Tajen University

Myeloid differentiation factor 88 (MyD88) signaling plays a central role in inflammatory pathway activation. Adipose-derived interleukin-10 (IL-10), which is induced by insulin and lipopolysaccharides, suppresses hepatic glucose production. This study investigated the role of MyD88/IL-10 signaling in diabetes-induced systemic inflammation and hepatic gluconeogenesis. Stromal vascular fractions (SVFs) were isolated from the adipose tissue of Leprdb/db and Leprdb/dbMyD88-/- mice and treated with IL-10 followed by analysis of inflammatory cytokine expression. IL-10 (10 or 50 ng) was injected into adipose tissue of type 2 DM (T2DM) (Leprdb/db) mice to investigate its effect on blood dipeptidyl peptidase-4 (DPP4) activity, insulin resistance, and hepatic gluconeogenic signaling. Hepatic inflammatory markers, gluconeogenic gene expression, and metabolic parameters were assessed. Compared with wild-type mice, Leprdb/db mice exhibited significantly reduced FOXP3 protein expression and IL-10 levels in adipose tissue, accompanied by increased blood DPP4 activity and adiponectin levels, elevated hepatic inflammatory cytokines, and increased G6pc and Pck1 mRNA expression. In contrast, Leprdb/dbMyD88-/- mice showed increased Foxp3 protein and PDGFα mRNA expression, decreased IL-6 and CCL2 mRNA expression in SVFs, increased IL-10 levels in adipose tissue, and lower blood adiponectin and ALT levels. MyD88 deletion also attenuated Kupffer cell accumulation, hepatic inflammatory cytokine expression, and gluconeogenic gene expression. In vitro, IL-10 treatment of SVFs from Leprdb/db mice significantly reduced IL-6 and CCL2 expression and increased Foxp3 mRNA expression. In vivo, adipose IL-10 injection increased Foxp3 and IL-10 expression, expanded Treg cells in SVFs, and activated hepatic Akt signaling, while suppressing pJNK and pNF-κB signaling. These changes were accompanied by reduced blood DPP4 activity, ALT and adiponectin levels, decreased Kupffer cell-derived inflammatory cytokines, reduced hepatic G6pc and Pck1 expression, and improved glucose tolerance. MyD88 signaling induces adipose IL-6 and CCL2, liver inflammation and gluconeogenesis, and blood DPP4 activity by reducing IL-10 and Foxp3 of adipose tissue in T2DM. Enhancing adipose IL-10 induces Treg expansion, inhibits JNK and NF-κB signaling, and alleviates hepatic gluconeogenesis and insulin resistance. MyD88 inhibition or IL-10 elevation in adipose tissue may represent a novel strategy for metabolic syndrome.

Background/Objective: Di-2-ethylhexyl phthalate and its bioactive metabolite mono-2-ethylhexyl phthalate (MEHP) are ubiquitous endocrine-disrupting chemicals implicated in carcinogenesis. However, the molecular mechanisms linking MEHP exposure, host genetic susceptibility, and prostate cancer progression remain incompletely defined. Methods: We integrated transcriptomic profiling of MEHP-exposed human prostate epithelial cells with a genetic association study of 630 patients with prostate cancer receiving androgen deprivation therapy. MEHP-responsive genes were identified from public microarray datasets and subjected to pathway enrichment analyses. Germline single-nucleotide polymorphisms (SNPs) in MEHP-regulated genes were evaluated for their association with progression-free survival, overall survival, and cancer-specific survival. The clinical and functional relevance of the key genes was further assessed using large-scale public prostate cancer expression datasets. Results: MEHP exposure induced widespread transcriptional reprogramming, prominently suppressing focal adhesion and cell-matrix interaction pathways. Genetic analyses identified multiple prognostically relevant SNPs within MEHP-responsive genes, with anoctamin 4 (ANO4) variants showing consistent associations across all clinical endpoints. The minor allele of rs17485225 in ANO4 was significantly associated with reduced all-cause and prostate cancer-specific mortality. Pooled analyses revealed reduced ANO4 expression levels in prostate cancer tissues and improved survival in patients with high ANO4 expression levels. Pathway analyses linked low ANO4 expression levels with enhanced cell cycle activity and compromised cell adhesion. Conclusions: Our findings suggest that ANO4 may act as a mediator of MEHP-associated prostate cancer progression and support a gene-environment interaction model in which environmental toxicant exposure and germline variation converge on focal adhesion dysregulation to potentially contribute to aggressive disease.

Obesity represents a significant global health challenge and is closely linked to the prevalence of metabolic syndromes and liver disorders. In Taiwan, the Ministry of Health and Welfare has instituted specific evaluation protocols for functional foods to mitigate body fat accumulation, underscoring mechanisms beyond caloric restriction. The present study sought to assess the anti-adipogenic and metabolic effects of pterostilbene (PTS) using a rat model of high fat diet (HFD)-induced obesity, in compliance with Taiwan's regulatory standards for health claims about "difficult-to-form body fat". Male Sprague-Dawley (SD) rats were fed a HFD for six months to induce obesity. Subsequently, the SD rats were administered PTS orally at dosages of 30 or 50 mg/kg/day for 45 days. This study evaluated various parameters, including body weight, food intake, feed efficiency, body fat percentage, liver weight, and serum biochemical markers. Forty-five day 30 and 50 mg/kg PTS oral treatment significantly reduced body weight gain, food intake, and feed efficiency (all p<0.05). Remarkably, over 70% of the rats exhibited reduction in body fat exceeding 0.02%, meeting the established regulatory efficacy standards. Furthermore, notable improvements were observed in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), and glucose (GLU) levels (all p<0.05). PTS is a promising natural compound for the formulation of health foods aimed at enhancing fat metabolism and providing liver protection. The observed effects are consistent with physiological expectations and aligned with the regulatory efficacy criteria established in Taiwan.

Penelitian ini bertujuan untuk menganalisis pengaruh pengembangan karir, motivasi kerja, dan kinerja terhadap produktivitas kerja karyawan tetap di Rumah Sakit Bedah Hasta Husada Kabupaten Malang. Jenis penelitian yang digunakan adalah kuantitatif dengan desain cross-sectional dan pendekatan survei. Sampel penelitian terdiri dari 140 responden yang diambil menggunakan teknik proportional random sampling. Instrumen penelitian berupa kuesioner skala Likert 1–5 yang mencakup variabel pengembangan karir, motivasi kerja, kinerja, dan produktivitas kerja. Data dianalisis menggunakan SPSS 26. Hasil penelitian menunjukkan bahwa regresi linier berganda menghasilkan persamaan Y = 0,642 + 0,415 X₁ + 0,327 X₂ + 0,298 X₃ + e, dengan nilai t signifikan untuk pengembangan karir (t = 4,663; p = 0,000), motivasi kerja (t = 4,192; p = 0,000), dan kinerja (t = 3,679; p = 0,000. Nilai Adjusted R² = 0,632 menunjukkan bahwa 63,2% variasi produktivitas kerja dijelaskan oleh ketiga variabel tersebut. Kesimpulannya, pengembangan karir, motivasi kerja, dan kinerja berpengaruh signifikan positif terhadap produktivitas kerja karyawan, dengan pengembangan karir sebagai faktor paling dominan. Temuan ini memberikan implikasi praktis bagi manajemen rumah sakit dalam merancang strategi peningkatan produktivitas karyawan.

Objectives: To describe the technique of mandibular reconstruction using a free scapular osteomyocutaneous flap in two clinical cases and evaluate the achieved functional and aesthetic outcomes. Methods: We conducted a descriptive analysis of two male patients (ages 60 and 54) with advanced T4a oral cavity cancer involving the mandible, who underwent surgery at Hue Central Hospital in October 2023 and February 2024. Both patients received curative tumor resection (segmental mandibulectomy with adequate margins and selective neck dissection) followed by immediate reconstruction of the mandibular defect using a free scapular osteomyocutaneous flap, performed with a two-team simultaneous microsurgical approach. Results: Both patients were successfully reconstructed with the scapular flap without any flap necrosis and were discharged at approximately 3 weeks post-operation. The mean operative time was ~9 hours (tumor resection and neck dissection ~4.5 hours; flap harvest and microsurgical anastomosis ~4 hours). All flaps had 100% survival, with bony union achieved by ~3 months and no evidence of bone resorption or non-union on X-ray. Masticatory function, swallowing, and speech improved markedly, and were nearly normal by 3 months post-op. Facial contour was restored with a harmonious mandibular border and no cervical soft-tissue depression. Both patients received adjuvant radiotherapy (56–60 Gy) as scheduled. At short-term follow-up (~6 months), no local recurrence was observed; one patient had two small pulmonary nodules under close surveillance with no progression noted. Conclusion: The free scapular osteomyocutaneous flap is a feasible, safe, and effective option for reconstructing segmental mandibular defects after cancer resection. This single-stage microsurgical technique achieves immediate restoration of mandibular continuity with a high flap success rate, significantly improving mastication, swallowing, speech, and facial aesthetics. Moreover, immediate free-flap reconstruction enables earlier initiation of adjuvant therapy, thereby optimizing overall cancer treatment outcomes. Keywords: free scapular bone flap, mandibular reconstruction, oral cavity cancer reconstruction, microsurgical reconstruction

BackgroundDisability and cognitive impairment are two significant age-related health issues in older adults. This study aims to simultaneously identify the bidirectional relationship between disability and cognitive impairment, and further pinpoint which one holds a more pivotal role in the relationship.MethodsA total of 628 participants aged 66.0 (SD = 7.3) were retrieved from the 2000 and 2006 Social Environment and Biomarkers of Aging Study (SEBAS). Cognitive function was assessed using the modified Short Portable Mental Status Questionnaire (SPMSQ). Disability was measured as a count of activity of daily living, instrumental activity of daily living, and mobility scales. Structural equation models with cross-lagged analysis were used to examine the temporal relationship between cognitive impairment and disability over six years.ResultsThe cross-lagged model was well constructed (χ2 (9) = 34.5941, p < 0.0001, RMSEA = 0.0673, CFI = 0.99, SRMR = 0.03). Baseline disability significantly predicted future cognitive impairment (β=−0.25, p < 0.05), and baseline cognition significantly predicted future disability (β=−0.03, p < 0.05). Fisher’s Z test indicated a stronger pathway from disability to future cognitive impairment compared to cognitive impairment to future disability (p < 0.001).ConclusionThis longitudinal study suggested that disability and cognition change were bidirectional, with disability showing a stronger impact on future cognitive impairment. Further dynamic investigations and mechanisms between cognitive change and disability are warranted.

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Background/AimProstate cancer, a leading global malignancy, exhibits variable progression influenced by angiogenesis, the formation of new blood vessels critical for tumor growth and metastasis. We investigated the impact of genetic variants of angiogenesis-related genes on the survival outcomes of patients with prostate cancer receiving androgen deprivation therapy (ADT).Materials and MethodsWe conducted a genetic association study of 87 single-nucleotide polymorphisms across seven angiogenic genes in 630 patients with prostate cancer undergoing ADT. Survival analysis was used to assess progression-free survival (PFS) and overall survival (OS). Functional analyses, including gene ontology and pathway enrichment, were performed to elucidate the underlying biological mechanisms.ResultsANGPT2 rs2959822 was significantly associated with PFS [hazard ratio (HR)=1.22, p=0.015] and OS (HR=1.22, p=0.021). The minor allele A increased the risk of disease progression and mortality. Functional analyses revealed that rs2959822 influenced ANGPT2 expression. Elevated ANGPT2 expression was correlated with higher Gleason score, advanced tumor stage, and shorter PFS. Gene set enrichment analysis linked ANGPT2 to epithelial-mesenchymal transition (EMT), demonstrating positive correlations with several key EMT genes, along with increased immune cell infiltration, indicating its multifaceted oncogenic roles.ConclusionANGPT2 rs2959822 influences the survival outcomes of patients with prostate cancer undergoing ADT. In addition to angiogenesis, ANGPT2 plays a critical role in prostate cancer progression by promoting EMT and modulating the tumor immune microenvironment.

The 2024 global cryptococcosis treatment guidelines suggests that fluconazole (FLC) combined with liposomal amphotericin B (AMB) and 5-flucytosine (5-FC) as the mainstay of treatment for systemic cryptococcosis. Although this 2024 guidelines also list recommend voriconazole (VRC), posaconazole (POS), and isavuconazole (ISA) as alternatives to FLC during the consolidation and maintenance phases, current data on distributions of minimum inhibitory concentrations (MICs) of global Cryptococcus isolates for antifungals-and studies evaluating the application of their pharmacokinetic (PK) profiles and pharmacodynamic (PD) indices in the treatment of systemic cryptococcosis-remain limited. To optimize antifungal dosing, integration of global MIC distributions for Cryptococcus isolates with PK/PD parameters for key antifungal agents is needed. This study analyzed the MIC distributions from the 2010-2023 antifungal Antimicrobial Testing Leadership and Surveillance database, and determined epidemiological cutoff values for major Cryptococcus species. The majority of invasive Cryptococcus isolates were classified as wild-type strains (>90%). We analyzed PK profiles (particularly central nervous system [CNS] penetration from the bloodstream), PD indices of antifungals (azoles and AMB) against yeasts. Based on 25 studies clearly describing PK-PD relationships, FLC and VRC were considered optimal choices because of superior CNS penetration. The optimal dose of FLC is 800-1,200mg/day, whereas dosages of VRC and ISA do not require adjustment. Nevertheless, therapeutic drug monitoring for VRC is warranted during its prescription due to significant variability in plasma concentrations influenced by multiple factors. POS is not suitable for induction therapy in systemic cryptococcosis. Additionally, ISA is preferred over POS for consolidation therapy for Cryptococcus meningitis/meningoencephalitis (MME) based on differences in their PK profiles. Furthermore, a single 10mg/kg dose of liposomal AMB-a cost-effective strategy-should be combined with 1,200mg/day FLC and 5-FC, or alternatively VRC, as an effective induction-phase regimen for treating Cryptococcus MME. Diverging from the 2024 guidelines, this study provides novel insights into the treatment of Cryptococcus MME based on MIC distributions and PK-PD indices for antifungal agents.