The elderly population is at risk of osteoarthritis (OA), a common, multifactorial, degenerative joint disease. Environmental, genetic, and epigenetic (such as DNA hydroxymethylation) factors may be involved in the etiology, development, and pathogenesis of OA. Here, comprehensive bioinformatic analyses were used to identify aberrantly hydroxymethylated differentially expressed genes and pathways in osteoarthritis to determine the underlying molecular mechanisms of osteoarthritis and susceptibility-related genes for osteoarthritis inheritance.Gene expression microarray data, mRNA expression profile data, and a whole genome 5hmC dataset were obtained from the Gene Expression Omnibus repository. Differentially expressed genes with abnormal hydroxymethylation were identified by MATCH function. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the genes differentially expressed in OA were performed using Metascape and the KOBAS online tool, respectively. The protein-protein interaction network was built using STRING and visualized in Cytoscape, and the modular analysis of the network was performed using the Molecular Complex Detection app.In total, 104 hyperhydroxymethylated highly expressed genes and 14 hypohydroxymethylated genes with low expression were identified. Gene ontology analyses indicated that the biological functions of hyperhydroxymethylated highly expressed genes included skeletal system development, ossification, and bone development; KEGG pathway analysis showed enrichment in protein digestion and absorption, extracellular matrix-receptor interaction, and focal adhesion. The top 10 hub genes in the protein-protein interaction network were COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL6A1, COL8A1, COL11A1, and COL24A1. All the aforementioned results are consistent with changes observed in OA.After comprehensive bioinformatics analysis, we found aberrantly hydroxymethylated differentially expressed genes and pathways in OA. The top 10 hub genes may be useful hydroxymethylation analysis biomarkers to provide more accurate OA diagnoses and target genes for treatment of OA.
Acetyl-CoA carboxylase (ACC) plays an important role in the metabolism of various cancer cells, but its role in head and neck squamous cell carcinoma (HNSCC) is uncertain. Therefore, in the present study, we explored the role of ACC2 in HNSCC.Western blot and immunohistochemistry assays were used to determine ACC2 protein expression levels in laryngocarcinoma and adjacent normal tissues derived from patients with laryngocarcinoma. ACC2 expression was knocked down in the hypopharyngeal cancer cell line FaDu to determine its effect on apoptosis. Lipid oil red staining was used to test the change of intracellular lipid.The results showed that the ACC2 protein was highly expressed in laryngocarcinoma and that the ACC2 expression level was positively associated with the clinical cancer stage and negatively associated with the degree of laryngocarcinoma cell differentiation. Kaplan-Meier analyses indicated that compared with patients having low levels of ACC2, those with high ACC2 levels had a decreased 5-year survival rate. The results of western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays showed that knockdown of ACC2 accelerated apoptosis in FaDu cells. Furthermore, knockdown of ACC2 significantly reduced the intracellular lipid levels in FaDu cells.These findings suggest that ACC2 may be an important prognostic marker for patients with HNSCC and that ACC2 may be a potential target in the treatment of HNSCC.
Previous study revealed that bufalin can inhibit proliferation, and induce apoptosis in some human cancer cell lines. However, the mechanism of its anticancer effect has not been fully understood. The present study was designed to investigate the effects of bufalin-induced apoptosis on Bcl-2 and PKC in human leukemic HL-60 cells. The cell viability was determined by trypan blue dye exclusion. The apoptosis was detected by morphology, flow cytometry and DNA agarose gel electrophoresis. The expressions of Bcl-2 and PKC were analyzed by Western blot, and activity of PKC was assayed by [gamma-(32)P] isotope incorporation method. The results showed as follows: (1) proliferation of HL-60 cells was inhibited by bufalin and the IC(50) at 24, 48, 72 hours were (25.8 +/- 2.1), (8.0 +/- 1.2) and (2.3 +/- 0.3) nmol/L, respectively. (2) apoptosis of HL-60 cells was induced when the cells were treated with bufalin at concentration of 50 nmol/L for 24 hours. (3) compared with control, treatment with bufalin at concentration of 50 nmol/L for 6 - 24 hours resulted in downregulation of protein expression, decrease of phosphorylation, and cleavage of Bcl-2, simultaneously. (4) the activity of total PKC was unchanged when HL-60 cells were exposed to 1 - 100 nmol/L bufalin for 30 minutes, but PKCbetaII underwent translocation from cytosol to membrane. It is concluded that apoptosis induced by bufalin is associated with downregulation of protein expression, dephosphorylation, and cleavage of Bcl-2 in HL-60 cells.
Abstract Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma japonicum . Because the parasite’s eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma. JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied S. japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S. japonicum . Mice infected with S. japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S. japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S. japonicum egg– induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S. japonicum . These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis. Author summary Among neglected tropical diseases, schistosomiasis is a serious disease caused by infection with the parasite Schistosomiasis japonicum . Treatment of schistosomiasis is currently almost exclusively with praziquantel, which kills mainly adult parasites, with minimal effectiveness against immature schistosomes and eggs. However, the parasite’s eggs are primarily responsible for schistosomiasis dissemination and pathology. In addition, overuse of praziquantel in epidemic areas has led to drug resistance and a reduced cure rate. Thus, new parasite targets for the development of novel therapeutics are crucial. Here, we evaluated the potential of JQ-1, a bromodomain and extra-terminal protein inhibitor, to suppress the production of S. japonicum eggs. Application of JQ-1 to S. japonicum in vitro decreased the number of mature germ cells, the rates of oviposition, and the number of eggs produced in each male-female pairing. JQ-1 treatment of mice infected with S. japonicum ameliorated hepatic granuloma and decreased serum liver enzymes, suggesting improved liver function. These results indicate that JQ-1 inhibits reproductive development and egg production in S. japonicum , providing supporting evidence that JQ-1 warrants additional study for use as a novel approach in the prevention or treatment of schistosomiasis.
Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma . Because the parasite’s eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma . JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied to S . japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S . japonicum . Mice infected with S . japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S . japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S . japonicum egg–induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S . japonicum . These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis.
Abstract Objective To investigate the effect of α-lipoic acid on contrast-induced nephropathy (CIN) in diabetic patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). Methods Patients diagnosed with type 2 diabetes mellitus and coronary heart disease scheduled for CAG or PCI treatment at the Department of Cardiovascular Medicine, General Hospital of Ningxia Medical University from February 1, 2021, to August 30, 2023, were recruited. After obtaining informed consent, patients were allocated into three groups: α-lipoic acid group (38 cases), adequate hydration group (60 cases), and routine hydration group (104 cases).The primary outcome observed was the incidence of CIN, and secondary endpoints included changes in SCr, TBiL, and GGT 72 hours after contrast agent administration. Results The incidence of CIN in the α-lipoic acid group was 2.63% (1/38), 1.67% (1/60) in the adequate hydration group, and 4.81% (5/104) in the routine hydration group, with no statistically significant difference among the three groups ( p =0.544). After PCI or CAG, SCr levels decreased slightly more in the α-lipoic acid group compared to the adequate hydration group, while the routine hydration group showed an increase, but the differences were not statistically significant ( p > 0.05). Conclusion α-Lipoic acid has a certain improvement effect on renal function indicators (Scr) after CAG or PCI, but it did not demonstrate a significant preventive effect on CIN. Adequate hydration showed greater reduction in oxidative stress damage after CAG or PCI compared to α-lipoic acid and routine hydration.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)