Impact of short-term irrigation of diverse distillery wastewater types on plant attributes and antioxidative enzymes of pea (Pisum sativum L. var. Rachna).

The study was focused on evaluating the short-term irrigation effect of three different types of distillery wastewater, i.e., untreated, primary treated, and secondary treated, on the germination, growth, photosynthetic pigments, and antioxidant enzymes of pea (Pisum sativum L. var. Rachna). The findings indicated that exposure to 50% secondary treated distillery wastewater (ST50) resulted in the maximum values for positive germination parameters of pea, including germination percentage, germination value, germination index, peak value, vigor index, speed of germination, and tolerance index. The minimum values were observed at 100% concentration of untreated wastewater (UT100). In contrast, the maximum values for various negative germination parameters, i.e., percent inhibition, seedling mortality, and germination period, were observed at UT100 and minimum at ST50. All the growth parameters studied, i.e., length of shoot, length of root and length of seedlings, fresh weight of shoot, fresh weight of root, dry weight of shoot, and dry weight of root, showed maximum values at ST50 and minimum at UT100. Photosynthetic pigment analysis also followed a similar trend. The antioxidative enzyme characterization of Pisum sativum L. var. Rachna revealed the minimum values of catalase, ascorbic peroxidase, glutathione reductase, and superoxide dismutase at ST25 (25% concentration of secondary treated distillery wastewater) and maximum values were observed at UT100.

Genetic Association of Transcription Factor 7-Like-2 rs7903146 Polymorphism With Type 2 Diabetes Mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) mainly results from the inability of muscle, fat, and liver cells to uptake glucose due to insulin resistance or deficiency of insulin production by the pancreas. Predisposition to T2DM may be due to environmental, hereditary, or both factors. Although there are many genes involved in causing T2DM, transcription factor 7-like-2 gene (TCF7L2) rs7903146 (C/T) single nucleotide polymorphism (SNP) found in genome-wide association studies (GWAS) is susceptible to T2DM. TCF7L2 is involved in pancreatic beta cell proliferation and differentiation via the Wnt signaling mechanism. OBJECTIVES: To find the genetic association of TCF7L2 rs7903146 (C/T) gene polymorphism in patients with T2DM. METHODS: A case-control study was conducted on 194 T2DM patients recruited from the endocrinology department at Indira Gandhi Institute of Medical Sciences, Patna, and 180 non-diabetic healthy controls that were age and sex-matched with the patients. All clinical examination and biochemical investigations like glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol; and determination of TCF7L2 gene polymorphism by allele-specific polymerase chain reaction (AS-PCR) were carried out for each subject. RESULTS:  The T allele of the rs7903146 (C/T) SNP was associated with a two-fold higher risk of T2DM and the heterozygous genotype (CT) with a 1.96 times higher risk. CONCLUSION: There is a high association of this SNP with the development of T2DM in the eastern Indian population. Serial monitoring of HbA1c should be done in an individual having this type of polymorphism for early detection of T2DM to prevent future complications.

Socio-economic and environmental vulnerability of urban slums: a case study of slums at Jammu (India).

Rapid urban population growth, the urbanization of poverty, and the proliferation of slums are being driven to a great extent by this dynamic form of globalization. Consequently, the multifaceted effects of globalization on the poor and low-income populations in the cities need to be better understood in this context, both at the individual level and within the community. Therefore, the present study was conducted to highlight the various determinants affecting the lives and enhancing the vulnerability of the dwellers of four slum settlements present in various areas of Jammu City, India. Emphasis was made to integrate biological, physical, social, and spatial facets of vulnerability to understand the complex dynamics of urban areas in developing countries. A descriptive survey design was used for questions concerning the social and environmental aspects. Social aspects including age, sex, education, religion, caste, profession, and family income that correspond to social stratification acted as baseline information, while both indoor and outdoor environments such as housing conditions, sanitation, personal habits, solid waste disposal, disaster proneness, and air and water pollution problems were taken into consideration to assess the environmental aspect. Results indicated that the slum settlement has a migratory population with permanent or temporary settlements. The status of education and skill level is poor which results in poor economic development and social well-being of the dwellers in slums. The study also identified vulnerability of the population on social and environmental front which could result into severe health issues. The study concluded and recommended policy planning specified for slums for uplifting such unprivileged populations.

Impact of pharmaceutical industry wastewater on stress physiological responses of Spirodela polyrhiza (L.) Schleiden.

Impact of pharmaceutical wastewater collected from aeration tank on aquatic macrophyte Spirodela polyrhiza (L.) Schleiden was studied in the present study. Various plant parameters such as chlorophyll, protein, and proline content of wastewater-exposed plants were examined to determine the toxic impacts of pharmaceutical wastewater. In addition to these parameters, electrolyte leakage (EL) and catalase (CAT) activities in S. polyrhiza were assessed for each day of exposure to the wastewater. S. polyrhiza was exposed to four different wastewater concentrations (25%, 50%, 75%, and 100%) under laboratory conditions for 7 days. The plants experienced severe toxicity as revealed by the reduction in photosynthetic pigments, increase in electrolyte leakage, and enhancement of antioxidant enzyme (CAT) activity in S. polyrhiza with an increase in concentration and time of exposure to pharmaceutical effluent.

Association of Thyroid Function With Lipid Profile in Patients With Metabolic Syndrome: A Prospective Cross-Sectional Study in the Indian Population.

Introduction Metabolic syndrome is a group of aberrant metabolic indicators including hypertension, dyslipidemia, impaired fasting blood glucose, and obesity. It has been reported that thyroid hormones have a strong influence on the cardiovascular system, and hypothyroidism has been linked to metabolic syndrome components. The objective of the study was to find out the association of thyroid function with lipid profile in patients with metabolic syndrome. Methods A prospective cross-sectional study was conducted in an apparently healthy adult population visiting the outpatient Department of Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India. Metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) criteria. Fasting blood glucose, triglyceride, and HDL levels were tested using the enzymatic photometric method. Thyroid-stimulating hormone (TSH), free T4, free T3, and insulin assays were performed using chemiluminescence immunoassay (CLIA). Results Out of 197 subjects recruited, 86 (51 males and 35 females) were diagnosed with metabolic syndrome according to the IDF criteria, and the rest 111 without metabolic syndrome were considered to be the controls. The mean age of subjects with and without metabolic syndrome was 45.8±8.5 and 46.4±9.6 years, respectively. The prevalence of thyroid dysfunction in the present study was 22%. In subjects with metabolic syndrome, most of the clinical and hormonal parameters (waist circumference, waist-height ratio, fasting blood sugar, fasting insulin, triglycerides, T3, and TSH) were significantly higher (p<0.001) as compared to those without metabolic syndrome. In case of lipid profile, the triglycerides in those with metabolic syndrome (262.8±112.3 mg/dL) were significantly higher (p<0.001) than those without metabolic syndrome (137.9±19.01 mg/dL), while the serum levels of HDL were significantly higher (p<0.001) in group without metabolic syndrome (50.5±3.9 mg/dL) as compared to those with metabolic syndrome (43.4±5.2 mg/dL). Also, the TSH levels were significantly higher (p<0.001) in subjects with metabolic syndrome (5.3±3.4 µl/mL) as compared to those without metabolic syndrome (2.6±1.4 µl/mL). Among all the components of metabolic syndrome, waist circumference and HDL showed a significant strong positive correlation (r=0.51) with TSH, and systolic blood pressure (r=0.39), diastolic blood pressure (r=0.39), and fasting blood sugar levels (r=0.44) showed significantly moderate positive correlation with TSH levels. T4 (OR=8.82; 95% CI: 1.56-49.8) and TSH (OR=1.61; 95% CI: 1.19-2.18) levels were observed to have significantly higher odds as risk factors for metabolic syndrome. Conclusion There is a significant association of thyroid function with lipid profile in metabolic syndrome. It was observed that along with metabolic alterations, cardiovascular symptoms of hypothyroidism and subclinical hypothyroidism are possible. Therefore, while evaluating people with metabolic syndrome, it may be appropriate to look into how well their thyroid glands are functioning.

Correlation Between Circulating Cell-Free DNA Levels and Breast Cancer Subtypes: A Prospective Observational Study.

INTRODUCTION: Breast cancer (BC), a heterogeneous disease, is one of the leading causes of cancer-related deaths among women worldwide. Circulating cell-free DNA (cfDNA) levels have been persistently reported to be elevated in BC patients. In the current study, we evaluated the correlation between the cfDNA levels in patients with BC and its subtypes. METHODS: We recruited newly diagnosed, histopathologically confirmed BC patients aged >18 years (N=39), who did not have any previous malignancy, from the Department of Surgical Oncology, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India. A total of 6 ml of venous blood was collected from each subject; of this, 1 ml was subjected to complete blood count (CBC), and 4 ml was transferred to a clot-activated collection vial for plasma separation and the cfDNA isolation thereof. In addition to the basic demographic history of each patient, the information on the cancer subtype was as also recorded from the medical records of each patient. All the data were analysed by GraphPad Prism Version 8 (Insightful Science, LLC, San Diego, California, United States). One-way ANOVA was used to test the difference between more than two groups. Pearson correlation was also estimated between cfDNA levels and various CBC indices. A two-tailed p-value<0.05 was considered statistically significant. RESULTS: The mean age of included patients was 48.6±8.20 years. The mean levels of cfDNA were 2.81±2.39 ng/µL. The mean counts of various blood cell types and other indices of CBC were in the normal range. Compared to BC patients with estrogen receptors (ER+), the cfDNA levels were significantly higher in patients with human epidermal growth factor receptor 2 (HER2+) and triple-negative BC (TNBC) (p<0.05).  Conclusion: The elevated levels of cfDNA in patients with BC can be a prognostic marker for the disease subtype. However, more replicative studies are warranted to substantiate our findings.

A Retrospective Study to Evaluate the Perioperative Clinical Characteristics and Outcomes of Rhino-Orbital Cerebral Mucormycosis in COVID-19 Patients at a Tertiary Care Hospital in India.

Background and aims A descriptive analysis of patients who underwent surgical debridement for coronavirus disease 2019 (COVID-19) related mucormycosis was described, which aimed at the evaluation of perioperative clinical characteristics, perioperative complications, and outcomes. Methods We conducted a retrospective study on patients who underwent surgical intervention for mucormycosis during the COVID-19 pandemic at a tertiary care institute in India from March 1, 2021, to June 30, 2021. The medical records of 92 patients were reviewed and analyzed. Results There was a male predominance with a mean age of 50.86 years. The most common comorbidity was diabetes mellitus (DM) (98.9%). Intra-operative complications included hypotension, hyperglycemia, and hypokalemia. Most of the patients (88%) were extubated inside the operation theater, and 48% of patients had mortality. Serum ferritin levels, computed tomography severity score (CTSS), and D-dimers were significantly high in the patient who had mortality. Conclusion The perioperative mortality in patients with COVID-19 associated mucormycosis was very high. DM was the most common comorbidity followed by hypertension. Pre-operative elevated serum ferritin, D-dimer, and high CTSS were associated with higher mortality; hypokalemia, followed by hypocalcemia, was the most common perioperative and post-operative electrolyte imbalance. Thorough pre-operative optimization, multidisciplinary involvement, and perioperative care are of the utmost importance to decrease mortality and improve outcomes.

Short-term impact of poultry biochar amendments to stimulate antioxidant enzyme activity of wheat (Triticum aestivum L. HD-2967) in response to greywater.

The present study was designed to test the hypothesis that poultry manure and biochar-amended soil alter the antioxidant enzyme activity of T. aestivum L. HD-2967. For this, a box experiment was conducted using poultry-amended soil (5 g and 10 g) irrigated with greywater (50% and 100%) which was analysed on 7 and 14 days of seed sowing. Antioxidant enzyme activity (catalase, ascorbate peroxidase, and guaiacol peroxidase ) was elucidated to be varied in response to soil biochar and manure amendments both for shoots and roots so as to counteract the reactive oxygen species generated by plants under stress. Also, it was observed to be decreased on a temporal basis. Moreover, soil-biochar amendments efficiently defend the irrigation stress, increase soil nutrition, and reduce waste quantity through sustainable reuse.

Comparative evaluation of effectiveness of twenty versus fifty percent autologous serum eye drops in treatment of dry eye.

Purpose: The objective of the study was to compare the efficacy and safety of two concentration of autologous serum (AS) 20% vs 50% in recalcitrant moderate-to-severe dry eye patients. Methods: A double-blind prospective, interventional, and randomized study was done on 44 patients (80 eyes) clinically diagnosed with moderate-to-severe dry eye disease (DED) that was refractory to conventional treatment, and all patients were treated with AS20% or AS50% for 12 weeks. We documented Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), OXFORD corneal staining score (OSS), and Schirmer test (ST) at baseline, 2,4,8, and 12 weeks. These parameters were compared in both groups and between the groups by using Student's t-test. The study included 11 males and 33 females. Results: Out of 80 eyes, 33 eyes had moderate and 47 had severe DED. The age of patients in AS20% was 44.73 ± 14.37 years, and in AS50% was 46.41 ± 14.47 years. The most common etiology associated with DED was secondary Sjogren syndrome. In moderate DED, both the groups showed significant improvement in both subjective and objective parameters. But in severe DED, the AS20% group failed to show any significant improvement objectively, though subjective improvement was present. Conclusion: In refractory severe DED patients, AS50% is better option for treatment and in moderate DED both concentrations of autologous serum are effective.

Impact of greywater on germination and physiological responses of Triticum aestivum L. HD 2967 in soil amended with poultry biochar.

ABSTRACTChemical fertilizers boost crop production; however, their continued use decreases soil fertility in the long run. Nutrient recycling by the beneficiation of poultry manure into biochar and application as a soil amendment is a long-term solution for plant nutrition. The effect of poultry manure, poultry biochar and crop irrigation with 50% and 100% greywater (GW) was assessed on soil properties and growth of wheat (Triticum aestivum L. HD-2967) on the 7th and 14th day of sowing. This resulted in greater nutrients (OC, OM, C:N have values of 3.51%, 6.58%, and 16.52, respectively) in soil on the 14th day after sowing irrigated with 100% GW for soil and 10 g biochar amendments than manure. The germination and growth were boosted to 100% on day 6 after seed sowing soil and 5 g biochar. The maximum number of leaflets (4), rootlets (7) and shoot length (26.58 cm) was obtained for soil and 10 g biochar amendments with 100% GW on the 14th day of sowing. The significance of the work is that greywater and poultry biochar has been used for the irrigation of wheat as a step towards the management of both solid and liquid waste. Biochar being a potential adsorbent reduces the pollutant load of greywater while increasing the nutritive value of soil substratum and influencing plant growth. The findings could offer crucial knowledge for creating agronomic procedures to repurpose the nutrients in poultry manure and biochar to grow crops by adding value to waste and meeting the goal of bioeconomic sustainability.

Virtual screening of gut microbiome bacteriocins as potential inhibitors of stearoyl-CoA desaturase 1 to regulate adipocyte differentiation and thermogenesis to combat obesity.

The gut bacterial strains and their metabolites have been shown to play a significant role in obesity, but the molecular mechanisms underlying this association are largely unresolved. Obesity is a multifactorial problem and is controlled by various mechanisms and pathways to produce and store fat cells. Bacteriocins are secondary metabolites produced by gut bacteria to defend themselves against their competitors. Recently, they have gained great attention due to their role in metabolic disorders, including obesity. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme involved in the differentiation of adipocytes. The aim of this study is to show the regulation of SCD1 by bacteriocins and thus their importance in obesity control. We screened the human gut bacteriome for the presence of bacteriocins, predicted their structures, and showed their inhibitory role by molecular docking with SCD1. Further, to confirm the docking results, MDS of six top scoring SCD1-bacteriocin complexes were carried out for 100 ns. These six bacteriocins namely, Plantaricin S-beta, Carnolysin, Lactococcin B, Bacteriocin Iic, Plantaricin N, and Thermophilin A, with strong binding affinities, are primarily produced by bacterial strains from the Lactobacillaeacea family. These findings can be the basis of further experiments for enhanced understanding of the underlying mechanisms for obesity control, specifically bacteriocins driven regulation of the SCD1 enzyme. In addition, a consortium of bacterial strains producing these bacteriocins can be developed and used as probiotics for the amelioration of obesity and other metabolic complications.Communicated by Ramaswamy H. Sarma.

Study of analytical error in lipase assay.

Background: Lipase and amylase are the most frequently used biomarker for the diagnosis of pancreatic diseases, especially acute pancreatitis. Lipase has better diagnostic accuracy in comparison to amylase for the analysis of acute pancreatitis. However, lipase assay in random access analyzer is sometimes difficult to perform as it is exposed to different types of samples or reagents which may act as interference. Materials and Methods: In our laboratory, we found the raised values (>500 IU/L) of lipase with normal amylase in some samples. However, the immediate rerun of these samples for lipase only showed normal (<80 IU/L) lipase level. To root out this fallacy, we performed reagent and sample carryover studies. Results: The cause of the falsely raised value of lipase was revealed by reagent carryover studies. All samples which assayed triglyceride (TGL) followed by lipase immediately after it showed elevated (>500 IU/L) lipase value. This is due to the interference of microbial lipase used in TGL reagents. This was corrected by separating the analysis of lipase and TGL into two different instruments. Conclusion: If interference testing is not done, the laboratories are prone to have an analytical error in reporting and hence lead to diagnostic error. Hence, after analyzer installation, interference testing should be included in the validation protocol.

Résumé Contexte: La lipase et l'amylase sont les biomarqueurs les plus fréquemment utilisés pour le diagnostic des maladies pancréatiques, en particulier la pancréatite aiguë. La lipase a une meilleure précision diagnostique par rapport à l'amylase pour l'analyse de la pancréatite aiguë. Cependant, le dosage de la lipase dans un analyseur à accès aléatoire est parfois difficile à réaliser car il est exposé à différents types d'échantillons ou de réactifs qui peuvent agir comme des interférences. Matériels et méthodes: Dans notre laboratoire, nous avons trouvé des valeurs élevées (> 500 UI/L) de lipase avec une amylase normale dans certains échantillons. Cependant, la réexécution immédiate de ces échantillons pour la lipase n'a montré qu'un niveau de lipase normal (<80 UI/L). Pour éliminer cette erreur, nous avons effectué des études de transfert de réactifs et d'échantillons. Résultats: La cause de la valeur faussement élevée de la lipase a été révélée par des études de transfert de réactif. Tous les échantillons qui dosaient les triglycérides (TGL) suivis de la lipase immédiatement après présentaient une valeur de lipase élevée (> 500 UI/L). Cela est dû à l'interférence de la lipase microbienne utilisée dans les réactifs TGL. Cela a été corrigé en séparant l'analyse de la lipase et de la TGL dans deux instruments différents. Conclusion: Si les tests d'interférence ne sont pas effectués, les laboratoires sont susceptibles d'avoir une erreur analytique dans les rapports et donc de conduire à une erreur de diagnostic. Par conséquent, après l'installation de l'analyseur, les tests d'interférence doivent être inclus dans le protocole de validation. Mots-clés: Pancréatite aiguë, amylase, erreur diagnostique, laboratoires, lipase.

Assessment of Serum Cortisol Levels in Hypothyroidism Patients: A Cross-Sectional Study.

BACKGROUND: Hypothyroidism, characterized by insufficient thyroid hormone production, affects a significant global population, particularly women and the elderly. Recent research has emphasized the interaction between hypothyroidism and the hypothalamic-pituitary-adrenal (HPA) axis, highlighting cortisol's crucial role in the disease's physiological manifestations. OBJECTIVE: This study aims to evaluate serum cortisol levels in hypothyroid patients, examining the intricate relationship between these two endocrine systems. By exploring the potential impact of altered cortisol levels on hypothyroidism's clinical presentation and progression, the study seeks to contribute valuable insights to enhance diagnostic approaches and develop more effective treatment strategies. METHODS: A cross-sectional observational study was conducted at the Indira Gandhi Institute of Medical Sciences, assessing 65 hypothyroid cases and 65 age-matched euthyroid controls. Demographic data, medical history, and blood samples were collected, and serum cortisol, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels were measured. The study adhered to ethical considerations and received institutional approval. RESULTS: The study included 65 hypothyroid cases (56 females, 9 males) and 65 euthyroid controls. Serum cortisol showed a significant correlation with TSH and T4 levels. Linear regression revealed a negative correlation between serum T4 and T3 levels and serum cortisol in hypothyroidism. A positive correlation was observed between TSH and cortisol. These findings align with previous studies, suggesting potential regulatory mechanisms and compensatory responses in hypothyroid patients. DISCUSSION: The study's results emphasize the complex interaction between cortisol and thyroid function, suggesting a direct relationship between serum cortisol and TSH levels in hypothyroidism. Patients with severe hypothyroidism exhibited elevated cortisol concentrations, indicating a potential compensatory mechanism initiated by the HPA axis. Integrating serum cortisol assessment with conventional thyroid function tests could offer comprehensive insights into hypothyroidism severity and progression, providing a more holistic approach to patient care. CONCLUSIONS: This study contributes to understanding the complex relationship between serum cortisol levels and hypothyroidism, emphasizing the need for further research to uncover underlying mechanisms and therapeutic implications. A comprehensive understanding holds the potential for more tailored and effective treatment strategies for individuals with hypothyroidism.

Evaluation of TiO2 Nanoparticles Physicochemical Parameters Associated with their Antimicrobial Applications.

Titanium dioxide nanoparticles (TiO2NPs) usage is increasing in everyday consumer products, hence, assessing their toxic impacts on living organisms and environment is essential. Various studies have revealed the significant role of TiO2NPs physicochemical properties on their toxicity. However, TiO2NPs are still poorly characterized with respect to their physicochemical properties, and environmental factors influencing their toxicity are either ignored or are too complex to be assessed under laboratory conditions. The outcomes of these studies are diverse and inconsistent due to lack of standard protocols. TiO2NPs toxicity also differs for in vivo and in vitro systems, which must also be considered during standardization of protocols to maintain uniformity and reproducibility of results. This review critically evaluates impact of different physicochemical parameters of TiO2NPs and other experimental conditions, employed in different laboratories in determining their toxicity towards bacteria. These important observations may be helpful in evaluation of environmental risks posed by these nanoparticles and this can further assist regulatory bodies in policymaking.

Emerging frontiers of antibiotics use and their impacts on the human gut microbiome.

Antibiotics, the primary drugs used to cure bacterial diseases, are increasingly becoming ineffective due to the emergence of multiple drug resistance (MDR) leading to recurrence of previously sensitive pathogens. Human gut microbiome (GM), known to play an important role in various physiological processes, consists of pool of diverse microbes. Indiscriminate use of antibiotics during the life span of an individual may lead to development of resistant microbes e.g. Vibrio, Acinetobacter, Escherichia, Klebsiella, Clostridia, etc. in the human GM. Transmission of antibiotic resistant genes (ARGs) between pathogenic and commensal bacteria occurs more frequently in microbiome communities wherein bacteria communicate and exchange cellular constituents both among themselves and with the host. Additionally, co-factors like 'early vs. late' exposure, type of antibiotics and duration of treatment modulate the adverse effects of antibiotics on GM maturation. Furthermore, factors like mode of birth, ethnicity, malnutrition, demography, diet, lifestyle, etc., which influence GM composition, can also indirectly alter the host response to antibiotics. Currently, advanced 'omics' and culturomics approaches are revealing novel avenues to study the interplay between antibiotics and the microbiome and to identify resistant genes in these bacterial communities. Here, we discuss the recent developments that have given insights into the effects of antibiotics on the homeostatic balance of the gut microbiome and thus on human health.

Bioenergetic Failure Drives Functional Exhaustion of Monocytes in Acute-on-Chronic Liver Failure.

Objective: The monocyte-macrophage system is central to the host's innate immune defense and in resolving injury. It is reported to be dysfunctional in acute-on-chronic liver failure (ACLF). The disease-associated alterations in ACLF monocytes are not fully understood. We investigated the mechanism of monocytes' functional exhaustion and the role of umbilical cord mesenchymal stem cells (ucMSCs) in re-energizing monocytes in ACLF. Design: Monocytes were isolated from the peripheral blood of ACLF patients (n = 34) and matched healthy controls (n = 7) and patients with compensated cirrhosis (n = 7); phagocytic function, oxidative burst, and bioenergetics were analyzed. In the ACLF mouse model, ucMSCs were infused intravenously, and animals were sacrificed at 24 h and day 11 to assess changes in monocyte function, liver injury, and regeneration. Results: Patients with ACLF (alcohol 64%) compared with healthy controls and those with compensated cirrhosis had an increased number of peripheral blood monocytes (p < 0.0001) which displayed significant defects in phagocytic (p < 0.0001) and oxidative burst capacity (p < 0.0001). ACLF patients also showed a significant increase in the number of liver macrophages as compared with healthy controls (p < 0.001). Bioenergetic analysis showed markedly reduced oxidative phosphorylation (p < 0.0001) and glycolysis (p < 0.001) in ACLF monocytes. Patients with monocytes having maximum mitochondrial respiration of <37.9 pmol/min [AUC = 0.822, hazard ratio (HR) = 4.5] and baseline glycolysis of ≤42.7 mpH/min (AUC = 0.901, HR = 9.1) showed increased 28-day mortality (p < 0.001). Co-culturing ACLF monocytes with ucMSC showed improved mitochondrial respiration (p < 0.01) and phagocytosis (p < 0.0001). Furthermore, ucMSC therapy increased monocyte energy (p < 0.01) and phagocytosis (p < 0.001), reduced hepatic injury, and enhanced hepatocyte regeneration in ACLF animals. Conclusion: Bioenergetic failure drives the functional exhaustion of monocytes in ACLF. ucMSCs resuscitate monocyte energy and prevent its exhaustion. Restoring monocyte function can ameliorate hepatic injury and promote liver regeneration in the animal model of ACLF.

Defects in energy metabolism are associated with functional exhaustion of bone marrow mesenchymal stem cells in cirrhosis.

OBJECTIVES: Cellular and functional exhaustion of bone marrow mesenchymal stem cells (BM-MSC) is significantly associated with the loss of HSCs and hepatic osteodystrophy in cirrhosis. The molecular mechanisms underlying the dysfunction of BM-MSCs are not well understood. We investigated the underlying mechanisms of cellular and functional exhaustion of BM-MSCs in cirrhosis. METHODS: The MSCs were isolated retrospectively from bone marrow of decompensated alcoholic cirrhosis patients {(Trial registration: ClinicalTrials.gov NCT01902511) (n=10; MELD=16.2±2.3; CTP=8.7±2.3)} and age and gender-matched healthy controls (n=8). Global gene expression profile of healthy bone marrow MSCs (hBM-MSCs) and cirrhosis patients BM-MSCs (cBM-MSCs) were done by mRNA sequencing. XFe24-bioanalyzer analyzed the bioenergetic potential of cells. Level of different cytokines and growth factors in BM-plasma and MSCs secretome were analyzed by Luminex-based bead array. RESULTS: Analysis of differentially expressed genes showed significant (P<0.01) up-regulation of genes associated with ubiquitination and catabolism of proteins; TNF signaling, insulin resistance, and down-regulation of genes associated with DNA repair, protein processing, cell cycle, and mitochondrial respiration in cBM-MSCs in comparison to hBM-MSCs. Compared to hBM-MSCs, cBM-MSCs showed a significant defect in glycolysis due to insulin resistance and poor glucose uptake (P=0.002). This led to compromised self-renewal capacity and cellular loss of MSCs in cirrhosis. cBM-MSCs also showed a significant impairment in Oxidative phosphorylation (OXPHOS) due to mitochondrial dysfunction leading to defects in the osteogenic differentiation with early aging and senescence. CONCLUSION: Compromised energy metabolism due to inflammatory and metabolic stress-induced insulin resistance underlies the cellular and functional exhaustion of BM-MSCs in cirrhosis.

Bioelectricity generation from human urine and simultaneous nutrient recovery: Role of Microbial Fuel Cells.

Urine is a 'valuable waste' that can be exploited to generate bioelectricity and recover key nutrients for producing NPK-rich biofertilizers. In recent times, improved and innovative waste management technologies have emerged to manage the rapidly increasing environmental pollution and to accomplish the goal of sustainable development. Microbial fuel cells (MFCs) have attracted the attention of environmentalists worldwide to treat human urine and produce power through bioelectrochemical reactions in presence of electroactive bacteria growing on the anode. The bacteria break down the complex organic matter present in urine into simpler compounds and release the electrons which flow through an external circuit generating current at the cathode. Many other useful products are harvested at the end of the process. So, in this review, an attempt has been made to synthesize the information on MFCs fuelled with urine to generate bioelectricity and recover value-added resources (nutrients), and their modifications to enhance productivity. Moreover, configuration and mode of system operation, and factors enhancing the performance of MFCs have been also presented.

MTHFR C677T and MTR A2756G Gene Polymorphism in Neural Tube Defect Patients and Its Association with Red Blood Cell Folate Level in Eastern Indian Population.

Introduction: Single-nucleotide polymorphism (SNP) is a single-nucleotide change in a deoxyribose nucleic acid (DNA) sequence that occurs in >1% of population. Methylene tetra hydro folate reductase (MTHFR) C677T (rs1801133) and methionine synthase enzyme (MTR) A2756G (rs1805087) are two such SNPs occurring in coding sequence of the respective genes, which are frequently seen with neural tube defects (NTDs). MTHFR and MTR genes are involved in folate metabolism. The folate level in the course of pregnancy is treated as vital in the etiopathogenesis of NTDs. This study aims to explore the association of SNPs of both genes and red blood cell (RBC) folate levels in the predisposition to NTDs. Aims and Objective: The purpose of this investigation was to determine the relationship of NTDs with polymorphisms in MTHFR and MTR genotype and to estimate and compare the RBC folate levels in NTD patients and controls. Materials and Methods: A total of 397 individuals were enrolled (163 patients and 234 controls) for this observational study. Genotyping to find out MTHFR C677T and MTR A2756G was performed by polymerase chain reaction-restriction fragment length polymorphism technique from DNA extracted from the subject's blood. RBC folate level was estimated by chemiluminescence immunoassay method with the same blood sample. Results: The total RBC folate levels were significantly less among cases compared to controls (P = 0.020). A significant difference for RBC folate was observed between case and control groups of various genotypes of MTHFR C677T, except heterozygote CT (P = 0.459). Among MTR A2756G, genotypes with only homozygous AA have significant difference (P = 0.003) for RBC folate levels. Among different types of NTDs, there were no significant differences for RBC folate levels. Among MTHFR C677T, T allele possessed 1.9 times risk compared to C allele for the occurrence of NTDs. In MTR A2756G polymorphism, the odds of developing NTDs were 1.6 times in heterozygous AG compared to homozygous AA. Similarly, the risk for NTDs was three times higher in subjects with both heterozygous AG and CT genotypes compared to wild-type homozygous AA and CC genotypes. Conclusion: The total RBC folate levels were significantly less among cases compared to controls, and the genotypes had no such effect in decrease in RBC folate levels. The presence of mutant allele in homozygous or heterozygous condition for both SNPs had increased risk associated with NTDs.

Establishment of a murine model of acute-on-chronic liver failure with multi-organ dysfunction.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a distinct clinical entity with high probability of organ failure and mortality. Since patients generally present late, experimental models are needed to understand the pathophysiology and natural course of the disease. METHODOLOGY: To reproduce the syndrome of ACLF, chronic liver disease was induced in C57BL6 mice (6-8 weeks; approximately 20-24 g weight) by intraperitoneal administration of carbon tetrachloride (CCl4) for 10 weeks followed by an acute injury with acetaminophen (APAP) and lipopolysaccharide (LPS). Blood, ascitic fluid, and organs were collected to study cell death, regeneration, and fibrosis. RESULTS: At 24 h post-APAP/LPS infusion, the liver tissue showed increased hepatocyte ballooning and endothelial cell TUNEL positivity. This was followed by progressive hepatocyte necrosis from perivascular region at day 7 to lobular region by day 11. ACLF (day 7 and day 11) animals showed increase in bilirubin (p < 0.05), prothrombin time (p < 0.0001), blood ammonia (p < 0.001), and portal pressure post-acute hepatocellular injury similar to human ACLF. Ascites was noticed by day 11 with median serum-ascites albumin gradient of 1.2 (1.1-1.3) g/dL. In comparison to cirrhosis, ACLF group (day 7 and day 11) showed significant decrease in Sirius red (p ≤ 0.0001), collagen1 (p < 0.0001), and a-SMA proportionate area (p < 0.0001) with loss of hepatocytes regeneration (p < 0.005). At day 11, ACLF animals also showed significant increase in serum creatinine (p < 0.05) and acute tubular necrosis suggestive of organ failure, compared to cirrhotic animals. CONCLUSION: The CCL4/APAP/LPS (CALPS) model of ACLF mimics the clinical, biochemical, and histological features of ACLF with demonstrable progressive hepatocellular necrosis, liver failure, impaired regeneration, development of portal hypertension, and organ dysfunction in an animal with chronic liver disease.