Exploring the Combined Effect of Exercise and Apigenin on Aluminium-Induced Neurotoxicity in Zebrafish.

Aluminium (AL) is a strong environmental neurotoxin linked to neurodegenerative disorders. Widespread industrial use leads to its presence in water systems, causing bioaccumulation in organisms. This, in turn, results in the bioaccumulation of AL in various organisms. Several studies have highlighted the benefits of enhanced physical activity in combating neurodegenerative diseases. Meanwhile widespread presence of apigenin in aquatic environment has been largely overlooked, in terms of its potential to counter AL-induced neurotoxicity. The combined impact of exercise and apigenin in mitigating the effects of AL-induced neurotoxicity in aquatic animals remains unexplored. Hence, the objective of this study is to determine whether the combined treatment of exercise and apigenin can effectively alleviate the chronic neurotoxicity induced by AL. Zebrafish that were exposed to AL showed behaviours resembling anxiety, increased aggression, unusual swimming pattern, and memory impairment, which are typical features observed in Alzheimer's disease (AD)-like syndrome. Combined treatment of exercise and apigenin protects zebrafish from AL-induced neurotoxicity, which was measured by improvements in memory, reduced anxiety and aggression, and increased levels of antioxidant enzymes and acetylcholinesterase (AChE) activity. Furthermore, AL exposure is associated with increased expression of genes related to neuroinflammation and AD. However, synergistic effect of exercise and apigenin counteract this effect in AL-treated zebrafish. These findings suggest that AL is involved in neurodegenerative diseases in fish, which could affect the integrity of aquatic ecosystem. Hence, there is a strong correlation between enhanced physical activity, apigenin, and the well-being of the ecosystem.

Synergetic effects of polyethylene microplastic and abamectin pesticides on the eyes of zebrafish larvae and adults through activation of apoptosis signaling pathways.

Although the toxicity of microplastics (MPs) and pesticides has recently been described, the possible effects of combining these pollutants are poorly understood. Thus, we evaluated the potential impact of exposure to polyethylene MP (PE-MP) and abamectin (ABM) (alone and combined) in zebrafish. After five days, the combined exposure to MP and ABM decreased the survival rate compared to exposures to individual pollutants. A significant increase in reactive oxygen species (ROS), lipid peroxidation, apoptosis, and impairment in antioxidant response was observed in zebrafish larvae. Morphological changes in the eyes of zebrafish significantly increased in the combined exposure group than in the individual exposure. Furthermore, the bax and p53 expression (specific apoptotic genes) was significantly upregulated after the combined exposure to PE-MP and ABM. So, the synergetic effect of MP and ABM cannot be ignored, and further research on other higher models is required to confirm its consequences.

Omega-3 Polyunsaturated Fatty Acids Provoke Apoptosis in Hepatocellular Carcinoma through Knocking Down the STAT3 Activated Signaling Pathway: In Vivo and In Vitro Study.

Hepatocellular carcinoma (HCC) is a common type of liver cancer and is a leading cause of death worldwide. Signal transducer and activator of transcription 3 (STAT3) is involved in HCC progression, migration, and suppression of apoptosis. This study investigates the apoptotic effect of the dietary antioxidant (n-3 PUFAs) on HepG2 cells and analyzes the underlying molecular mechanisms of this effect both in vivo and in vitro. In vivo study: Seventy-five adult male albino rats were divided into three groups (n = 25): Group I (control): 0.9% normal saline, intraperitoneal. Group II: N-Nitrosodiethylamine (200 mg/kg b.wt) intraperitoneal, followed by phenobarbital 0.05% in drinking water. Group III: as group II followed by n-3 PUFAs intubation (400 mg/kg/day). In vivo study: liver specimens for biochemical, histopathological, and immunohistochemical examination. In vitro study: MTT assay, cell morphology, PCR, Western blot, and immunohistochemical analysis. n-3 PUFAs significantly improved the histopathologic features of HCC and decreased the expression of anti-apoptotic proteins. Further, HepG2 cells proliferation was suppressed through inhibition of the STAT3 signaling pathway, cyclin D1, and Bcl-2 activity. Here we report that n-3 PUFAs may be an ideal cancer chemo-preventive candidate by targeting STAT3 signaling, which is involved in cell proliferation and apoptosis.

In Silico Screening of Synthetic and Natural Compounds to Inhibit the Binding Capacity of Heavy Metal Compounds against EGFR Protein of Lung Cancer.

Inorganic pollutant, specifically heavy metals' contamination, is a significant matter of concern and is one of the key contributors in various health disorders including cancer. However, the interaction of heavy metals (HMs) with lung cancer has rarely been explored yet. Therefore, the present study was intended with the aim to identify the interactions of HMs with the target protein "epidermal growth factor receptor (EGFR)" of lung cancer and explore potential drug candidates, which could inhibit the active site of EGFR against HM exposure. The molecular operating environment (MOE) tool was used to study the interactions of HMs with EGFR protein. The drug-drug interaction (DDI) network approach was used to identify the potential drug candidates, which were further confirmed and compared with the commercial medicines/control group. Various compounds of twenty-three HMs were docked with EGFR protein. Out of which tinidazole, thallium bromodimethyl, and silver acetate (Sn, Ti, and Ag compounds) showed strong interactions with EGFR based on lowest-scoring values (-20.42, -7.86, and -7.74 kcal/mol, respectively). Among 1280 collected drug candidates, three synthetic compounds viz., ZINC00602803, ZINC00602685, and ZINC06718468 and three natural compounds (berberine chloride, transresveratrol, and ellagic acid) depicted strong binding capacity with EGFR. Specifically, the scoring value of ZINC00602803 (-30.99 kcal/mol) was even lowest than standard lung cancer drugs (afatinib, erlotinib, and gefitinib). Our findings revealed that both natural and synthetic compounds having strong associations with EGFR protein could be potential candidates to inhibit the interaction between HMs and lung cancer protein and can also be used as an alternative for the prevention and treatment of lung cancer. However, in vitro and in vivo studies should be conducted to validate the aforementioned natural and synthetic compounds.

Identification of Ascorbic Acid and Gallic Acid as Novel Inhibitors of Secreted Frizzled-Related Protein for the Treatment of Obesity-Induced Type 2 Diabetes.

Type 2 diabetes mellitus (T2D) has been reported as major public health issue rising at an alarming rate worldwide, and obesity is the leading risk factor for the development of T2D. Secreted frizzled-related protein 4 (SFRP4) released with inflammatory mediators from adipose tissues constrains the exocytosis of insulin containing granules from the pancreatic islets that leads towards the development to T2D. The significant overexpression of SFRP4 in diabetic patients and its involvement in islet dysfunction suggest its critical role in the development of diabetes. Thus, this study was designed to explore the potential of ascorbic acid (AA) and gallic acid (GA) against SFRP4 for the treatment of diabetes. Molecular docking approach was used for the prediction of binding interactions of AA and GA at the active pocket of SFRP4. Docking analysis indicated strong binding interactions of AA and GA to the amino acid residues at the active site of SFRP4. A significant reduction in the level of SFRP4 was observed in transfected cells treated with AA and GA. For the evaluation of the cytotoxicity of AA and GA against HepG2 cells, MTT assay was performed. The results of MTT assay demonstrated that AA and GA are non-cytotoxic towards HepG2 cells at concentration of 15 µM. The oral administration of AA and GA to diet-induced obese mice caused significant reduction in body weight, blood glucose level, and SFRP4 expression. The results of this study suggest that AA and GA have potential for the treatment of obesity-induced T2D.

Knowledge extraction of sonophotocatalytic treatment for acid blue 113 dye removal by artificial neural networks.

Removing decolorizing acid blue 113 (AB113) dye from textile wastewater is challenging due to its high stability and resistance to removal. In this study, we used an artificial neural network (ANN) model to estimate the effect of five different variables on AB113 dye removal in the sonophotocatalytic process. The five variables considered were reaction time (5-25 min), pH (3-11), ZnO dosage (0.2-1.0 g/L), ultrasonic power (100-300 W/L), and persulphate dosage (0.2-3 mmol/L). The most effective model had a 5-7-1 architecture, with an average deviation of 0.44 and R2 of 0.99. A sensitivity analysis was used to analyze the impact of different process variables on removal efficiency and to identify the most effective variable settings for maximum dye removal. Then, an imaginary sonophotocatalytic system was created to measure the quantitative impact of other process parameters on AB113 dye removal. The optimum process parameters for maximum AB 113 removal were identified as 6.2 pH, 25 min reaction time, 300 W/L ultrasonic power, 1.0 g/L ZnO dosage, and 2.54 mmol/L persulfate dosage. The model created was able to identify trends in dye removal and can contribute to future experiments.

Diabetes induced renal complications by leukocyte activation of nuclear factor κ-B and its regulated genes expression.

Type 2 diabetes mellitus (T2D) is a metabolic disorder characterized by inappropriate insulin function. Despite wide progress in genome studies, defects in gene expression for diabetes prognosis still incompletely identified. Prolonged hyperglycemia activates NF-κB, which is a main player in vascular dysfunctions of diabetes. Activated NF-κB, triggers expression of various genes that promote inflammation and cell adhesion process. Alteration of pro-inflammatory and profibrotic gene expression contribute to the irreversible functional and structural changes in the kidney resulting in diabetic nephropathy (DN). To identify the effect of some important NF-κB related genes on mediation of DN progression, we divided our candidate genes on the basis of their function exerted in bloodstream into three categories (Proinflammatory; NF-κB, IL-1B, IL-6, TNF-α and VEGF); (Profibrotic; FN, ICAM-1, VCAM-1) and (Proliferative; MAPK-1 and EGF). We analyzed their expression profile in leukocytes of patients and explored their correlation to diabetic kidney injury features. Our data revealed the overexpression of both proinflammatory and profibrotic genes in DN group when compared to T2D group and were associated positively with each other in DN group indicating their possible role in DN progression. In DN patients, increased expression of proinflammatory genes correlated positively with glycemic control and inflammatory markers indicating their role in DN progression. Our data revealed that the persistent activation NF-κB and its related genes observed in hyperglycemia might contribute to DN progression and might be a good diagnostic and therapeutic target for DN progression. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.

Molecular diversity and hydrolytic enzymes production abilities of soil bacteria.

Soil is an integral part of ecosystem which is niche for varieties of microflora. The present study was investigated to isolate varied strains of bacteria from soil samples of three different geographical regions of Tamil Nadu (India) and evaluate their hydrolytic enzymes (amylase, cellulase, and inulinase) producing potentialities. Among 72 bacterial cultures isolated from Ambattur Industrial Estate, Neyveli Lignite Corporation, and Arignar Anna Zoological Park regions, 41.66, 38.88, and 36.11% of isolates were observed amylase, cellulase, and inulinase producers, respectively. On the other hand, 20.83% of total bacteria isolated from all three regions exhibited concurrent production of amylase, cellulase, and inulinase. Potent isolates depicting maximum enzyme activities were identified as Bacillus anthracis strain ALA1, Bacillus cereus strain ALA3, Glutamicibacter arilaitensis strain ALA4, and Bacillus thuringiensis strain ALA5 based on molecular characterization tools. Further, the thermodynamics parameters, open reading frames (ORFs) regions, and guanine-cytosine (GC) content were determined by distinct bioinformatics tools using 16S rRNA sequences of strains. Minimum free energy values for strain ALA1, strain ALA3, strain ALA4, and strain ALA5 were calculated as -480.73, -478.76, -496.63, and -479.03 kcal/mol, respectively. Mountain plot and entropy predicted the hierarchical representation of RNA secondary structure. The GC content of sequence for strain ALA1, strain ALA3, strain ALA4, and strain ALA5 was calculated as 53.06, 52.94, 56.78, and 53.06%, respectively. Nine ORFs were obtained for strain ALA1, strain ALA3, and strain ALA5 while 10 ORFs were observed for strain ALA4. Additionally, bootstrap tree demonstrated close resemblance of strains with existing bacteria of similar genus. Findings showed higher variability of bacterial diversity as hydrolytic enzymes producers in the investigated geographical regions.

Synthesis, Antitumor Activity, Molecular Docking and DFT Study of Novel Pyrimidiopyrazole Derivatives.

BACKGROUND: In this investigation, 2-cyano-N-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl) acetamide (3) reacts with dimethylformamide dimethyl acetal (DMF-DMA) to afford the corresponding (E)- 2-cyano-3-(dimethylamino)-N-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acrylam-ide (4) utilizing microwave irradiation. The condensation reactions of acrylamide derivative 4 with hydrazine derivatives obtain pyrazole derivatives 6a and 6b; respectively. The synthesized compounds demonstrate in vitro antitumor activity against liver tumor cell line HepG2. Furthermore, additional studies were carried out on the most effective compound 6b to evaluate the potential interaction against 4hdq synthase complex with ΔE= -4.5Kcal/mol and with short distance = 1.727Å and 2.027Å, respectively. The comprehensive theoretical studies of compounds 6a and 6b is based on bond length, bond angles and energy gap HOMO-LUMO. In addition, the vibrational frequencies of optimized compounds 6a and 6b were examined through DFT/B3LYP/6+31G(d) basis set. METHODS: In this research, synthesis of novel pyrimidiopyrazole derivatives calculated the computational studies to find suitable drug-receptor interactions and biological activity. RESULTS AND DISCUSSION: The synthesized pyrimidiopyrazole derivative 6b exhibited high antitumor activity IC50 =12.6 µg/ml and interacted it with 4hdq synthase complex with ΔE=-4.5Kcal/mol and with short distance = 1.727Å and 2.027Å. Furthermore, the optimized compounds utilize Gaussian 09W. CONCLUSION: In the optimized pyrimidiopyrazole derivatives, 6b showed better antitumor activity HeG-2 against 5-flurouracil due to its energy and confirmed more potent of hydrogen bond interaction with protein pocket.

In Vitro Antihepatoma Activity of Novel 3D-Copper Cyanide Supramolecular Coordination Polymers.

This study aimed to investigate the inhibitory effect of novel 3D-organocopper supramolecular coordination polymers (SCPs) on the invasive potential of HepG2 cells. Chemoprevention could represent an important means to inhibit the process of hepatocarcinogenesis. The inhibitory effect of an SCP compound on the proliferation of HepG2 hepatoma cells was evaluated by cell vibility assay. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of the SCP compound on phosphorylated ERK1/2, Bcl-2, and ß-catenin protein expression of HepG2 cells was analyzed by Western blot. The SCP compound exerted an inhibitory effect on HepG2 cell proliferation in a dose-dependent manner. This inhibitory effect was confirmed by examination of cell morphology and DNA fragmentation. Furthermore, Western blot analysis revealed that phosphorylated ERK1/2 and ß-catenin protein expression was inhibited after 24 h of treatment with the SCP compound, and that this event was associated with decreased Bcl-2 expression. We concluded that SCP can effectively inhibit the invasive potential of the ERK signaling pathway in HepG2 cells by altering apoptosis and by inhibiting Bcl-2 and ß-catenin, which may play a significant role in this process.