19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Recent advancements in tuberculosis treatment research emphasize innovative strategies that enhance treatment efficacy, reduce adverse effects, and adhere to patient-centered care principles. As tuberculosis remains a significant global health challenge, integrating new and repurposed drugs presents promising avenues for more effective management, particularly against drug-resistant strains. Recently, the spectrum concept in tuberculosis infection and disease has emerged, underscoring the need for research aimed at developing treatment plans specific to each stage of the disease. The application of precision medicine to tailor treatments to individual patient profiles is crucial for addressing the diverse and complex nature of tuberculosis infections. Such personalized approaches are essential for optimizing therapeutic outcomes and improving patient adherence—both of which are vital for global tuberculosis eradication efforts. The role of tuberculosis cohort studies is also emphasized, as they provide critical data to support the development of these tailored treatment plans and deepen our understanding of disease progression and treatment response. To advance these innovations, a robust tuberculosis policy framework is required to foster the integration of research findings into practice, ensuring that treatment innovations are effectively translated into improved health outcomes worldwide.

Objectives: This study aimed to evaluate the correlation between mast cell (MC) density in rosacea-affected skin and the expression of key inflammatory mediators, including IL-6, TNF-α, and cathelicidin LL-37. By comparing lesions rich in MCs with those having fewer MCs, we sought to elucidate the role of MCs in the inflammatory mechanisms underlying rosacea pathogenesis.

Methods: Specimens were collected from 20 patients diagnosed with rosacea who attended the outpatient clinic between 2008 and 2013. Each specimen underwent staining using hematoxylin/eosin, Giemsa, IL-6, LL-37, and TNF-α for both histopathological and immunohistochemical analyses. The number of stained cells was counted across 10 randomly selected dermal layers at a magnification of ×400 using light microscopy. The results were categorized based on the number of MCs counted: more than 10 MCs were classified as MC-rich, and 10 or fewer MCs as MC-poor.

Results: Among the 20 patients (10 MC-rich and 10 MC-poor), the MC-rich group demonstrated significantly higher MC counts than the MC-poor group (P<0.001). However, there were no significant differences in the expression levels of IL-6, LL-37, or TNF-α between the two groups. Additionally, MC density did not show any significant associations with patient demographics, clinical characteristics, or systemic comorbidities.

Conclusion: Increased MC density was not associated with differences in IL-6, TNF-α, or LL-37 expression in rosacea lesions. These findings suggest that MC infiltration may not directly influence the inflammatory mediator profile in rosacea. Further research is required to identify distinctive pathological features or markers that can elucidate the mechanisms of rosacea.

The prevalence of postpartum depression (PPD) in Asia is reported to range from 13.53% to 22.31%. However, there remains a gap in the identification of PPD, particularly regarding cultural cutoff points. Therefore, the purpose of this scoping review was to determine the prevalence and associated factors of PPD in Eastern, South-eastern, Western, and Southern Asian countries and analyze the cutoff points of the Edinburgh Postnatal Depression Scale (EPDS) used across these countries. Following Arksey and O'Malley’s five-step scoping review framework, the population was defined as mothers, the concept as the EPDS, and the context as the Asian region. A literature search was conducted using PubMed, Embase, CINAHL, PsycINFO, and Web of Science. The data analysis focused on demographic characteristics, EPDS cutoffs and features, PPD prevalence, and its associated factors. Nineteen studies were selected. Most countries used translated versions of the EPDS with demonstrated reliability and validity. The cutoff scores varied, with most using scores of 10 or higher. The prevalence of PPD ranged from 5.1% to 78.7%. Key associated factors for PPD included cultural factors such as relationships with in-laws and preferences for the newborn’s sex. To improve the accuracy of PPD screening in Asia, the EPDS should be used consistently, and appropriate cutoff criteria must be established. In addition, prevention strategies and programs that reflect the cultural characteristics and social context of Asia need to be developed for the early detection and prevention of PPD.

Background: Histone deacetylase 6 (HDAC6), belonging to class IIb of histone deacetylases, regulates theacetylation of the cytoplasmic protein α-tubulin. The overexpression of HDAC6 is linked to the development oftumors, and inhibiting HDAC6 is known to trigger apoptosis in multiple myeloma cells. In addition to its application in cancer treatment, bortezomib, a proteasome inhibitor, is widely used in managing multiple myeloma and has shown effectiveness in patients with both newly diagnosed and relapsed disease. However, the treatment regimen may be delayed or discontinued due to the risk of peripheral neuropathy, a significant non-hematologic side effect. Methods: Animal models of peripheral neuropathy induced by various anti-cancer drugs were established, confirming the potential of HDAC6 inhibitors as a treatment for this condition. Six- to eight-week-old male Sprague Dawley rats were utilized to create these models. Mechanical allodynia and electron microscopy served as indicators of peripheral neuropathy. The HDAC6 inhibitor CKD-011 was administered at doses of 5, 10, 20, and 40 mg/kg. Results: In an animal model of bortezomib-induced peripheral neuropathy, CKD-011, an HDAC6 inhibitor, effectively ameliorated peripheral neuropathy. Similarly, CKD-011 administration demonstrated recovery from peripheral neuropathy in models induced with oxaliplatin, paclitaxel, and cisplatin. Conclusions These findings suggest that HDAC6 inhibitors have the potential to mitigate peripheral neuropathy induced by chemotherapeutic agents.

The 5-hydroxytryptamine type3 (5-HT3 ) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission. It has been implicated in various neuropsychiatric disorders. This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT3 receptor-mediated currents in NCB20 neuroblastoma cells. Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism. Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC50 without altering the maximal response (Emax ), suggesting a competitive inhibition. Quetiapine's IC50 varied with 5-HT concentration and treatment condition. The IC50 value of quetiapine was 0.58 μM with 3μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration. Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC50 from 25.23 μM to 0.20 μM.Interaction kinetics experiments revealed an IC50 of 5.17 μM for an open state of the 5-HT3 receptor, suggesting weaker affinity during receptor activation. Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states. Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics. Inhibition of the 5-HT3 receptor by quetiapine was voltage-independent, and quetiapine exhibited no usedependency, further supporting its role as a competitive antagonist. These findings provide insights into inhibitory mechanism of quetiapine on 5-HT3 receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.

Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT) 3 receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT3 receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (E max ) and an increase in EC 50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT3 receptors. Haloperidol inhibited the activation of 5-HT3 receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT3 receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT3 receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT3 receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT3 receptors and pharmacological actions of antipsychotics.

Background: Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker. Methods: A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely “0–2 breakfasts per week” and “3–7 breakfasts per week”; hs-CRP concentrations were measured through blood tests. Results: Comparing between the “infrequent breakfast consumption (0–2 breakfasts per week)” and “frequent breakfast consumption (3–7 breakfasts per week)” groups, the mean hs-CRP was found to be significantly higher in the “infrequent breakfast consumption” group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036). Conclusion Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.

In forensic science, age estimation is essential for identifying both living and deceased individuals. Teeth and jawbones serve as reliable indicators due to their gradual age-related changes and resistance to environmental factors. Among the various methods, attrition and pulp cavity size are commonly used to estimate adult age. This study aimed to enhance the accuracy of age estimation in Korean adults by combining measurements of tooth attrition and pulp cavity size obtained from panoramic radiographs of mandibular first molars. We evaluated 118 patients (62 male, 56 female) who visited Pusan National University Dental Hospital between 2010 and 2024. Radiographs and clinical photographs were analyzed for grade C teeth with exposed dentin using Takei’s method, and the pulp chamber height ratio (PCHR) and width ratio (PCWR) were measured using Jeon’s method. Intraobserver reliability was high (intraclass correlation coefficient>0.6), with no significant sex-based differences in PCHR and PCWR. Both ratios negatively correlated with age, with PCWR showing a stronger correlation, particularly in females (r=–0.606). This study derived an improved age estimation formula with R² values ranging from 0.540 to 0.546 when both PCHR and PCWR were combined. Despite the limitations of this study, such as its small sample size and reliance on panoramic radiographs, the findings suggest that combining tooth wear and pulp cavity size offers a more robust tool for age estimation in clinical and forensic settings.