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Protein S-palmitoylation is a powerful post-translational modification that regulates protein trafficking, localization, turnover, and signal transduction. Palmitoylation controls several important cellular processes, and, if dysregulated, can lead to cancer, cardiovascular disease, and neurological disorders. The role of protein palmitoylation in mediating resistance to systemic cisplatin-based chemotherapies in cancer is currently unknown. This is of particular interest because cisplatin is currently the gold standard of treatment for bladder cancer (BC), and there are no feasible options after resistance is acquired. Using unbiased global proteomic profiling of purified S-palmitoylated peptides combined with intensive bioinformatics analyses, we identified 506 candidate palmitoylated proteins significantly enriched in cisplatin-resistant BC cells. One of these proteins included PD-L1, which is highly palmitoylated in resistant cells. Pharmacological inhibition of fatty acid synthase (FASN) suppressed PD-L1 palmitoylation and expression, which suggests the potential use of FASN-PD-L1-targeted therapeutic strategies in BC patients. Taken together, these results highlight the role of protein palmitoylation in mediating BC chemoresistance.The emergence of SARS-CoV-2 virus and its associated disease COVID-19 have triggered significant threats to public health, in addition to political and social changes. An important number of studies have reported the onset of symptoms compatible with pneumonia accompanied by coagulopathy and lymphocytopenia during COVID-19. Increased cytokine levels, the emergence of acute phase reactants, platelet activation and immune checkpoint expression are some of the biomarkers postulated in this context. selleck inhibitor As previously observed in prolonged sepsis, T-cell exhaustion due to SARS-CoV-2 and even their reduction in numbers due to apoptosis hinder the response to the infection. In this review, we synthesized the immune changes observed during COVID-19, the role of immune molecules as severity markers for patient stratification and their associated therapeutic options.
The main aim of this study is to estimate the economic burden and prevalence of bites and stings injuries in Saudi Arabia.
A retrospective, cross-sectional study was conducted at King Saud University Medical City (KSUMC) for all bites and stings cases presented to the Emergency Department (ED) between the period June 2015 and May 2019.
A total of 1328 bites and stings cases were treated in the ED at KSUMC. There were 886 insect bites and stings cases, 376 animal bites, 22 human bites, 34 scorpion stings, and ten snakebites. Most cases were reported in April - June. Females account for 62% of the reported cases, and the mean age was 24years old. The total management cost of bite and sting cases during the study period was 3.4 million Saudi Riyal (SR). The spending cost of the management of animal bites was the highest as it cost 1,681,920.76 SR, followed by insect's management costing 1,228,623.68 SR.
Bites and stings have a considerable health care burden on our society. Although the vast majority of the cases were not associated with a severe life-threatening condition, many were visit ED and associated with high medical costs. Increased awareness of the hazards of animal-related injuries, especially during spring and summer, where most cases take place may lower its incidence and decrease EDs visits.
Bites and stings have a considerable health care burden on our society. Although the vast majority of the cases were not associated with a severe life-threatening condition, many were visit ED and associated with high medical costs. Increased awareness of the hazards of animal-related injuries, especially during spring and summer, where most cases take place may lower its incidence and decrease EDs visits.Sennoside A (dianthrone glycoside) shows laxative properties and used as a folk traditional medicine. Sennoside A capped silver nanoparticles (Ag/sennoside A) were synthesized at room temperature for the first time by using sennoside A as reducing and capping agent. UV-visible spectroscopic data reveals that the absorption peaks of pure sennoside A was appeared at 266, and 340 nm, which red shifted to 304, and 354 nm at higher sennoside A concentration. Upon addition of the Ag+ ions, an additional peak also observed at 398 nm, indicating the formation of spherical sennoside A capped silver nanoparticles (Ag/sennoside A). Cetyltrimethylammonium bromide (CTAB) was used a stabilizing agent to determine the role of cationic micelles on the nucleation and growth processes of Ag/sennoside A NPs formation. The 2,2-diphenyl-1-picrylhydrazyl nitrogen radical (DPPH · ), two bacteria strains (Staphylococcus aureus and Escherichia coli) and two yeast strains (Candida albicans ATCC 10231 and Candida parapsilosis ATCC 22019) were used to determine the antioxidant and antimicrobial properties of Ag/sennoside A NPs. In addition, Rhein-9-anthrone (4,5-dihydroxy-10-oxo-9H-anthracene-2-carboxylate) was isolated from the acidic hydrolysis of glycoside linkage of sennoside A and characterized. The antioxidant and antimicrobial activities of rhein-9-anthrone were also determined against DPPH radical, antibacterial and antifungal strains. The minimum inhibitory concentration was determined and discussed.The present study involves the development of Dipivefrin hydrochloride (DV) containing Poloxamers (P407 and P188)-Carbopol-934 (CP) based thermoresponsive-gels for the management of elevated intraocular pressure (IOP). Optimal formulation was evaluated for gelation temperature (Tgel), physicochemical and viscoelastic properties, in-vitro gel dissolution and drug release studies. The in-vivo safety, precorneal retention, ocular pharmacokinetics and efficacy in reducing IOP were also evaluated. Tgel of DV-containing thermoresponsive-gels were between 35.1 and 38.9 °C and it was Poloxamers and CP concentrations dependent. The optimal formulation (F8), composed of 20% P407, 5% P188 and 0.15% CP (w/v), had a Tgel of 35 °C. Its viscosity indicated good flow at room temperature and ability to convert to gel at ocular temperature and the rheology studies revealed favorable characteristics for its ocular use. In precorneal retention experiment, F8 indicated significantly higher area under concentrations curves as compared to DV-aqueous suspension (DV-AqS).
Homepage: https://www.selleckchem.com/products/nuciferine.html
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