STAT1-induced upregulation of lncRNA LINP1 promotes cell proliferation and inhibits apoptosis via AMPK signaling pathway in papillary thyroid cancer.

OBJECTIVE: The purpose of this study was to detect the relative expression of long non-coding ribonucleic acid (lncRNA) in non-homologous end joining pathway 1 (LINP1) in papillary thyroid cancer (PTC) tissues and cells, and to investigate the molecular mechanisms of abnormal expression and biological function of LINP1. PATIENTS AND METHODS: The relative expression of LINP1 in PTC tissues and cells was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the impact of small interfering (si)-LINP1 on the proliferative capacity of PTC cells was studied using Cell Counting Kit-8 (CCK-8) and colony formation assays. After the expression of LINP1 in PTC cells was interfered, flow cytometry was applied to determine the changes in cell cycle distribution and apoptosis rate. The transcription factors binding to the promoter region of LINP1 were predicted by bioinformatics. Next, qRT-PCR assay was adopted to measure the changes in LINP1 expression after interference in the expression of signal transducer and activator of transcription 1 (STAT1). Finally, the changes in the expressions of molecular markers of the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway were examined via Western blotting assay after the expressions of STAT1 and LINP1 were interfered. RESULTS: It was shown in qRT-PCR results that LINP1 expression was upregulated in 42 out of 53 cases of PTC tissues and in all PTC cells. After interference in the expression of LINP1 in PTC cells, the results of CCK-8 and colony formation assays indicated that the proliferative capacity of the cells was repressed. According to the results of flow cytometry, the cell cycle was arrested at the G1/G0 phase, and the apoptosis rate was increased. In addition, the bioinformatics predicted that STAT1 could bind to the promoter region of LINP1, and the results of qRT-PCR indicated that the expression of LINP1 declined after STAT1 expression was interfered. Moreover, it was indicated in the Western blotting assay after interference in the expressions of STAT1 and LINP1 that the expression of molecular marker (Phosphorylation AMPK, p-AMPK) of the AMPK signaling pathway was altered but the expression of total AMPK did not change. CONCLUSIONS: The transcription factor STAT1 promotes the expression of LINP1 in PTC, and highly expressed LINP1 facilitates the proliferation and inhibits the apoptosis of PTC by suppressing the AMPK signaling pathway.

Body mass index, waist-to-hip ratio, waist circumference and waist-to-height ratio cannot predict male semen quality: a report of 1231 subfertile Chinese men.

There were controversial results between obesity-associated markers and semen quality. In this study, we investigated the correlations between age, obesity-associated markers including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and waist circumference (WC), the combination of age and obesity-associated markers, semen parameters and serum reproductive hormone levels in 1231 subfertile men. The results showed that BMI, WC, WHR and WHtR were positively related to age, and there were also positive relations between BMI, WHR, WC and WHtR and between sperm concentration (SC), total sperm count (TSC), progressive motility (PR), sperm motility and per cent of normal sperm morphology (NSM). However, age, each of obesity-associated markers and the combination of obesity-associated markers and age were unrelated to any of semen parameters including total normal-progressively motile sperm count (TNPMS). Age, BMI, WHR, WC and WHtR were negatively related to serum testosterone and SHBG levels. However, only serum LH and FSH levels were negatively related to sperm concentration, NSM and sperm motility. In a conclusion, although age and obesity have significant impacts on reproductive hormones such as testosterone, SHBG and oestradiol, semen parameters related to FSH and LH could not be influenced, indicating that obesity-associated markers could not predict male semen quality.

Plasma FGF23 levels and heart rate variability in patients with stage 5 CKD.

UNLABELLED: Fibroblast growth factor 23(FGF23) is a bone-derived hormone which regulates mineral homeostasis but may also have a role in cardiovascular disease. Here, we found that higher plasma FGF23 was independently associated with decreased heart rate variability in stage 5 CKD patients and parathyroidectomy may reverse these abnormal indicators. INTRODUCTION: Lower heart rate variability (HRV) in patients with chronic kidney disease (CKD) compared with healthy controls is associated with increased risk of cardiovascular disease (CVD). Higher levels of plasma FGF23 also predict higher risk of CVD. Here, we aimed to evaluate the relationship between plasma FGF23 levels and HRV in patients with stage 5 CKD and to investigate longitudinal changes of them together with the correlation between their changes in two severe secondary hyperparathyroidism (SHPT) subgroups with successful parathyroidectomy (PTX) and persistent SHPT. METHODS: This cross-sectional study included 100 stage 5 CKD patients, 78 controls, and a prospective study in two PTX subgroups classified as successful PTX (n = 24) and persistent SHPT (n = 4) follow-up. Blood examination and 24-h Holter monitoring for HRV were measured. RESULTS: Most HRV indices were lower in stage 5 CKD patients than in healthy controls, and plasma FGF23 levels were higher. In multivariate stepwise regression models, levels of plasma FGF23 and serum parathyroid hormone (PTH) were correlated with HRV. The successful PTX subgroup had significant improvements over baseline in HRV indices. Persistent SHPT subgroup had numerically similar changes in HRV indices. However, plasma FGF23 levels decreased in both subgroups. CONCLUSIONS: Plasma FGF23 levels were higher in CKD patients than in controls, much higher in patients with severe SHPT. FGF23 was independently associated with decreased HRV in stage 5 CKD. Successful PTX may reverse these abnormal indicators and contribute to decreases in the risk of cardiovascular disease.

Major histocompatibility complex class II polymorphisms in forest musk deer (Moschus berezovskii) and their probable association with purulent disease.

Genes of the major histocompatibility complex (MHC) family are crucial in immune responses because they present pathogenic peptides to T cells. In this study, we analysed the genetic variation in forest musk deer (Moschus berezovskii) MHC II genes and its potential association with musk deer purulent disease. In total, 53 purulent disease-susceptible and 46 purulent disease-resistant individuals were selected for MHC II exon 2 fragment analysis. Among them, 16 DQ alleles and four additional DR alleles were identified, with DQ exon 2 fragments displaying a low level of polymorphism. The nonsynonymous substitutions exceeded the synonymous substitutions in the peptide-binding sites of DQA2, DQB1 and DQB2. Then, 28 MHC II alleles were used to analyse the distribution patterns of purulent disease between the susceptible and resistant groups. Among them, three alleles (DQA1*01, DQA1*02 and DQA2*04) were found to be resistant, and five alleles (DRB3*07, DQA1*03, DQA1*04, DQA2*05 and DQA2*06) were found to increase susceptibility. Additionally, three haplotypes were found to be putatively associated with musk deer purulent disease. However, these three haplotypes were only found in the resistant or susceptible group, and their frequencies were low. The results from our study support a contributory role of MHC II polymorphisms in the development of purulent disease in forest musk deer.

Studies on apoptosis of spermatogenic cells in normal fertile men treated with supraphysiological doses of testosterone undecanoate.

AIM: To study the anti-spermatogenic mechanism of supra-physiological doses of testosterone undecanoate (TU). METHODS: Twenty fertile adult men received four intramuscular injections of TU at monthly intervals, 1000 mg upon admission and 500 mg for the subsequent injections. The apoptotic germ cells in the semen were studied under light microscope with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Wright-Giemsa staining methods. RESULTS: After treatment, the sperm density and the number of spermatogenic cells in the semen were significantly decreased (P < 0.01), while the apoptotic ratios of spermatocytes and spermatids increased significantly (P < 0.01) as compared with the pretreatment levels. Apoptosis was found to be augmented in the whole series of castoff spermatogenic cells. CONCLUSION: Besides its suppressive effect on spermatogenesis through a negative feed-back mechanism, TU enhances apoptosis of spermatogenic cells, which may be an additional mechanism of its anti-spermatogenic activity.