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Background: Hypertrophic scar (HS) is associated with cosmetic defects, mobility, and functional impairments, pruritus, and pain. Previous circRNA microarray analysis identified reduced expression of circRNA_SLC8A1 in HS tissues. Therefore, this study aims to investigate the role of circRNA_SLC8A1 in modulating the abnormal behavior of HS-derived fibroblasts (HSFs) in vitro. Methods: RT-qPCR and FISH assays were used to assess the differential expression and localization of circRNA_SLC8A1 in normal and HS tissues. Following modulation of circRNA_SLC8A1 expression, CCK-8, flow cytometry, Transwell, and wound healing assays were employed to evaluate the effects of circRNA_SLC8A1 on the biological behaviors of HSFs. The Starbase database, dual-luciferase reporter assays, and Ago2-RIP assays were utilized to predict and validate the interaction between circRNA_SLC8A1 and downstream miRNAs. Results: CircRNA_SLC8A1 was found to be downregulated in HS tissues and was primarily localized in the cytoplasm. Overexpression of circRNA_SLC8A1 reduced cell viability, cell invasion, wound healing, and the expression of Vimentin, N-cadherin, Col I, and Col III, while enhancing apoptosis and E-cadherin expression in HSFs. CircRNA_SLC8A1 activates the Nrf2-ARE pathway by competitively binding to miRNA-27a-3p. miRNA-27a-3p and Nrf2 exhibited high and low expression, respectively in HS tissues, with an inverse correlation between their levels. Overexpression of miRNA-27a-3p counteracted the effects of circRNA_SLC8A1 in HSF proliferation, apoptosis, migration, EMT, collagen deposition, and Nrf2-ARE pathway activity. Conclusion: CircRNA_SLC8A1 inhibits the proliferation, migration, EMT, and collagen deposition of HSF through competitive binding with miRNA-27a-3p, thereby activating the Nrf2-ARE pathway. The circRNA_SLC8A1/miRNA-27a-3p/Nrf2-ARE axis may offer a promising molecular target for HS therapy. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E virus (HEV) infection is a common cause of acute hepatitis worldwide and causes approximately 30% case fatality rate among pregnant women. Pregnancy serum (PS), which contains a high concentration of estradiol, facilitates HEV replication in vitro through the suppression of the PI3K–AKT–mTOR and cAMPK–PKA–CREB signaling pathways. However, the proteomics of the complex host responses to HEV infection, especially how PS facilitates viral replication, remains unclear. Methods: In this study, the differences in the proteomics of HEV-infected HepG2 cells supplemented with fetal bovine serum (FBS) from those of HEV-infected HepG2 cells supplemented with serum from women in their third trimester of pregnancy were quantified by using isobaric tags for relative and absolute quantification technology. Results: A total of 1511 proteins were identified, among which 548 were defined as differentially expressed proteins (DEPs). HEV-infected cells supplemented with PS exhibited the most significant changes at the protein level. A total of 328 DEPs, including 66 up-regulated and 262 down-regulated proteins, were identified in HEV-infected cells supplemented with FBS, whereas 264 DEPs, including 201 up-regulated and 63 down-regulated proteins, were found in HEV-infected cells supplemented with PS. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that in HEV-infected cells, PS supplementation adjusted more host genes and signaling pathways than FBS supplementation. The DEPs involved in virus–host interaction participated in complex interactions, especially a large number of immune-related protein emerged in HEV-infected cells supplemented with PS. Three significant or interesting proteins, including filamin-A, thioredoxin, and cytochrome c, in HEV-infected cells were functionally verified. Conclusions: The results of this study provide new and comprehensive insight for exploring virus–host interactions and will benefit future studies on the pathogenesis of HEV in pregnant women. [ABSTRACT FROM AUTHOR]

Objective. The goal was to confirm the mechanism by which miR-125b-5p influences melanocyte biological behavior and melanogenesis in vitiligo by regulating MITF. Methods. oe-MITF, sh-MITF, miR-125b-5p mimic, NC-mimic, NC-inhibitor, and miR-125b-5p inhibitor were transfected into cells by cell transfection. Western blotting was used to detect the related protein expression, qRT–PCR was used to detect miR-125b-5p and MITF expression, immunohistochemistry was used to detect the MITF-positive cells in vitiligo patients tissues, and a dual-luciferase reporter system was used to detect the target of miR-125b-5p and MITF. PIG1 and PIG3V cell proliferation by the CCK-8 method, cell cycle progression and apoptosis by flow cytometry, apoptosis was detected by TUNEL, Tyr activity and melanin content were measured using Tyr and melanin content assay kits. Results. Compared with the healthy control group, the expression of miR-125b-5p in the tissues and serum of vitiligo patients was upregulated, and the expression of MITF was downregulated; compared with PIG1 cells, the expression of miR-125b-5p and MITF in the PIG3V group was consistent with the above. Compared with the NC-minic group, the cell proliferation activity of the miR-125b-5p mimic group decreased, apoptosis increased, and the expression levels of melanogenesis-related proteins Tyr, Tyrp1, Tyrp2, and DCT were downregulated. Compared with the NC-inhibitor group, the above indices in the miR-125b-5p inhibitor group were all opposite to those in the miR-125b-5p mimic group. Transfection of oe-MITF into the miR-125b-5p mimic group reversed the effect of the miR-125b-5p mimic, while transfection of sh-MITF enhanced the effect of the miR-125b-5p mimic. Conclusion. miR-125b-5p affects vitiligo melanocyte biological behavior and melanogenesis by downregulating MITF expression. [ABSTRACT FROM AUTHOR]

To evaluate whether uterine injury caused by hepatitis E virus (HEV) infection is responsible for adverse pregnancy outcomes. HEV-infected female BALB/c mice were coupled with healthy male BALB/c mice at 0, 7, 14, 21, and 91 dpi to explore the uterine injury caused by HEV infection. Mice were euthanized after 10 days of copulation, and uteruses were collected for HEV RNA and antigen detection and histopathological analysis. Inflammatory responses; apoptosis; and estrogen receptor ɑ (ER-ɑ), endomethal antibody (ERAb), cytokeratin-7 (CK7), vimentin (VIM), and vascular endothelial growth factor (VEGF) expression levels were evaluated. After 10 days of copulation, miscarriage and nonpregnancy, as well as enlarged uteruses filled with inflammatory cytokines, were found in HEV-infected mice. HEV RNA and antigens were detected in the sera and uteruses of HEV-infected mice. Significant endometrial thickness (EMT) thinning, severe inflammatory responses, and aggravated apoptosis in the uteruses of HEV-infected mice that experienced miscarriage might contribute to adverse pregnancy outcomes. Furthermore, significantly suppressed ER-ɑ expression and increased ERAb, CK7, VIM, and VEGF expression levels were found in the uteruses of HEV-infected mice that had miscarried. However, uterine damage recovered after complete HEV clearance, and impaired fertility was improved. EMT injury, severe inflammatory responses, and aggravated apoptosis in the uterus caused by HEV infection are responsible for poor pregnancy outcomes. [ABSTRACT FROM AUTHOR]