The cancer anorexia cachexia syndrome is a systemic metabolic disorder characterized by the catabolism of stored nutrients in skeletal muscle and adipose tissue that is particularly prevalent in nonsmall cell lung cancer (NSCLC). Loss of skeletal muscle results in functional impairments and increased mortality. The aim of the present study was to characterize the changes in systemic metabolism in a genetically engineered mouse model of NSCLC. We show that a portion of these animals develop loss of skeletal muscle, loss of adipose tissue, and increased inflammatory markers mirroring the human cachexia syndrome. Using noncachexic and fasted animals as controls, we report a unique cachexia metabolite phenotype that includes the loss of peroxisome proliferator-activated receptor-α (PPARα) -dependent ketone production by the liver. In this setting, glucocorticoid levels rise and correlate with skeletal muscle degradation and hepatic markers of gluconeogenesis. Restoring ketone production using the PPARα agonist, fenofibrate, prevents the loss of skeletal muscle mass and body weight. These results demonstrate how targeting hepatic metabolism can prevent muscle wasting in lung cancer, and provide evidence for a therapeutic strategy.

Fangcang shelter hospitals were established in China during the coronavirus disease 2019 (COVID-19) pandemic as a countermeasure to stop the spread of the disease. To our knowledge, no research has been conducted on mental health problems among patients in Fangcang shelter hospitals. This study aimed to determine the prevalence and major influencing factors of anxiety and depressive symptoms among COVID-19 patients admitted to Fangcang shelter hospitals. From February 23, 2020, to February 26, 2020, we obtained sociodemographic and clinical characteristics information of COVID-19 patients in Jianghan Fangcang Shelter Hospital (Wuhan, China) and assessed their mental health status and sleep quality. Data were obtained with an online questionnaire. The questionnaire consisted of a set of items on demographic characteristics, a set of items on clinical characteristics, the Self-Rating Anxiety Scale, Self-Rating Depression Scale, and Pittsburgh Sleep Quality Index. Three hundred seven COVID-19 patients who were admitted to Jianghan Fangcang Shelter Hospital participated in this study. The prevalence of anxiety and depressive symptoms were 18.6% and 13.4%, respectively. Poor sleep quality and having � two current physical symptoms were independent risk factors for anxiety symptoms. Female sex, having a family member with confirmed COVID-19, and having � two current physical symptoms were independent risk factors for depressive symptoms. Anxiety and depressive symptoms were found to be common among COVID-19 patients in Fangcang Shelter Hospital, with some patients being at high risk.

Together, our study provided the first evidence that MALAT1 knockdown could suppress inflammatory response by up-regulating miR-146a in LPS-induced ALI, which provided a potential therapeutic target for the treatment of ALI.

SUMMARY Mammalian folate metabolism is comprised of cytosolic and mitochondrial pathways with nearly identical core reactions, yet the functional advantages of such an organization are not well understood. Using genome-editing and biochemical approaches, we find that ablating folate metabolism in the mitochondria of mammalian cell lines results in folate degradation in the cytosol. Mechanistically, we show that QDPR, an enzyme in tetrahydrobiopterin metabolism, moonlights to repair oxidative damage to tetrahydrofolate (THF). This repair capacity is overwhelmed when cytosolic THF hyperaccumulates in the absence of mitochondrially produced formate, leading to THF degradation. Unexpectedly, we also find that the classic antifolate methotrexate, by inhibiting its well-known target DHFR, causes even more extensive folate degradation in nearly all tested cancer cell lines. These findings shed light on design features of folate metabolism, provide a biochemical basis for clinically observed folate deficiency in QDPR-deficient patients, and reveal a hitherto unknown and unexplored cellular effect of methotrexate.

BackgroundNoninvasive ventilation (NIV) has proved to be a useful technique for breathing support. However, complications, discomfort, and failure of NIV were commonly caused by the mask. Therefore, the helmet was developed to improve performance and reduce complications; however, there has been no conclusive results on its effect until now. Thus, we performed a systematic review and meta-analysis to investigate the effect of NIV with a helmet versus the control strategy in patients with acute respiratory failure (ARF).MethodsWe searched Cochrane Library, PubMed, Ovid, and Embase databases and bibliographies of relevant articles published before June 2016. Randomized and case-control studies that adopted the helmet as an NIV interface and compared it with another interface were included. The primary outcomes were hospital mortality, intubation rate, and complications. The secondary outcomes included the length of intensive care unit (ICU) stay, gas exchange, and respiratory rate. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by the Mantel-Haenszel method and mean difference by the inverse variance method in a fixed effect model or random effects model according to the heterogeneity.ResultsA total of 11 studies involving 621 patients were included. The overall hospital mortality was 17.53 % in the helmet NIV group versus 30.67 % in the control group. Use of the helmet was associated with lower hospital mortality (OR 0.43, 95 % CI 0.26 to 0.69, p = 0.0005), intubation rate (OR 0.32, 95 % CI 0.21 to 0.47, P < 0.00001), and complications (OR 0.6, 95 % CI 0.4 to 0.92, P = 0.02). In contrast, there was no significant difference in gas exchange and ICU stay (P >0.05). Subgroup analysis found the helmet reduced mortality mainly in hypoxemic ARF patients (P < 0.05) and a lower intubation rate was shown in randomized trials; fewer complications caused by the helmet might be restricted to case-control trials. Additionally, the effect of the helmet on PaCO2 was influenced by type of ARF and ventilation mode (P <0.00001).ConclusionNIV with a helmet was associated with reduced hospital mortality and intubation requirement. The helmet was as effective as the mask in gas exchange with no additional advantage. Large randomized controlled trials are needed to provide more robust evidence.

BackgroundmiRNA-184 is an oncogene in human hepatocellular carcinoma but acts as a tumor suppressor in tongue squamous cell carcinoma. Studies have shown that miR-184 was down-regulated in glioma and TNFα-induced protein 2 (TNFAIP2) was closely related to tumorigenesis. This study aimed to determine the functions of miR-184 in glioma and the mechanisms of miRNA-184-TNFAIP2 mediated glioma progression.MethodsReal-time reverse-transcription PCR detected expression of miR-184 and TNFAIP2. U87 and U251 cells were transfected with miR-184 mimic, inhibitor, or negative control miRNA, and their invasion abilities were assayed. Cellular proliferation was measured by the cell counting kit-8 assay. miR-184 effects on glioma cell apoptosis and cell cycle were assessed by flow cytometer. Biological information software have predicted that miR-184 could target TNFα-induced protein 2 (TNFAIP2), Which was further validated by Western blot and qRT-PCR in glioma cells. In vivo, U87 cells transduced with either lentiviral over-expressed miR-184 or control lentivirus were injected into nude mice subcutaneously and intracranial respectively.ResultsExpression of miR-184 was significantly lower in glioma tissues and cell-lines compared to normal brain tissues. Protein and mRNA expression of TNFAIP2 were inversely correlated with miR-184 in glioma. In vitro, proliferation and invasion abilities were also decreased in U87 and U251 cells after transfection with miR-184 mimic. In vivo, the xenografted tumor size in the miR-184 overexpressing group were smaller than the miR-NC group. Concordantly, U87 and U251 cells transfected with miR-184 mimic had a higher apoptosis rate, triggering an accumulation of cells at the G0/G1 phase and decreased cells in S-phase.ConclusionsmiR-184 could regulate TNFAIP2 expression and affected its translation in glioma. miR-184 could also inhibit glioma progression and might serve as a novel therapeutic target in glioma.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0142-9) contains supplementary material, which is available to authorized users.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is among the most abundant and highly conserved lncRNAs, which has been detected in a wide variety of human tumors, including gastric cancer, gallbladder cancer, and so on. Previous research has showed that MALAT1 can activate LTBP3 gene in mesenchymal stem cells. However, the specific roles of MALAT1 in glioma stem cells (GSCs) remain unclear. In this study, we aimed to identify the effects of MALAT1 on proliferation and the expression of stemness markers on glioma stem cell line SHG139S. Our results showed that downregulation of MALAT1 suppressed the expression of Sox2 and Nestin which are related to stemness, while downregulation of MALAT1 promoted the proliferation in SHG139S. Further research on the underlying mechanism showed that the effects of MALAT1 downregulation on SHG139S were through regulating ERK/MAPk signaling activity. And we also found that downregulation of MALAT1 could activate ERK/MAPK signaling and promoted proliferation in SHG139 cells. These findings show that MALAT1 plays an important role in regulating the expression of stemness markers and proliferation of SHG139S, and provide a new research direction to target the progression of GSCs.

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