Bioaccumulation of Lead and Mercury in Water, Sediment, and Fish Samples of Baraila Lake, Vaishali, Bihar.

In the current study, a protected subtropical wetland in Bihar (India), Baraila Lake, was investigated for heavy metal (Pb and Hg) status. These metals tend to bioaccumulate in fish, posing a concern to human health. This study reported the concentration of lead and mercury in water, sediment, and fish muscles of Baraila Lake in the year 2022. The samples were collected from pre-monsoon and post-monsoon seasons at four sampling locations, i.e., Loma, Dhulwar, Chakaiya, and Kawai Baraila, and were analyzed in triplicates. Lead concentration in water samples of all four sites of Baraila Lake observed during pre-monsoon and post-monsoon season exceeded the permissible limit for drinking water, while the mercury concentration of all sites was under the permissible limit in both seasons as prescribed by WHO. The extent of elemental pollution was evaluated using the Geo-accumulation index (Igeo), contamination factor (CF), contamination degree (Cd), ecological risk factor (Er), and the potential ecological risk index (Ri). Lead concentration in fish muscles of both seasons exceeded the permissible limit, while the concentration of mercury exceeded in Xenentodon cancila (0.55 ± 0.07 µg/g) during the pre-monsoon season. Also, estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI) were calculated in different fish muscles to assess potential human health risks. A higher THQ value of 1303 was observed in carnivore fish during the pre-monsoon season.

Unveiling the Rising Threat of Cadmium Pollution and Alarming Health Risks Associated with the Consumption of 15 Commercially Important Fish Species in the Middle Stretch of River Ganga, at Patna, India.

Among environmental contaminants, the rising level of cadmium in freshwater ecosystems is one of the most significant global concerns. The study addresses the current pollution status of cadmium in the middle stretch of River Ganga and explores the potential hazard associated with the consumption of 15 commercially important fish species by the inhabitants. Together 72 water and sediment samples were analyzed from the four representative sampling sites of River Ganga after the surveillance of major anthropogenic stressors. The concentration of cadmium ranges from 0.003 to 0.011 mg/l and 0.2 to 3.48 mg/kg in water and sediment respectively in 2022. The average concentration of cadmium was recorded to be the highest in Channa punctatus (1.35 mg/kg), followed by Rita rita = Johnius coitor (1.15 mg/kg), and the lowest in Labeo bata (0.2 mg/kg). The finding highlights greater exposure duration and feeding preferences of fish species have played a significant role in the bioaccumulation of the metal in the riverine system. Notably, the domestic effluents, agricultural runoffs, and pollutants brought along by the tributaries of River Ganga are identified as the main anthropogenic stressors for the moderate to considerably polluted status of the River Ganga. The target hazard quotient (THQ) and target carcinogenic risk (TCR) have revealed a higher susceptibility to cadmium contamination in children followed by females, and males. In addition, hierarchical cluster analysis (HCA) has noted intake of Rita rita, Channa punctata, Puntius sophore, and Johnius coitor could be more detrimental to children's health than adults.

Spatio-temporal evaluation of the impact of anthropogenic stressors on physico-chemical characteristics and water quality of the River Ganga using GIS-based approach in the middle Gangetic Plains at Patna, Bihar, India.

The present study aimed to assess the impact of anthropogenic stressors on the physico-chemical characteristics and water quality of the River Ganga employing a GIS-based approach in the middle Gangetic Plain at Patna, India. After the survey, sand mining, bridge construction, and disposal of untreated domestic and sewage wastes were selected as major anthropogenic stressors. A total of 48 samples were collected in pre-monsoon and post-monsoon seasons of 2022 and were analyzed for 16 physico-chemical parameters, namely water temperature (WT), pH, electrical conductivity (EC), total dissolved solids (TDS), turbidity, dissolved oxygen (DO), biological oxygen demand (BOD), total hardness (TH), Ca2+, Mg2+, Na+, K+, Cl- and SO42- ions, following standard protocols. The WQI was calculated using the Weighted Arithmetic Water Quality Index (WAQWI) method and spatial maps were created using ArcGIS software. The result revealed significant seasonal variation in several physico- chemical parameters except for Ca2+, K+ and TA (p > 0.05). ANOVA revealed significant variation for BOD and COD at Ghagha and Triveni, whereas for nitrate at Gai Ghat reference and impact sites, respectively. The Water Quality Index (WQI) revealed a deterioration in water quality by 60% in post-monsoon season. HCA revealed that the WQI was mostly governed by TDS, TH, TA, and EC.

Melatonin modulates L-arginine metabolism in tumor-associated macrophages by targeting arginase 1 in lymphoma.

L-Arginine metabolism plays a crucial role in determining the M1/M2 polarization of macrophages. The M1 macrophages express inducible nitric oxide synthase (iNOS), while the M2 macrophages express arginase 1 and metabolize arginine into nitric oxide and urea, respectively. The tumor microenvironment promotes M2 macrophage polarization and consequently switches the metabolic fate of arginine from nitric oxide towards urea production. Importantly, infiltration of M2 macrophages or tumor-associated macrophages (TAMs) has been correlated with poor prognosis of various cancer types. Melatonin is well reported to have antitumor and immunomodulatory properties. However, whether and how it impacts the polarization of TAMs has not been elucidated. Considering the crucial role of arginine metabolism in macrophage polarization, we were interested to know the fate of L-arginine in TAMs and whether it can be reinstated by melatonin or not. We used a murine model of Dalton's lymphoma and established an in vitro model of TAMs. For TAMs, we used the ascitic fluid of tumor-bearing hosts to activate the macrophages in the presence and absence of lipopolysaccharide (LPS). In these groups, L-arginine metabolism was evaluated, and then the effect of melatonin was assessed in these groups, wherein the metabolic fate of arginine as well as the expression of iNOS and arginase 1 were checked. Furthermore, in the in vivo system of the tumor-bearing host, the effect of melatonin was assessed. The in vitro model of TAMs showed a Th2 cytokine profile, reduced phagocytic activity, and increased wound healing ability. Upon investigating arginine metabolism, we observed high urea levels with increased activity and expression of arginase 1 in TAMs. Furthermore, we observed reduced levels of LPS-induced nitric oxide in TAMs; however, their iNOS expression was comparable. With melatonin treatment, urea level decreased significantly, while the reduction in nitric oxide level was not as significant as observed in its absence in TAMs. Also, melatonin significantly reduced arginase activity and expression at the transcriptional and translational levels, while iNOS expression was affected only at the translational level. This effect was further investigated in the in vivo system, wherein melatonin treatment reversed the metabolic fate of arginine, from urea towards nitric oxide, within the tumor microenvironment. This effect was further correlated with pro-apoptotic tumor cell death in the in vivo system. Our results reinforced the immunomodulatory role of melatonin and offered a strong prospect for activating the anti-tumor immune response in cancer conditions.

Lipopolymeric Nanocarrier Enables Effective Delivery of CRISPR/Cas9 Expressing Plasmid.

CRISPR/Cas9 has proven its accuracy and precision for gene editing by making a double-strand break at the predetermined site. Despite being a mainstream gene editing tool, CRISPR/Cas9 has limitations for its in vivo delivery due to the physico-chemical properties such as high molecular weight, supranegative charge, degradation in the presence of nucleases, etc. Hereby, a cationic lipopolymer is explored for its efficiency in delivering CRISPR/Cas9 plasmid (pCas9) in vitro and in vivo. The lipopolymer is utilized to form blank cationic nanoplexes having a zeta potential of +15.8 ± 0.7 mV. Being cationic, the blank nanoplexes are able to condense the pCas9 plasmid at a ratio of 1:20 with a complexation efficiency of ≈98% and show a size and zeta potential of ≈141 ± 16 nm and 4.2 mV ± 0.7, respectively. The pCas9-loaded nanoplexes show a transfection efficiency of ≈69% in ARPE-19 cells and show ≈22% of indel frequency, indicating the successful translation of Cas9 protein and guide RNA in the cytosol. Further, they are found to be stable under in vivo environment when given intravenously in Swiss albino mice. These lipopolymeric nanoplexes can be a potential carrier for CRISPR plasmids for genome editing applications.

Assessing the geochemical processes controlling groundwater quality and their possible effect on human health in Patna, Bihar.

This research was conducted in the urban area of Patna region, the capital and largest city of Bihar, which is part of the Indo-Gangetic alluvium plain. This study aims to identify the sources and processes controlling groundwater's hydrochemical evolution in the Patna region's urban area. In this research, we evaluated the interplay between several measures of groundwater quality, the various possible causes of groundwater pollution, and the resulting health risks. Twenty groundwater samples were taken from various locations and examined to determine the water quality. The average EC of the groundwater in the investigated area was 728 ± 331.84 µS/cm, with a range of around 300-1700 µS/cm. Positive loadings were seen for total dissolved solids (TDS), electrical conductivity (EC), calcium (Ca2+), magnesium (Mg2+), sodium (Na+), chloride (Cl-), and sulphate (SO42-) in principal component analysis (PCA), demonstrating that these variables accounted for 61.78% of the total variance. In the groundwater samples, the following main cations are the most prevalent such as Na+ > Ca2+ > Mg2+ > K+, while the dominant anions are HCO3- > Cl- > SO42-. The elevated HCO3- and Na+ ions indicate that carbonate mineral dissolution might affect the study area. The result demonstrated that 90% of samples fall into the Ca-Na-HCO3 type, remaining in the mixing zone. The presence of the NaHCO3 kind of water is suggestive of shallow meteoric water, which may have originated from the river Ganga that is located nearby. The results show that a multivariate statistical analysis and graphical plots successfully identify the parameters controlling groundwater quality. In accordance with guidelines for safe drinking water, the electrical conductivity and potassium ion concentrations in the groundwater samples are 5% higher than acceptable levels. People who take large amounts of salt replacements report feeling tight in the chest, vomiting, having diarrhoea, developing hyperkalaemia, having trouble breathing, and even experiencing heart failure.

Chemometric approach to evaluate the chemical behavior of rainwater at high altitude in Shaune Garang catchment, Western Himalaya.

The present research has been performed to analyze the chemical behavior of rainwater of the Shaune Garang catchment (32.19° N, 78.20° E) in the Baspa basin, located at a high elevation (4221 m above mean sea level) in the Himachal Himalaya, India. During the study period, sixteen rainwater samples were collected from the Shaune Garang catchment at five different sites. The volume-weighted mean (VWM) pH value of rainwater ranged between 4.59 and 6.73, with an average value of 5.47 ± 0.69, indicating the alkaline nature of rainfall. The total ionic strength in the rainwater ranged from 113.4 to 263.3 µeq/l with an average value of 169.1 ± 40.4 µeq/l. The major dominant cations were Ca2+ (43.10%) and Na+ (31.97%) and anions were Cl- (37.68%), SO42- (28.71%) and NO3- (23.85%) in rainwater. The ionic ratios were calculated among all the ions. The fraction of (NO3- +Cl-) with SO42- was measured as 2.3, which specifies sour faces of rainwater due to HNO3, H2SO4, and HCl. A multivariate statistical assessment of rainwater chemistry through Principal Component Analysis (PCA) shows the significance of four factors controlling 78.37% of the total variance, including four-component (PC1 explained 27.89%, PC2 explained 24.98%, PC3 explained 14.64%, PC4 explained 10.85%). However, the individual contribution of Factor 1(PC1) explains 27.89% of the total variance (78.37%) and displays a strong optimistic loading for Ca2+ and Cl-. Further, high loading of Ca2+ and NO3- and moderate loading of SO42- signify the contribution of burning fossil fuel and soil dust. Anthropogenic and natural pollutants influence the composition of rainwater in the pristine Himalayas due to local and long-distance transportation. The study area receives precipitation from the West and North-West, transporting dust and fossil fuel emissions from the Thar Desert and Northwestern countries.

Circulating extracellular vesicles induce monocyte dysfunction and are associated with sepsis and high mortality in cirrhosis.

BACKGROUND: Sepsis is common in cirrhosis and is often a result of immune dysregulation. Specific stimuli and pathways of inter-cellular communications between immune cells in cirrhosis and sepsis are incompletely understood. Immune cell-derived extracellular vesicles (EV) were studied to understand mechanisms of sepsis in cirrhosis. METHODS: Immune cell-derived EV were measured in cirrhosis patients [Child-Turcotte-Pugh (Child) score A, n = 15; B n = 16; C n = 43 and Child-C with sepsis (n = 38)], and healthy controls (HC, n = 11). In vitro and in vivo functional relevance of EV in cirrhosis and associated sepsis was investigated. RESULTS: Monocyte, neutrophil and hematopoietic stem cells associated EV progressively increased with higher Child score (P < .001)and correlated with liver disease severity indices (r2  > 0.3, P < .001), which further increased in Child C sepsis than without sepsis(P < .001); monocyte EV showing the highest association with disease stage [P = .013; Odds ratio-4.14(1.34-12.42)]. A threshold level of monocyte EV of 53/µl predicted mortality in patients of Child C with sepsis [Odds ratio-6.2 (2.4-15.9), AUROC = 0.76, P < .01]. In vitro EV from cirrhotic with sepsis compared without sepsis, induced mobilization arrest in healthy monocytes within 4 hours (P = .004), reduced basal oxygen consumption rate (P < .001) and induced pro-inflammatory genes (P < .05). The septic-EV on adoptive transfer to C57/BL6J mice, induced sepsis-like condition within 24 h with leukocytopenia (P = .005), intrahepatic inflammation with increased CD11b + cells (P = .03) and bone marrow hyperplasia (P < .01). CONCLUSION: Extracellular vesicles induce functional impairment in circulating monocytes and contribute to the development and perpetuation of sepsis. High levels of monocyte EV correlate with mortality and can help early stratification of sicker patients.

Risk assessment of low arsenic exposure using biomarkers of oxidative and genotoxic stress in a piscine model.

The high level exposure to arsenic induces marked oxidative and genotoxic stress. However, information on the potential of low level arsenic exposure in this context is still scanty. In the present study, the extent of oxidative stress and genetic toxicity induced by low arsenic exposure was explored in freshwater fish Channa punctatus. Fish were exposed to low levels of arsenic (10 and 50 µg L-1) as well as to its high level (500 µg L-1) using sodium arsenite in aquaria water for 14 consecutive days. The TBARS assay for lipid peroxidation exhibited the increased occurrence of oxidative damage in the erythrocytes of fish at both the lower and higher levels of arsenic exposure. The level of reduced glutathione was also elevated in all the three arsenic exposed groups of fish compared to control. In contrast, significant decline was observed in the levels of three major antioxidant enzymes namely, superoxide dismutase, catalase and glutathione peroxidase, upon exposure to higher as well as lower levels of arsenic. Significant increases in micronucleus induction were found in the erythrocytes of fish even at the low levels of arsenic exposure. The study further revealed the occurrence of DNA fragmentation in the erythrocytes of fish at low arsenic exposures as well. The low level exposure to arsenic (using sodium arsenite), therefore, appeared to be capable of inducing noticeable oxidative stress as well as potential genotoxic effect in Channa punctatus. Moreover, the ability of arsenic to induce oxidative stress invariably appeared correlated with its genotoxic potential.

Amelioration of Dalton's lymphoma-induced angiogenesis by melatonin.

For tumor to grow beyond 1-2 mm3 size, tumor recruits new blood vessels referred as angiogenesis; therefore, targeting angiogenesis can be a promising strategy to suppress cancer progression. In this study, in order to develop a good angiogenesis model, we investigated effect of Dalton's lymphoma on angiogenesis and further monitored the role of melatonin on regulation of angiogenesis. To evaluate angiogenesis, endothelial cells were isolated from main thoracic aorta and cultured in vitro in the presence or absence of Dalton's lymphoma supplemented with or without melatonin to monitor their role on its proliferation and migration, a hallmark of angiogenesis. Chick chorioallantoic membrane as well as mice mesentery which allows in vivo studies of tumor angiogenesis and testing of anti-angiogenic molecules was used to validate the in vitro analysis. To further extend our understanding about the regulation of the angiogenesis, we evaluated expression of tissue inhibitor of metalloproteinases 3, vascular endothelial growth factor, vascular endothelial growth factor receptor, and fibroblast growth factor in Dalton's lymphoma cells and mesentery by semiquantitative and quantitative reverse transcription polymerase chain reaction analysis. Dalton's lymphoma ascites induced significant increase in endothelial cell proliferation, migration, and sprouting of the tertiary branching in chorioallantoic membrane and mesentery of Dalton's lymphoma-bearing mice, whereas melatonin treatment led to their inhibition in a dose-dependent manner. Semiquantitative and quantitative reverse transcription polymerase chain reaction analysis of melatonin-treated Dalton's lymphoma cells and mesentery tissue clearly demonstrated restoration of angiogenesis-related genes tissue inhibitor of metalloproteinases 3 and reduction of vascular endothelial growth factor, vascular endothelial growth factor receptor, and fibroblast growth factor messenger RNA expression. Taken together, our results strongly demonstrate that Dalton's lymphoma provides pro-angiogenic environment leading to significant increase in angiogenesis, and further melatonin treatment reduced the Dalton's lymphoma ascites-induced angiogenesis implying that Dalton's lymphoma can serve as a very good model to study angiogenesis as well as for screening of drugs that can target angiogenesis.

Concentration of organochlorines in Ganges River dolphins from Patna, Bihar.

Concentrations of DDT, HCH, aldrin and endosulfan were determined in river dolphins from the River Ganges, Patna. Among the organochlorines studied in the dolphins, DDT concentration was highest followed by HCH. This shows exposure of dolphins to these organochlorine pesticides. Presences of organochlorines to higher degree in tissues suggest that the river dolphins be at greater risk due to pesticidal contamination of the river system.