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OBJECTIVES Semaglutide is a glucagon-like peptide-1 receptor agonist that improves glycemic control and reduces body weight in patients with type 2 diabetes. This study aimed to evaluate the effect of Semaglutide with standard Metformin on glycemic control and BMI after 3 and 6 months of treatment. Additionally, we compared the glycemic control and weight benefits of Semaglutide vs. liraglutide. METHODOLOGY This longitudinal cohort study was conducted in a general practice clinic in Clifton and a family medicine health center in Ziauddin University, Karachi from April 2022 till April 2023. We enrolled 128 patients with type 2 diabetes who were treated with metformin alone. Patients received Semaglutide 2mg once weekly in addition to standard metformin 1gm bid for 6 months. HbA1C and BMI were measured at baseline, 3 months, and 6 months. We compared the glycemic control and weight loss of Semaglutide with a cohort of participants taking Liraglutide over a period of 6 months in the same catchment area in 2021 to determine which drug has an edge over the other. RESULTS Semaglutide was superior to Liraglutide in controlling sugars (HbA1c% reduction 1.13 vs 0.94) as well as in weight loss (10.6 vs 6.2kg) respectively. Single sample t-test showed a statistically significant difference from the hypothetical mean of HbA1C

Antimicrobial resistance is attributed to acquiring new mechanisms by microbes to combat antimicrobial agents, highlighting the necessity to discover new antimicrobial agents to protect human health. Graphene and its derivatives have shown antimicrobial potential due to their physical and chemical distinctive features. Potent antibacterial properties were observed by decorating the surface of graphene and its derivatives with inorganic nanoparticles, such as metal and metal oxide. In an attempt to reliably overcome antimicrobial resistance, the multifunctional nanocomposites, including FeO/NiO, FeO/NiO/GO, FeO/NiO/N-GO, and FeO/NiO/S-GO, were synthesized using a wet chemical method. Accordingly, the structural analysis was performed using X-ray diffraction (XRD), infrared spectroscopy (IR), energy dispersive X-ray (EDX), ultraviolet-visible spectroscopy (UV–vis), and scanning electron microscopy (SEM). For antibacterial potential, the synthesized nanocomposites were tested against non-resistant and resistant strains of bacteria. Notably, moderate antibacterial potential was found for FeO/NiO/N-GO nanocomposite with a MIC value of 12.5 μg/mL, compared to the MIC of pure Ciprofloxacin, a positive control, with a value of 1.25 μg/mL. Toward antifungal potential, the synthesized nanocomposites were assessed against various spores of fungal strains. In this regard, the synthesized nanocomposites were demonstrated as potent antifungal agents. Among the synthesized nanocomposites, FeO/NiO and FeO/NiO/S-GO exhibited the highest ZOI against Aspergillus flavus. Additionally, the activity of these nanocomposites was evaluated by means of total reducing power (TRP), total antioxidant capacity (TAC), and free radical scavenging. Further, the antioxidant, brine shrimp lethality, and hemolytic potential of the synthesized nanocomposites were evaluated to compare their effectiveness. According to brine shrimp lethality, all synthesized nanocomposites were sufficiently active, with a calculated median lethal concentration (LC50) showing ≥ 50 % mortality. The obtained results provide a promising base for the incorporation of nanocomposites in pharmaceutical and biomedical products.

Objective(s): Concerns regarding increased breast cancer cases worldwide have spurred interest in the discovery of novel approaches to overcome this deadly disease. Although several treatment strategies have been developed to treat breast cancer including chemotherapy, an efficient drug delivery system remains a challenge. Here, we study the drug distribution and boosting the efficiency of Panobinostat, a histone deacetylase inhibitor, by using silver nanoparticles as a controlled drug delivery system.Materials and Methods: Green synthesis of silver nanoparticles, as nanocarriers for drug delivery was synthesized by using Rhazya stricta extract and loaded with the drug. These drug-loaded nanoparticles were characterized by UV-vis spectroscopy, XRD, FTIR, SEM, and EDX techniques. Results: The AgNPs had an average size of 20 nm and were stable over a period. The evaluation of drug encapsulation effectiveness and drug release capacity revealed 56% encapsulation efficiency and sustained drug release. The kinetics study of drug release showed the first-order reaction which means that drug concentration is proportional to drug release. The MTT assay showed that drug-loaded AgNPs had a potent and dose-dependent anticancer activity on the breast cancer cell lines (MDA-MB-231). Conclusion: As the successfully green synthesized Panobinostat-AgNPs were stable and exhibited increased in vitro anticancer activity compared with free Panobinostat, our data demonstrate that the combination of AgNPs with Panobinostat improves the drug’s long-term viability, effectiveness, and active targeting as a potential targeted therapeutic molecule for the treatment of cancer. To strengthen the utilization of this combination therapy in cancer therapy trials, further research is warranted in vivo.

Background: Newcastle disease virus (NDV) is a highly contagious and economically devastating pathogen affecting poultry worldwide, leading to significant losses in the poultry industry. Despite existing vaccines, outbreaks continue to occur, highlighting the need for more effective vaccination strategies. Developing a multi-epitopic peptide vaccine offers a promising approach to enhance protection against NDV. Objectives: Here, we aimed to design and evaluate a multi-epitopic vaccine against NDV using molecular dynamics (MD) simulation. Methodology: We retrieved NDV sequences for the fusion (F) protein and hemagglutinin–neuraminidase (HN) protein. Subsequently, B-cell and T-cell epitopes were predicted. The top potential epitopes were utilized to design the vaccine construct, which was subsequently docked against chicken TLR4 and MHC1 receptors to assess the immunological response. The resulting docked complex underwent a 1 microsecond (1000 ns) MD simulation. For experimental evaluation, the vaccine’s efficacy was assessed in mice and chickens using a controlled study design, where animals were randomly divided into groups receiving either a local ND vaccine or the peptide vaccine or a control treatment. Results: The 40 amino acid peptide vaccine demonstrated strong binding affinity and stability within the TLR4 and MHC1 receptor–peptide complexes. The root mean square deviation of peptide vaccine and TLR4 receptor showed rapid stabilization after an initial repositioning. The root mean square fluctuation revealed relatively low fluctuations (below 3 Å) for the TLR4 receptor, while the peptide exhibited higher fluctuations. The overall binding energy of the peptide vaccine with TLR4 and MHC1 receptors amounted to −15.7 kcal·mol−1 and −36.8 kcal·mol−1, respectively. For experimental evaluations in mice and chicken, the peptide vaccine was synthesized using services of GeneScript Biotech® (Singapore) PTE Limited. Experimental evaluations showed a significant immune response in both mice and chickens, with the vaccine eliciting robust antibody production, as evidenced by increasing HI titers over time. Statistical analysis was performed using an independent t-test with Type-II error to compare the groups, calculating the p-values to determine the significance of the immune response between different groups. Conclusions: Multi-epitopic peptide vaccine has demonstrated a good immunological response in natural hosts.

Upon host cell infection, viruses modulate their host cells to better suit their needs, including the downregulation of virus entry receptors. ADAM17, a cell surface sheddase, is an essential factor for infection of bovine cells with several pestiviruses. To assess the effect of pestivirus infection on ADAM17, the amounts of cellular ADAM17 and its presence at the cell surface were determined. Mature ADAM17 levels were reduced upon infection with a cytopathic pestivirus bovis (bovine viral diarrhea virus, cpBVDV), pestivirus suis (classical swine fever virus, CSFV) or pestivirus giraffae (strain giraffe), but not negatively affected by pestivirus L (Linda virus, LindaV). A comparable reduction of ADAM17 surface levels, which represents the bioactive form, could be observed in the presence of E2 of BVDV and CSFV, but not LindaV or atypical porcine pestivirus (pestivirus scrofae) E2. Superinfection exclusion in BVDV infection is caused by at least two proteins, glycoprotein E2 and protease/helicase NS3. To evaluate whether the lowered ADAM17 levels could be involved in superinfection exclusion, persistently CSFV- or LindaV-infected cells were challenged with different pestiviruses. Persistently LindaV-infected cells were significantly more susceptible to cpBVDV infection than persistently CSFV-infected cells, whilst the other pestiviruses tested were not or only hardly able to infect the persistently infected cells. These results provide evidence of a pestivirus species-specific effect on ADAM17 levels and hints at the possibility of its involvement in superinfection exclusion.

Background: Severe COVID-19 leads to acute respiratory distress syndrome (ARDS) and causes lung injury and covid Pneumonia. This lung injury is accompanied by a strong inflammatory response marked by very high levels of various cytokines in the serum. The objective of this study was to analyze the frequency of covid pneumonia in all affected patients and to observe the clinical cascade determining the poor prognostic markers. Methods: This cross-sectional study selected 83 patients (>18 years) with reactive RT-PCR from April 2020 to March 2021. Non-reactive patients on RT-PCR but proven Covid 19 on HRCT, CO-RADS Category 5 and 6 were also included in the study. Clinical cascade was observed in week 1 and week 2 along with cytokine storm markers. Data were analyzed using SPSS version 20. The correlation was assessed through an independent t-test and p-value

The search for ecofriendly products to reduce crop dependence on synthetic chemical fertilizers presents a new challenge. The present study aims to isolate and select efficient native PGPB that can reduce reliance on synthetic NPK fertilizers. A total of 41 bacteria were isolated from the sediment and roots of mangrove trees (Avicennia marina) and assessed for their PGP traits under in vitro conditions. Of them, only two compatible strains of Bacillus species were selected to be used individually and in a mix to promote tomato seedling growth. The efficiency of three inoculants applied to the soil was assessed in a pot experiment at varying rates of synthetic NPK fertilization (0, 50, and 100% NPK). The experiment was set up in a completely randomized design with three replications. Results showed that the different inoculants significantly increased almost all the studied parameters. However, their effectiveness is strongly linked to the applied rate of synthetic fertilization. Applying bacterial inoculant with only 50% NPK significantly increased the plant height (44-51%), digital biomass (60-86%), leaf area (77-87%), greenness average (29-36%), normalized difference vegetation index (29%), shoot dry weight (82-92%) and root dry weight (160-205%) compared to control plants. Concerning the photosynthetic activity, this treatment showed a positive impact on the concentrations of chlorophyll a (25-31%), chlorophyll b (34-39%), and carotenoid (45-49%). Interestingly, these increases ensured the highest values significantly similar to or higher than those of control plants given 100% NPK. Furthermore, the highest accumulation of N, P, K, Cu, Fe, Zn, and Ca in tomato shoots was recorded in plants inoculated with the bacterial mix at 50% NPK. It was proven for the first time that the native PGP bacteria derived from mangrove plant species A. marina positively affects the quality of tomato seedlings while reducing 50% NPK.

Muteb Alanazi,1 Hassan Mohammed Alqahtani,1 Mohammad Khalid Alshammari,1 Raad Mohammed Alshammari,1 Jonaid Ahmad Malik,2,3 Sakeel Ahmed,4 Mir Aroosa,5 Mrunal Shinde,6 Tareq Nafea Alharby,1 Mukhtar Ansari,1 Arshad Hussain,1 Fahad F Alkhrshawy,7 Sirajudheen Anwar8 1Department of Clinical Pharmacy, College of Pharmacy, University of Hail, Hail, Saudi Arabia; 2Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Guwahati, India; 3Department of Biomedical Engineering, Indian Institute of Technology Ropar, Rupnagar, India; 4Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Ahmedabad, India; 5Department of Pharmacology and Toxicology, Jamia Hamdard, New Delhi, India; 6Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Guwahati, India; 7Pharmaceutical Care Department, Hail General Hospital - Hail Health Cluster, Hail, Saudi Arabia; 8Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail, Saudi ArabiaCorrespondence: Sirajudheen Anwar, Email si.anwar@uoh.edu.saObjective: Identifying the burden of disease and the condition of the Saudi population is in high demand from both a surveillance and analytical standpoint. The objective of this study was to determine the most prevalent infections among hospitalized patients (both community-acquired and hospital-acquired), the antibiotics prescribing pattern, and their relationship with patient characteristics like age and gender.Methods: A retrospective study was conducted comprising 2646 patients with infectious diseases or complications admitted to a tertiary hospital in the Hail region of Saudi Arabia. A standardized form was used to collect information from patient’s medical records. Demographic data such as age, gender, prescribed antibiotics, and culture-sensitivity tests were included in the study.Results: Males represented about two-thirds (66.5%, n = 1760) of the patients. Most patients (45.9%) who suffered from infectious diseases were between the ages of 20 and 39. The most prevalent infectious ailment was respiratory tract infection (17.65%, n = 467). Furthermore, the most common multiple infectious diseases were gallbladder calculi with cholecystitis (40.3%, n = 69). Similarly, COVID-19 had the greatest impact on people over 60. Beta-lactam antibiotics were the most commonly prescribed (37.6%), followed by fluoroquinolones (26.26%) and macrolides (13.45%). But performing culture sensitivity tests were rather uncommon (3.8%, n = 101). For multiple infections, beta-lactam antibiotics (such as amoxicillin and cefuroxime) were the most commonly prescribed antibiotics (2.26%, n = 60), followed by macrolides (such as azithromycin and Clindamycin) and fluoroquinolones (eg, ciprofloxacin and levofloxacin).Conclusion: Respiratory tract infections are the most prevalent infectious disease among hospital patients, who are primarily in their 20s. The frequency of performing culture tests is low. Therefore, it is important to promote culture sensitivity testing in order to support the prudent use of antibiotics. Guidelines for anti-microbial stewardship programs are also highly recommended.Keywords: antibiotics, infections, prescribing pattern, Hail region, Saudi Arabia