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Abstract Background Heat shock protein 70, a stress protein, has been implicated in tumor progression. However, its role in nasopharyngeal carcinoma (NPC) progression has not yet been clearly investigated. Methods Immunohistochemistry (IHC) was employed to examine the expression patterns of Hsp70, human leukocyte antigen –A (HLA-A) in NPC tissue samples. Results The expression of Hsp70 exhibited different spatial patterns among nuclear, membrane and cytoplasm in 507 NPC tumor tissues. Kaplan-Meier survival analysis demonstrated that different Hsp70 expression patterns are correlated with different patient outcomes. High membranal and cytoplasmic levels of Hsp70 predicted good survival of patients. In contrast, high nuclear abundance of Hsp70 correlated with poor survival. Moreover, the membranal and cytoplasmic levels of Hsp70 were positively correlated with levels of the MHC I molecule HLA-A. Conclusions Different Hsp70 expression patterns had distinct predictive values. The different spatial abundance of Hsp70 may imply its important role in NPC development and provide insight for the development of novel therapeutic strategies involving immunotherapy for NPC.

ObjectiveTo observe the efficacy of kinesio taping combined with Vitalstim electrical stimulation therapy in patients with post-stroke dysphagia.MethodsA total of 90 patients with post-stroke dysphagia treated in the Department of Acupuncture, Tuina and Rehabilitation and Neurosurgery Department of the First Hospital of Hunan University of Chinese Medicine from January 2021 to January 2023 were selected as the study subjects. They were randomly divided into kinesio tape group, Vitalstim electrical stimulation group, and combined group, with 30 cases in each group. All three groups received conventional swallowing rehabilitation treatment (including swallowing training, ice stimulation, 1 time per day, 20 minutes each time, 10 times for 1 course of treatment, and a total of 2 courses of treatment). In addition, the kinesio tape group was treated with kinesio taping therapy (1 time per day and kept for at least 12 hours, 10 sessions for 1 course of treatment, and a total of 2 courses of treatment), the Vitalstim electrical stimulation group received Vitalstim electrical stimulation therapy (1 time per day, 20 minutes each time, 10 times for a course of treatment, and a total of 2 courses of treatment) and the combined group was treated with the combination of the two. After treatment, the three groups were compared in terms of clinical efficacy, incidence of aspiration, standardized swallowing assessment (SSA), water swallowing test (WST), functional oral intake scale (FOIS), and indicators of nutritional status.ResultsThe water swallowing test ratings of all three groups after treatment improved significantly compared with those before treatment (PPP>0.05). In terms of total effective rate, the combined group was significantly higher than that of the kinesio tape group and the Vitalstim electrical stimulation group (PP>0.05). In comparison of the incidence of aspiration, the combined group showed significantly lower aspiration incidence than the kinesio tape group and the Vitalstim electrical stimulation group (PP>0.05). SSA scores were reduced in all three groups after treatment (PPPPPP>0.05). Comparison of nutritional indicators showed that BMI, ALB, and Hb indexes increased in all three groups after treatment (PPP>0.05).ConclusionThe application of kinesio taping combined with Vitalstim electrical stimulation therapy in patients with post-stroke swallowing dysfunction can significantly improve therapeutic efficacy, reduce the incidence of aspiration, improve feeding safety, and improve swallowing function as well as nutritional status.

ObjectiveTo observe the clinical effect of auricular acupressure combined with transcranial direct current stimulation (tDCS) for nicotine dependence.MethodsA total of 90 patients with nicotine dependence were divided into three groups (combination group, tDCS group and auricular acupressure group), using the method of random number table, with 30 cases in each group. In the auricular acupressure group, vaccaria segetalis were applied at the point representing the lung,stomach, shenmen, mouth, pizhixia and heart. The patients were asked to self-administrate auricular acupressure for two minutes per session, five times a day. When the desire to smoke was strong, patients were adviced to press and pinch it for 3 minutes. In addition, the auricular acupressure pads were changed every 2 days, three times per week, for four weeks. In the tDCS group, tDCS was applied at the dorsolateral prefrontal cortex, 1.4 mA in intensity, 20 min each time, three times per week, for four weeks. In the combination group, we applied the auricular acupressure combined with tDCS and the methods were the same as the tDCS group and the auricular acupressure group. Before treatment and 2, 4 weeks after treatment, the smoking frequency a day, Fagerström test of nicotine dependence (FTND) score, the questionnaire of smoking urges (QSU) score, Minnesota nicotine withdrawal scale (MNWS) score and the concentration of cotinine in urine were observed in all three groups.ResultsThere was no significant difference in daily smoking frequency, FTND score, QSU score, MNWS score and cotinine concentration in urine before treatment (PPPPPPPPPP

MicroRNA-214 (MiR-214) is aberrantly expressed in several human tumors such as ovarian cancer and breast cancer. However, the role of miR-214 in nasopharyngeal carcinoma (NPC) is still unknown. In this study, we report that miR-214 was overexpressed in NPC cell lines and tissues. Silencing of miR-214 by LNA-antimiR-214 in NPC cells resulted in promoting apoptosis and suppressing cell proliferation in vitro, and suppressed tumor growth in nude mice in vivo. Luciferase reporter assay was performed to identify Bim as a direct target of miR-214. Furthermore, this study showed that low Bim expression in NPC tissues correlated with poor survival of NPC patients. Taken together, our findings suggest that miR-214 plays an important role in NPC carcinogenesis. [ABSTRACT FROM AUTHOR]

C9orf86 which is a novel subfamily within the Ras superfamily of GTPases, is overexpressed in the majority of primary breast tumors. Few functional studies have focused on the C9orf86 protein; therefore, in this study, we explored the role of C9orf86 in breast carcinogenesis. In our study, we found that silencing of C9orf86 by siRNA in MCF-7 and SK-BR-3 cells resulted in suppressed cell proliferation as well as in vitro cell invasion capabilities. Moreover, knockdown of C9orf86 inhibited tumor growth in nude mice. Cell cycle and apoptotic assays showed that the anti-proliferative effect of C9orf86-siRNA was mediated by arresting cells in the G1 phase and promoting apoptosis. In addition, we found that patients with high levels of C9orf86 expression showed a significant trend towards worse survival compared to patients with low C9orf86 expression (P = 0.002). These results provide evidence that C9orf86 represents a novel and clinically useful biomarker for BC patients and plays an important role during the progression of BC. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor-1 (HIF-1) plays a key role in cell adaptation to low oxygen and stabilization of HIF-1 is vital to ensure cell survival under hypoxia. Diabetes has been associated with impairment of the cell response to hypoxia and downregulation of HIF-1 is most likely the event that transduces hyperglycemia into increased cell death in diabetes-associated hypoxia. In this study, we aimed at identifying the molecular mechanism implicated in destabilization of HIF-1 by high glucose. In this work, we identified a new molecular mechanism whereby methylglyoxal (MGO), which accumulates in high-glucose conditions, led to a rapid proteasome-dependent degradation of HIF-1α under hypoxia. Significantly, MGO-induced degradation of HIF-1α did not require the recruitment of the ubiquitin ligase pVHL nor did it require hydroxylation of the proline residues P402/P564 of HIF-1α. Moreover, we identified CHIP (Carboxy terminus of Hsp70-Interacting Protein) as the E3 ligase that ubiquitinated HIF-1α in the presence of MGO. Consistently, silencing of endogenous CHIP and overexpression of glyoxalase I both stabilized HIF-1α under hypoxia in the presence of MGO. Data shows that increased association of Hsp40/70 with HIF-1α led to recruitment of CHIP, which promoted polyubiquitination and degradation of HIF-1α. Moreover, MGO-induced destabilization of HIF-1α led to a dramatic decrease in HIF-1 transcriptional activity. Altogether, data is consistent with a new pathway for degradation of HIF-1α in response to intracellular accumulation of MGO. Moreover, we suggest that accumulation of MGO is likely to be the link between high glucose and the loss of cell response to hypoxia in diabetes.

The eye lens presents a unique opportunity to explore roles for specific molecules in cell proliferation, differentiation and development because cells remain in place throughout life and, like red blood cells and keratinocytes, they go through the most extreme differentiation, including removal of nuclei and cessation of protein synthesis. Ubiquitination controls many critical cellular processes, most of which require specific lysines on ubiquitin (Ub). Of the 7 lysines (K) least is known about effects of modification of K6.We replaced K6 with tryptophan (W) because K6 is the most readily modified K and W is the most structurally similar residue to biotin. The backbone of K6W-Ub is indistinguishable from that of Wt-Ub. K6W-Ub is effectively conjugated and deconjugated but the conjugates are not degraded via the ubiquitin proteasome pathways (UPP). Expression of K6W-ubiquitin in the lens and lens cells results in accumulation of intracellular aggregates and also slows cell proliferation and the differentiation program, including expression of lens specific proteins, differentiation of epithelial cells into fibers, achieving proper fiber cell morphology, and removal of nuclei. The latter is critical for transparency, but the mechanism by which cell nuclei are removed has remained an age old enigma. This was also solved by expressing K6W-Ub. p27(kip), a UPP substrate accumulates in lenses which express K6W-Ub. This precludes phosphorylation of nuclear lamin by the mitotic kinase, a prerequisite for disassembly of the nuclear membrane. Thus the nucleus remains intact and DNAseIIβ neither gains entry to the nucleus nor degrades the DNA. These results could not be obtained using chemical proteasome inhibitors that cannot be directed to specific tissues.K6W-Ub provides a novel, genetic means to study functions of the UPP because it can be targeted to specific cells and tissues. A fully functional UPP is required to execute most stages of lens differentiation, specifically removal of cell nuclei. In the absence of a functional UPP, small aggregate prone, cataractous lenses are formed.