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The plateau environment impacts male reproductive function, causing decreased sperm quality and testosterone levels. l-carnitine can improve the semen microenvironment. However, the role of l-carnitine in a high-altitude environment remains unclear. In our study, we investigated the effects of l-carnitine administration in a male Wistar rat reproductive system injury model in the context of a simulated high-altitude environment. Rats were randomly divided into a normal control group (group A1, A2-low dose and A3-high dose) and high-altitude model groups (group B, C-low dose and D-high dose) with 20 rats in each group. With the exception of the normal control group exposed to normoxic conditions, the other groups were maintained in a hypobaric oxygen chamber that simulated an altitude of 6000 m for 28 days. In the experimental period, the low-dose groups (A2 and C) were administered 50 mg/kg l-carnitine via intraperitoneal injection once a day, and the high-dose groups (A3 and D) were given 100 mg/kg. After the feeding period, blood samples were collected to assess blood gas, serum hormone levels and oxidative stress. Sperm from the epididymis were collected to analyse various sperm parameters. After obtaining the testicular tissue, the morphological and pathological changes were observed under a light microscope and transmission electron microscopy (TEM). The impact of the simulated high-altitude environment on the rat testis tissue is obvious. Specifically, a decreased testicular organ index and altered indices of arterial blood gas and serum sex hormone levels caused testicular tissue morphological damage, reduced sperm quality, increased sperm deformity rate and altered malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) concentrations. The results demonstrate that l-carnitine can be administered as a preventive intervention to reduce the reproductive damage caused by high-altitude hypobaric and hypoxic environments and improve semen quality in a rat model.

Background: CRYAB is closely related to apoptosis, invasion and migration of tumor cells. Nevertheless, the relationship between CRYAB, outcomes of prostate cancer (PCa), and the potential mechanisms have not been studied. Material and Methods: The TPM format RNA sequencing (RNAseq) and methylation data on differential expression came from the cancer genome atlas (TCGA) database. R software and packages were used to analyze the different expression of CRYAB in TCGA database, the correlation between gene expression and immune cell infiltration, receiver operating characteristic curve, cox regression, Kaplan-Meier curve, nomogram models and calibration curve. Then, the bio-function of CRYAB in prostate cancer cell lines was detected via cell counting kit‑8, invasion and terminal deoxynucleotidyl transferase dUTP nick end labelling assay. Results: Compared to normal tissues, CRYAB was down-regulated in prostate cancer tissues based on the TCGA database, and was corrected with Gleason score. The promoter methylation level of CRYAB in PCa was significantly higher than that in normal. Immune cell infiltration analysis showed that the infiltration of all these immune cells except TReg was positively related to CRYAB expression. ROC curve and KM curve demonstrated that CRYAB had a meaningful diagnosis and prognostic value. Cox regression analysis indicated that higher T stage, N stage, PSA, Gleason score, and lower CRYAB expression were prognostic indicators of PCa. Cell function experiments suggested that up-regulated CRYAB can inhibit the proliferation, invasion and migration of prostate cancer cells, and promote apoptosis. Conclusion:We found that CRYAB was down-expressed in tumor tissues, and was related with anti-tumor function in PCa cells. We identified CRYAB had a significant diagnosis and prognostic value in PCa.

Background: Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare types of PPGLs with a worse prognosis. However, there are no effective diagnostic molecular markers and the specific mechanism is still unclear. In this study, we screened the molecular diagnostic markers and predicted the metastasis mechanism of metastatic PPGLs through mRNA sequencing results in the Gene Expression Omnibus (GEO) dataset GSE67066 by bioinformatics. Methods and results: Data were obtained from GEO dataset GSE67066. R software and packages were used for differentially expressed genes (DEGs) analysis, receiver operating characteristic curve (ROC) assessment, logistic model construction, correlation analysis. Gene Data in The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database were included in the pan-cancer analysis. Finally, 35 up-regulated genes and 38 down-regulated genes were identified. All malignant tumors can be distinguished from the benign group by logistics regression equation (= 957.8354 + 49.148*IRX3 + -14.1748*GALNT10 + -30.2242*BAIAP3 + -34.7723*RAPGEF4 + -9.3218*PACRG + -51.3402*PRKCZ + 7.5959*CAMK2N1 + -43.7049*RD3). CNTN4, PAPPA, LPL, TG, FGF14, OPCT, ABAT, GSTO2, SLC24A2, SGSM1, ATCAY and BAIAP3 may be important genes for the metastasis of PPGLs through NORCH signaling and TNF/HIF1α/VEGF signaling pathways. KCNG3, PXMP2, SHROOM3, KIF18B and FAM49A expression was related to mutation types. Many DEGs’ expression presented the anti-tumor potential correlated with immunity checkpoints in the metastatic process of PPGLs.Conclusions: Combined gene mRNA expression model increases the diagnostic efficiency of the metastatic potential of PPGLs. Multiple genes including CNTN4, PAPPA, LPL, TG, FGF14, OPCT, ABAT, GSTO2, SLC24A2, SGSM1, ATCAY and BAIAP3 may participate in the metastasis of PPGLs through NORCH signaling and TNF/HIF1α/VEGF signaling pathways.

Circular RNA (circRNA) is a member of the non-coding RNA family that is formed by trans-splicing. Because of its unique structure and characteristics, it has extraordinary value for the diagnosis, treatment, and prognosis of diseases, particularly for tumors. Study of the role of circRNAs in the occurrence and development of prostate cancer has made considerable progress, but many areas remain that require further exploration and improvement. This article describes research into sequencing expression profiles, expression regulation, potential value as biomarkers, mechanism in the occurrence and development, therapy resistance, relationship with clinicopathological features, and prognostic value of circRNAs in prostate cancer from the past few years.

Hypoxia induced epithelial-to-mesenchymal transition (EMT) to facilitate the tumor biology. Phosphatidylethanolamine-binding protein 4 (PEBP4) is a member of the PEBP family and has been reported to be upregulated in various cancer types. The definite function of PEBP4 in regulating the EMT of prostate cancer, however, is still unclear. Here, we examined the functional role of PEBP4 and the underlying molecular mechanisms in hypoxia-induced EMT in prostate cancer cells. Our results showed that PEBP4 mRNA and protein expression was markedly increased in the human prostate cancer tissues and cell lines. Knockdown of PEBP4 significantly inhibited hypoxia-induced migration/invasion and EMT program. Furthermore, knockdown of PEBP4 prevented hypoxia-induced the expression of p-Akt and p-mTOR in prostate cancer cells. Taken together, this study reported here provided evidence that knockdown of PEBP4 inhibited hypoxia-induced EMT in prostate cancer cells. Our study uncovered a novel role for PEBP4 in prostate cancer progression, which might support the potential for PEBP4 targeting in prostate cancer therapy.