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Aim:To investigate the mechanisms by which berberine suppressed the proliferation of human multiple myeloma cells.Methods:Human U266 multiple myeloma cell line was tested. Cell proliferation, apoptosis, ultramicrostructure and secretion function were examined using Cell Counting Kit-8 (CCK8), flow cytometry (FCM), electron and fluorescence microscopy, as well as ELISA assay. The microRNAs (miRs) and transcription factors in U266 cells were detected using arrays and verified by qRT-PCR. EMSA and luciferase assays were used to verify the p65-dependent transactivation of miR-21 gene.Results:Treatment of U266 cells with berberine (40−160 μmol/L) suppressed cell proliferation and IL-6 secretion in dose- and time-dependent manners. Meanwhile, berberine dose-dependently induced ROS generation, G2/M phase arrest and apoptosis in U266 cells, and decreased the levels of miR-21 and Bcl-2. Overexpression of miR-21 counteracted berberine-induced suppression of cell proliferation and IL-6 secretion. In U266 cells treated with berberine (80 μmol/L), the activity of NF-κB was decreased by approximately 50%, followed by significant reduction of miR-21 level. berberine (80−160 μmol/L) increased the level of Set9 (lysine methyltransferase) by more than 2-fold, caused methylation of the RelA subunit, which inhibited NF-κB nuclear translocation and miR-21 transcription. In U266 cells treated with berberine (80 μmol/L), knockdown of Set9 with siRNAs significantly increased NF-κB protein level accompanying with a partial recovery of proliferation.Conclusion:In U266 cells, berberine suppresses NF-κB nuclear translocation via Set9-mediated lysine methylation, leads to decrease in the levels miR21 and Bcl-2, which induces ROS generation and apoptosis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between central serous chorioretinopathy (CSC) and Helicobacter pylori (Hp) by summarizing all available evidence., Methods: The Scopus, Embase, EBSCO, PubMed, Web of Science, and Cochrane Library databases for all relevant studies published from inception to October 2022 were searched, and manually searched for relevant reference lists as a supplement. Studies investigating the association between CSC and Hp infection were included. Finally, 8 case-control studies were included in the Meta-analysis after study selection., Results: The results showed no significant correlation between Hp infection and CSC [odds ratio (OR) 1.89, 95% confidential interval (CI) 0.58-6.15, I 2 =96%, P =0.29]. After subgroup analysis based on the degree of development of the study (developing/developed countries), it was found that the results of the two subgroups were the same as the whole, and no significant difference between the two subgroups existed. Meta-regression showed that the effect of sample size on heterogeneity among studies was more prominent ( P <0.01, adjusted R 2 =89.72%), which can explain 89.72% of the sources of heterogeneity., Conclusion: This Meta-analysis reveals no significant correlation between Hp infection and CSC, which still warrants further well-designed extensive sample studies to reach a more reliable conclusion and promote a better understanding of the treatment of CSC., Competing Interests: Conflicts of Interest: Wu DW, None; Jiang FP, None; Ge G, None; Zhang MX, None., (International Journal of Ophthalmology Press.)

Aim: To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze the advantages, limitations, and possible solutions common to all tasks., Methods: We searched three academic databases, including PubMed, Web of Science, and Ovid, with the date of August 2022. We matched and screened according to the target keywords and publication year and retrieved a total of 4358 research papers according to the keywords, of which 23 studies were retrieved on applying deep learning in diagnosing ophthalmic disease with ultrawide-field images., Results: Deep learning in ultrawide-field images can detect various ophthalmic diseases and achieve great performance, including diabetic retinopathy, glaucoma, age-related macular degeneration, retinal vein occlusions, retinal detachment, and other peripheral retinal diseases. Compared to fundus images, the ultrawide-field fundus scanning laser ophthalmoscopy enables the capture of the ocular fundus up to 200° in a single exposure, which can observe more areas of the retina., Conclusion: The combination of ultrawide-field fundus images and artificial intelligence will achieve great performance in diagnosing multiple ophthalmic diseases in the future., (International Journal of Ophthalmology Press.)

Aim: To identify and understand the relationship between co-expression pattern and clinic traits in uveal melanoma, weighted gene co-expression network analysis (WGCNA) is applied to investigate the gene expression levels and patient clinic features. Uveal melanoma is the most common primary eye tumor in adults. Although many studies have identified some important genes and pathways that were relevant to progress of uveal melanoma, the relationship between co-expression and clinic traits in systems level of uveal melanoma is unclear yet. We employ WGCNA to investigate the relationship underlying molecular and phenotype in this study., Methods: Gene expression profile of uveal melanoma and patient clinic traits were collected from the Gene Expression Omnibus (GEO) database. The gene co-expression is calculated by WGCNA that is the R package software. The package is used to analyze the correlation between pairs of expression levels of genes. The function of the genes were annotated by gene ontology (GO)., Results: In this study, we identified four co-expression modules significantly correlated with clinic traits. Module blue positively correlated with radiotherapy treatment. Module purple positively correlates with tumor location (sclera) and negatively correlates with patient age. Module red positively correlates with sclera and negatively correlates with thickness of tumor. Module black positively correlates with the largest tumor diameter (LTD). Additionally, we identified the hug gene (top connectivity with other genes) in each module. The hub gene RPS15A, PTGDS, CD53 and MSI2 might play a vital role in progress of uveal melanoma., Conclusion: From WGCNA analysis and hub gene calculation, we identified RPS15A, PTGDS, CD53 and MSI2 might be target or diagnosis for uveal melanoma.

Objective: To observe the effect of small interfering RNA (siRNA) targeting multidrug resistance-related protein (MRP) and bcl-2 genes in modulating drug resistance and apoptosis of K562 and K562/ADM cells., Methods: Two siRNA constructs targeting respectively bcl-2 and MRP genes, were synthesized and transfected either alone or in combination into K562 and K562/ADM cells via lipofectamine2000. MTT assay was used to evaluate the viability of the transfected cells at 24, 48 and 72 h Post-fransfection, and RT-PCR was performed to determine the mRNA levels of bcl-2 and MRP. The effects of MRP siRNA and bcl2 siRNA on the apoptosis and the protein expression of Bcl-2 and MRP were evaluated with flow cytometry., Results: In K562/ADM cells, the IC (50) decreased from 12.81 microg/ml (ADM group) to 3.74 microg/ml (ADM+MRP siRNA group), 6.82 microg/ml (ADM+bcl2 siRNA group) and 2.51 microg/ml (ADM+MRP siRNA+bcl2 siRNA). Similarly, in K562 cells, the IC50 decreased significantly from 6.75 microg/ml (ADM) to 3.22 microg/ml (ADM+MRP siRNA), 3.56 microg/ml (ADM+bcl2 siRNA) and 1.84 microg/ml (ADM+MRP siRNA+bcl2 siRNA) (P<0.05). Flow cytometry demonstrated significantly increased apoptosis of the cells following MRP siRNA and bcl2 siRNA transfection, which also resulted in significantly decreased expressions of MRP and bcl-2 proteins (P<0.05)., Conclusion: Treatment with both MRP and bcl-2 siRNAs inhibits the target gene expression, and increases the drug sensitivity and apoptosis of K562 and K562/ADM cells.