Linc00513 sponges miR-7 to modulate TGF-ß signaling in azoospermia.

Azoospermia, or the complete absence of sperm in the ejaculate, affects about 1% of men worldwide and is a significant fertility challenge. This study investigates Linc00513, a long non-coding RNA, and its potential role in regulating the TGF-ß signaling pathway, a key player in spermatogenesis, in the context of azoospermia. We show that Linc00513 expression is significantly lower in testicular tissues from azoospermic patients than in HS1 controls. Linc00513 interacts directly with microRNA-7 (miR-7) via complementary base pairing, acting as a competing endogenous RNA (ceRNA). This interaction effectively inhibits miR-7's inhibitory action on the TGF-ß receptor 1 (TGFBR1), a critical component of the TGF-ß signaling cascade. Downregulating Linc00513 reduces TGFBR1 repression and increases TGF-ß signaling in azoospermic testes. Functional assays with spermatogonial cell lines support these findings. Silencing Linc00513 leads to increased cell proliferation and decreased apoptosis, similar to TGF-ß inhibition. Overexpression of miR-7 inhibits the effects of Linc00513 on TGF-ß signaling. Our study sheds new light on how Linc00513, miR-7, and the TGF-ß signaling pathway interact in azoospermia. Linc00513 regulates TGFBR1 expression and thus influences spermatogonial cell fate by acting as a miR-7 ceRNA. These findings identify a potential therapeutic target for azoospermia treatment, paving the way for future research into restoring fertility in affected individuals.

Bioinformatics analysis of microarray data to identify hub genes, as diagnostic biomarker of HELLP syndrome: System biology approach.

BACKGROUND: HELLP syndrome is one of the disorders characterized by hemolysis, increased liver enzymes and decreased platelet count. So far, many molecular pathways and genes have been identified in relation to the pathogenesis of this syndrome; however, the main cause of the incidence and progression of the disease has not been identified. Using the biological system approach is a way to target patients by identifying genes and molecular pathways. In this study, we investigated genes and important molecular factors in the pathogenesis of HELLP syndrome. MATERIAL AND METHODS: In this study, the microarray dataset was downloaded from Gene Expression Omnibus (GEO) database and analyzed using the GEO2R online tool for identifying differentially expressed genes (DEGs). Enrichment analysis of DEGs was evaluated using the Enrichr database. Then, protein-protein interaction (PPI) networks were constructed via the STRING database; they were visualized by Cytoscape. Then the STRING database was used to construct PPI networks. The hub genes were recognized using the cytoHubba. Ultimately, the interaction of the miRNA-hub genes and drug-hub genes were also evaluated. RESULT: After analysis, it was found that some genes with the highest degree of connectivity are involved in the pathogenesis of HELLP syndrome, which are known as the hub genes. These genes are as follows: KIT, JAK2, LEP, EP300, HIST1H4L, HIST1H4F, HIST1H4H, MMP9, THBS2, and ADAMTS3. Has-miR-34a-5p was also most associated with hub genes. CONCLUSION: Finally, it can be said, that the identification of genes and molecular pathways in HELLP syndrome can be helpful in identifying the pathogenesis pathways of the disease, and designing therapeutic targets.

Upregulation of elafin expression in the fallopian tube of ectopic tubal pregnancies compared to the normal tubes.

BACKGROUND: Ectopic pregnancy is one of the most important causes of maternal deaths and fallopian tubes are the location of 95% of ectopic pregnancies. Elafin is a natural antimicrobial molecule that plays an important role as an anti-inflammatory agent in mucosal surfaces and has been found in the female reproductive tract. OBJECTIVES: The aim of this study was to investigate elafin expression, in the fallopian tube mucosa of ectopic pregnancies compared to the normal tubes using immunohistochemistry (IHC) techniques and quantitative reverse transcription (qRT)-PCR. METHODS: In this case-control study, uterine tube samples were obtained from patients with an indication for surgical removal of the tubes. The case group (n = 20) consisted of patients who were undergoing salpingectomy due to an ectopic pregnancy, the control group (n = 20) included patients who had a salpingectomy and hysterectomy. Using qRT-PCR and IHC, the expression of elafin was investigated in both study groups. RESULTS: Immunohistochemical expression of elafin in the epithelium and connective tissue was significantly increased in the implantation site of the patients in comparison with the control group (P < 0.001). The level of elafin mRNA increased in the mucous membrane of the fallopian tube from patients with the ectopic pregnancy compared to the normal mucosa (P < 0.001). CONCLUSION: Increasing expression of elafin during an ectopic pregnancy may be a mechanism for enhancing innate immune response and be involved in related pathological conditions such as infection and ectopic implantation.