Background Multisystem inflammatory syndrome in children (MIS-C) is a serious health condition that develops from and is linked to coronavirus disease 2019. MIS-C is considered a multi-organ dysfunction involving cardiac, renal, respiratory, hematologic, gastrointestinal and neurological symptoms and groups of signs and symptoms such as rash or bilateral non-purulent conjunctivitis, hypotension or shock and acute gastrointestinal problems, which require immediate therapeutic intervention to prevent the aggravation of the patient’s health condition. MIS-C is relatively new in the field of evidence-based medicine; however, there are several clinical guidelines for good clinical practice. For every disorder, the guidelines have different suggestions. Hence, based on the current status of the evidence, recommendations have been combined to form a unified guideline for therapeutic management. Methods This paper compares and evaluates the current MIS-C-specific clinical practice guidelines (namely, American Academy of Pediatrics, American College of Rheumatology, Helen DeVos Children’s Hospital Foundation, Children’s Hospital of The King’s Daughters, and the Infectious Diseases Society of America). The compiled literature was then assessed by the authors separately, and an algorithm was proposed for each disorder, taking into consideration the various guidelines proposed for the management of the disorder. Results The features of MIS-C patients are unified; this is very helpful in managing its symptoms and decreasing mortality rates. In addition, recommendations for pharmacological treatment for MIS-C symptoms are formulated after cross-comparison across five different guidelines. Conclusions This study provides a general interpretation of the results in the context of other evidence and implications for future research. It proposes a unified guideline based on the current evidence, with the best potential to maintain suitable clinical standards in the Saudi Arabian Ministry of Health.

NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. The role of TG2 in NGF-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with NGF in N2a and SH-SY5Y cells. NGF mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON (Z-ZON-Val-Pro-Leu-OMe; Benzyloxycarbonyl-(6-Diazo-5-oxonorleucinyl)-l-valinyl-l-prolinyl-l-leucinmethylester) and R283 (1,3,dimethyl-2[2-oxo-propyl]thio)imidazole chloride) and by pharmacological inhibition of extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase B (PKB) and protein kinase C (PKC), and removal of extracellular Ca. Fluorescence microscopy demonstrated NGF induced in situ TG2 activity. TG2 inhibition blocked NGF-induced attenuation of hypoxia-induced cell death and neurite outgrowth in both cell lines. Together, these results demonstrate that NGF stimulates TG2 transamidase activity via a ERK1/2, PKB and PKC-dependent pathway in differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. Furthermore, NGF-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results suggest a novel and important role of TG2 in the cellular functions of NGF.

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Many medicinal plants have been utilized for centuries despite the lack of scientific evidence of their therapeutic effects. This study evaluated the phytochemical and dual biological profiling, namely, antibacterial and cytotoxic properties, of three plant species, namely, Tribulus terrestris L., Typha domingensis Pers., and Ricinus communis L., in order to explore potential relationships (if any) with their ethnopharmacological uses. GC-MS was used to achieve phytochemical screening of two plant extracts (T. terrestris and T. domingensis). The primary chemicals detected in varying amounts in both extracts were siloxane derivatives, fatty acid esters, diisooctyl phthalate, phytosterol, and aromatic acid esters. According to the findings, the major component detected in both extracts was 1,2-benzenedicarboxylic acid and diisooctyl ester (antibacterial and antifungal). T. domingensis contained a low level of benzoic acid, methyl ester (antibacterial). Both extracts included stigmasterol and sitosterol, as well as six different forms of fatty acid esters. Antimicrobial, antioxidant, anticancer, thyroid inhibitor, and anti-inflammatory properties have all been described. Human breast adenocarcinoma (MCF7), human ovary adenocarcinoma (A2780), and human colon adenocarcinoma (HT29), as well as normal human fetal lung fibroblasts (MRC5), all showed cytotoxic activity. The most potent activity against A2780 cells was seen in T. terrestris and T. domingensis extracts (IC50: 3.69 and 5.87 g/mL, respectively). R. communis was more active against MCF7 cells (1.52 μg/mL) followed by A2780 and HT29 cells, respectively. R. communis showed a dose-dependent clonogenic effect against MCF7 cells. The antibacterial activity of all three plant extracts was tested against three standard Gram-positive, four standard Gram-negative, and two clinical bacterial strains. Among the three extracts examined, T. terrestris was the most effective, followed by R. communis, and finally, T. domingensis plant extract was effective against various isolated bacteria. This study, interestingly, sheds light on the bioactive components found in plant extracts that can be utilized for cytotoxic and antibacterial purposes.

Breast cancer is a complex and multi-drug resistant (MDR) disease, which could result in the failure of many chemotherapeutic clinical agents. Discovering effective molecules from natural products or by derivatization from known compounds is the interest of many research studies. The first objective of the present study is to investigate the cytotoxic combinatorial, chemosensitizing, and apoptotic effects of an isatin derived compound (5,5-diphenylimidazolidine-2,4-dione conjugated with 5-substituted isatin, named HAA2021 in the present study) against breast cancer cells (MCF7) and breast cancer cells resistant to doxorubicin (MCF7/ADR) when combined with doxorubicin. The second objective is to investigate the binding mode of HAA2021 withP-glycoprotein (P-gp) and heat shock protein 90 (Hsp90), and to determine whether their co-inhibition by HAA2021 contribute to the increase of the chemosensitization of MCF7/ADR cells to doxorubicin. The combination of HAA2021, at non-toxic doses, with doxorubicin synergistically inhibited the proliferation while inducing significant apoptosis in MCF7 cells. Moreover, HAA2021 increased the chemosensitization of MCF7/ADR cells to doxorubicin, resulting in increased cytotoxicity/selectivity and apoptosis-inducing efficiency compared with the effect of doxorubicin or HAA2021 alone against MCF7/ADR cells. Molecular modeling showed that two molecules of HAA2021 bind to P-gp at the same time, causing P-gp inhibitory effect of the MDR efflux pump, and accumulation of Rhodamine-123 (Rho123) in MCF7/ADR cells. Furthermore, HAA2021 stably interacted with Hsp90α more efficiently compared with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), which was confirmed with the surface plasmon resonance (SPR) and molecular modeling studies. Additionally, HAA2021 showed multi-target effects via the inhibition of Hsp90 and nuclear factor kappa B (NF-𝜅B) proteins in MCF7 and MCF7/ADR cells. Results of real time-PCR also confirmed the synergistic co-inhibition of P-gp/Hsp90α genes in MCF7/ADR cells. Further pharmacokinetic and in vivo studies are warranted for HAA2021 to confirm its anticancer capabilities.

Substance use disorders (SUDs) patients have longer lengths of hospital stay, and more unplanned readmissions than other hospitalized patients. We aim to evaluate SUD-related rehospitalization and length of hospital stay in a major rehabilitation center that serves countries of the Gulf States. In a retrospective cohort study for 16-year data set in Al-Amal Hospital Electronic Health Record in the city of Dammam, Eastern region of Saudi Arabia, patients received services from the SUD treatment programs in the period of January 1, 2005, to December 31, 2021. We used cause-specific Cox proportional hazards regression model to estimate risk of readmission, and general linear model to examine the association between substance use disorders and length of hospital stay. Of the total cohort, 4398 (30.17%) were readmitted within 1 year of discharge date. More than half of the cohort were unemployed patients (52.93%). Patients diagnosed with amphetamine use disorder were 1.36 higher risk of readmission compared to no amphetamine disorder (HR = 1.36; CI (1.04, 1.78) P.02). Patients diagnosed with mental disorder had 7.25 times higher risk of longer hospital stay compared to no mental health disorder (coefficient = 7.25; P < .0001). Amphetamine use disorder increased the risk of readmission. A secondary diagnosis of mental disorders among SUD patients increased length of hospital stay. As a targeted region of amphetamine smuggling in the world, policy and clinical decision-makers in Saudi Arabia and the Gulf States should consider taking proactive steps to minimize the future anticipated high demand for addiction treatment in the region.

Purpose Obesity and overweight pose a threat to health and are more common than undernutrition among adults. It is categorized by fat accumulation and a body mass index (BMI) of > 30. A significant increase in worldwide obesity has been ongoing over several decades. Over the past few years, several strategies have been followed for weight management and to counteract the increasing prevalence of the disease; however, room for improvement with pharmacological options still exists. This review aimed to digest selected past clinical and experimental studies and understand the role of semaglutide treatment for obesity. Methods Articles related to the clinical uses of semaglutide, mechanism of action, pharmacokinetics, pharmacodynamics, and side effects of the drug were identified. Only studies with human subjects who used Semaglutide for obesity management were included and assessed. Results Semaglutide promotes weight loss via appetite and hunger suppression, decreases energy intake, controls eating, and depresses the relative fondness for fatty, energy-dense foods. Moreover, the relationship between obesity and Semaglutide has been widely investigated, and most studies reveal the efficacy of Semaglutide on weight loss. Overall, the pharmacokinetics of semaglutide shows a drop in glycosylated hemoglobin A1c (HbA1c) and total body weight. The usual adverse effects observed in patients treated with Semaglutide include gastrointestinal adverse events, like nausea, vomiting, diarrhea, constipation, and abdominal cramps. Conclusion The findings from the review suggest that semaglutide appears to be beneficial, most notably in its contribution to weight reduction.

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