A phenanthroline-based erbium (III) complex: molecular docking, DNA/BSA -binding and biological evaluation.

With the help of both theoretical as well as experimental research, in vitro binding research with CT-DNA (calf thymus) and BSA (bovine serum albumin) were carefully examined to figure out the chemotherapeutic and pharmacokinetic facets of the Erbium complex, which contains 1,10-phenanthroline (Phen). The binding characteristics and the mechanism of complex's interaction with DNA as well as the protein were determined utilizing fluorescence quenching method. Findings indicated that the complex's interaction with DNA via groove binding into DNA's minor grooves, with their binding constants falling within the 104 M-1 range. Furthermore, thermodynamic characteristics and the fluorescence emission of the tryptophan residues of the protein were obtained through fluorescence quenching studies at different temperatures. According to the results of the binding constants, the protein's interactions with the Er- complex were moderate, demonstrating that the compound may be transported effectively by the protein. Molecular docking results supported that of the experimental research. The HeLa and MCF-7 cancer cell lines, along with the normal human fibroblast cell line, were used in an MTT assay evaluation of the Er-complex cytotoxicity. The Er-complex displayed a selective inhibitory effect on the proliferation of different cancer cells.Communicated by Ramaswamy H. Sarma.

Targeting inflammation and oxidative stress for protection against ischemic brain injury in rats using cupressuflavone.

Inflammatory responses and oxidative stress contribute to the pathogenesis of brain ischemia/reperfusion (IR) injury. Naturally occurring bioflavonoids possess antioxidant and anti-inflammatory properties. The phytochemicals of Juniperus sabina L., known as "Abhal" in Saudi Arabia, have been studied and cupressuflavone (CUP) has been isolated as the major bioflavonoid. This study aimed to investigate the neuroprotective potential of CUP in reducing brain IR damage in rats and to understand probable mechanisms. After 60 min of inducing cerebral ischemia by closing the left common carotid artery (CCA), blood flow was restored to allow reperfusion. The same surgical procedure was performed on sham-operated control rats, excluding cerebral IR. CUP or vehicle was given orally to rats for 3 days prior to ischemia induction and for a further 3 days following reperfusion. Based on the findings of this study, compared to the IR control group, CUP-administered group demonstrated reduced neurological deficits, improved motor coordination, balance, and locomotor activity. Additionally, brain homogenates of IR rats showed a decrease in malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) content, and an increase in catalase (CAT) enzyme activity following CUP treatment. CUP suppressed neuro-inflammation via reducing serum inflammatory cytokine levels, particularly those of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) and enhancing the inflammatory cytokine levels, such as Nuclear factor kappa- B (NF-κB), TANK-binding kinase-1 (TBK1), and interferon beta (IFN-ß) in brain tissues. Furthermore, CUP ameliorated the histological alterations in the brain tissues of IR rats. CUP significantly suppressed caspase-3 expression and downregulated the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway as a result of suppressing High mobility group box 1 (HMGB1). To our knowledge, this is the first study to document the neuroprotective properties of CUP. Thus, the study findings revealed that CUP ameliorates IR-induced cerebral injury possibly by enhancing brain antioxidant contents, reducing serum inflammatory cytokine levels, potentiating the brain contents of TBK1 and IFN-ß and suppressing the HMGB1/TLR-4 signaling pathway. Hence, CUP may serve as a potential preventive and therapeutic alternative for cerebral stroke.

Antibacterial activity and DNA interaction of triazine iron and ruthenium complexes: spectroscopic, voltammetric and theoretical studies.

The 2,4,6-tris(2-pyridyl)-1,3,5-triazine (tptz), [Ru(µ-tptz)2]Cl2 and [Fe(µ-tptz)2]Cl2, complexes containing Ru (1) and Fe (2) are created. Using electronic absorption spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, viscosity measurement and electrochemistry, as well as two complexes with Fish Salmon DNA (FS-DNA), the binding interactions of these complexes were investigated. According to binding assays, complexes bind to DNA through a mild intercalation mechanism, most likely via the DNA helix's base pairs being intercalated by the tptz ligand. Additionally, complex (2) is more capable of binding than complex (1). The electrochemical method offers a quick and easy way to determine the binding constant (Kb). The antibacterial performance of these complexes versus Gram-positive and Gram-negative bacteria was examined using the zone of inhibition test, MIC, and MBC method, and the results revealed that complex (2) exhibits strong antibacterial activity against these bacteria. The outcomes of this investigation will help in understanding DNA interaction mechanisms as well as the creation of a prospective one. Additionally, the density functional theory (DFT) computation included probes of DNA structure and conformation as well as potential pharmacological regulators for particular disorders to fully explain the experimental results.

Development of a Novel Vaccine Candidates against Cardiobacterium valvarum through Reverse Vaccinology and Computational Approaches.

Antibiotic resistance is a major public health concern that has resulted in high healthcare costs, increased mortality, and the emergence of novel bacterial diseases. Cardiobacterium valvarum, an antibiotic-resistant bacterium, is one of the leading causes of heart disease. Currently, there is no licensed vaccination against C. valvarum. In this research, an in silico-based vaccine was designed against C. valvarum using reverse vaccinology, bioinformatics, and immunoinformatics techniques. 4206 core proteins, 2027 nonredundant proteins, and 2179 redundant proteins were predicted. Among nonredundant proteins, 23 proteins were predicted in an extracellular membrane, 30 in the outer membrane, and 62 in the periplasmic membrane region. After applying several subtractive proteomics filters, two proteins, TonB-dependent siderophore receptor and hypothetical protein, were chosen for epitope prediction. In the epitope selection phase, B and T-cellepitopes were analyzed and shortlisted for vaccine design. The vaccine model was designed by linking selected epitopes with GPGPG linkers to avoid flexibility. Furthermore, the vaccine model was linked to cholera toxin B adjuvant to induce a proper immune response. The docking approach was utilized to analyze binding affinity to immune cell receptors. Molecular docking results predicted 12.75 kcal/mol for a Vaccine with MHC-I, 6.89 for a vaccine with MHC-II, and 19.51 vaccine with TLR-4. The MMGBSA estimated -94, -78, and -76 kcal/mol for TLR-4 and vaccine, MHC-I and vaccine, and MHC-II and vaccine, while the MMPBSA analysis estimated -97, -61, and -72 kcal/mol for TLR-4 with the vaccine, MHC-I with vaccine, and MHC-II with a vaccine. Molecular dynamic simulation analysis revealed that the designed vaccine construct has proper stability with immune cell receptors as it is essential for inducing an immune response. In conclusion, we observed that the model vaccine candidate has the potency to induce an immune response in the host. However, the study is designed purely on a computational basis; hence, experimental validation is strongly recommended.

Samarcandin protects against testicular ischemia/reperfusion injury in rats via activation of Nrf2/HO-1-mediated antioxidant responses.

The purpose of this study was to evaluate the effectiveness of samarcandin (SMR) in preventing testicular injury caused by ischemia/reperfusion (I/R) in rats. Rats were divided into 4 groups at random: the sham group, the T/D control group (CONT), the T/D group receiving SMR treatment at 10 mg/kg (SMR-10), and the T/D group receiving SMR treatment at 20 mg/kg (SMR-20). When compared to the CONT group, SMR improved the oxidant/antioxidant balance by reducing malondialdehyde (MDA), nitric oxide (NOx), and increasing reduced glutathione (GSH), gluta-thione peroxide (GSH-Px), and superoxide dismutase (SOD). Moreover, SMR increased the levels of the steroid hormones' testosterone (TST), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in the blood as well as controlled the inflammatory mediators; interleukin-6 (IL6), tumor necrosis factor alpha (TNF-α), and nuclear factor κB (NF-κB). Nevertheless, SMR-treated animals showed a considerable downregulation of the apoptotic marker caspase-3. The T/D-induced histopathological changes were reduced and Proliferating Cell Nuclear Antigen (PCNA) protein expression was enhanced by SMR. These effects are associated with upregulation of testicular (Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), and downregulation of NF-κB mRNA expression levels. These findings suggest that SMR may be able to prevent T/D-induced testis damage by mainly regulating the expression of Nrf2 and NF-B, which seems to mediate its promising antioxidant, anti-inflammatory and antiapoptotic effects seen in this study.

Computational Modeling and Evaluation of Potential mRNA and Peptide-Based Vaccine against Marburg Virus (MARV) to Provide Immune Protection against Hemorrhagic Fever.

A hemorrhagic fever caused by the Marburg virus (MARV) belongs to the Filoviridae family and has been classified as a risk group 4 pathogen. To this day, there are no approved effective vaccinations or medications available to prevent or treat MARV infections. Reverse vaccinology-based approach was formulated to prioritize B and T cell epitopes utilizing a numerous immunoinformatics tools. Potential epitopes were systematically screened based on various parameters needed for an ideal vaccine such as allergenicity, solubility, and toxicity. The most suitable epitopes capable of inducing immune response were shortlisted. Epitopes with population coverage of 100% and fulfilling set parameters were selected for docking with human leukocyte antigen molecules, and binding affinity of each peptide was analyzed. Finally, 4 CTL and HTL each while 6 B cell 16-mers were used for designing multiepitope subunit (MSV) and mRNA vaccine joined via suitable linkers. Immune simulations were used to validate the constructed vaccine's capacity to induce a robust immune response whereas molecular dynamics simulations were used to confirm epitope-HLA complex stability. Based on these parameter's studies, both the vaccines constructed in this study offer a promising choice against MARV but require further experimental verification. This study provides a rationale point to begin with the development of an efficient vaccine against Marburg virus; however, the findings need further experimental validation to confirm the computational finding of this study.

Barbigerone Potentially Alleviates Rotenone-Activated Parkinson's Disease in a Rodent Model by Reducing Oxidative Stress and Neuroinflammatory Cytokines.

BACKGROUND: Parkinson's disease (PD) is a common age-related and slowly progressive neurodegenerative disease that affects approximately 1% of the elderly population. In recent years, phytocomponents have aroused considerable interest in the research for PD treatment as they provide a plethora of active compounds including antioxidant and anti-inflammatory compounds. Herein, we aimed to investigate the anti-Parkinson's effect of barbigerone, a natural pyranoisoflavone possessing antioxidant activity in a rotenone-induced rat model of PD. METHODS: To evaluate antioxidant activity, a 0.5 mg/kg dose of rotenone was injected subcutaneously into rats. Barbigerone (10 and 20 mg/kg) was administered to rats for 28 days 1 h prior to rotenone. All behavioral parameters were assessed before sacrificing the rats. On the 29th day, all of the rats were humanely killed and assessed for biochemical changes in antioxidant enzymes (superoxide dismutase, glutathione, malondialdehyde, and catalase), neurotransmitter levels (dopamine, 5-hydroxyindoleacetic acid, serotonin, dihydroxyphenylacetic acid, and homovanillic acid levels), and neuroinflammatory cytokines [interleukin (IL)-1ß, tumor necrosis factor-α, nuclear factor kappa B, and IL-6]. RESULTS: The data presented in this study has shown that barbigerone attenuated rotenone-induced motor deficits including the rotarod test, catalepsy, akinesia, and open-field test. Additionally, barbigerone has shown improvements in the biochemical and neuroinflammatory parameters in the rotenone-induced rat model of PD. CONCLUSION: The results demonstrated that barbigerone exhibits antioxidant and anti-inflammatory actions via reducing oxidative stress and inflammatory cytokines. Altogether, these findings suggest that barbigerone could potentially be utilized as a therapeutic agent against PD.

Boron nitride nanocage as drug delivery systems for chloroquine, as an effective drug for treatment of coronavirus disease: A DFT study.

Research has shown that chloroquine (CQ) can effectively help control COVID-19 infection. B24N24 nanocage is a drug delivery system. Thus, through density functional theory, the present study analyzed pristine nanocage-CQ interaction and CQ interaction with Si- and Al -doped nanocage. The findings revealed that nanocage doping, particularly with Si and Al, yields more satisfactory drug delivery for CQ due to their greater electronic and energetic characteristics with CQ.

Vulgarin, a Sesquiterpene Lactone from Artemisia judaica, Improves the Antidiabetic Effectiveness of Glibenclamide in Streptozotocin-Induced Diabetic Rats via Modulation of PEPCK and G6Pase Genes Expression.

The current investigation assessed the effect of the eudesmanolid, Vulgarin (VGN), obtained from Artemisia judaica (A. judaica), on the antidiabetic potential of glibenclamide (GLB) using streptozotocin (STZ) to induce diabetes. Seven groups of rats were used in the study; the first group received the vehicle and served as normal control. The diabetic rats of the second to the fifth groups were treated with the vehicle (negative control), GLB at 5 mg/kg (positive control), VGN at 10 mg/kg (VGN-10) and VGN at 20 mg/kg (VGN-20), respectively. The diabetic rats of the sixth and seventh groups were administered combinations of GLB plus VGN-10 and GLB plus VGN-20, respectively. The diabetic rats treated with GLB plus VGN-20 combination showed marked improvement in the fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c), as well as the lipid profile, compared with those treated with GLB alone. Further, the pancreatic tissues of the diabetic rats that received the GLB+VGN-20 combination showed superior improvements in lipid peroxidation and antioxidant parameters than those of GLB monotherapy. The insulin content of the ß-cells was restored in all treatments, while the levels of glucagon and somatostatin of the α- and δ-endocrine cells were reduced in the pancreatic islets. In addition, the concurrent administration of GLB+VGN-20 was the most effective in restoring PEPCK and G6Pase mRNA expression in the liver. In conclusion, the results demonstrated that the GLB+VGN-20 combination led to greater glycemic improvement in diabetic rats compared with GLB monotherapy through its antioxidant effect and capability to modulate PEPCK and G6Pase gene expression in their livers.

Europinidin Inhibits Rotenone-Activated Parkinson's Disease in Rodents by Decreasing Lipid Peroxidation and Inflammatory Cytokines Pathways.

Background: Europinidin is a derivative of delphinidin obtained from the plants Plumbago Europea and Ceratostigma plumbaginoides. This herb has wide medicinal applications in treating various diseases but there are very few studies available on this bioactive compound. Considering this background, the present study is designed for the evaluation of Europinidin against Parkinson's disease. Aim: The investigation aims to assess the effect of Europinidin in the rotenone-activated Parkinson's paradigm. Methods: To evaluate neuroprotective activity, rotenone (1.5 mg/kg s.c) and europinidin (10 mg/kg and 20 mg/kg) was administered in rats for 21 days. The behavioural parameters were performed before sacrificing the rats. On the 22nd day, all the rats were assessed for biochemical markers (SOD, GSH, MDA, Catalase), neurotransmitter levels (Dopamine, 5-HIAA, DOPAC, and HVA levels), and neuroinflammatory markers (IL-6, IL-1ß and TNF-α). Results: It was found that rotenone produced significant (p < 0.001) oxidative damage, a cholinergic deficit, dopaminergic loss, and a rise in neuroinflammatory markers in rats. Conclusion: The study concludes that europinidin possesses anti-oxidant and anti-inflammatory properties. The results suggest the therapeutic role of europinidin against rotenone-activated behavioural, biochemical, and neuroinflammatory alterations in rats.

mRNA-Based Vaccine Designing against Epstein-Barr Virus to Induce an Immune Response Using Immunoinformatic and Molecular Modelling Approaches.

Epstein-Barr Virus (EBV) is a human pathogen that has a morbidity rate of 90% in adults worldwide. Infectious mononucleosis is caused by EBV replication in B cells and epithelial cells of the host. EBV has also been related to autoimmune illnesses, including multiple sclerosis and cancers like nasopharyngeal carcinomas and Burkitt's lymphoma. Currently, no effective medications or vaccinations are available to treat or prevent EBV infection. Thus, the current study focuses on a bioinformatics approach to design an mRNA-based multi-epitope (MEV) vaccine to prevent EBV infections. For this purpose, we selected six antigenic proteins from the EBV proteome based on their role in pathogenicity to predict, extract, and analyze T and B cell epitopes using immunoinformatics tools. The epitopes were directed through filtering parameters including allergenicity, toxicity, antigenicity, solubility, and immunogenicity assessment, and finally, the most potent epitopes able to induce T and B cell immune response were selected. In silico molecular docking of prioritized T cell peptides with respective Human Leukocytes Antigens molecules, were carried out to evaluate the individual peptide's binding affinity. Six CTL, four HTL, and ten linear B cell epitopes fulfilled the set parameters and were selected for MEV-based mRNA vaccine. The prioritized epitopes were joined using suitable linkers to improve epitope presentation. The immune simulation results affirmed the designed vaccine's capacity to elicit a proper immune response. The MEV-based mRNA vaccine constructed in this study offers a promising choice for a potent vaccine against EBV.

Momordica charantia Extract Protects against Diabetes-Related Spermatogenic Dysfunction in Male Rats: Molecular and Biochemical Study.

More than 90% of diabetic patients suffer from sexual dysfunction, including diminished sperm count, sperm motility, and sperm viability, and low testosterone levels. The effects of Momordica charantia (MC) were studied by estimating the blood levels of insulin, glucose, glycosylated hemoglobin (HbA1c), testosterone (TST), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in diabetic rats treated with 250 and 500 mg/kg b.w. of the total extract. Testicular antioxidants, epididymal sperm characteristics, testicular histopathology, and lesion scoring were also investigated. Testicular mRNA expression of apoptosis-related markers such as antiapoptotic B-cell lymphoma-2 (Bcl-2) and proapoptotic Bcl-2-associated X protein (Bax) were evaluated by real-time PCR. Furthermore, caspase-3 protein expression was evaluated by immunohistochemistry. MC administration resulted in a significant reduction in blood glucose and HbA1c and marked elevation of serum levels of insulin, TST, and gonadotropins in diabetic rats. It induced a significant recovery of testicular antioxidant enzymes, improved histopathological changes of the testes, and decreased spermatogenic and Sertoli cell apoptosis. MC effectively inhibited testicular apoptosis, as evidenced by upregulation of Bcl-2 and downregulation of Bax and caspase-3. Moreover, reduction in apoptotic potential in MC-treated groups was confirmed by reduction in the Bax/Bcl-2 mRNA expression ratio.

Cymbopogon Proximus Essential Oil Protects Rats against Isoproterenol-Induced Cardiac Hypertrophy and Fibrosis.

Cardiac hypertrophy is an independent risk factor of many cardiovascular diseases. Several cardiovascular protective properties of Cymbopogon proximus have been reported. However, no reports investigating the direct effect of C. proximus essential oil on the heart are available. The goal of this study was to explore the cardioprotective effect of C. proximus on cardiac hypertrophy and fibrosis. Male albino rats were administered C. proximus essential oil in the presence or absence of hypertrophic agonist isoproterenol. Cardiac hypertrophy and fibrosis were assessed using real-time polymerase chain reaction (PCR) and histological examination. Pre- treatment of rats with C. proximus decreased the ratio of heart weight to body weight and gene expression of hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ß-myosin heavy chain (ß-MHC), which were induced by isoproterenol. Moreover, C. proximus prevented the increase in gene expression of fibrosis markers procollagen I and procollagen III and alleviated the collagen volume fraction caused by isoproterenol. The pre- treatment with C. proximus essential oil conferred cardio-protection against isoproterenol- induced cardiac hypertrophy and fibrosis.

Mechanistic Evaluation of Benzo[a]pyrene's Developmental Toxicities Mediated by Reduced Cyp19a1b Activity.

Benzo[a]pyrene (BaP) is a ubiquitous environmental contaminant that is both an endocrine disruptor and a carcinogen. Aromatase (CYP19) is a key enzyme in steroidogenesis that is responsible for conversion of androgens to estrogens and thus plays a key role in steroid homeostasis. We hypothesized that some of the adverse outcomes of early developmental exposure to BaP are the result of reduced Cyp19a1b activity. Our goal was to investigate the role of estrogen homeostasis during early development and determine the role of aromatase inhibition as a relevant mechanism in BaP's developmental toxicities. One-cell zebrafish embryos were injected with a Cyp19a1b-morpholino (MO) or control-MO. Other non-injected embryos were exposed to waterborne BaP, fadrozole (a Cyp19 inhibitor), estradiol (E2), BaP + E2, Cyp19a1b MO + E2, or fadrozole + E2 for 96 hours post-fertilization (hpf). Adverse outcomes were compared between treatments, and the ability of E2 co-exposure to rescue each observed dysmorphology was assessed. BaP significantly decreased cyp19a1b gene expression in 96 hpf zebrafish larvae homogenates. Concentrations of E2 in 48 hpf larvae were significantly decreased by BaP, fadrozole and Cyp19a1b-MO. Cumulative mortality of zebrafish larvae was significantly increased following BaP or fadrozole exposure or Cyp19a1b knockdown compared to controls. E2 co-treatment rescued mortality caused by 10 µg/L BaP, 10 µg/L fadrozole, or Cyp19a1b-MO. In a treatment-blinded morphological assessment of larvae at 96 hpf, several phenotypes were negatively impacted by BaP, fadrozole, or Cyp19a1b knockdown and rescued by exogenous E2 co-treatment; these included body length, optic vesicle size, swim bladder inflation, pericardial and abdominal edema, and incidence of normal larval tail shape. Abnormal pectoral fins were caused by BaP exposure only. Uninflated swim bladders were caused by all treatments including E2 alone. Our results indicate that certain BaP-mediated adverse developmental outcomes were mechanistically in accordance with BaP-mediated Cyp19a1b inhibition.