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.

Comprehensive analysis of lysine crotonylation modification in patients with chronic renal failure.

BACKGROUND: Post-translational modifications (PTMs) are at the heart of many cellular signaling events, which changes the function of protein. Crotonylation, one of the most important and common PTMs, plays a crucial role in the regulation of various biological processes. However, no study has evaluated the role of lysine crotonylation modification in chronic renal failure (CRF) patients. METHODS: Here, we comparatively evaluated the crotonylation proteome of normal controls and chronic renal failure patients using liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with highly sensitive immune-affinity purification. RESULTS: A total of 1109 lysine modification sites were identified, of which 772 sites were up-regulated and 69 sites were down-regulated. This suggested that crotonylation modification maintains high levels in the patients with chronic renal failure. Gene ontology(GO) enrichment analysis showed that the crotonylated proteins were significantly enriched in the platelet alpha granule lumen, platelet degradulation, and cell adhesion molecule binding. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG)-based functional enrichment analysis in the Kyoto encyclopedia showed that crotonylated protein was enriched in CD36, which is closely linked to renal failure. CONCLUSIONS: This is the first report of the global crotonylation proteome in chronic renal failure patients. Crotonylation of histone and non-histone may play important roles in delaying the continuous deterioration of renal function in patients with chronic renal failure.

Insulinoma-associated protein 1(INSM1) is a superior marker for the diagnosis of gastroenteropancreatic neuroendoerine neoplasms: a meta-analysis.

PURPOSE: An increasing number of studies have shown that insulinoma-associated protein 1 (INSM1) is a robust marker for the diagnosis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). The overall diagnostic accuracy of INSM1 for GEP-NEN remains unclear. The purpose of this study is to estimate the diagnostic value of INSM1 for GEP-NEN through a meta-analysis. METHODS: We searched relevant studies addressing the accuracy of INSM1 in the diagnosis of GEP-NEN from PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) as well as from reference lists since the establishment of the database to January 12, 2021. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves were used to comprehensively evaluate the diagnostic value of INSM1 for GEP-NEN. Statistical analysis was performed by Stata 15.0 and RevMan 5.4. RESULTS: Nine studies with a total of 393 patients were included in the meta-analysis. The meta-analysis results showed that the pooled sensitivity and specificity of INSM1 for the diagnosis of GEP-NEN were 0.99 (95% CI: 0.87-1.00) and 0.96 (95% CI: 0.93-0.98), respectively. The PLR and NLR were 23.3 (95% CI: 13.3-40.8) and 0.01 (95% CI: 0.00-0.14), respectively. The DOR was 380.31 (95% CI: 164.14-881.21), and the area under the curve (AUC) of SROC curve was 0.98 (95% CI: 0.96-0.99). CONCLUSIONS: The results show that INSM1 is an effective marker for the diagnosis of GEP-NEN with high sensitivity and specificity. INSM1 is recommended for clinical application to improve the diagnostic accuracy of GEP-NEN. However, more high-quality studies are needed to confirm these findings.

Circular RNA expression profiles of peripheral blood mononuclear cells in rheumatoid arthritis patients, based on microarray chip technology.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovial inflammation and finally leads to variable degrees of bone and cartilage erosion. The diagnosis of RA is not an accurate indicator, but a series of scores and the mechanisms underlying it remain only partially understood. The present study explored whether circular RNAs (circRNAs) contribute to the RA pathophysiological mechanism. Total RNA from peripheral blood mononuclear cells of 10 RA patients and 10 healthy controls were extracted and circRNA expression profiling was followed by microarray analysis. In addition, circRNA interactions with microRNAs were performed and microRNA response elements were listed to identify differentially expressed binding site targets in RA. Reverse transcription­quantitative polymerase chain reaction amplification (RT­qPCR) was used to verify the differential expression of circRNAs. A total of 584 circRNAs were differentially expressed in RA patients vs. healthy controls, by circRNA microarray, including 255 circRNAs which were significantly upregulated and 329 downregulated among the RA samples. RT­qPCR validation demonstrated that the expression levels of hsa_circRNA_104194, hsa_circRNA_104593, hsa_circRNA_103334, hsa_circRNA_101407 and hsa_circRNA_102594 were consistent with the results from the microarray analysis. The current study presented differentially expressed circRNAs and their corresponding microRNA binding sites in RA. circRNAs may exhibit a role in the regulation of expression of symbol genes that influence the occurrence and development of RA.