Conectar
by Ryosuke Segawa, Makiko Yagisawa, Chihiro Miyata, Noriyasu Hirasawa
Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that induces type 2 immune responses through dendritic cell activation, and its aberrant regulation is implicated in TSLP-associated inflammatory disorders including atopic dermatitis. We previously demonstrated that hypoxia-inducible factor (HIF) suppresses TSLP expression in human keratinocyte cells; however, the underlying mechanism remained unclear. In this study, we aimed to explore the suppressive mechanism of enarodustat, an HIF-prolyl hydroxylase inhibitor. Enarodustat selectively suppressed TSLP expression induced by the fibroblast-stimulating lipopeptide (FSL-1), a toll like receptor 2/6 agonist in HaCaT, a human keratinocyte cell line. Although both the nuclear factor-κB (NF-κB) and activator protein (AP)-1 contributed to FSL-1-induced TSLP induction, enarodustat preferentially attenuated AP-1 signaling by reducing c-Jun N-terminal kinase (JNK) phosphorylation. This JNK dephosphorylation required both HIF1α and HIF2α and was accompanied by increased expression of dual-specificity phosphatases (DUSPs), which target JNK for dephosphorylation. Collectively, our findings identify a previously uncharacterized HIF–DUSP–JNK axis that negatively regulates TSLP expression. This study provides mechanistic insight into how HIF activation shapes epithelial cytokine responses, offering a basis for understanding the pathogenesis of TSLP-associated diseases such as atopic dermatitis.Pre-exposure prophylaxis (PrEP) use among cisgender female sex workers (FSWs), a population at disproportionately high HIV acquisition risk in Uganda, remains suboptimal. Uptake and continued use are constrained by barriers, such as limited clinical hours, long distances to access facility-based PrEP services, and high mobility among FSWs. Community pharmacies may offer a more accessible PrEP delivery model due to extended operating hours and convenient locations. This study aims to evaluate the accessibility and capacity of pharmacies in Kampala, Uganda, to serve as potential sites for PrEP delivery.
We will conduct a concurrent mixed-methods study combining geospatial mapping, structured surveys, a discrete choice experiment (DCE), and in-depth interviews (IDIs). First, the study will compare the reach and accessibility of PrEP services through community pharmacies versus public healthcare facilities. To highlight PrEP service reach, we will use geospatial analysis to map pharmacies, PrEP clinics, FSW hotspots (i.e., areas where sex is exchanged), and HIV incidence. We will also calculate a PrEP facility needs ratio (number of PrEP facilities/HIV incidence) for each of Kampala’s administrative divisions and estimate travel distance and time to access PrEP services using cost–distance analysis. Perceived accessibility of PrEP services will be assessed through FSW surveys (n=50) and IDIs (n=20–30), guided by Levesque’s framework. Then, we will evaluate pharmacy capacity via surveys (n=274) and IDIs (n=20–30), exploring infrastructure, resources, and staff perspectives, informed by the Consolidated Framework for Implementation Research. Additionally, a DCE will be embedded in the pharmacy survey to elicit staff preferences for delivery approaches and analysed using mixed logit models. Finally, we will integrate quantitative and qualitative findings to provide a broad assessment of whether pharmacies are suitable venues for PrEP delivery to FSWs in Kampala. Enrolment will begin by April 2026 for FSWs and July 2026 for pharmacy staff.
Ethical approval has been obtained from the Infectious Diseases Institute Research Ethics Committee (IDI-REC-2025-175) and the Uganda National Council for Science and Technology (HS6178ES). Written informed consent will be obtained from all participants. We will disseminate study findings through stakeholder meetings, scientific conferences, and peer-reviewed publications.
Preoperative biliary drainage (PBD) is often required for patients with pancreatic cancer accompanied by biliary obstruction to ensure the safe administration of neoadjuvant chemotherapy or to manage cholangitis and jaundice. Although endoscopic retrograde cholangiopancreatography (ERCP) is the standard approach for PBD, it carries a significant risk of post-ERCP pancreatitis. Endoscopic ultrasound-guided biliary drainage (EUS-BD), particularly via hepaticogastrostomy (EUS-HGS), offers a promising alternative that avoids papillary manipulation. However, the clinical utility of EUS-BD as primary drainage for PBD remains unclear due to a lack of prospective studies. This multicentre prospective trial aims to evaluate the safety and efficacy of EUS-HGS as primary drainage for PBD in patients with resectable or borderline resectable pancreatic cancer.
This multicentre prospective study involves seven institutions in Japan. Eligible patients will undergo EUS-HGS using a 7Fr plastic stent. The primary endpoint is clinical success, defined by improvements in bilirubin or liver enzyme levels within 14 days postprocedure. Secondary endpoints include technical success rate, adverse event incidence, stent patency and surgical outcomes. A total of 30 patients will be enrolled, considering an expected clinical success rate of 90% and a 10% dropout allowance.
This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2024-084). The results of this study will be reported at an international conference and published in an international peer-reviewed journal.
UMIN ID: 000055173.
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