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Diabetic retinopathy (DR) is a frequent diabetes-associated microvascular disorder, and its underlying mechanism of pathogenesis remains unclear. Previous studies have suggested that YAP1 is involved in endothelial activation and vascular inflammation. In the present study, we explored the biological role of YAP1 in retinal vascular endothelial cells (RVECs) in response to high glucose (HG). YAP1 expression was first evaluated in retinal endothelial cells cultured with HG. In retinal endothelial cells, the consequences of HG exposure and the alteration of YAP1 expression were systematically evaluated, focusing on cell growth, survival, tube formation, migration, and activation of autophagy. To further evaluate the protective effect of YAP1 inhibition on retinal endothelial cells in vivo, a streptozocin-induced DR mouse model was employed. First, we discovered that YAP1 expression was dose-dependently elevated under glucose treatment in retinal endothelial RF/6A and human primary retinal endothelial cells. Accordingly, suppression of YAP1 exhibited a protective role in HG-treated retinal endothelial cells by decreasing cell viability and suppressing apoptotic deaths. Moreover, inhibition of YAP1 impairs migration and tube formation of retinal cells and alleviates autophagy in response to HG. Additionally, YAP1 knockdown reversed glucose-induced nucleus translocation of NF-κB. This study demonstrated that inhibition of YAP1 exhibits a protective role against HG-induced RVEC injury, representing a novel target for the management and therapy of DR in clinics.

Primary hepatic angiosarcoma (PHA) is a rare malignancy, and the occurrence of a dual malignancy involving both gastric cancer (GC) and PHA is even more exceptional. Here, we present a case of a 63-year-old man who complained of hiccups. PET-CT and Abdomen & Pelvis Routine Enhanced Scan results revealed a single liver mass and thickening of the inner wall of the gastric antrum. The pathologic biopsy confirmed the presence of GC in the antrum along the greater curvature. The initial diagnosis indicated GC with solitary liver metastasis, given the rarity of PHA. The patient underwent a radical distal gastrectomy and right posterior hepatic lobectomy. Postoperative pathology revealed early GC and PHA without any signs of lymphatic or distant metastases.

Although there has been research on the toxicity of Rhizoma Paridis (Chong Lou), a systematic and comprehensive evaluation, as well as targeted strategies for mitigating its toxicity, remains lacking. This review aims to provide a thorough assessment of the toxicological properties of Rhizoma Paridis, offering reliable guidance for its safe application. The article focuses on the toxicity and underlying mechanisms of Rhizoma Paridis and reviews the applications of both traditional Chinese medicine and modern scientific technologies in detoxification. Finally, it proposes future research directions, emphasizing the need for further exploration of chronic toxicity mechanisms and advocating for the integration of traditional and modern detoxification methods to ensure the safe clinical use of Rhizoma Paridis. This review provides the latest theoretical foundation for the safe use and further development of Rhizoma Paridis.

[This retracts the article DOI: 10.1515/biol-2018-0059.].

Endometrial cancer (EC) exhibits increasing incidence and mortality, necessitating novel prognostic biomarkers and therapeutic targets. This study systematically investigates EPHB2 as a potential biomarker through comprehensive bioinformatics (TIMER 2.0, Human Protein Atlas, Xanadu Academic Online, Sento Academic Online, TCGA, GeneMANIA, GSEA, BEST database, and SCAR database) and experimental analyses (si-EPHB2 and OE-EPHB2 RL95-2 cell models with RT-qPCR, western blot, CCK-8, wound healing, Transwell, and TUNEL assays). Our findings demonstrate that EPHB2 is significantly overexpressed in EC, correlating with advanced pathological grade, histological type, and poor prognosis, while its high expression activates PI3K/AKT/MAPK signaling and promotes proliferation, migration, invasion, and suppresses apoptosis; conversely, EPHB2 knockdown exhibits opposite effects, revealing its critical role in EC progression through immune modulation and oncogenic signaling activation, thereby establishing EPHB2 as a promising therapeutic target for EC treatment.

This study investigates the mechanism by which lipoxin A4 (LXA4) attenuates myocardial ischemia/reperfusion injury (MIRI). Using a rat MIRI model, we evaluated coronary flow, histopathology, cardiac enzymes (cTnI/CK-MB), oxidative stress markers (superoxide dismutase, SOD; malondialdehyde, MDA; glutathione peroxidase, GSH-Px), and protein expression (neurogenic locus notch homolog protein 1 [Notch1], hairy and enhancer of split 1 [Hes1], nuclear factor-erythroid 2-related factor 2 [Nrf2], β-tubulin). Pharmacological inhibitors N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butylester (DAPT; Notch1) and ML385 (Nrf2) were co-administered with LXA4. Results demonstrated that I/R injury significantly increased microtubule disruption (48.5 ± 6.7% vs control 4.8 ± 0.9%; p < 0.01), decreased SOD (42.1 ± 5.3 vs 89.6 ± 8.7 U/mg), and GSH-Px (15.2 ± 2.1 vs 34.8 ± 4.5 U/mg), and elevated MDA (6.9 ± 0.8 vs 2.1 ± 0.3 nmol/mg; p < 0.05). Notch1, Hes1, and nuclear Nrf2 decreased by 58, 63, and 52%, respectively. LXA4 treatment reversed these effects (23.6 ± 3.6% microtubule disruption; p < 0.05), with DAPT or ML385 abolishing LXA4's protection. These findings indicate that LXA4 protects against MIRI by preserving microtubule integrity and activating the Notch1/Hes1/Nrf2 pathway, revealing a novel mechanism for oxidative stress suppression in cardiomyocytes.

Src homology phosphotyrosyl phosphatase 2 (SHP-2) has been implicated in the pathogenesis of diabetic nephropathy (DN), while pyroptosis, an inflammatory form of programmed cell death, has also been associated with disease progression. However, the regulatory interplay between SHP-2 and pyroptosis in DN remains incompletely understood. In this study, we established DN rat models using a single intraperitoneal injection of streptozotocin (STZ) and HK-2 cells cultured under high-glucose (HG) conditions. Hematoxylin and eosin staining was performed to assess the histopathological changes in renal tissues, while immunofluorescence and Western blotting were used to evaluate SHP-2 and NLRP3 expression in both rat kidney tissues and HK-2 cells. Lentiviral transfection was performed to overexpress SHP-2 or NLRP3, following which the expression of pyroptosis-related proteins, activation of the NLRP3 inflammasome, and cell apoptosis were assessed by Western blot and flow cytometry. The results demonstrated that STZ-treated rats exhibited significant weight loss, hyperglycemia, and renal tissue injury. We observed an increase in SHP-2 expression in the kidney tissues of DN rats and in HK-2 cells exposed to high glucose, along with an elevated expression of NLRP3. SHP-2 knockdown suppressed NLRP3 inflammasome activation and mitigated HG-induced pyroptosis in renal tubular epithelial cells. Notably, overexpression of NLRP3 partially reversed the protective effects conferred by SHP-2 knockdown. These findings suggest that SHP-2 knockdown alleviates renal tubular epithelial cell injury in DN by inhibiting NLRP3 inflammasome-mediated pyroptosis.

Von Willebrand disease (VWD) is one of the most common bleeding disorders, stemming from irregularities in the Von Willebrand factor (VWF). Globally, type 1 VWD (VWD1) is the most prevalent form, characterized by decreased levels of VWF in the blood. Genotyping studies have found causative genetic variants in approximately 65% of VWD1 cases, revealing the presence of ethnic-specific VWF variants. This study is limited by its exclusive focus on exon 26, warranting further investigation of other exons and the inclusion of functional analyses. Moreover, these findings emphasize the importance of understanding genetic variability in population-specific contexts, supporting the necessity for future studies on additional exons and potential epigenetic interactions. Between 2018 and 2019, samples and relevant medical data were collected at King Fahad Hospital of the University in Al Khobar. Sanger sequencing of the exonic and flanking intronic regions of exon 26 was performed on 22 index cases clinically diagnosed with VWD1 and their first-degree relatives. Analysis revealed four exonic and 11 intronic variants in VWF exon 26 among the participants. None of the identified variants appeared to explain the VWD-related clinical features in these individuals. However, findings suggest a higher prevalence of specific VWF variants within the Saudi population compared to global databases. Further investigation, including sequencing of additional exons or next-generation sequencing, may help to uncover potential disease-causing variants in this cohort. Establishing a national sequencing project could also enhance our understanding of both common and rare variants in the genetic basis of complex diseases, such as VWD1.

Escin, a natural medicinal saponin, has garnered significant attention in recent years for its pharmacological effects in various diseases. Though the structure and pharmacodynamic targets of escin are documented, reviews on its efficacy and mechanisms were still mainly from the clinical application perspective at the organ level or animal models. Deeper discussion at the tissue microenvironment level remains sparse, as the sophisticated cell and molecular technique is required. Contradictory conclusion might occur if such experiment setups are not carefully distinguished. This article reviews and analyzes literature to discuss escin's ability to improve the tissue microenvironment of blood vessel walls and elucidates the underlying mechanisms. Escin demonstrates significant anti-inflammatory properties and neutralizes free radicals, thereby protecting vascular endothelial cells from oxidative stress. Additionally, escin's anticoagulant properties reduce blood viscosity, preventing clot formation and maintaining vessel patency. These mechanisms collectively enhance the tissue microenvironment of blood vessel walls and promote cardiovascular health, which provides a multi-target therapeutic strategy for cardiovascular diseases (CVD), integrating anti-inflammatory, antioxidant, endothelial repair, and microcirulation-enhancing mechanisms, consistent with current pathophysiological insights. The article also addresses the current research status, challenges, and future potential of escin in vascular protection, offering new perspectives and strategies for CVD treatment and prevention.

To investigate the clinicopathological features of three patients with Merkel cell carcinoma (MCC). The clinicopathological features, immunophenotypes, diagnosis and differential diagnosis, treatment, and prognosis of the three patients with MCC were analyzed retrospectively. Among the three patients, two were male and one was female. The age range of the patients was 55-79 years, while their mean age was 66.6 years. The maximum and mean tumor diameters were 1.8-2.5 cm and 2.1 cm, respectively. The tumors were located in surface areas such as the face and forearm. The tumor masses were mostly round, with a gray, solid appearance and qualitative sections. Microscopic examination revealed that the MCCs of the three patients had roughly the same morphology. Light microscopy indicated that the MCCs appeared as an intradermal mass with a narrow "Grenz band" separated from the epidermis, often accompanied by necrosis (apoptotic bodies) and patchy lymphocyte infiltration. Histological assessment of the MCCs showed monomorphic cell hyperplasia with cables, trabeculae, or sheet formation, hyperchromatic nuclei, vacuoles, cytoplasm with a "salt and pepper" appearance, and nuclear division. Immunophenotyping found tumor cells that were CK (+), CD56 (+), Syn (+), EMA (+), β-catenin (membrane +), LCA (-), CD99 (-), S100 (-), HMB-45 (-), SOX-10 (-), TTF-1 (-), CDX-2 (-), and CD34 (-), along with a Ki-67 proliferation index of 60-70%. Of the three patients with MCC, two were immunophenotypic CgA negative and one was positive. Additionally, two immunophenotypes exhibited CK20 negativity, and one showed paranuclear punctate positivity for CK20. MCC is a highly malignant cutaneous neuroendocrine carcinoma, requiring the combination of pathological morphology examination and immunophenotyping to confirm the diagnosis. Moreover, the primary MCC treatment of surgical treatment should be supplemented with chemotherapy and/or local radiotherapy to alleviate its poor prognosis, easy recurrence or metastasis, and high mortality.