Revolutionizing scandium detection in real samples: Unleashing the power of sol-gel-based optical sensor.

The development of a highly selective and ultra-sensitive optical sensor for detecting scandium (Sc3+) ions involves incorporating the reagent 2,3-dichloro-6-(3-carboxy-2-hydroxy-1-naphthylazo)quinoxaline (DCHNAQ) into a silica sol-gel thin film on a glass substrate. This innovative approach utilizes tetraethoxy-silane (TEOS) as the precursor, maintaining a sol-gel pH level of 4.5, a water-to-alkoxide ratio of 5:1, and a DCHNAQ concentration of 5.0 × 10-4 M. A detailed exploration of the impact of sol-gel parameters on the sensing capabilities of the developed sensor has been meticulously undertaken. This innovative sensor demonstrates remarkable selectivity in evaluating Sc3+ ions over a dynamic range of 7.5-170 ng/mL, with limits of quantification and detection recorded at 7.3 and 2.20 ng/mL, respectively. Consistent results are achieved with a minimal RSD of 1.47 and 0.94% for Sc3+ ions at 50 and 100 ng/mL, respectively, coupled with a swift response time of three min. Assessments of interference demonstrate a noteworthy preference for Sc3+ions, accomplished by enclosing DCHNAQ within the sol-gel framework and making optimal structural modifications to the doped sol-gel. The sensor offers straightforward regeneration using a 0.25 M EDTA solution, exhibiting complete reversibility. Comparative analysis with other methodologies underscores the efficacy in determining Sc3+ions in various reference materials, including plant leaves, fish, water, alloys, ores, and monazite samples.

Probing protein aggregation through spectroscopic insights and multimodal approaches: A comprehensive review for counteracting neurodegenerative disorders.

Aberrant accumulation of protein misfolding can cause aggregation and fibrillation and is one of the primary characteristic features of neurodegenerative diseases. Because they are disordered, misfolded, and aggregated proteins pose a significant setback in drug designing. The structural study of intermediate steps in these kinds of aggregated proteins will allow us to determine the conformational changes as well as the probable pathways encompassing various neurodegenerative disorders. The analysis of protein aggregates involved in neurodegenerative diseases relies on a diverse toolkit of biophysical techniques, encompassing both morphological and non-morphological methods. Additionally, Thioflavin T (ThT) assays and Circular Dichroism (CD) spectroscopy facilitate investigations into aggregation kinetics and secondary structure alterations. The collective application of these biophysical techniques empowers researchers to comprehensively unravel the intricate nature of protein aggregates associated with neurodegeneration. Furthermore, the topics covered in this review have summed up a handful of well-established techniques used for the structural analysis of protein aggregation. This multifaceted approach advances our fundamental understanding of the underlying mechanisms driving neurodegenerative diseases and informs potential therapeutic strategies.

Bat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets.

Influenza A viruses (IAVs) of subtype H9N2 have reached an endemic stage in poultry farms in the Middle East and Asia. As a result, human infections with avian H9N2 viruses have been increasingly reported. In 2017, an H9N2 virus was isolated for the first time from Egyptian fruit bats (Rousettus aegyptiacus). Phylogenetic analyses revealed that bat H9N2 is descended from a common ancestor dating back centuries ago. However, the H9 and N2 sequences appear to be genetically similar to current avian IAVs, suggesting recent reassortment events. These observations raise the question of the zoonotic potential of the mammal-adapted bat H9N2. Here, we investigate the infection and transmission potential of bat H9N2 in vitro and in vivo, the ability to overcome the antiviral activity of the human MxA protein, and the presence of N2-specific cross-reactive antibodies in human sera. We show that bat H9N2 has high replication and transmission potential in ferrets, efficiently infects human lung explant cultures, and is able to evade antiviral inhibition by MxA in transgenic B6 mice. Together with its low antigenic similarity to the N2 of seasonal human strains, bat H9N2 fulfils key criteria for pre-pandemic IAVs.

HPLC-ESI/MS-MS metabolic profiling of white pitaya fruit and cytotoxic potential against cervical cancer: Comparative studies, synergistic effects, and molecular mechanistic approaches.

Natural approach became a high demand for the prevention and treatment of such diseases for their proven safety and efficacy. This study is aimed to perform comparative phytochemical analysis of white pitaya (Hylocereus undatus) peel, pulp and seed extracts via determination of total flavonoid content, phenolic content, and antioxidant capacity, coupled with HPLC-ESI/MS-MS analysis. Further, we evaluated the synergistic cytotoxic potential with Cisplatin against cervical cancer cells with investigation of underlying mechanism. The highest content of phenolics and antioxidants were found in both seed and peel extracts. The HPLC-ESI/MS-MS revealed identification of flavonoids, phenolic acids, anthocyanin glycosides, lignans, stilbenes, and coumarins. The cytotoxicity effects were evaluated by MTT assay against prostate, breast and cervical (HeLa) and Vero cell lines. The seed and peel extracts showed remarkable cytotoxic effect against all tested cell lines. Moreover, the selectivity index confirmed high selectivity of pitaya extracts to cancer cells and safety on normal cells. The combined therapy with Cisplatin effectively enhanced its efficacy and optimized the treatment outcomes, through the apoptotic ability of pitaya extracts in HeLa cells, as evaluated by flow cytometry. Besides, RT-PCR and western blotting analysis showed downregulation of Bcl-2 and overexpression of P53, BAX among HeLa cells treated with pitaya extracts, which eventually activated apoptosis process. Thus, pitaya extract could be used as adjuvant therapy with cisplatin for treatment of cervical cancer. Furthermore, in-vivo extensive studies on the seed and peel extracts, and their compounds are recommended to gain more clarification about the required dose, and side effects.

Cross-species spill-over potential of the H9N2 bat influenza A virus.

In 2017, a novel influenza A virus (IAV) was isolated from an Egyptian fruit bat. In contrast to other bat influenza viruses, the virus was related to avian A(H9N2) viruses and was probably the result of a bird-to-bat transmission event. To determine the cross-species spill-over potential, we biologically characterize features of A/bat/Egypt/381OP/2017(H9N2). The virus has a pH inactivation profile and neuraminidase activity similar to those of human-adapted IAVs. Despite the virus having an avian virus-like preference for α2,3 sialic acid receptors, it is unable to replicate in male mallard ducks; however, it readily infects ex-vivo human respiratory cell cultures and replicates in the lungs of female mice. A/bat/Egypt/381OP/2017 replicates in the upper respiratory tract of experimentally-infected male ferrets featuring direct-contact and airborne transmission. These data suggest that the bat A(H9N2) virus has features associated with increased risk to humans without a shift to a preference for α2,6 sialic acid receptors.

Disease prognosis and therapeutic strategies in patients with advanced non-small cell lung cancer (NSCLC): a 6-year epidemiological study between 2015-2021.

Background: Lung cancer is the top cause of mortality in males and the second largest cause of cancer-related fatalities in women worldwide. Non-small cell lung cancer (NSCLC) cases are discovered at an advanced stage, raising major challenges in disease management and survival outcomes. This study aimed to investigate the clinical findings and management of stage IIIB and IV NSCLC patients for better decision-making, disease management, and understanding of this fatal disease. Methods: In this cohort study of 340 patients, a total of 140 (41.2%) were diagnosed with advanced-stage NSCLC at a mean age of 64 years. The electronic data of patients from 2015 to 2021 who met the inclusion criteria were retrieved from two tertiary hospitals in Riyadh, Saudi Arabia, and an Excel sheet was used to record the variables. Patients' data including all categorical variables such as gender, stage, metastasis, ALK, EGFR, and ROS, etc., and continuous variables such as age and body mass index (BMI) were retrieved and analyzed. Results: The multivariate Cox-regression model indicated that smoking was the significant risk factor of death for two-thirds of male smokers (37.9%), with a median survival time of 123 days. Disease progression was higher with pleural and brain metastasis, and localized metastasis was the highest in 75% of patients. The intent of treatment was mainly palliative, however, a statistically significant association was found with the simultaneous use of chemotherapy and immunotherapy. Patients' response to first-line treatment revealed a significant improvement if chemotherapy treatment was maintained at the same dose without interruption of dosage. Conclusions: The overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required for better decision-making to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.

Doping zinc oxide and titanium dioxide nanoparticles with gold induces additional oxidative stress, membrane damage, and neurotoxicity in Mytilus galloprovincialis: Results from a laboratory bioassay.

BACKGROUND: While previous studies have provided insights into the effects of zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles (NPs) on aquatic organisms, there is still a substantial amount of information lacking about the possible effects of their doped counterparts. The goal of the current work was to address this gap by examining Mytilus galloprovincialis reaction to exposure to doped and undoped nanoparticles. METHODS: Two concentrations (50 or 100 µg/L) of undoped ZnO and TiO2 NPs, as well as their gold (Au) doped counterparts, were applied on mussels for 14 days, and the effects on biomarkers activities in digestive glands and gills were assessed by spectrophotometry. RESULTS: The NPs were quasi-spherical in shape (below 100 nm), stable in seawater, and with no aggregation for both doped and undoped forms. Analytical results using inductively coupled plasma atomic emission spectroscopy indicated the uptake of NPs in mussels. Furthermore, it was found that biometal dyshomeostasis could occur following NP treatment and that doping the NPs aggravated this response. At the biochemical level, exposure to undoped NPs caused membrane damage, neurotoxic effect, and changes in the activities in the gills and digestive glands of superoxide dismutase, catalase, and glutathione-S-transferase, in a concentration and organ-dependent manner. CONCLUSION: Doping ZnO NPs and TiO2NPs with Au induced additional oxidative stress, membrane damage, and neurotoxicity in mussels.

Risk of Ovarian Malignancy Algorithm and Pelvic Mass Score for the prediction of malignant ovarian tumors: a prospective comparative study.

Aim: Ovarian cancer is the seventh most common female cancer worldwide. Nevertheless, there is no available universal screening method for malignant ovarian masses. This study compares the value of the Risk of Ovarian Malignancy Algorithm (ROMA) and Pelvic Mass Score (PMS) scoring systems in the diagnosis of malignant ovarian masses. Material and methods: This prospective comparative study was conducted from March 2021 until April 2022. A total of 258 women diagnosed with ovarian mass and eligible for surgical intervention according to institutional guidelines were enrolled in the study. Ultrasound was performed for the assessment of masses, ascites and metastases, also color flow Doppler was done to measure the resistance index of the mass vasculature. Preoperative venous blood samples were collected to measure CA 125 and HE4. PMS and ROMA scoring systems were calculated for each patient. All women were subjected to a surgical intervention (according to applicable institutional guidelines), using either open or laparoscopic techniques. Histopathological examination of the removed specimens was done, and in line with the recognized gold standard, the results were compared with the pre-operative diagnosis of both scoring systems. Results: Both PMS and ROMA showed a high predictive probability for ovarian malignancies (AUC = 0.93, sensitivity = 83.3%, specificity = 90.37%; AUC = 0.91, sensitivity = 84.4%, specificity = 95.56%, respectively), yet no statistical significant difference was found between the two scoring systems (p = 0.353, 95% CI -0.025 to 0.070). Conclusions: Both PMS and ROMA seem to be promising scoring systems for discriminating benign from malignant ovarian masses, but more research is needed to determine the optimum diagnostic pathway, especially one yielding the least false-negative results.

The anti-staphylococcal fusidic acid as an efflux pump inhibitor combined with fluconazole against vaginal candidiasis in mouse model.

BACKGROUND: Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC). OBJECTIVES: This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates. METHODS: The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis. RESULTS: Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue. CONCLUSION: The current findings highlight FA's potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.

Low dose post-transplant cyclophosphamide and sirolimus induce mixed chimerism with CTLA4-Ig or lymphocyte depletion in an MHC-mismatched murine allotransplantation model.

Allogeneic hematopoietic cell transplantation (allo-HCT) offers a curative option for patients with certain non-malignant hematological diseases. High-dose post-transplant cyclophosphamide (PT-Cy) (200 mg/kg) and sirolimus (3 mg/kg), (HiC) synergistically induce stable mixed chimerism. Further, sirolimus and cytotoxic T lymphocyte-associated antigen-4 immunoglobulin (CTLA4-Ig), also known as Abatacept (Aba), promote immune tolerance and allograft survival. Here, in a major histocompatibility complex (MHC)-mismatched allo-HCT murine model, we combined Aba and/or T-cell depleting anti-Thy1.2 (Thy) with a lower dose of PT-Cy (50 mg/kg) and Sirolimus (3 mg/kg), (LoC). While mice in the LoC group showed graft rejection, the addition of Thy to LoC induced similar donor chimerism levels when compared to the HiC group. However, the addition of Aba to LoC led to graft acceptance only in younger mice. When Thy was added to the LoC+Aba setting, graft acceptance was restored in both age groups. Engrafted groups displayed significantly reduced frequencies of recipient-specific interferon-γ-producing T cells as well as an increased frequency in regulatory T cells (Tregs) except in the LoC+Aba group. Splenocytes from engrafted mice showed no proliferation upon restimulation with Balb/c stimulators. Collectively, in combination with Aba or Thy, LoC may be considered to reduce graft rejection in patients who undergo allo-HCT.

Role of research Laboratories in pandemic and epidemic response in the Eastern Mediterranean Region: Experiences from COVID-19, avian influenza, and MERS-CoV.

We share the experience of research laboratories in the Eastern Mediterranean Region (EMR) that contributed to preparedness and response to highly pathogenic avian influenza (HPAI), Middle-East respiratory syndrome coronavirus (MERS-CoV), and coronavirus disease (COVID-19). Research groups in the region were pivotal in identifying, characterizing the pathogens and describing their evolution, distribution, transmission routes, and the immunological profile of exposed populations. They demonstrated the capacity to develop and test antivirals and potential vaccines. The EMR experience is a model of how national systems can work with researchers to improve regional preparedness and response to future epidemics and pandemics.

Facile synthesis and characterization of a magnetic biosorbent derived from sodium alginate and activated graphite schist: Experimental and statistical physics analysis for Mn(VII) remediation.

H2O2-modified graphite schist (GS) and sodium alginate (SA) interface was loaded by Fe3O4 nanoparticles (MNPs) to prepare a magnetic biosorbent that was employed in removing Mn(VII) from solutions. The prepared GS/SA/MNPs adsorbent was investigated using a variety of techniques, including elemental mapping, TEM, XPS, FTIR, FESEM, EDX, XRD, XPS, and zeta potential. An experimental study supported by statistical physics calculations was carried out to obtain a new outline of the Mn(VII) uptake mechanism. The classical Freundlich and the statistical physical double-layer models adequately described the Mn(VII) uptake process at pH 3.0 and a temperature of 25-55 °C. The removed number of Mn ions (such as Mn+7 and Mn+2) per GS/SA/MNPs active site ranged from 0.70 to 0.84, indicating a mixed adsorption orientation driven by surface complexation and attraction forces mechanisms. The adsorption energies (∆E) calculated by the double-layer model ranged from 18.79 to 24.94 kJ/mol, suggesting that the interaction between Mn(VII) and GS/SA/MNPs was controlled by physical forces. Increasing the adsorption capacity at saturation (Qsat) from 333.14 to 369.52 mg/g with temperature proposed an endothermic capture process. Thermodynamic functions clarified the viability and spontaneity of Mn(VII) uptake on the GS/SA/MNPs adsorbent.

The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice.

PURPOSE: Roux-en-Y gastric bypass (RYGB) leads to the improvement of many obesity-associated conditions. The degree to which post-operative macronutrient composition contributes to metabolic improvement after RYGB is understudied. METHODS: A mouse model of RYGB was used to examine the effects of diet on the post-operative outcomes of RYGB. Obese mice underwent either Sham or RYGB surgery and were administered either chow or HFD and then monitored for an additional 8 weeks. RESULTS: After RYGB, reductions to body weight, fat mass, and lean mass were similar regardless of diet. RYGB and HFD were independently detrimental to bone mineral density and plasma vitamin D levels. Independent of surgery, HFD accelerated hematopoietic stem and progenitor cell proliferation and differentiation and exhibited greater myeloid lineage commitment. Independent of diet, systemic iron deficiency was present after RYGB. In both Sham and RYGB groups, HFD increased energy expenditure. RYGB increased fecal energy loss, and HFD after RYGB increased fecal lipid content. RYGB lowered fasting glucose and liver glycogen levels but HFD had an opposing effect. Indices of insulin sensitivity improved independent of diet. HFD impaired improvements to dyslipidemia, NAFLD, and fibrosis. CONCLUSION: Post-operative diet plays a significant role in determining the degree to which RYGB reverses obesity-induced metabolic abnormalities such as hyperglycemia, dyslipidemia, and NAFLD. Diet composition may be targeted in order to assist in the treatment of post-RYGB bone mineral density loss and vitamin D deficiency as well as to reverse myeloid lineage commitment. HFD after RYGB continues to pose a significant multidimensional health risk.

Preparation of novel S-allyl cysteine chitosan based nanoparticles for use in ischemic brain treatment.

Objective: To enhance the brain bioavailability of S-allyl-l-cysteine (SC) by developing novel S-allyl-l-cysteine chitosan nanoparticles (SC CS NPs) and examining the quantity of SC by developing a novel method of ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in ischemic rat brain treatment. Methods: The ionotropic gelation method was used to develop S-allyl cysteine-loaded CS NPs. The 4-factor, 5-level central composite design was optimized to determine the effect of independent variables, i.e., particle size, polydispersity index (PDI), zeta potential, EE, and loading capacity, together with their characterization, followed by drug release and intranasal permeation to enhance the brain bioavailability and examination of their neurobehavioral and biochemical parameters with their histopathological examination. Results: SC CS NPs were optimized at the particle size of 93.21 ± 3.31 nm (PDI: 0.317 ± 0.003), zeta potential of 44.4 ± 2.93, and drug loading of 41.23 ± 1.97% with an entrapment efficiency of 82.61 ± 4.93% having sustain and controlled release (79.92 ± 3.86%) with great permeation (>80.0%) of SC. SC showed the retention time of 1.021 min and 162.50/73.05 m/z. SC showed good linearity in the range of 5.0-1300.0 ng mL-1, % inter-and-intraday accuracy of 96.00-99.06% and CV of 4.38-4.38%. We observed significant results, i.e., p < 0.001 for improved (AUC)0-24 and Cmax delivered via i.v. and i.n. dose. We also observed the highly significantly observations of SC CS NPs (i.n.) based on their treatment results for the biochemical, neurobehavioral, and histopathological examination in the developed ischemic MCAO brain rat model. Conclusion: The excellent significant role of mucoadhesive CS NPs of SC was proven based on the enhancement in the brain bioavailability of SC via i.n. delivery in rats and easy targeting of the brain for ischemic brain treatment followed by an improvement in neuroprotection based on a very small dose of SC.

Anti-rheumatic colchicine phytochemical exhibits potent antiviral activities against avian and seasonal Influenza A viruses (IAVs) via targeting different stages of IAV replication cycle.

BACKGROUND: The continuous evolution of drug-resistant influenza viruses highlights the necessity for repurposing naturally-derived and safe phytochemicals with anti-influenza activity as novel broad-spectrum anti-influenza medications. METHODS: In this study, nitrogenous alkaloids were tested for their viral inhibitory activity against influenza A/H1N1 and A/H5N1 viruses. The cytotoxicity of tested alkaloids on MDCK showed a high safety range (CC50 > 200 µg/ml), permitting the screening for their anti-influenza potential. RESULTS: Herein, atropine sulphate, pilocarpine hydrochloride and colchicine displayed anti-H5N1 activities with IC50 values of 2.300, 0.210 and 0.111 µg/ml, respectively. Validation of the IC50 values was further depicted by testing the three highly effective alkaloids, based on their potent IC50 values against seasonal influenza A/H1N1 virus, showing comparable IC50 values of 0.204, 0.637 and 0.326 µg/ml, respectively. Further investigation suggests that colchicine could suppress viral infection by primarily interfering with IAV replication and inhibiting viral adsorption, while atropine sulphate and pilocarpine hydrochloride could directly affect the virus in a cell-free virucidal effect. Interestingly, the in silico molecular docking studies suggest the abilities of atropine, pilocarpine, and colchicine to bind correctly inside the active sites of the neuraminidases of both influenza A/H1N1 and A/H5N1 viruses. The three alkaloids exhibited good binding energies as well as excellent binding modes that were similar to the co-crystallized ligands. On the other hand, consistent with in vitro results, only colchicine could bind correctly against the M2-proton channel of influenza A viruses (IAVs). This might explicate the in vitro antiviral activity of colchicine at the replication stage of the virus replication cycle. CONCLUSION: This study highlighted the anti-influenza efficacy of biologically active alkaloids including colchicine. Therefore, these alkaloids should be further characterized in vivo (preclinical and clinical studies) to be developed as anti-IAV agents.

Synthesis and biological evaluation of new nicotinic acid derivatives as potential anti-inflammatory agents with enhanced gastric safety profile.

Two innovative series derived from nicotinic acid scaffold were synthesized and evaluated for their anti-inflammatory activity. Ibuprofen, celecoxib and indomethacin were used as standard drugs. All the newly synthesized compounds were in vitro screened for their anti-inflammatory activity adopting 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide dye (MTT), as well as Griess assays. The results showed that all compounds exhibited significant anti-inflammatory activity without affecting the viability of the macrophages compared to ibuprofen. In addition, compounds 4d, 4f, 4g, 4h and 5b exhibited the most potent nitrite inhibition activity and consequently superior anti-inflammatory activity with MTT results ranging between values 86.109 ± 0.51 to 119.084 ± 0.09. The most active compounds were subjected to evaluation of TNF-α, IL-6, iNOS and COX-2 levels in LPS/INF γ-stimulated RAW 264.7 macrophage cells in comparison to ibuprofen as a reference compound. The five compounds showed comparable inhibition potency of these inflammatory cytokines compared to ibuprofen. Same compounds were further in vivo evaluated for their anti-inflammatory activity via carrageenan induced arthritis in rats. Regarding the ulcerogenic profile, compound 4h showed mild infiltration of gastric mucosa superb to compound 5b displayed severe gastritis. Molecular docking of 4h and 5b in the COX-2 active site was performed to evaluate their preferential COX-2 inhibitory potency. The docking results were in accordance with the biological findings.

The Anti-Virulence Activities of the Antihypertensive Drug Propranolol in Light of Its Anti-Quorum Sensing Effects against Pseudomonas aeruginosa and Serratia marcescens.

The development of bacterial resistance is an increasing global concern that requires discovering new antibacterial agents and strategies. Bacterial quorum sensing (QS) systems play important roles in controlling bacterial virulence, and their targeting could lead to diminishing bacterial pathogenesis. In this context, targeting QS systems without significant influence on bacterial growth is assumed as a promising strategy to overcome resistance development. This study aimed at evaluating the anti-QS and anti-virulence activities of the ß-adrenoreceptor antagonist propranolol at sub-minimal inhibitory concentrations (sub-MIC) against two Gram-negative bacterial models Pseudomonas aeruginosa and Serratia marcescens. The effect of propranolol on the expression of QS-encoding genes was evaluated. Additionally, the affinity of propranolol to QS receptors was virtually attested. The influence of propranolol at sub-MIC on biofilm formation, motility, and production of virulent factors was conducted. The outcomes of the propranolol combination with different antibiotics were assessed. Finally, the in vivo protection assay in mice was performed to assess propranolol's effect on lessening the bacterial pathogenesis. The current findings emphasized the significant ability of propranolol at sub-MIC to reduce the formation of biofilms, motility, and production of virulence factors. In addition, propranolol at sub-MIC decreased the capacity of tested bacteria to induce pathogenesis in mice. Furthermore, propranolol significantly downregulated the QS-encoding genes and showed significant affinity to QS receptors. Finally, propranolol at sub-MIC synergistically decreased the MICs of different antibiotics against tested bacteria. In conclusion, propranolol might serve as a plausible adjuvant therapy with antibiotics for the treatment of serious bacterial infections after further pharmacological and pharmaceutical studies.

Prolonging the Durability of Maritime Constructions through a Sustainable and Salt-Resistant Cement Composite.

This research investigates the long-term resilience of an environmentally friendly cement blend comprising Egyptian Ordinary Portland Cement OPC and Ground-Granulated Blast Furnace Slag GGBFS when exposed to a corrosive seawater environment. This scientific investigation explores the effects of exposure to seawater on various properties of cement pastes, encompassing parameters such as free lime content (FLC), chemically combined water content (CWC), bulk density (BD), total porosity (ϕ), total sulfate content, total chloride content, and compressive strength (CS). By contrast, Differential Thermal Analysis (DTA), FT-IR spectroscopy, and X-ray diffraction (XRD) analysis can be utilized to investigate the influence of exposure to seawater on the hydration products of GGBFS cement pastes over a period of up to one year. This analytical approach offers valuable insights into the alterations that occur in hydration products and their resilience when subjected to seawater conditions. The results obtained from this investigation reveal that all cement pastes incorporating GGBFS exhibit heightened resistance to deterioration in seawater, with slag cement containing 60 wt. % GGBFS and achieving a notable compressive strength of 85.7 Mpa after one year of immersion in seawater. These findings underscore the capacity of these cement blends to effectively withstand challenges in durability in marine environments.

Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E.

Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus 229E (HCoV-229E), were investigated using in silico and in vitro studies. We identified potential broad-spectrum inhibitor effects of Hydroxocobalamin and Methylcobalamin against the three tested CoVs. Cyanocobalamin could selectively affect SARS-CoV-2 but not MERS-CoV and HCoV-229E. Methylcobalamin showed significantly higher inhibition values on SARS-CoV-2 compared with Hydroxocobalamin and Cyanocobalamin, while Hydroxocobalamin showed the highest potent antiviral activity against MERS-CoV and Cyanocobalamin against HCoV-229E. Furthermore, in silico studies were performed for these promising vitamins to investigate their interaction with SARS-CoV-2, MERS-CoV, and HCoV-229E viral-specific cell receptors (ACE2, DPP4, and hAPN protein, respectively) and viral proteins (S-RBD, 3CL pro, RdRp), suggesting that Hydroxocobalamin, Methylcobalamin, and Cyanocobalamin may have significant binding affinity to these proteins. These results show that Methylcobalamin may have potential benefits for coronavirus-infected patients.