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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with the progressive loss of motor neurons, leading to a fatal paralysis. According to whether there is a family history of ALS, ALS can be roughly divided into two types: familial and sporadic. Despite decades of research, the pathogenesis of ALS is still unelucidated. To this end, we review the recent progress of ALS pathogenesis, biomarkers, and treatment strategies, mainly discuss the roles of immune disorders, redox imbalance, autophagy dysfunction, and disordered iron homeostasis in the pathogenesis of ALS, and introduce the effects of RNA binding proteins, ALS-related genes, and non-coding RNA as biomarkers on ALS. In addition, we also mention other ALS biomarkers such as serum uric acid (UA), cardiolipin (CL), chitotriosidase (CHIT1), and neurofilament light chain (NFL). Finally, we discuss the drug therapy, gene therapy, immunotherapy, and stem cell-exosomal therapy for ALS, attempting to find new therapeutic targets and strategies. A challenge is to study the various mechanisms of ALS as a syndrome. Biomarkers that have been widely explored are indispensable for the diagnosis, treatment, and prevention of ALS. Moreover, the development of new genes and targets is an urgent task in this field.

BackgroundNumerous studies reported that dyslipidemia was associated with cancer risk. However, few studies investigated the associations between dyslipidemia and non-small cell lung cancer (NSCLC).MethodsFour hundred twenty-four histologically confirmed NSCLC cases and 414 controls, matched for age and sex, were enrolled to examine the relationship between dyslipidemia and NSCLC. Demographic and clinical data were obtained from patients’ medical records and telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression.ResultsAbnormal triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels showed statistically significant coexistence with NSCLC compared with controls. Higher levels of TG were associated with a higher risk of NSCLC (OR = 1.541, 95% CI, (1.072–2.215)). The odds ratios (ORs) for NSCLC for normal and high levels of HDL-C versus those with a low level of HDL-C were 0.337(95% CI, (0.242–0.468)) and 0.288(95% CI, (0.185–0.448)), respectively. After adjustment for age, sex, smoking status, hypertension, body mass index, diabetes and lipid profiles, the adjusted OR for normal and high levels of HDL-C were 0.320(95% CI, (0.218–0.470)) and 0.233(95% CI, (0.134–0.407)), respectively. However, after adjustment, high levels of TG increased the risk of NSCLC but not significantly (OR = 1.052, 95% CI (0.671–1.649)).ConclusionsThis study provided evidence that dyslipidemia increased the risk of NSCLC in Chinese population.

Abstract. The aim of this study was to improve our understanding and the current treatment of denervation-induced skeletal muscle atrophy. We used isobaric tags for relative and absolute quantification (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) to identify the differentially expressed proteins in the tibialis anterior (TA) muscle of rats at 1 and 4 weeks following sciatic nerve transection. A total of 110 proteins was differentially expressed and was further classified using terms from the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to unravel their molecular functions. Among the differentially expressed metabolic enzymes involved in glycolysis, Krebs cycle and oxidative phosphorylation, α-and β-enolase displayed an increased and decreased expression, respectively, which was further validated by western blot analysis and immunohistochemistry. These findings suggest that the enolase isozymic switch during denervation-induced muscle atrophy is the reverse of that occurring during muscle maturation. Notably, protein-protein interaction analysis using the STRING database indicated that the protein expression of tumor necrosis factor receptor-associated factor-6 (TRAF6), muscle ring-finger protein 1 (MuRF1) and muscle atrophy F-box (MAFBx) was also upregulated during denervation-induced skeletal muscle atrophy, which was confirmed by western blot analysis. TRAF6 knockdown experiments in L6 myotubes suggested that the decreased expression of TRAF6 attenuated glucocorticoid-induced myotube atrophy. Therefore, we hypothesized that the upregulation of TRAF6 may be involved in the development of denervation-induced muscle atrophy, at least in part, by regulating the expression of MAFBx and MuRF1 proteins. The data from the present study provide valuable insight into the molecular mechanisms regulating denervation-induced muscle atrophy.