In silico evaluation of anti-colorectal cancer inhibitors by Resveratrol derivatives targeting Armadillo repeats domain of APC: molecular docking and molecular dynamics simulation.

Colorectal cancer is the second leading cause of cancer-related deaths. In 2018, there were an estimated 1.8 million cases, and this number is expected to increase to 2.2 million by 2030. Despite its prevalence, the current therapeutic option has a lot of side effects and limitations. Therefore, this study was designed to employ a computational approach for the identification of anti-cancer inhibitors against colorectal cancer using Resveratrol derivatives. Initially, the pass prediction spectrum of 50 derivatives was conducted and selected top seven compounds based on the maximum pass prediction score. After that, a comprehensive analysis, including Lipinski Rule, pharmacokinetics, ADMET profile study, molecular orbitals analysis, molecular docking, molecular dynamic simulations, and MM-PBSA binding free energy calculations. The reported binding affinity ranges of Resveratrol derivatives from molecular docking were -6.1 kcal/mol to -7.9 kcal/mol against the targeted receptor of human armadillo repeats domain of adenomatous polyposis coli (APC) (PDB ID: 3NMW). Specifically, our findings reported that two compounds [(03) Resveratrol 3-beta-mono-D-glucoside, and (29) Resveratrol 3-Glucoside] displayed the highest level of effectiveness compared to all other derivatives (-7.7 kcal/mol and -7.9 kcal/mol), and favorable drug-likeness, and exceptional safety profiles. Importantly, almost all the molecules were reported as free from toxic effects. Subsequently, molecular dynamic simulations conducted over 100ns confirmed the stability of the top two ligand-protein complexes. These findings suggest that Resveratrol derivatives may be effective drug candidate to manage the colorectal cancer. However, further experimental research, such as in vitro/in vivo studies, is essential to validate these computational findings and confirm their practical value.

Echinacea purpurea root extract mitigates hepatotoxicity, genotoxicity, and ultrastructural changes induced by hexavalent chromium via oxidative stress suppression.

Environmental and occupational exposure to hexavalent chromium (CrVI) is mostly renowned as a possible hepatotoxic in mammals. Echinacea purpurea (L.) Moench, a phenolic-rich plant, is recurrently used for its therapeutic properties. Therefore, this investigation was done to explore whether E. purpurea (EP) root extract would have any potential health benefits against an acute dose of CrVI-induced oxidative damage and hepatotoxicity. Results revealed that GC-MS analysis of EP root extract has 26 identified components with a significant amount of total phenolic and flavonoid contents. Twenty-four Male Wistar rats were divided into four groups: control, EP (50 mg/kg BW/day for 21 days), CrVI (15 mg/kg BW as a single intraperitoneal dosage), and EP + CrVI, respectively. Rats treated with CrVI displayed a remarkable rise in oxidative stress markers (TBARS, H2O2, PCC), bilirubin, and lactate dehydrogenase activity, and a marked decrease in enzymatic and non-enzymatic antioxidants, transaminases, and alkaline phosphatase activities, and serum protein level. Also, CrVI administration induced apoptosis and inflammation in addition to histological and ultrastructural abnormalities in the liver tissue. The examined parameters were improved significantly in rats pretreated with EP and then intoxicated with CrVI. Conclusively, EP had a potent antioxidant activity and could be used in the modulation of CrVI-induced hepatotoxicity.

Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.

Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy.

In the realm of cancer immunotherapy, a profound evolution has ushered in sophisticated strategies that encompass both traditional cancer vaccines and emerging viral vaccines. This comprehensive Review offers an in-depth exploration of the methodologies, clinical applications, success stories, and future prospects of these approaches. Traditional cancer vaccines have undergone significant advancements utilizing diverse modalities such as proteins, peptides, and dendritic cells. More recent innovations have focused on the physiological mechanisms enabling the human body to recognize and combat precancerous and malignant cells, introducing specific markers like peptide-based anticancer vaccines targeting tumor-associated antigens. Moreover, cancer viral vaccines, leveraging engineered viruses to stimulate immune responses against specific antigens, exhibit substantial promise in inducing robust and enduring immunity. Integration with complementary therapeutic methods, including monoclonal antibodies, adjuvants, and radiation therapy, has not only improved survival rates but also deepened our understanding of viral virulence. Recent strides in vaccine design, encompassing oncolytic viruses, virus-like particles, and viral vectors, mark the frontier of innovation. While these advances hold immense potential, critical challenges must be addressed, such as strategies for immune evasion, potential off-target effects, and the optimization of viral genomes. In the landscape of immunotherapy, noteworthy innovations take the spotlight from the use of immunomodulatory agents for the enhancement of innate and adaptive immune collaboration. The emergence of proteolysis-targeting chimeras (PROTACs) as precision tools for cancer therapy is particularly exciting. With a focus on various cancers, from melanoma to formidable solid tumors, this Review critically assesses types of cancer vaccines, mechanisms, barriers in vaccine therapy, vaccine efficacy, safety profiles, and immune-related adverse events, providing a nuanced perspective on the underlying mechanisms involving cytotoxic T cells, natural killer cells, and dendritic cells. The Review also underscores the transformative potential of cutting-edge technologies such as clinical studies, molecular sequencing, and artificial intelligence in advancing the field of cancer vaccines. These tools not only expedite progress but also emphasize the multidimensional and rapidly evolving nature of this research, affirming its profound significance in the broader context of cancer therapy.

Citrus reticulata peel extract mitigates oxidative stress and liver injury induced by abamectin in rats.

The prevalent use of abamectin (ABM) has latterly raised safety attention as it has different toxicities to non-target living organisms. Citrus fruits are widely renowned for their nutritional and health-promoting qualities, and their peels are full of phenolic constituents. The purpose of the current study was to evaluate the modulatory effectiveness of Citrus reticulata peel extract (CPE) against abamectin-induced hepatotoxicity and oxidative injury. Rats were distributed into 4 groups as follows: control, CPE (400 mg/kg bw orally for 14 days), ABM (2 mg/kg bw for 5 days), and CPE + ABM at the doses mentioned above. Results revealed that GC-MS analysis of CPE has 19 identified components with significant total phenolic and flavonoid contents. Treatment with ABM in rats displayed significant variations in enzymatic and non-enzymatic antioxidants, oxidative stress markers (MDA, H2O2, PCC), liver and kidney function biomarkers, hematological parameters, lipids, and protein profile as well as histopathological abnormalities, inflammation and apoptosis (TNF-α, Caspase-3, NF-κB, and Bcl-2 genes) in rats' liver. Supplementation of CPE solo dramatically improved the antioxidant state and reduced oxidative stress. C. reticulata peel extract pretreatment alleviated ABM toxicity by modulating most of the tested parameters compared to the ABM group. Conclusively, CPE had potent antioxidant activity and could be used in the modulation of ABM hepatotoxicity presumably due to its antioxidant, anti-inflammatory, and gene-regulating capabilities.

Postbiotic, anti-inflammatory, and immunomodulatory effects of aqueous microbial lysozyme in broiler chickens.

Lysozymes, efficient alternative supplements to antibiotics, have several benefits in poultry production. In the present study, 120, one-day-old, Ross 308 broiler chickens of mixed sex, were allocated into 2 equal groups, lysozyme treated group (LTG) and lysozyme free group (LFG), to evaluate the efficacy of lysozyme (Lysonir®) usage via both drinking water (thrice) and spray (once). LTG had better (p = 0.042) FCR, and higher European production efficiency factor compared to LFG (p = 0.042). The intestinal integrity score of LTG was decreased (p = 0.242) compared to that of LFG; 0.2 vs. 0.7. Higher (p ≤ 0.001) intestinal Lactobacillus counts were detected in chickens of LTG. Decreased (p ≤ 0.001) IL-1ß and CXCL8 values were reported in LTG. The cellular immune modulation showed higher (p ≤ 0.001) opsonic activity (MΦ and phagocytic index) in LTG vs. LFG at 25 and 35 days. Also, higher (p ≤ 0.001) local, IgA, and humoral, HI titers, for both Newcastle, and avian influenza H5 viruses were found in LTG compared to LFG. In conclusion, microbial lysozyme could improve feed efficiency, intestinal integrity, Lactobacillus counts, anti-inflammatory, and immune responses in broiler chickens.

Exogenous aqueous and spray microbial lysozyme enhanced growth in commercial broiler chickensThe postbiotic effects of microbial lysozyme modulated intestinal integrity.Anti-inflammatory, as well as local, cellular, and humoral immune response were stimulated by lysozyme supplementation.

Berberine alleviates chlorpyrifos-induced nephrotoxicity in rats via modulation of Nrf2/HO-1 axis.

Chlorpyrifos (CPS), an organophosphorus insecticide, is widely used for agricultural and non-agricultural purposes with hazardous health effects. Berberine (BBR) is a traditional Chinese medicine and a phytochemical with anti-inflammatory and anti-oxidative properties. The present study evaluated the effects of BBR against kidney damage induced by CPS and the underlying mechanisms. An initial study indicated that BBR 50 mg/kg was optimal under our experimental conditions. Then, 24 rats (6/group) were randomized into: control, BBR (50 mg/kg/day), CPS (10 mg/kg/day), and CPS + BBR. BBR was administration 1 h prior to CPS. Each treatment was delivered daily for a period of 28 consecutive days using a gastric gavage tube. Compared to CPS-alone treated rats, BBR effectively improved renal function by preventing the rise in serum urea, creatinine, and uric levels. The reno-protective effects of BBR were confirmed through a histological examination of kidney tissues. BBR restored oxidant-antioxidant balance in renal tissues mediated by Keap1/Nrf2/HO-1 axis modulation. In addition, BBR decreased nitric oxide (NO) and myeloperoxidase (MPO) activity. This was paralleled with the potent down-regulation of NF-κB. Furthermore, BBR exhibited anti-apoptotic activities supported by the upregulation of Bcl-2 and down-regulation of Bax and caspase-3 expression. In conclusion, our data suggest that BBR attenuates CPS-induced nephrotoxicity in rats by restoring oxidant-antioxidant balance and inhibiting inflammatory response and apoptosis in renal tissue. This is mediated, at least partly, by modulation of the Nrf2/HO-1 axis.

Dissemination of mcr-1 and ß-lactamase genes among Pseudomonas aeruginosa: molecular characterization of MDR strains in broiler chicks and dead-in-shell chicks infections.

OBJECTIVES: Pseudomonas aeruginosa (P. aeruginosa) is one of the most serious pathogens implicated in antimicrobial resistance, and it has been identified as an ESKAPE along with other extremely significant multidrug resistance pathogens. The present study was carried out to explore prevalence, antibiotic susceptibility phenotypes, virulence-associated genes, integron (int1), colistin (mcr-1), and ß-lactamase resistance' genes (ESBls), as well as biofilm profiling of P. aeruginosa isolated from broiler chicks and dead in-shell chicks. DESIGN: A total of 300 samples from broiler chicks (n = 200) and dead in-shell chicks (n = 100) collected from different farms and hatcheries located at Mansoura, Dakahlia Governorate, Egypt were included in this study. Bacteriological examination was performed by cultivation of the samples on the surface of both Cetrimide and MacConkey's agar. Presumptive colonies were then subjected to biochemical tests and Polymerase Chain Reaction (PCR) targeting 16S rRNA. The recovered isolates were tested for the presence of three selected virulence-associated genes (lasB, toxA, and exoS). Furthermore, the retrieved isolates were subjected to phenotypic antimicrobial susceptibility testing by Kirby-Bauer disc diffusion method as well as phenotypic detection of ESBLs by both Double Disc Synergy Test (DDST) and the Phenotypic Confirmatory Disc Diffusion Test (PCDDT). P. aeruginosa isolates were then tested for the presence of antibiotic resistance genes (ARGs): int1, mcr-1, and ESBL genes (OXA-10, OXA-2, VEB-1, SHV, TEM, and CTX-M). Additionally, biofilm production was examined by the Tube Adherent method (TA) and Microtiter Plate assay (MTP). RESULTS: Fifty -five isolates were confirmed to be P. aeruginosa, including 35 isolates from broiler chicks and 20 isolates from dead in-shell chicks. The three tested virulence genes (lasB, toxA, and exoS) were detected in all isolates. Antibiogram results showed complete resistance against penicillin, amoxicillin, ceftriaxone, ceftazidime, streptomycin, erythromycin, spectinomycin, and doxycycline, while a higher sensitivity was observed against meropenem, imipenem, colistin sulfate, ciprofloxacin, and gentamicin. ESBL production was confirmed in 12 (21.8%) and 15 (27.3%) isolates by DDST and PCDDT, respectively. Antibiotic resistance genes (ARGs): int1, mcr-1, and ESBL genes (OXA-10, SHV, TEM, and CTX-M), were detected in 87.3%, 18.2%, 16.4%, 69.1%, 72.7%, and 54.5% of the examined isolates respectively, whereas no isolate harbored the OXA-2 or VEB-1 genes. Based on the results of both methods used for detection of biofilm formation, Kappa statistics [kappa 0.324] revealed a poor agreement between both methods. CONCLUSIONS: the emergence of mcr-1 and its coexistence with other resistance genes such as ß-lactamase genes, particularly blaOXA-10, for the first time in P. aeruginosa from young broiler chicks and dead in-shell chicks in Egypt pose a risk not only to the poultry industry but also to public health.

From nature to nanotechnology: The interplay of traditional medicine, green chemistry, and biogenic metallic phytonanoparticles in modern healthcare innovation and sustainability.

As we navigate the modern era, the intersection of time-honoured natural remedies and contemporary scientific approaches forms a burgeoning frontier in global healthcare. For generations, natural products have been foundational to health solutions, serving as the primary healthcare choice for 80% to 85% of the world's population. These herbal-based, nature-derived substances, significant across diverse geographies, necessitate a renewed emphasis on enhancing their quality, efficacy, and safety. In the current century, the advent of biogenic phytonanoparticles has emerged as an innovative therapeutic conduit, perfectly aligning with principles of environmental safety and scientific ingenuity. Utilizing green chemistry techniques, a spectrum of metallic nanoparticles including elements such as copper, silver, iron, zinc, and titanium oxide can be produced with attributes of non-toxicity, sustainability, and economic efficiency. Sophisticated herb-mediated processes yield an array of plant-originated nanomaterials, each demonstrating unique physical, chemical, and biological characteristics. These attributes herald new therapeutic potentials, encompassing antioxidants, anti-aging applications, and more. Modern technology further accelerates the synthesis of natural products within laboratory settings, providing an efficient alternative to conventional isolation methods. The collaboration between traditional wisdom and advanced methodologies now signals a new epoch in healthcare. Here, the augmentation of traditional medicine is realized through rigorous scientific examination. By intertwining ethical considerations, cutting-edge technology, and natural philosophy, the realms of biogenic phytonanoparticles and traditional medicine forge promising pathways for research, development, and healing. The narrative of this seamless integration marks an exciting evolution in healthcare, where the fusion of sustainability and innovation crafts a future filled with endless possibilities for human well-being. The research in the development of metallic nanoparticles is crucial for unlocking their potential in revolutionizing fields such as medicine, catalysis, and electronics, promising groundbreaking applications with enhanced efficiency and tailored functionalities in future technologies. This exploration is essential for harnessing the unique properties of metallic nanoparticles to address pressing challenges and advance innovations across diverse scientific and industrial domains.

Laying performance, genetic parameters, and the expression of FSHß, LHß, FSHR, and LHR genes in Japanese quails selected for early egg production.

Investigating the impact of early egg production selection (the first 90 d of laying) on egg production features, cumulative selection response (CSR), and the mRNA expression of gonadotropins (FSHß and LHß), and their receptors (FSHR and LHR), in Japanese quails was the goal. The selection experiment involved 1293 females in all, 257 from the base group and 1036 from the 4 selected generations. Age and body weight at sexual maturity (ASM, BWSM), weight of the first egg (WFE), days to the first 10 eggs (DF10E), egg mass for the first 10 eggs (EMF10E), egg weight (EW), egg number at the first 90 d of laying (EN90D), and egg mass at the first 90 d of laying (EM90D) were all recorded. Most egg production traits had heritability estimates that were low to moderate and ranged from 0.17 to 0.33., where the highest estimates were reported for EN90D (0.33) and BWSM (0.32). With the exception of EN90D, low to moderate positive genetic correlations were observed between ASM and other egg production traits (0.17-0.44). The fourth generation showed significantly (P < 0.05) lower ASM and DF10E but higher BWSM, WFE, EN90D, EM10E, and EM90D when compared with the base generation. CSR were significant (P < 0.05) for ASM (-6.67 d), BWSM (27.13 g), WFE (0.93 g), DF10E (-1.25 d), EN90D (7.24 egg), EM10E (10.57 g), and EM90D (140.0 g). FSHß, LHß, FSHR, and LHR gene mRNA expression was considerably (P < 0.05) greater in the fourth generation compared to the base generation. In conclusion, selection programs depending on the efficiency of egg production (EN90D) could improve the genetic gain of egg production traits and upregulate the mRNA expression of FSHß, LHß, FSHR, and LHR genes in selected quails (fourth generation). These findings might help to enhance breeding plans and create commercial lines of high egg production Japanese quails.

Mitigative potential of kaempferide against polyethylene microplastics induced testicular damage by activating Nrf-2/Keap-1 pathway.

Polyethylene microplastics (PE-MPs) are one of the environmental contaminants that instigate oxidative stress (OS) in various organs of the body, including testes. Kaempferide (KFD) is a plant-derived natural flavonol with potential neuroprotective, hepatoprotective, anti-cancer, anti-oxidant and anti-inflammatory properties. Therefore, the present study was designed to evaluate the alleviative effects of KFD against PE-MPs-prompted testicular toxicity in rats. Fourty eight adult male albino rats were randomly distributed into 4 groups: control, PE-MPs-administered (1.5 mgkg-1), PE-MPs (1.5 mgkg-1) + KFD (20 mgkg-1) co-treated and KFD (20 mgkg-1) only treated group. PE-MPs intoxication significantly (P < 0.05) lowered the expression of Nrf-2 and anti-oxidant enzymes, while increasing the expression of Keap-1. The activities of anti-oxidants i.e., catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), hemeoxygene-1 (HO-1) and glutathione peroxidase (GPx) were reduced, besides malondialdehyde (MDA) and reactive oxygen species (ROS) contents were increased significantly (P < 0.05) following the PE-MPs exposure. Moreover, PE-MPs exposure significantly (P < 0.05) reduced the sperm motility, viability and count, whereas considerably (P < 0.05) increased the dead sperm number and sperm structural anomalies. Furthermore, PE-MPs remarkably (P < 0.05) decreased steroidogenic enzymes and Bcl-2 expression, while increasing the expression of Caspase-3 and Bax. PE-MPs exposure significantly (P < 0.05) reduced the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, whereas inflammatory indices were increased. PE-MPs exposure also induced significant histopathological damages in the testes. Nevertheless, KFD supplementation significantly (P < 0.05) abrogated all the damages induced by PE-MPs. The findings of our study demonstrated that KFD could significantly attenuate PE-MPs-instigated OS and testicular toxicity, due to its anti-oxidant, anti-inflammatory, androgenic and anti-apoptotic potential.

Spirulina platensis ameliorates hepatic oxidative stress and DNA damage induced by aflatoxin B1 in rats.

Aflatoxin B1 (AFB1) is a widely distributed mycotoxin, causing hepatotoxicity and oxidative stress. One of the most famous unicellular cyanobacteria is Spirulina platensis (SP) which is well known for its antioxidant characteristics against many toxicants. Therefore, this study aimed to investigate the antioxidant potential and hepatoprotective ability of SP against oxidative stress and cytotoxicity in male Wistar albino rats intraperitoneally injected with AFB1. Rats were separated into five groups as follows: negative control administered with saline; SP (1000 mg/kg BW) for two weeks; AFB1 (2.5 mg/kg BW) twice on days 12 and 14; AFB1 (twice) + 500 mg SP/kg BW (for two weeks) and AFB1 (twice) + 1000 mg SP/kg BW (for two weeks). Liver and blood samples were assembled for histological and biochemical analyses. AFB1 intoxicated rats showed a marked elevation in serum biochemical parameters (ALP, ALT, and AST), hepatic lipid peroxidation (MDA and NO), and proliferating cell nuclear antigen (PCNA) indicating DNA damage. Moreover, AFB1 caused suppression of antioxidant biomarkers (SOD, GHS, GSH-Px, and CAT). However, the elevated serum levels of biochemical parameters and PCNA expression were reduced by SP. Moreover, SP lowered oxidative stress and lipid peroxidation markers in a dose-dependent manner. To sum up, SP supplementation is capable of decreasing AFB1 toxicity through its powerful antioxidant activity.

Association between diabetes distress and sociodemographic and/or socioeconomic factors among adults: A cross-sectional study.

Diabetes-related distress (DRD) is a psychological syndrome with worsened prognosis in uncontrolled diabetic patients. The current study aimed to assess the factors contributing to DRD among the Lebanese population using the Diabetes Distress Scale (DDS-17) score and its sub-scores. A cross-sectional analysis was conducted between March and September 2021 enrolling. 125 diabetic from six Lebanese governorates through an online survey. The survey included two parts: the first section gathered sociodemographic data sociodemographic and socioeconomic data and the second one focused on assessing the Diabetes Distress Scale (DDS-17) score. Participants 30 years old and above had higher emotional distress compared to younger patients, (65.2 % versus 45.5 %). Those with a primary educational level showed significantly higher emotional distress than those with a secondary and tertiary level of education (72.5 %, versus 66.7 % and 46.4 %). Participants who were treated with both insulin and non-insulin medications or had a diastolic blood pressure of more than 90 mmHg showed significantly moderate to high distress (63.6 % or 53.8 %). Participants who lived in rural areas showed higher distress (35.6 %). Obese and overweight had significant moderate to high distress (64.1 %, and 48.0 %). The same results were found in non-married (divorced or widowed) and married participants (76.9 % and 51.3 %). The association between medical history with total distress showed that participants with glycemic store HbA1c of more than 6.5 followed by those who had HbA1c between 5.7 and 6.4 showed moderate to high total distress (45.9 % and 40.0 %). It is concluded that the prevalence of DRD is high in Lebanon, more common among rural residents, and among participants high HbA1c, low educational level, unmarried and on complex treatment regimens. Screening for DRD and providing better support can optimize clinical outcomes.

Acute aflatoxin B1-induced hepatic and cardiac oxidative damage in rats: Ameliorative effects of morin.

Aflatoxins (AFs) are secondary metabolites produced by the fungus Aspergillus flavus, of which Aflatoxin-B1 (AFB1) appears to be the most cancerogenic and of the highest toxicity. AFB1 causes serious effects on several organs including the liver. Morin is a flavonol that exists in many fruits and plants and has diverse biological properties including anticancer, anti-atherosclerotic, antioxidant, anti-inflammatory, immunomodulatory, and multi-organ protective activities. The present study aims to evaluate the potential protective effects of morin against acute AFB1-induced hepatic and cardiac toxicity in rats. Forty rats were divided into five groups (n = 8) as follows: control received the vehicle, morin was orally administered 30/mg/kg body weight (MRN30), the AFB1 was administered orally at a dose of 2.5 mg/kg, twice on days 12 and 14 of the experiment for the 3rd, 4th, and 5th groups., AFB1-MRN15 was orally given morin at a dose of 15 mg/kg body weight, and AFB1-MRN30 orally received morin at 30 mg/kg body weight. The results indicated a significant decrease in serum AST, ALP, LDH, GGT, CK, CK-MB, 8-OHdG, IL-1ß, IL-6, TNF-a levels in MRN30 compared to AFB1, and AFB1-MRN15 groups. However, the results indicated non-significant differences in the serum levels between MRN30, control, and AFB1-MRN30 groups. Meanwhile, regarding the hepatic and cardiac parameters, there were significant differences in the levels of MDA, NO, GSH, GSH-Px, SOD, and CAT in MRN30 compared to AFB1, and AFB1-MRN15 groups, overall implying the protective effects of morin. To conclude, morin at a dose of 30 mg/kg b. wt. showed significant enhancements in acute AFB1-induced hepatic and cardiac toxicity in rats, which could play a role in limiting the public health hazards of AFs.

Rhamnetin, a nutraceutical flavonoid arrests cell cycle progression of human ovarian cancer (SKOV3) cells by inhibiting the histone deacetylase 2 protein.

Overexpression of HDAC 2 promotes cell proliferation in ovarian cancer. HDAC 2 is involved in chromatin remodeling, transcriptional repression, and the formation of condensed chromatin structures. Targeting HDAC 2 presents a promising therapeutic approach for correcting cancer-associated epigenetic abnormalities. Consequently, HDAC 2 inhibitors have evolved as an attractive class of anti-cancer agents. This work intended to investigate the anti-cancer abilities and underlying molecular mechanisms of Rhamnetin in human epithelial ovarian carcinoma cells (SKOV3), which remain largely unexplored. We employed various in vitro methods, including MTT, apoptosis study, cell cycle analysis, fluorescence microscopy imaging, and in vitro enzymatic HDAC 2 protein inhibition, to examine the chemotherapeutic sensitivity of Rhamnetin in SKOV3 cells. Additionally, we conducted in silico studies using molecular docking, MD simulation, MM-GBSA, DFT, and pharmacokinetic analysis to investigate the binding interaction mechanism within Rhamnetin and HDAC 2, alongside the compound's prospective as a lead candidate. The in vitro assay confirmed the cytotoxic effects of Rhamnetin on SKOV3 cells, through its inhibition of HDAC 2 activity. Rhamnetin, a nutraceutical flavonoid, halted at the G1 phase of the cell cycle and triggered apoptosis in SKOV3 cells. Furthermore, computational studies provided additional evidence of its stable binding to the HDAC 2 protein's binding site cavity. Based on our findings, we conclude that Rhamnetin effectively promotes apoptosis and mitigates the proliferation of SKOV3 cells through HDAC 2 inhibition. These results highlight Rhamnetin as a potential lead compound, opening a new therapeutic strategy for human epithelial ovarian cancer.Communicated by Ramaswamy H. Sarma.

Unveiling a novel terpolymer-metal complex: A detailed exploration of synthesis, characterization, and its potential as an antimicrobial and antioxidant agent.

In an innovative approach to push the boundaries of antimicrobial and antioxidant strategies, we present the synthesis and characterization of a novel terpolymer derived from N-Phenyl-p-phenylenediamine and 2-aminopyrimidine with formaldehyde in the presence of dimethylformamide as a reaction medium through polycondensation technique. Leveraging this terpolymer as a ligand, we introduce an intriguing terpolymer-metal complex, created with Ni (II) metal ion. In our pursuit to validate the structure and properties of these substances, we performed meticulous characterizations using important spectral studies such as FTIR, electronic, and 1H NMR spectroscopy. This provided us with a unique fingerprint for the (N-Phenyl-p-phenylenediamine-2-aminopyrimidine-formaldehyde) terpolymeric ligand (PAF) and its metal complex. In addition, the molecular weights of PAF terpolymer were established using gel permeation chromatography. Upon investigation, PAF terpolymer and PAF-Ni complex exhibited impressive antimicrobial activity, tested by the disc-diffusion technique. Both demonstrated potency against a range of harmful bacterial and fungal strains, including Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger. In an extension to their biological applications, we evaluated the free radical scavenging activity of PAF terpolymer and PAF-Ni complex using the DPPH assay. The complex PAF-Ni showcased an enhanced scavenging activity 73.94% (IC50 = 17.58) compared to the ligand PAF 63.06% (IC50 = 27.61) at 100 µg/ml indicating its potential role in oxidative stress management.

Antimalarial drug discovery against malaria parasites through haplopine modification: An advanced computational approach.

The widespread emergence of antimalarial drug resistance has created a major threat to public health. Malaria is a life-threatening infectious disease caused by Plasmodium spp., which includes Apicoplast DNA polymerase and Plasmodium falciparum cysteine protease falcipain-2. These components play a critical role in their life cycle and metabolic pathway, and are involved in the breakdown of erythrocyte hemoglobin in the host, making them promising targets for anti-malarial drug design. Our current study has been designed to explore the potential inhibitors from haplopine derivatives against these two targets using an in silico approach. A total of nine haplopine derivatives were used to perform molecular docking, and the results revealed that Ligands 03 and 05 showed strong binding affinity compared to the control compound atovaquone. Furthermore, these ligand-protein complexes underwent molecular dynamics simulations, and the results demonstrated that the complexes maintained strong stability in terms of RMSD (root mean square deviation), RMSF (root mean square fluctuation), and Rg (radius of gyration) over a 100 ns simulation period. Additionally, PCA (principal component analysis) analysis and the dynamic cross-correlation matrix showed positive outcomes for the protein-ligand complexes. Moreover, the compounds exhibited no violations of the Lipinski rule, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions yielded positive results without indicating any toxicity. Finally, density functional theory (DFT) and molecular electrostatic potential calculations were conducted, revealing that the mentioned derivatives exhibited better stability and outstanding performance. Overall, this computational approach suggests that these haplopine derivatives could serve as a potential source for developing new, effective antimalarial drugs to combat malaria. However, further in vitro or in vivo studies might be conducted to determine their actual effectiveness.

Harnessing role of sesamol and its nanoformulations against neurodegenerative diseases.

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.