Novel spiroimidazopyridine derivative SAK3 improves methimazole-induced cognitive deficits in mice.

Methimazole (MMI) is a first-line therapy used to manage hyperthyroidism and Graves' disease. Despite its therapeutic benefit, chronic MMI administration can lead to hypothyroidism and perturb brain homeostasis in patients, resulting in neuropsychiatric disorders such as depression and cognitive dysfunction. We recently developed the spiroimidazopyridine derivative SAK3 as cognitive enhancer; however, mechanisms underlying its activity remained unclear. Here, we show that SAK3 potentially improves cognitive impairment seen following MMI-induced hypothyroidism. Twenty-four hours after MMI (75 mg/kg, i.p.) treatment, we administered SAK3 (0.1, 0.5 and 1 mg/kg, p.o.) to mice daily for 7 days. MMI treatment alone disrupted olfactory bulb (OB) glomerular structure, as assessed by staining with the olfactory marker protein (OMP), reduced the number of choline acetyl transferase (ChAT)-immunoreactive neurons in medial septum (MS), and significantly impaired cognition. SAK3 (0.5 and 1 mg/kg, p.o.) administration significantly restored the number of cholinergic MS neurons in MMI-treated mice, and SAK3 treatment at a higher dose significantly improved cognitive deficits seen in MMI-treated control mice. Overall, our study suggests that SAK3 treatment could antagonize such impairment in patients with hypothyroidism.

Awareness and Preparedness of Fomite Transmission Among Malaysian Online Shoppers: A Cross-Sectional Survey

@#Introduction: COVID-19 outbreak is the greatest communicable disease that hit globally, caused by SARS-CoV-2 virus. Malaysia commenced a Movement Control Order (MCO) to contain the epidemic, and thereby altered consumer’s purchasing pattern drastically into online shopping, thus increase the demand of delivery services. The virus able to survive on surfaces up until 9 days depending on the type of surface. Nonetheless, the negligence of proper hygiene management among the vendor, the courier or the user can trigger fomite transmission. The aims of this study were to determine the level of awareness and readiness of fomite transmission caused by COVID-19 among Malaysian online shoppers by evaluating knowledge, precautionary measurements and psychological state. Methods: Convenience sampling method was used for data collection, and 416 respondents participated. The survey instrument comprised of 2 parts; socio-demographic characteristics and the second part consist of COVID-19 transmission as well as its survivability, precautions and psychological state during the outbreak. This was transferred to a Google form and the link was shared through social medias. Data were analysed using SPSS software v.23.0. Results: In spite of the fact that 88% of respondents worried about being infected with COVID-19 and well informed regarding fomite transmission, almost half of respondents (42.3%) did not sanitize their parcels received from outside. Conclusion: In light of this, health authorities should implement more campaigns to emphasize the utmost importance of disinfection of any foreign items by consumers and it is strongly believed that it will provide enhanced protection against fomite transmission.

Dillenia suffruticosa exhibited antioxidant and cytotoxic activity through induction of apoptosis and G2/M cell cycle arrest.

ETHNOPHARMACOLOGICAL RELEVANCE: Dillenia suffruticosa (Family: Dilleniaceae) locally known as Simpoh air has been reported to be used traditionally to treat cancerous growth. Therefore, the present study was attempted to investigate the antioxidant and cytotoxic properties of different parts (root, flower, fruit and leaf) of D. suffruticosa extracts. METHODS AND MATERIALS: In this study, direct solvent extraction (aqueous and methanol) from different parts of D. suffruticosa (root, flower, fruit and leaf) were carried out. Antioxidant activities of D. suffruticosa extract were determined by using DPPH, ABTS FRAP and ß-carotene bleaching assays. Cytotoxicity and cell cycle arrest of the active extract were determined using MTT assay and flow cytometer, respectively. Sequential solvent extraction (hexane, DCM, EtOAc, and MeOH) were also carried out in root of D. suffruticosa to further evaluate the antioxidant and cytotoxic activity of the different solvent extracts. RESULTS: Methanol (MeOH) root extract showed the highest TPC, antioxidant and cytotoxic activities (especially towards HeLa) compared to others (P<0.05). Based on the results, sequential solvent extraction (hexane, DCM, EtOAc and MeOH) was carried out in the roots of D. suffruticosa. MeOH extract exhibited the highest antioxidant activities among others and significantly correlated (P<0.05) with TPC, suggesting the important contribution of phenolic compounds to its antioxidant activity. On the other hand, the DCM and EtOAc exhibited higher cytotoxic activity to selected cancer cells (HeLa, MCF-7, MDA-MB-231, A549 and HT29) compared to others. In short, there is no established correlation between antioxidant and cytotoxic activities of D. suffruticosa extracts indicating that an agent with high antioxidant activities will not necessarily possesses good cytotoxic activities in return. Qualitative phytochemical screening of D. suffruticosa extracts suggested the presence of saponins, triterpenes, sterols, and polyphenolic compounds which are believed to contribute to the cytotoxic activities. CONCLUSION: It is suggested that the cytotoxicity of the active extracts in HeLa was due to the induction of apoptosis and cell cycle arrest at G2/M.