Objective: Cancer cachexia is often present in patients with advanced malignant tumors, and the subsequent body weight reduction results in poor quality of life. However, there has been no progress in developing effective clinical therapeutic strategies for skeletal muscle wasting in cancer cachexia. Herein, we explored the functions of pantoprazole on cancer cachexia skeletal muscle wasting. Methods: The mouse colon adenocarcinoma cell line C26 was inoculated in the right forelimb of male BALB/C mice to establish a cancer cachexia model. The animals were treated with or without different concentrations of pantoprazole orally, and the body weight, tumor growth, spontaneous activity, and muscle functions were determined at various time points. Two weeks later, the levels of serum IL-6 and TNF-α, the mRNA levels of gastrocnemius JAK2 and STAT3, and the expression levels of p-JAK2, p-STAT3, Fbx32, and MuRF1 were examined with ELISA assay, qRT-PCR assay, and Western blotting, respectively. Further studies were performed to assess the levels of Fbx32 and MuRF1 expression and morphological changes. Results: Pantoprazole can alleviate cancer cachexia-induced body weight reduction and inhibit skeletal muscle wasting in a dose-dependent manner. Our results indicated that pantoprazole treatment can decrease the levels of serum IL-6 and TNF-α (56.3% and 67.6%, respectively), and inhibit the activation of the JAK2/ STAT3 signaling pathway. Moreover, the expression levels of MuRF1 and Fbx32 were also suppressed after pantoprazole treatment. Conclusion: Our findings suggested that pantoprazole can alleviate cancer cachexia skeletal muscle wasting by inhibiting the inflammatory response and blocking the JAK2/STAT3 or ubiquitin proteasome pathway.

BackgroundEffects of extreme sleep duration on risk of mortality and cardiovascular outcomes remain controversial. We aimed to quantify the dose‐response relationships of sleep duration with risk of all‐cause mortality, total cardiovascular disease, coronary heart disease, and stroke.Methods and ResultsPubMed and Embase were systematically searched for prospective cohort studies published before December 1, 2016, that examined the associations between sleep duration and at least 1 of the 4 outcomes in generally healthy populations. U‐shaped associations were indicated between sleep duration and risk of all outcomes, with the lowest risk observed for ≈7‐hour sleep duration per day, which was varied little by sex. For all‐cause mortality, when sleep duration was <7 hours per day, the pooled relative risk (RR) was 1.06 (95% CI, 1.04–1.07) per 1‐hour reduction; when sleep duration was >7 hours per day, the pooled RR was 1.13 (95% CI, 1.11–1.15) per 1‐hour increment. For total cardiovascular disease, the pooled RR was 1.06 (95% CI, 1.03–1.08) per 1‐hour reduction and 1.12 (95% CI, 1.08–1.16) per 1‐hour increment of sleep duration. For coronary heart disease, the pooled RR was 1.07 (95% CI, 1.03–1.12) per 1‐hour reduction and 1.05 (95% CI, 1.00–1.10) per 1‐hour increment of sleep duration. For stroke, the pooled RR was 1.05 (95% CI, 1.01–1.09) per 1‐hour reduction and 1.18 (95% CI, 1.14–1.21) per 1‐hour increment of sleep duration.ConclusionsOur findings indicate that both short and long sleep duration is associated with an increased risk of all‐cause mortality and cardiovascular events.

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