Efficacy of Intravitreal Injections Anti-Vascular Endothelial Growth Factor Treatment for Radiation Retinopathy: A Systematic Review and Meta-analysis.

PURPOSE: This study aims to appraise the therapeutic effectiveness of intravitreal injections anti-vascular endothelial growth factor (anti-VEGF) vs alternative therapies in managing radiation retinopathy (RR). DESIGN: Systematic review and meta-analysis. METHODS: We obtained comprehensive data retrieval using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library from their inception until December 15, 2023. This review included randomized controlled trials (RCTs) and nonrandomized studies (NRSs) reporting on best-corrected visual acuity (BCVA) among RR patients treated with intravitreal anti-VEGF. Study selection and data extraction were meticulously performed by 2 independent reviewers. The Cochrane Risk of Bias Tool 2.0 (RoB 2.0) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) scales were utilized for bias risk assessment. Quantification of heterogeneity was executed using Q, H, and I2 statistics. The primary endpoint was the BCVA at the final observation point of each study. Secondary endpoints included central retinal thickness (CRT), foveal avascular zone (FAZ) area, and capillary density (CD) at the level of superficial capillary plexus. Subgroup analyses were undertaken to explore potential heterogeneity sources possibly due to treatment duration and study design. Sensitivity analyses were conducted to ascertain result stability. RESULTS: This analysis incorporated 7 studies (including 3 RCTs) encompassing 922 patients afflicted with RR. Relative to other treatment modalities, intravitreal anti-VEGF therapy was associated with a statistically significant mean decrease in BCVA of -0.34 logMAR (95% CI, -0.39 to -0.30 logMAR; I2 = 87.70%; P < .001), and a substantial reduction in CRT of -34.65 µm (95% CI, -50.70 to -18.60 µm; I2 = 30.40%; P < .001). Additionally, a reduction in the FAZ area by -0.69 mm² (95% CI, -0.91 to -0.46 mm², I2 = 0%; P < .001) was observed. A positive tendency was noted in CD at the superficial capillary plexus between anti-VEGF and other therapeutic interventions. CONCLUSIONS: Intravitreal anti-VEGF injections, in comparison to other treatments, demonstrate superior efficacy in enhancing BCVA and reducing CRT, thereby underscoring the potential of anti-VEGF in ameliorating radiation retinopathy outcomes. However, the conclusions are constrained by the incorporation of data from some NRSs and the small sample sizes.

Risk factors for postoperative urinary retention in patients undergoing colorectal surgery: a systematic review and meta-analysis.

PURPOSE: Postoperative urinary retention (POUR) is a common complication following colorectal surgery. The incidence of POUR among colorectal surgery patients varies widely, and the risk factors and outcomes of POUR are also debatable. This meta-analysis aims to systematically evaluate the risk factors for POUR in patients after colorectal surgery. METHODS: PubMed, Web of Science, the Cochrane Library, Embase, Medline, and Chinese databases (CBM, CNKI, and WanFang Databases) were searched to identify relevant cohort studies (from inception to August 2022). Two researchers independently conducted literature quality evaluation and data extraction. All data were analyzed by using the Review Manager 5.4 software. RESULTS: Nineteen studies with 101,025 patients were included in this meta-analysis. The risk factors for POUR in colorectal surgery patients were male sex, older age, diabetes mellitus, urological diseases, tumor location in the lower rectum, APR, laparoscopic surgery, operation time ≥ 4 h, postoperative date of urinary catheter removal, excessive intraoperative intravenous fluid volume, and postoperative ileus. The postoperative anastomotic leak, on the other hand, was not a risk factor for POUR. CONCLUSIONS: Multiple risk factors influence the incidence of POUR in patients undergoing colorectal surgery. To reduce the incidence of POUR in colorectal surgery patients, medical staff should identify risk factors early and enforce interventions to prevent them.

GABA transporter sustains IL-1ß production in macrophages.

Accumulating evidence shows that nervous system governs host immune responses; however, how γ-aminobutyric acid (GABA)ergic system shapes the function of innate immune cells is poorly defined. Here, we demonstrate that GABA transporter (GAT2) modulates the macrophage function. GAT2 deficiency lowers the production of interleukin-1ß (IL-1ß) in proinflammatory macrophages. Mechanistically, GAT2 deficiency boosts the betaine/S-adenosylmethionine (SAM)/hypoxanthine metabolic pathway to inhibit transcription factor KID3 expression through the increased DNA methylation in its promoter region. KID3 regulates oxidative phosphorylation (OXPHOS) via targeting the expression of OXPHOS-related genes and is also critical for NLRP3-ASC-caspase-1 complex formation. Likewise, GAT2 deficiency attenuates macrophage-mediated inflammatory responses in vivo, including lipopolysaccharide-induced sepsis, infection-induced pneumonia, and high-fat diet-induced obesity. Together, we propose that targeting GABAergic system (e.g., GABA transporter) could provide previously unidentified therapeutic opportunities for the macrophage-associated diseases.

Luteolin Induces Apoptosis and Autophagy in Mouse Macrophage ANA-1 Cells via the Bcl-2 Pathway.

Plants rich in luteolin have been used as Chinese traditional medicines for inflammatory diseases, hypertension, and cancer. However, little is known about the effect of luteolin on the apoptosis or autophagy of the macrophages. In this study, mouse macrophage ANA-1 cells were incubated with different concentrations of luteolin. The viability of the cells was determined by an MTT assay, apoptosis was determined by flow cytometric analysis, the level of cell autophagy was observed by confocal microscopy, and the expression levels of apoptotic or autophagic and antiapoptotic or antiautophagic proteins were detected by Western blot analysis. The results showed that luteolin decreased the viability of ANA-1 cells and induced apoptosis and autophagy. Luteolin induced apoptosis accompanied by downregulation of the expression of Bcl-2 and upregulation of the expression of caspase 3 and caspase 8. And luteolin increased FITC-LC3 punctate fluorescence accompanied by the increased expression levels of LC3-I, ATG7, and ATG12, while it suppressed the expression level of Beclin-1. Luteolin treatment resulted in obvious activation of the p38, JNK, and Akt signaling pathways, which is important in modulating apoptosis and autophagy. Thus, we concluded that luteolin induced the apoptosis and autophagy of ANA-1 cells most likely by regulating the p38, JNK, and Akt pathways, inhibiting the activity of Bcl-2 and Beclin-1 and upregulating caspase 3 and caspase 8 expression. These results provide novel insights into a therapeutic strategy to prevent and possibly treat macrophage-related diseases through luteolin-induced apoptosis and autophagy.

Monopolar spindle-one-binder protein 2 regulates the activity of large tumor suppressor/yes-associated protein to inhibit the motility of SMMC-7721 hepatocellular carcinoma cells.

Accumulating evidence implicates monopolar spindle-one-binder protein (MOB)2 as an inhibitor of nuclear-Dbf2-related kinase (NDR) by competing with MOB1 for interaction with NDR1/2. NDR/large tumor suppressor (LATS) kinases may function similarly to yes-associated protein (YAP) kinases and be considered as members of the Hippo core cassette. MOB2 appears to serve roles in cell survival, cell cycle progression, responses to DNA damage and cell motility. However, the underlying mechanisms involved remain unclarified. In the present study, it was demonstrated that the knockout of MOB2 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 promoted migration and invasion, induced phosphorylation of NDR1/2 and decreased phosphorylation of YAP in SMMC-7721 cells when compared with the blank vector-transduced cells. By contrast, the overexpression of MOB2 resulted in the opposite results. Mechanistically, MOB2 regulated the alternative interaction of MOB1 with NDR1/2 and LATS1, which resulted in increased phosphorylation of LATS1 and MOB1 and thereby led to the inactivation of YAP and consequently inhibition of cell motility. The results of the present study provide evidence of MOB2 serving a positive role in LATS/YAP activation by activating the Hippo signaling pathway.

Plasma orexin-A level associated with physical activity in obese people.

OBJECTIVE: To measure the amount of physical activity (PA) among obese adults, investigate the association between plasma orexin-A level and PA patterns, and explore the effect of orexin on the prevention and control of obesity. METHODS: Interviews were conducted in 218 participants (106 obese; 73 overweight; and 39 normal) who ranged in age between 18 and 70 years using a survey that included sociodemographic variables. The International Physical Activity Questionnaire (IPAQ-long version) was used to measure PA. A total of 178 participants agreed to submit blood sample collections, and plasma orexin-A content was measured by ELISA testing. RESULTS: The average level of orexin-A was 85.34 ± 42.85 ng/L in the obese group, 97.38 ± 36.72 ng/L in the overweight group, and 106.56 ± 52.09 ng/L in the control group, which was significantly different (P = 0.03). The concentration of plasma orexin-A correlated with the total PA (P = 0.000), moderate PA (obese = 0.007; overweight: P = 0.000; control: P = 0.000), and walking PA (P = 0.000) in all three groups. Working and domestic PAs were significantly associated with the plasma orexin-A level (P < 0.0001). CONCLUSIONS: The plasma orexin-A level was associated with PA in obese and overweight people, including many aspects of daily life, such as working, domestic work, and walking especially.

Immediate early response protein 2 regulates hepatocellular carcinoma cell adhesion and motility via integrin ß1-mediated signaling pathway.

Human immediate early response 2 (IER2) has been reported to function as a potential transcriptional factor or transcriptional co­activator and seems to play a pivotal role in tumor cell motility and metastasis, however, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unknown. Herein, we demonstrated that overexpression of IER2 in HCC cells increased cell adhesion to fibronectin, migration and invasion, whereas knockdown of IER2 displayed the opposite effects. In agreement with this phenotype, IER2 expression was positively correlated with the metastatic potential and integrin ß1 (ITGB1) expression in HCC cell lines. Moreover, we demonstrated a critical role for IER2 in regulation of HCC cell­extracellular matrix (ECM) adhesion and motility by the transcriptionally promoted ITGB1. Furthermore, we showed that ITGB1­focal adhesion kinase (FAK)­Src­paxillin signal pathway activated by IER2 may contribute to the HCC cell­ECM adhesion and motility. These results demonstrated that IER2 promoted HCC cell adhesion and motility probably by directly increasing ITGB1 expression and subsequently activating the ITGB1­FAK­Src­paxillin signal pathway.

Identification of immediate early response protein 2 as a regulator of angiogenesis through the modulation of endothelial cell motility and adhesion.

Human immediate early response 2 (IER2) has been characterized as a putative nuclear protein that functions as a transcription factor or transcriptional co­activator in the regulation of cellular responses, and may be involved in the regulation of tumor progression and metastasis. Data from our previous gene expression profile of the human microvascular endothelial cells during capillary morphogenesis showed a significant alteration of IER2 expression, suggesting that IER2 may participate in the regulation of the endothelial cell morphogenesis and angiogenesis. The aim of the present study was to investigate the role of IER2 in cell motility, cell­matrix adhesion and in vitro capillary­like structures formation of the human umbilical vein endothelium cells (HUVECs). IER2 was constitutively expressed in HUVECs, and lentiviral­mediated depletion of IER2 significantly reduced the cell motility, cell­matrix adhesion and capillary­like structures formation of HUVECs. Results also showed that depletion and overexpression of IER2 altered the actin cytoskeleton rearrangement in HUVECs. Furthermore, results from western blot analysis showed that the activity of the focal adhesion kinase (FAK) can be regulated by IER2. These results indicated that IER2 regulates endothelial cell motility, adhesion on collagen type I matrix and the capillary tube formation, as the result of the regulation of the actin cytoskeleton rearrangement presumably via a FAK­dependent mechanism.

miR-30c negatively regulates the migration and invasion by targeting the immediate early response protein 2 in SMMC-7721 and HepG2 cells.

miR-30c has been reported to act as a tumor suppressor and negatively regulate cancer metastasis by directly targeting metastasis associated genes; however, miR-30c has also been shown to promote the invasion of metastatic breast cancer cells, suggesting that miR-30c might be involved in cancer cell metastasis in different ways via targeting different genes. In this study, we demonstrated that over-expression and knockdown of immediate early response protein 2 (IER2) modulated the general capacity of the migration and invasion in hepatocellular carcinoma cell line SMMC-7721 and HepG2, whereas overexpression and knockdown of miR-30c decreased and promoted cell motility, respectively. Further studies revealed that miR-30c overexpression down-regulated the expression of IER2 protein but not its mRNA level, and miR-30c can directly target the 3' untranslated region (3'UTR) of IER2, and subsequently reducing its expression. Moreover, we also showed that suppression of cell motility by miR-30c was partially rescued by IER2 re-expression. Our results indicated that miR-30c may function as a negative regulator in cell motility, with IER2 as a direct and functional target in SMMC-7721 and HepG2 cells.

Apigenin induces the apoptosis and regulates MAPK signaling pathways in mouse macrophage ANA-1 cells.

Apigenin is a naturally occurring plant flavonoid that possesses antioxidant, anti-cancer and anti-inflammatory properties. However, there are few reports has been done on the ability of apigenin to induce apoptosis in macrophages. In this study, mouse macrophage ANA-1 cells were incubated with different concentrations of apigenin. The cell viability was determined by an MTT assay. The cell apoptosis were analyzed by flow cytometric analysis. Apoptosis were also analyzed using a TUNEL assay and a DNA ladder. The level of intracellular ROS was detected using a dichlorofluorescein -diacetate probe. The expression levels of apoptosis-related proteins were detected by western blot analysis. The results showed that apigenin decreased the viability of ANA-1 cells and induced apoptosis in a dose- and time-dependent manner. Apigenin increased the level of intracellular ROS, downregulated the expression of Bcl-2 and upregulated the expression of caspase-3 and caspase-8 in ANA-1 cells. Furthermore, apigenin downregulated the expression of phospho-ERK and phospho-JNK, upregulated the expression of phospho-p38 and had no significant effect on the expression of Bax, ERK, JNK and p38. The results suggested that apigenin induced cell apoptosis in mouse macrophage ANA-1 cells may via increasing intracellular ROS, regulating the MAPK pathway, and then inhibiting Bcl-2 expression.

[Bilateral regulation of luteolin on spleen cells and sarcoma S180 cells of ICR mice: an experimental study].

OBJECTIVE: To study the regulation of luteolin on spleen cells and sarcoma S180 cells in normal ICR mice. METHODS: Spleen cells and S180 cells were incubated with different concentrations of luteolin (50, 100, 200, and 400 µmol/L). The effect of luteolin on spleen cells and sarcoma S180 cells was determined by MTT assay. The apoptosis was detected using propidium iodide staining flow cytometry. Intracellular reactive oxygen species (ROS) was determined by flow cytometric analysis. Activities of free radicals scavenging were determined by hydroxyl radical and DPPH tests. RESULTS: Compared with the solvent control group, 200 and 400 µmol/L luteolin increased the spleen cells viability (P < 0.05). Luteolin at 100, 200, and 400 µmol/L decreased activities of S180 cells (P < 0.01). The proportion of sub-G1 phase spleen cells was reduced after treated with 200 and 400 µmol/L luteolin (P < 0.05). The proportion of sub-G1 phase S180 cells was elevated after treated with 200 and 400 µmol/L luteolin (P < 0.05). Compared with the solvent control group, levels of intracellular ROS in spleen cells of ICR mice all increased; levels of intracellular ROS in S180 cells all decreased after treated with 50, 100, 200, and 400 µmol/L luteolin (P < 0.05). Luteolin scavenged hydroxyl radical and DPPH in a dose dependent manner. CONCLUSION: Luteolin had bilateral regulation on viability and apoptosis of spleen cells and S180 cells (promoting the viability of spleen cells, inhibiting apoptosis of spleen cells, inhibiting the viability of S180 cells, and promoting apoptosis of S180 cells), which was worth further study and exploration.