The efficacy of these drugs against ZIKV can be further analyzed through in-vitro and in-vivo studies.Based on the pharmacophore model of melatonin (MT1) receptor, we recently synthesized a series of indole derivatives that showed anticonvulsant activity with low neurotoxicity and hepatotoxicity in rodents. In the present study, the three most potent C3-modified derivatives with hydrazine structure 3c, 3e, and 3f, with 2-chlorophenyl, 2-furyl, and 2-thienyl fragments, respectively, were selected, and their neurobiological activity was explored in mice. In Experiment #1, the dose-dependent anxiolytic effect of a single i.p. administration of the novel compounds at doses of 10, 30, and 60 mg/kg were studied in the open field (OF) test. In Experiment#2, the analgesic effect of 3c, 3e, and 3f (30-100 mg/kg) was tested in the hot plate test and formalin test. Experiment#3 was designed to assess the antidepressant-like activity of 3c, 3e, and 3f (10-60 mg/kg). The forced swimming test (FST) and tail suspension test (TST)-induced effect on markers of oxidative stress in the frontal cortex (FC), and the hippocampus was evaluated. Melatonin was used in the same doses as melatonin analogs in all three experiments as a positive control. Desipramine (10 mg/kg) was also applied as a control in the FST. The three melatonin analogs bearing hydrazide/hydrazone substitution at 3C of the indol scaffold demonstrated improved antidepressant-like activity compared to the melatonin. The tested substances are devoided of anxiolytic effects. The antioxidant activity of the melatonin analogs and analgesic potential is comparable to that of melatonin. The 3C substitution with hydrazide/hydrazone moiety substantially contributes to the antidepressant and antioxidant activity of the melatonin analogs.Conjunctivitis, caused by bacterial infections, represents health concern and diagnosis of the disease is pivotal for the proper selection of the treatment. The main causes of bacterial conjunctivitis vary in different countries. The current study investigated the common bacterial causes of bacterial conjunctivitis from eye clinics' attendants and evaluated the effectiveness of different therapeutic approaches. Eye swabs from patients, diagnosed with conjunctivitis, were assessed microbiologically and the isolated bacteria were identified using the standard biochemical identification and sequencing of the 16S rRNA gene. Antibiotics' susceptibility of the conjunctivitis-associated bacterial pathogens was evaluated against nineteen broad-spectrum antibiotics. In the meanwhile, cell-free preparations from probiotic Lactobacillus and Bifidobacterium strains were used to evaluate their antagonistic activities. Findings from this study showed that out of 52 specimen, 17 eye swabs from patients with conjunctivitis were bacterial culture-positive. The identity of the bacterial species, using the biochemical identification system, was Staphylococcus aureus (4 isolates) and S. epidermidis (13 isolates). Staphylococcus spp. showed susceptibility to linezolid, vancomycin, novobiocin, and fluoroquinolones (norfloxacin, ofloxacin, ciprofloxacin and levofloxacin). However, isolates from the two Staphylococcus spp. expressed resistance to penicillin G, oxacillin, and cephalexin. As alternatives to antibiotics, the growth of Staphylococcus spp., including isolates with antibiotic resistance, was inhibited by cell-free preparations of the 4 probiotic Lactobacillus and the 2 Bifidobacterium strains. These findings provide evidence that topical antibiotics such as fluoroquinolones are still effective antimicrobial agents against staphylococci associated with conjunctivitis whereas probiotic preparations could be promising for further research to pave the way for their therapeutic applications against ophthalmic diseases.Rheumatoid arthritis (RA) is considered a debilitating disease that increases the risk of significant morbidity and premature mortality. To circumvent drug-related toxicity and ineffectiveness of anti-inflammatory drugs, there is a significant need for an advanced delivery system that increases bioavailability. The feasibility of in situ gel of methotrexate sodium (MTS) as an effective management for Rheumatoid arthritis was investigated. It was formulated with pluronic F-127 (PLF-127) as primary polymer, hydroxypropyl methylcellulose K4M (HK4M), and polycarbophil (PCL) as a copolymer and characterized by various parameters. The efficacy evaluation by Freund's complete adjuvant (FCA) model, biocompatibility assessment by histopathological studies conducted. The optimized in situ gel (M4) was thermoresponsive, released 93.26 ± 2.39% MTS at 96 hours. In addition, distribution of MTS was even in the optimized sterile and syringeable in situ gel. In vivo studies on wistar rats demonstrated a substantial reduction in paw oedema during the 28-day study period and were biocompatible with the tissues at the injection site. The study was successful in formulating, optimizing MTS in situ gel for effective management of RA.The aim of this study was to develop hydrogel loaded with capsicum extract nanoparticles and wax gourd extract for transdermal delivery of capsaicin. buy kira6 The addition of wax gourd extract was supposed to reduce cytotoxicity of capsaicin in capsicum extract against HaCaT keratinocyte cell line. Capsicum extract nanoparticles were prepared by solvent displacement method using hyaluronic acid as a stabilizer. The physical and chemical stability of capsicum extract nanoparticles were investigated by dynamic light scattering technique and UV-Visible spectrophotometry, respectively. Hydrogel loaded with capsicum extract nanoparticles and wax gourd fruit extract was then formulated by using Carbopol 940® as a gelling agent for transdermal delivery. The skin permeability of capsaicin from the hydrogel was evaluated by Franz diffusion cell approach. The cytotoxicity reduction of capsicum extract nanoparticles and capsicum extract nanoparticles by mixing with wax gourd extract was determined by MTT assay The results showedcytotoxicity, thus may provide a new approach for delivery of capsaicin to reduce cytotoxicity to skin cells.