Search

LIVIN, a member of the inhibitor of apoptosis proteins (IAPs), is reported playing important roles in the development and progression of multiple human cancers. However, its underlined mechanisms in human renal cell carcinoma (RCC) are still needed to be clarified. In the present study, we reported that inhibition of miR‐214 promoted the expression of LIVIN, then facilitated RCC cells growth and reduced the sensitivity of RCC cells to chemotherapeutic drugs. In constant, overexpression of miR‐214 had contradictory effects. Further investigation showed that miR‐214 was down‐regulated in RCC because of abnormal methylation. In addition, DNA methyltransferase DNMT1, miR‐214 and LIVIN are directly correlated in RCC patients. In conclusion, these results suggest that abnormal miR‐214 methylation negatively regulates LIVIN, which may promote RCC cells growth and reduced the sensitivity of RCC cells to chemotherapeutic drugs.

Background At present, there are no new method for establishing operative channels for the unilateral biportal endoscopic(UBE)system. Objective This paper describes a new method for establishing operative channels in UBE surgery. Meanwhile, we assessed the preliminary efficacy of unilateral biportal endoscopic discectomy (UBED) in treating degenerative disc disease. Methods We retrospectively reviewed 52 patients who underwent UBED from February 2020 to August 2020 via our new method. The Oswestry Disability Index (ODI) and visual analogue scale (VAS) score were measured preoperatively and 1 month, 3 months, 6 months and 12 months postoperatively. Repeated measures one-way analysis of variance (RM-ANOVA) was performed to compare the pre-and postoperative VAS scores and ODIs. Post hoc pairwise comparisons (paired t-tests) was used to compare the postoperative VAS scores and ODIs. Results The postoperative ODIs and VAS scores of low back pain and leg pain were significantly lower than those before surgery, and differences were statistically significant (all p < 0.05). Further pairwise comparisons brought out significant differences in the ODI at each time point after surgery (all p < 0.008). Significant differences were found in the VAS score of leg pain between 1 month and 6 months, 1 month and 12 months, and 3 months and 12 months (all p < 0.008). Pairwise comparisons in the VAS score of back pain between 1 month and 12 months differences (p < 0.008). Conclusion The modified channel establishment can provide a clear field of view in UBE surgery. UBED can yield a satisfactory curative effect in treating degenerative disc disease.

Occurrence and development of cancers are governed by complex networks of interacting intercellular and intracellular signals. The technology of single-cell RNA sequencing (scRNA-seq) provides an unprecedented opportunity for dissecting the interplay between the cancer cells and the associated microenvironment. Here we combined scRNA-seq data with clinical bulk gene expression data to develop a computational pipeline for identifying the prognostic and predictive signature that connects cancer cells and microenvironmental cells. The pipeline was applied to glioma scRNA-seq data and revealed a tumor-associated microglia/macrophage-mediated EGFR/ERBB2 feedback-crosstalk signaling module, which was defined as a multilayer network biomarker (MNB) to predict survival outcome and therapeutic response of glioma patients. We used publicly available clinical data sets from large cohorts of glioma patients to examine the prognostic significance and predictive accuracy of the MNB, which outperformed conventional gene biomarkers and other methods. Additionally, the MNB was found to be predictive of the sensitivity or resistance of glioma patients to molecularly targeted therapeutics. Moreover, the MNB was an independent and the strongest prognostic factor when adjusted for clinicopathologic risk factors and other existing gene signatures. The robustness of the MNB was further tested on additional data sets. Our study presents a promising scRNA-seq transcriptome-based multilayer network approach to elucidate the interactions between tumor cell and tumor-associated microenvironment and to identify prognostic and predictive signatures of cancer patients. The proposed MNB method may facilitate the design of more effective biomarkers for predicting prognosis and therapeutic resistance of cancer patients.

Background Radicular pain, caused by a lesion or autologous nucleus pulposus (NP) implantation, is associated with alteration in gene expression of the pain-signaling pathways. lncRNAs have been shown to play critical roles in neuropathic pain. However, the mechanistic function of lncRNAs in lumbar disc herniation (LDH) remains largely unknown. Identifying different lncRNA expression under sham and NP-implantation conditions in the spinal cord is important for understanding the molecular mechanisms of radicular pain. Methods LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. The mRNA and lncRNA microarray analyses demonstrated that the expression profiles of lncRNAs and mRNAs between the LDH and sham groups were markedly altered at 7 days post operation. The expression patterns of several mRNAs and lncRNAs were further proved by qPCR. Results LDH produced persistent mechanical and thermal hyperalgesia. A total of 19 lncRNAs was differentially expressed (>1.5-folds), of which 13 was upregulated and 6 was downregulated. In addition, a total of 103 mRNAs was markedly altered (>1.5-folds), of which 40 was upregulated and 63 downregulated. Biological analyses of these mRNAs further demonstrated that the most significantly upregulated genes in LDH included chemotaxis, immune response, and positive regulation of inflammatory responses, which might be important mechanisms underlying radicular neuropathic pain. These 19 differentially expressed lncRNAs have overlapping mRNAs in the genome, which are related to glutamatergic synapse, cytokine-cytokine receptor interaction, and the oxytocin-signalling pathway. Conclusion Our findings revealed the alteration of expression patterns of mRNAs and lncRNAs in the spinal cord of rats in a radicular pain model of LDH. These mRNAs and lncRNAs might be potential therapeutic targets for the treatment of radicular pain.

// Guo Dai 1, * , Di Zheng 1, * , Qianliang Wang 2 , Jian Yang 1 , Gaiwei Liu 1 , Qi Song 1 , Xiangran Sun 1 , Chunjie Tao 1 , Qingzhu Hu 1 , Tian Gao 3 , Ling Yu 1 and Weichun Guo 1 1 Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P. R. China 2 Department of Urology Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P. R. China 3 Department of Orthopedic Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Beijing 100000, P. R. China * These authors have contributed equally to this work Correspondence to: Weichun Guo, email: guoweichun@aliyun.com Ling Yu, email: scaling@whu.edu.cn Keywords: baicalein, osteosarcoma, proliferation, apoptosis, Wnt signaling pathway Received: July 17, 2017 Accepted: August 29, 2017 Published: September 18, 2017 ABSTRACT Osteosarcoma is a very common type of malignant bone tumor in children and young adults and aberrant activation of Wnt/β-catenin signaling pathway has been discovered in osteosarcoma. The traditional Chinese medicine baicalein was proved to have anti-proliferative and anti-metastatic properties in osteosarcoma, but the mechanism remained poorly understood. In the present study, we assessed the effects of baicalein on osteosarcoma and detected the potential molecular mechanism. We found that baicalein significantly suppressed the proliferation of osteosarcoma cells in a concentration- and time-dependent manner. In additional, baicalein could induce apoptosis and cell cycle arrest and reduce cell motility. Moreover, the level of β-catenin and its target genes, including c-myc, cyclinD1, and survivin significantly decreased in baicalein-treated osteosarcoma cells, whereas exogenous expression of β-catenin could reverse the anti-proliferative and anti-metastatic effects of baicalein. Subsequently, we established a 143B xenograft tumor model and found that baicalein treatment significantly inhibited tumor growth accompanied with inhibiting Wnt/β-catenin pathway. Thus, these findings suggest that baicalein may be a potentially effective Chinese herbal medicine for therapeutics of osteosarcoma and Wnt/β-catenin signaling pathway may serve as an efficient molecular marker or predictive target for osteosarcoma.

Low back pain and sciatica are the most common symptoms of patients with lumbar disc herniation (LDH). The pathophysiology of lumbocrural pain and sciatica is not fully understood. The aim of the present study was to define the membrane properties and activities of voltage-gated sodium channels of dorsal root ganglion (DRG) neurons in a rat model of LDH. LDH was established by transplantation of autologous nucleus pulposus (NP) to lumbar 5 and 6 spinal nerves (L5–L6 DRG) of adult male rats. Mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL) were measured 1 day before and through 35 days after transplantation of NP. Changes in expression of VGSCs were determined by western blotting. L5–L6 DRGs neurons innervating the hindpaw were labeled with DiI and acutely dissociated for measuring excitability and sodium channel currents under whole-cell patch clamp configurations. NP transplantation significantly reduced the PWT and PWL in association with a significant reduction in rheobase and an increase in numbers of action potentials evoked by 2X and 3X rheobase current stimulation. Voltage-gated sodium current density was significantly enhanced in L5–L6 DRG neurons from LDH rats. The inactivation curve showed a leftward shift in LDH rats while activation curve did not significantly alter. However, NP transplantation remarkably enhanced expression of NaV1.7 and NaV1.8 in L5–L6 DRGs but not in T10–12 DRGs. These data suggest that NP application produces pain-related behavior and potentiates sodium current density of DRG neurons, which is most likely mediated by enhanced expression of NaV1.7 and NaV1.8.

Lumbar disc herniation (LDH) is a major cause of discogenic low back pain and sciatica, but the underlying mechanisms remain largely unknown. Hydrogen sulfide (H2S) is becoming recognized for its involvement in a wide variety of processes including inflammation and nociception. The present study was designed to investigate the roles of the H2S signaling pathway in the regulation of expression and function of purinergic receptors (P2XRs) in dorsal root ganglion (DRG) neurons from rats with LDH. LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. Implantation of autologous NP induced persistent pain hypersensitivity, which was partially reversed by an intrathecal injection of A317491, a potent inhibitor of P2X3Rs and P2X2/3Rs. The NP induced persistent pain hypersensitivity was associated with the increased expression of P2X3Rs, but not P2X1Rs and P2X2Rs, receptors in L5-6 DRGs. NP implantation also produced a 2-fold increase in ATP-induced intracellular calcium signals in DRG neurons when compared to those of controls (P < 0.05). Interestingly, NP implantation significantly enhanced expression of the endogenous hydrogen sulfide producing enzyme, cystathionine-β-synthetase (CBS). Systematic administration of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, suppressed the upregulation of P2X3R expression and the potentiation of ATP-induced intracellular calcium signals in DRG neurons (P < 0.05). Intrathecal injection of AOAA markedly attenuated NP induced- persistent pain hypersensitivity. Our results suggest that sensitization of P2X3Rs, which is likely mediated by CBS-H2S signaling in primary sensory neurons, contributes to discogenic pain. Targeting CBS/H2S-P2X3R signaling may represent a potential treatment for neuropathic pain caused by LDH.