Calcineurin suppresses rat H9c2 cardiomyocyteprotective autophagy under chronic intermittent hypoxia by downregulating the AMPK pathway.

Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes. However, whether calcineurin can regulate cardiomyocyte autophagy under conditions of chronic intermittent hypoxia (CIH) remains unclear. Here, we showed that CIH induced calcineurin activity in H9c2 cells, which attenuated adenosine monophosphate-activated protein kinase (AMPK) signaling and inhibited autophagy. In H9c2 cells, autophagy levels, LC3 expression, and AMPK phosphorylation were significantly elevated under conditions of CIH within 3 days. However, after 5 days of CIH, these effects were reversed and calcineurin activity and apoptosis were significantly increased. The calcineurin inhibitor 17-Allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl) -1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo- [22.3.1.04,9]octacos-18- ene-2,3,10,16-tetrone (FK506) restored AMPK activation and LC3 expression and attenuated CIH-induced H9c2 cell apoptosis. In contrast, calcineurin overexpression significantly attenuated the increase in LC3 expression and enhanced H9c2 cell apoptosis under conditions of CIH. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9c2 cells expressing a kinase-dead K45R AMPK mutant. Autophagy inhibition abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicate that calcineurin suppresses adaptive autophagy during CIH by downregulating AMPK activation. Our findings reveal the underlying mechanism of calcineurin and autophagy regulation during H9c2 cell survival under conditions of CIH and may provide a new strategy for preventing CIH-induced cardiomyocyte damage.

Dysregulated transient receptor potential channel 1 expression and its correlation with clinical features and survival profile in surgical non-small-cell lung cancer patients.

BACKGROUND: Transient receptor potential channel 1 (TRPC1) facilitates the tumor growth, metastasis, and chemoresistance in a series of neoplasms, while its correlation with clinical features and survival profile in NSCLC patients remains elusive. Hence, this study aimed to explore this topic. METHODS: Totally, 192 NSCLC patients were enrolled. Protein and mRNA expression of TRPC1 in carcinoma tissue and para-carcinoma tissue were evaluated by immunohistochemistry (IHC) assay and reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay, respectively. RESULTS: Immunohistochemistry score and mRNA expression of TRPC1 were higher in carcinoma tissue compared with para-carcinoma tissue (both p < 0.001). Besides, increased TRPC1 IHC score (p = 0.004) and elevated TRPC1 mRNA overexpression (p = 0.016) were linked with occurrence of LYN metastasis; meanwhile, increased TRPC1 IHC score (p = 0.015) and raised TRPC1 mRNA expression (p = 0.009) were also linked with advanced TNM stage, whereas TRPC1 IHC score and TRPC1 mRNA expression were not correlated with other clinical features (all p > 0.05). Additionally, TRPC1 protein high (p = 0.007) and TRPC1 mRNA high (p = 0.015) were correlated with poor disease-free survival (DFS) but not correlated with overall survival (OS). Moreover, multivariate Cox's proportional hazards regression analysis showed that high TRPC1 protein expression (p = 0.046) and advanced TNM stage (p < 0.001) were independently correlated with poor DFS. However, TRPC1 protein and mRNA expression were not linked with OS (both p > 0.05), while poor differentiation (p = 0.003) and advanced TNM stage (p < 0.001) were independently associated with worse OS. CONCLUSIONS: TRPC1 is unregulated in NSCLC tissue with its overexpression relating to the occurrence of LYN metastasis and worse DFS in NSCLC patients.

[Medicinal vesiculation combined with quick cupping at Shenque (CV 8) for allergic rhinitis with syndrome of yang deficiency: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy differences between medicinal vesiculation combined with quick cupping at Shenque (CV 8) and regular medication for allergic rhinitis with syndrome of yang deficiency. METHODS: Eighty-two cases were randomly divided into an observation group (42 cases) and a control group (40 cases). The observation group was treated with medicinal vesiculation combined with quick cupping at Shenque (CV 8). The medicinal vesiculation was applied at Feishu (BL 13), Gaohuang (BL 43), Fengmen (BL 12), Mingmen (GV 4) on the dog days in the summer, one treatment on the 1st dog-day, 2nd dog-day and last dog-day respectively with an interval of 10 days between two treatments. Three treatments were taken as one course, and totally one course was given. The quick cupping was applied at Shenque (CV 8), once a day, ten treatments were taken as one course, and totally three courses was given. The control group was treated with oral administration of loratadine and nasal spray of budesonide. The loratadine was given 10 mg per time, once a day for continuous 14 days; budesonide was given once a day, ten treatments were taken as one course, and totally three courses was given. The clinical efficacy in two groups after treatment was observed, and the contents of immune globulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5) and tumor necrosis factor-α (TNF-α) in peripheral serum were measured before and after the treatments. RESULTS: Of all the 82 patients, 79 cases completed the treatment, and 1 patient in the observation group and 2 patients in the control group dropped out. The effective rate was 87.8% (36/41) in the observation group, which was superior to 78.9% (30/38) in the control group (P<0.05). After treatment, both groups effectively reduced the contents of IgE, IL-4, IL-5 and TNF-α, and the observation group had superior effect on reducing IgE and IL-4 to the control group (P<0.05). CONCLUSION: The medicinal vesiculation combined with quick cupping at Shenque (CV 8) have better effect for allergic rhinitis with syndrome of yang deficiency than oral administration of loratadine and nasal spray of budesonide.