Enhancement of nutraceutical and anti-diabetic potential of fenugreek (Trigonella foenum-graecum). Sprouts with natural elicitors.

Trigonella foenum-graecum has been extensively used for centuries in traditional medicine systems for the cure of health ailments including diabetes. Improving the medicinal attributes of plants through the elicitation strategy is gaining great interest in the recent past. In the current study, an attempt is made to reveal the role and possible mechanism of action of vitamin C elicit phytochemical-rich aqueous extract of 4th day germinated IM6 genotype fenugreek sprouts in the form of lyophilized powder (IM6E) under both in vitro and in vivo conditions. The IM6E demonstrated strong α-glucosidase activity (95.24 %) and moderate α-amylase and invertase inhibition activities under in vitro conditions. The High Performance Thin Layer Chromatography (HPTLC) based analysis demonstrated that IM6E possess significantly higher concentration of phenolic phytochemical quercetin (0.148 %) as compared to diosgenin and trigonelline bioactive anti-diabetic nutraceuticals. In normal rats after loading with glucose and sucrose, the IM6E administration in a dose-dependent manner significantly reduced the post-prandial hyperglycemia, in a similar fashion as the anti-diabetic drug voglibose as evident from the area under curves (AUC) of oral glucose tolerance test (OGTT) and oral sucrose tolerance test (OSTT) tests. The administration of IM6E in streptozotocin (STZ) induced diabetic rats drastically improved the antioxidant activity of plasma in them as determined by Ferric Reducing Ability of Plasma (FRAP) and the effect was found to be dose-dependent. The oral administration of IM6E in diabetic rats normalized almost all the deregulated biochemical markers like liver enzymes, lipids and significantly decreased higher blood glucose levels with increasing insulin levels as compared to diabetic control. The best concentration of IM6E was found to be 300 mg/kg b.w after 21 days of experimentation. The intra-peritoneal glucose tolerance test (IPGTT) in diabetic rats responded very well to IM6E treatment and 100 mg/kg.b.w. behaved almost like the administration of 0.5U insulin/kg bw, and thus indicating the insulinotropic nature of IM6E. Our findings clearly reveal the use of IM6E for diabetes management and at the same it possesses great potential when combined with voglibose to ameliorate diabetes and its associated complications to a greater extent due to synergistic effects as compared to monotherapy. However, more clinical trials need to be performed before recommending IM6E as an anti-diabetic alternative medicine.

Roles of breast cancer resistance protein and organic anion transporting polypeptide 2B1 in gastrointestinal toxicity induced by SN-38 under inflammatory conditions.

Drug transporters are among the factors that determine the pharmacokinetic profiles after drug administration. In this study, we investigated the roles of drug transporters involved in transport of SN-38, which is an active metabolite of irinotecan, in the intestine under inflammatory conditions in vitro and determined their functional consequences. The expression alterations of breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 2B1 were determined at the mRNA and protein levels, and the subsequent functional alterations were evaluated via an accumulation study with the representative transporter substrates [prazosin and dibromofluorescein (DBF)] and SN-38. We also determined the cytotoxicity of SN-38 under inflammatory conditions. Decreased BCRP expression and increased OATP2B1 expression were observed under inflammatory conditions in vitro, which led to altered accumulation profiles of prazosin, DBF, and SN-38, and the subsequent cytotoxic profiles of SN-38. Treatment with rifampin or novobiocin supported the significant roles of BCRP and OATP2B1 in the transport and cytotoxic profile of SN-38. Collectively, these results suggest that BCRP and OATP2B1 are involved in the increased cytotoxicity of SN-38 under inflammatory conditions in vitro. Further comprehensive research is warranted to completely understand SN-38-induced gastrointestinal cytotoxicity and aid in the successful treatment of cancer with irinotecan.

Efficacy of Probiotic Strains Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 in Management of Obesity: An In Vitro and In Vivo Analysis.

The prevalence of obesity, characterized by an excessive accumulation of adipose tissue and adipocyte hypertrophy, presents a major public health challenge. This study investigates the therapeutic potential of two probiotic strains, Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093, in the context of obesity. Utilizing 3T3-L1 cell-derived human adipocytes, we assessed Probio65's and Probio-093's capacity to mitigate triglyceride accumulation and influence adipocytokine production in vitro. Subsequently, an in vivo trial with male C57BL/6J mice examined the effects of both probiotic strains on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. This study employed both live and ethanol-extracted bacterial cells. The results demonstrated significant reductions in the triglyceride deposition, body weight, and adipose tissue mass in the treated groups (p < 0.05). Furthermore, both strains modulated adipokine profiles by downregulating proinflammatory markers such as PAI-1, leptin, TNF-α, STAMP2, F4/80, resistin, and MCP-1, and upregulating the insulin-sensitive transporter GLUT4 and the anti-inflammatory adiponectin (p < 0.05). Our findings suggest that Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 are promising agents for microbiome-targeted anti-obesity therapies, offering the effective mitigation of obesity and improvement in adipocyte function in a murine model.

Survey to identify the metal accumulation pathway in humans using hair and nail as biomarkers from fisherfolk population.

Human hair and nail samples from Cuddalore fisherfolk populations were used as biomarkers for assessing metal concentrations in humans. Hair samples from 80 participants (47 men and 33 women) and nail samples from 40 participants (21 men and 19 women) were collected, and the concentrations of Cd, Cu, Pb, and Zn were assessed using an atomic absorption spectrophotometer (AAS). Metal data from AAS were compared with the survey questionnaire's personal and dietary parameters. Results indicate that both personal and dietary parameters may influence metal exposure; however, majority of the sources may have originated from metal-contaminated seafood. Higher metal accumulation in communities, especially those which consume seafood on a daily basis, may increase the possibility for them to get affected by metal-related diseases. Based on environmental parameters, people who live ≤500 m from industrial zones accumulate more metals. Further extensive studies with more individuals and more questionnaire parameters are needed to identify the metal accumulation pathway in humans.

Heavy metal contamination along different tidal zones of a tropical Bay of Bengal coastal environment influenced by various anthropogenic activities.

The spatiotemporal variations of five heavy metals (Cd, Cu, Cr, Pb, and Zn) in the beach sediments along the Tamil Nadu coast sourced from various anthropogenic activities were assessed using atomic absorption spectrophotometry (AAS). Various pollution monitoring indices were computed to clearly understand the metal pollution status along the Tamil Nadu coastline. The metal concentrations in sediments were typically higher in the summer season than in the monsoon season. In the monsoon season, metal concentration followed a decreasing order of Zn > Cr > Cu > Pb > Cd, and in the summer season, the order was Cr > Zn > Cu > Pb > Cd. During the monsoon season, freshwater runoff from the rainfall dilutes the sediments and their trace element load. However, due to a lack of freshwater influx during the summer season, the heavy metals in the sediments get concentrated and showed elevated levels. Geo-accumulation index, ecological risk index, pollution load index, and contamination degree clearly depict that Cd and Pb have higher accumulation and pose greater hazard when compared with other metals. The rivers flowing in the region also transport the heavy metals from the mainland to the estuaries and coastal environments. Metal levels along the Tamil Nadu coast are influenced by various anthropogenic activities persistent along the coastline. Some of the activities that cause metal contamination are mining, milling, electroplating, furnishing, pharmaceutical industries, fishing, harbor activities, urban runoff, and agricultural runoff, which release a variety of toxic metals into the coastal environment.

Modeling of Valeriana wallichii Habitat Suitability and Niche Dynamics in the Himalayan Region under Anticipated Climate Change.

An increase in atmospheric greenhouse gases necessitates the use of species distribution models (SDMs) in modeling suitable habitats and projecting the impact of climate change on the future range shifts of the species. The present study is based on the BIOMOD ensemble approach to map the currently suitable habitats and predict the impact of climate change on the niche shift of Valeriana wallichii. We also studied its niche dynamics using the ecospat package in R software. Values of the area under curve (AUC) and true skill statistics (TSS) were highly significant (>0.9), which shows that the model has run better. From 19 different bioclimatic variables, only 8 were retained after correlation, among which bio_17 (precipitation of driest quarter), bio_1 (annual mean temperature), and bio_12 (annual mean precipitation) received the highest gain. Under future climate change, the suitable habitats will be significantly contracted by −94% (under representative concentration pathway RCP 8.5 for 2070) and −80.22% (under RCP 8.5 for 2050). There is a slight increase in habitat suitability by +16.69% (RCP 4.5 for 2050) and +8.9% (RCP 8.5 for 2050) under future climate change scenarios. The equivalency and similarity tests of niche dynamics show that the habitat suitability for current and future climatic scenarios is comparable but not identical. Principal Component Analysis (PCA) analysis shows that climatic conditions will be severely affected between current and future scenarios. From this study, we conclude that the habitats of Valeriana wallichii are highly vulnerable to climate shifts. This study can be used to alleviate the threat to this plant by documenting the unexplored populations, restoring the degraded habitats through rewilding, and launching species recovery plans in the natural habitats.

Parasitic anomalies observed in snow trout due to anthropogenic stress in water bodies.

There is interrelationship of the environmental conditions and fish health. Decrease or increase of pollution in aquatic ecosystem have direct impact on presence or absence of parasites. Fish living under optimum environmental, well-nourished conditions are more resistant to diseases than fish weakened by malnutrition caused by parasite infestation or due to deterioration of environmental conditions because ofpollution. Fish encounters common parasites in wild and in culture systems. Parasites attach to the host through suckers and hooks and make their way inside the host through different means, which include skin, through mouth along with food, by means of gills. The hosts were collected during Jan 2019 to Jan 2020 from river Veshaw. During this study it was observed that presence of parasites causes some changes in fish which can serve as indicators of deterioration in aquatic habitat. Clinical signs were noticed in fish hosts collected from sites which received waste due to anthropogenic activities. Parasitic anomalies in the host collected from polluted site was observed to include body deformaties, gastric distention, lesions in gut, increased mucus production, damage in gill filaments etc.

Study of Ultrastructural Abnormalities in the Renal Cells of Cyprinus carpio Induced by Toxicants.

Transmission Electron Microscopic (TEM) assessments were performed on the renal cells of common carp Cyprinus carpio to observe the deleterious effects of two organophosphate insecticides, Phorate and Dimethoate. Pesticides such as Phorate and Dimethoate often pollute aquatic systems where they may negatively impact fish, but so far, the ultrastructural toxicity of these pesticides remains poorly understood. Here, we use Transmission Electron Microscopy (TEM) to determine how acute exposure to sublethal concentrations of these two pesticides may affect the renal cells of common carp Cyprinus carpio. For each insecticide, the fish were divided in four experimental conditions: a control and three different exposure concentrations of the pesticide. The Phorate treated fish were exposed to three sublethal concentrations of 0.2 mg/L, 0.4 mg/L, 0.6 mg/L for a duration of 24, 48 & 72 h. The dimethoate treated fish were exposed to three sublethal concentrations of 0.005 mL/L, 0.01 mL/L, 0.015 mL/L for a duration of 24, 48 and 72 h. The two-dimensional transmission electron microscopy revealed ultrastructural abnormalities in the treated fish renal cells when exposed to two toxicants including deformation in the glomerulus, vacuolization of cytoplasm, degenerative nucleus and damaged mitochondria. Furthermore, the ultrastructural abnormalities were more prominent with the increase in the concentrations of both the insecticides and also with their exposure period. Overall, these results provide important baseline data on the ultrastructural toxicity of Phorate and Dimethoate and will allow important follow-up studies to further elucidate the underlying cellular mechanisms of pesticide toxicity in wildlife.

Elicitation of the in vitro Cultures of Selected Varieties of Vigna radiata L. With Zinc Oxide and Copper Oxide Nanoparticles for Enhanced Phytochemicals Production.

This study was conducted to develop a protocol for in vitro shoot multiplication and callus induction of various mung bean varieties to obtain enhanced phytochemical content with the help of elicitors. For shoot multiplication, two types of explants (shoot tips and nodal tips) of three varieties of mung bean (Mung NCM-13, MgAT-7, and MgAT-4) were used. Both types of explants from in vitro and in vivo sources were cultured on the MS medium supplemented with different concentrations (0.25-3.0 mg/L, increment of 0.5 mg/L) and combinations of BAP and IBA as independent treatments. For callus induction, leaf explants (in vitro source) were cultured on MS medium supplemented with 2,4-D (1-3 mg/L) alone or in combination with BAP or NAA (0.5 and 1.0 mg/L). For the enhanced production of phenolics and glycosides, calli were cultured on MS media supplemented with zinc oxide (0.5 mg/L) and copper oxide nanoparticles (0.5 mg/L) as nano-elicitors. Results showed that in vitro explants responded better in terms of shoot length, number of shoots, and number of leaves per explant when compared to in vivo explants. Moreover, shoot tips were better than nodal explants to in vitro culturing parameters. All three varieties showed the optimized results in the MS medium supplemented with 1 mg/L BAP, while roots were produced only in cultures fortified with 1 mg/L IBA. The leaf explants of in vitro and soil-grown plantlets showed a maximum callogenic response of 90 and 80%, respectively, on MS medium supplemented with 2,4-D (3 mg/ml). Maximum phenolic content (101.4 µg of gallic acid equivalent/g) and glycoside content (34 mg of amygdalin equivalent/g of plant material) was observed in the calli cultured on MS medium supplemented with 3 mg/L of 2,4-D. Furthermore, the addition of zinc oxide (0.5 mg/L) and copper oxide (0.5 mg/L) nanoparticles to the callus culture medium significantly enhanced the phenolic content of Mung NCM-13 (26%), MgAT-7 (25.6%), and MgAT-4 (22.7%). Glycosidic content was also found to be increased in Mung NCM-13 (50%), MgAT-7 (37.5%), and MgAT-4 (25%) varieties when compared to the control. It is suggested that elicitation of in vitro cultures of mung beans with nanoparticles could be an effective strategy for the enhanced production of secondary metabolites.

Effect of dietary supplementation of Neem, Azadirachta indica leaf extracts on enhancing the growth performance, chemical composition and survival of rainbow trout, Oncorhynchus mykiss.

Rainbow trout Oncorhynchus mykiss has a great nutritional value and delicious taste. A 90-days experimental trial was conducted to investigate the effect of dietary leaf extract of neem tree Azadirachta indica as a feeding supplement on the growth performance and proximate composition of O. mykiss. Four experimental diets were designed as T1 (with 5% A. indica leaf extract), T2 (with 7% of A. indica leaf extract), T3 (with 10% A. indica leaf extract), and T4 (control group feed with a regular diet with 0% A. indica leaf extract). The average initial weight of fry 0.4 ± 0.14 g was stocked at 25 fish/tank with two replicates per treatment (4 × 2 = 8). After 90 days of the experimental trial, One-way ANOVA showed significant differences in final body weight, weight gain, specific growth rate, feed conversion ratio, and survival rate among the treatment groups (p < 0.05). The highest final body weight (48.10 g) and weight gain (47.70 g) was observed in T2 with 7% A. indica leaf extract, which was significantly different from the other treatments (p < 0.05). The lowest FCR was recorded in T2 (1.90), which was significantly different compared to other treatment groups (p < 0.05). Inclusion of A. indica leaf extract in formulated feed for rainbow trout had significant effects in the hepatosomatic index, viscerosomatic index and Fulton's condition factor (p < 0.05), but there was no significant difference in the survival rate of rainbow trout fry treated with different experimental diets (p > 0.05). The phenomenal regression indicates that 7.5% A. indica inclusion is optimum for best growth performance for rainbow trout under a controlled environment. Thus, the present study suggests that the dietary leaf extract has performed an excellent nutritional supplement by enhancing growth performance and health conditions of rainbow trout in the hatchery conditions.

Genome-Wide Analysis of Cytochrome P450s of Alternaria Species: Evolutionary Origin, Family Expansion and Putative Functions.

Cytochrome P450s are a group of monooxygenase enzymes involved in primary, secondary and xenobiotic metabolisms. They have a wide application in the agriculture sector where they could serve as a target for herbicides or fungicides, while they could function in the pharmaceutical industry as drugs or drugs structures or for bioconversions. Alternaria species are among the most commonly encountered fungal genera, with most of them living as saprophytes in different habitats, while others are parasites of plants and animals. This study was conducted to elucidate the diversity and abundance, evolutionary relationships and cellular localization of 372 cytochrome P450 in 13 Alternaria species. The 372 CYP proteins were phylogenetically clustered into ten clades. Forty (40) clans and seventy-one (71) cyp families were identified, of which eleven (11) families were found to appear in one species each. The majority of the CYP proteins were located in the endomembrane system. Polyketide synthase (PKS) gene cluster was the predominant secondary metabolic-related gene cluster in all the Alternaria species studied, except in A. porriof, where non-ribosomal peptide synthetase genes were dominant. This study reveals the expansion of cyps in these fungal genera, evident in the family and clan expansions, which is usually associated with the evolution of fungal characteristics, especially their lifestyle either as parasites or saprophytes, with the ability to metabolize a wide spectrum of substrates. This study can be used to understand the biology, physiology and toxigenic potentials of P450 in these fungal genera.

Network Pharmacology and Bioinformatics Approach Reveals the Multi-Target Pharmacological Mechanism of Fumaria indica in the Treatment of Liver Cancer.

Liver cancer (LC), a frequently occurring cancer, has become the fourth leading cause of cancer mortality. The small number of reported data and diverse spectra of pathophysiological mechanisms of liver cancer make it a challenging task and a serious economic burden in health care management. Fumaria indica is a herbaceous annual plant used in various regions of Asia to treat a variety of ailments, including liver cancer. Several in vitro investigations have revealed the effectiveness of F. indica in the treatment of liver cancer; however, the exact molecular mechanism is still unrevealed. In this study, the network pharmacology technique was utilized to characterize the mechanism of F. indica on liver cancer. Furthermore, we analyzed the active ingredient-target-pathway network and uncovered that Fumaridine, Lastourvilline, N-feruloyl tyramine, and Cryptopine conclusively contributed to the development of liver cancer by affecting the MTOR, MAPK3, PIK3R1, and EGFR gene. Afterward, molecular docking was used to verify the effective activity of the active ingredients against the prospective targets. The results of molecular docking predicted that several key targets of liver cancer (along with MTOR, EGFR, MAPK3, and PIK3R1) bind stably with the corresponding active ingredient of F. indica. We concluded through network pharmacology methods that multiple biological processes and signaling pathways involved in F. indica exerted a preventing effect in the treatment of liver cancer. The molecular docking results also provide us with sound direction for further experiments. In the framework of this study, network pharmacology integrated with docking analysis revealed that F. indica exerted a promising preventive effect on liver cancer by acting on liver cancer-associated signaling pathways. This enables us to understand the biological mechanism of the anti liver cancer activity of F. indica.

Implications of Decreased Expression of miR-125a with Respect to Its Variant Allele in the Pathogenesis of Recurrent Pregnancy Loss: A Study in a High Incidence Zone.

Pregnancy is controlled by several types of genes and the regulation of their expression is tightly controlled by miRNAs. The present study was carried out to explore the association between miR-125a polymorphic sequence variation and its expression and recurrent pregnancy loss (RPL) compared to full-term healthy controls. A total of 150 women that had experienced two or more RPLs and 180 healthy controls (two or more full-term pregnancies) were recruited, along with 50 product of conception (POC) samples from the corresponding RPL patients, and evaluated for miR-125a SNPs by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP), which was confirmed by high resolution melting (HRM)/DNA sequencing. Additionally, the expression of miR-125a was quantified with q−PCR in the maternal plasma of 40 corresponding RPL patients against healthy controls. The frequency of variant genotype CC was significantly higher in RPL cases (19.3%) than controls (10.5%), with an odds ratio of >2 (p = 0.025). The expression levels of miR-125a were markedly decreased in RPL cases compared to healthy controls (p < 0.05). Variant genotype CC was found significantly more often in RPL cases than controls (0.34 vs. 0.20; p < 0.05).In this study, miR-125a rs12976445 C/T revealed that the homozygous CC genotype and C allele were associated with the risk of RPL and significant expression indicates that miR-125a has an important role in RPL etiopathogenesis.

Assessment of renal and hepatic dysfunction by co-exposure to toxic metals (Cd, Pb) and fluoride in people living nearby an industrial zone.

Togo's phosphate processing plant at Kpeme discharges waste, containing Cd, Pb, and fluoride, into the sea and on the soil. Heavy metals toxicity on kidneys and the liver has been studied. However, fluoride toxicity on these organs remains to be investigated. The present study deals with the variation in renal and hepatic functioning parameters due to fluoride, Cd and Pb. Totally, 350 volunteers were recruited from five different localities around this phosphate processing plant for sample collection. Cd and Pb contents in blood samples were determined by spectrophotometry and fluoride by the titanium chloride method. Biochemical parameters were measured using Biolab kits. The pollutant contents were elevated in polluted areas where ASAT, ALAT, creatinine, and urea increased, and total protein decreased. Correlation and multivariate tests showed that fluoride is related to the various pathologies mentioned. PCA revealed that phosphate processing in Togo is a source of renal and hepatic toxicity.

Lactobacillus Sps in Reducing the Risk of Diabetes in High-Fat Diet-Induced Diabetic Mice by Modulating the Gut Microbiome and Inhibiting Key Digestive Enzymes Associated with Diabetes.

Obesity caused by a high-fat diet (HFD) affects gut microbiota linked to the risk of type-2 diabetes (T2D). This study evaluates live cells and ethanolic extract (SEL) of Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 as natural anti-diabetic compounds. In-vitro anti-diabetic effects were determined based on the inhibition of α-glucosidase and α-amylase enzymes. The SEL of Probio65 and Probio-093 significantly retarded α-glucosidase and α-amylase enzymes (p < 0.05). Live Probio65 and Probio-093 inhibited α-glucosidase and α-amylase, respectively (p < 0.05). In mice fed with a 45% kcal high-fat diet (HFD), the SEL and live cells of both strains reduced body weight significantly compared to HFD control (p < 0.05). Probio-093 also improved blood glucose level compared to control (p < 0.05). The gut microbiota modulatory effects of lactobacilli on HFD-induced diabetic mice were analyzed with qPCR method. The SEL and live cells of both strains reduced phyla Deferribacteres compared to HFD control (p < 0.05). The SEL and live cells of Probio-093 promoted more Actinobacteria (phyla), Bifidobacterium, and Prevotella (genus) compared to control (p < 0.05). Both strains exerted metabolic-modulatory effects, with strain Probio-093 showing more prominent alteration in gut microbiota, substantiating the role of probiotics in gut microbiome modulations and anti-diabetic effect. Both lactobacilli are potential candidates to lessen obesity-linked T2D.