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The kinetics of type I interferon (IFN) induction versus the virus replication compete, and the result of the competition determines the outcome of the infection. Chaperone proteins that involved in promoting the activation kinetics of PRRs rapidly trigger antiviral innate immunity. We have previously shown that prior to the interaction with MAVS to induce type I IFN, 14-3-3η facilitates the oligomerization and intracellular redistribution of activated MDA5. Here we report that the cleavage of 14-3-3η upon MDA5 activation, and we identified Caspase-3 activated by MDA5-dependent signaling was essential to produce sub-14-3-3η lacking the C-terminal helix (αI) and tail. The cleaved form of 14-3-3η (sub-14-3-3η) could strongly interact with MDA5 but could not support MDA5-dependent type I IFN induction, indicating the opposite functions between the full-length 14-3-3η and sub-14-3-3η. During human coronavirus or enterovirus infections, the accumulation of sub-14-3-3η was observed along with the activation of Caspase-3, suggesting that RNA viruses may antagonize 14-3-3η by promoting the formation of sub-14-3-3η to impair antiviral innate immunity. In conclusion, sub-14-3-3η, which could not promote MDA5 activation, may serve as a negative feedback to return to homeostasis to prevent excessive type I IFN production and unnecessary inflammation.

Background: Hemodialysis (HD) is a public health issue, and HD-induced infection is a major risk factor for mortality. Toll-like receptor 4 (TLR4) plays a key role in the pathogenesis of infection. However, polymorphisms of TLR4 contribute to infection are still unknown. Aim: This study aimed to examine the correlation between polymorphisms of TLR4 and mortality among HD patients. Methods: This retrospective cohort study included 585 participants from Tri-Service General Hospital in Taipei from 2011 to 2015. All participants were genotyped for TLR4 rs10116253T/C and rs7873784G/C by the iPLEX Gold single-nucleotide polymorphisms assay. Analysis of the conditional Cox proportional hazard model was used to test the association between TLR4 polymorphisms and mortality. Results: Our results show that adjustment with age and gender, TLR4 rs10116253T/C demonstrates an association with mortality (hazard ratio [HR] =1.38, 95% confidence interval [CI] =1.00–1.89) in a dominant model, especially in infection-related mortality (HR = 2.14, 95% CI = 1.04–4.43) of HD patients. Conclusion: The results demonstrate that TLR4 rs10116253T/C may play a role in the etiology of infection among HD patients.

Background: Gliomas, prevalent and lethal brain tumors, present limited treatment options despite advancements in understanding their molecular features. SLC4A7, an SLC4 family member and potential biomarker, is involved in acid-base regulation, affecting cancer cell growth. Targeting this mechanism may offer new therapeutic strategies. Aim: This study examines SLC4A7's role in gliomas and its potential as a therapeutic target. Methods: Genomic, whole exon sequencing, and single-cell sequencing datasets from glioma patients were processed and analyzed, followed by gene set enrichment analysis (GSEA). Cellular components and immune cell populations were investigated using 12-cell state and CIBERSORT analyses. Tissue microarray and immunohistochemistry were employed, with an automated semi-quantitative system scoring staining. ANOVA determined the significance of immunostaining scores related to clinical parameters. Results: Our data found increased SLC4A7 in tumor components correlated with higher tumor grading and poorer prognosis. Immunohistochemistry confirmed a relationship between SLC4A7 protein expression with tumor grade and the proliferation index. GSEA linked high SLC4A7 to cell proliferation and inflammation signaling. PIK3CAs were identified as a potential upstream in IDH mutant glioma but not in IDH wildtype. A positive correlation between heightened SLC4A7 expression and tumor mutation burden suggested genomic instability's role in SLC4A7 upregulation. Cellular heterogeneity analysis highlighted the importance of inflammatory cells, particularly macrophage M0. Conclusion: This study emphasizes SLC4A7's significance in adult gliomas, associating increased expression with high tumor grade, poor prognosis, enhanced proliferation, and inflammation. Investigating SLC4A7 may provide insights into cancer biology and contribute to developing innovative therapeutic targets for improved brain tumor treatments.

Multicentric Castleman disease (MCD) is a systemic lymphoproliferative disorder that can lead to mass lesions in various body parts, including the lungs, kidneys, and extranodal sites. Meanwhile, orbital Castleman disease is extremely rare. Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized fibroinflammatory disorder and is characterized by the formation of tumor-like lesions with lymphoplasmacytic infiltrates, which are enriched in IgG4-positive plasma cells and may present with a characteristic storiform pattern of fibrosis to variable degrees. In this study, we report a case of a 67-year-old Taiwanese man with a 7-year history of bilateral eyelid swelling and proptosis. Orbital magnetic resonance imaging revealed soft tissue lesions in the bilateral intraconal region, demonstrating strong enhancement in the lacrimal glands, and extension into the bilateral infraorbital foramen, suggesting an orbital lymphoproliferative disease. The histopathological results of the intraorbital tumor excision were suggestive of a plasma-cell-predominant mixed-cell variant of MCD. However, the patient also showed definitive signs of IgG4-RD, including lacrimal gland enlargement and histopathological results of plasmacytosis, fibrosis, and germinal centers, with an increased ratio of IgG4 cells and elevated serum IgG4 levels. This case suggests a potential interacting pathway between these two disease entities that needs further studies.

Hemangioblastomas (HBs) are uncommon tumors that occur as sporadic lesions or multiple lesions associated with von Hippel–Lindau (VHL) disease. We report a case of a 77-year-old male with an unusual clinical presentation of HB mimicking meningioma, involving the left anterior temporal fossa, skull, infratemporal fossa, and orbit, and compressing the lateral rectus muscle and optic nerve causing exophthalmos, without a diagnosis of VHL-related HB.

Endometrial carcinoma (EC) is the most common gynecological cancer. However, there is currently no routinely used biomarker for differential diagnosis of malignant and premalignant endometrial lesions. Ten-eleven translocation (TET) proteins, especially TET1, were found to play a significant role in DNA demethylation, via conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1, 5-mC, and 5-hmC expression profiles in endometrial carcinogenesis are currently unclear. We conducted a hospital-based retrospective review of the immunohistochemical expression of TET1, 5-mC, and 5-hmC in 181 endometrial samples. A “high” TET1 and 5-hmC expression score was observed in all cases of normal endometrium (100.0% and 100.0%, respectively) and in most samples of endometrial hyperplasia without atypia (90.9% and 78.8%, respectively) and atypical hyperplasia (90.6% and 93.8%, respectively), but a “high” score was found in only less than half of the EC samples (48.8% and 46.5%, respectively). The TET1 and 5-hmC expression scores were significantly higher in normal endometrium and premalignant endometrial lesions than in ECs (p < 0.001). A “high” 5-mC expression score was observed more frequently for ECs (81.4%) than for normal endometrium (40.0%), endometrial hyperplasia without atypia (51.5%), and atypical hyperplasia (53.1%) (p < 0.001). We also found that TET1 mRNA expression was lower in ECs compared to normal tissues (p = 0.0037). TET1 immunohistochemistry (IHC) scores were highly proportional to the TET1 mRNA levels and we summarize that the TET1 IHC scoring can be used for biomarker determinations. Most importantly, a higher TET1 score in EC cases was associated with a good overall survival (OS) rate, with a hazard ratio (HR) of 0.31 for death (95% confidence interval: 0.11–0.84). Our findings suggest that TET1, 5-mC, and 5-hmC expression is a potential histopathology biomarker for the differential diagnosis of malignant and premalignant endometrial lesions. TET1 is also a potential prognostic marker for EC.