RNF219 Promotes Nasopharyngeal Carcinoma Progression by Activating the NF-κB Pathway.

In Southeast Asia, the prevalence of nasopharyngeal carcinoma (NPC) is high; however, the molecular mechanism governing the progression of NPC is unclear. The results of the present study revealed upregulation of ring finger protein 219 (RNF219) expression in NPC tissues and cells. Overexpression of RNF219 enhanced NPC cell invasion, migration, and proliferation; whereas knockdown of RNF219 had the opposite effects. Mechanistically, RNF219 activated the nuclear factor kappa B (NF-κB) pathway, mainly reflected by increased p65 nuclear translocation, and increased NF-κB pathway target gene expression. NF-κB pathway inhibition in cells overexpressing RNF219 resulted in reduced invasion, migration, and proliferation, confirming that progression of NPC was promoted by RNF219-mediated NF-κB pathway activation. In addition, the expression of RNF219 correlated positively with the activity of the NF-κB pathway, verifying that RNF219 regulates the activity of the NF-κB pathway in the clinical setting. Our results identified a novel therapeutic target that could promote the development of novel treatments for NPC.

The potential signaling pathway between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha in renal interstitial fibrosis disease.

Peroxisome proliferator-activated receptorγ (PPARγ) can regulate the process of cell apoptosis and is related to the progression of renal disorders. Retinoic acid receptor alpha (RARα) is one of the nuclear receptors involved in a variety of kidney diseases. Renal interstitial fibrosis (RIF) is a common denominator of chronic kidney disease (CKD). This study investigated whether a potential signaling pathway existed between PPARγ and RARα in RIF rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into four groups: a model group subjected to UUO (GU), and three other groups treated with rosiglitazone sodium (GRS), GW9662 and dimethyl sulfoxide (DMSO), n = 40, respectively. Renal tissues were collected two and four weeks after post-surgery. The relevant indicators were detected. In comparison with the GU group, the expressions of PPARγ and RARα (protein and mRNA) were increased in the GRS group, and decreased in the GW9662 group (all p < 0.01). The RIF index, mRNA and protein expression of transforming growth factor-ß1 (TGF-ß1), and the protein expressions of collagen-IV (Col-IV) and fibronectin (FN) in the GRS group were more markedly reduced than those in the GU group; their levels in the GW9662 group were elevated (all p < 0.01). PPARγ or RARα was negatively correlated to the RIF index, TGF-ß1, Col-IV and FN. PPARγ was positively correlated with RARα (all p < 0.01). In conclusion, PPARγ agonist can elevate the expression of PPARγ or RARα in RIF rats. There might be a potential signaling pathway between PPARγ and RARα in RIF disease.

Association of peroxisome proliferator-activated receptors/retinoic acid receptors with renal diseases.

Peroxisome proliferator-activated receptor-γ (PPARγ), belongs to the nuclear receptor superfamily, and is a nuclear transcription receptor involving in the regulation of several biochemical pathways, such as cell growth, differentiation, and apoptosis. The nuclear retinoic acid receptors (RARs) are transcriptional transregulators that control the expression of specific subsets of genes in a ligand-dependent manner, and include three subtypes (RARα, RARß, and RARγ). These control the expression of specific gene subsets subsequent to ligand binding and to strictly control phosphorylation processes. The current status of knowledge indicates that there might be inter- or overlapping actions between PPARγ and RARs, and there might be an association of PPARγ/RARs with renal diseases. Various agonists of both receptor families seem to prevent or retard the progression of renal disease. Herein, we review if causal relationships can be established between PPARγ/RARs and renal diseases and its manifestations.

A randomized controlled trail of combination therapy of neuromuscular electrical stimulation and balloon dilatation in the treatment of radiation-induced dysphagia in nasopharyngeal carcinoma patients.

Dysphagia is a most common complication induced by radiotherapy in nasopharyngeal carcinoma (NPC) patients. This randomized controlled trail (RCT) was performed to evaluate the therapeutic effect of combination therapy of neuromuscular electrical stimulation (NMES) and balloon dilatation in the treatment of radiation-induced dysphagia in NPC patients. Sixty NPC patients with radiation-induced dysphagia were assigned to either the combination rehabilitation group (treatment group) or the routine rehabilitation group (control group) at random. Both groups were subjected to routine rehabilitation treatment, while the combination rehabilitation group also received combination therapy of NMES and balloon dilatation for 4 months. The water swallow test (WST) and videofluoroscopic swallowing study (VFSS) were used to evaluate the severity of dysphagia. The treatment group showed a significant improvement in swallowing function when compared with the control group. When the WST was used, the efficacy rate (percentage of patients with excellent and effective results) of treatment group was higher than that of control group (90.1 vs. 76.3%), and the difference was statistically significant (χ(2) = 8.55, p = 0.036). When the VFSS was used, the videofluoroscopy results in our study showed that the values of oral transit time (OTT), swallow reaction time (SRT), pharyngeal transit time (PTT) and laryngeal closure duration (LCD) in treatment group were notably improved when compared with those in control group. In conclusion, combination rehabilitation treatment can improve swallow function in the treatment of radiation-induced dysphagia in NPC patients.

Association of retinoic acid receptors with extracellular matrix accumulation in rats with renal interstitial fibrosis disease.

The nuclear retinoic acid receptors (RARs) function as ligand-dependent transcriptional regulators and include three subtypes (RARα, RARß and RARγ), which control the expression of specific gene subsets subsequent to ligand binding and to strictly controlled phosphorylation processes. Extracellular matrix (ECM) accumulation is the most important characteristic of renal interstitial fibrosis (RIF). This study was performed to investigate whether RARs were associated with ECM accumulation in the progression of RIF in rats. Eighty Wistar male rats were divided into a sham operation group (SHO) and a model group subjected to unilateral ureteral obstruction (GU) at random; n = 40, respectively. The RIF disease in GU group was established by left ureteral ligation. The renal tissues were collected at two weeks and four weeks after surgery. Protein expressions of RARα, RARß, RARγ, transforming growth factor-ßl (TGF-ß1), collagen-IV (Col-IV) and fibronectin (FN) were detected using immunohistochemical analysis, and mRNA expressions of RARα, RARß, RARγ and TGF-ß1 in renal tissue were detected by real time reverse transcription polymerase chain reaction. RIF index in renal interstitium was also calculated. When compared with those in SHO group, expressions of RARα and RARß (protein and mRNA) were markedly reduced in the GU group (each p < 0.01). There was no marked difference for the expression of RARγ (protein and mRNA) between the SHO group and the GU group. The expressions of TGF-ß1, Col-IV, FN and the RIF index in the GU group were markedly increased when compared with those in the SHO group (each p < 0.01). The protein expression of RARα/RARß was negatively correlated with protein expression of TGF-ß1, Col-IV or FN and the RIF index (all p < 0.01). In conclusion, the low expression of RARα/RARß is associated with ECM accumulation in the progression of RIF in rats, suggesting that RARα/RARß is a potentially therapeutic target for prevention of RIF.

A meta-analysis of the efficacy of acupuncture in treating dysphagia in patients with a stroke.

BACKGROUND: Dysphagia, or deglutition difficulty, is a common manifestation in patients with a stroke and its management is an important aspect of rehabilitation. Acupuncture, a complementary and alternative therapy, is the subject of growing public interest for treatment of stroke. OBJECTIVE: A meta-analysis was performed to study the effect of acupuncture for treatment of dysphagia in patients affected by a stroke. METHODS: Randomised controlled trials (RCTs) comparing acupuncture treatment with non-acupuncture treatment of dysphagia in patients with a stroke were identified from the databases of PubMed, Embase, Cochrane Library and CBM disc (China Biological Medicine Database). Eligible investigations were included and data on the effectiveness of acupuncture were extracted and synthesised by meta-analysis using RevMan 5.1.4. Results were expressed as OR for dichotomous data; 95% CIs were also calculated. RESULTS: Seventy-two RCTs (3208 patients in the treatment group and 2926 patients in the control group) were identified. Details of randomisation and blinding were not reported and information on withdrawals and dropouts was missing in most of included reports. Meta-analysis showed that the effectiveness of treatment in the group receiving acupuncture was higher than that in the non-acupuncture group (OR=5.17, 95% CI 4.18 to 6.38; p<0.00001). However, the study quality was generally low and of insufficient quality to make recommendations about using acupuncture in the rehabilitation of patients with dysphagia due to stroke. CONCLUSIONS: Acupuncture might be beneficial in the rehabilitation of patients with dysphagia caused by stroke, and the evidence justifies future high-quality studies.