Antimony exposure promotes bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy.

Antimony is one of the heavier pnictogens and is widely found in human food chains, water sources, and as an air pollutant. Recent years have seen steadily increasing concentrations of antimony in the ecological environment; critically, several studies have indicated that antimony might pose a tumorigenic risk factor in several cancers. Therefore, antimony toxicity has attracted increasing research attention, with the molecular mechanisms underlying suspected antimony-mediated tumor transformation of greatest interest. Our results showed that the serum concentration of antimony was higher in bladder tumor patients relative to levels in non-tumor patients. Moreover, that such high antimony serum concentration were closely associated with poorer outcome in bladder tumor patients. Additionally, we demonstrated that the presence of antimony promoted both in vitro and in vivo bladder tumor cell growth. Our results also indicated that low-dose antimony resulted in significantly decreased mitochondrial membrane potential, mitochondrial respiratory enzyme complex I/II/III/IV activity, ATP/ADP ratio, and ATP concentration relative to the control group. These findings suggested that antimony caused mitochondrial damage. Finally, we found that low-dose antimony(0.8uM) inhibited mitophagy by deregulating expression of PINK1, Parkin, and p(ser65)-Parkin, and activation of PINK1-Parkin pathway by CCCP could inhibit antimony-induced tumor cell growth. Collectively, this inhibited the proliferation of bladder tumor cells. Overall, our study suggested that antimony promoted bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy. These findings highlight the therapeutic potential in targeting molecules within this antimony induced-PINK1/Parkin signaling pathway and may offer a new approach for the treatment of bladder cancer.

Identification and Immunocorrelation of Prognosis-Related Genes Associated With Development of Muscle-Invasive Bladder Cancer.

Improved understanding of the molecular mechanisms and immunoregulation of muscle-invasive bladder cancer (MIBC) is essential to predict prognosis and develop new targets for therapies. In this study, we used the cancer genome atlas (TCGA) MIBC and GSE13507 datasets to explore the differential co-expression genes in MIBC comparing with adjacent non-carcinoma tissues. We firstly screened 106 signature genes by Weighted Gene Co-expression Network Analysis (WGCNA) and further identified 15 prognosis-related genes of MIBC using the univariate Cox progression analysis. Then we systematically analyzed the genetic alteration, molecular mechanism, and clinical relevance of these 15 genes. We found a different expression alteration of 15 genes in MIBC comparing with adjacent non-carcinoma tissues and normal tissues. Meanwhile, the biological functions and molecular mechanisms of them were also discrepant. Among these, we observed the ANLN was highly correlated with multiple cancer pathways, molecular function, and cell components, revealing ANLN may play a pivotal role in MIBC development. Next, we performed a consensus clustering of 15 prognosis-related genes; the results showed that the prognosis, immune infiltration status, stage, and grade of MIBC patients were significantly different in cluster1/2. We further identified eight-genes risk signatures using the least absolute shrinkage and selection operator (LASSO) regression analysis based on the expression values of 15 prognosis-related genes, and also found a significant difference in the prognosis, immune infiltration status, stage, grade, and age in high/low-risk cohort. Moreover, the expression of PD-1, PD-L1, and CTLA4 was significantly up-regulated in cluster1/high-risk-cohort than that in cluster2/low-risk-cohort. High normalized enrichment score of the Mitotic spindle, mTORC1, Complement, and Apical junction pathway suggested that they might be involved in the distinct tumor immune microenvironment (TIME) of cluster1/2 and high-/low-risk-cohort. Our study identified 15 prognosis-related genes of MIBC, provided a feasible stratification method to help for the future immunotherapy strategies of MIBC patients.

Effects of different acupuncture methods combined with routine rehabilitation on gait of stroke patients.

BACKGROUND: Stroke refers to a group of cerebrovascular diseases associated with organic brain injury. It is characterized by the sudden and rapid onset of focal or diffuse dysfunction. In recent years, in addition to routine treatment, Chinese medicine acupuncture has been administered to patients with hemiplegia, and it can be considered a new treatment for rehabilitation. AIM: To investigate the effects of eye acupuncture needle retention and body acupuncture combined with routine rehabilitation on gait performance and plantar pressure in patients recovering from stroke. METHODS: Thirty-two stroke patients who met the inclusion criteria were randomly divided into an experimental group and a control group, with 16 patients in each group. Both groups underwent routine rehabilitation. The experimental group was treated by eye acupuncture needle retention, and the control group was treated by body acupuncture. Before and after 4 wk of treatment, both groups underwent kinematic and plantar pressure synchronous tests to assess gait performance. RESULTS: The step length, gait speed, step frequency, joint angles of the lower limbs, and ground reaction force impulse in the anterior region of the affected foot in both groups significantly increased from before to after treatment (P < 0.05); the center of mass displacement, peak pressure values, and impulse in the anterior region of the healthy foot and posterior regions of both the affected and healthy feet significantly decreased from before to after treatment (P < 0.05). The patients in the experimental group showed greater improvement in the following parameters than the control group: Step length, gait speed, step frequency, lower extremity joint angles, center of gravity displacement, and peak pressure values and impulse in the anterior and posterior regions of both the affected and healthy feet (P < 0.05). CONCLUSION: Eye acupuncture needle retention and body acupuncture combined with routine rehabilitation can effectively improve the gait performance of patients recovering from stroke. Between these two treatments, eye acupuncture needle retention combined with routine treatment is better than body acupuncture, and it can be considered a practical and effective clinical treatment.