From molecular subgroups to molecular targeted therapy in rheumatoid arthritis: A bioinformatics approach.

1Background: Rheumatoid Arthritis (RA) is a heterogeneous autoimmune disease with multiple unidentified pathogenic factors. The inconsistency between molecular subgroups poses challenges for early diagnosis and personalized treatment strategies. In this study, we aimed to accurately distinguish RA patients at the transcriptome level using bioinformatics methods. 2Methods: We collected a total of 362 transcriptome datasets from RA patients in three independent samples from the GEO database. Consensus clustering was performed to identify molecular subgroups, and clinical features were assessed. Differential analysis was employed to annotate the biological functions of specifically upregulated genes between subgroups. 3Results: Based on consensus clustering of RA samples, we identified three robust molecular subgroups, with Subgroup III representing the high-risk subgroup and Subgroup II exhibiting a milder phenotype, possibly associated with relatively higher levels of autophagic ability. Subgroup I showed biological functions mainly related to viral infections, cellular metabolism, protein synthesis, and inflammatory responses. Subgroup II involved autophagy of mitochondria and organelles, protein localization, and organelle disassembly pathways, suggesting heterogeneity in the autophagy process of mitochondria that may play a protective role in inflammatory diseases. Subgroup III represented a high-risk subgroup with pathological processes including abnormal amyloid precursor protein activation, promotion of inflammatory response, and cell proliferation. 4Conclusion: The classification of the RA dataset revealed pathological heterogeneity among different subgroups, providing new insights and a basis for understanding the molecular mechanisms of RA, identifying potential therapeutic targets, and developing personalized treatment approaches.

Curcumin inhibits the activity and induces apoptosis of activated hepatic stellate cell by suppressing autophagy.

Curcumin, a kind of natural compound, has been previously proven to inhibit the autophagy in hepatic stellate cells (HSCs) and induce their apoptosis. However, it is not clear whether the enhanced apoptosis of activated HSCs (aHSCs) caused by curcumin depends on autophagy inhibition. We aim to verify this hypothesis and explore the potential mechanisms in this study. Immortalized human HSC line LX-2 was used as an experimental specimen and pretreated with transforming growth factor ß1(TGF-ß1) for 24 h to activate it before drug application. The levels of autophagy, apoptosis, cell activity, lipid metabolism, and the activity of the PI3K/Akt/mTOR signal pathway were evaluated by multiple methods, such as Western blotting, mcherry-EGFP-LC3B adenoviruses transfection, immunofluorescence, Nile Red staining, flow cytometry among others. Our results showed that rapamycin, an autophagy activator, could partly offset the effects of curcumin on autophagy and apoptosis of LX-2 cells, while 3-Methyladenine (3-MA), an autophagy inhibitor, could enhance these effects. Furthermore, curcumin could promote the activity of the PI3K/Akt/mTOR signal pathway in LX-2 cells, while PI3K inhibitor could partly offset this effect and increase the autophagy level. Overall, we demonstrated that curcumin could inhibit the activity and promote LX-2 cells apoptosis by suppressing autophagy by activating the PI3K/Akt/mTOR signal pathway. In addition, lipid recovery and energy deprivation due to autophagy inhibition may be the exact mechanism by which curcumin attenuates the pro-fibrotic activity of LX-2.

The impacts of probiotics in eradication therapy of Helicobacter pylori.

Helicobacter pylori (H. pylori) is a well-known pathogen that infects approximately half of the world's population. It is a pathogenic agent with potential health hazards related to diverse diseases, especially digestive diseases, such as chronic gastritis, peptic ulcer, and gastric carcinoma. In clinical, antibiotics are commonly applied in eradication therapy of H. pylori. However, the increase in antibiotic resistance and side effects has induced the failure of eradication therapy. Recent studies have shown that probiotic supplementation has promising application prospects. It can restore the gastrointestinal microbiota balance and prevent dysbacteriosis caused by antibiotics. Furthermore, it has been reported to have direct or indirect inhibitory effects on H. pylori. Probiotics may have a beneficial effect on H. pylori eradication. However, the strain, dosages, duration times, and safety of probiotic supplementation need further study before clinical applications.

Family Exit and Firms' Investment Efficiency Based on Dynamic Changes: Evidence from Chinese Family Firms.

This study provides evidence about the influence of family exit on firms' investment efficiency using a sample of 6,842 firm-year observations of Chinese family (and family-exiting) firms from 2003 to 2019. Based on panel data, we find that family exit has negative effects on firms' investment efficiency. Further analysis also indicates that family exit can decrease firms' investment efficiency under low investment levels and increase their investment efficiency under high investment levels. We test the market reaction when family members are punished by the SEC and find that the market's reaction is significantly negative, which implies that the capital market cares about family managers and controllers.