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Retinal ischemia reperfusion injury (RIRI) is a conventional pathological process in various retinal vascular diseases. Many studies select only one specific time point to apply drugs and then assess the therapeutic effect of drugs; however, the baselines are not the same at different time points, which may cause variation in the judgement. Therefore, further investigation is needed. Accordingly, this study aimed to investigate the pathological changes of retinal structure, expression of JAK-STAT signaling pathway hallmark proteins, and apoptosis at different time points after retinal ischemia reperfusion injury in rats. Sixty-six male SPF Sprague-Dawley rats were randomly divided into six groups: control group, RIRI 0, 6-, 24-, 72-, and 144-h groups. RIRI models were induced by perfusing equilibrium solution into the right eye anterior chamber to increase intraocular pressure to 110 mmHg for 60 min. Rats were sacrificed at different time points after reperfusion. Then hematoxylin-eosin staining, transmission electron microscope, immunohistochemistry, western blot, and TUNEL were used. Hematoxylin-eosin showed the pathological changes while transmission electron microscope revealed the ultra-structure changes of retina after RIRI. Immunohistochemistry showed that JAK2, STAT3, p-JAK2, p-STAT3, Bax, and Bcl-2 proteins mainly located in ganglion cell layer and inner nuclear layer, the relative expression of former five proteins had significant differences vs. control group (p < 0.05), while Bcl-2 had no significant difference. In western blot, the protein expressing of JAK2, STAT3, p-JAK2, p-STAT3, p-Akt, and Bax had significant differences vs. control group (p < 0.05), while Akt and Bcl-2 had no significant differences. TUNEL staining showed the number of apoptosis positive cells rose initially but declined later, with a peak value at RIRI 24 h group. The dynamic changes of hallmark proteins at different time points after RIRI indicate that JAK-STAT signaling pathway activates rapidly but weakens later and plays a vital role in RIRI, and apoptosis is involved in RIRI with a peak value at 24 h in the process, suggesting a potential therapeutic direction and time window for treating RIRI.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy and its damage to vision is irreversible. Therefore, early diagnosis assisted by biomarkers is essential. Although there were multiple researches on the identification of POAG biomarkers, few studies systematically revealed the transcriptome dysregulation mechanism of POAG from the perspective of pre- and post-transcription of genes. Here, we have collected multiple sets of POAG’s aqueous humor (AH) tissue transcription profiles covering long non-coding RNA (lncRNA), mRNA and mircoRNA (miRNA). Through differential expression analysis, we identified thousands of significant differentially expressed genes (DEGs) between the AH tissue of POAG and non-glaucoma. Further, the DEGs were used to construct a competing endogenous RNA (ceRNA) regulatory network and 1,653 qualified lncRNA-miRNA-mRNA regulatory units were identified. Two ceRNA regulatory subnets were identified based on the random walk algorithm and revealed to be involved in the regulation of multiple complex diseases. At the pre-transcriptional regulation level, a transcriptional regulatory network was constructed and three transcription factors (FOS, ATF4, and RELB) were identified to regulate the expression of multiple genes and participate in the regulation of T cells. Moreover, we revealed the immune desert status of AH tissue for POAG patients based on immune infiltration analysis and identified a specific AL590666.2-hsa−miR−339−5p-UROD axis can be used as a biomarker of POAG. Taken together, the identification of regulatory mechanisms and biomarkers will contribute to the individualized diagnosis and treatment for POAG.

Song Liu,1,&ast; Xiaojun Cai,1,&ast; Tao Wang,1 Jiwen Xu,2 Weilun Cheng,3 Xuling Wang,1 Gangjie Wei,4 Shuang Yan5 1Endocrinology Department, Traditional Chinese Medicine Academy of Heilongjiang, Harbin, Heilongjiang Province, People’s Republic of China; 2Anatomy, Histology and Embryology Teaching and Research Section, School of Basic Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, People’s Republic of China; 3Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 4Medical Department, Traditional Chinese Medicine Academy of Heilongjiang, Harbin, Heilongjiang Province, People’s Republic of China; 5Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuang Yan, Email yan8028397483@126.comPurpose: Skeletal muscle insulin resistance (IR) is an important etiology of type 2 diabetes mellitus (T2DM); however, its molecular mechanism is yet to be fully defined. This study attempted to identify the gene expression patterns and molecular disorders in T2DM patients’ skeletal muscle samples.Methods: First, the difference in genetic expression among GSE25462 data was analyzed. Next, PPI network analysis of differential genes was carried out, after which the maladjustment module was identified. Then, an enrichment analysis and gene set enrichment analysis (GSEA) were carried out. Finally, the transcription factors that regulate the modular genes by raid were predicted.Results: Most differentially expressed genes were found to be able to form an interaction network and cluster into 9 modules. These modular genes were shown to possess a significant correlation with immune inflammation and metabolic response. Importantly, the top 15 genes of area under receiver operating characteristic curve (AUC) were identified, and the expression of 10 genes by GSE12643, GSE18732 and GSE29221 was confirmed. The expression and AUC value of ALDH6A1 were then verified according to three sets of data, where ALDH6A1 was found to be negatively correlated with follicular helper T cells. However, among the predicted transcription regulators, HDAC was shown to have a better regulatory effect.Conclusion: The findings highlight that the dysregulation of ALDH6A1 expression in IR of T2DM may serve as a potential therapeutic target. ALDH6A1 is involved in the immune inflammation and metabolic pathways.Keywords: type 2 diabetes mellitus, ALDH6A1, immune inflammatory response, metabolic pathway, HDAC