BACKGROUND Helenalin is a pseudoguaianolide natural product with anti-cancer activities. This study investigated the underlying mechanism of the anti-prostate cancer effects of helenalin in vitro. MATERIAL AND METHODS CCK-8 assay was performed to detect the optimal concentrations of helenalin in DU145 and PC-3 cells. After exposure to helenalin and/or reactive oxygen species (ROS) inhibitor, ROS production was assessed by DCFH-DA staining. Thioredoxin reductase-1 (TrxR1) expression was detected by RT-qPCR and western blot. Moreover, apoptosis and cell cycle were evaluated by flow cytometry. Following TrxR1 knockdown or overexpression, TrxR1 expression, ROS generation, apoptosis, cell cycle, migration, and invasion were examined in cells co-treated with helenalin. RESULTS Helenalin distinctly repressed the viability of prostate cancer cells in a concentration-dependent manner. We chose 8 μM and 4 μM as the optimal concentrations of helenalin for DU145 and PC-3 cells, respectively. Helenalin treatment markedly triggered ROS production and lowered TrxR1 expression, which was ameliorated by ROS inhibitor. Exposure to helenalin facilitated apoptosis as well as G0/G1 cell cycle arrest, which was reversed by ROS inhibitor. Helenalin relieved the inhibitory effect of TrxR1 on ROS production. Furthermore, helenalin ameliorated the decrease in apoptosis rate and the shortening of G0/G1 phase as well as the increase in migration and invasion induced by TrxR1 overexpression. CONCLUSIONS Our findings revealed that helenalin accelerated ROS-mediated apoptosis and cell cycle arrest via targeting TrxR1 in human prostate cancer cells.

To develop a natural mineral-based electrochemical enzyme biosensor, natural molybdenite (MLN), tyrosinase (TYR), and acridine orange (AO) were coadsorbed onto a glassy carbon electrode (GCE). The developed TYR/AO/MLN-GCE-based amperometric TYR biosensor exhibited excellent performance for highly sensitive determination of catechol (linear range, 0.1-80 μM; sensitivity, 0.0315 μA/μM; LOD, 0.029 μM; response time, <4 s) with good reproducibility and good operational and storage stabilities. The electrochemical impedance spectroscopy (EIS) and quartz crystal microbalance with dissipation (QCM-D) revealed interesting roles of AO: (1) an efficient glue for enhancing the amount of the adsorbed TYR on the MLN-GCE, (2) an anchor for efficient orientation of the adsorbed TYR on the MLN-GCE, and (3) a stabilizer providing a suitable microenvironment for the adsorbed TYR on the MLN-GCE surface. This physical adsorption-based AO-coupled enzyme-modification strategy onto natural MLN would be a versatile strategy to develop cost-effective and environment-friendly natural mineral-based electrochemical biosensors and bioelectronic devices.

Background: Hypertension is a leading cause of cardiovascular-related morbidity and mortality. Elevated blood pressure (BP) in children is related to long-term adverse health effects. Until recently, few studies have reported the secular trend and associated factors of hypertension phenotypes in Chinese children and adolescents. Methods: From the China Health and Nutrition Survey (CHNS) 1991-2015, a total of 15,143 records of children aged 7-17 years old were included. Following definitions of hypertension from the Chinese Child Blood Pressure References Collaborative Group, we estimated the prevalence of prehypertension, hypertension, stage 1 hypertension, stage 2 hypertension and its phenotypes (ISH, isolated systolic hypertension; IDH, isolated diastolic hypertension; SDH, combined systolic and diastolic hypertension). General estimation equation was used to analyze the trends in the prevalence of hypertension and hypertension phenotypes, and a multivariable logistic regression was constructed to explore the associated factors. Results: During 1991-2015, increasing trends were revealed in BP and hypertension prevalence (P < 0.001) in Chinese children and adolescents. For ISH, IDH and SDH, the age-standardized prevalence increased dramatically from 0.9 to 2.2%, from 6.2 to 14.1%, and from 1.4 to 2.9%, respectively (all P < 0.001). Adolescents aged 13-17 years (OR = 1.76, 95% CI: 1.56-1.97, P < 0.001), general obesity (OR = 2.69, 95% CI: 2.10-3.44, P < 0.001) and central obesity (OR = 1.49, 95% CI: 1.21-1.83, P < 0.001) were positively associated with hypertension, whereas the South region (OR = 0.65, 95% CI: 0.58-0.73, P < 0.001) was a negative factor. Furthermore, body mass index (BMI) and general obesity were linked to the presence of ISH, IDH and SDH. Age, waist circumference (WC) and central obesity were additionally associated with ISH, and sex, age, urban/rural setting, North/South region, WC and central obesity were additionally associated with IDH. Conclusion: BP levels and prevalence of hypertension and phenotypes increased dramatically in Chinese children and adolescents from 1991 to 2015. Regional discrepancy, demographic features, BMI, WC and overweight/obesity status were associated factors of hypertension among youths.

RNA-binding proteins (RBPs) have been shown to be dysregulated in cancer transcription and translation, but few studies have investigated their mechanism of action in soft tissue sarcoma (STS). Here, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to identify differentially expressed RBPs in STS and normal tissues. Through a series of biological information analyses, 329 differentially expressed RBPs were identified. Functional enrichment analysis showed that differentially expressed RBPs were mainly involved in RNA transport, RNA splicing, mRNA monitoring pathways, ribosome biogenesis and translation regulation. Through Cox regression analyses, 9 RBPs (BYSL, IGF2BP3, DNMT3B, TERT, CD3EAP, SRSF12, TLR7, TRIM21 and MEX3A) were all up-regulated in STS as prognosis-related genes, and a prognostic model was established. The model calculated a risk score based on the expression of 9 hub RBPs. The risk score could be used for risk stratification of patients and had a high prognostic value based on the receiver operating characteristic (ROC) curve. We also established a nomogram containing risk scores and 9 key RBPs to predict the 1-year, 3-year, and 5-year survival rates of patients in STS. Afterwards, methylation analysis showed significant changes in the methylation degree of BYSL, CD3EAP and MEX2A. Furthermore, the expression of 9 hub RBPs was closely related to immune infiltration rather than tumor purity. Based on the above studies, these findings may provide new insights into the pathogenesis of STS and will provide candidate biomarkers for the prognosis of STS.

This study investigated the effect of melatonin (MT) on cell cycle (G1/S/G2/M) of parthenogenetic zygotes developed from vitrified-warmed mouse metaphase II (MII) oocytes and elucidated the potential mechanism of MT action in the first cleavage of embryos.

Recently, more and more studies have highlighted the critical regulatory roles of circular RNAs (circRNAs), a class of non-coding RNAs, in the progression of many human cancers, including prostate cancer (PCa). circRNA microarray analysis was performed to identify circRNAs that are differentially expressed in PCa tissues.

Taraxacum kok-saghyz Rodin (TKS) is an important potential alternative source of natural inulin and rubber production, which has great significance for the production of industrial products. In this study, we sequenced 58 wild TKS individuals collected from four different geography regions worldwide to elucidate the population structure, genetic diversity, and the patterns of evolution. Also, the first flowering time, crown diameter, morphological characteristics of leaf, and scape of all TKS individuals were measured and evaluated statistically. Phylogenetic analysis based on SNPs and cluster analysis based on agronomic traits showed that all 58 TKS individuals could be roughly divided into three distinct groups: (a) Zhaosu County in Xinjiang (population AB, including a few individuals from population C and D); (b) Tekes County in Xinjiang (population C); and (c) Tuzkol lake in Kazakhstan (population D). Population D exhibited a closer genetic relationship with population C compared with population AB. Genetic diversity analysis further revealed that population expansion from C and D to AB occurred, as well as gene flow between them. Additionally, some natural selection regions were identified in AB population. Function annotation of candidate genes identified in these regions revealed that they mainly participated in biological regulation processes, such as transporter activity, structural molecule activity, and molecular function regulator. We speculated that the genes identified in selective sweep regions may contribute to TKS adaptation to the Yili River Valley of Xinjiang. In general, this study provides new insights in clarifying population structure and genetic diversity analysis of TKS using SNP molecular markers and agronomic traits.

Benign prostatic hyperplasia (BPH) is a frequently encountered disease in older men that affects sexual function and is capable of causing lower urinary tract dysfunction. Unfortunately, current treatment options for BPH primarily seek to address the lower urinary tract dysfunction aspect of the disease and do not improve sexual function. Yohimbine has been effectively used for decades to treat erectile dysfunction. Therefore, the objective of this study was to evaluate the inhibitory effect of yohimbine on BPH and explore the associated underlying mechanisms. Thirty-six rats were randomly divided into the control, BPH, finasteride (1 mg/kg), and yohimbine (2, 4, and 8 mg/kg) groups. Except for the rats in the control group, those in the other groups were subcutaneously injected testosterone propionate (5 mg/kg/day) daily for a period of 4 weeks to establish BPH models. They were also administration the corresponding drug daily for a period of 6 weeks. After the treatments, in addition to determining prostate wet weight and index, the histopathological status of the prostate was observed, and the levels of testosterone, dihydrotestosterone, prostatic acid phosphatase, the prostate-specific antigen, proliferating cell nuclear antigen, and steroid 5α-reductase were determined. Specifically, the administration of 2, 4, and 8 mg/kg yohimbine inhibited prostatic index increase by 46.7, 55.1, and 69.3%, respectively, in BHP rats. Further, yohimbine significantly reduced the levels of dihydrotestosterone, prostatic acid phosphatase, prostate-specific antigen, proliferating cell nuclear antigen, and steroid 5α-reductase, suggesting that it exerts beneficial effects against BPH by modulating the steroid 5α-reductase pathway.

Cholestasis patients often suffer from pain desensitization, resulting in serious complications in perioperative period. This study was aim to investigate the mechanism of bilirubin in cholestasis mediating pain desensitization through 5-hydroxytryptamine 3A (5-HT3A ) receptor activation in spinal dorsal horn (SDH).

Vascular smooth muscle cell (VSMC) apoptosis is a major defining feature of abdominal aortic aneurysm (AAA) and mainly caused by inflammatory cell infiltration. Smooth muscle (SM) 22α prevents AAA formation through suppressing NF-κB activation. However, the role of SM22α in VSMC apoptosis is controversial. Here, we identified that SM22α loss contributed to apoptosis of VSMCs via activation of macrophages. Firstly, deficiency of SM22α enhanced the interaction of VSMCs with macrophages. Macrophages were retained and activated by Sm22α -/- VSMCs via upregulating VCAM-1 expression. The ratio of apoptosis was increased by 1.62-fold in VSMCs treated with the conditional media (CM) from activated RAW264.7 cells, compared to that of the control CM (P < 0.01), and apoptosis of Sm22α -/- VSMCs was higher than that of WT VSMCs (P < 0.001). Next, circRasGEF1B from activated macrophages was delivered into VSMCs promoting ZFP36 expression via stabilization of ZFP36 mRNA. Importantly, circRasGEF1B, as a scaffold, guided ZFP36 to preferentially bind to and decay Bcl-2 mRNA in a sequence-specific manner and triggered apoptosis of VSMCs, especially in Sm22α -/- VSMCs. These findings reveal a novel mechanism by which the circRasGEF1B-ZFP36 axis mediates macrophage-induced VSMC apoptosis via decay of Bcl-2 mRNA, whereas Sm22α -/- VSMCs have a higher sensitivity to apoptosis.

Bromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F-actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL-stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

Castration-resistant prostate cancer (CRPC) is an advanced stage of prostate cancer that can progress rapidly even in patients treated with castration. Previously, we found that tumor-associated macrophages (TAM) can be recruited by CSF-1 secreted by docetaxel-treated prostate cancer cells and promote the survival of cancer cells in response to chemotherapy. The inhibition of CSF-1R can impede this effect and significantly prolong survival in xenograft mice. However, the actual mechanism of how TAM improves cancer cell survival still remains elusive and controversial. Here, for the first time, we found that the enhanced survival of cancer cells achieved by TAM was mainly mediated by CXCR4 activation from the increased secretion of CXCL12 from CSF-1 activated TAM. This finding helps to clarify the mechanism of chemoresistance for second-line chemotherapy using docetaxel, facilitating the development of novel drugs to overcome immune tolerance in castration-resistant prostate cancer.

This study aimed to investigate the prognostic value of CIP2A (cancerous inhibitor of protein phosphatase 2A) and the NLR (neutrophil-lymphocyte ratio) in the serum of patients with CRC (colorectal cancer) after resection.

Fusobacterium nucleatum (Fn) has been considered as a significant contributor in promoting colorectal carcinoma (CRC) development by suppressing host anti-tumor immunity. Recent studies demonstrated that the aggregation of M2 macrophage (Mφ) was involved in CRC progress driven by Fn infection. However, the underlying molecular mechanisms are poorly characterized. Here, we investigated the role of Fn in Mφ polarization as well as its effect on CRC malignancy. Fn infection facilitated differentiation of Mφ into the M2-like Mφ phenotype by in vitro study. Histological observation from Fn-positive CRC tissues confirmed the abundance of tumor-infiltrating M2-like Mφ. Fn-induced M2-like Mφ polarization was weakened once inhibiting a highly expressed damage-associated molecular pattern (DAMP) molecule S100A9 mainly derived from Fn-challenged Mφ and CRC cells. In addition, Fn-challenged M2-like Mφ conferred CRC cells a more malignant phenotype, showing stronger proliferation and migration characteristics in vitro and significantly enhanced tumor growth in vivo, all of which were partially inhibited when S100A9 was lost. Mechanistic studies further demonstrated that activation of TLR4/NF-κB signaling pathway mediated Fn-induced S100A9 expression and subsequent M2-like Mφ activation. Collectively, these findings indicate that elevated S100A9 in Fn-infected CRC microenvironment participates in M2-like Mφ polarization, thereby facilitating CRC malignancy. Furthermore, targeting TLR4/NF-κB/S100A9 cascade may serve as promising immunotherapeutic strategy for Fn-associated CRC.

Cancer cells use glucose via glycolysis to maintain tumor cell proliferation. However, the effect of long non-coding RNAs (lncRNAs) on glycolysis in osteosarcoma (OS) cells remains unclear. The present study aimed to investigate the involvement of the lncRNA XLOC_005950/hsa-microRNA (miR)-542-3p/phosphofructokinase, muscle (PFKM) axis in the regulation of glucose metabolism, cell proliferation and apoptosis in the progression of OS. lncRNA XLOC_005950, hsa-miR-542-3p and PFKM expression in OS tissues and cells was detected via reverse transcription-quantitative PCR analysis. CRISPR/Cas9 gene editing was used to knockout lncRNA XLOC_005950 expression in MG63 cells. Cell Counting Kit-8 assay, flow cytometry, PFKM activity, and glucose and lactic acid content determination were performed to assess the effects of lncRNA XLOC_005950 knockout and overexpression of hsa-miR-542-3p on the phenotypes of OS cells. The dual-luciferase reporter assay was performed to confirm the targeting associations between lncRNA XLOC_005950, hsa-miR-542-3p and PFKM. The results demonstrated that lncRNA XLOC_005950 expression was upregulated in OS tissues and cells. Functional experiments indicated that lncRNA XLOC_005950 knockout decreased PFKM activity, the intracellular glucose and lactic acid content, and cell proliferation, while increasing apoptosis of OS cells. Furthermore, lncRNA XLOC_005950 knockout upregulated hsa-miR-542-3p expression and downregulated PFKM expression. Overexpression of hsa-miR-542-3p suppressed PFKM expression. Furthermore, lncRNA XLOC_005950, as the molecular sponge of miR-542-3p in OS, modulated the downstream target gene, PFKM. Taken together, the results of the present study suggest that lncRNA XLOC_005950 knockout may inhibit the progression of OS via hsa-miR-542-3p-mediated regulation of PFKM expression.

Cotton produces natural fiber for the textile industry. The genetic effects of genomic structural variations underlying agronomic traits remain unclear. Here, we generate two high-quality genomes of Gossypium hirsutum cv. NDM8 and Gossypium barbadense acc. Pima90, and identify large-scale structural variations in the two species and 1,081 G. hirsutum accessions. The density of structural variations is higher in the D-subgenome than in the A-subgenome, indicating that the D-subgenome undergoes stronger selection during species formation and variety development. Many structural variations in genes and/or regulatory regions potentially influencing agronomic traits were discovered. Of 446 significantly associated structural variations, those for fiber quality and Verticillium wilt resistance are located mainly in the D-subgenome and those for yield mainly in the A-subgenome. Our research provides insight into the role of structural variations in genotype-to-phenotype relationships and their potential utility in crop improvement.

Glioma is a common primary central nervous system tumour, and therapeutic drugs that can effectively improve the survival rate of patients in the clinic are lacking. Bufalin is effective in treating various tumours, but the mechanism by which it promotes the apoptosis of glioma cells is unclear. The aim of this study was to investigate the drug targets of bufalin in glioma cells and to clarify the apoptotic mechanism.

Linc00312 is dysregulated in nasopharyngeal carcinoma (NPC) and participates in the initiation and progression of NPC. Our previous studies suggested that linc00312 was able to enhance the sensitivity of NPC cells to irradiation and NPC patients with higher expression of linc00312 was associated with better short-term curative effect and overall survival. The single nucleotide polymorphisms (SNPs) of lncRNAs may influence the disease course and outcome by affecting the expression, secondary structure or function of lncRNAs. However, the role of SNPs in linc00312 on the occurrence and survival of NPC remains unknown.

Carbonation as a sensory enhancement strategy for prevention of aspiration of thin liquids has not been thoroughly studied. The aim of our study was to examine the effect of carbonation on penetration-aspiration and pharyngeal residue in dysphagia patients using Fiber-Optic Endoscopic Evaluation of Swallowing (FEES) and to identify parameters associated with a response to carbonation.

Cryopreservation induces transcriptomic and epigenetic modifications that strongly impairs sperm quality and function, and thus decrease reproductive performance. N6-methyladenosine (m6A) RNA methylation varies in response to stress and has been implicated in multiple important biological processes, including post-transcriptional fate of mRNA, metabolism, and apoptosis. This study aimed to explore whether cryopreservation induces m6A modification of mRNAs associated with sperm energy metabolism, cryoinjuries, and freezability.