Distinct negative-sense RNA viruses induce a common set of transcripts encoding proteins forming an extensive network.

The large group of negative-strand RNA viruses (NSVs) comprises many important pathogens. To identify conserved patterns in host responses, we systematically compared changes in the cellular RNA levels after infection of human hepatoma cells with nine different NSVs of different virulence degrees. RNA sequencing experiments indicated that the amount of viral RNA in host cells correlates with the number of differentially expressed host cell transcripts. Time-resolved differential gene expression analysis revealed a common set of 178 RNAs that are regulated by all NSVs analyzed. A newly developed open access web application allows downloads and visualizations of all gene expression comparisons for individual viruses over time or between several viruses. Most of the genes included in the core set of commonly differentially expressed genes (DEGs) encode proteins that serve as membrane receptors, signaling proteins and regulators of transcription. They mainly function in signal transduction and control immunity, metabolism, and cell survival. One hundred sixty-five of the DEGs encode host proteins from which 47 have already been linked to the regulation of viral infections in previous studies and 89 proteins form a complex interaction network that may function as a core hub to control NSV infections.IMPORTANCEThe infection of cells with negative-strand RNA viruses leads to the differential expression of many host cell RNAs. The differential spectrum of virus-regulated RNAs reflects a large variety of events including anti-viral responses, cell remodeling, and cell damage. Here, these virus-specific differences and similarities in the regulated RNAs were measured in a highly standardized model. A newly developed app allows interested scientists a wide range of comparisons and visualizations.

Lifestyle interventions in cardiometabolic HFpEF: dietary and exercise modalities.

Heart failure with preserved ejection fraction (HFpEF) is rapidly growing as the most common form of heart failure. Among HFpEF phenotypes, the cardiometabolic/obese HFpEF - HFpEF driven by cardiometabolic alterations - emerges as one of the most prevalent forms of this syndrome and the one on which recent therapeutic success have been made. Indeed, pharmacological approaches with sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have proved to be effective due to metabolic protective effects. Similarly, lifestyle changes, including diet and exercise are crucial in HFpEF management. Increasing evidence supports the important role of diet and physical activity in the pathogenesis, prognosis, and potential reversal of HFpEF. Metabolic derangements and systemic inflammation are key features of HFpEF and represent the main targets of lifestyle interventions. However, the underlying mechanisms of the beneficial effects of these interventions in HFpEF are incompletely understood. Hence, there is an unmet need of tailored lifestyle intervention modalities for patients with HFpEF. Here we present the current available evidence on lifestyle interventions in HFpEF management and therapeutics, discussing their modalities and potential mechanisms.

Evaluation of serum irisin level and severity of erectile dysfunction in diabetic males: a cross sectional prospective study.

BACKGROUND: Irisin is an exercise-induced myokine that alleviates endothelial dysfunction and reduces insulin resistance in type 2 diabetes mellitus (T2DM). The current study aimed to assess the serum level of irisin in T2DM men with erectile dysfunction (ED) compared to T2DM patients with normal erectile function and healthy controls, as well as investigate the association between serum irisin level and the severity of ED in T2DM patients. PATIENTS AND METHODS: A cross-sectional study was conducted on 90 males, divided into three groups: 32 T2DM patients with ED, 24 T2DM patients without ED, and 34 healthy controls. Socio-demographic characteristics and scores of the validated Arabic version of the international Index of Erectile Function-5 (ArIIEF-5), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were obtained. Furthermore, routine laboratory tests employed for diabetes monitoring and serum levels of total testosterone and irisin were assessed within these groups. RESULTS: T2DM men with ED had significantly lower serum levels of irisin and testosterone, as well as a lower ArIIEF-5 score, but their GAD-7 and PHQ-9 scores were significantly higher than those without ED or controls (p < 0.001). Among T2DM men, serum irisin levels positively associated with ArIIEF-5 scores and serum testosterone (r = 0.413, p = 0.002; r = 0.936, p < 0.001, respectively) but negatively associated with glycosylated hemoglobin levels (r = -0.377, p = 0.004). Multivariate regression analysis to predict ED in T2DM patients found that GAD-7 score was the only most significant predictor for ED (ꞵ = - 1.176, standard error = 0.062, p < 0.001). CONCLUSION: The current study had demonstrated that irisin positively correlated with the ArIIEF-5 and serum testosterone but negatively correlated with HbA1c in T2DM men. Nevertheless, further validation of these findings is necessary through cohort studies.

Knowledge, attitude, and practice of Egyptian medical students towards healthcare workers' recommended vaccines: a nationwide cross-sectional survey.

BACKGROUND: Vaccination of healthcare workers (HCWs) is pivotal in decreasing the incidence of contagious infections in hospital settings. In this study, we assessed the knowledge, attitude, and practice regarding HCWs' recommended vaccines among medical students and interns in Egypt. METHODS: A multicenter, cross-sectional study was conducted using a structured, pilot-tested, and self-administered questionnaire among Egyptian medical students and interns. We invited 1332 participants to our survey using a systematic random sampling that included participants across nine medical schools in Egypt during the 2021-2022 academic year. RESULTS: Out of 1332 participants, 1141 completed our questionnaire with a response rate of 85.7%. Overall, 43% of the participants had intermediate knowledge (knew 2-3 HCWs' recommended vaccines). Furthermore, 36.7% had received a booster dose of at least one of the HCWs' recommended vaccines over the last 10 years, with only 6.1% having received all recommended vaccines. Hepatitis B vaccine was the most widely known (71%) and received (66.7%). Interns were more likely to know, receive, and recommend HCWs' recommended vaccines. The majority (> 90%) agreed that vaccination is beneficial and safe, with a median score of eight (interquartile range [IQR: Q25-Q75]: 7-9) out of ten for vaccine efficacy and eight (IQR: 7-8) for safety. However, the median score for hesitancy was five (IQR: 2-7). The most common influential and limiting factors for vaccination were scientific facts (60.1%) and fear of vaccine side effects (44.9%). CONCLUSION: Although medical students in Egypt have good knowledge of and attitudes towards vaccination, there is a gap in their practices. Interventions are needed to improve vaccination uptake among medical students in Egypt.

Novel compounds with dual inhibition activity against SARS-CoV-2 critical enzymes RdRp and human TMPRSS2.

COVID-19 caused major worldwide problems. The spread of variants and limited treatment encouraged the design of novel anti-SARS-CoV-2 compounds. A series of compounds RH1-23 were designed to dually target RNA-dependent RNA polymerase (RdRp) and transmembrane serine protease 2 (TMPRSS2). Compared to remdesivir, in vitro screening indicated the highest selectivity and potent activity of RH11-13 with half maximum inhibitory concentration (IC50) 3.9, 5.7, and 19.72 nM, respectively. RH11-12 showed superior inhibition activity against TMPRSS2 and RdRP with IC50 (1.7 and 4.2), and (6.1 and 4.42) nM, respectively. WaterMap analysis and molecular dynamics studies demonstrated the superior enzyme binding activity of RH11 and RH12. On Vero-E6 cells, RH11 and RH12 significantly inhibited the viral replication with 66 % and 63.2 %, and viral adsorption with 44 % and 65 %, alongside virucidal effect with 51.40 % and 90.5 %, respectively. Furthermore, the potent activity of RH12 was tested on TMPRSS2-expressing cells (Calu-3) compared to camostat. RH12 exhibited selectivity index (26.05) similar to camostat (28.01) and comparable to its SI on Vero-E6 cells (22.6). RH12 demonstrated also a significant inhibition of the viral adsorption on Calu-3 cells with 60 % inhibition at 30 nM. The designed compounds exhibited good physiochemical properties. These findings indicate a broad-spectrum antiviral efficacy of the designed compounds, particularly RH12, with a promise for further development.

Reduced levels of MRE11 cause disease phenotypes distinct from ataxia telangiectasia-like disorder.

The MRE11/RAD50/NBS1 (MRN) complex plays critical roles in cellular responses to DNA double-strand breaks. MRN is involved in end binding and processing, and it also induces cell cycle checkpoints by activating the ataxia-telangiectasia mutated (ATM) protein kinase. Hypomorphic pathogenic variants in the MRE11, RAD50, or NBS1 genes cause autosomal recessive genome instability syndromes featuring variable degrees of dwarfism, neurological defects, anemia, and cancer predisposition. Disease-associated MRN alleles include missense and nonsense variants, and many cause reduced protein levels of the entire MRN complex. However, the dramatic variability in the disease manifestation of MRN pathogenic variants is not understood. We sought to determine if low protein levels are a significant contributor to disease sequelae and therefore generated a transgenic murine model expressing MRE11 at low levels. These mice display dramatic phenotypes including small body size, severe anemia, and impaired DNA repair. We demonstrate that, distinct from ataxia telangiectasia-like disorder caused by MRE11 pathogenic missense or nonsense variants, mice and cultured cells expressing low MRE11 levels do not display the anticipated defects in ATM activation. Our findings indicate that ATM signaling can be supported by very low levels of the MRN complex and imply that defective ATM activation results from perturbation of MRN function caused by specific hypomorphic disease mutations. These distinct phenotypic outcomes underline the importance of understanding the impact of specific pathogenic MRE11 variants, which may help direct appropriate early surveillance for patients with these complicated disorders in a clinical setting.

Evaluation of OVOL1 and Filaggrin immunohistochemical expression and clinical relevance in psoriasis.

BACKGROUND: Psoriasis is a disease of overactive immune system. OVOL1 and Filaggrin have been associated with many inflammatory skin lesions. To the best of our knowledge, the correlation between OVOL1 and Filaggrin in psoriasis was not previously investigated. This work aims to search the immunohistochemical expression and correlation between OVOL1 and Filaggrin in psoriasis. MATERIALS AND METHODS: Slides cut from paraffin blocks of 30 psoriasis cases and 30 control subjects were stained with OVOL1 and Filaggrin. Clinicopathological data were correlated with the results of staining. RESULTS: OVOL1 and Filaggrin expression in epidermis showed a significant gradual reduction from normal skin to peri-lesional and psoriasis biopsies (P < 0.001). In contrast, psoriasis dermis showed a significant overexpression of OVOL1 in inflammatory cells in relation to peri-lesional biopsies (P < 0.002). OVOL1 demonstrated a significant direct correlation with Filaggrin expression in psoriasis (r = 0.568, P < 0.004). OVOL1 and Filaggrin expression in psoriasis skin epidermis demonstrated a statistically significant negative correlation with PASI score. CONCLUSION: OVOL1 and Filaggrin might be involved in psoriasis-associated inflammation and skin hyperproliferation. OVOL1 might have a protective barrier function in the skin and could be used to stratify progressive disease. Filaggrin may play a role in progression of psoriasis. OVOL1 inhibition could be considered in suppression of Filaggrin function. OVOL1 agonists may be beneficial in psoriasis treatment.

Fitz-Hugh-Curtis Syndrome in a Male Patient.

We report the case of a 38-year-old Middle Eastern man with intractable right upper quadrant (RUQ) abdominal pain and several emergency department visits during the last seven years, with extensive and repeated radiologic and endoscopic workups proven negative for biliary or upper gastrointestinal disease. He presented to our outpatient surgical clinic in March 2023 complaining of worsening RUQ and epigastric pain and was scheduled for a robotic cholecystectomy for presumed biliary dyskinesia following a repeat cholescintigraphy (hepatobiliary iminodiacetic acid) scan. During a cholecystectomy, extensive bilobar perihepatic adhesions were found, indicative of Fitz-Hugh-Curtis syndrome (FHCS). A thorough lysis of adhesions was performed along with a wedge liver biopsy, with subsequent histological examination showing chronic cholecystitis, perihepatic mesothelial fibrosis with mild subcapsular hepatic steatosis, and no evidence of liver fibrosis. The patient was examined in the clinic two weeks after surgery with complete resolution of symptoms. This case highlights the importance of considering FHCS in the differential diagnosis of male patients presenting with refractory RUQ abdominal pain despite a negative workup. Early recognition and prompt treatment can prevent unnecessary extensive, repeat testing and delays in intervention in these patients.

Insights into the sustainability of liquid chromatographic methods for favipiravir bioanalysis: a comparative study.

The introduction of favipiravir as a broad-spectrum antiviral agent, particularly in treating influenza and exploring its potential against COVID-19, emphasizes the necessity for efficient analytical methods. Liquid chromatography has emerged as a commonly utilized technique for quantifying favipiravir in biological fluids. However, the environmental and health concerns linked to classical analytical methods mean a transition toward green analytical chemistry is required. This study investigates the environmental impact of 19 liquid chromatographic methods utilized in the bioanalysis of favipiravir. Recognizing the importance of eco-friendly practices in pharmaceutical analysis, the study employs three widely accepted greenness assessment tools: Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI), and Analytical Greenness Calculator (AGREE). Moreover, it incorporates a comprehensive evaluation on a global scale utilizing the whiteness assessment tool Red-Green-Blue 12 (RGB 12). The comprehensive evaluation aims to extend beyond traditional validation criteria and considerations of green chemistry, providing insights into the development of practically efficient, eco-friendly and economical analytical methods for favipiravir determination. This study emphasizes the necessity of planning for the environmental impact and overall sustainability of analytical methods before laboratory trials. Additionally, the integration of greenness/whiteness evaluation in method validation protocols is strongly advocated, emphasizing the importance of critical and global evaluations in analytical chemistry.

Potent neutralization by a receptor binding domain monoclonal antibody with broad specificity for SARS-CoV-2 JN.1 and other variants.

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. While increasing herd immunity, current vaccines, and therapeutics have improved outcomes for some; prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed. Using a rationally designed SARS-CoV-2 Receptor Binding Domain (RBD) - ACE2 fusion protein and differential selection process with native Omicron RBD protein, we developed a recombinant human monoclonal antibody (hmAb) from a convalescent individual following SARS-CoV-2 Omicron infection. The resulting hmAb, 1301B7 potently neutralized a wide range of SARS-CoV-2 variants including the original Wuhan and more recent Omicron JN.1 strain, as well as SARS-CoV. Structure determination of the SARS-CoV-2 EG5.1 Spike/1301B7 Fab complex by cryo-electron microscopy at 3.1Å resolution demonstrates 1301B7 contacts the ACE2 binding site of RBD exclusively through its VH1-69 heavy chain, making contacts using CDRs1-3, as well as framework region 3 (FR3). Broad specificity is achieved through 1301B7 binding to many conserved residues of Omicron variants including Y501 and H505. Consistent with its extensive binding epitope, 1301B7 is able to potently diminish viral burden in the upper and lower respiratory tract and protect mice from challenge with Omicron XBB1.5 and Omicron JN.1 viruses. These results suggest 1301B7 has broad potential to prevent or treat clinical SARS-CoV-2 infections and to guide development of RBD-based universal SARS-CoV-2 prophylactic vaccines and therapeutic approaches.

Correlation between Serum Levels of Nitric Oxide and Adropin and Erectile Dysfunction in Males with Nonalcoholic Fatty Liver Disease: An Observational Study.

The current study aimed to evaluate the serum levels of nitric oxide (NO) and adropin in males with non-alcoholic fatty liver disease (NAFLD) induced erectile dysfunction (ED) and NAFLD patients without ED and controls. The current study selected 165 participants from the hepatology department from November 2021 to November 2022. The patients were either suffering from NAFLD with normal liver functions or non-alcoholic steatohepatitis with abnormal liver functions. They were diagnosed by abdominal ultrasonography. Participants were evaluated using the validated Arabic version of the International Index of Erectile Function (ArIIEF-5), the Arabic form of the Generalized Anxiety Disorder-7 (GAD-7) questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Noteworthy, there were significant positive correlations between ArIIEF-5 score, NO, adropin and total testosterone (r = 0.380, p = 0.001; r = 0.507, p = < 0.001; r = 0.246, p = 0.038, respectively). Meanwhile, there were significant negative correlations between ArIIEF-5 score, creatinine, duration of the disease and scores of GAD-7 and PHQ-9 (r = -0.656, p = < 0.001; r = -0.368, p = 0.002; r = -0.663, p = < 0.001; r = -0.248, p = 0.037, respectively). Finally, a linear regression analysis revealed that GAD-7, creatinine, and adropin were the only strong independent predictors of ArIIEF-5, as the 95% confidence interval in the form of upper and lower bounds was -0.349, -0.843, p < 0.001, -6.507, -18.402, p < 0.001, 0.476, 0.117, and p 0.002, respectively. Impaired NO and adropin levels play a potential role in the development of ED in patients with NAFLD.

In vitro biological evaluation and in silico insights into the antiviral activity of standardized olive leaves extract against SARS-CoV-2.

There is still a great global need for efficient treatments for the management of SARS-CoV-2 illness notwithstanding the availability and efficacy of COVID-19 vaccinations. Olive leaf is an herbal remedy with a potential antiviral activity that could improve the recovery of COVID-19 patients. In this work, the olive leaves major metabolites were screened in silico for their activity against SARS-CoV-2 by molecular docking on several viral targets such as methyl transferase, helicase, Plpro, Mpro, and RdRp. The results of in silico docking study showed that olive leaves phytoconstituents exhibited strong potential antiviral activity against SARS-CoV-2 selected targets. Verbacoside demonstrated a strong inhibition against methyl transferase, helicase, Plpro, Mpro, and RdRp (docking scores = -17.2, -20, -18.2, -19.8, and -21.7 kcal/mol.) respectively. Oleuropein inhibited 5rmm, Mpro, and RdRp (docking scores = -15, -16.6 and -18.6 kcal/mol., respectively) respectively. Apigenin-7-O-glucoside exhibited activity against methyl transferase and RdRp (docking score = -16.1 and -19.4 kcal/mol., respectively) while Luteolin-7-O-glucoside inhibited Plpro and RdRp (docking score = -15.2 and -20 kcal/mol., respectively). The in vitro antiviral assay was carried out on standardized olive leaf extract (SOLE) containing 20% oleuropein and IC50 was calculated. The results revealed that 20% SOLE demonstrated a moderate antiviral activity against SARS-CoV-2 with IC50 of 118.3 µg /mL. Accordingly, olive leaf could be a potential herbal therapy against SARS-CoV-2 but more in vivo and clinical investigations are recommended.

The Interplay Between Human Leukocyte Antigen Antibody Profile and COVID-19 Vaccination in Waitlisted Renal Transplant Patients.

CONTEXT.­: Mass COVID-19 vaccination is mandated in vulnerable populations in our renal transplant waitlist cohort. However, the anti-human leukocyte antigen (anti-HLA) profile after COVID-19 vaccination is controversial, and the side effects are yet to be discerned. OBJECTIVE.­: To evaluate the status of HLA antibodies in waitlist renal transplant patients before and 3 weeks after each vaccination and if comorbidities are associated with the HLA antibody profile. DESIGN.­: A total of 59 waitlisted kidney transplant patients were included in this study. The anti-HLA antibodies were analyzed before and 6 months after their last COVID-19 vaccination. The mean fluorescence intensity change in the anti-HLA antibody levels was used to classify patients into 3 groups: high inducers, low inducers, and noninducers. RESULTS.­: There were significant HLA antibody profile changes after COVID-19 vaccination, showing 21 antibodies generated against HLA class I antigens and 7 against HLA class II antigens to their baseline. Compared with the noninducers, the high and low inducers showed a higher prevalence of COVID-19 infection, COVID-19 vaccine type, and background hypertension history. CONCLUSIONS.­: Our data suggest that COVID-19 vaccination propagates anti-HLA class I and II antibodies for waitlisted renal transplant patients. The clinical significance of these antibodies needs further study. Furthermore, comorbidities, such as history of COVID-19 infection and hypertension, supplemented this effect. Anti-HLA antibody monitoring may be warranted in vaccinated, waitlisted renal transplant patients with COVID-19 vaccinations, and a history of COVID-19 infection or hypertension.

Influenza A virus replicates productively in primary human kidney cells and induces factors and mechanisms related to regulated cell death and renal pathology observed in virus-infected patients.

Introduction: Influenza A virus (IAV) infection can cause the often-lethal acute respiratory distress syndrome (ARDS) of the lung. Concomitantly, acute kidney injury (AKI) is frequently noticed during IAV infection, correlating with an increased mortality. The aim of this study was to elucidate the interaction of IAV with human kidney cells and, thereby, to assess the mechanisms underlying IAV-mediated AKI. Methods: To investigate IAV effects on nephron cells we performed infectivity assays with human IAV, as well as with human isolates of either low or highly pathogenic avian IAV. Also, transcriptome and proteome analysis of IAV-infected primary human distal tubular kidney cells (DTC) was performed. Furthermore, the DTC transcriptome was compared to existing transcriptomic data from IAV-infected lung and trachea cells. Results: We demonstrate productive replication of all tested IAV strains on primary and immortalized nephron cells. Comparison of our transcriptome and proteome analysis of H1N1-type IAV-infected human primary distal tubular cells (DTC) with existing data from H1N1-type IAV-infected lung and primary trachea cells revealed enrichment of specific factors responsible for regulated cell death in primary DTC, which could be targeted by specific inhibitors. Discussion: IAV not only infects, but also productively replicates on different human nephron cells. Importantly, multi-omics analysis revealed regulated cell death as potential contributing factor for the clinically observed kidney pathology in influenza.

Molecular characterization of the whole genome of H9N2 avian influenza virus isolated from Egyptian poultry farms.

H9N2 avian influenza viruses (AIVs) affect both poultry and humans on a global level, and they are especially prevalent in Egypt. In this study, we sequenced the entire genome of AIV H9N2 isolated from chickens in Egypt in 2021, using next-generation sequencing (NGS) technology. Phylogenetic analysis of the resulting sequences showed that the studied strain was generally monophyletic and grouped within the G1 sublineage of the Eurasian lineage. Four segments (polymerase basic 2 [PB2], polymerase basic 1 [PB1], polymerase acidic [PA], and non-structural [NS]) were related to Egyptian genotype II, while the nucleoprotein (NP), neuraminidase (NA), matrix (M), and haemagglutinin (HA) segments were related to Egyptian genotype I. Molecular analysis revealed that HA protein contained amino acid residues (191H and 234L) that suggested a predilection for attaching to human-like receptors. The antigenic sites of HA had two nonsynonymous mutations: V194I at antigenic site A and M40K at antigenic site B. Furthermore, the R403W and S372A mutations, which have been observed in H3N2 and H2N2 strains that caused human pandemics, were found in the NA protein of the detected strain. The internal proteins contained virulence markers: 504V in the PB2 protein, 622G, 436Y, 207K, and 677T in the PB1 protein, 127V, 550L, and 672L in PA protein, and 64F and 69P in the M protein. These results show that the detected strain had undergone intrasubtype reassortment. Furthermore, it contains changes in the viral proteins that make it more likely to be virulent, raising a question about the tendency of AIV H9N2 to become highly pathogenic in the future for both poultry and humans.

Polymeric nanofiber leveraged co-delivery of anti-stromal PAK1 inhibitor and paclitaxel enhances therapeutic effects in stroma-rich 3D spheroid models.

The role of tumor stroma in solid tumors has been widely recognized in cancer progression, metastasis and chemoresistance. Cancer-associated fibroblasts (CAFs) play a crucial role in matrix remodeling and promoting cancer cell stemness and resistance via reciprocal crosstalk. Residual tumor tissue after surgical removal as well as unresectable tumors face therapeutic challenges to achieve curable outcome. In this study, we propose to develop a dual delivery approach by combining p21-activated kinase 1 (PAK1) inhibitor (FRAX597) to inhibit tumor stroma and chemotherapeutic agent paclitaxel (PTX) to kill cancer cells using electrospun nanofibers. First, the role of the PAK1 pathway was established in CAF differentiation, migration and contraction using relevant in vitro models. Second, polycaprolactone polymer-based nanofibers were fabricated using a uniaxial electrospinning technique to incorporate FRAX597 and/or PTX, which showed a uniform texture and a prolonged release of both drugs for 16 days. To test nanofibers, stroma-rich 3D heterospheroid models were set up which showed high resistance to PTX nanofibers compared to stroma-free homospheroids. Interestingly, nanofibers containing PTX and FRAX597 showed strong anti-tumor effects on heterospheroids by reducing the growth and viability by > 90 % compared to either of single drug-loaded nanofibers. These effects were reflected by reduced intra-spheroidal expression levels of collagen 1 and α-smooth muscle actin (α-SMA). Overall, this study provides a new therapeutic strategy to inhibit the tumor stroma using PAK1 inhibitor and thereby enhance the efficacy of chemotherapy using nanofibers as a local delivery system for unresectable or residual tumor. Use of 3D models to evaluate nanofibers highlights these models as advanced in vitro tools to study the effect of controlled release local drug delivery systems before animal studies.

Identification of potential antiviral compounds from Egyptian sea stars against seasonal influenza A/H1N1 virus.

BACKGROUND: One of the most dangerous problems that the world faced recently is viral respiratory pathogens. Marine creatures, including Echinodermata, specially Asteroidea class (starfish) have been extensively studied due to their miscellaneous bioactivities, excellent pharmacological properties, and complex secondary metabolites, including steroids, steroidal glycosides, anthraquinones, alkaloids, phospholipids, peptides, and fatty acids. These chemical constituents show antiviral activities against a wide range of viruses, including respiratory viruses. RESULTS: The present study aimed at the identification of potential antiviral compounds from some starfish species. The bioactive compounds from Pentaceraster cumingi, Astropecten polyacanthus, and Pentaceraster mammillatus were extracted using two different solvents (ethyl acetate and methanol). The antiviral activity against influenza A/H1N1 virus showed that ethyl acetate extract from Pentaceraster cumingi has the highest activity, where the selective index was 150.8. The bioactive compounds of this extract were identified by GC/MS analysis. The molecular docking study highlighted the virtual mechanism of binding of the identified compounds towards polymerase basic protein 2 and neuraminidase for H1N1 virus. Interestingly, linoleic acid showed promising binding energy of -10.12 Kcal/mol and -24.20 Kcal/mol for the selected two targets, respectively, and it formed good interactive modes with the key amino acids inside both proteins. CONCLUSION: The molecular docking analysis showed that linoleic acid was the most active antiviral compound from P. cumingi. Further studies are recommended for in-vitro and in-vivo evaluation of this compound against influenza A/H1N1 virus.

Fabrication of cellulose nanocrystals/carboxymethyl cellulose/zeolite membranes for methylene blue dye removal: understanding factors, adsorption kinetics, and thermodynamic isotherms.

This study introduces environmentally-friendly nanocellulose-based membranes for AZO dye (methylene blue, MB) removal from wastewater. These membranes, made of cellulose nanocrystals (CNCs), carboxymethyl cellulose (CMC), zeolite, and citric acid, aim to offer eco-friendly water treatment solutions. CNCs, obtained from sugarcane bagasse, act as the foundational material for the membranes. The study aims to investigate both the composition of the membranes (CMC/CNC/zeolite/citric acid) and the critical adsorption factors (initial MB concentration, contact time, temperature, and pH) that impact the removal of the dye. After systematic experimentation, the optimal membrane composition is identified as 60% CNC, 15% CMC, 20% zeolites, and 5% citric acid. This composition achieved a 79.9% dye removal efficiency and a 38.3 mg/g adsorption capacity at pH 7. The optimized membrane exhibited enhanced MB dye removal under specific conditions, including a 50 mg adsorbent mass, 50 ppm dye concentration, 50 mL solution volume, 120-min contact time, and a temperature of 25°C. Increasing pH from neutral to alkaline enhances MB dye removal efficiency from 79.9% to 94.5%, with the adsorption capacity rising from 38.3 mg/g to 76.5 mg/g. The study extended to study the MB adsorption mechanisms, revealing the chemisorption of MB dye with pseudo-second-order kinetics. Chemical thermodynamic experiments determine the Freundlich isotherm as the apt model for MB dye adsorption on the membrane surface. In conclusion, this study successfully develops nanocellulose-based membranes for efficient AZO dye removal, contributing to sustainable water treatment technologies and environmental preservation efforts.

Antiviral responses versus virus-induced cellular shutoff: a game of thrones between influenza A virus NS1 and SARS-CoV-2 Nsp1.

Following virus recognition of host cell receptors and viral particle/genome internalization, viruses replicate in the host via hijacking essential host cell machinery components to evade the provoked antiviral innate immunity against the invading pathogen. Respiratory viral infections are usually acute with the ability to activate pattern recognition receptors (PRRs) in/on host cells, resulting in the production and release of interferons (IFNs), proinflammatory cytokines, chemokines, and IFN-stimulated genes (ISGs) to reduce virus fitness and mitigate infection. Nevertheless, the game between viruses and the host is a complicated and dynamic process, in which they restrict each other via specific factors to maintain their own advantages and win this game. The primary role of the non-structural protein 1 (NS1 and Nsp1) of influenza A viruses (IAV) and the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively, is to control antiviral host-induced innate immune responses. This review provides a comprehensive overview of the genesis, spatial structure, viral and cellular interactors, and the mechanisms underlying the unique biological functions of IAV NS1 and SARS-CoV-2 Nsp1 in infected host cells. We also highlight the role of both non-structural proteins in modulating viral replication and pathogenicity. Eventually, and because of their important role during viral infection, we also describe their promising potential as targets for antiviral therapy and the development of live attenuated vaccines (LAV). Conclusively, both IAV NS1 and SARS-CoV-2 Nsp1 play an important role in virus-host interactions, viral replication, and pathogenesis, and pave the way to develop novel prophylactic and/or therapeutic interventions for the treatment of these important human respiratory viral pathogens.