The incidence of retinopathy of prematurity (ROP) has increased continuously in recent years. However, the therapeutic effects of current treatments still remain undesired. This study aims to investigate the role of C-CBL in retinal angiogenesis in ROP and its potential as a therapeutic target. Mouse retina microvascular endothelial cells (mRMECs) and induced experimental ROP/ oxygen-induced retinopathy (OIR) mice were employed to investigate the role of C-CBL in angiogenesis with combined molecular and cellular approaches, and histopathology methods. OIR mouse pups at postnatal day 12 (P12) were either injected intravitreally with adenovirus overexpressing c-Cbl or c-Cbl siRNA. Retinal neovascularization and avascular status were evaluated by retinal immunofluorescence (IF) staining, whole-mounts and hematoxylin and eosin (H&E) staining. C-CBL inhibits neovascularization by negatively regulating JAK2/STAT3/VEGF signaling axis in a ubiquitination-dependent manner. Knockdown of c-Cbl by siRNA reduced ubiquitin-mediated JAK2 degradation and increased levels of p-JAK2, p-STAT3, VEGF, and neovascularization in mRMECs, which can be reversed by JAK2 inhibitor treatment. While knockdown of c-Cbl significantly increased neovascular (NV) zone in the retinas, c-Cbl overexpression inhibited neovascularization in the retinal tissues in OIR mice. We found that C-CBL is required for anti-neovascularization process in ROP development by inhibiting JAK2/STAT3-dependent angiogenesis. Thus, our finding strongly suggest that C-CBL may be a potential novel therapeutic target for treating ROP.

Lymphoma is a serious malignant tumor that contains more than 70 different types and seriously endangers the body’s lymphatic system. The lymphatic system is the regulatory center of the immune system and is important in the immune response to foreign antigens and tumors. Studies showed that multiple genetic variants are associated with lymphoma but determining the pathogenic mechanisms remains a challenge. In the present study, we first applied the Gene Ontology (GO) and KEGG pathway enrichment analyses of lymphoma‐associated and lymphoma‐nonassociated genes. Next, the Boruta and max‐relevance and min‐redundancy feature selection methods were performed to filter and rank features. Then, features preselected and ranked using the incremental feature selection method were applied for the decision tree model to identify the best GO terms and KEGG pathways and extract classification rules. Results indicate that our predicted features, such as B‐cell activation, negative regulation of protein processing, negative regulation of mast cell cytokine production, and natural killer cell‐mediated cytotoxicity, are associated with the biological process of lymphoma, consistent with those of recent publications. This study provides a new perspective for future research on the molecular mechanisms of lymphoma.

Lymphoma is a serious type of cancer, especially for adolescents and elder adults, although this malignancy is quite rare compared with other types of cancer. The cause of this malignancy remains ambiguous. Genetic factor is deemed to be highly associated with the initiation and progression of lymphoma, and several genes have been related to this disease. Determining the pathogeny of lymphoma by identifying the related genes is important. In this study, we presented a random walk-based method to infer the novel lymphoma-associated genes. From the reported 1,458 lymphoma-associated genes and protein–protein interaction network, raw candidate genes were mined by using the random walk with restart algorithm. The determined raw genes were further filtered by using three screening tests (i.e., permutation, linkage, and enrichment tests). These tests could control false-positive genes and screen out essential candidate genes with strong linkages to validate the lymphoma-associated genes. A total of 108 inferred genes were obtained. Analytical results indicated that some inferred genes, such as RAC3, TEC, IRAK2/3/4, PRKCE, SMAD3, BLK, TXK, PRKCQ, were associated with the initiation and progression of lymphoma.

Objective To explore the association between age-related macular degeneration (AMD) and arthritis in a representative sample of the US population. Design Population-based, cross-sectional study. Setting The National Health and Nutrition Examination Survey (NHANES) 2005–2008. Participants A total of 4813 participants aged 40 years and older with available information on AMD and arthritis in the 2005–2008 NHANES. Methods The status and types of arthritis were obtained from questionnaires. Non-mydriatic fundus photographs were collected. The types of AMD were assessed using the modified Wisconsin Age-Related Maculopathy Grading Classification Scheme. The association between arthritis and AMD was evaluated using logistic regression models. Results After adjusting for covariates, participants with any or early AMD had significantly lower odds of having any type of arthritis (any AMD: OR=0.56, 95% CI: 0.36–0.86; early AMD: OR=0.55, 95% CI: 0.34–0.88) or osteoarthritis (OA) (any AMD: OR=0.43, 95% CI: 0.26–0.71; early AMD: OR=0.44, 95% CI: 0.25–0.76) compared with those without AMD. When considering AMD as the outcome, significant negative associations were also found between any arthritis or OA and any (any arthritis: OR=0.64, 95% CI: 0.43–0.94; OA: OR=0.52, 95% CI: 0.33–0.82) or early AMD (any arthritis: OR=0.61, 95% CI: 0.40–0.93; OA: OR=0.51, 95% CI: 0.31–0.86) in the multivariable logistic models. There was no significant association between different types of arthritis and late AMD. Conclusions People with arthritis, especially those with OA, were less likely to have AMD compared with those without arthritis and vice versa. Further studies are needed to confirm this potential protective effect of arthritis and/or arthritis treatment on AMD and to explore the underlying mechanisms.