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The development of sensitive and specific diagnostic tools for hepatitis B virus (HBV) and hepatitis C virus (HCV) remains crucial for effective disease management and control. In this study, we utilized CRISPR-Cas12 and CRISPR-Cas13 systems for the detection of HBV (DNA virus) and HCV (RNA virus), respectively. We designed and tested multiple guide RNAs (gRNAs) targeting both viruses, confirming successful cleavage of target sequences through gel electrophoresis and a fluorescent reporter assay. Using optimized gRNAs, we developed a lateral flow assay (LFA) for sensitive detection of HBV and HCV, demonstrating a concentration-dependent signal increase. Importantly, no cross-reactivity was observed with other viral targets. To further enhance sensitivity, we employed a dual-enzyme approach, combining Cas12 and Cas13 in a single reaction, which significantly improved detection limits for both viruses. Finally, we developed a dual antigen detection LFA strip capable of simultaneously detecting both HBV and HCV in a single sample. This approach holds promise for point-of-care (POC) diagnostics where the specific viral infection is unknown. This study addresses the current limitations in CRISPR-Cas based diagnostics, namely, the need for ultrasensitive detection methods and the ability to detect multiple antigens using a single test strip. Our findings demonstrate the feasibility of using CRISPR-Cas systems for highly sensitive and specific detection of HBV and HCV, paving the way for potential POC application.

Malignancies of the liver and colon are the most prevalent forms of digestive system cancer globally. Chemotherapy, one of the most significant treatments, has severe side effects. Chemoprevention using natural or synthetic medications can potentially reduce cancer severity. Acetyl-L-carnitine (ALC) is an acetylated derivative of carnitine essential for intermediate metabolism in most tissues. This study aimed to investigate the effects of ALC on the proliferation, migration, and gene expression of human liver (HepG2) and colorectal (HT29) adenocarcinoma cell lines. The cell viability and half maximal inhibitory concentration of both cancer cell lines were determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Wound healing after treatment was assessed using a migration assay. Morphological changes were imaged using brightfield and fluorescence microscopy. Post treatment, apoptotic DNA was detected using a DNA fragmentation assay. The relative mRNA expressions of matrix metallopeptidase 9 (MMP9) and vascular endothelial growth factor (VEGF) were evaluated using RT-PCR. The results showed that ALC treatment affects the wound-healing ability of HepG2 and HT29 cell lines. Changes in nuclear morphology were detected under fluorescent microscopy. ALC also downregulates the expression levels of MMP9 and VEGF in HepG2 and HT29 cell lines. Our results indicate that the anticancer action of ALC is likely mediated by a decrease in adhesion, migration, and invasion.

Five hundred and sixty broilers were placed into seven groups. The first negative control (A) was fed the baseline diet (BD); the second positive control (B) was fed BD and exposed to clostridium infection; and the third and fourth groups (C, D) were the same as the positive control with 500 and 1000 g/ton of feed, respectively. The fifth group (E) served as a positive control for the addition of lincomycin, whereas the sixth and seventh groups (F, G) received the same designed diet as the E group but supplemented with HA at 500 and 1000 g/ton of feed, respectively. Birds infected with Clostridium perfringens had considerably decreased body weight. However, a dietary combination of HA and lincomycin resulted in a greater improvement in growth. Body weight increased after 35 days, but feed intake dropped, therefore HA and lincomycin supplementation enhanced feed conversion ratio. Supplementing with HA and lincomycin increased crude protein retention. Furthermore, these additions mitigated the detrimental effects of clostridial infection on the gut by reducing degenerative changes in intestinal villi and increasing villi length, particularly at higher HA/lincomycin doses. In conclusion, nutritional supplementation with humic acid and lincomycin improved blood biochemistry, and gut morphology in broilers infected with Clostridium difficile.

Background: COVID-19 is an infectious disease declared as a global pandemic caused by SARS-CoV-2 virus. Genomic changes in the receptor binding domain (RBD) region of SARS‐CoV‐2 led to an increased, infectivity in humans through interaction with the angiotensin-converting enzyme2 (ACE2) receptor. Simultaneously, the genetic variants in ACE2 provide an opportunity for SARS‐CoV‐2 infection and severity. We demonstrate the binding efficiencies of RBDs of SARS‐CoV‐2 strain with ACE2 variants of the human host. Methodology: A Total of 615 SARS‐CoV‐2 genomes were retrieved from repository. Eighteen variations were identified contributing to structural changes in RBD that are distributed in 615 isolates. An analyses of 285 single nucleotide variances at the coding region of the ACE2 receptor showed 34 to be pathogenic. Homology models of 34 ACE2 and 18 RBD structures were constructed with 34 and 18 structural variants, respectively. Protein docking of 612 (34 *18) ACE2-RBD complexes showed variable affinities compared to wildtype Wuhan's and other SARS‐CoV‐2 RBDs, including Omicron B.1.1.529. Finally, molecular dynamic simulation was performed to determine the stability of the complexes. Results: Among 612, the top 3 complexes showing least binding energy were selected. The ACE2 with rs961360700 variant showed the least binding energy (−895.2 Kcal/mol) on binding with the RBD of Phe160Ser variant compared to Wuhan's RBD complex. Interestingly, the binding energy of RBD of Omicron B.1.1.529 with ACE2 (rs961360700) structure showed least binding energy of −1010 Kcal/mol. Additionally, molecular dynamics showed structure stability for all the analysed complexes with the RMSD (0.22–0.26 nm), RMSF (0.11–0.13 nm), and Rg (2.53–2.56 nm). Conclusion: In conclusion, our investigation highlights the clinical variants contributing to structural variants in ACE2 receptors that lead to efficient binding of SARS‐CoV‐2. Therefore, screening of these ACE2 polymorphisms will help detect COVID‐19 risk population so as to provide additional care and for safe management.

Introduction: Several recent studies pointed out that chromodomain-helicase-DNA-binding protein 1-like (CHD1L) is a putative oncogene in many human tumors. However, up to date, there is no pan-cancer analysis performed to study the different aspects of this gene expression and behavior in tumor tissues.Methods: Here, we applied several bioinformatics tools to make a comprehensive analysis for CHD1L. Firstly we assessed the expression of CHD1L in several types of human tumors and tried to correlate that with the stage and grade of the analyzed tumors. Following that, we performed a survival analysis to study the correlation between CHD1L upregulation in tumors and the clinical outcome. Additionally, we investigated the mutation forms, the correlation with several immune cell infiltration, and the potential molecular mechanisms of CHD1L in the tumor tissue.Result and discussion: The results demonstrated that CHD1L is a highly expressed gene across several types of tumors and that was correlated with a poor prognosis for most cancer patients. Moreover, it was found that CHD1L affects the tumor immune microenvironment by influencing the infiltration level of several immune cells. Collectively, the current study provides a comprehensive overview of the oncogenic roles of CHD1L where our results nominate CHD1L as a potential prognostic biomarker and target for antitumor therapy development.

Hepatocellular carcinoma (HCC) is the most common form of malignancy in the liver. Autophagy was found to have a significant effect in controlling HCC. Anthocyanins, which are naturally occurring pigments in a variety of fruits and vegetables, have been thoroughly documented to be involved in a variety of bioactive activities and are widely employed for their antioxidant capabilities. Cyanidin-3-glucoside (C3G) extracted from Morus alba L. has promising antioxidant and anti-tumour activities. The current study aims to examine the protective action of C3G against hepatocellular carcinoma through the investigation of the autophagy protein ATG16L1 expression along with its related RNA molecules (hsa_circ_0001345 and miRNA106b) in Wistar rats. In vivo precancerous lesions (PCL) were induced using diethylnitrosamine (DEN) and acetamidofluorene (2-AAF). Rats were treated with C3G (10, 15, and 20 mg/kg; 4 times weekly) for 112 days (16 weeks). Liver function tests, alfa fetoprotein, ATG16L1 expression, hsa_circ_0001345, and miRNA106b differential expression were examined. Liver sections were examined by histological and immunohistochemical approaches. The current study’s findings indicated that C3G administration protects against the negative effects of DEN-2-AAF on liver functions and liver histopathological sections, which nominated C3G as a potential prophylactic agent against HCC.

Background: Mammalian WD-repeat protein 12 (WDR12), a family member of proteins containing repeats of tryptophan-aspartic acid (WD), is a potential homolog of yeast Ytm1p and consists of seven repeats of WD.Aim of the study: This study aims to investigate the potential oncogenic effects of WDR12 in various human malignancies throughout a pan-cancer analysis that has been carried out to examine the various patterns in which this gene is expressed and behaves in tumor tissues.Methods: Herein, we used The Cancer Genome Atlas (TCGA) and various computational tools to explore expression profiles, prognostic relevance, genetic mutations, immune cell infiltration, as well as the functional characteristics of WDR12 in multiple human cancers.Results: We found that WDR12 was inconsistently expressed in various cancers and that variations in WDR12 expression predicted survival consequences for cancer patients. Furthermore, we observed a significant correlation between WDR12 gene mutation levels and the prognosis of some tumors. Furthermore, significant correlations were found between WDR12 expression patterns and cancer-associated fibroblast (CAF) infiltration, myeloid-derived suppressor cells (MDSCs), tumor mutation burden, microsatellite instability and immunoregulators. Ultimately, pathway enrichment analysis revealed that WDR12-related pathways are involved in carcinogenesis.Conclusions: The findings of our study are stisfactory, demonstrating that WDR12 could serve as a promising reliable prognostic biomarker, as well as a therapeutic target for novel cancer therapeutic approaches.

BackgroundA deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (hBD-2) and cathelicidin LL-37] in the defense against SARS-CoV-2, it became important to identify the damaging missense mutations in the genes of these molecules and study their role in the pathogenesis of COVID-19.MethodsWe conducted a comprehensive analysis with multiple in silico approaches to identify the damaging missense SNPs for hBD-2 and LL-37; moreover, we applied docking methods and molecular dynamics analysis to study the impact of the filtered mutations.ResultsThe comprehensive analysis reveals the presence of three damaging SNPs in hBD-2; these SNPs were predicted to decrease the stability of hBD-2 with a damaging impact on hBD-2 structure as well. G51D and C53G mutations were located in highly conserved positions and were associated with differences in the secondary structures of hBD-2. Docking-coupled molecular dynamics simulation analysis revealed compromised binding affinity for hBD-2 SNPs towards the SARS-CoV-2 spike domain. Different protein–protein binding profiles for hBD-2 SNPs, in relation to their native form, were guided through residue-wise levels and differential adopted conformation/orientation.ConclusionsThe presented model paves the way for identifying patients prone to COVID-19 in a way that would guide the personalization of both the diagnostic and management protocols for this serious disease.

Our study was designed to highlight the efficacy of fish meal (FM) replacement with dried bovine hemoglobin (DBH) on the Oreochromis niloticus (O. niloticus) growth, health antioxidant activity, and antioxidant-related gene expression for 70 days. Fish (n = 225, average weight: 36.37 ± 0.05 g) were fed diets with different replacement percentage of FM with DBH: 0 % (DBH0), 2.5 % (DBH2.5), 5 % (DBH5), 7.5 % (DBH7.5) and 10 % (DBH10), where DBH0 was kept as control diet. At the end of the feeding trial, the fish were exposed to bacterial challenge with the pathogenic bacteria Aeromonas veronii (A. veronii). Compared to the DBH0 group, there was a notable increase in the growth parameters with a lower feed conversion ratio in all DBH groups, with DBH10 recording the highest growth. The DBH (0–5 %) diets did not alter the leukogram and erythrogram of O. niloticus, whist, the DBH (7.5–10 %) diets badly affected the leukogram and erythrogram of the fish. The DBH7.5 and DBH10 diets significantly increased (p

Background Obesity and diabetes are becoming increasingly prevalent around the world. Inflammation, oxidative stress, insulin resistance, and glucose intolerance are linked to both obesity and type 2 diabetes, and these disorders are becoming major public health issues globally. Methods This study evaluated the effects of obesity, diabetes, and hypoxia on the levels of pro- and anti-inflammatory cytokines in rats. We divided 120 Wistar rats in two groups, male and female, each including six subgroups: control (CTRL), obese (high-fat diet (HFD)), diabetic (streptozotocin (STZ)-treated), hypoxic (HYX), obese + diabetic (HFD/STZ), and obese + diabetic + hypoxic (HFD/STZ/HYX). We examined the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL10, and leptin in pancreatic tissues and serum. Results No significant difference was observed in serum levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) between HYX and CTRL in either sex. However, they were significantly increased, whereas high-density lipoprotein (HDL) was significantly decreased in HFD, STZ, HFD/STZ, and HFD/STZ/HPX compared with CTRL in both sexes. The expression of Tnf-α, Il6, and Lep was significantly upregulated in all subgroups compared with CTRL in both sexes. STZ and HYX showed no significant differences in the expression of these genes between sexes, whereas Tnf-α and Il6 were upregulated in male HFD, HFD/STZ, and HFD/STZ/HYX compared with females. Protein levels showed similar patterns. Combination subgroups, either in the absence or presence of hypoxia, frequently exhibited severe necrosis of endocrine components in pancreatic lobules. The combination of obesity, diabetes, and hypoxia was associated with inflammation, which was verified at the histopathological level.

This project was designed to explore the xanthine oxidase (XO) inhibitory mechanism of eight structurally diverse phenolic compounds [quercetin: C1, quercetin-3-rhamnoside: C2, 4, 5-O-dicaffeoylquinic acid: C3, 3, 5-O-dicaffeoylquinic acid: C4, 3, 4-O-di-caffeoylquinic acid: C5, 4-O-caffeoylquinic acid (C6), 3-O-caffeoylquinic acid: C7, and caffeic acid: C8]. For this purpose, in-vitro and different computational methods were applied to determine the xanthine oxidase (XO) inhibitory potential of eight structurally diverse phenolic compounds. The results revealed that phenolic compounds (C1–C8) possess strong to weak XO inhibitory activity. These results were further confirmed by atomic force microscopy (AFM) and 1H NMR analysis. Furthermore, computational study results revealed that phenolic compounds (C1–C8) bind with the surrounding amino acids of XO at the molybdenum (MO) site. These in-vitro and in-silico results divulge that phenolic compounds have a strong potential to lower uric acid levels via interacting with the XO enzyme and can be used to combat hyperuricemia.

Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy with a steadily increasing global incidence in recent decades. The pathogenesis of PTC is poorly understood, and the present diagnostic protocols are deficient. Thus, identifying novel prognostic biomarkers to improve our understanding of the mechanisms of pathogenesis, diagnosis, and designing therapeutic strategies for PTC is crucial. In this study, we integrated 27 PTC transcriptomic datasets and identified overlapping differentially expressed genes (DEGs) and differentially expressed microRNAs, collectively known as thyroid tumor-enriched proteins (TTEPs), and TTEmiRs, respectively. Our integrated bioinformatics analysis revealed that TTEPs were associated with tumor stages, poor surgical outcomes, distant metastasis, and worse prognoses in PTC cohorts. In addition, TTEPs were found to be associated with tumor immune infiltrating cells and immunosuppressive phenotypes of PTC. Enrichment analysis suggested the association of TTEPs with epithelial-to-mesenchymal transition (EMT), cell-matrix remodeling, and transcriptional dysregulation, while the TTEmiRs (miR-146b-5p and miR-21-5p) were associated with the modulation of the immune response, EMT, migration, cellular proliferation, and stemness. Molecular docking simulations were performed to evaluate binding affinities between TTEPs and antrocinnamomin, antcin, and antrocin, the bioactive compounds from one of the most reputable Taiwan indigenous medicinal plants (Antrodia camphorata). Our results revealed that antcin exhibited higher binding efficacies toward FN1, ETV5, and NRCAM, whereas antrocin demonstrated the least. Among the targets, fibronectin (FN1) demonstrated high ligandability potential for the compounds whereas NRCAM demonstrated the least. Collectively, our results hinted at the potential of antcin for targeting TTEPs. In conclusion, this comprehensive bioinformatics analysis strongly suggested that TTEPs and TTEmiRs could be used as potential diagnostic biomarker signatures and be exploited as potential targets for therapeutics development.

Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm2 /h and 0.310–3 cm2 /h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery.

The NRAS gene is a well-known oncogene that acts as a major player in carcinogenesis. Mutations in the NRAS gene have been linked to multiple types of human tumors. Therefore, the identification of the most deleterious single nucleotide polymorphisms (SNPs) in the NRAS gene is necessary to understand the key factors of tumor pathogenesis and therapy. We aimed to retrieve NRAS missense SNPs and analyze them comprehensively using sequence and structure approaches to determine the most deleterious SNPs that could increase the risk of carcinogenesis. We also adopted structural biology methods and docking tools to investigate the behavior of the filtered SNPs. After retrieving missense SNPs and analyzing them using six in silico tools, 17 mutations were found to be the most deleterious mutations in NRAS. All SNPs except S145L were found to decrease NRAS stability, and all SNPs were found on highly conserved residues and important functional domains, except R164C. In addition, all mutations except G60E and S145L showed a higher binding affinity to GTP, implicating an increase in malignancy tendency. As a consequence, all other 14 mutations were expected to increase the risk of carcinogenesis, with 5 mutations (G13R, G13C, G13V, P34R, and V152F) expected to have the highest risk. Thermodynamic stability was ensured for these SNP models through molecular dynamics simulation based on trajectory analysis. Free binding affinity toward the natural substrate, GTP, was higher for these models as compared to the native NRAS protein. The Gly13 SNP proteins depict a differential conformational state that could favor nucleotide exchange and catalytic potentiality. A further application of experimental methods with all these 14 mutations could reveal new insights into the pathogenesis and management of different types of tumors.

The current research sought to assess the effects of paulownia leaves extract (PLE) on performance, blood hematological, antioxidant activity, and immunological response of broiler chicken. In total, two hundred 1-day-old male Cobb500 chicks were allocated randomly into four equal treatments with 5 replicates. The first treatment served as a control (CNT) and was fed the basal diet only, while the other treated treatments were fed on the basal diet supplemented with 0.1, 0.3, and 0.5 g/kg diet of PLE, respectively. The performance results showed significant increments (P < 0.05) in live body weight (LBW), weight gain (WG), and European production efficiency factors (EPEIs) (linearly; p < 0.001) in cooperated with increasing PLE levels in broiler diets. At the same time, feed conversion ratio (FCR) and livability percentages were numerically enhanced under the effects of PLE supplementation. Moreover, a notable increase (P < 0.05 or 0.01) in oxidative remarks activity (GSH, glutathione; SOD, super oxide-dismutase and CAT, catalase) and elevated levels of immunoglobulin (IgM, immunoglobulin M and IgG, immunoglobulin G) were noted (P < 0.05) for treatments fed with PLE in a dose-dependent manner. Also, a dramatic linear increase was observed in mRNA expression of IGF-1, GHR, IL-1β, and IL-10 genes of broiler chickens. This study concluded that enriched broiler feeds with 0.5 g/kg PLE might be a beneficial strategy to promote broiler health and production.

Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, β-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.

Adaptive immunity, orchestrated by B-cells and T-cells, plays a crucial role in protecting the body from pathogenic invaders and can be used as tools to enhance the body’s defense mechanisms against cancer by genetically engineering these immune cells. Several strategies have been identified for cancer treatment and evaluated for their efficacy against other diseases such as autoimmune and infectious diseases. One of the most advanced technologies is chimeric antigen receptor (CAR) T-cell therapy, a pioneering therapy in the oncology field. Successful clinical trials have resulted in the approval of six CAR-T cell products by the Food and Drug Administration for the treatment of hematological malignancies. However, there have been various obstacles that limit the use of CAR T-cell therapy as the first line of defense mechanism against cancer. Various innovative CAR-T cell therapeutic designs have been evaluated in preclinical and clinical trial settings and have demonstrated much potential for development. Such trials testing the suitability of CARs against solid tumors and HIV are showing promising results. In addition, new solutions have been proposed to overcome the limitations of this therapy. This review provides an overview of the current knowledge regarding this novel technology, including CAR T-cell structure, different applications, limitations, and proposed solutions.

This study was aimed to determine the potentialities of Pimpinella stewartii leaves extracts fractions towards the inhibition of acetylcholinesterase (AChE) activity as well as reduction of iron-induced lipid peroxidation in male Wistar rats (age – 50 days; weight – 280–300 g). Initially, animals were divided into 17 groups with 7 rats in each group. Gallic acid and quercetin were used as standards. The AChE activities of aqueous and ethanolic extract fractions of P. stewartii leaves were determined using standard protocol. Results showed that ethyl acetate extract fractions significantly (P = 0.01) inhibited the enzyme in a concentration dependent manner when compared to the aqueous extract fractions and the control group. Gallic acid and quercetin depicted higher inhibition of AChE activities than ethyl acetate extract fractions. Additionally, the IC50 values for aqueous extract fractions, ethyl acetate extract fractions, gallic acid, and quercetin were estimated as 72.6 ± 2.72, 30.41 ± 0.56, 8.4 ± 0.22, and 6.82 ± 0.2 µg/mL, respectively. Furthermore, the lipid peroxidation activities of extracts fractions were assessed by estimating thiobarbituric acid reactive substances (TBARS) production. Both the extracts fractions showed significant protection against lipid peroxidation but the ethyl acetate extract fractions exhibited comparatively higher reductions in TBARS levels (P = 0.001). However, gallic acid and quercetin revealed higher reductions of pro-oxidants than the extracts fractions. In conclusion, findings of this study demonstrated pronounced AChE inhibitory activity and reduced lipid peroxidation trait of ethyl acetate extract fractions of P. stewartii leaves, and thus, suggested its paramount role as therapeutics against Alzheimer disease.

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared by the World Health Organization (WHO) as a global pandemic on March 11, 2020. SARS-CoV-2 targets the respiratory system, resulting in symptoms such as fever, headache, dry cough, dyspnea, and dizziness. These symptoms vary from person to person, ranging from mild to hypoxia with acute respiratory distress syndrome (ARDS) and sometimes death. Although not confirmed, phylogenetic analysis suggests that SARS-CoV-2 may have originated from bats; the intermediary facilitating its transfer from bats to humans is unknown. Owing to the rapid spread of infection and high number of deaths caused by SARS-CoV-2, most countries have enacted strict curfews and the practice of social distancing while awaiting the availability of effective U.S. Food and Drug Administration (FDA)-approved medications and/or vaccines. This review offers an overview of the various types of coronaviruses (CoVs), their targeted hosts and cellular receptors, a timeline of their emergence, and the roles of key elements of the immune system in fighting pathogen attacks, while focusing on SARS-CoV-2 and its genomic structure and pathogenesis. Furthermore, we review drugs targeting COVID-19 that are under investigation and in clinical trials, in addition to progress using mesenchymal stem cells to treat COVID-19. We conclude by reviewing the latest updates on COVID-19 vaccine development. Understanding the molecular mechanisms of how SARS-CoV-2 interacts with host cells and stimulates the immune response is extremely important, especially as scientists look for new strategies to guide their development of specific COVID-19 therapies and vaccines.

Escherichia coli (E. coli) is a Gram-negative bacterium that belongs to the family Enterobacteriaceae. While E. coli can stay as an innocuous resident in the digestive tract, it can cause a group of symptoms ranging from diarrhea to live threatening complications. Due to the increased rate of antibiotic resistance worldwide, the development of an effective vaccine against E. coli pathotypes is a major health priority. In this study, a reverse vaccinology approach along with immunoinformatics has been applied for the detection of potential antigens to develop an effective vaccine. Based on our screening of 5,155 proteins, we identified lipopolysaccharide assembly protein (LptD) and outer membrane protein assembly factor (BamA) as vaccine candidates for the current study. The conservancy of these proteins in the main E. coli pathotypes was assessed through BLASTp to make sure that the designed vaccine will be protective against major E. coli pathotypes. The multitope vaccine was constructed using cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell lymphocyte (BCL) epitopes with suitable linkers and adjuvant. Following that, it was analyzed computationally where it was found to be antigenic, soluble, stable, and non-allergen. Additionally, the adopted docking study, as well as all-atom molecular dynamics simulation, illustrated the promising predicted affinity and free binding energy of this constructed vaccine against the human Toll-like receptor-4 (hTLR-4) dimeric state. In this regard, wet lab studies are required to prove the efficacy of the potential vaccine construct that demonstrated promising results through computational validation.

The complete hydrolysis of xylan can be facilitated by the coordinated action of xylanase and other de-branching enzymes. Here, a GH43 α-l-arabinofuranosidase/β-xylosidase (CAX43) from Caldicellulosiruptor saccharolyticus was cloned, sequenced, and biochemically investigated. The interaction of the enzyme with various substrates was also studied. With a half-life of 120 h at 70°C, the produced protein performed maximum activity at pH 6.0 and 70°C. The enzyme demonstrated a higher activity (271.062 ± 4.83 U/mg) against para nitrophenol (pNP) α-L-arabinofuranosides. With xylanase (XynA), the enzyme had a higher degree of synergy (2.30) in a molar ratio of 10:10 (nM). The interaction of the enzyme with three substrates, pNP α-L-arabinofuranosides, pNP β-D-xylopyranosides, and sugar beet arabinan, was investigated using protein modeling, molecular docking, and molecular dynamics (MD) simulation. During the simulation time, the root mean square deviation (RMSD) of the enzyme was below 2.5 Å, demonstrating structural stability. Six, five, and seven binding-interacting residues were confirmed against pNP α-L-arabinofuranosides, pNP β-D-xylopyranosides, and arabinan, respectively, in molecular docking experiments. This biochemical and in silico study gives a new window for understanding the GH43 family’s structural stability and substrate recognition, potentially leading to biological insights and rational enzyme engineering for a new generation of enzymes that perform better and have greater biorefinery utilization.

Cannabis abuse is a common public health issue and may lead to considerable adverse effects. Along with other effects, the dependence on cannabis consumption is a serious problem which has significant consequences on biochemical and clinical symptoms. This study intends to evaluate the harmful effects of the use of cannabis on thyroid hormonal levels, cardiovascular indicators, and psychotic symptoms in the included patients. This prospective multicenter study was conducted on cannabis-dependent patients with psychotic symptoms (n = 40) vs. healthy control subjects (n = 40). All participants were evaluated for psychiatric, biochemical, and cardiovascular physiological effects. Patients were selected through Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and urine samples, exclusively for the evaluation of cannabis presence. Serum thyroid stimulating hormone (TSH), T3, and T4 levels were measured using the immunoassay technique. Patients were assessed for severity of depressive, schizophrenic, and manic symptoms using international ranking scales. Various quantifiable factors were also measured for the development of tolerance by cannabis. Among the patients of cannabis abuse, 47.5% were found with schizophrenia, 20% with schizoaffective symptoms, 10% with manic symptoms, and 22.5% with both manic and psychotic symptoms. In the group–group and within-group statistical analysis, the results of thyroid hormones and cardiovascular parameters were non-significant. The psychiatric assessment has shown highly significant (p < 0.001) difference of positive, negative, general psychopathology, and total scores [through Positive and Negative Syndrome Scale (PANSS) rating scales] in patients vs. the healthy control subjects. The study revealed that cannabis abuse did not significantly alter thyroid hormones and cardiovascular parameters due to the development of tolerance. However, the cannabis abuse might have a significant contributing role in the positive, negative, and manic symptoms in different psychiatric disorders.

Plant-derived bioactive compounds with promising nutritional and therapeutic attributes (phytogenics) are among the top priorities in the aquaculture sector. Therefore, the impact of thymol (Thy) and/or thymoquinone (ThQ) on the growth, immune response antioxidant capacity, and Aeromonas sobria (A. sobria) resistance of Nile tilapia was investigated. Four fish groups were fed a control diet and three basal diets supplemented with 200 mg/kg diet of Thy or ThQ and a blend of both Thy and ThQ at a level of 200 mg/kg diet each. At the end of the feeding trial (12 weeks), the tilapias were challenged intraperitoneally with virulent A. sobria (2.5 × 108 CFU/mL) harboring aerolysin (aero) and hemolysin (hly) genes. The results revealed that tilapias fed diets fortified with a combination of Thy and ThQ displayed significantly enhanced growth rate and feed conversion ratio. Notably, the expression of the genes encoding digestive enzymes (pepsinogen, chymotrypsinogen, α-amylase and lipase) and muscle and intestinal antioxidant enzymes (glutathione peroxidase, catalase and superoxide dismutase) was significantly upregulated in Thy/ThQ-fed fish. An excessive inflammatory response was subsided more prominently in the group administrated Thy/ThQ as supported by the downregulation of il-β, il-6 and il-8 genes and in contrast, the upregulation of the anti-inflammatory il-10 gene. Remarkably, dietary inclusion of Thy/ThQ augmented the expression of autophagy-related genes, whilst it downregulated that of mtor gene improving the autophagy process. Furthermore, Thy/ThQ protective effect against A. sobria was evidenced via downregulating the expression of its aero and hly virulence genes with higher fish survival rates. Overall, the current study encouraged the inclusion of Thy/ThQ in fish diets to boost their growth rates, promote digestive and antioxidant genes expression, improve their immune responses and provide defense against A. sorbia infections with great economic benefits.

This study aimed to investigate the impact of dietary addition of lavender essential oil (Lavandula angustifolia L.) (LEO) on the growth performance, tissue histoarchitecture, and fatty acid profile in breast muscles, as well as blood biochemistry and immune expression of pro-inflammatory cytokines of broiler chickens. A total of 200 three-day-old broiler chickens (average body weight 101.3 ± 0.24 g) were assigned to a completely randomized design consisting of four dietary treatments (n = 50 per treatment, each replicate consisting of 10 birds) that included lavender essential oil at concentrations of 0 (control group), 200, 400, and 600 mg Kg−1 diet. The experiment lasted for 35 days. The results revealed that supplementation of lavender essential oil at 200, 400, or 600 mg/kg in broiler diets had no effect (p > 0.05) on the growth performance throughout the experimental periods (3–10, 11–23, and 24–35 days of age). According to the broken line regression model, the optimal level for dietary LEO addition was the 460 mg kg−1 diet based on the total body weight gain and feed conversion ratio results. The diets supplemented with lavender essential oil had no effect (p > 0.05) on the percentages of carcass yield or internal organs. Dietary addition of LEO significantly increased the percentages of omega-3 polyunsaturated fatty acids PUFA (n-3), omega-6 polyunsaturated fatty acids (n-6), and the n-3/n-6 ratio (p < 0.05) in the breast muscles of chickens in a level-dependent manner. The blood concentration of alanine aminotransferase was significantly increased in lavender essential oil at 600 mg kg−1 compared with other treatments. The dietary addition of LEO at 200, 400, and 600 mg kg−1 significantly reduced the malondialdehyde level. Still, they significantly increased the serum enzyme activities of total antioxidant capacity, catalase, superoxide dismutase, and the pro-inflammatory cytokine (interleukine-1 beta and interferon γ) compared with the unsupplemented group. The LEO-supplemented groups showed normal liver histomorphology as in the control group. However, the immunoexpression of the pro-inflammatory cytokine transforming growth factor β was significantly increased by increasing the level of LEO. It can be concluded that lavender essential oil can be included in broiler chicken diets up to 460 mg kg −1 with no positive effect on the bird’s growth. It can improve the antioxidant capacity and enrich the breast muscles with PUFA. An increased level of supplementation (600 mg kg−1) increased the inflammatory responses in broiler chickens.

Wendlandia tinctoria var. grandis (Roxb.) DC. (Family: Rubiaceae) is a semi-evergreen shrub distributed over tropical and subtropical Asia. The present research intended to explore the pharmacological potential of the stem extract of W. tinctoria, focusing on the antioxidant, hypoglycemic, and antidiarrheal properties, and to isolate various secondary metabolites as mediators of such activities. A total of eight phenolic compounds were isolated from the dichloromethane soluble fraction of the stem extract of this plant, which were characterized by electrospray ionization (ESI) mass spectrometric and 1H NMR spectroscopic data as liquiritigenin (1), naringenin (2), apigenin (3), kaempferol (4), glabridin (5), ferulic acid (6), 4-hydroxybenzoic acid (7), and 4-hydroxybenzaldehyde (8). The dichloromethane soluble fraction exhibited the highest phenolic content (289.87 ± 0.47 mg of GAE/g of dried extract) and the highest scavenging activity (IC50 = 18.83 ± 0.07 µg/mL) against the DPPH free radical. All of the isolated compounds, except 4-hydroxybenzaldehyde, exerted a higher antioxidant effect (IC50 = 6.20 ± 0.10 to 16.11 ± 0.02 μg/mL) than the standard butylated hydroxytoluene (BHT) (IC50 = 17.09 ± 0.01 μg/mL). Significant hypoglycemic and antidiarrheal activities of the methanolic crude extract at both doses (200 mg/kg bw and 400 mg/kg bw) were observed in a time-dependent manner. Furthermore, the computational modeling study supported the current in vitro and in vivo findings, and the isolated constituents had a higher or comparable binding affinity for glutathione reductase and urase oxidase enzymes, glucose transporter 3 (GLUT 3), and kappa-opioid receptor, inferring potential antioxidant, hypoglycemic, and antidiarrheal properties, respectively. This is the first report of all of these phenolic compounds being isolated from this plant species and even the first demonstration of the plant stem extract’s antioxidant, hypoglycemic, and antidiarrheal potentials. According to the current findings, the W. tinctoria stem could be a potential natural remedy for treating oxidative stress, hyperglycemia, and diarrhea. Nevertheless, further extensive investigation is crucial for thorough phytochemical screening and determining the precise mechanisms of action of the plant-derived bioactive metabolites against broad-spectrum molecular targets.

Z-configurated isomers are kinetically preferred molecules. Compounds with Z-configuration are contained in many natural products, biologically active compounds and as synthons for organic synthesis. Two series of new thiazole-based analogs were synthesized from appropriate starting materials hydrazinecarbothioamide derivatives (Z)-2a,b to be evaluated for their inhibitory activity towards VEGFR-2. The prepared thiazole compounds 3a-5b were screened for their cytotoxic potency against the MDA-MB-231 breast cancer cell line and their percentage inhibition against VEGFR-2. Compound 4d exhibited good VEGFR-2 inhibitory activity. A DNA flow cytometry analysis was conducted, and compound 4d demonstrated cell cycle arrest at the G1 and G2/M phases of the cell cycle profile and an apoptosis-inducing effect by increasing the percentage of pre-G1 phase. Compound 4d was further evaluated for its apoptosis-inducing effect by studying the effect on mitochondrial membrane potential (MMP) and p53 activation. It was found to boost the level of p53 and reduce the level of MMP compared with the untreated control cells.

Circulating cell-free mitochondrial DNA (cf-mtDNA) has been found in the plasma of severely ill COVID-19 patients and is now known as a strong predictor of mortality. However, the underlying mechanism of mtDNA release is unexplored. Here, we show a novel mechanism of SARS-CoV-2-mediated pro-inflammatory/pro-apoptotic mtDNA release and a rational therapeutic stem cell-based approach to mitigate these effects. We systematically screened the effects of 29 SARS-CoV-2 proteins on mitochondrial damage and cell death and found that NSP4 and ORF9b caused extensive mitochondrial structural changes, outer membrane macropore formation, and the release of inner membrane vesicles loaded with mtDNA. The macropore-forming ability of NSP4 was mediated through its interaction with BCL2 antagonist/killer (BAK), whereas ORF9b was found to inhibit the anti-apoptotic member of the BCL2 family protein myeloid cell leukemia-1 (MCL1) and induce inner membrane vesicle formation containing mtDNA. Knockdown of BAK and/or overexpression of MCL1 significantly reversed SARS-CoV-2-mediated mitochondrial damage. Therapeutically, we engineered human mesenchymal stem cells (MSCs) with a simultaneous knockdown of BAK and overexpression of MCL1 (MSCshBAK+MCL1) and named these cells IMAT-MSCs (intercellular mitochondrial transfer-assisted therapeutic MSCs). Upon co-culture with SARS-CoV-2-infected or NSP4/ORF9b-transduced airway epithelial cells, IMAT-MSCs displayed functional intercellular mitochondrial transfer (IMT) via tunneling nanotubes (TNTs). The mitochondrial donation by IMAT-MSCs attenuated the pro-inflammatory and pro-apoptotic mtDNA release from co-cultured epithelial cells. Our findings thus provide a new mechanistic basis for SARS-CoV-2-induced cell death and a novel therapeutic approach to engineering MSCs for the treatment of COVID-19.

Cisplatin (CP) is a powerful chemotherapeutic agent; however, its therapeutic use is restricted due to its nephrotoxicity. In this work, we profiled the phytoconstituents of Jasminum grandiflorum flower extract (JGF) using LC-MS/MS and explored the possible molecular mechanisms against acute renal failure through pharmacological network analysis. Furthermore, the possible molecular mechanisms of JGF against acute renal failure were verified in an in vivo nephrotoxicity model caused by cisplatin. LC-MS analysis furnished 26 secondary metabolites. Altogether, there were 112 total hit targets for the identified metabolites, among which 55 were potential consensus targets related to nephrotoxicity based on the network pharmacology approach. Upon narrowing the scope to acute renal failure, using the DisGeNET database, only 30 potential targets were determined. The computational pathway analysis illustrated that JGF might inhibit renal failure through PI3K-Akt, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance. This study was confirmed by in vivo experiment in which kidneys were collected for histopathology and gene expression of mitogen-activated protein kinase 4 (MKK4), MKK7, I-CAM 1, IL-6, and TNF receptor-associated factor 2 (TRAF2). The animal-administered cisplatin exhibited a substantial rise in the expression levels of the MMK4, MKK7, I CAM 1, and TRFA2 genes compared to the control group. To summarize, J. grandiflorum could be a potential source for new reno-protective agents. Further experiments are needed to confirm the obtained activities and determine the therapeutic dose and time.

Biofumigant and crop sequencing are effective and safe control system activators that maintain soil fertility and reduce pest populations. The study goals were to find new pesticide-free therapies for root-knot nematode management on cucumbers to maintain high yields and protect the environment and human health. In 2018 and 2019, the research employed a fully randomized block design under field conditions with five treatments and control: two bio- fumigants, cultivation of cucumber after broccoli plantlets incorporation (BPI) and radish plantlets incorporation (RPI), two crop sequence treatments (cultivation after broccoli (BCS) and radish (RCS), and nematicide treatment). Cucumber cultivation after BPI treatment exhibited the best horticultural traits, which reflected positively on early and total productivity. The increased yield was gained by suppressing all nematode parameters, the number of nematode larvae, galls, and egg masses, as well as egg hatching reduction. The most effective biocides, total phenols, myrosinase activity, total glucosinolates (GSLs), and isothiocyanates (ITCs) in brassica crops were estimated for their pesticide properties. The highest amount was released with BPI treatment, compared to adult plants and radish in its two stages. The bio-managed treatments revealed superior effectiveness compared to nematicide application and control to suppress the nematode population while enhancing cucumber growth and production.

Human Group IIA secreted phospholipase A2 (sPLA2-IIA) enzyme plays a crucial role in several chronic inflammatory diseases such asasthma, atherosclerosis, gout, bronchitis, etc. Several studies showed that the antioxidants exert an anti-inflammatory function by inhibiting the sPLA2-IIA enzyme. Hence, the present study evaluated an antioxidant molecule, sinapic acid, for sPLA2-IIA inhibition as an anti-inflammatory function. Initially, the antioxidant efficacy of sinapic acid was evaluated, and it showed greater antioxidant potency. Further, sinapic acid inhibited 94.4 ± 4.83% of sPLA2-IIA activity with an IC50 value of 4.16 ± 0.13 µM. The mode of sPLA2-IIA inhibition was examined by increasing the substrate concentration from 30 to 120nM and the calcium concentration from 2.5 to 15 mM, which did not change the level of inhibition. Further, sinapic acid altered the intrinsic fluorescence and distorted the far UltraViolet Circular Dichroism (UV-CD) spectra of the sPLA2-IIA, indicating the direct enzyme-inhibitor interaction. Sinapic acid reduced the sPLA2-IIA mediated hemolytic activity from 94 ± 2.19% to 12.35 ± 2.57% and mouse paw edema from 171.75 ± 2.2% to 114.8 ± 1.98%, demonstrating the anti-inflammatory efficiency of sinapic acid by in situ and in vivo methods, respectively. Finally, sinapic acid reduced the hemorrhagic effect of Vipera russelli venom hemorrhagic complex-I (VR-HC-I) as an anti-hemorrhagic function. Thus, the above experimental results revealed the sinapic acid potency to be an antioxidant, anti-inflammatory and anti-hemorrhagic molecule, and therefore, it appears to be a promising therapeutic agent.

A novel series of amides based TMP moiety was designed, synthesized and evaluated for their antiproliferative as well as enzyme inhibition activity. Compounds 6a and 6b showed remarkable cytotoxic activity against HepG2 cells with IC50 values 0.65 and 0.92 μM, respectively compared with SAHA and CA-4 as reference compounds. In addition, compound 6a demonstrated good HDAC-tubulin dual inhibition activity as it showed better HDAC activity as well as anti-tubulin activity. Moreover, compound 6a exhibited G2/M phase arrest and pre-G1 apoptosis as demonstrated by cell cycle analysis and Annexin V assays. Further apoptosis studies demonstrated that compound 6a boosted the level of caspase 3/7. Caspase 3/7 activation and apoptosis induction were evidenced by decrease in mitochondrial permeability suggesting that activation of caspase 3/7 may occur via mitochondrial apoptotic pathway.

The α-D-glucopyranoside and its derivatives were as the cardinal investigation for developing an effective medication to treat the highest deadly white spot syndrome virus (WSSV) diseases in Shrimp. In our forthcoming work, both computational tools, such as molecular docking, quantum calculations, pharmaceutical kinetics, ADMET, and their molecular dynamics, as well as the experimental trial against WSSV, were executed to develop novel inhibitors. In the beginning, molecular docking was carried out to determine inhibitors of the four targeted proteins of WSSV (PDB ID: 2ED6, 2GJ2, 2GJI, and 2EDM), and to determine the binding energies and interactions of ligands and proteins after docking. The range of binding affinity was found to be between −5.40 and −7.00 kcal/mol for the protein 2DEM, from −5.10 to 6.90 kcal/mol for the protein 2GJ2, from −4.70 to −6.2 kcal/mol against 2GJI, and from −5.5 kcal/mol to −6.6 kcal/mol for the evolved protein 2ED6 whereas the L01 and L03 display the highest binding energy in the protein 2EDM. After that, the top-ranked compounds (L01, L02, L03, L04, and L05), based on their high binding energies, were tested for molecular dynamics (MD) simulations of 100 ns to verify the docking validation and stability of the docked complex by calculating the root mean square deviation (RMSD) and root mean square fluctuation (RMSF). The molecules with the highest binding energy were then picked and compared to the standard drugs that were been applied to fish experimentally to evaluate the treatment at various doses. Consequently, approximately 40–45% cure rate was obtained by applying the dose of oxytetracycline (OTC) 50% with vitamin C with the 10.0 g/kg feed for 10 days. These drugs (L09 to L12) have also been executed for molecular docking to compare with α-D-glucopyranoside and its derivatives (L01 to L08). Next, the evaluation of pharmacokinetic parameters, such as drug-likeness and Lipinski’s principles; absorption; distribution; metabolism; excretion; and toxicity (ADMET) factors, were employed gradually to further evaluate their suitability as inhibitors. It was discovered that all ligands (L01 to L12) were devoid of hepatotoxicity, and the AMES toxicity excluded L05. Additionally, all of the compounds convey a significant aqueous solubility and cannot permeate the blood-brain barrier. Moreover, quantum calculations based on density functional theory (DFT) provide the most solid evidence and testimony regarding their chemical stability, chemical reactivity, biological relevance, reactive nature and specific part of reactivity. The computational and virtual screenings for in silico study reveals that these chosen compounds (L01 to L08) have conducted the inhibitory effect to convey as a possible medication against the WSSV than existing drugs (L09, L10, L11 and L12) in the market. Next the drugs (L09, L10, L11 and L12) have been used in trials.

The aim of the study was to conduct phytochemical and pharmacological investigations of Wrightia coccinea (Roxb. ex Hornem.) Sims via several in vitro, in vivo, and in silico models. A total of four compounds were identified and isolated from the methanol extract of the bark and the methanol extract of the seed pulp of W. coccinea through successive chromatographic techniques and were characterized as 3β-acetyloxy-olean-12-en-28-ol (1), wrightiadione (2), 22β-hydroxylupeol (3), and β-sitosterol (4) by spectroscopic analysis. The aqueous fraction of the bark and chloroform fraction of the fruits provided the most potent antioxidant capacity (IC50 = 7.22 and 4.5 µg/mL, respectively) in DPPH free radical scavenging assay compared with the standard ascorbic acid (IC50 = 17.45 µg/mL). The methanol bark extract and the methanol fruit coat extract exerted anti-diarrheal activity by inhibiting 74.55 ± 0.67% and 77.78 ± 1.5% (mean ± SEM) of the diarrheal episode in mice, respectively, after four hours of loading the samples. In the hypoglycemic test, the methanol bark extract and the methanol fruit coat extract (400 mg/kg) produced a significant (p < 0.05) reduction in the blood glucose level in mice. Both doses of the plant extracts (200 mg/kg and 400 mg/kg) used in the study induced a significant (p < 0.05) increase in pain reaction time. The in vitro and in vivo findings were supported by the computational studies. The isolated compounds exhibited higher binding affinity compared with the standard drugs towards the active binding sites of glutathione reductase, epidermal growth factor receptor (EGFR), kappa opioid receptor, glucose transporter 3 (GLUT 3), Mu opioid receptor, and cyclooxygenase 2 (COX-2) proteins due to their potent antioxidant, cytotoxic, anti-diarrheal, hypoglycemic, and central and peripheral analgesic properties, respectively. The current findings concluded that W. coccinea might be a potential natural source for managing oxidative stress, diarrhea, hyperglycemia, and pain. Further studies are warranted for extensively phytochemical screening and establishing exact mechanisms of action.

The objective of this study was to evaluate the Glycyrrhiza glabra effect on growth performance, blood parameters, antioxidant and lysosomal activity, histology and immunohistochemistry of liver and intestine, and the gene expression profile of broiler chickens. A total of 180 Cobb500 broiler chicks (one-week-old) were used in this study. Chicks were distributed randomly into three treatment groups; the first group received drinking water without any supplementation (control group). In contrast, birds in groups 2 and 3 received licorice supplementation in drinking water with 0.4 and 0.8 g licorice/liter, respectively. Results revealed that licorice at a 0.4 g/L of water level improved body weight, weight gain, feed intake, and FCR. Licorice also exhibits a broad range of biological activities such as hypolipidemic, hypoglycemic, hepatoprotective, immunostimulant, and antioxidant effects. The morphometric analysis of different parameters of the intestine revealed a significant increase in the intestinal villi length, width, and villi length/crypt depth in the group supplemented with licorice 0.4 gm/L compared to other groups. The number of CD3 positive in both duodenum and ileum was increased in the licorice 0.4 gm/L group compared to other groups. The expression of growth-related genes was significantly increased with licorice supplementation and modulation of the lipid metabolism genes in the liver and upregulated to the mRNA expression of both superoxide dismutase (SOD1) and Catalase (CAT). Our results revealed that licorice supplementation increased the growth performance of broiler chickens and impacted the birds’ antioxidant activity through modulation of the growth-related genes, lipid metabolic markers, and antioxidant-related pathways.

The histologic properties of tumors seem to affect their biological behavior, and the same holds good for solid multicystic ameloblastoma (SMA), a benign, locally destructive lesion. Hyalinization is one such histological factor that has been demonstrated to correlate with the biological behavior of neoplasms. The present study aimed to analyze the correlation between the severity of hyalinization (SOH) and the recurrence potential of SMAs. The study was performed on formalin-fixed, paraffin-embedded (FFPE) diagnosed archival cases of SMA, follicular SMA (n = 35) and plexiform SMA (n = 25). The cases were evaluated for SOH and scored from 0–3, and the correlation between SOH and recurrence was analyzed for statistical significance. The clinical parameters of the lesion were analyzed for statistical correlation with recurrence. The SOH significantly correlated with the recurrence of SMA (p = 0.001). The histologic type did not influence the biological behavior of SMA. The location of SMA in the body of the mandible (p = 0.036), multilocular radiolucency (p = 0.001) and root resorption (p = 0.002) also showed strong statistical correlation with recurrence. It is evident from the present study that hyalinization strongly correlates with the biological behavior of SMA. Future studies with advanced investigations could validate the presence of hyalinization and identify the origin of the hyalinized product in SMAs.

Background: Machine learning (ML) is a key component of artificial intelligence (AI). The terms machine learning, artificial intelligence, and deep learning are erroneously used interchangeably as they appear as monolithic nebulous entities. This technology offers immense possibilities and opportunities to advance diagnostics in the field of medicine and dentistry. This necessitates a deep understanding of AI and its essential components, such as machine learning (ML), artificial neural networks (ANN), and deep learning (DP). Aim: This review aims to enlighten clinicians regarding AI and its applications in the diagnosis of oral diseases, along with the prospects and challenges involved. Review results: AI has been used in the diagnosis of various oral diseases, such as dental caries, maxillary sinus diseases, periodontal diseases, salivary gland diseases, TMJ disorders, and oral cancer through clinical data and diagnostic images. Larger data sets would enable AI to predict the occurrence of precancerous conditions. They can aid in population-wide surveillance and decide on referrals to specialists. AI can efficiently detect microfeatures beyond the human eye and augment its predictive power in critical diagnosis. Conclusion: Although studies have recognized the benefit of AI, the use of artificial intelligence and machine learning has not been integrated into routine dentistry. AI is still in the research phase. The coming decade will see immense changes in diagnosis and healthcare built on the back of this research. Clinical significance: This paper reviews the various applications of AI in dentistry and illuminates the shortcomings faced while dealing with AI research and suggests ways to tackle them. Overcoming these pitfalls will aid in integrating AI seamlessly into dentistry.

Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non-invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR-34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2–negative (p < 0.001), estrogen receptor–positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.

Background Growing evidence indicates that proanthocyanidins (PACs) may be effective in treating and preventing various cancers. The fundamental mechanism of PACs inhibiting the proliferation at cellular and molecular levels in most of the cancer types remains unclear. Objective The anticancer efficacy of PACs was investigated in vitro using three human cancer cell lines: human colorectal adenocarcinoma (HT-29), human breast carcinoma (MCF-7), and human prostatic adenocarcinoma (PC-3). Methods Cytotoxicity was evaluated by MTT assay, while cell proliferation was measured by trypan blue exclusion method. Cell migration was measured by wound healing assay, and DAPI staining was used to evaluate apoptotic nucleus morphology. RT-PCR was used to analyze the expression of Bax and Bcl-2, and caspase enzyme activity assay was measured by caspase colorimetric assay. Results PACs could inhibit both cellular viability and proliferation in a concentration- and time-dependent fashion in all investigated cells. Further, all tested cells showed similarly decreased migration after 24- and 48-h PAC treatment. We observed increased apoptotic nucleus morphology in treated cells (p ≤ 0.01). BAX expression significantly increased in HT-29 (p

Background Little is known regarding the toxic and therapeutic doses of amygdalin. Treatment regimens and schedules can vary between humans and animal models, and there have been reports of cyanide toxicity due to amygdalin use. Objective The aim of this study was to evaluate the effect of different doses of amygdalin on antioxidant gene expression and suppression of oxidative damage in mice. Methods Forty adult male mice were divided randomly into four groups (n = 10) as follows and treated orally for two weeks: a control group treated with saline solution, a group treated with amygdalin at 200 mg/kg body weight, a group treated with amygdalin at 100 mg/kg body weight, and a group treated with amygdalin at 50 mg/kg body weight. Liver and testis samples were collected for gene expression, biochemical and histopathological analyses. Results The mice treated with medium-dose amygdalin (100 mg/kg) showed upregulated mRNA expression of glutathione peroxidase (P < 0.01) and superoxide dismutase (P < 0.05) and significantly decreased lipid peroxidation (P < 0.05) in hepatic and testicular tissues compared to those in the untreated groups (controls), with mild histopathological effects. The mice treated with high-dose of amygdalin (200 mg/kg) showed downregulated mRNA expression of glutathione peroxidase and superoxide dismutase (P < 0.01) and significantly increased lipid peroxidation (P < 0.05) in both hepatic and testicular tissues compared to those in the untreated groups (controls), with an apparent effect at the histopathological level. No effects were observed in the mice treated with low-dose amygdalin (50 mg/kg) at the gene, protein and histopathological level. Conclusion Low-and medium-dose amygdalin did not induce toxicity in the hepatic and testicular tissues of male mice, unlike high-dose amygdalin, which had a negative effect on oxidative balance in mice. Therefore, amygdalin at a moderate dose may improve oxidative balance in mice.

Deep learning models have been successfully applied in a wide range of fields. The creation of a deep learning framework for analyzing high-performance sequence data have piqued the research community’s interest. N4 acetylcytidine (ac4C) is a post-transcriptional modification in mRNA, is an mRNA component that plays an important role in mRNA stability control and translation. The ac4C method of mRNA changes is still not simple, time consuming, or cost effective for conventional laboratory experiments. As a result, we developed DL-ac4C, a CNN-based deep learning model for ac4C recognition. In the alternative scenario, the model families are well-suited to working in large datasets with a large number of available samples, especially in biological domains. In this study, the DL-ac4C method (deep learning) is compared to non-deep learning (machine learning) methods, regression, and support vector machine. The results show that DL-ac4C is more advanced than previously used approaches. The proposed model improves the accuracy recall area by 9.6 percent and 9.8 percent, respectively, for cross-validation and independent tests. More nuanced methods of incorporating prior bio-logical knowledge into the estimation procedure of deep learning models are required to achieve better results in terms of predictive efficiency and cost-effectiveness. Based on an experiment’s acetylated dataset, the DL-ac4C sequence-based predictor for acetylation sites in mRNA can predict whether query sequences have potential acetylation motifs.

Colorectal cancer is the third most common cancer. Because curcumin (CUR) has anti-inflammatory and anticancer properties, research has been undertaken to indicate that nanocurcumin compounds can be used to treat a variety of cancers. CUR in nanoform has been found to have a stronger effect than conventional CUR. The purpose of this study was to show that CUR-loaded poly lactic-co-glycolic acid nanoparticles (PLGA) (CUR-loaded PLGA) have anti-inflammatory and anticancer effects on colon carcinogenesis in male dimethyl hydrazine (DMH) mice as a comparative study between the nanoform of curcumin and normal curcumin, focusing on the anticancer effect of nanocurcumin. Mice were separated into six groups: No treatment was given to Group I (negative Group-I). Group II was treated with CUR. Group III was treated with CUR-loaded PLGA. Group IV was treated with DMH. Group V received DMH and curcumin. Group VI received DMH and CUR-loaded PLGA. At the conclusion of the trial, the animals were slain (6 weeks). Inflammatory indicators and vascular endothelial growth factor (VEGF) levels all changed significantly in this study, as the following inflammatory markers as TNF showed percent of change compared to the DMH group. Recovery percentage for Groups V and VI, respectively, were 9.18 and 55.31%. In addition, IL1 was 7.45 and 50.37% for Groups V and VI, respectively. The results of IL6 were 4.86 and 25.79% for Groups V and VI, respectively. The vascular endothelial growth factor (VEGF) recovery percent was 16.98 and 45.12% for Groups V and VI, respectively. Following the effect of DMH on colon mucosa shape, the researchers looked at the effect of CUR-loaded PLGA on colon histology. It was shown that CUR-loaded PLGA affects the cell cycle and PCNA expression. We conclude that nanocurcumin is an important anti-inflammatory and cancer-fighting agent.

Peroxisome proliferator-activated receptor gamma (PPAR-γ) is ubiquitously expressed in testicular tissue and plays a crucial role in regulating various physiological processes. Pioglitazone (PIO) is one of the PPAR-γ agonists, having anti-oxidant and anti-inflammatory effects. Patients on gentamycin treatment may undergo serious side effects such as testicular damage. To the best of our knowledge, this was the first study to investigate the possible protective anti-inflammatory and anti-apoptotic effects of PIO on gentamycin-induced testicular damage. Fifty adult male Wistar albino rats included in the study as the control group (CTL) received normal saline; a gentamycin-induced testicular damage group (GM) received gentamycin (100 mg/kg); PIO5, PIO10, PIO20 groups received PIO at a dose of 5, 10, and 20 mg/ kg, respectively, for 21 days, and gentamycin was started at day 15 of the experiment for 6 days. The parameters of spermatozoa and histopathological alterations in the testes were significantly improved in the PIO20 group. Moreover, MDA levels, inflammatory mediators, and apoptotic Bax expression were decreased. The activity of glutathione peroxidase, catalase, total antioxidant capacity, and anti-apoptotic Bcl-2 genes expression were increased. It was concluded that PIO20 could protect against gentamycin-induced testicular damage in Wistar rats through its anti-oxidant, anti-inflammatory, and antiapoptotic effects.

In recent times, resistant foodborne pathogens, especially of the Campylobacter species, have created several global crises. These crises have been compounded due to the evolution of multidrug-resistant (MDR) bacterial pathogens and the emergence of extensively drug-resistant (XDR) and pan-drug-resistant (PDR) strains. Therefore, this study aimed to investigate the development of resistance and the existence of both XDR and PDR among Campylobacter isolates. Moreover, we explored the use of the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) technique for the detection of fluoroquinolone (FQ)-resistant Campylobacter isolates. A total of 120 Campylobacter isolates were identified depending on both phenotypic and genotypic methods. Of note, cefoxitin and imipenem were the most effective drugs against the investigated Campylobacter isolates. Interestingly, the majority of our isolates (75%) were MDR. Unfortunately, both XDR and PDR isolates were detected in our study with prevalence rates of 20.8% and 4.2%, respectively. All FQ-resistant isolates with ciprofloxacin minimum inhibitory concentrations ≥4 µg/mL were confirmed by the genetic detection of gyrA chromosomal mutation via substitution of threonine at position 86 to isoleucine (Thr-86-to-Ile) using the PCR-RFLP technique. Herein, PCR-RFLP was a more practical and less expensive method used for the detection of FQ resistant isolates. In conclusion, we introduced a fast genetic method for the identification of FQ-resistant isolates to avoid treatment failure through the proper description of antimicrobials.

The limitations in the therapeutic options for foodborne pathogens lead to treatments failure, especially for multidrug-resistant (MDR) Salmonella sp., worldwide. Therefore, we aimed to find alternative and complementary therapies against these resistant foodborne pathogens. Out of 100 meat products samples, the prevalence rate of salmonella was 6%, serotyped only as S. Typhimurium and S. Enteritidis. According to the antibiotic susceptibility assays, the majority of our isolates were MDR and susceptible to cefotaxime. Out of the 13 tested plant extracts, five only showed an inhibition zone in the range of 8–50 mm against both serotypes. Based on their promising activity, the oily extract of cinnamon and aqueous extract of paprika represented the highest potency. Surprisingly, a significant synergistic effect was detected between cinnamon oil and cefotaxime. Depending on Gas Chromatography/Mass Spectrometry (GC-MS), the antimicrobial activity of cinnamon oil was attributed to four components including linalool, camphor, (Z)-3-Phenylacrylaldehyde and its stereoisomer 2-Propenal-3-phenyl. The anti-virulence activities of these compounds were confirmed on the basis of computational molecular docking studies. Accordingly, we recommended the use of cinnamon oil as a food additive to fight the resistant foodborne pathogens. Additionally, we confirmed its therapeutic uses, especially when co-administrated with other antimicrobial agents.

The olive tree is a venerable Mediterranean plant and often used in traditional medicine. The main aim of the present study was to evaluate the effect of Olea europaea L. cv. Arbosana leaf extract (OLE) and its encapsulation within a spanlastic dosage form on the improvement of its pro-oxidant and antiproliferative activity against HepG-2, MCF-7, and Caco-2 human cancer cell lines. The LC-HRESIMS-assisted metabolomic profile of OLE putatively annotated 20 major metabolites and showed considerable in vitro antiproliferative activity against HepG-2, MCF-7, and Caco-2 cell lines with IC50 values of 9.2 ± 0.8, 7.1 ± 0.9, and 6.5 ± 0.7 µg/mL, respectively. The encapsulation of OLE within a (spanlastic) nanocarrier system, using a spraying method and Span 40 and Tween 80 (4:1 molar ratio), was successfully carried out (size 41 ± 2.4 nm, zeta potential 13.6 ± 2.5, and EE 61.43 ± 2.03%). OLE showed enhanced thermal stability, and an improved in vitro antiproliferative effect against HepG-2, MCF-7, and Caco-2 (IC50 3.6 ± 0.2, 2.3 ± 0.1, and 1.8 ± 0.1 µg/mL, respectively) in comparison to the unprocessed extract. Both preparations were found to exhibit pro-oxidant potential inside the cancer cells, through the potential inhibitory activity of OLE against glutathione reductase and superoxide dismutase (IC50 1.18 ± 0.12 and 2.33 ± 0.19 µg/mL, respectively). These inhibitory activities were proposed via a comprehensive in silico study to be linked to the presence of certain compounds in OLE. Consequently, we assume that formulating such a herbal extract within a suitable nanocarrier would be a promising improvement of its therapeutic potential.

The vascular endothelial growth factor receptor 2 (VEGFR-2) is largely recognized as a potent therapeutic molecular target for the development of angiogenesis-related tumor treatment. Tumor growth, metastasis and multidrug resistance highly depends on the angiogenesis and drug discovery of the potential small molecules targeting VEGFR-2, with the potential anti-angiogenic activity being of high interest to anti-cancer research. Multiple small molecule inhibitors of the VEGFR-2 are approved for the treatment of different type of cancers, with one of the most recent, tivozanib, being approved by the FDA for the treatment of relapsed or refractory advanced renal cell carcinoma (RCC). However, the endogenous and acquired resistance of the protein, toxicity of compounds and wide range of side effects still remain critical issues, which lead to the short-term clinical effects and failure of antiangiogenic drugs. We applied a combination of computational methods and approaches for drug design and discovery with the goal of finding novel, potential and small molecule inhibitors of VEGFR2, as alternatives to the known inhibitors’ chemical scaffolds and components. From studying several of these compounds, the derivatives of pyrido[1,2-a]pyrimidin-4-one and isoindoline-1,3-dione in particular were identified.

Since the beginning of the coronavirus 19 (COVID-19) pandemic in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been evolving through the acquisition of genomic mutations, leading to the emergence of multiple variants of concern (VOCs) and variants of interest (VOIs). Currently, four VOCs (Alpha, Beta, Delta, and Gamma) and seven VOIs (Epsilon, Zeta, Eta, Theta, Iota, Kappa, and Lambda) of SARS-CoV-2 have been identified in worldwide circulation. Here, we investigated the interactions of the receptor-binding domain (RBD) of five SARS-CoV-2 variants with the human angiotensin-converting enzyme 2 (hACE2) receptor in host cells, to determine the extent of molecular divergence and the impact of mutation, using protein-protein docking and dynamics simulation approaches. Along with the wild-type (WT) SARS-CoV-2, this study included the Brazilian (BR/lineage P.1/Gamma), Indian (IN/lineage B.1.617/Delta), South African (SA/lineage B.1.351/Beta), United Kingdom (UK/lineage B.1.1.7/Alpha), and United States (US/lineage B.1.429/Epsilon) variants. The protein-protein docking and dynamics simulation studies revealed that these point mutations considerably affected the structural behavior of the spike (S) protein compared to the WT, which also affected the binding of RBD with hACE2 at the respective sites. Additional experimental studies are required to determine whether these effects have an influence on drug–S protein binding and its potential therapeutic effect.

This study aims to determine the prevalence of STEC in she-camels suffering from mastitis in semi-arid regions by using traditional culture methods and then confirming it with Serological and molecular techniques in milk samples, camel feces, as well as human stool samples for human contacts. In addition, an antibiotic susceptibility profile for these isolates was investigation. Mastitic milk samples were taken after California Mastitis Test (CMT) procedure, and fecal samples were taken from she-camels and human stool samples, then cultured using traditional methods to isolate Escherichiacoli. These isolates were initially classified serologically, then an mPCR (Multiplex PCR) was used to determine virulence genes. Finally, both camel and human isolates were tested for antibiotic susceptibility. Out of a total of 180 she-camels, 34 (18.9%) were mastitic (8.3% clinical and 10.6% sub-clinical mastitis), where it was higher in camels bred with other animals. The total presence of E. coli was 21.9, 13.9, and 33.7% in milk, camel feces, and human stool, respectively, whereas the occurrence of STEC from the total E. coli isolates were 36, 16, and 31.4% for milk, camel feces, and stool, respectively. Among the camel isolates, stx1 was the most frequently detected virulence gene, while hlyA was not detected. The most detected virulence gene in human isolates was stx2 (45.5%), followed by stx1. Camel STEC showed resistance to Oxytetracycline only, while human STEC showed multiple drug resistance to Amoxicillin, Gentamycin, and Clindamycin with 81.8, 72.7, and 63.6%, respectively. Breeding camels in semi-arid areas separately from other animals may reduce the risk of infection with some bacteria, including E. coli; in contrast, mixed breeding with other animals contributes a significant risk factor for STEC emergence in camels.

Cancer is one of the most serious public health issues worldwide, ranking second only to cardiovascular diseases as a cause of death. Numerous plant extracts have extraordinary health benefits and have been used for centuries to treat a variety of ailments with few side effects. Olive leaves have a long history of medicinal and therapeutic use. In this study, the anti-cancer properties of an olive leaf extract were investigated in vitro using colorectal and prostate cancer cell lines (HT29 and PC3, respectively). A high-performance liquid chromatography analysis showed that the olive leaf extract contained a high chlorogenic acid content. Accordingly, chlorogenic acid may be related to the observed effects of the aqueous extract on cancer cells, including increased inhibition of cancer cell growth, migration, DNA fragmentation, cell cycle arrest at the S phase, reactive oxygen species (ROS) production, and altered gene expression. The effects of the extracts were greater in HT29 than in PC3 cells. These results suggest that chlorogenic acid, the main constituent in the olive extract, is a promising new anti-cancer agent. Further analyses should focus on its in vivo effects on colorectal tumor models, both alone and in combination with established agents.