Long noncoding RNAs have been implicated in neuropathy. Here, we identify and validate a long noncoding RNA, MRAK009713, as the primary regulator of neuropathic pain in chronic constriction injury (CCI) rats. MRAK009713 expression was markedly increased in CCI rats associated with enhanced pain behaviors, and small interfering RNA against MRAK009713 significantly reduced both mechanical and thermal hyperalgesia in the CCI rats. MRAK009713 is predicted to interact with the nociceptive P2X3 receptor by CatRAPID, a bioinformatics technology. Overexpression of MRAK009713 markedly increased expression of P2X3 in the dorsal root ganglia of the control rats, and MRAK009713 small interfering RNA significantly inhibited the P2X3 expression in the dorsal root ganglia of the CCI rats. MRAK009713 directly interacted with the P2X3 protein heterologously expressed in the human embryonic kidney (HEK) 293 cells and potentiated P2X3 receptor function. Thus, MRAK009713 is a novel positive regulator of neuropathic pain in rats through regulating the expression and function of the P2X3 receptor.
Irritable bowel syndrome (IBS) and inflammatory bowel disease often display visceral hypersensitivity. Visceral nociceptors after inflammatory stimulation generate afferent nerve impulses through dorsal root ganglia (DRG) transmitting to the central nervous system. ATP and its activatedpurinergic 2X 7 (P2X 7 ) receptor play an important role in the transmission of nociceptive signal. Purinergic signaling is involved in the sensory transmission of visceral pain. Moxibustion is a therapy applying ignited mugwort directly or indirectly at acupuncture points or other specific parts of the body to treat diseases. Heat-sensitive acupoints are the corresponding points extremely sensitive to moxa heat in disease conditions. In this study, we aimed to investigate the relationship between the analgesic effect of moxibustion on a heatsensitive acupoint "Dachangshu" and the expression levels of P2X 7 receptor in rat DRG after chronic inflammatory stimulation of colorectal distension. Heat-sensitive moxibustion at Dachangshu acupoint inhibited the nociceptive signal transmission by decreasing the upregulated expression levels of P2X 7 mRNA and protein in DRG induced by visceral pain, and reversed the abnormal expression of glial fibrillary acidic protein (GFAP, a marker of satellite glial cells) in DRG. Consequently, abdominal withdrawal reflex (AWR) score in a visceral pain model was reduced, and the pain threshold was elevated. Therefore, heat-sensitive moxibustion at Dachangshu acupoint can produce a therapeutic effect on IBS via inhibiting the nociceptive transmission mediated by upregulated P2X 7 receptor.
As a novel immune‐active agent for cancer treatment, viruses have the ability of infecting and replicating in tumor cells. The safety and efficacy of viruses has been tested and confirmed in preclinical and clinical trials. In the last decade, virotherapy has been adopted as a monotherapy or combined therapy with immunotherapy, chemotherapy, or radiotherapy, showing promising outcomes against cancer. In this review, the current strategies of viruses used in clinical trials are classified and described. Besides this, the challenge and future prospects of virotherapy in the management for cancer patients are discussed in this review.
Cancer cell-derived extracellular vesicles (CEVs), a novel type of therapeutic agent in cancer treatment, can be prepared from the autocrine secretion of various cancer cells, the direct extraction of cancer cells and the combination of cancer cell-derived membranes with advanced materials. With various bioactive molecules, exosomes are produced by cells for intercellular communication. Although cancer cell-derived exosomes are known to inhibit tumor apoptosis and promote the progression of cancer, researchers have developed various innovative strategies to prepare anti-tumor vesicles from cancer cells. With current strategies for anti-tumor vesicles, four different kinds of CEVs are classified including irradiated CEVs, advanced materials combined CEVs, chemotherapeutic drugs loaded CEVs and genetically engineered CEVs. In this way, CEVs can not only be the carriers for anti-tumor drugs to the target tumor area but also act as immune-active agents. Problems raised in the strategies mainly concerned with the preparation, efficacy and application. In this review, we classified and summarized the current strategies for utilizing the anti-tumor potential of CEVs. Additionally, the challenges and the prospects of this novel agent have been discussed.
Purpose: Population-based data on the clinical correlates and prognostic value of the pattern of metastases among patients with bladder cancer are needed.
Patients and methods: Surveillance , epidemiology and end results(SEER)database has been explored through SEER program. For each of four distant metastatic sites (bone, brain, liver, lung ),relevant correlation with baseline characteristics were reported. Survival analysis has been conducted through Kaplan-Meier analysis , and multivariate analysis has been conducted through a cox proportional hazard model. The precision of the nomogram was evaluated and compared using concordance index(C-index),and the area under receiver operating characteristic curve(AUC).
Results: A total 2715 patients with metastatic bladder cancer were identidied from 2005-2019.Patients with medium risk have the best overall survival,followed by patients with low risk followed by patients with high risk metastases. Multivariate analysis showed that patients who were older than 80 at the time of diagnosis, single, no Chemotherapy, no complete cystectomy and bone metastases were associated with poor survival. A nomogram based on 7 independent risk factors has a good predictive power for the 12-month, 24-month and 36-month prognosis of patients with bladder cancer. The C index of the nomogram has high consistency in evaluating the survival rate of bladder cancer patients(C index=0.722,95% CI=0.712-0.732).The values of AUC for 12-month, 24-month, and 36-month were 0.775, 0.73, and 0.692.Conclusion: Build Nomogram prediction method validation of bladder tumor, according to the results of the Nomogram has good capability of identification and correction, suggests that these column chart.
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