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Gestational diabetes mellitus (GDM) continues to pose a significant challenge to maternal and fetal health, driving the need for advanced diagnostic and therapeutic strategies. Biomarker discovery has proven essential for early detection, mechanistic insights, and targeted interventions. This review provides an in-depth examination of biomarkers related to GDM, focusing on glucose metabolism, insulin resistance, inflammatory signaling, adipokines, oxidative stress markers, and genetic/epigenetic determinants. We also evaluate novel biomarkers emerging from omics technologies and their translational potential in clinical practice. Additionally, we explore the role of microRNAs and extracellular vesicles as emerging biomarkers that could offer new perspectives on GDM pathophysiology. Integration of these biomarkers into predictive models holds the potential to improve risk assessment and patient health outcomes., (© Journal of The Association of Physicians of India 2025.)

Retinal pericytes (PCs) are contractile microvascular smooth muscle cells that wrap around the endothelial cells (ECs) maintaining intact retinal vasculature (RV) with a 1:1 ratio. Microvascular complications like diabetic retinopathy (DR) due to chronic diabetes causes apoptotic loss of PCs followed by diminished vessel stability, EC apoptosis, and ischemia, leading to retinal angiogenesis, and eventually severe vision loss. This study aimed to analyze the proteins in PCs isolated from the RV of diabetic human donor eyes and compare them with remaining mixed population (MP) of retinal vascular cells. PCs and MP proteomes were analyzed using semi-quantitative proteomics. Proteins were extracted, quantified, and analyzed in duplicate using LC-MS/MS on a Tandem mass spectrometer. Overall, 42 PC and 27 MP proteins, with 19 shared proteins, were identified. Functional enrichment analysis indicated that PC proteins share common biological processes, such as negative regulation of fibrinolysis and vLDL particle remodeling, nitric oxide transport, phospholipid efflux, positive control over the clearance of apoptotic cells, chondrocyte proliferation, lipoprotein lipase activity, and oxidative stress-induced intrinsic atrophic signaling pathways. In the fold enrichment analysis, the PC proteins were associated with cholesterol metabolism, Complement and coagulant, ECM-receptor interaction, longevity regulating pathway, Peroxisome proliferator-activated receptors (PPAR), focal adhesion and PI3 Akt signaling pathways. Among the PC proteins, vitronectin, gelsolin, hornerin, apolipoprotein A1, C3, H, and complement Factors C3, C4, and C9 were identified as the most highly ranked proteins in diabetes. The identified unique proteins of retinal PC could prove beneficial as a therapeutic target in the management of DR., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Poor aqueous solubility and bioavailability limit the translation of new drug candidates into clinical applications. Nanocrystal formulations offer a promising approach for improving the dissolution rate and saturation solubility. These formulations are applicable for various routes of administration, with each presenting unique opportunities and challenges posed by the physiological barriers. The development of nanocrystal formulation requires comprehensive understanding of these barriers and the biological environment, along with strategic modulation of particle size, surface properties, and charge to facilitate improved bioavailability to the target site. This review focuses on applications of nanocrystals for diverse administration routes and strategies in overcoming anatomical and physiological delivery barriers. The orally administered nanocrystals benefit from increased solubility, prolonged gastrointestinal retention, and enhanced permeation. However, the nanocrystals, due to their small size and high surface area, are susceptible to aggregation in the presence of gastric fluids and are more prone to enzymatic degradation compared to the macrocrystalline form. Although nanocrystal formulations are composed of pure API, the application of excipients like stabilizers reduces the aggregation and improves formulation stability, solubility, and bioavailability. Some excipients can facilitate sustained drug release. Emerging research in nanocrystals include their application in blood-brain barrier transport, intranasal delivery, stimuli responsiveness, multifunctionality, and diagnostic purposes. However, the challenges related to toxicity, scale-up, and clinical translation still need further attention. Overall, nanocrystal engineering serves as a versatile platform for expanding the therapeutic potential of insoluble drugs and enabling dose reduction for existing drugs, which can minimize toxicity and improve bioavailability at lower dosages., Competing Interests: The authors report no conflicts of interest in this work., (© 2025 Yanamadala et al.)

γ-Glutamyl transpeptidase (GGT) regulates glutathione (GSH), essential for cell functions and linked to cancer. High GGT levels in tumors make it a valuable cancer biomarker. Current GGT detection methods often lack sensitivity and specificity. To address this, we developed XM-Glu, a new near-infrared (NIR) fluorescent probe. XM-Glu features a xanthene-based structure with a hydroxy xanthene fluorophore and a malononitrile group for NIR emission and reduced background noise. It has a self-immolating linker masked with glutamate acid, which activates fluorescence when GGT is present. XM-Glu can detect GGT in the range of 1.0 to 20 mU with a low detection limit of 0.067 mU mL -1 . It showed high specificity and minimal interference in cellular assays. In mice, XM-Glu effectively detected GGT in tumor, liver, and kidney tissues. Its NIR properties provide real-time insights into GGT activity, improving cancer diagnosis and monitoring. This new technology enhances cancer research and helps better understand GGT's role in cancer progression.

The present study investigated the effect of low vs high-dietary-Advanced Glycation End products-based diets on oral disposition index-(DIo)-a marker of islet β-cell function and cardiometabolic risks factors in 38-overweight and obese Asian Indian-adults (aged 25-45 years with body-mass-index (BMI) ≥23kg/m 2 ) through 12-week isocaloric crossover feeding trial. Biochemical-measures included-glucose tolerance test (GTT), Insulin assay (0,30 and 120 min), lipid-profile, serum-adiponectin, serum-AGE and serum-Thiobarbituric acid reactive substances-(TBARS) assessed both at baseline and end of each intervention. Generalised linear models showed that low-dAGE diet significantly improved in oral disposition index [Least Square Mean (SE), +0.3 (0.1); p =  0.03] compared to high-dAGE diet. The low-dAGE diet also showed a significant reduction in 30-minutes plasmapost-glucose-challenge-value:(-8.1[3.8] (mg/dl) vs 3.8 [3.8] (mg/dl); p  = 0.01), serum-AGEs-(-3.2 [0.2] (μg/ml) vs -0.8 [0.2] (μg/ml); p = <0.0001) compared to high-dAGE diet. In summary, low-dAGE diets exhibited improvement in the insulin-sensitivity and reduction in the inflammatory levels compared to high-dAGE diets. Hence, study first time in India revealed that low dAGE diets could be a potential strategy to reduce diabetes risk.

Introduction: More than half of the world's population consumes rice as their primary food. The majority of rice production is concentrated in Asia, with the top 10 rice-growing countries accounting for 84% of the world's total rice cultivation. However, rice production is also strongly linked to environmental changes. Among all the global sources of greenhouse gas (GHG) emissions, paddy cultivation stands out as a significant contributor to global methane (CH 4 ) and nitrous oxide (N 2 O) emissions. This contribution is expected to increase further with the projected increase of 28% in global rice output by 2050. Hence, modifications to rice management practices are necessary both to increase yield and mitigate GHG emissions., Methods: We investigated the effect of seedling treatment, soil application, and foliar application of a methane-derived microbial biostimulant on grain yield and GHG emissions from rice fields over three seasons under 100% fertilizer conditions. Further, microbial biostimulant was also tested under 75% nitrogen (N) levels to demonstrate its effect on grain yield. To understand the mechanism of action of microbial biostimulant on crop physiology and yield, a series of physiological, transcript, and metabolite analyses were also performed., Results: Our three-season open-field studies demonstrated a significant enhancement of grain yield, up to 39%, with a simultaneous reduction in CH 4 (31%-60%) and N 2 O (34%-50%) emissions with the use of methane-derived microbial biostimulant. Under 75% N levels, a 34% increase in grain yield was observed with microbial biostimulant application. Based on the physiological, transcript, and metabolite analyses data, we were further able to outline the potential mechanisms for the diverse synergistic effects of methane-derived microbial biostimulant on paddy, including indole-3-acetic acid production, modulation of photosynthesis, tillering, and panicle development, ultimately translating to superior yield., Conclusion: The reduction in GHG emission and enhanced yield observed under both recommended and reduced N conditions demonstrated that the methane-derived biostimulant can play a unique and necessary role in the paddy ecosystem. The consistent improvements seen across different field trials established that the methane-derived microbial biostimulant could be a scalable solution to intensify rice productivity with a lower GHG footprint, thus creating a win-win-win solution for farmers, customers, and the environment., Competing Interests: Authors SRK, GP, SA, CB, GN, PSA, PS, KZ, BRB, MUP, GR, PB, SKC, VMLK, ES were employed by String Bio Private Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kumar, David, Pavithra, Kumar, Lesharadevi, Akshaya, Basavaraddi, Navyashree, Arpitha, Sreedevi, Zainuddin, Firdous, Babu, Prashanth, Ravikumar, Basavaraj, Chavana, Kumar, Parthasarathi and Subbian.)

The extensive use of chemical pesticides has significantly boosted agricultural food crop yields. Nevertheless, their excessive and unregulated application has resulted in food contamination and pollution in environmental, aquatic, and agricultural ecosystems. Consequently, the on-site monitoring of pesticide residues in agricultural practices is paramount to safeguard global food and conservational safety. Traditional pesticide detection methods are cumbersome and ill-suited for on-site pesticide finding. The systematic review provides an in-depth analysis of the current status and perspectives of nanobiosensors (NBS) for pesticide detection in the agricultural arena. Furthermore, the study encompasses the fundamental principles of NBS, the various transduction mechanisms employed, and their incorporation into on-site detection platforms. Conversely, the assortment of transduction mechanisms, including optical, electrochemical, and piezoelectric tactics, is deliberated in detail, emphasizing its advantages and limitations in pesticide perception. Incorporating NBS into on-site detection platforms confirms a vital feature of their pertinence. The evaluation reflects the integration of NBS into lab-on-a-chip systems, handheld devices, and wireless sensor networks, permitting real-time monitoring and data-driven decision-making in agronomic settings. The potential for robotics and automation in pesticide detection is also scrutinized, highlighting their role in improving competence and accuracy. Finally, this systematic review provides a complete understanding of the current landscape of NBS for on-site pesticide sensing. Consequently, we anticipate that this review offers valuable insights that could form the foundation for creating innovative NBS applicable in various fields such as materials science, nanoscience, food technology and environmental science., (© 2024 Wiley Periodicals LLC.)

Using colorimetric and fluorescent probes has garnered significant interest in detecting NAD(P)H within practical systems and biological organisms. Herein, we synthesized a mitochondrial targetable fluorescent probe (ISQM) for fast NAD(P)H detection in <1 min. The ISQM is positively impacted because of the quinolinium reduction facilitated by NAD(P)H. It consequently liberates the push-pull fluorophore ISQM-H with a large Stokes shift (110 nm). This release leads to a turn-on response of red-emitting fluorescence, accompanied by a meager detection limit of 59 nM. To compare the differences in the NAD(P)H levels of tumor cells and normal cells, we used ISQM to measure the fluorescent signal intensities of HeLa cells (tumor cells) and RAW 264.7 cells (normal cells), respectively. Surprisingly, the experiment, including the measurement of colocalization over time, indicated that the probe exhibits a reaction with mitochondrial NAD(P)H and trace NAD(P)H in hypoxia conditions in cancer cells. Moreover, we effectively used the probe ISQM to identify the NAD(P)H in tumor mice.

Background and Aims: Obesity has reached epidemic proportions, emphasizing the importance of reliable biomarkers for detecting early metabolic alterations and enabling early preventative interventions. However, our understanding of the molecular mechanisms and specific lipid species associated with childhood obesity remains limited. Therefore, the aim of this study was to investigate plasma lipidomic signatures as potential biomarkers for adolescent obesity., Methods and Results: A total of 103 individuals comprising overweight/obese (n = 46) and normal weight (n = 57) were randomly chosen from the baseline ORANGE (Obesity Reduction and Noncommunicable Disease Awareness through Group Education) cohort, having been followed up for a median of 7.1 years. Plasma lipidomic profiling was performed using the UHPLC-HRMS method. We used three different models adjusted for clinical covariates to analyze the data. Clustering methods were used to define metabotypes, which allowed for the stratification of subjects into subgroups with similar clinical and metabolic profiles. We observed that lysophosphatidylcholine (LPC) species like LPC.16.0, LPC.18.3, LPC.18.1, and LPC.20.3 were significantly (p < 0.05) associated with baseline and follow-up BMI in adolescent obesity. The association of LPC species with BMI remained consistently significant even after adjusting for potential confounders. Moreover, applying metabotyping using hierarchical clustering provided insights into the metabolic heterogeneity within the normal and obese groups, distinguishing metabolically healthy individuals from those with unhealthy metabolic profiles., Conclusion: The specific LPC levels were found to be altered and increased in childhood obesity, particularly during the follow-up. These findings suggest that LPC species hold promise as potential biomarkers of obesity in adolescents, including healthy and unhealthy metabolic profiles., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Zileuton is a leukotriene inhibitor used to treat asthma. As a BCS class II drug it exhibits challenges with solubility which likely impact its absorption. As patient gender significantly impacts the pharmacokinetics of many drugs, this study aimed to investigate potential gender-based pharmacokinetic differences after oral zileuton administration in rats. Male and female Sprague Dawley rats received single oral gavage doses of pure zileuton as an active pharmaceutical ingredient (30 mg/kg body weight (bw)), physical mixture (PM; at 30 mg/kg bw of the formulation contains zileuton, kollidon VA64 fine, dowfax2A1 and trehalose), and nanocrystalline formulation of zileuton (NfZ; at 30 mg/kg bw of the formulation). Plasma, tissue, and urine concentrations were quantified using high performance liquid chromatography (HPLC). Noncompartmental pharmacokinetic analysis showed higher zileuton levels in the plasma of female versus male rats across all evaluated forms of zileuton (API, PM, and NfZ). Female rats demonstrated higher peak plasma concentrations (C max ) and increased area under the plasma concentration-time curve (AUC) relative to males, regardless of formulation. These findings reveal substantial gender disparities in the pharmacokinetics of zileuton in the rat model. This study emphasizes the critical need to evaluate gender differences during preclinical drug development to enable gender-based precision dosing strategies for equivalent efficacy/safety outcomes in male and female patients. Additional studies are warranted to investigate underlying mechanisms of such pharmacokinetic gender divergences., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Aims: To study the association of pro-inflammatory markers with incident diabetes in India., Methods: We did a nested case-control study within the CARRS (Centre for Ardiometabolic Risk Reduction in South Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use., Results: Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95% CI:1.39, 6.30]) and quartile-4 (OR: 2.58 [95% CI: 1.15, 5.79]) of TNF-α and quartile-4 of MCP-1 (OR: 2.55 [95% CI: 1.06, 6.16]) were positively associated with diabetes after adjusting for baseline FPG and BMI. These associations did not remain after adjusting for family history. High level (quartile-4) of IL-6 was negatively associated with diabetes after adjusting for all factors (OR: 0.18 [95% CI: 0.06, 0.55])., Conclusions: Higher TNF-α and MCP-1 levels and lower IL-6 were associated with higher risk of developing diabetes. Better understanding and potential methods of addressing these biomarkers, especially in relation to family history, are needed to address diabetes in South Asians., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Triclosan (TCS), a broad-spectrum antibacterial chemical, is detected in human urine, breast milk, amniotic fluid, and feces; however, little is known about its impact on the intestinal microbiome and host mucosal immunity during pregnancy and early development. Pregnant female rats were orally gavaged with TCS from gestation day (GD) 6 to postpartum (PP) day 28. Offspring were administered TCS from postnatal day (PND) 12 to 28. Studies were conducted to assess changes in the intestinal microbial population (16S-rRNA sequencing) and functional analysis of microbial genes in animals exposed to TCS during pregnancy (GD18), and at PP7, PP28 and PND28. Microbial abundance was compared with the amounts of TCS excreted in feces and IgA levels in feces. The results reveal that TCS decreases the abundance of Bacteroidetes and Firmicutes with a significant increase in Proteobacteria . At PND28, total Operational Taxonomic Units (OTUs) were higher in females and showed correlation with the levels of TCS and unbound IgA in feces. The significant increase in Proteobacteria in all TCS-treated rats along with the increased abundance in OTUs that belong to pathogenic bacterial communities could serve as a signature of TCS-induced dysbiosis. In conclusion, TCS can perturb the microbiome, the functional activities of the microbiome, and activate mucosal immunity during pregnancy and early development.

Nanocrystal drug formulation involves several critical manufacturing procedures that result in complex structures to improve drug solubility, dissolution, bioavailability, and consequently the efficacy of poorly soluble Biopharmaceutics Classification System (BCS) II and IV drugs. Nanocrystal formulation of an already approved oral drug may need additional immunotoxic assessment due to changes in the physical properties of the active pharmaceutical ingredient (API). In this study, we selected Zileuton, an FDA-approved drug that belongs to BCS-II for nanocrystal formulation. To evaluate the efficacy and mucosal immune profile of the nanocrystal drug, 10-week-old rats were dosed using capsules containing either API alone or nanocrystal formulated Zileuton (NDZ), or with a physical mixture (PM) using flexible oral gavage syringes. Control groups consisted of untreated, or placebo treated animals. Test formulations were administrated to rats at a dose of 30 mg/kg body weight (bw) once a day for 15 days. The rats treated with NDZ or PM had approximately 4.0 times lower (7.5 mg/kg bw) API when compared to the micron sized API treated rats. At the end of treatment, mucosal (intestinal tissue) and circulating cytokines were measured. The immunological response revealed that NDZ decreased several proinflammatory cytokines in the ileal mucosa (Interleukin-18, Tumor necrosis Factor-α and RANTES [regulated upon activation, normal T cell expressed and secreted]). A similar pattern in the cytokine profile was also observed for the micron sized API and PM treated rats. The cytokine production revealed that there was a significant increase in the production of IL-1β and IL-10 in the females in all experimental groups. Additionally, NDZ showed an immunosuppressive effect on proinflammatory cytokines both locally and systemically, which was similar to the response in micron sized API treated rats. These findings indicate that NDZ significantly decreased several proinflammatory cytokines and it displays less immunotoxicity, probably due to the nanocrystal formulation. Thus, the nanocrystal formulation is more suitable for oral drug delivery, as it exhibited better efficacy, safety, and reduced toxicity.

Microplastics (MPs) are one of the emerging pollutants, causing potential harm to aquatic ecosystems and serious concern in achieving UN Sustainable Development Goals (SDGs). Realizing the occurrence of varying concentrations of MPs in the environment, this investigation presents multi-dimensional insights into the ecological and bioeconomic implications at environmentally relevant concentrations. We pursued a multi-step approach to gain a comprehensive understanding on the effects of microalgae‒MPs interactions and their expansive implications toward SDGs. Baseline data generated using a model microalga, Raphidocelis subcapitata, and three MPs (polyethylene terephthalate, PET; polyvinyl chloride, PVC; and polystyrene, PS) indicated 10‒15 % reduction in microalgal growth rate relative to the control, pointing to a heightened energy demand. The biochemical impacts displayed concentration-dependent variability. Using the baseline data, we developed a linear regression model to dissect the interaction effects around the primary dimensions of Ecology and Bioeconomy. Notably, a correlation matrix for carbon allocation pinpointed PET as having a more pronounced impact compared to PVC and PS, with the model accounting for 33.72 % of the observed variance. Extending our insights from the model, we adopted an evidence-based methodology to outline the broader implications across the Ecology and Bioeconomy domains, and subsequently identified their associations with specific SDGs. Further probing into microalgae‒MPs interaction effects at environmentally relevant concentration, our model revealed that the selected MPs perturbed the ecological variables. Interestingly, when carbon allocation was assessed to study bioeconomic implications, there were contrasting effects on starch synthesis (beneficially) and lipid synthesis (detrimentally). The present combined analysis revealed that MPs, beyond their traditional association with SDG 14 (Life Below Water), directly and indirectly affect five other SDGs through their interactions with microalgae. This study thus underscores the complex and interconnected nature of MPs pollution at environmentally relevant concentrations and their impacts on ecological and bioeconomic aspects of SDGs, thereby highlighting the urgent need for additional research and effective mitigation strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Reconstruction using microvascular free flaps has become the standard of care in head and neck cancer surgery, and their success lies in appropriate planning, adequate revascularization, and early detection of flap compromise so that prompt salvage is possible. This study evaluates the role of infrared thermography in the planning, execution, and postoperative monitoring of microvascular flaps in head and neck reconstructions., Methods: This is a single institutional, prospective observational study conducted at a tertiary care hospital in South India for 13 months. Twenty patients were included, and their thermographic images were captured in the preoperative, intraoperative, and postoperative settings using the infrared camera FLIR T400. These images were analyzed along with the Doppler, and clinical monitoring findings in all the settings and the temperature difference were calculated postoperatively., Results: Hotspot perforator marking was made using infrared camera, and perforator marking was made using hand-held Doppler preoperatively, which correlated in 93% of cases. Intraoperatively, flap rewarming was successfully demonstrated in 19 of 20 cases. Postoperatively, flap compromise was observed on infrared thermography during the first 24 hours but not on clinical monitoring in three cases. The temperature difference values recorded were 5.4°C, 2.4°C, and 4.9°C. The mean of temperature difference of the healthy flaps was 1.0°C (range 0.1°C-1.8°C)., Conclusion: Infrared thermography provides simple and reliable imaging, which can be used in perforator marking and flap designing preoperatively and checking the flap perfusion and vascular anastomosis patency intra- and postoperatively., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objective: In previous research, we found that Sestrin2 has a strong association with plasma atherogenicity and combats the progression of atherogenesis by regulating the AMPK-mTOR pathway. Metformin, an activator of AMPK, is widely used as a first-line therapy for diabetes, but its role in preventing atherosclerosis and cardiac outcomes is unclear. Hence, we aimed to assess the effect of metformin on preventing atherosclerosis and its regulatory role in the Sestrin2-AMPK -mTOR pathway in obese/diabetic rats., Methods: Animals were fed a high-fat diet to induce obesity, administered streptozotocin to induce diabetes, and then treated with metformin (150 mg/kg body weight) for 14 weeks. Aorta and heart tissues were analyzed for Sestrin2 status by western blotting and immunohistochemistry, AMPK and mTOR activities were investigated using western blotting, and atherogenicity-related events were evaluated using reverse transcription quantitative polymerase chain reaction and histology., Results: Obese and diabetic rats showed significant decrease in Sestrin2 levels and AMPK activity, accompanied by increased mTOR activity in the heart and aorta tissues. Metformin treatment significantly restored Sestrin2 and AMPK levels, reduced mTOR activity, and restored the altered expression of inflammatory markers and adhesion molecules in obese and diabetic rats to normal levels. A histological analysis of samples from obese and diabetic rats showed atherosclerotic lesions both in aorta and heart tissues. The metformin-treated rats showed a decrease in atherosclerotic lesions, cardiac hypertrophy, and cardiomyocyte degeneration., Conclusion: This study presents further insights into the beneficial effects of metformin and its protective role against atherosclerosis through regulation of the Sestrin2-AMPK-mTOR pathway., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2023 The Korean Society of Lipid and Atherosclerosis.)

Only a few probes are suited for highly acidic environments and sensitive to pH values below 4. Thus, finding a solution for detecting strong acidic (pH value below 2) conditions is still challenging. Herein, we constructed and created a pH-switched fluorescent probe based on pyrene and a heteroatom containing pyridine unit. When exposed to acidic environments (pH 2.0), the probe's fluorescence redshifted with distinct colour and fluorescence changes owing to protonation on the nitrogen atom containing pyridine moiety, which could be deprotonated by HS - selectively compared to other competing analytes. Pyr can detect HS - with a rapid response within 5 s and showed very good quantum yield under acidic environments. The sensing mechanism was confirmed by Density Functional Theory (DFT) studies using the B3LYP and 6-31G+ (d) basis sets. Furthermore, the probe was utilized to monitor HS - in actual water samples and identify H 2 S gas by a simple paper strip test.

The human gut microbiome regulates brain function through the microbiome-gut-brain axis and is implicated in several neuropsychiatric disorders. However, the relationship between the gut microbiome and the pathogenesis of schizophrenia (SCZ) is poorly defined, and very few studies have examined the effect of antipsychotic treatment response. We aim to study the differences in the gut microbiota among drug-naïve (DN SCZ) and risperidone-treated SCZ patients (RISP SCZ), compared to healthy controls (HCs). We recruited a total of 60 participants, from the clinical services of a large neuropsychiatric hospital, which included DN SCZ, RISP SCZ and HCs (n = 20 each). Fecal samples were analyzed using 16s rRNA sequencing in this cross-sectional study. No significant differences were found in taxa richness (alpha diversity) but microbial composition differed between SCZ patients (both DN and RISP) and HCs (PERMANOVA, p = 0.02). Linear Discriminant Analysis Effect Size (LEfSe) and Random Forest model identified the top six genera, which significantly differed in abundance between the study groups. A specific genus-level microbial panel of Ruminococcus, UCG005, Clostridium&#95;sensu&#95;stricto&#95;1 and Bifidobacterium could discriminate SCZ patients from HCs with an area under the curve (AUC) of 0.79, HCs vs DN SCZ (AUC: 0.68), HCs vs RISP SCZ (AUC: 0.93) and DN SCZ vs RISP SCZ (AUC: 0.87). Our study identified distinct microbial signatures that could aid in the differentiation of DN SCZ, RISP SCZ, and HCs. Our findings contribute to a better understanding of the role of the gut microbiome in SCZ pathophysiology and suggest potential targeted interventions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: Early identification of at-risk individuals for diabetic nephropathy would help in preventing or delaying end-stage renal failure. We measured the levels of circulating soluble tumor necrosis factor receptor 1 (sTNFR1) in various stages of proteinuria (MAC) to determine the association of this marker with diabetic nephropathy., Materials and Methods: The study was performed on 160 subjects, and a case-control methodology was employed. Type 2 diabetic subjects were recruited based on albuminuria and were grouped as (1) normoalbuminuria (NA); (2) microalbuminuria (MIC); (3) MAC; (4) normal glucose tolerance (NGT) subjects who served as healthy controls. sTNFR1 levels were measured by quantitative enzyme-linked immunosorbent assay (ELISA)., Results: Soluble tumor necrosis factor receptor 1 (sTNFR1) levels were highest in the MAC group, followed by the microMAC group. The sTNFR1 levels were not statistically different between the NGT and NA groups. On regression models, sTNFR1 was associated with MIC [odds ratio (OR)- 6.491, 95% confidence interval (CI)-1.868-22.55] and MAC (OR per standard deviation-15.28; 95% CI-3.76-62.15; p &lt; 0.001) even after controlling for all the possible confounding factors. Receiver operator curve (ROC) analysis revealed sTNFR1 cut-point of 1832 pg/mL had a C-statistic of 0.685 to discriminate MI from NA with 52% sensitivity. Whereas the sTNFR1 cut-point of 2050 pg/mL with a C-statistic of 0.8177 had 77% sensitivity for identifying MAC., Conclusion: Soluble tumor necrosis factor receptor 1 (sTNFR1) is significantly associated with MIC and MAC group in type 2 diabetes, and this suggests a potential early diagnostic biomarker role of sTNFR1 for MAC among Asian Indians., (© Journal of the Association of Physicians of India 2011.)

Accumulation of advanced glycation end products (AGEs) occurs with aging and in various disease states. There are no reliable screening techniques to measure AGEs in clinical settings. In this study, a point-of-care (POC) device was used to validate skin AGE measurements with serum AGE levels and to assess its usefulness to identify individuals with abnormal glucose tolerance (AGT)., Materials and Methods: The study group comprised individuals with normal glucose tolerance (NGT: n = 47) and with AGT, that is, either diabetes or prediabetes (n = 68). Intrinsic AGE fluorescence was measured spectrofluorimetrically using multimode plate reader in the serum by exciting the samples at 370 nm and emission readouts at 440 nm. Skin AGEs were acquired using a CE-marked Scout DS commercial device. Serum levels of biomarkers carboxymethyl lysine (CML), carboxyethyl lysine (CEL), and pentosidine were analyzed by enzyme-linked immunosorbent assay (ELISA)., Results: In subjects with AGT, the skin AGEs [61.3 vs 53.7 arbitrary units (AU), p&lt;0.0001] and serum AGEs (3.5 vs 2.8 AU, p&lt;0.0001) were significantly higher than in individuals with NGT. The levels of CML, CEL, and pentosidine were also significantly higher in the subjects with AGT when compared with NGT (138 vs 89 pg/mL; 2.4 vs 1.4 nmol/mL, and 64 vs 48 pmol/mL, p&lt;0.0001), respectively. Pearson correlation analysis showed a significant positive association of skin AGEs with serum AGEs (r = 0.344) (p&lt;0.001), CML (r = 0.323) (p&lt;0.001), CEL (r = 0.308) (p&lt;0.001), and pentosidine (r = 0.251) (p&lt;0.001). In addition, it also showed a positive correlation with fasting plasma glucose (FPG) (p&lt;0.001), 2-hour post-glucose (p&lt;0.001), glycated hemoglobin (HbA1c) (p&lt;0.001), and body mass index (BMI) (p&lt;0.05). Multiple logistic regression analysis using AGT as a dependent variable showed that skin AGE scores were significantly (p&lt;0.001) associated with AGT (odds ratio: 1.133, confidence intervals: 1.067-1.203)., Conclusion: This study shows that the measurement of skin AGEs using a POC device may be suitable for mass screening of AGT even in low-resource settings., (© Journal of the Association of Physicians of India 2011.)

Developing and implementing visible light active organic-inorganic hybrid semiconductor nanomaterials with enhanced photocatalytic properties find newer environmental and energy treatment capabilities. Here, we are reporting polymeric g-C 3 N 4 layers coated with different propositions of erbium oxide nanoparticles, characterized using XPS, UV-Vis-DRS, FT-IR, HR-TEM, FE-SEM, elemental mapping, XRD and surface area techniques and its photocatalytic activities were evaluated under visible light irradiations. The hybrid nanocomposite materials possess better crystalline nature and erbium oxide particles were on the surface of polymeric g-C 3 N 4 . The surface area and bandgap energy of the polymeric g-C 3 N 4 -erbium oxide (5 wt%) nanohybrid composite were 99.9 m 2 /g and 2.52 eV. The photocatalytic activities as prepared nanohybrid composites were assessed for the oxidation of orange G dye molecules in the presence of visible light and were highly active in a broader range of pH with the presence of various inorganic anions. The rate of photocatalytic oxidation of dye molecules varied from 4.79 × 10 -4 to 1.77 × 10 -4  min -1 for the initial concentration of 5 to 20 ppm and retained its activities above 95% up to three cycles of reusability. Hence, the organic-inorganic novel catalytic nanohybrid composite may find more comprehensive applications in the area of environmental and energy applications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

First-pass metabolism alters arsenic biotransformation and its immunomodulatory activities. This study aims to determine the mRNA expression of intestinal-immunity- and permeability-associated genes, levels of cytokine/chemokines and levels of immunoglobulin isotypes when CD-1 mice were exposed to a single dose of intravenous (IV) sodium arsenite (50 µg/kg body weight (BW)) and to compare these responses to exposure via oral gavage (OG) (50 µg/kg BW). Samples were collected at 1, 4, 24 and 48 h post IV exposure and 24 and 48 h post OG. Sodium arsenite IV exposure led to a transient modulation of mRNA expression and protein levels of immunity-related genes involved in inflammation/apoptotic pathways and production of cytokines/chemokines, whereas it also led to downregulated expression of genes encoding tight junction, focal adhesion, and gap junction proteins, which are responsible for maintaining cell permeability. Oral exposure perturbed fewer cell-permeability-related genes at 24 and 48 h post exposure. At 24 h post exposure, OG decreased IgA and IgG2b levels; however, IV exposure significantly increased IgG2b, IgG3 and IgA in ileal tissue. Earlier, we showed significant downregulation of mRNA expression of genes involved in the immune-related pathways during OG in the intestinal mucosa of the same animals. Cumulatively, these results provide evidence that the exposure route of a xenobiotic can differentially impact the intestinal responses due to the impact of first-pass metabolism.

Colorimetric and fluorescent probes have received a lot of attention for detecting lethal analytes in realistic systems and in living things. Herein, a dual-approachable Benzo-hemicyaninebased red-emitting fluorescent probe PBiSMe, for distinct and instantaneous detection of CN - and HS - was synthesized. The PBiSMe emitted red fluorescence (570 nm) can switch to turn-off (570 nm) and blue fluorescence (465 nm) in response to CN - and HS - , respectively. Other nucleophilic reagents, such as reactive sulfur species (RSS) and anions, have no contact or interference with the probe; instead, a unique approach is undertaken to exclusively interact with CN - and HS - over a wide pH range. The measured detection limits for CN - (0.43 μM) and HS - (0.22 μM) ions are lower than the World Health Organization's (WHO) recommended levels in drinking water. We confirmed 1:1 stoichiometry ratio using Job's plot and observed good quantum yield for both analytes. The probe-coated paper strips were used to detect the H 2 S gas produced by food spoilage (such as eggs, raw meat, and fish) via an eye-catching visual response. Moreover, fluorescence bioimaging studies of living cells was done to confirm the probe's potential by monitoring the presence of CN - and HS - in a living system.

Background: Asian Indians have an increased susceptibility to type 2 diabetes and premature coronary artery disease. Nuts, like almonds, are rich in unsaturated fat and micronutrients with known health benefits., Objectives: This study aimed to assess the efficacy of almonds for reduction of insulin resistance and improving lipid profile in overweight Asian Indian adults., Methods: This parallel-arm, randomized, controlled trial was conducted in Chennai, India on 400 participants aged 25-65 years with a body mass index ≥ 23 kg/m 2 . The intervention group received 43 g of almonds/day for 12 weeks, while the control group was advised to consume a customary diet but to avoid nuts. Anthropometric, clinical, and dietary data were assessed at periodic intervals. Glucose tolerance, serum insulin, glycated hemoglobin, C-peptide and lipid profile were assessed at baseline and end of the study. Insulin resistance (homeostasis assessment model-HOMA IR) and oral insulin disposition index (DIo) were calculated., Results: A total of 352 participants completed the study. Significant improvement was seen in DIo [mean (95% CI) = + 0.7 mmol/L (0.1, 1.3); p = 0.03], HOMA IR (-0.4 (-0.7, -0.04; p = 0.03) and total cholesterol (-5.4 mg/dl (-10.2, -0.6); p = 0.03) in the intervention group compared to the control group. Incremental area under the curve (IAUC) and mean amplitude of glycemic excursion (MAGE) assessed using continuous glucose monitoring systems were also significantly lower in the intervention group. Dietary 24-h recalls showed a higher significant reduction in carbohydrate and increase in mono unsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake in the intervention group compared to the control group., Conclusion: Daily consumption of almonds increased the intake of MUFA with decrease in carbohydrate calories and decreases insulin resistance, improves insulin sensitivity and lowers serum cholesterol in Asian Indians with overweight/obesity. These effects in the long run could aid in reducing the risk of diabetes and other cardiometabolic disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gayathri, Abirami, Kalpana, Manasa, Sudha, Shobana, Jeevan, Kavitha, Parkavi, Anjana, Unnikrishnan, Gokulakrishnan, Beatrice, Krishnaswamy, Pradeepa, Mattes, Salas-Salvadó, Willett and Mohan.)

Fluorescent bio-imaging will be the future in the medical diagnostic for visualising inner cellular and tissues. Near-infrared (NIR) emitting fluorescent probes serve dynamically for targeted fluorescent imaging of live cells and tissues. NIR imaging is advantageous because of its merits like deep tissue penetration, minimum damage to the tissue, reduced auto fluorescence from the background, and improved resolution in imaging. The Development of the NIR emitting probe was well explored recently and growing drastically. In this review, we summarise recent achievements in NIR probes in between 2018-2021. The merits and future applications have also been discussed in this review., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Diabetic Retinopathy is prevalent among patients with uncontrolled hyperglycemia resulting in vision loss. Despite numerous challenges to create a link among these conditions, the characterization of pathological neovascularization causing retinal damage due to the prognosis of early non-proliferative diabetic retinopathy to late proliferative diabetic retinopathy needs deep understanding. In this study, meta-analysis-based integration of gene expression datasets for the fibrovascular membrane of PDR and neural retina of NPDR were compared, to investigate the differentially expressed genes involved in retinal angiogenesis. Human samples with gene expression profiling of the same experiment type and platform with sufficient information for analysis were included in the study. The studies from cell lines and non-human studies, human samples that include serum, cornea, lens, and/or other ocular tissues or fluids, and studies that lack basic information for analysis were excluded. The microarray datasets available in the Gene Expression Omnibus database of the early and late stages in DR were screened to find common gene expression profiles. Using the INMEX bioinformatics tool, significantly upregulated and downregulated genes in the neural retina of Non-Proliferative Diabetic Retinopathy and fibrovascular membrane of Proliferative Diabetic Retinopathy were compared and studied by the combine effect size method. Using the STRING database PPI network, 50 upregulated and 50 downregulated genes were used to find the key candidate genes involved in retinal disease/degeneration in eye/retinal tissues. In the extensive gene expression meta-analysis performed using INMEX bioinformatics tool, overall, 7935 differentially expressed genes were identified and the respective heatmap was created by using the visualization tools of INVEX. STRING database PPI network identified Retinol Binding Protein 3, Neural Retina Leucine Zipper, S-Antigen Visual Arrestin, Peripherin 2, and Aryl Hydrocarbon Receptor Interacting Protein Like-1 to be the most highly ranked hub genes. The newly discovered potential genes related to retinal angiogenesis causing FVM formation in DR may provide insight into the cellular pathogenesis of NPDR to PDR., Competing Interests: Declaration of compting interest The authors declare no potential conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

An efficient rhodium-catalyzed synthesis of C2-alkylated NH-free indoles has been achieved from substituted indoles and cyclopropanols. The reaction allows the synthesis of various C2-alkylated products in good to excellent yield. Important features of the method include the use of a N , N -dialkylcarbamoyl group as a traceless directing group, C-H/C-C bond functionalization, good functional group tolerance, broad scope, synthesis of pyrrolo[1,2- a ]indole, and identification of potential intermediates.

A general and efficient Cp*Co III -catalyzed C2-alkylation of N -pyridylindoles has been achieved utilizing cyclopropanols as an alkylating reagent. Employing the developed method, diverse C2-alkylated indoles were accomplished in good yield. Additionally, the synthesized C2-alkylated indoles were utilized for the construction of tetrahydrocyclopenta-[ b ]indole, and 2-(3,3-arylallyl)-1-(pyridin-2-yl)-1 H -indoles. Additionally, a plausible mechanism was also proposed.

Bacterial species have evolved with a wide variety of cellular devices, and they employ these devices for communication and transfer of genetic materials and toxins. They are classified into secretory system types I to VI based on their structure, composition, and functional activity. Specifically, the bacterial type IV secretory system (T4SS) is a more versatile system than the other secretory systems because it is involved in the transfer of genetic materials, proteins, and toxins to the host cells or other bacterial species. The T4SS machinery is made up of several proteins with distinct functions and forms a complex which spans the inner and outer membranes. This secretory machinery contains three ATPases that are the driving force for the functionality of this apparatus. At the initial stage of the secretion process, the selection of substrate molecules and processing occurs at the cytoplasmic region (also known as relaxosome), and then transfer mechanisms occur through the secretion complex. In this process, the VirD4 ATPase is the first molecule that initiates substrate selection, which is subsequently delivered to the secretory machinery. In the protein data bank (PDB), no structural information is available for the VirD4 ATPase to understand the functional property. In this manuscript, we have modeled VirD4 structure in the Gram-negative bacterium Salmonella enterica and described the predicted functional importance. The sequence alignment shows that VirD4 of S. enterica contains several insertion regions as compared with the template structure (pdb:1E9R) used for homology modeling. In this study, we hypothesized that the insertion regions could play a role in the flexible movement of the hexameric unit during the relaxosome processing or transfer of the substrate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gokulan, Khare and Foley.)

Aim: The prevalence of latent tuberculosis infection (LTBI) among diabetes patients is poorly studied. In the present study, the prevalence of LTBI among pre-diabetes and diabetes patients was studied, along with immunoendocrine biomarkers ( n = 804)., Methods: LTBI was screened by Quantiferon TB gold in Normal glucose tolerance [(NGT); n = 170, [Pre-diabetes (PDM; n = 209), Newly diagnosed diabetes (NDM; n = 165) and Known diabetes (KDM; n = 260) subjects. CRP, TNF-α, IL-6, IL-1β, IFN-β, IL-12, IFN-γ, IL-2, insulin, leptin, and adiponectin levels in serum and IFN-γ levels in quantiferon supernatants were quantified by ELISA. The expression of T-bet was quantified using qRT-PCR. Serum TBARS and nitrite levels were quantified by colorimetry., Results: The LTBI prevalence was 32% in NGT, 23% in PDM, 24% in NDM, and 32% in KDM groups, with an adjusted OR of 0.61 ( p < 0.05). Downregulation of CRP, TNF-α, and nitrites and upregulation of adiponectin could be responsible for LTBI mediated protection against insulin resistance (IR), while the high levels of IL-1β, IL-12, and leptin could be responsible for IR mediated anti-TB immunity. The defective antigen-specific IFN-γ response, as seen in the KDM group, could be responsible for the low detection rate of LTBI and high probability of endogenous reactivation., Conclusion: There appears to be a biphasic relationship between diabetes-latent tuberculosis: At the early stages of diabetes it is reciprocal, while at a late stage it is synergistic, this important phenomenon obviously needs further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aravindhan, Bobhate, Sathishkumar, Patil, Kumpatla and Viswanathan.)

The gastrointestinal tract (GIT) is exposed to xenobiotics, including drugs, through both: local (oral) and systemic routes. Despite the advances in drug discovery and in vitro pre-clinical models, there is a lack of appropriate translational models to distinguish the impact of these routes of exposure. Changes in intestinal permeability has been observed in different gastrointestinal and systemic diseases. This study utilized one such xenobiotic, arsenic, to which more than 200 million people around the globe are exposed via their food, drinking water, work environment, soil, and air. The purpose of this study was to establish an in vitro model to mimic gastrointestinal tract exposure to xenobiotics via oral or intravenous routes. To achieve this, we compared the route (mimicking oral and intravenous exposure to GIT and the dose response (using threshold approach) of trivalent and pentavalent inorganic arsenic species on the permeability of in vitro cultured polarized T84 cells, an example of intestinal epithelial cells. Arsenic treatment to polarized T84 cells via the apical and basolateral compartment of the trans-well system reflected oral or intravenous routes of exposure in vivo, respectively. Sodium arsenite, sodium arsenate, dimethyl arsenic acid sodium salt (DMA V ), and disodium methyl arsonate hydrate (MMA V ) were assessed for their effects on intestinal permeability by measuring the change in trans-epithelial electrical resistance (TEER) of T-84 cells. Polarized T-84 cells exposed to 12.8 µM of sodium arsenite from the basolateral side showed a marked reduction in TEER. Cytotoxicity of sodium arsenite, as measured by release of lactate dehydrogenase (LDH), was increased when cells were exposed via the basolateral side. The mRNA expression of genes related to cell junctions in T-84 cells was analyzed after exposure with sodium arsenite for 72 h. Changes in TEER correlated with mRNA expression of focal-adhesion-, tight-junction- and gap-junction-related genes (upregulation of Jam2, Itgb3 and Notch4 genes and downregulation of Cldn2, Cldn3, Gjb1, and Gjb2) . Overall, exposure to sodium arsenite from the basolateral side was found to have a differential effect on monolayer permeability and on cell-junction-related genes as compared to apical exposure. Most importantly, this study established a preclinical human-relevant in vitro translational model to assess the changes in permeability and cytotoxicity during exposure, mimicking oral or intravenous routes.

Background and Purpose: Emerging studies have shown that gut-derived endotoxins might play a role in intestinal and systemic inflammation. Although the significance of intestinal permeability in modulating the pathogenesis of Schizophrenia (SCZ) is recognized, not much data on the specific role of intestinal permeability biomarkers, viz., zonulin, lipopolysaccharide-binding protein (LBP), and intestinal alkaline phosphatase (IAP) in SCZ is available. Therefore, we measured the plasma levels of zonulin, LBP, and IAP and its correlation with neutrophil-to-lymphocyte ratio (NLR); a marker of systemic inflammation in patients with SCZ., Methods: We recruited 60 individuals, patients with SCZ ( n = 40) and healthy controls ( n = 20), from a large tertiary neuropsychiatry center. Plasma levels of zonulin, IAP, and LBP were quantified by enzyme-linked immunosorbent assay., Results: Plasma levels of both LBP and zonulin were significantly increased ( P <0.05), whereas the IAP levels ( P <0.05) were significantly decreased in patients with SCZ compared to healthy controls. Pearson correlation analysis revealed that zonulin and LBP had a significant positive correlation with NLR, and IAP negatively correlated with NLR. Individuals with SCZ had higher independent odds of zonulin [odds ratio (OR): 10.32, 95% CI: 1.85-57.12], LBP [OR: 1.039, 95% CI: 1.02-1.07], and IAP [OR: 0.643, 95% CI: 0.471-0.879], even after adjusting for potential confounders., Conclusion: Our study demonstrates an association of zonulin, LBP, and IAP in Asian Indian SCZ patients and correlates with NLR. Our results indicate that low-grade inflammation induced by metabolic endotoxemia might be implicated in the pathoetiology of SCZ., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 Indian Academy of Neurosciences (IAN).)

IL-38 is a recently discovered, novel anti-inflammatory cytokine, which belongs to the IL-1β family. The role played by this cytokine in diabetes-tuberculosis nexus is not known. Serum levels of IL-38, TNF-α, IL-6, and IL-1β in Normal Glucose Tolerance (NGT) and chronic Diabetes (DM) subjects, both with and without latent tuberculosis (LTB) (n = 256) were quantified by ELISA. While, serum levels of IL-38 were significantly reduced, the levels of TNF-α, IL-6, and IL-1β were not altered, in LTB infected diabetes patients. While no significant secretion of IL-38 was detected in the quantiferon supernatant, secretion of TNF-α, IL-6, and IL-1β was significantly reduced in LTB infected diabetes patients. The decreased systemic levels of IL-38 and reduced in vitro secretion of other pro-inflammatory cytokines might represent a crucial pathway associated with diabetes-tuberculosis nexus., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose of Review: To review recent data on the microbiome of the lungs and how it changes with the evolution of COPD. To explore initial data with respect to COPD and the gut-lung axis. An expanded understanding of the pathogenesis of COPD may lead to new therapeutic targets., Recent Findings: Intermittent pulmonary seeding is essential to health. The lung inflammation of chronic obstructive pulmonary disease (COPD) appears to change the lung milieu such that there is a shift in the microbiome of the lung as COPD progresses. Current data contain internal contradictions, but viewed in to suggest that the lung microbiome participates in the ongoing process of inflammation and destruction (in contrast to the role of the 'healthy lung' microbiome). Gut and lung 'communicate' and share some functions. COPD is associated with increased intestinal permeability (a dysfunction associated with inflammation). COPD has an impact upon the gastrointestinal microbiome. The gastrointestinal tract may, thus play a role in the progression of COPD., Summary: Lung injury/inflammation alters the milieu of the lung and favors an evolving microbiome, which reflects and probably participates in the processes of inflammation and injury. There is some evidence that the gastrointestinal tract participates in that inflammatory process., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

As blood-derived miRNAs (c-miRNAs) are modulated by exercise and nutrition, we postulated that they might be used to monitor the effects of a lifestyle intervention (LI) to prevent diabetes development. To challenge this hypothesis, obese Asian Indian pre-diabetic patients were submitted to diet modifications and physical activity for 4 months (LI group) and compared to a control group which was given recommendations only. We have considered 2 periods of time to analyze the data, i.e.; a first one to study the response to the intervention (4 months), and a second one post-intervention (8 months). At basal, 4 months and 8 months post-intervention the levels of 17 c-miRNAs were quantified, selected either for their relevance to the pathology or because they are known to be modulated by physical activity or diet. Their variations were correlated with variations of 25 metabolic and anthropometric parameters and cytokines. As expected, fasting-glycaemia, insulin-sensitivity, levels of exercise- and obesity-induced cytokines were ameliorated after 4 months. In addition, the levels of 4 miRNAs (i.e.; miR-128-3p, miR-374a-5p, miR-221-3p, and miR-133a-3p) were changed only in the LI group and were correlated with metabolic improvement (insulin sensitivity, cytokine levels, waist circumference and systolic blood pressure). However, 8 months post-intervention almost all ameliorated metabolic parameters declined indicating that the volunteers did not continue the protocol on their own. Surprisingly, the LI positive effects on c-miRNA levels were still detected, and were even more pronounced 8 months post-intervention. In parallel, MCP-1, involved in tissue infiltration by immune cells, and Il-6, adiponectin and irisin, which have anti-inflammatory effects, continued to be significantly and positively modified, 8 months post-intervention. These data demonstrated for the first time, that c-miRNA correlations with metabolic parameters and insulin sensitivity are in fact only indirect and likely associated with the level systemic inflammation. More generally speaking, this important result explains the high variability between the previous studies designed to identify specific c-miRNAs associated with the severity of insulin-resistance. The results of all these studies should take into account the level of inflammation of the patients. In addition, this finding could also explain why, whatever the pathology considered (i.e.; cancers, diabetes, neurodegenerative disorders, inflammatory diseases) the same subset of miRNAs is always found altered in the blood of patients vs healthy subjects, as these pathologies are all associated with the development of inflammation., Competing Interests: The authors have declared that no competing interests exist.

Sustainability evaluation of wastewater treatment helps to reduce greenhouse gas emissions, as it emphasizes the development of green technologies and optimum resource use rather than the end-of-pipe treatment. The conventional approaches for treating acid mine drainages (AMDs) are efficient; however, they need enormous amounts of energy, making them less sustainable and causing greater environmental concern. We recently demonstrated the potential of immobilized acid-adapted microalgal technology for AMD remediation. Here, this novel approach has been evaluated following emergy and carbon footprint analysis for its sustainability in AMD treatment. Our results showed that imported energy inputs contributed significantly (>90%) to the overall emergy and were much lower than in passive and active treatment systems. The microalgal treatment required 2-15 times more renewable inputs than the other two treatment systems. Additionally, the emergy indices indicated higher environmental loading ratio and lower per cent renewability, suggesting the need for adequate renewable inputs in the immobilized microalgal system. The emergy yield ratio for biodiesel production from the microalgal biomass after AMD treatment was >1.0, which indicates a better emergy return on total emergy spent. Based on greenhouse gas emissions, carbon footprint analysis (CFA), was performed using default emission factors, in accordance with the IPCC standards and the National Greenhouse Energy Reporting (NGER) program of Australia. Interestingly, CFA of acid-adapted microalgal technology revealed significant greenhouse gas emissions due to usage of various construction materials as per IPCC, while SCOPE 2 emissions from purchased electricity were evident as per NGER. Our findings indicate that the immobilized microalgal technology is highly sustainable in AMD treatment, and its potential could be realized further by including solar energy into the overall treatment system.

Background and Aims: The burden of chronic kidney disease (CKD) in India is extremely high with the prevalent twin epidemic of diabetes and hypertension. Fast declining phenotype of renal function has yet not been reported in Indian context. Here, we report the prevalence of rapid decliners phenotype in Indian population., Methods: Between the period 2014-2019, electronic records of 104636 subjects were reviewed. Subjects with serum creatinine values of at least one year apart were selected for further analysis. The study population was categorized based on eGFR, non-decliners < 1 mL/min/1.73 m 2 /year; progressive decliners 1-5 mL/min/1.73 m 2 /year and rapid decliners >5 mL/min/1.73 m 2 /year. Data on diabetes, hypertension, coronary artery disease and cerebrovascular disease were analyzed., Results: During the mean follow up of 4 years, the prevalence of non-decliners, progressive and rapid decliners were 61%, 20% and 19% respectively. Diabetes was higher at 44% in rapid decliners when compared to non-decliners (35.1%); progressive decliners (39.2%). The progression of CKD to end stage renal disease (ESRD) was higher in rapid decliners (32%) in comparison to progressive decliners (19%) CONCLUSIONS: There is a high prevalence of rapid decliner phenotype in India and progression to ESRD is greater and probably is a risk factor for early progression to ESRD., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Introduction: To evaluate the effect of metabolic surgery on microvascular changes associated with diabetic retinopathy (DR) and diabetic kidney disease (DKD) in obese Asian Indians with type 2 diabetes (T2DM), one year after metabolic surgery., Methods: This is a follow up study in 21 obese Asian Indians with T2DM who underwent metabolic surgery (MS). Diabetic microvascular complications were assessed before and one-year post surgery using urinary albumin, protein creatinine ratio, eGFR, retinal colour photography and Optical coherence tomography (OCT)., Results: Microalbuminuria (54±26 vs 28±16 vs 21±6 µg/mg, p&lt;0.001) and protein creatinine ratio (0.4±0.1 vs 0.2±0.03 vs 0.1±0.02, p&lt;0.05) reduced significantly 6 months and one year after Metabolic surgery (MS) respectively compared to baseline values. Estimated Glomerular Filtration (eGFR) rate and creatinine was stable and there was no decline in renal function one year after MS. DR was present in eight individuals at baseline. After metabolic surgery, 12 % of individuals achieved regression of DR and 12% individuals showed a one step regression from severe to moderate non proliferative DR while 12 % individuals progressed from moderate to severe non proliferative DR. Of the 14 (53.8%) individuals who had micro or macroalbuminuria at baseline, 43% individuals reverted back to normoalbuminuria. There was also a reduction in the usage of anti- hypertensive medications after MS., Conclusion: In obese Asian Indians with T2DM, metabolic surgery reduced urinary microalbuminuria and protein creatinine ratios at one-year post MS. MS resulted in stable D. Retionpathy status one-year post surgery. MS may help to improve in stabilisation of the microvascular complications in obese patients with T2DM., (© Journal of the Association of Physicians of India 2011.)

A general and efficient rhodium-catalyzed redox-neutral annulation of N -acetoxyacetanilides, readily accessible from nitroarenes, with alkynes has been accomplished for the synthesis of substituted indole derivatives. A wide range of substituted 2,3-diarylindoles were achieved from various substituted N -acetoxyacetanilides and symmetrical/unsymmetrical alkynes in good to excellent yields. The developed method was successfully integrated with the synthesis of N -acetoxyacetanilides for the efficient one-pot synthesis of indoles from nitroarenes. The important features are the introduction of N -acetoxyacetamide as a new directing group, redox-neutral annulation, an additive-free approach, wide functional group tolerance, an intramolecular version, and a one-pot reaction of nitroarenes. The method was further extended to the synthesis of potent higher analogues of indole, viz. , pyrrolo[3,2- f ]indoles and dibenzo[ a , c ]carbazoles. In addition, a plausible mechanism was proposed based on the isolation and stoichiometric study of a potential aryl-Rh intermediate.

Purpose: To evaluate and correlate retinal microvascular changes in prediabetic and diabetic patients with functional and systemic parameters., Methods: Optical coherence tomography angiography (OCTA) was performed on all subjects after medical evaluation and laboratory investigations for blood sugar, glycosylated hemoglobin, and others. Automated quantification of vascular indices of the superficial plexus were analyzed., Results: Hundred and eleven persons (222 eyes) were grouped into prediabetic (PDM) (60 eyes), diabetic without retinopathy (NDR) (56 eyes), diabetic with retinopathy (DR) (66 eyes), and healthy controls (CTR) (40 eyes). The superficial retinal capillary plexus showed no significant changes in the prediabetic and NDR groups; however, central foveal thickness (CFT) was significantly reduced in PDM (P = 0.04). The circularity of the foveal avascular zone (FAZ) (P = 0.03) and the vessel density (VD) (P = 0.01) showed significant reduction from PDM to NDR. All vascular parameters were significantly reduced in DR and correlated with disease severity. The CFT correlated significantly with FAZ area. The VD and perfusion density were seen to correlate significantly with HbA1c and contrast sensitivity. The visual acuity was significantly correlated with the FAZ. Logistic regression revealed VD [OR 20.42 (7.9-53)] and FAZ perimeter [OR 9.8 (4.2-23.2)] as the strongest predictors of DR., Conclusion: The changes in OCTA can help predict onset of DR. FAZ changes are seen in early stages and are correlated well with systemic parameters, making it an easy target to monitor and screen for severity of DR. Significant reduction in the CFT in PDM suggests that neuronal damage precedes vascular changes., Competing Interests: None

Toxicology studies on pristine graphene are limited and lack significant correlations with actual human response. The goal of the current study was to determine the response of total colonic human tissue to pristine graphene exposure. Biopsy punches of colon tissues from healthy human were used to assess the biological response after ex vivo exposure to graphene at three different concentrations (1, 10, and 100 µg/mL). mRNA expression of specific genes or intestinal cytokine abundance was assessed using real-time PCR or multiplex immunoassays, respectively. Pristine graphene-activated genes that are related to binding and adhesion ( GTPase and KRAS ) within 2 h of exposure. Furthermore, the PCNA (proliferating cell nuclear antigen) gene was upregulated after exposure to graphene at all concentrations. Ingenuity pathway analysis revealed that STAT3 and VEGF signaling pathways (known to be involved in cell proliferation and growth) were upregulated. Graphene exposure (10 µg/mL) for 24 h significantly increased levels of pro-inflammatory cytokines IFNγ, IL-8, IL-17, IL-6, IL-9, MIP-1α, and Eotaxin. Collectively, these results indicated that graphene may activate the STAT3-IL23-IL17 response axis. The findings in this study provide information on toxicity evaluation using a human-relevant ex vivo colon model and serve as a basis for further exploration of its bio-applications.

Cyclopropenes are highly strained three-membered carbocycles, which offer unique reactivity in organic synthesis. Herein, Cp*Co III -catalyzed ring-opening isomerization of cyclopropenes to cobalt vinylcarbene has been utilized for the synthesis of multisubstituted allylarenes via directing group-assisted functionalization of C-H bonds of arenes and heteroarenes. Employing this methodology, various substituents can be introduced at all three carbons of the allyl moiety with high selectivity. The important highlights are excellent functional group tolerance, multisubstituted allylation, high selectivity, gram scale synthesis, removable directing group, and synthesis of cyclopenta[ b ]indoles. In addition, a potential cobaltocycle intermediate was identified and a plausible mechanism is also proposed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aims: Two post-authorisation studies assessed the safety and persistence of patients' use of nalmefene., Methods: The START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted 'all comers' without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities., Results: START study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were 'goal reached' and 'drug cost'. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups.MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year., Conclusions: Despite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits., (© The Author(s) 2021. Medical Council on Alcohol and Oxford University Press.)

Studying potential dietary exposure to antimicrobial drug residues via meat and dairy products is essential to ensure human health and consumer safety. When studying how antimicrobial residues in food impact the development of antimicrobial drug resistance and disrupt normal bacteria community structure in the intestine, there are diverse methodological challenges to overcome. In this study, traditional cultures and molecular analysis techniques were used to determine the effects of tetracycline at chronic subinhibitory exposure levels on human intestinal microbiota using an in vitro continuous flow bioreactor. Six bioreactor culture vessels containing human fecal suspensions were maintained at 37 °C for 7 days. After a steady state was achieved, the suspensions were dosed with 0, 0.015, 0.15, 1.5, 15, or 150 µg/mL tetracycline, respectively. Exposure to 150 µg/mL tetracycline resulted in a decrease of total anaerobic bacteria from 1.9 × 10 7 ± 0.3 × 10 7 down to 2 × 10 6 ± 0.8 × 10 6 CFU/mL. Dose-dependent effects of tetracycline were noted for perturbations of tetB and tetD gene expression and changes in acetate and propionate concentrations. Although no-observed-adverse-effect concentrations differed, depending on the traditional cultures and the molecular analysis techniques used, this in vitro continuous flow bioreactor study contributes to the knowledge base regarding the impact of chronic exposure of tetracycline on human intestinal microbiota.

Silicon is a beneficial element to improve the biological process, growth, development, and crop productivity. The review mainly focuses on the advantage of crops supplemented with silicon, how Si alleviate abiotic stress as well as regulate the genes and proteins involved in metabolic and biological functions in plants. Abiotic stress causes damage to the proteins, nucleic acids, affect transpiration rate, stomatal conductance, alter the nutrient balance, and cell desiccation which could reduce the growth and development of the plants. To overcome from this problem researchers, focus on beneficial element like silicon to protect the plants against various abiotic stresses. The previous review reports are based on the application of silicon on salinity and drought stress, plant defense mechanism, the elevation of plant metabolism, enhancement of the biochemical and physiological properties, regulation of secondary metabolites and plant hormone. Here, we discuss about the silicon uptake and accumulation in plants, and silicon regulates the reactive oxygen species under abiotic stress, further we mainly focus on the genes and proteins which play a vital role in plants with silicon supplementation. The study can help the researchers to focus further on plants to improve the advancement in them under abiotic stress., (Copyright © 2021 Elsevier B.V. All rights reserved.)