Environmental epigenetics: Exploring phenotypic plasticity and transgenerational adaptation in fish.

Epigenetics plays a vital role in the interaction between living organisms and their environment by regulating biological functions and phenotypic plasticity. Considering that most aquaculture activities take place in open or natural habitats that are vulnerable to environmental changes. Promising findings from recent research conducted on various aquaculture species have provided preliminary evidence suggesting a link between epigenetic mechanisms and economically valuable characteristics. Environmental stressors, including climate changes (thermal stress, hypoxia, and water salinity), anthropogenic impacts such as (pesticides, crude oil pollution, nutritional impacts, and heavy metal) and abiotic factors (infectious diseases), can directly trigger epigenetic modifications in fish. While experiments have confirmed that many epigenetic alterations caused by environmental factors have plastic responses, some can be permanently integrated into the genome through genetic integration and promoting rapid transgenerational adaptation in fish. These environmental factors might cause irregular DNA methylation patterns in genes related to many biological events leading to organs dysfunction by inducing alterations in genes related to oxidative stress or apoptosis. Moreover, these environmental issues alter DNA/histone methylation leading to decreased reproductive competence. This review emphasizes the importance of understanding the effects of environmentally relevant issues on the epigenetic regulation of phenotypic variations in fish. The goal is to expand our knowledge of how epigenetics can either facilitate or hinder species' adaptation to these adverse conditions. Furthermore, this review outlines the areas that warrant further investigation in understanding epigenetic reactions to various environmental issues.

Blockade of L-Type Ca2+ Channel Activity Alleviates Oligodendrocyte Pathology following Brain Injury in Male Rats.

A growing body of studies suggests that Ca2+ signaling controls a variety of biological processes in brain elements. Activation of L-type voltage-operated Ca2+ channels (VOCCs) plays a role in the development of oligodendrocyte (OL) lineage loss, and indicates that the blocking of these channels may be an effective way to inhibit OL lineage cell loss. For this study, 10.5-day-old male Sprague-Dawley rats were used to generate cerebellar tissue slices. The slice tissues were cultured and randomly allocated to one of four groups (six each) and treated as follows: Group I, (sham control); Group II, 0.1% dimethyl sulfoxide (DMSO) only (vehicle control); Group III, injury (INJ); Group IV, (INJ and treatment with NIF). The injury was simulated by exposing the slice tissues to 20 min of oxygen-glucose deprivation (OGD). At 3 days post-treatment, the survival, apoptosis, and proliferation of the OL lineages were measured and compared. Results: In the INJ group, there was a decrease in mature myelin basic protein+ OLs (MBP+ OLs) and their precursors, NG2+ OPCs (Nerve-glia antigen 2+ oligodendrocyte precursor cell), compared with controls. A significant elevation was observed in the NG2+ OPCs and apoptotic MBP+ OLs as confirmed by a TUNEL assay. However, the cell proliferation rate was decreased in NG2+ OPCs. NIF increased OL survival as measured by apoptosis rate in both OL lineages and preserved the rate of proliferation in the NG2+ OPCs. Conclusions: Activation of L-type VOCCs may contribute to OL pathology in association with reduced mitosis of OPCs following brain injury as a strategy to treat demyelinating diseases.

Incredible affinity of Kattosh with PPAR-γ receptors attenuates STZ-induced pancreas and kidney lesions evidenced in chemicobiological interactions.

Since ancient times, plants have been used as green bioresources to ensure a healthier life by recovering from different diseases. Kattosh (Lasia spinosa L. Thwaites) is a local plant with various traditional uses, especially for arthritis, constipation and coughs. This research investigated the effect of Kattosh stem extract (LSES) on streptozotocin-induced damage to the pancreas, kidney, and liver using in vitro, in vivo and in silico methods. In vitro phytochemical, antioxidative and anti-inflammatory effects of LSES were accomplished by established methods followed by antidiabetic actions in in vivo randomized controlled intervention in STZ-induced animal models for four weeks. In an in silico study, LSES phytocompounds interacted with antidiabetic receptors of peroxisome proliferator-activated receptor-gamma (PPAR, PDB ID: 3G9E), AMP-activated protein kinase (AMPK, PDB ID: 4CFH) and α-amylase enzyme (PDB ID: 1PPI) to verify the in vivo results. In addition, LSES showed promising in vitro antioxidative and anti-inflammatory effects. In contrast, it showed a decrease in weekly blood glucose level, normalized lipid profile, ameliorated liver and cardiac markers, managed serum AST and ALT levels, and increased glucose tolerance ability in the animal model study. Restoration of pancreatic and kidney damage was reflected by improving histopathological images. In ligand-receptor interaction, ethyl α-d-glucopyranoside of Kattosh showed the highest affinity for the α-amylase enzyme, PPAR, and AMPK receptors. Results demonstrate that the affinity of Kattosh phytocompounds potentially attenuates pancreatic and kidney lesions and could be approached as an alternative antidiabetic source with further clarification.

Synthesis of New Naphthyl Aceto Hydrazone-Based Metal Complexes: Micellar Interactions, DNA Binding, Antimicrobial, and Cancer Inhibition Studies.

In the present study, naphthyl acetohydrazide (HL) ligand was prepared and used for the synthesis of new six amorphous transition metal (Co(II), Ni(II), Cu(II), Zn(II), Pb(II), Cd(II)) complexes. All the compounds were characterized by elemental analysis, UV-vis, FT-IR, 1H- and 13C-NMR, and Matrix-Assisted Laser Desorption Ionization (MALDI). The solubilization study was carried out by estimating the interaction between the metal complexes with surfactants viz. sodium stearate (SS) and Cetyltrimethylammonium bromide (CTAB). UV-Visible spectroscopy was employed to determine partitioning and binding parameters, whereas electrical conductivity measurements were employed to estimate critical micellar concentration (CMC), the extent of dissociation, and free energy of micellization. The CT-DNA interaction of synthesized compounds with DNA represents the major groove binding. The synthesized ligand and metal complexes were also tested against bacterial and fungal strains and it has been observed that Cu(II) complex is active against all the strains except Candida albicans, while Cd(II) complex is active against all bacterial and fungal strains except Pseudomonas. Among all compounds, only the Pd(II) complex shows reasonable activity against cervical cancer HeLa cell lines, representing 97% inhibition.

New Heteroleptic 3D Metal Complexes: Synthesis, Antimicrobial and Solubilization Parameters.

The microbial resistance to current antibiotics is increasing day by day, which in turn accelerating the development of new effective drugs. Several studies have proved the high antimicrobial potential of the interaction of several organic ligands with a variety of metal ions. In the present study, a conventional method has been adopted in the synthesis of twelve new heteroleptic complexes of cobalt (II), nickel (II), copper (II) and zinc (II) using three aldimines, namely, (HL1 ((E)-2-((4-chloro-2-hydroxybenzylidene)amino)-3,4-dimethyl-5-phenylcyclopent-2-en-1-one), HL2 ((Z)-3-((4-chlorobenzylidene)amino)-4-hydroxy-5-nitrobenzenesulfonic acid) HL3 (2,2'-((1,2-phenylenebis(azaneylylidene))bis(methaneylylidene))diphenol)) as primary ligands, while phenyl glycine was the secondary ligand. The synthesized compounds were characterized by UV-vis, IR and multinuclear (1H and 13C) NMR spectroscopy, elemental analysis, and electrical conductance. The IR study revealed the coordination of the aldimine derivatives with the -OH and N atom of imine moiety. In contrary to this, the phenyl glycine coordinated to the metal ions via oxygen of carboxylate and nitrogen of the amino group. The spectroscopic analysis unveiled the tetrahedral geometry of the synthesized metal (II) complexes, except for ligand HL3 which exhibited octahedral geometry. The synthesized compounds generally showed antibacterial activity for all microbes, except Ni (II) complexes lacking sensitivity. Furthermore, to access the bioavailability, the synthesized complexes were screened for their solubilization in the micellar media of sodium lauryl sulphate. The metal complex-surfactant interaction was revealed by UV-vis spectroscopy and electrical conductivity measurements.

The influence of polyatomic primary ion chemistry on matrix effects in secondary ion mass spectrometry analysis.

RATIONALE: The application of mass spectrometry imaging techniques to determine two- (2D) and three- (3D) dimensional chemical distribution ideally provides uniform, high sensitivity to multiple components and reliable quantification. These criteria are typically not met due to variations in sensitivity due to the chemistry of the analyte and surrounding surface chemistry. Here we explore the influence of projectile beam chemistry and sample chemistry in time-of-flight secondary ion mass spectrometry (TOF-SIMS). To the authors' knowledge this is the first time the combined effects of projectile chemistry and sample environment on the quantitative determination of mixed samples have been systematically studied. METHODS: Secondary ion yields of lipid and amino acid mixtures were measured under 20 keV C60 , Arn , and (H2 O)n cluster ion bombardment (n = 2000 or 4000) using TOF-SIMS. Ion suppression/enhancement effects were studied in dry sample films and in trehalose and water ice matrices. RESULTS: The extent of the matrix effects and the secondary ion yield were found to depend on the chemistry of the primary ion beam and (for C60 , Arn ) on the nature of the sample matrix. Under (H2 O)n bombardment the sample matrix had negligible effect on the analysis. CONCLUSIONS: Compared with C60 and Arn , water-containing cluster projectiles enhanced the sensitivity of TOF-SIMS determination of the chosen analytes and reduced the effect of signal suppression/enhancement in multicomponent samples and in different sample matrices. One possible explanation for this is that the (H2 O)4000 projectile initiates on impact a nanoscale matrix environment that is very similar to that in frozen-hydrated samples in terms of the resulting ionisation effects. The competition between analytes for protons and the effect of the sample matrix are reduced with water-containing cluster projectiles. These chemically reactive projectile beams have improved characteristics for quantitative chemical imaging by TOF-SIMS compared with their non-reactive counterparts.

Investigation of pesticide residues level on commonly consumed leafy vegetables picked from the central market in Jeddah, Saudi Arabia.

This study aimed to investigate the presence of pesticide residues in a variety of commonly consumed leafy vegetables, including Grape leaves, Lettuce, Arugula, Spinach, Purslane, Ocimum, Parsley, Jew's mallow, Celery, Coriander, and Mint. A total of 100 samples were collected from the Central Market of Jeddah, Kingdom of Saudi Arabia. Our methodology involved employing the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) extraction method in combination with Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) to analyze a comprehensive database of 237 distinct pesticides. The range for limit of detection (LOD) and limit of quantification (LOQ) of the method were 0.0001 to 0.0014 mg. Kg-1 and 0.0010 to 0.0064 mg. Kg-1 for tested pesticides, respectively. The recoveries were in the range of 70-172.9%, with a relative standard deviation (RSD) of less than 19.0% for all tested pesticides. The results revealed that 60% of the analyzed samples were free from pesticide residues, while 40% exhibited contamination with 17 different pesticide residues. Notably, the most prevalent pesticide detected was Triallate in the Ocimum samples, followed by Metalaxyl in Grape leaves, Mint, and Spinach, and Methomyl in Celery. Approximately 45% of the samples contained pesticide residues that fell below or were equal to the European Union Maximum Residue Levels (EU MRLs), while the remaining 55% exceeded these MRLs. Remarkably, high pesticide concentrations were observed in all Ocimum samples (Triallate, Pyridaben, Hexythiazox, Imidacloprid), 67% of Grape leaves (Metalaxyl, Azoxystrobin, Difenoconazole Isomer), and 40% of Celery (Azoxystrobin, Methomyl). In conclusion, this study sheds light on the contamination levels of commonly consumed domestically produced and purchased leafy vegetables in the Central Market of Jeddah. To ensure food safety and the well-being of consumers, we strongly recommend enhanced scientific assessments and continued monitoring of pesticide usage in agricultural practices.

Nigella sativa Oil Alleviates Mouse Testis and Sperm Abnormalities Induced by BPA Potentially through Redox Homeostasis.

BACKGROUND & AIM: Significant evidence indicates that endocrine disrupted bisphenol A (BPA) seriously endangers human health. In males, BPA affects testis architecture and sperm quality, and ultimately reduces fertility. This study explored the therapeutic potential of Nigella sativa (NS) seed extract on testis and sperm abnormalities in BPA-exposed mice and characterized the underlying mechanism. METHODS: Forty male Swiss albino mice (5.5 weeks old, N = 8 per group) were randomly divided into five groups: Group I, normal control, Group II, vehicle control (sterile corn oil); Group III, NS-exposed (oral 200 mg/kg); Group IV, BPA-exposed (oral 400 µg/kg body weight); Group V, BPA + NS-exposed mice. Animals were treated for 6 weeks and sacrificed for biochemical and histological examination. RESULTS: The results indicated that BPA exposure results in significant testis and sperm abnormalities. Specifically, BPA promoted a marked reduction in the body and testis compared with the control group. Histopathological findings showed that BPA caused a widespread degeneration of spermatogenic cells of the seminiferous epithelium, decreased sperm counts and motility, and augmented sperm abnormalities, and whereas little alteration to sperm DNA was observed. In addition, BPA increased the levels of the lipid peroxidation marker, malondialdehyde (MDA), and reduced the levels of the antioxidant marker, reducing glutathione (GSH). Treatment with NS oil extract during BPA exposure significantly alleviated testis and sperm abnormalities, reduced MDA levels, and enhanced GSH levels. CONCLUSION: The results demonstrate that NS oil protects mice against BPA-induced sperm and testis abnormalities, likely by suppressing levels of the oxidative stress marker, MDA, and enhancing the levels of the antioxidant marker, GSH.

Exploring novel fluorine-rich fuberidazole derivatives as hypoxic cancer inhibitors: Design, synthesis, pharmacokinetics, molecular docking, and DFT evaluations.

Sixteen fuberidazole derivatives as potential new anticancer bioreductive prodrugs were prepared and characterized. The in vitro anticancer potential was examined to explore their cytotoxic properties by employing apoptosis, DNA damage, and proliferation tests on chosen hypoxic cancer cells. Eight substances (Compound 5a, 5c, 5d, 5e, 5g, 5h, 5i, and 5m) showed promising cytotoxicity values compared to the standard control. The potential of compounds was also examined through in silico studies (against human serum albumin), including chem-informatics, to understand the structure-activity relationship (SAR), pharmacochemical strength, and the mode of interactions responsible for their action. The DFT calculations revealed that only the 5b compound showed the lowest ΔET (2.29 eV) while 5i showed relatively highest ßtot (69.89 x 10-31 esu), highest αave (3.18 x 10-23 esu), and dipole moment (6.49 Debye). This study presents a novel class of fuberidazole derivatives with selectivity toward hypoxic cancer cells.

Therapeutic potential of vitamin D against bisphenol A-induced spleen injury in Swiss albino mice.

Bisphenol A (BPA), a ubiquitous plasticizer, is capable of producing oxidative splenic injury, and ultimately led to spleen pathology. Further, a link between VitD levels and oxidative stress was reported. Hence the role of VitD in BPA-induced oxidative splenic injury was investigated in this study. Sixty male and female Swiss albino mice (3.5 weeks old) were randomly divided into control and treated groups 12 mice in each (six males and six females). The control groups were further divided into sham (no treatment) and vehicle (sterile corn oil), whereas the treatment group was divided into VitD (2,195 IU/kg), BPA (50 µg/kg), and BPA+VitD (50 µg/kg + 2,195 IU/kg) groups. For six weeks, the animals were dosed intraperitoneally (i.p). One week later, at 10.5 weeks old, mice were sacrificed for biochemical and histological analyses. Findings showed BPA triggered neurobehavioral abnormalities and spleen injury with increased apoptotic indices (e.g. DNA fragmentation) in both sexes. A significant increase was found in lipid peroxidation marker, MDA in splenic tissue, and leukocytosis. Conversely, VitD treatment altered this scenario into motor performance preservation, reducing oxidative splenic injury with a decrease in the percent apoptotic index. This protection was significantly correlated with preserving leukocyte counts and reduced MDA levels in both genders. It can be concluded from the above findings that VitD treatment has an ameliorative effect on oxidative splenic injury induced by BPA, highlighting the continuous crosstalk between oxidative stress and the VitD signaling pathway.

Correction: Rashid et al. Natural Compounds of Lasia spinosa (L.) Stem Potentiate Antidiabetic Actions by Regulating Diabetes and Diabetes-Related Biochemical and Cellular Indexes. Pharmaceuticals 2022, 15, 1466.

In the published publication [...].

COVID-19 Candidate Genes and Pathways Potentially Share the Association with Lung Cancer.

COVID-19 is considered as the most challenging in the current situation but lung cancer is also the leading cause of death in the global population. These two malignancies are among the leading human diseases and are highly complex in terms of diagnostic and therapeutic approaches as well as the most frequent and highly complex and heterogeneous in nature. Based on the latest update, it is known that the patients suffering from lung cancer, are considered to be significantly at higher risk of COVID-19 infection in terms of survival and there are a number of evidences which support the hypothesis that these diseases may share the same functions and functional components. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major sources which promote a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutics. With so many challenges, it is critical to understand the relationships and the common shared aberrations between them which is difficult to unravel and understand. A simple approach has been applied for this study where differential gene expression analysis, pathway enrichment, and network level understanding are carried out. Since, gene expression changes and genomic alterations are related to the COVID-19 and lung cancer but their pattern varies significantly. Based on the recent studies, it appears that the patients suffering from lung cancer and and simultaneously infected with COVID-19, then survival chance is lessened. So, we have designed our goal to understand the genes commonly overexpressed and commonly enriched pathways in case of COVID-19 and lung cancer. For this purpose, we have presented the summarized review of the previous works where the pathogenesis of lung cancer and COVID-19 infection have been focused and we have also presented the new finding of our analysis. So, this work not only presents the review work but also the research work. This review and research study leads to the conclusion that growth promoting pathways (EGFR, Ras, and PI3K), growth inhibitory pathways (p53 and STK11), apoptotic pathways (Bcl- 2/Bax/Fas), and DDR pathways and genes are commonly and dominantly altered in both the cases COVID-19 and lung cancer.

Development of instant paneer type product from groundnut using microwave dehydration.

The present study aimed at the development of a groundnut-based dehydrated paneer type product which could serve as an instant vegan protein source. In the process of preparing groundnut paneer, a ratio of 1:5 of groundnut to water and 2.0% calcium chloride (CaCl2) solution was used for the preparation of groundnut paneer and the product was evaluated for physicochemical, instrumental color, instrumental textural, and sensory characteristics. The developed paneer cubes (1.5 × 1.5 × 1 cm) were dehydrated using a vacuum-assisted microwave dryer at different microwave powers (200-600 W, 250 mbar vacuum). The minimum bulk density (0.55 g/cc) and maximum rehydration ratio (2.9) were recorded in the sample dehydrated at 600 W. The samples dried at 600 W also showed significantly (p < .05) higher L* values, softer texture and high sensory scores for color, aroma, taste, texture, and overall acceptability after rehydration.

Natural Compounds of Lasia spinosa (L.) Stem Potentiate Antidiabetic Actions by Regulating Diabetes and Diabetes-Related Biochemical and Cellular Indexes.

Natural biometabolites of plants have been reported to be useful in chronic diseases including diabetes and associated complications. This research is aimed to investigate how the biometabolites of Lasia spinosa methanol stem (MEXLS) extract ameliorative diabetes and diabetes-related complications. MEXLS was examined for in vitro antioxidant and in vivo antidiabetic effects in a streptozotocin-induced diabetes model, and its chemical profiling was done by gas chromatography-mass spectrometry analysis. The results were verified by histopathological examination and in silico ligand-receptor interaction of characterized natural biometabolites with antidiabetic receptor proteins AMPK (PDB ID: 4CFH); PPARγ (PDB ID: 3G9E); and mammalian α-amylase center (PDB ID: 1PPI). The MEXLS was found to show a remarkable α-amylase inhibition (47.45%), strong antioxidant action, and significant (p < 0.05) decrease in blood glucose level, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein (LDL), urea, uric acid, creatinine, total cholesterol, triglyceride (TG), liver glycogen, creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase in serum insulin, glucose tolerance, and high-density lipoprotein (HDL). Rat's pancreas and kidney tissues were found to be partially recovered in histopathological analyses. Methyl α-d-galactopyranoside displayed the highest binding affinity with AMPK (docking score, −5.764), PPARγ (docking score, −5.218), and 1PPI (docking score, −5.615) receptors. Data suggest that the MEXLS may be an exciting source to potentiate antidiabetic activities affirming a cell-line study.

Natural Compounds from Hatikana Extract Potentiate Antidiabetic Actions as Displayed by In Vivo Assays and Verified by Network Pharmacological Tools.

BACKGROUND: Hatikana is a traditional medicinal plant used to treat inflammation, urolithiasis, goiter, cancer, wounds and sores, gastrointestinal, tumor, tetanus, arthritis, hepatic damage, neurodegeneration, and other ailments. The goal of this study is to investigate the antidiabetic properties of Hatikana extract (HKEx) and to construct the effects of its natural constituents on the genes and biochemical indices that are connected with them. METHODS: HKEx was evaluated using GC-MS and undertaken for a three-week intervention in fructose-fed STZ-induced Wistar albino rats at the doses of HKEx50, HKEx100, and HKEx200 mg/kg bw. Following intervention, blood serum was examined for biochemical markers, and liver tissue was investigated for the mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD1) by RTPCR analysis. Most abundant compounds (oleanolic acid, 7α, 28-olean diol, and stigmasterol) from GC-MS were chosen for the network pharmacological assay to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba. RESULTS: In vivo results showed a significant (P < 0.05) decrease of blood sugar, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase of liver glycogen, glucose load, and serum insulin. Out of three antioxidative genes, catalase (CAT) and superoxide dismutase (SOD1) were found to be few fold increased. Oleanolic acid and stigmasterol were noticed to strongly interact with 27 target proteins. Oleanolic acid interacted with the proteins AKR1B10, CASP3, CASP8, CYP1A2, CYP1A2, HMGB1, NAMPT, NFE2L2, NQO1, PPARA, PTGIR, TOP1, TOP2A, UGT2B10, and UGT2B11 and stigmasterol with ABCA1, ABCG5, ABCG8, CTSE, HMGCR, IL10, CXCL8, NR1H2, NR1H3, SLCO1B1, SREBF2, and TNF. Protein-protein interaction (PPI) analysis revealed the involvement of 25 target proteins out of twenty seven. Cytoscape plugin cytoHubba identified TNF, CXCL8, CASP3, PPARA, SREBF2, and IL10 as top hub genes. Pathway analysis identified 31 KEGG metabolic, signaling, and immunogenic pathways associated with diabetes. Notable degree of PPI enrichment showed that SOD1 and CAT are responsible for controlling signaling networks and enriched pathways. CONCLUSION: The findings show that antioxidative genes have regulatory potential, allowing the HKEx to be employed as a possible antidiabetic source pending further validation.

Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats.

Cellular elements of maturing brain are vulnerable to insults, which lead to neurodevelopmental defects. There are no established treatments at present. Here we examined the efficacy of selective adenosine A2A receptor inhibitor SCH58261 to combat brain injury, particularly oligodendrocyte (OL) lineage cells, in young rats. Wistar rats (n = 24, 6.5 days old) were randomly divided into equal groups of four. The sham (SHAM) group received no treatment, the vehicle (VEHICLE) group received 0.1% dimethylsufoxide, the injury (INJ) group was exposed to oxygen-glucose deprivation insult, and the injury+SCH58261 (INJ+SCH58261) group was exposed to the insult and received 1 µM SCH58261. Immunocytochemical experiments revealed that there was a significant reduction in the populations of mature OL (MBP+ OLs) and immature OL precursors (NG2+ OPCs) in the INJ group compared to SHAM group. Furthermore, there was also a significant increase in the percent of apoptotic MBP+ OL and NG2+ OPC populations as evidenced by TUNEL assay. In addition, there was a significant reduction in the proliferation rate among NG2+ OPCs, which was confirmed by BrdU immunostaining. On the other hand, treatment with SCH58261 significantly enhanced survival, evidenced by the reduction in apoptotic indices for both cell types, and it is preserved the NG2+ OPC proliferation. Activation of adenosine A2A receptors may contribute to OL lineage cell loss in association with decreased mitotic behavior of OPCs in neonatal brains upon injury. Future investigations assessing ability of SCH58261 to regenerate myelin will provide insights into its wider clinical relevance.

Paternal bisphenol A exposure induces testis and sperm pathologies in mice offspring: Possibly due to oxidative stress?

Bisphenol A (BPA), an endocrine and metabolic disruptor, is widely used to manufacture polycarbonate plastics and epoxy resins. Accumulating evidence suggests that paternal BPA exposure adversely affects male germlines and results in atypical reproductive phenotypes that might persist for generations to come. Our study investigated this exposure on testicular architecture and sperm quality in mouse offspring, and characterised underlying molecular mechanism(s). A total of 18 immature male Swiss albino mice (3.5 weeks old) were randomly divided into three groups and treated as follows: Group I, no treatment (sham control); Group II, sterile corn oil only (vehicle control); Group III, BPA (400 µg/kg) in sterile corn oil. At 9.5 weeks old, F0 males were mated with unexposed females. F0 offspring (F1 generation) were monitored for postnatal development for 10 weeks. At 11.5 weeks old, the animals were sacrificed to examine testicular architecture, sperm parameters, including DNA integrity, and oxidative stress biomarkers. Results showed that BPA significantly induced changes in the body and testis weights of the F0 and F1 generation BPA lineages compared to F0 and F1 generation control lineages. A decrease in sperm count and motility with further, increased sperm abnormalities, no or few sperm DNA alterations and elevated levels of MDA, PC and NO were recorded. Similar effects were found in BPA exposed F0 males, but were more pronounced in the F0 offspring. In addition, BPA caused alterations in the testicular architecture. These pathological changes extended transgenerationally to F1 generation males' mice, but the pathological changes were more pronounced in the F1 generation. Our findings demonstrate that the biological and health BPA impacts do not end in paternal adults, but are passed on to offspring generations. Hence, linking observed testis and sperm abnormalities in the F1 generation to BPA exposure of their parental line was evident in this work. The findings also illustrate that oxidative stress appears to be a molecular component of the testis and sperm pathologies.

The Antioxidative Role of Natural Compounds from a Green Coconut Mesocarp Undeniably Contributes to Control Diabetic Complications as Evidenced by the Associated Genes and Biochemical Indexes.

The purpose of this study was to look into the effects of green coconut mesocarp juice extract (CMJE) on diabetes-related problems in streptozotocin- (STZ-) induced type 2 diabetes, as well as the antioxidative functions of its natural compounds in regulating the associated genes and biochemical markers. CMJE's antioxidative properties were evaluated by the standard antioxidant assays of 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide radical, nitric oxide, and ferrous ions along with the total phenolic and flavonoids content. The α-amylase inhibitory effect was measured by an established method. The antidiabetic effect of CMJE was assayed by fructose-fed STZ-induced diabetic models in albino rats. The obtained results were verified by bioinformatics-based network pharmacological tools: STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba bioinformatics tools. The results showed that GC-MS-characterized compounds from CMJE displayed a very promising antioxidative potential. In an animal model study, CMJE significantly (P < 0.05) decreased blood glucose, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, uric acid, and lipid levels and increased glucose tolerance as well as glucose homeostasis (HOMA-IR and HOMA-b scores). The animal's body weights and relative organ weights were found to be partially restored. Tissue architectures of the pancreas and the kidney were remarkably improved by low doses of CMJE. Compound-protein interactions showed that thymine, catechol, and 5-hydroxymethylfurfural of CMJE interacted with 84 target proteins. Of the top 15 proteins found by Cytoscape 3.6.1, 8, CAT and OGG1 (downregulated) and CASP3, COMT, CYP1B1, DPYD, NQO1, and PTGS1 (upregulated), were dysregulated in diabetes-related kidney disease. The data demonstrate the highly prospective use of CMJE in the regulation of tubulointerstitial tissues of patients with diabetic nephropathy.

Carbamazepine induces a bioenergetics disruption to microvascular endothelial cells from the blood-brain barrier.

Carbamazepine (CBZ) is a widely employed anti-seizure medication that crosses the blood-brain barrier (BBB) to exert its anti-convulsant action. The effects of CBZ on components of the BBB have yet to be completely delineated. Hence the current study evaluated the effects of CBZ upon mitochondrial functionality of BBB-derived microvascular endothelial cells isolated from Albino rats. The influence of CBZ on cell viability and barrier functions were evaluated by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), lactate dehydrogenase, and electrophysiological assays over a drug concentration range of 0.1-1000 µM. Bioenergetics effects were measured via ATP production, mitochondrial complexes I and III activities, lactate production, and oxygen consumption rates (OCRs), and mitochondrial membrane potential, fluidity and lipid content. CBZ was cytotoxic to microvascular endothelial cells in a concentration and duration dependent manner. CBZ significantly diminished the endothelial cell's barrier functions, and impacted upon cellular bioenergetics: reducing mitochondrial complex activities with a parallel decrease in OCRs and increased anaerobic lactate production. CBZ significantly decreased mitochondrial membrane potential and induced an increase of membrane fluidity and decrease in levels of mitochondrial saturated and unsaturated fatty acids. In summary, CBZ disrupted functional activity of BBB endothelial cells via damage and modification of mitochondria functionality at therapeutically relevant concentrations.

Chemoprotective effects of inositol hexaphosphate against cyclophosphamide-induced testicular damage in rats.

Cyclophosphamide (CP) is commonly used as an anticancer agent but has been associated with high toxicity in several animal organs, including the testes. Inositol hexaphosphate (IP6) is a polyphosphorylated carbohydrate that is present in foods with high fibre contents and has a wide range of essential physiological and pathological activities. Thus, we estimated the defensive effects of IP6 against CP-related testicular toxicity in rats. Sperm counts, motilities, viabilities and abnormalities and levels of testosterone, luteinising hormone and follicle-stimulating hormone were evaluated. Testicle specimens were also processed for histological and biochemical analyses, including determinations of malondialdehyde, nitric oxide, total antioxidant capacity, alkaline phosphatase, acid phosphatase, gamma glutamyl transferase, ß-glucuronidase, c-reactive protein, monocyte chemoattractant protein and leukotriene-4 and in comet assays. CP treatments were associated with deleterious histopathological, biochemical and genetic changes in rat testicles, and these were ameliorated by IP6 supplements in drinking water.