Mechanistic interplay of dual environmental stressors: Bisphenol-A and cadmium-induced ovarian follicular damage and hepatocyte dysfunction in vivo.

This study investigates the individual and combined toxic effects of Bisphenol A (BPA) and Cadmium (Cd) in zebrafish, recognizing the complex mixture of pollutants organisms encounter in their natural environment. Examining developmental, neurobehavioral, reproductive, and physiological aspects, the study reveals significant adverse effects, particularly in combined exposures. Zebrafish embryos exposed to BPA + Cd exhibit synergistically increased mortality, delayed hatching, and morphological abnormalities, emphasizing the heightened toxicity of the combination. Prolonged exposure until 10 days post-fertilization underscores enduring effects on embryonic development. BPA and Cd induce oxidative stress, as evidenced by increased production of reactive oxygen species and lipid peroxidation. This oxidative stress disrupts cellular functions, affecting lipid metabolism and immune response. Adult zebrafish exposed to BPA and Cd for 40 days display compromised neurobehavioral functions, altered antioxidant defenses, and increased oxidative stress, suggesting potential neurotoxicity. Additionally, disruptions in ovarian follicle maturation and skeletal abnormalities indicate reproductive and skeletal impacts. Histological analysis reveals significant liver damage, emphasizing the synergistic hepatotoxicity of BPA and Cd. Molecular assessments further demonstrate compromised cellular defense mechanisms, synaptic function, and elevated cellular stress and inflammation-related gene expression in response to combined exposures. Bioaccumulation analysis highlights differential tissue accumulation patterns. In conclusion, this study provides comprehensive insights into the multifaceted toxicological effects of BPA and Cd in zebrafish, raising concerns about potential adverse impacts on environmental ecosystems and human health.

Neuroprotective potential of pyrazole benzenesulfonamide derivative T1 in targeted intervention against PTZ-induced epilepsy-like condition in in vivo zebrafish model.

Epilepsy is a chronic neurological disease characterized by a persistent susceptibility to seizures. Pharmaco-resistant epilepsies, impacting around 30 % of patients, highlight the urgent need for improved treatments. Neuroinflammation, prevalent in epileptogenic brain regions, is a key player in epilepsy, prompting the search for new mechanistic therapies. Hence, in this study, we explored the anti-inflammatory potential of pyrazole benzenesulfonamide derivative (T1) against pentylenetetrazole (PTZ) induced epilepsy-like conditions in in-vivo zebrafish model. The results from the survival assay showed 79.97 ± 6.65 % at 150 µM of T1 compared to PTZ-group. The results from reactive oxygen species (ROS), apoptosis and histology analysis showed that T1 significantly reduces cellular damage due to oxidative stress in PTZ-exposed zebrafish. The gene expression analysis and neutral red assay results demonstrated a notable reduction in the inflammatory response in zebrafish pre-treated with T1. Subsequently, the open field test unveiled the anti-convulsant activity of T1, particularly at a concentration of 150 µM. Moreover, both RT-PCR and immunohistochemistry findings indicated a concentration-dependent potential of T1, which inhibited COX-2 in zebrafish exposed to PTZ. In summary, T1 protected zebrafish against PTZ-induced neuronal damage, and behavioural changes by mitigating the inflammatory response through the inhibition of COX-2.

Exploring the Efficacy of Pellitorine as an Antiparasitic Agent Against Argulus: Impacts on Antioxidant Levels and Immune Responses in Goldfish (Carassius auratus).

INTRODUCTION: Argulus spp. infestation is a significant challenge for aquaculture, currently, there are no approved medications available to efficiently manage this parasite. Consequently, mechanical removal of parasites using forceps and natural substances like herbs are being explored as alternative treatment methods. Pellitorine (PLE) is a naturally occurring compound found in several plant species. It is classified as an alkaloid and belongs to the class of compounds known as amides. MATERIALS AND METHODS: This study aimed to evaluate the effectiveness of PLE in preventing Argulus spp. infestations in goldfish (Carassius auratus) and to determine the optimal dosage of PLE for the detachment of Argulus spp. RESULTS: The findings of this study revealed that PLE enhanced the immune response of goldfish by promoting superoxide dismutase (SOD) and catalase (CAT) in Argulus-infected goldfish. Additionally, PLE induces reactive oxygen species (ROS) generation and cellular damage in the Argulus. PLE at a dosage of 5 mg/mL was able to detach 80% of the argulus from goldfish within 12 h. Therapeutic index was found to be 5.99, suggesting that PLE is the safest drug. CONCLUSIONS: Therefore, our findings suggest that PLE can be a suitable and effective treatment option for preventing Argulus infestations in goldfish. The results of this study can guide the use of PLE at an optimal dosage to control Argulus infestation in goldfish.

Sustainable food packaging: Harnessing biowaste of Terminalia catappa L. for chitosan-based biodegradable active films for shrimp storage.

Shrimp, a globally consumed perishable food, faces rapid deterioration during storage and marketing, causing nutritional and economic losses. With a rising environmental consciousness regarding conventional plastic packaging, consumers seek sustainable options. Utilizing natural waste resources for packaging films strengthens the food industry. In this context, we aim to create chitosan-based active films by incorporating Terminalia catappa L. leaves extract (TCE) to enhance barrier properties and extend shrimp shelf life under refrigeration. Incorporation of TCE improves mechanical, microstructural, UV, and moisture barrier properties of the chitosan film due to cross-linking interactions, resulting in robust, foldable packaging film. Active TCE film exhibits high antioxidant property due to polyphenols. These films also exhibited low wettability and showed hydrophobicity than neat CH films which is essential for meat packaging. These biodegradable films offer an eco-friendly end-of-life option when buried in soil. TCE-loaded films effectively control spoilage organisms, prevent biochemical spoilage, and maintain shrimp freshness compared to neat CH films during refrigerated condition. The active TCE film retains sensory attributes better than neat chitosan, aligning with consumer preference. The developed edible and active film from waste sources might offer sustainable, alternative packaging material with a lower carbon footprint than petroleum-based sources.

Deacetylepoxyazadiradione ameliorates diabesity in in-vivo zebrafish larval model by influencing the level of regulatory adipokines and oxidative stress.

Obesity and diabetes constitute significant global health issues associated with one another. In contrast to diabetes, which is characterised by oxidative stress that enhances cellular damage and the following complications. Obesity dynamics involve chronic inflammation that promotes insulin resistance and metabolic disruptions. Anti-inflammatory and antioxidant agents, therefore, hold promise for synergistic effects, addressing inflammation and oxidative stress, key factors in managing obesity and diabetes. These agents can be utilized in novel drug delivery approaches. The complex interactions between deacetylepoxyazadiradione (DEA) and zebrafish larva subjected to metabolic impairment due to a high-fat diet (HFD) are examined in this study. The survival assay showed a significantly lower rate (79% survival rate) in the larvae exposed to HFD. Contrastingly, DEA treatment showed significant results with survival rates increasing dose-dependently (84%, 89%, and 94% at concentrations of 50 µM, 100 µM, and 150 µM, respectively). Further investigations revealed that DEA could reduce hyperlipidemic and hyperglycemic conditions in zebrafish larvae. Glucose levels significantly dropped in the DEA treatment, which was associated with a decline in larval weight, lipid accumulation, oxidative stress and apoptosis. Enzyme assays revealed higher antioxidant enzyme concentrations in DEA treated in-vivo larval models, which were associated with reduced expression of pro-inflammatory genes. In conclusion, the results demonstrate that DEA can alleviate oxidative stress and inflammation, effectively easing the diabesity-like state in zebrafish larvae. This offers potential avenues for developing DEA as a valuable drug candidate to manage the intricate diabesity condition.

Osteoporosis in polycystic ovary syndrome (PCOS) and involved mechanisms.

Polycystic Ovary Syndrome (PCOS) and osteoporosis, though seemingly unrelated, exhibit intricate connections influenced by genetic and epigenetic factors. PCOS, characterized by elevated androgen levels, insulin resistance, and increased body weight, has historically been considered protective against bone fragility disorders. However, emerging research suggests that chronic inflammation, prevalent in PCOS, can adversely affect bone health. Studies have demonstrated variable bone mineral density loss in PCOS, often associated with leptin resistance and hyperinsulinemia. Key genes such as INS, IGF1, CTNNB1, AKT1, and STAT3 play pivotal roles in the complex interplay between PCOS and osteoporosis, influencing insulin signaling, oxidative stress, and inflammatory pathways. Oxidative stress, a prominent element in PCOS, can lead to osteoporosis through hormonal imbalances, chronic inflammation, insulin resistance, and lifestyle factors. The insulin signaling pathway also significantly impacts both conditions by contributing to hormonal imbalances and bone health alterations. This intricate network of genetic and epigenetic factors underscores the need for a deeper understanding of their interrelationships. Thus, this review elucidates the multifaceted genetic, epigenetic, and inflammatory connections between PCOS and osteoporosis, highlighting their implications for bone health management in individuals with PCOS.

Toxic ties: Unraveling the complex relationship between endocrine disrupting chemicals and chronic kidney disease.

Environmental pollution is inherently linked to several metabolic diseases and high mortality. The kidney is more susceptible to environmental pollutants compared to other organs as it is involved in concentrating and filtering most of these toxins. Few epidemiological studies revealed the intrinsic relationship between exposure to Endocrine Disrupting Chemicals (EDCs) and CKD development. Though EDCs have the potential to cause severe pathologies, the specific molecular mechanisms by which they accelerate the progression of CKD remain elusive. In particular, our understanding of how pollutants affect the progression of chronic kidney disease (CKD) through the gut-kidney axis is currently limited. EDCs modulate the composition and function of the gut microbial community and favor the colonization of harmful gut pathogens. This alteration leads to an overproduction of uremic toxin and membrane vesicles. These vesicles carry several inflammatory molecules that exacerbate inflammation and renal tissue damage and aggravate the progression of CKD. Several experimental studies have revealed potential pathways by which uremic toxin further aggravates CKD. These include the induction of membrane vesicle production in host cells, which can trigger inflammatory pathways and insulin resistance. Reciprocally, CKD can also modulate gut bacterial composition that might further aggravate CKD condition. Thus, EDCs pose a significant threat to kidney health and the global CKD burden. Understanding this complicated issue necessitates multidisciplinary initiatives such as strict environmental controls, public awareness, and the development of novel therapeutic strategies targeting EDCs.

Combined effects of a high-fat diet and polyethylene microplastic exposure induce impaired lipid metabolism and locomotor behavior in larvae and adult zebrafish.

Microplastics (MP), tiny plastic particles, can be ingested by fish through their habitat or contaminated food sources. When combined with a high-fat diet (HFD), MP exposure may lead to increased MP accumulation in fish and negative impacts on their health. However, the underlying mechanisms of how MP and HFD interact to promote fat accumulation in fish remain poorly understood. In this study, we aimed to evaluate the combined effect of HFD and polyethylene MP (PE-MP) in the zebrafish model (Danio rerio) and decipher its molecular mechanisms. Adult zebrafish exposed to the combined HFD and PE-MP showed elevated lipid accumulation, total cholesterol, triglycerides, and abnormal swimming behavior compared to HFD-fed fish. Histological and gene expression analysis revealed severe hepatic inflammation and injury, resembling nonalcoholic fatty liver disease (NAFLD) in the HFD + PE-MP exposed zebrafish. Moreover, HFD and PE-MP exposure upregulated genes related to lipogenesis (SREBP1, FAS, and C/EBPα) and inflammation (tnfα, il1ß, and il-6) in the liver. These findings underscore the interactive effect of environmental pollutants and fish diet, emphasizing the importance of improving fish culture practices to safeguard fish health and human consumers from microplastic contamination through the food chain. This research sheds light on the complex interactions between microplastics and diet, providing valuable insights into the potential risks of microplastic pollution in aquatic ecosystems and the implications for human health. Understanding the underlying molecular mechanisms will contribute to international research efforts to mitigate the adverse effects of microplastics on both environmental and public health.

Deacetyl epoxyazadiradione ameliorates BPA-induced neurotoxicity by mitigating ROS and inflammatory markers in N9 cells and zebrafish larvae.

Bisphenol A (BPA) leaches from plastic products have become a major inevitable concern among the research society. Human exposure to BPA leads to deleterious effects on multiple organs by the induced hyper inflammatory and oxidative stress responses. Due to the compromised antioxidant mechanism, the brain environment was highly susceptible and required special concern to ameliorate the effects of BPA. Hence, this study investigates the potential of neem-derived semi natural deacetyl epoxyazadiradione (DEA) against the oxidative stress and inflammatory response induced by BPA exposure in N9 cells and zebrafish larvae. The results from the in vitro analyses showed a decrease in cell viability in the MTT assay and a decline in mitochondrial damage in BPA-exposed N9 cells. Further in vivo, results revealed that pre-treatment of DEA to zebrafish larvae has significantly reduced the level of superoxide anion and increased the production of antioxidant enzymes such as SOD, CAT, GST, GPx and GR. We also found a significant decrease in the production of nitric oxide (p < 0.0001) and iNOS gene expression at 150 µM concentration. Further, DEA pre-treatment improved the behaviour of zebrafish larvae by ameliorating the production of the AChE enzyme. In conclusion, DEA protected zebrafish larvae from BPA toxicity by ameliorating oxidative stress and inflammatory responses.

Expanding germ-organ theory: Understanding non-communicable diseases through enterobacterial translocation.

Diverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known as human microbiome, plays a vital role in maintaining the health. However, changes in the composition and functions of human microbiome can result in chronic low-grade inflammation, which can damage the epithelial cells and allows pathogens and their toxic metabolites to translocate into other organs such as the liver, heart, and kidneys, causing metabolic inflammation. This dysbiosis of human microbiome has been directly linked to the onset of several non-communicable diseases. Recent metabolomics studies have revealed that pathogens produce several uraemic toxins. These metabolites can serve as inter-kingdom signals, entering the circulatory system and altering host metabolism, thereby aggravating a variety of diseases. Interestingly, Enterobacteriaceae, a critical member of Proteobacteria, has been commonly associated with several non-communicable diseases, and the abundance of this family has been positively correlated with uraemic toxin production. Hence, this review provides a comprehensive overview of Enterobacterial translocation and their metabolites role in non-communicable diseases. This understanding may lead to the identification of novel biomarkers for each metabolic disease as well as the development of novel therapeutic drugs.

Trihydroxy piperlongumine protects aluminium induced neurotoxicity in zebrafish: Behavioral and biochemical approach.

Aluminium (Al) is proven to be a potent environmental neurotoxin involved in progressive neurodegeneration. Al primarily induces oxidative stress by free radical generation in the brain, followed by neuronal apoptosis. Antioxidants are promising therapeutic options for Al toxicity. Piperlongumine is traditionally long known for its medicinal properties. Therefore, the present study has been designed to explore the antioxidant role of trihydroxy piperlongumine (THPL) against Al-induced neurotoxicity in the zebrafish model. Zebrafish exposed to AlCl3 exhibited higher oxidative stress and altered locomotion. Adult fish displayed anxiety comorbid with depression phenotype. THPL increases antioxidant enzyme activity by quenching Al-induced free radicals and lipid peroxidation, thus minimizing oxidative damage in the brain. THPL rescues behavior deficits and improves anxiety-like phenotype in adult fish. Histological alterations caused by Al were also attenuated on administration with THPL. Results of the study demonstrate the neuroprotective role of THPL against Al-induced oxidative damage and anxiety, which could be exploited as a psychopharmacological drug.

Functionalized Sulfur-Containing Heterocyclic Analogs Induce Sub-G1 Arrest and Apoptotic Cell Death of Laryngeal Carcinoma In Vitro.

In this study, we speculate that the hydroxyl-containing benzo[b]thiophene analogs, 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP), might possess antiproliferative activity against cancer cells. Hydroxyl-containing BP and EP show selectivity towards laryngeal cancer cells (HEp2), with IC50 values of 27.02 ± 1.23 and 35.26 ± 2.15 µM, respectively. The hydroxyl group present in the third position is responsible for the anticancer activity and is completely abrogated when the hydroxyl group is masked. BP and EP enhance the antioxidant enzyme activity and reduce the ROS production, which are correlated with the antiproliferative effect in HEp-2 cells. An increase in the BAX/BCL-2 ratio occurs during the BP and EP treatment and activates the caspase cascade, resulting in apoptosis stimulation. It also arrests the cells in the Sub-G1 phase, indicating the induction of apoptosis. The molecular docking and simulation studies predicted a strong interaction between BP and the CYP1A2 protein, which could aid in combinational therapy by enhancing the bioavailability of the drugs. BP and EP possess an antioxidant property with low antiproliferative effects (~5.18 µg/mL and ~7.8 µg/mL) as a standalone drug, therefore, they can be combined with other drugs for effective chemotherapy that might trigger the effect of pro-oxidant drug on healthy cells.

Hepatoprotective effect of dihydroxy piperlongumine in high cholesterol-induced non-alcoholic fatty liver disease zebrafish via antioxidant activity.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are a growing epidemic and the most common liver diseases. Consumption of a western diet with high fats alters redox status, induces inflammation, and impairs the physiological function of hepatocytes. However, the pharmacological market lacks anti-NAFLD/NASH drugs. Long pepper (Piper longum L) is used in traditional Mongolian medicine for treating hyperlipidemia. Piperlongumine (PL) is a bioactive compound of Piper longum L, which usually possesses anticancer activities due to its ROS elevation property. However, when PL was demethylated they behave as an antioxidant. Previously, we found dihydroxy piperlongumine (DHPL) possesses high antioxidant activity among the hydroxy piperlongumines, which makes us curious to reveal the anti-NAFLD effect. A high-cholesterol diet (HCD) was chosen to induce NAFLD zebrafish model, and the antioxidant and lipid-lowering effects of DHPL were evaluated. Histological alterations of NAFLD were also scored along with gene expression to explore the molecular mechanism. DHPL reduced lipid accumulation in both short-term and long-term feeding trials. DHPL increases antioxidant activity and lipid-lowering gene expression and decreases hepatic triglyceride, oxidative stress, and lipogenic genes. In conclusion, DHPL halted the progression of HCD-induced NAFLD in the zebrafish model.

Gut Enterobacteriaceae and uraemic toxins - Perpetrators for ageing.

Ageing is a complex process that is associated with changes in the composition and functions of gut microbiota. Reduction of gut commensals is the hallmarks of ageing, which favours the expansion of pathogens even in healthy centenarians. Interestingly, gut Enterobacteriaceae have been found to be increased with age and also consistently observed in the patients with metabolic diseases. Thus, they are associated with all-cause mortality, regardless of genetic origin, lifestyle, and fatality rate. Moreover, Enterobacteriaceae are also implicated in accelerating the ageing process through telomere attrition, cellular senescence, inflammasome activation and impairing the functions of mitochondria. However, acceleration of ageing is likely to be determined by intrinsic interactions between Enterobacteriaceae and other associated gut bacteria. Several studies suggested that Enterobacteriaceae possess genes for the synthesis of uraemic toxins. In addition to intestine, Enterobacteriaceae and their toxic metabolites have also been found in other organs, such as adipose tissue and liver and that are implicated in multiorgan dysfunction and age-related diseases. Therefore, targeting Enterobacteriaceae is a nuance approach for reducing inflammaging and enhancing the longevity of older people. This review is intended to highlight the current knowledge of Enterobacteriaceae-mediated acceleration of ageing process.

Syringol, a wildfire residual methoxyphenol causes cytotoxicity and teratogenicity in zebrafish model.

Natural toxicants, particularly methoxy phenols (MPs) generated by wildfire lignin, can accumulate in the environment, and cause serious health hazards in living organisms. Although the toxicity of MPs such as guaiacol and catechol has recently been described, there is minimal evidence of ecotoxicological effects of syringol. As a result, this study focuses on determining the toxicity by evaluating the cytotoxic and teratogenic effects of syringol in vitro and in vivo in human embryonic kidney (HEK-293) cells and zebrafish embryos, respectively. The ecotoxicity of syringol was predicted to be 63.8 mg/L using the ECOSAR (ECOlogical Structure Activity Relationship) prediction tool, and molecular docking analysis was used to determine the interaction and binding affinities of syringol with human apoptotic proteins in silico. In HEK-293 cells, exposure of syringol (0.5-2 mg/L) has induced cytotoxicity in a concentration-dependent manner. In zebrafish larvae, exposure of syringol (0.5-2 mg/L) has induced dose-dependent embryo toxic effects (or growth abnormalities such as yolk sac edema, pericardial edema, skeletal abnormality, and hyperemia), and changes in growth morphometrics (head height, eye, yolk sac, and pericardial area, heart rate) in particular, the heart rate of larvae was found to be significantly decreased (p<0.001). After a 4-day experimental trial, the accumulated concentration of syringol in zebrafish larvae was confirmed both qualitatively (HPLC-MS - High Performance Liquid Chromatography-Mass spectrometry) and quantitatively (LC-QTOF-HRMS - Liquid Chromatography-Quadrupolar Time of Flight-High Resolution Mass spectrometry). The craniofacial abnormalities induced by syringol exposure (0.5-2 mg/L) were detected as anomalies in cartilaginous development and locomotor deficits using alcian blue staining and locomotor analyses, respectively. Significant increase in oxidative stress parameters (including reactive oxygen species generation, lipid peroxidation, superoxide dismutase, catalase, lactate dehydrogenase and nitric oxide production) (p<0.001) and substantial decrease in glutathione levels were observed (p<0.05) in syringol exposed zebrafish larvae through enzymatic analysis. Additionally, through acridine orange staining and gene expression analyses, syringol (2 mg/L) was found to activate apoptosis in zebrafish larvae. Considering the cytotoxic, embryotoxic (teratogenicity), and oxidative stress-related apoptotic effects of syringol in the zebrafish model, syringol has the potential to emerge as a potent environmental toxicant posing serious health hazards in many living systems; however, further research on its toxicological effects on the actual ecosystem and in higher animal models is required to confirm its consequences.

Withaferin A targets the membrane of Pseudomonas aeruginosa and mitigates the inflammation in zebrafish larvae; an in vitro and in vivo approach.

Infections due to multidrug-resistant Pseudomonas aeruginosa are prevalent among patients with cystic fibrosis. The emergence of antibiotic-resistant pathogens necessitated the development of novel low-risk natural antibacterial compounds. Herbal medicines are used from dates of the origin of mankind and still serve their purpose as therapeutic agents. We demonstrated the antibacterial activity of Withaferin A extracted from the traditional herb, ashwagandha or winter cherry (Withania somnifera). Withaferin A exhibits strong antibacterial activity against P. aeruginosa with a minimum inhibitory concentration of 60 µM and minimum bactericidal concentration of 80 µM. Results obtained from membrane stabilization assay and electron microscopic analysis showed that Withaferin A acts by damaging the cell membrane of P. aeruginosa. Additionally, we investigated oxidative stress and inflammatory response after Withaferin A treatment in P. aeruginosa infected zebrafish larvae model. The results indicate that the level of ROS, and its related lipid peroxidation and apoptosis were significantly reduced after treated with Withaferin A. Consequently, an increment in antioxidant enzymes level such as superoxide dismutase (SOD) and catalase (CAT) was observed. Macrophage localization experiment showed a smaller number of localized macrophages in zebrafish, which indicates the reduction in inflammatory response. In conclusion, Withaferin A could serve as an alternative natural product in the treatment of infections caused by P. aeruginosa.

Neuroprotective effect of Biochanin a against Bisphenol A-induced prenatal neurotoxicity in zebrafish by modulating oxidative stress and locomotory defects.

Exogenous toxicants cause oxidative stress and damage to brain cells, resulting in inflammation. Neuroinflammation is important in the pathobiology of various neurological illnesses, including Alzheimer's disease (AD). In this context, Bisphenol A (BPA), a common toxin, causes oxidative damage and has been linked to neurological problems. An O-methylated isoflavone known as Biochanin A (5,7-dihydroxy-4'-methoxy-isoflavone, BCA) is considered to be a phytoestrogen, which is abundant in some legume plants and soy which have preventive effects against cancer, osteoporosis, menopausal symptoms and oxidative stress. However, the mechanism by which BCA protected the prenatal neurological stress are not known. So that, in this study we investigated the BCA neuroprotective effect against BPA-induced neuroinflammation in zebrafish embryo models. For this study, fertilized zebrafish embryos are exposed to BPA (1 µM) with or without BCA. Our finding suggested that BCA co-exposure prevented the depletion of antioxidant defense enzymes by BPA and reduced the production of intracellular ROS production, superoxide anion (O2-), lipid peroxidation (LPO), lactate dehydrogenase (LDH) and nitric oxide (NO) levels in the head that aided in safeguarding neuronal development. Baseline locomotion was rendered and a total distance was calculated to assess the motor function. Exposure to BCA increased acetylcholinestrase (AChE) and improved motor neuron functions. It also reduced the pro-inflammatory response expression and prevented neuroinflammation. Our study suggests that BCA has a positive role in the attenuation or amelioration of neuronal oxidative damage and locomotory behaviour induced by BPA.

Deacetylated nimbin analog N2 fortifies alloxan-induced pancreatic ß-cell damage in insulin-resistant zebrafish larvae by upregulating phosphoenolpyruvate carboxykinase (PEPCK) and insulin levels.

This study aims to evaluate the protective behaviour of N2, a semi-natural analog of nimbin, for its anti-diabetic efficacy against alloxan-induced oxidative damage and ß-cell dysfunction in in-vivo zebrafish larvae. A 500 µM of alloxan was exposed to zebrafish larvae for 24 h to induce oxidative stress in the pancreatic ß-cells and co-exposed with N2 to study the protection of N2 by inhibiting ROS by DCFH-DA, DHE and NDA staining along with Cellular damage, apoptosis and lipid peroxidation. The zebrafish was further exposed to 500 µM alloxan for 72 h to induce ß-cell destruction along with depleted glucose uptake and co-exposed to N2 to study the protective mechanism. Glucose levels were estimated, and PCR was used to verify the mRNA expression of phosphoenolpyruvate carboxykinase (PEPCK) and insulin. Alloxan induced (24 h) oxidative stress in the pancreatic ß-cells in which N2's co-exposure inhibited ROS by eliminating O-2 radicals and restoring the glutathione levels, thus preventing cellular damage and lipid peroxidation. The zebrafish exposed to 500 µM alloxan for 72 h was observed with ß-cell destruction along with depleted glucose uptake when stained with 2NBDG, wherein N2 was able to protect the pancreatic ß-cells from oxidative damage, promoted high glucose uptake and reduced glucose levels. N2 stimulated insulin production and downregulated PEPCK by inhibiting gluconeogenesis, attenuating post-prandial hyperglycemia. N2 may contribute to anti-oxidant protection against alloxan-induced ß-cell damage and anti-hyperglycemic activity, restoring insulin function and suppressing PEPCK expression.

Intercellular communication and social behaviors in mycobacteria.

Cell-to-cell communication is a fundamental process of bacteria to exert communal behaviors. Sputum samples of patients with cystic fibrosis have often been observed with extensive mycobacterial genetic diversity. The emergence of heterogenic mycobacterial populations is observed due to subtle changes in their morphology, gene expression level, and distributive conjugal transfer (DCT). Since each subgroup of mycobacteria has different hetero-resistance, they are refractory against several antibiotics. Such genetically diverse mycobacteria have to communicate with each other to subvert the host immune system. However, it is still a mystery how such heterogeneous strains exhibit synchronous behaviors for the production of quorum sensing (QS) traits, such as biofilms, siderophores, and virulence proteins. Mycobacteria are characterized by division of labor, where distinct sub-clonal populations contribute to the production of QS traits while exchanging complimentary products at the community level. Thus, active mycobacterial cells ensure the persistence of other heterogenic clonal populations through cooperative behaviors. Additionally, mycobacteria are likely to establish communication with neighboring cells in a contact-independent manner through QS signals. Hence, this review is intended to discuss our current knowledge of mycobacterial communication. Understanding mycobacterial communication could provide a promising opportunity to develop drugs to target key pathways of mycobacteria.