Psoriasis is a prototypic example of an immune-mediated skin disorder, characterized by abnormal keratinocyte differentiation, barrier dysfunction, and excessive production of pro-inflammatory cytokines. Here, a psoriasis-like human reconstructed epidermis (RHE-Pso) model was established by cytokine treatment of HaCaT keratinocytes with a cytokine mixture (IL-1α, TNFα, IFN-γ). This model manifested a psoriasis-like phenotype, characterized by reduced TER values, altered epidermal histomorphology, as well as a reduction in Filaggrin (FLG) expression at the protein as well as mRNA levels, accompanied by a marked enhancement in the release of cytokines like IL-1α, IL-8, TNFα, and IFN-γ. Later, this RHE-Pso model has been employed to assess various pharmacologic as well as natural agents. Clobetasol propionate emerged as one of the most effective agents in reclaiming TER values, increasing FLG mRNA expression (3.40 ± 0.37-fold of control), as well as curtailing the release of cytokines. Retinoic acid increased FLG mRNA (2.85 ± 0.35-fold of control) as well as moderately inhibited cytokine secretion, whereas calcipotriol partially relieved barrier restoration. A comparative analysis of natural agents revealed that quercetin increased FLG mRNA as well as inhibited TNFα & IFN-γ levels, whereas resveratrol relieved TER values as well as specifically inhibited cytokine release. Conversely, curcumin exhibited minimal activity. Taken together, this data propose that the HaCaT-derived RHE-Pso model can act as a promsing pre-clinical in vitro model in defining anti-psoriasis drug leads as well as natural bioactive agents.
The Malvaceae (formerly Tiliaceae) family's Grewia serrulata DC has remarkable medicinal characteristics and its many parts are utilized in traditional medicine. However, scientific evidence supporting its pharmacological activities remains limited, particularly regarding the bioactivity of its leave extracts and solvent fractions. Therefore, the present study aimed to evaluate the phytochemical profile and antioxidant, anti-inflammatory, and antidiarrheal activities of the methanol extract of G. serrulata leaves and solvent fractions. To investigate the antioxidant effect, a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay was conducted in vitro, while in vivo anti-inflammatory and antidiarrheal activities were evaluated using the carrageenan-induced paw edema model and the castor oil-induced diarrhea model in mice, respectively. G. serrulata methanol extract (GSME) and its n-Hexane fraction (GSNH) showed significant potential in DPPH scavenging at higher doses with showing IC50 values of 11.7886μg/mL and 89.86μg/mL, respectively. Also, GSME, GSNH & Dichloromethane fractions (GSDM) displayed significant (p <0.001) anti-inflammatory and antidiarrheal effects compared to control. GSME, GSNH & GSDM reduced inflammation at a rate of 88.48%, 66.03% & 58.46% during 4th hour of post-injection. GSME & GSNH demonstrated a highly significant (p <0.001) reduction (71.21% & 62.12% inhibition, respectively) in diarrhea, while Loperamide showed an inhibition of 72.73%. The findings indicate that G. serrulata leaves exhibit promising antioxidant, anti-inflammatory and antidiarrheal activities. The results provide preliminary pharmacological support for the traditional use of this plant and highlight its potential as a source of bioactive compounds for future drug discovery, though further investigations including bioassay-guided isolation, mechanistic investigations, and safety evaluations are required.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that is increasing in prevalence and is a leading cause of death due to cardiovascular, renal, and neurological complications. Dipeptidyl peptidase-4 inhibitors (DPP-4i) have been increasingly used due to their ability to provide stable glycemic control and their suitability for elderly patients. The aim of this study was to investigate the effectiveness of treatment regimens containing DPP-4 inhibitor in outpatients with T2DM. A retrospective descriptive study conducted over 6 months, compared pre- and post-treatment outcomes on 308 T2DM outpatients who were prescribed DPP-4 inhibitors at Dong Nai General Hospital from January 2024 to May 2025. Results showed that the median age of patients was 67 years, with a higher proportion of females than males (60.4%). Most patients had comorbidities such as lipid disorder (93.2%) and hypertension (73.4%). The DPP-4 inhibitors prescribed were primarily sitagliptin and vildagliptin, administered at doses appropriate to renal function. Metformin, insulin, and sulfonylureas were the most commonly co-administered drugs with DPP-4 inhibitors. Following the DPP-4 inhibitor–based regimen, mean HbA1c decreased by 0.7%, FBG decreased by 0.94 mmol/L, and the proportion of patients achieving HbA1c < 7% increased to 28.2%, which was statistically significant (p < 0.05). In conclusion, DPP-4 inhibitors demonstrated a moderate glucose-lowering effect, making them suitable for elderly T2DM patients with comorbidities or a high risk of hypoglycemia. Drug use adhered to clinical guidelines and was appropriate in most cases.
The rising use of cannabis and its constituents for therapeutic and recreational purposes has intensified interest in understanding its neurobehavioral effects. Zebrafish (Danio rerio) have emerged as a robust model for behavioral neuroscience due to their genetic similarity to humans and conserved endocannabinoid system. This narrative review explores the behavioral effects of major cannabinoids including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on anxiety, learning and memory, and social interaction in zebrafish. Findings indicate that THC induces dose-dependent anxiogenic effects, particularly at higher concentrations, characterized by hypolocomotion and increased bottom-dwelling. Conversely, CBD shows anxiolytic potential at moderate doses but may produce biphasic effects depending on dose and exposure timing. In cognitive assays, THC impairs learning and memory performance in spatial and associative tasks, while CBD’s effects vary based on administration phase. Limited studies on social behavior suggest cannabinoids may modulate sociability, although outcomes remain inconsistent. This review highlights methodological gaps, such as the underrepresentation of chronic exposure studies, sex-based analyses, and minor cannabinoids like CBC, CBG, and CBN. Furthermore, few studies integrate behavioral outcomes with molecular or neurophysiological endpoints. By consolidating current findings, this review underscores the potential of zebrafish as a translational model in cannabinoid research and advocates for more standardized, mechanistically informed investigations to clarify the behavioral impact of cannabis constituents.
Potentially inappropriate medications (PIMs) are associated with adverse outcomes in older adults. The Asian explicit criteria, compiled from 15 quality-assessed country-specific guidelines, provide a regionally relevant and comprehensive framework for evaluating PIM use. This study investigates the prevalence, predictors, and hospitalisation outcomes of PIM use, as defined by the Asian criteria, among older outpatients in Thailand. A retrospective cohort study was conducted using data on patients aged ≥60 years who received outpatient care, obtained from the electronic medical records of three public hospitals in Thailand. Outpatient prescriptions from 2023 were analysed to identify PIM use, categorised into disease-independent, disease-specific, and drug–drug interaction (DDI)-based groups. Predictors were examined using multivariable logistic regression, while associations with hospitalisation outcomes in 2024 were assessed using generalised linear models. Among 76,361 older outpatients (mean age: 69.59 ± 7.63 years; 55.66% female), 82.99% received at least one PIM. The prevalence of disease-independent, disease-specific, and DDI-based PIMs was 82.71%, 31.09%, and 10.24%, respectively. Predictors of PIM use included care at lower-level hospitals, female sex, multimorbidity, and polypharmacy, including hyperpolypharmacy. In adjusted analyses, overall PIM use was significantly associated with a 1.17-fold increased risk of all-cause hospitalisation, 1.86-fold for adverse drug event-related hospitalisation, 1.46-fold for in-hospital mortality, and a higher number of admissions. PIM use was widespread among older outpatients and associated with adverse hospitalisation outcomes. The Asian criteria facilitated a comprehensive and context-specific evaluation of PIMs in Asian settings. Integrating these criteria into clinical practice may enhance prescribing safety and help reduce PIM-related risks.
