problem all over the world. Salt formulations supplemented with encapsulated iron and iodine (double-fortified) were tested for their efficacy in managing iron deficiency anemia. In this study, we have checked the effect of these double-fortified salt formulations (iron and iodine) on hemoglobin (Hb) levels in anemic Wistar male rats. (2) Methods: The study was divided into two phases, viz., the development of anemia in the first phase and then the random division of anemic rats into five groups (Groups A to E). These rats were fed with three different salt formulations (Groups A to C); Group D was continued on a low iron diet, and Group E was on a normal pellet diet over a period of 84 days. The level of Hb was tested in each group. (3) Results: The rats in Groups A, B, C, and E recovered from anemia significantly, with higher Hb levels. On day 84, however, the Hb level in Group D continued to decrease. The bodyweight of the rats was not affected in any way. In all of the groups, histopathology examinations in various organs revealed no significant changes. (4) Conclusions: All of the three different salt formulations showed significant recovery in the anemic rats as compared to the rats fed with a normal pelleted diet.

Targeting COPD with PLGA-Based Nanoparticles: Current Status and Prospects.

Chronic obstructive pulmonary disease (COPD) is pulmonary emphysema characterized by blockage in the airflow resulting in the long-term breathing problem, hence a major cause of mortality worldwide. Excessive generation of free radicals and the development of chronic inflammation are the major two episodes underlying the pathogenesis of COPD. Currently used drugs targeting these episodes including anti-inflammatory, antioxidants, and corticosteroids are unsafe, require high doses, and pose serious side effects. Nanomaterial-conjugated drugs have shown promising therapeutic potential against different respiratory diseases as they are required in small quantities which lower overall treatment costs and can be effectively targeted to diseased tissue microenvironment hence having minimal side effects. Poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) are safe as their breakdown products are easily metabolized in the body. Drugs loaded on the PLGA NPs have been shown to be promising agents as anticancer, antimicrobial, antioxidants, and anti-inflammatory. Surface modification of PLGA NPs can further improve their mechanical properties, drug loading potential, and pharmacological activities. In the present review, we have presented a brief insight into the pathophysiological mechanism underlying COPD and highlighted the role, potential, and current status of PLGA NPs loaded with drugs in the therapy of COPD.

Quantitative proteomic analysis of GnRH agonist treated GBM cell line LN229 revealed regulatory proteins inhibiting cancer cell proliferation.

BACKGROUND: Gonadotropin-releasing hormone (GnRH) receptor, a rhodopsin-like G-protein coupled receptor (GPCR) family member involved in GnRH signaling, is reported to be expressed in several tumors including glioblastoma multiforme (GBM), one of the most malignant and aggressive forms of primary brain tumors. However, the molecular targets associated with GnRH receptor are not well studied in GBM or in other cancers. The present study aims at investigating the effect of GnRH agonist (Gosarelin acetate) on cell proliferation and associated signaling pathways in GBM cell line, LN229. METHODS: LN229 cells were treated with different concentrations of GnRH agonist (10-10 M to 10-5 M) and the effect on cell proliferation was analyzed by cell count method. Further, total protein was extracted from control and GnRH agonist treated cells (with maximum reduction in cell proliferation) followed by trypsin digestion, labeling with iTRAQ reagents and LC-MS/MS analysis to identify differentially expressed proteins. Bioinformatic analysis was performed for annotation of proteins for the associated molecular function, altered pathways and network analysis using STRING database. RESULTS: The treatment with different concentrations of GnRH agonist showed a reduction in cell proliferation with a maximum reduction of 48.2% observed at 10-6 M. Quantitative proteomic analysis after GnRH agonist treatment (10-6 M) led to the identification of a total of 29 differentially expressed proteins with 1.3-fold change (23 upregulated, such as, kininogen-1 (KNG1), alpha-2-HS-glycoprotein (AHSG), alpha-fetoprotein (AFP), and 6 downregulated, such as integrator complex subunit 11 (CPSF3L), protein FRG1 (FRG1). Some of them are known [KNG1, AHSG, AFP] while others such as inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), ITIH4, and LIM domain-containing protein 1 (LIMD1) are novel to GnRH signaling pathway. Protein-protein interaction analysis showed a direct interaction of KNG1, a hub molecule, with GnRH, GnRH receptor, EGFR and other interactors including ITIH2, ITIH4 and AHSG. Overexpression of KNG1 after GnRH agonist treatment was validated using Western blot analysis, while a significant inhibition of EGFR was observed after GnRH agonist treatment. CONCLUSIONS: The study suggests a possible link of GnRH signaling with EGFR signaling pathways likely via KNG1. KNG1 inhibitors may be investigated independently or in combination with GnRH agonist for therapeutic applications.

Serum 25(OH)D Concentration and Cardiovascular Disease Risk Markers Among Middle-Aged Healthy and Type 2 Diabetic Subjects.

Vitamin D deficiency is a major widespread health concern and is linked to a high risk of cardiovascular disease (CVD). Thus, we have investigated the association of vitamin D with various CVD risk markers. The present study comprises 90 control and 90 type 2 diabetes mellitus (T2DM) subjects of both sexes (age range, 30-50 years). The 25 hydroxyvitamin D [25(OH)D] and CVD risk markers including high sensitive C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), intact parathyroid hormone (I-PTH), fibroblast growth factor (FGF)-23, erythrocyte sedimentation rate (ESR), and fibrinogen were measured by using standard assays. Blood viscosity and atherogenic index of plasma calculated using standard formulae. The ten-year cardiovascular risk was assessed using the Framingham risk score (FRS). 25(OH)D, hs-CRP, MCP-1, FGF-23, ESR, fibrinogen, atherogenic index of plasma and FRS were significantly different between control and T2DM groups (p<0.05). 25(OH)D showed a significant negative correlation with MCP-1, ESR, blood viscosity, atherogenic index of plasma and FRS among total study subjects. Further, logistics regression analysis showed an association of 25(OH)D with MCP-1, hematocrit, fibrinogen, and blood viscosity. The association between 25(OH)D and various CVD risk markers suggests that 25(OH)D might help in the prediction of CVD risk.

A systematic review of utility of urine lipoarabinomannan in detecting tuberculosis among HIV-positive tuberculosis suspects.

Sputum smear microscopy (SSM), though regarded as an inexpensive and popular method for detecting tuberculosis (TB), lacks adequate sensitivity, specifically in adult people living with HIV/AIDS (PLHIV). Urine lipoarabinomannan (LAM) is a promising diagnostic tool among PLHIV with CD4 cell count < 200 cells/µl. We attempted to review all the studies undertaken in identifying the utility of urine LAM in diagnosing TB, especially among PLHIV. We searched PubMed, Google Scholar, and MEDLINE databases for studies reporting diagnostic utility of urine LAM status in PLHIV, published in the last 20 years till December 2019. The keywords used for searching were "Tuberculosis," "HIV/AIDS," "Diagnosis," "Screening" "Lipoarabinomannan," and "Urine." Our search resulted in 137 shortlisted citations, of which 67 related manuscripts were identified for detailed study. Based on inclusion and exclusion criteria, 37 studies were reviewed in detail. Average sample size of these studies was 464 (range = 81-2528; SD = 427). Crude average sensitivity of urine LAM in culture-confirmed TB cases was 44.1% (range = 8.3-93) while that of SSM was 38.6% (range = 14-65). However, sensitivity of urine LAM + SSM was 60.4% (range = 38.3-92.7), demonstrating the utility of SSM + urine LAM combination for detecting TB. Specificity was similar between urine LAM and SSM with 92.7% (range = 76-100) and 97.9% (range = 93.9-100), respectively. Majority of the studies demonstrated higher sensitivity of urine LAM in those with lesser the CD4 count, with immunocompromised and with debilitation who cannot produce self-expectorated sputum. We conclude that urine LAM is a potential diagnostic test in the algorithms involving immunocompromised, debilitated patients and specifically in PLHIV whose CD4 count is ≤100 cells/µl.

Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients.

The human leucocyte antigen (HLA) association with type 1 diabetes (T1D) is well known but there are limited studies investigating the association between ß-cell autoantibodies and HLA genes. We evaluated the prevalence of GAD65 and IA-2 autoantibodies (GADA and IA2A) in 252 T1D patients from North India and investigated the genetic association of GADA and IA2A with HLA class I and class II genes/haplotypes. GADA and IA2A were detected in 50.79% and 15.87% of T1D patients, respectively, while only 8.73% had both GADA and IA2A. HLA-DRB1∗03 was observed to be significantly higher in GADA+ T1D patients as compared to GADA- (91.41% vs. 66.13%, Bonferroni-corrected P (P c) = 1.11 × 10-5; OR = 5.45; 95% CI: 2.67-11.08). Similarly, HLA-DQB1∗02 was found to be significantly increased in GADA+ patients (94.53%, P c = 2.19 × 10-5; OR = 6.27; 95% CI: 2.7-14.49) as compared to GADA- (73.39%). The frequencies of HLA-DRB1∗04 and DQB1∗03 were increased in IA2A+ patients (45.0% and 52.5%, respectively) as compared to that in IA2A- (25.94% and 33.96%, respectively). Further, the frequency of DRB1∗03-DQB1∗02 haplotype was found to be significantly increased in GADA+ T1D patients as compared to GADA- (60.55% vs. 41.94%, P = 3.94 × 10-5; OR = 2.13; 95%CI = 1.49-3.03). Similarly, HLA-DRB1∗04-DQB1∗03 haplotype was found to be significantly increased in IA2A+ T1D patients compared to IA2A- patients (22.5% vs. 12.97%; P = 0.041; OR = 1.95; 95%CI = 1.08-3.52). None of the HLA class I genes (HLA-A, B, and Cw) was found to be associated with GADA or IA2A in people with T1D. Our findings suggest that HLA-DRB1∗03/DQB1∗02 and HLA-DRB1∗04/DQB1∗03 might play an important role in the development of GADA and IA2A, respectively.

HOMA-Adiponectin Closely Associates with Cardiometabolic Risk Markers in Middle-Aged Indians with Metabolic Syndrome.

BACKGROUND: Unhealthy dietary habits and sedentary lifestyles have raised alarming concerns for the rising prevalence of metabolic syndrome (MetS) and associated cardiometabolic risk among Indians at an early age. Insulin resistance and adiposity are the important risk factors associated with MetS. The present study aimed to investigate the relationship between a modified marker of insulin resistance (homeostatic model assessment-adiponectin (HOMA-AD)) and cardiometabolic risk among middle-aged Indians. METHODS: The study comprised of 144 subjects of age-group 31-50 years, where 83 subjects were diagnosed for MetS according to the guidelines given by the International Diabetes Federation. We measured cardiometabolic risk indicators such as fasting blood glucose (FPG), fasting plasma insulin (FPI), homeostatic model assessment- insulin resistance (HOMA-IR), adiponectin, high sensitivity C-reactive protein (hs-CRP), oxidized LDL (oxLDL), monocyte chemoattractant protein-1 (MCP-1), and atherogenic index, among others. We calculated HOMA-AD by the formula: [FPG (mmol/l) × FPI (µIU/ml)] / [22.5 × Adiponectin (µg/ml)]. RESULTS: HOMA-IR and HOMA-AD were highly increased (p<0.001) in the MetS subjects than controls. Adiponectin was significantly (p<0.01) lower whereas cardiac risk markers such as atherogenic index, hs-CRP, oxLDL, and MCP-1 were significantly (p<0.01) elevated in MetS group than controls. Linear regression showed positive and significant associations (p<0.01) of HOMA-AD with all the cardiometabolic risk markers except MCP-1. HOMA-AD showed higher AUC (0.806) than HOMA-IR (0.791) for predicting MetS. CONCLUSION: HOMA-AD could be a surrogate adipokine-based marker correlated significantly with components of MetS and cardiometabolic risk indicators. It appeared to be a better predictor of MetS among middle-aged Indians than HOMA-IR.

Platelet indices as a predictive marker in neonatal sepsis and respiratory distress in preterm prelabor rupture of membranes.

Preterm Prelabor rupture of membranes (PPROM) accompanies 2-3% of all pregnancies and 1/3rd of all preterm deliveries leading to intraamniotic infection, postpartum infections, sepsis along with perinatal morbidity and mortality worldwide. Early diagnosis and treatment can prevent the complications of PPROM and improve mother and child health. The platelet indices (platelet count, Mean platelet volume, Plateletcrit and Immature platelet fraction) could be a useful predictive parameters in PPROM, as platelets are acute phase reactants and there parameters may vary with inflammation and increased platelet consumption/production. In the present study, Mean Platelet volume (MPV) levels showed significant increase in cases as compared to controls (10.47 ± 1.92 fl Vs 8.84 ± 1.30 fl; P < 0.004). Plateletcrit (PCT) levels were also significantly increased in cases with respect to controls (0.22 ± 0.10% Vs 0.18 ± 0.05%; P = 0.004). Immature platelet fraction (IPF) is significantly increased in cases than in control subjects (8.73 ± 6.67% Vs 4.43 ± 1.75%; P < 0.001). Also, Mean Platelet volume (MPV) levels were found to be significantly higher in subjects whose neonate had developed sepsis(11.39 ± 1.69 fl Vs 8.91 ± 1.31 fl; P < 0.001) and respiratory distress (10.62 ± 2.09 fl Vs 9.26 ± 1.56 fl; P = 0.003). Similarly, PCT was significantly higher in groups with positive neonatal sepsis (0.32 ± 0.74% Vs 0.19 ± 0.65%; P = 0.010) and with respiratory distress (0.24 ± 0.78% Vs 0.18 ± 0.59%; P < 0.001). Levels of IPF were also increased in positive neonatal sepsis group (10.11 ± 6.27% Vs 5.06 ± 4.07%; P < 0.001) and respiratory distress group (9.11 ± 6.38% Vs 5.54 ± 4.43%; P = 0.009). The findings suggest that maternal platelet parameters (MPV, PCT and IPF) can be utilized as evidence of early predictors of development of neonatal sepsis and respiratory distress and may be considered as a predictive markers for adverse neonatal outcome.

Middle-Aged Indians with Type 2 Diabetes Are at Higher Risk of Biological Ageing with Special Reference to Serum CDKN2A.

Sedentary lifestyle and high visceral adiposity have elevated the risk of type 2 diabetes (T2DM) among Indians at younger age. In this study, we aimed to investigate the association of oxidative stress and chronic inflammatory mediators with ageing with special reference to the biological ageing marker cyclin-dependent kinase inhibitor 2A (CDKN2A) among middle-aged (31-50 years) Indian healthy and T2DM subjects. Malondialdehyde (MDA), oxidized LDL (oxLDL), interleukin-6 (IL-6), interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and CDKN2A were measured in T2DM patients (n = 80) and controls (n = 80) aged 31-50 years, further grouped into G1: 31-40 years and G2: 41-50 years. IL-6, TNF-α, MCP-1, and CDKN2A showed a significant association with ageing among both T2DM patients and controls. But the strength of the association of MCP-1 and CKDN2A with ageing was significantly stronger in T2DM patients than the controls. All the oxidative stress and proinflammatory mediators showed nonsignificant associations with CDKN2A in the controls. However, IL-6, TNF-α, and MCP-1 showed a strong association with CDKN2A in T2DM patients. An increased risk of high levels of CDKN2A was found in G1 T2DM patients (OR: 3.484 (95% CI: 1.246-9.747) p = 0.017) and G2 T2DM patients (OR: 5.000 (95% CI: 1.914-13.061), p = 0.001) with reference to the respective control groups. Our study reveals that the middle-aged Indians with T2DM are at higher risk of biological ageing. The development of T2DM is more common among middle-aged Indians. T2DM may exacerbate the ageing process and may subsequently predispose Indians to various age-related complications at a much early age.

Blood Viscosity, Glycemic Markers and Blood Pressure: A Study in Middle-Aged Normotensive and Hypertensive Type 2 Diabetics.

Altered blood viscosity (BV) may affect blood pressure (BP) and develops further complications in diabetes. A case-control study was performed to examine the relationship of erythrocyte sedimentation rate (ESR), hematocrit, fibrinogen, and BV with glycemic markers and BP in middle-aged normotensive and hypertensive type 2 diabetic patients and healthy controls. A total of 145 participants between age group 30-50 years divided into three groups; controls (n = 60), type 2 diabetes mellitus (T2DM, n = 55), and T2DM with hypertension (T2DM + HTN, n = 30). ESR and hematocrit were determined by Wintrobe's method. Plasma fibrinogen was measured using Lempert method and BV calculated using Merill's formula. T2DM and T2DM + HTN patients had higher fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), ESR, and fibrinogencompared to controls. In both male and female SBP, DBP, MAP, FPG, and HbA1c were significantly higher in T2DM and T2DM + HTN groups, compared to controls. Further, linear regression analysis revealed a positive association of ESR and fibrinogen with SBP, DBP, MAP, FPG, HbA1c, and positive diabetic status in all participants. Also, in the same analysis, BV showed a positive association with SBP, DBP, and MAP. The association of ESR and fibrinogenwith glycemic markers and BP in diabetes supporting the value of emerging marker's for early prediction of T2DM and hypertension.

Serum 25(OH)D concentration and its association with inflammation and oxidative stress in the middle-aged Indian healthy and diabetic subjects.

BACKGROUND: Vitamin D deficiency is associated with inflammation and oxidative stress. We have studied the association of 25-hydroxyvitamin D [25(OH)D] with markers of inflammation and oxidative stress. METHODS: We have recruited total 180 male and female subjects aged between 30 and 50 years and divided them into two groups as control (n = 90) and T2DM (n = 90). We have measured 25(OH)D concentration, markers of inflammation including interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α) and markers of oxidative stress including malondialdehyde (MDA) and oxidized low-density lipoprotein (Ox-LDL) by using standard methods. RESULTS: We stratified control and T2DM groups by 25(OH)D concentration and it indicates that in severe deficiency and sufficiency category IL-6, IL-1ß, TNF-α, and Ox-LDL were significantly different while in moderate deficiency category only MDA was significantly different, among control and T2DM groups. In an insufficiency category, IL-6, IL-1ß, TNF-α, MDA, and Ox-LDL were significantly different among control and T2DM groups. Correlation analysis indicates a negative correlation of 25(OH)D with IL-6, IL-1ß, TNF-α, and Ox-LDL among total subjects. Further, logistic regression analysis demonstrated a significant association of different categories of 25(OH)D with IL-6, IL-1ß, TNF-α, and Ox-LDL before and after adjustment to body mass index and waist to hip ratio. CONCLUSION: This study suggest that vitamin D may have significant implications in the prevention of inflammation and oxidative stress.

Senescence-associated miR-34a and miR-126 in middle-aged Indians with type 2 diabetes.

Rapid urbanization and unhealthy dietary patterns critically increase the risk of type 2 diabetes (T2D) in middle-aged Indians. However, despite recent evidence of senescence-associated microRNAs (SA-miRNAs) in regulating complex pathways of ageing, their expressions in middle-aged Indians with T2D remain unexplored. Hence we aimed to investigate the changes in expressions of SA-miRNAs miR-34a and miR-126 in middle-aged T2D patients. A total of 30 T2D patients and 30 controls were recruited of age 31-50 years. The expressions of plasma miR-34a and miR-126 were determined by quantitative PCR. Oxidized LDL (OxLDL) and malondialdehyde (MDA) levels were quantified using enzyme-linked immunosorbent assay (ELISA). The effect of different glucose concentrations on miR-34a, miR-126, senescence-associated, and oxidative stress-responsive genes were also studied in an in vitro model of mice pancreatic ß-cells. MiR-34a was significantly upregulated, whereas miR-126 was nonsignificantly reduced in T2D patients as compared to controls. T2D patients showed elevated levels of oxidative stress markers than controls. Analysis of cultured mice pancreatic ß-cells exposed to high glucose showed significant upregulation of miR-34a, miR-126, p53, and superoxide dismutase 2 (SOD2). We found that circulating miR-34a levels and oxidative stress markers levels were elevated in the middle-aged Indians with T2D as compared to controls. The presence of diabetes may aggravate the normal ageing process in the middle-aged Indians. These SA-miRNAs can also be used to check the cellular dysfunctions and ageing of pancreatic ß-cells.

Association of vitamin D deficiency with insulin resistance in middle-aged type 2 diabetics.

BACKGROUND: Vitamin D deficiency contributes to the pathophysiology of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). We investigated the association of 25-hydroxyvitamin D [25(OH)D] with IR and ß-cell function in middle-aged participants. METHODS: We enrolled 90 controls and 90 T2DM patients of both genders aged 30-50 years. Serum 25(OH)D, fasting plasma insulin (FPI), fasting plasma glucose (FPG), HbA1c, and lipid profile were measured by standard methods. Insulin resistance and sensitivity were assessed by triglyceride glucose (TyG) index, homeostatic model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and ß-cell function by HOMA-B. RESULTS: 25(OH)D deficiency was reported as 40% in control and 70% in T2DM patients. 25(OH)D concentration was positively associated with age, blood pressure, T2DM duration, FPG, HbA1c, TyG index, and HOMA-IR and negatively associated with HOMA-B and QUICKI among all the participants (p ≤.001). Participants with severe 25(OH)D deficiency (<10 ng/ml) were 39 times higher odds of being T2DM, while, those with moderate deficiency (10-19ng/ml) and insufficiency (20-29 ng/ml) were 16 times and 13 times higher odds of being T2DM, respectively. CONCLUSION: Sufficient 25(OH)D concentration may lower the risk of development of IR and T2DM in middle-aged control and diabetic participants.

Beyond LDL-c: The importance of serum oxidized LDL in predicting risk for type 2 diabetes in the middle-aged Asian Indians.

AIMS: Oxidized low-density lipoprotein (OxLDL) as the residual lipid plays a crucial role in cardiovascular complications and type 2 diabetes. This study aimed to evaluate the relationship of OxLDL with the conventional risk markers and to find the association of OxLDL with the risk of development of type 2 diabetes in middle-aged (30-50 years) Asian Indians. MATERIALS AND METHODS: A total of 78 type 2 diabetes patients and 78 age-matched controls were recruited. The serum OxLDL concentration was assessed by enzyme-linked immunosorbent assay (ELISA). Other anthropometric and biochemical measures were also carried out. Multiple logistic regression was used to determine the association of OxLDL and OxLDL to non-oxidized lipoproteins with the occurrence of type 2 diabetes. RESULTS: OxLDL was significantly higher in type 2 diabetes cases than controls (p < 0.001) even though there was no significant difference in LDL cholesterol (LDL-c) between type 2 diabetes patients and controls. OxLDL correlated significantly with fasting plasma glucose (FPG) and insulin resistance (HOMA-IR). OxLDL did not show any significant correlation with LDL-c. Multiple logistic regression showed a significant association of OxLDL, OxLDL/LDL-c and OxLDL/HDL-c with type 2 diabetes (p < 0.001). LDL-c showed no association with type 2 diabetes. ROC-AUC curve analyses showed OxLDL/HDL-c to have highest discriminatory power for type 2 diabetes (AUC: 0.710 with 95% CI: 0.629-0.791, p < 0.001). CONCLUSION: Our findings highlight the possibly more attention has to be given to OxLDL for managing lipids and diabetes progression as well as reducing cardiac risk in middle-aged type 2 diabetes patients.

Influence of High Light Intensity and Nitrate Deprivation on Growth and Biochemical Composition of the Marine Microalgae Isochrysis galbana

Abstract Isochrysis galbana is a brown microalgae widely used as a feed for marine organism in aquaculture. The aim of present study is to investigate the growth, biochemical composition, fatty acid profile, photosynthetic parameters and antioxidant activity (radical scavenging activity) of Isochrysis galbana cells cultivated under different levels (sub-optimum; 50 ± 1.5,optimum; 125 ± 2.5 and supra-optimum; 325 ± 3.5 µmol photons m-2 s -1) of photosynthetic active radiation (PAR), and subsequently treated with different concentration of nitrate deprivation (8mM, 2mM and 0.5mM). The experiment was carried out under controlled conditions utilizing a factorial design 3x3 (light intensity and nitrate concentration). The result depicts that PAR positively influences the growth of Isochrysis galbana which is maximum under supra-optimum PAR. Nitrate deprivation (2mM & 0.5mM) induced decline in growth in terms of dry weight is observed as 60.1% & 61.9% in suboptimum and 26.5% and 34.9% in supra-optimum respectively over the values recorded in their respective controls. Supra-optimum PAR decreased primary photosynthetic pigment Chl a and Chl c by 15.7% and 8.5%, whereas carotenoid content increased by 45.9% in supra-optimum PAR which displays potential interest as antioxidant agent in addition to total phenolic content and radical scavenging activity. The results suggest that combined stress of high light and nitrogen deprivation shifts the metabolic physiology from protein synthesis to energy reserve (carbohydrate and lipid) and accumulation of saturated fatty acid on expense of unsaturated fatty acid except docosahexaenoic acid. These valuable compounds exhibit potential applications in mariculture, nutraceutical and biofuel industry.

Role of MicroRNAs in Type 2 Diabetes and Associated Vascular Complications.

Type 2 diabetes mellitus (T2DM) has become a major health threat worldwide. MicroRNAs (miRNAs) are a group of non-coding RNAs known to regulate various biological processes including the pathogenesis of T2DM. Recent studies have pointed out that specific miRNAs play a critical role in controlling ß cell activities and the development of diabetic vascular complications. Their association with the disease pathogenesis and omnipresence in body fluids have made them important players for prognosis, diagnosis and management of T2DM. Owing to the limitations of classical biomarkers of diabetes such as fasting plasma glucose, glycosylated haemoglobin (HbA1c) lack in predicting the risk of development of diabetes complications in a susceptible population. The miRNAs can act as ideal biomarkers for diabetes associated complications. Identification of specific miRNA signatures to detect diabetes and ideally to find out the risk of development of diabetes-associated complications in susceptible population is the essential requirement of the present clinical strategies for controlling diabetes worldwide. In this article, we summarize the potential miRNAs and miRNA signatures involved in the ß cell activities and diabetes associated macrovascular and microvascular complications.