Comparison of the therapeutic effects of photodynamic therapy, transpupillary thermotherapy, and their combination on circumscribed choroidal haemangioma.

OBJECTIVE: To characterize the clinical and imaging features of circumscribed choroidal hemangioma (CCH), and to evaluate individualized treatment efficiency of photodynamic therapy (PDT), transpupillary thermotherapy (TTT), or their combination, followed by retrobulbar injection of betamethasone on CCH resolvement. METHODS: Forty-nine patients with CCHs who underwent PDT, TTT or PDT+TTT treatments were retrospectively analyzed. Their treatment efficacy was compared by analyzing the change of best corrected visual acuity (BCVA), subretinal fluid (SRF) and CCH lesion characteristics. RESULTS: PDT, TTT and PDT+TTT were respectively administrated in 17, 11 and 21 patients. No significant difference in age, gender, affected eyes and tumor location across the three groups. Baseline BCVA were 0.41 ± 0.28, 0.62 ± 0.30 and 0.24 ± 0.24 for PDT, TTT and PDT+TTT groups, respectively (F = 6.572, P = 0.003). CCH treated by three strategies showed significant difference in maximum tumor basal diameter, SRF areas and macula involvement prior to the treatment (P < 0.05). Patients receiving PDT+TTT exhibited larger tumor basal diameter, more SRF, higher ratio of macular involvement than other groups. A total of 38 (77.6 %) cases had good visual acidity with final BCVA ≥0.5 after treatments. PDT and PDT+TTT treatment groups acquired more vision improvement (0.27 ± 0.23 and 0.31 ± 0.26) in BCVA than TTT group (0.09 ± 0.13). All SRF were resolved within two weeks of treatment and no recurrent SRF were found. CONCLUSION: The three treatments showed good performance in improving visual function and controlling SRF, and individualized treatment should be selected primarily by the tumor location, and then the tumor size and presence of SRF.

Shank3 ameliorates neuronal injury after cerebral ischemia/reperfusion via inhibiting oxidative stress and inflammation.

Shank3, a key molecule related to the development and deterioration of autism, has recently been found to downregulate in the murine brain after ischemia/reperfusion (I/R). Despite this discovery, however, its effects on neuronal injury and the mechanism underlying the effects remain to be clarified. To address this, in this study, based on genetically modified mice models, we revealed that the expression of Shank3 showed a time-dependent change in murine hippocampal neurons after I/R, and that conditional knockout (cko) of Shank3 in neurons resulted in aggravated neuronal injuries. The protective effects of Shank3 against oxidative stress and inflammation after I/R were achieved through direct binding STIM1 and subsequent proteasome-mediated degradation of STIM1. The STIM1 downregulation induced the phosphorylation of downstream Nrf2 Ser40, which subsequently translocated to the nucleus, and further increased the expression of antioxidant genes such as NQO1 and HO-1 in HT22 cells. In vivo, the study has further confirmed that double knockout of Shank3 and Stim1 alleviated oxidative stress and inflammation after I/R in Shank3cko mice. In conclusion, the present study has demonstrated that Shank3 interacts with STIM1 and inhibits post-I/R neuronal oxidative stress and inflammatory response via the Nrf2 pathway. This interaction can potentially contribute to the development of a promising method for I/R treatment.

Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

Overexpression of actin-depolymerizing factor blocks oxidized low-density lipoprotein-induced mouse brain microvascular endothelial cell barrier dysfunction.

The aim of present work was to elucidate the role of actin-depolymerizing factor (ADF), an important regulator of actin cytoskeleton, in the oxidized low-density lipoprotein (ox-LDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to ox-LDL. Treatment with LDL served as control. It was found that ADF mRNA level and protein expression were decreased when exposed to ox-LDL in MBMECs. Then, we investigated the influence of ADF overexpression on ox-LDL-treated MBMECs. Structurally, overexpression of ADF inhibited ox-LDL-induced F-actin formation. Functionally, overexpression of ADF attenuated ox-LDL-induced disruption of endothelial barrier marked by restoration of transendothelial electrical resistance, permeability of Evans Blue and expression of tight junction-associated proteins including ZO-1 and occludin, and blocked ox-LDL-induced oxidative stress marked by inhibition of reactive oxygen species (ROS) formation and activity of NADPH oxidase and Nox2 expression. However, overexpression of ADF in control cells had no significant effect on endothelial permeability and ROS formation. In conclusion, overexpression of ADF blocks ox-LDL-induced disruption of endothelial barrier. In addition, siRNA-mediated downregulation of ADF expression aggravated ox-LDL-induced disruption of endothelial barrier and ROS formation. These findings identify ADF as a key signaling molecule in the regulation of BBB integrity and suggest that ADF might be used as a target to modulate diseases accompanied by ox-LDL-induced BBB compromise.

Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway.

BACKGROUND: Atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS) to imitate inflammatory conditions. RESULTS: In our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP) as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4) antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB), which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1), compared with transforming growth factor-ß1 (TGF-ß1). CONCLUSIONS: Taken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial infection contributes to the pathological process of atherosclerosis.

Treatment with XMU-MP-1 erases hyperglycaemic memory in hearts of diabetic mice.

Hyperglycaemic memory refers to the damages occurred under early hyperglycaemic environment in organs of diabetic patients persisting after intensive glycaemic control. Mammalian sterile 20-like kinase 1 (Mst1) contributes to the development of diabetic cardiomyopathy. Here, we investigated the role of Mst1 in hyperglycaemic memory and test the effect of XMU-MP-1, a Mst1 inhibitor, on hyperglycaemic memory in hearts. Eight weeks after induction of type 1 diabetes by injection with streptozotocin (STZ) in mice, glycaemic control was obtained by means of insulin treatment and maintained for 4 additional weeks. In the diabetic mice, insulin treatment alone did not reduce phosphorylation of Mst1 or improve cardiac function. Treatment with XMU-MP-1 alone immediately after induction of diabetes for 12 weeks did not improve myocardial function in mice. But treatment with XMU-MP-1 for the later 4 weeks relieved myocardial dysfunction when glycaemic control was obtained by insulin treatment simultaneously. Mst1 deficiency and glycaemic control synergistically improved myocardial function and reduced apoptosis in myocardium of diabetic mice. Mechanistically, when Mst1 was deficient or inhibited by XMU-MP-1, AMPK was activated and mitochondrial dysfunction was attenuated. In vitro, treatment with AMPK activator reversed the detrimental effects of Mst1 overexpression in cultured cardiomyocytes. XMU-MP-1 might thus be envisaged as a complement for insulin treatment against diabetic cardiomyopathy.

Integrated analysis of different microarray studies to identify candidate genes in type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D), an autoimmune disease, occurs most commonly in children. Identifying altered gene expression in peripheral blood mononuclear cells (PBMCs) of T1D may lead to new strategies for preserving or improving ß-ell function in patients with T1D. METHODS: The Gene Expression Omnibus database was searched for microarray studies in PBMCs of T1D. Subsequently, gene expression datasets from multiple microarray studies were integrated to obtain differentially expressed genes (DEGs) between T1D and normal controls (NC). Gene function analysis was performed to determine the functions of the DEGs identified. RESULTS: Four microarray studies were available for analysis, including 199 T1D samples and 74 NC samples. Analysis revealed 695 genes that were significantly differentially expressed in PBMCs from T1D compared with NC samples, with 450 upregulated and 245 downregulated. Signal transduction (gene ontology [GO]: 0007165; false discovery rate [FDR] = 1.54 × 10-7 ) and protein binding (GO: 0005515; FDR = 2.93 × 10-24 ) were significantly enriched for the GO categories of biological processes and molecular functions, respectively. The most significant pathway in the Kyoto Encyclopedia of Genes and Genomes analysis was arachidonic acid metabolism (FDR = 1.44 × 10-3 ). Protein-protein interaction network analysis showed that the significant hub proteins contained immature colon carcinoma transcript 1 (ICT1; degree = 214; clustering coefficient [C] = 4.39 × 10-5 ), zinc finger and BTB domain containing 16 (ZBTB16; degree = 112; C = 8.04 × 10-4 ), and SERTA domain containing 1 (SERTAD1; degree = 38; C = 0.0014). CONCLUSIONS: This integrated analysis will help develop improved therapies and interventions for T1D by identifying novel drug targets.

[Inhibition of IL-6 antisense oligonucleotide on IL-6 expression by human retinal pigment epithelium in vitro].

OBJECTIVE: To investigate the inhibition of IL-6 antisense oligonucleotide (ASON) on IL-6 expression by retinal pigment epithelium (RPE) cells on the basis of previous study. METHODS: Cultured human RPE cells was treated with IL-1 beta and IL-6 ASON. IL-6 mRNA and protein expression were detected by enzyme linked immunosorbent assay (ELISA), immunohistochemistry and in situ hybridization histochemistry (ISH). RESULTS: It was demonstrated that the IL-6 expression by RPE cells was dose and time dependent after the stimulation of IL-1 beta. IL-6 in the conditioned media or in the control group was 2.00 x 10(-6) g/L cells after the exposed to IL-1 beta for 8 hours. IL-6 ASON (2.00 x 10(-5) mol/L) obviously inhibited IL-6 (5.50 x 10(-7) g/L cells, t = 4.518, P < 0.01) production. Immunohistochemistry study showed dark blue staining in RPE cytoplasm after stimulation with IL-1 beta, while the cells treated with IL-6 ASON showed light staining in RPE cytoplasma. ISH displayed that there was a marked reduction in mRNA expression in IL-6 ASON treated group compared with that in the control group (t = 3.746, P < 0.01). CONCLUSION: Cultured RPE cells express IL-6 protein and mRNA in dose and time dependent manners when RPE cells are stimulated with IL-1 beta. The expressions of IL-6 protein and mRNA can be significantly inhibited by IL-6 ASON in cultured human RPE cells.

Incidence and risk factors for medical complications and 30-day end points after carotid artery stenting.

With the extensive use of carotid artery stenting (CAS) surgeries, scholars are paying more attention to the safety and efficiency of CAS. Our study aims to analyze the clinical efficiency, safety, and technical feasibility of CAS surgery in the treatment of carotid artery stenosis. A total of 379 cases of CAS were collected and retrospectively analyzed. The outcomes were summarized according to decrease in stenosis extent, incidence of early complications after procedure, 30-day end point events, and the follow-up data. Logistic regression was employed to analyze the correlations between risk factors and complications within 30 days and 30-day end points of stroke, myocardial infarctions (MIs), and mortality. The average extent of stenosis reduced from preoperative (81% ± 17%) to postoperative (26% ± 17%). In all, 53 patients had 72 medical complications, including 6 (1.58%) cerebral hemorrhage, 7 (1.85%) cerebral infarction, 5 (1.32%) transient ischemic attack (TIA), 5 (1.32%) heart failure, 10 (2.63%) symptomatic hypertension, 21 (5.54%) symptomatic hypotension, 10 (2.63%) symptomatic bradycardia, and 8 other complications; 15 patients had at least 2 complications. Advanced age, diabetes, and heart failure were associated with the high incidence of early complications (P < .05). Asymptomatic stenosis (odds ratio [OR] = 0.39, 95% confidence interval [CI]: 0.131-1.131, P = .0426) and diabetes (OR = 3.38, 95% CI: 1.340-8.574, P = .0099) were correlated with the incidence of 30-day end point events. Diabetes and symptomatic stenosis are independent risk factors for 30-day end point events of CAS. Advanced age, hypertension, and vascular unstable plaque will increase the risk of postoperative complications.

Platelet-derived growth factor induced alpha-smooth muscle actin expression by human retinal pigment epithelium cell.

PURPOSES: (1) To evaluate the association between expression of α-smooth muscle actin (α-SMA) in proliferative vitreoretinopathy (PVR) and the pathological grading of PVR, and the effect of platelet-derived growth factor (PDGF) on the expression of α-SMA by human retinal pigment epithelial (RPE) cells. (2) To investigate the potential induction of PDGF on the proliferation and migration of human RPE cells as well as the signaling pathways responsible. METHODS: We immunohistochemically investigated the expression of α-SMA in PVR. To further investigate the effect of PDGF and the downstream signaling, exogenous PDGF-BB and signaling inhibitors were added to cultured human RPE cells. The MTT method was performed to detected cell proliferation, while cell migration was also measured. RESULTS: α-SMA expression was positively correlated with the pathological grading of PVR. PDGF-BB could stimulate the proliferation and migration of cultured RPE cells through the participation of mitogen-activated protein kinase. In addition, PDGF induced α-SMA expression. The promotion of proliferate/migration and α-SMA expression by PDGF-BB was enhanced by the presence of serum. CONCLUSIONS: PDGF and α-SMA are 2 potential therapeutic targets for the treatment of PVR.

Treatment with hydrogen sulfide alleviates streptozotocin-induced diabetic retinopathy in rats.

BACKGROUND AND PURPOSE: Retinopathy, as a common complication of diabetes, is a leading cause of reduced visual acuity and acquired blindness in the adult population. The aim of present study was to investigate the therapeutic effect of hydrogen sulfide on streptozotocin (STZ)-induced diabetic retinopathy in rats. EXPERIMENTAL APPROACH: Rats were injected with a single i.p. injection of STZ (60 mg·kg⁻¹) to induce diabetic retinopathy. Two weeks later, the rats were treated with NaHS (i.p. injection of 0.1 mL·kg⁻¹·d⁻¹ of 0.28 mol·L⁻¹ NaHS, a donor of H2S) for 14 weeks. KEY RESULTS: Treatment with H2S had no significant effect on blood glucose in STZ-induced diabetic rats. Treatment with exogenous H2S enhanced H2S levels in both plasma and retinas of STZ-induced diabetic rats. Treatment with H2S in STZ-treated rats improved the retinal neuronal dysfunction marked by enhanced amplitudes of b-waves and oscillatory potentials and expression of synaptophysin and brain-derived neurotrophic factor, alleviated retinal vascular abnormalities marked by reduced retinal vascular permeability and acellular capillary formation, decreased vitreous VEGF content, down-regulated expressions of HIF-1α and VEGFR2, and enhanced occludin expression, and attenuated retinal thickening and suppressed expression of extracellular matrix molecules including laminin ß1 and collagen IVα3 expression in retinas of STZ-induced diabetic rats. Treatment with H2S in retinas of STZ-induced diabetic rats abated oxidative stress, alleviated mitochondrial dysfunction, suppressed NF-κB activation and attenuated inflammation. CONCLUSIONS AND IMPLICATIONS: Treatment with H2S alleviates STZ-induced diabetic retinopathy in rats possibly through abating oxidative stress and suppressing inflammation.

Negative correlation between serum syndecan-1 and apolipoprotein A1 in patients with type 2 diabetes mellitus.

Heparan sulfate proteoglycans (HSPGs) are involved in the regulation of cell growth, apoptosis and lipid metabolism in vitro. Syndecans are the primary form of HSPGs. Syndecan-1 is involved in the processes of cell growth, differentiation, adhesion, wound healing and inflammation. Additionally, as a sinusoidal transmembrane HSPG facing the plasma compartment, syndecan-1 is a promising target to be involved in lipoprotein physiology. We aimed to examine the possible correlation of syndecan-1 and lipid profile in type 2 diabetes mellitus. In this study, serum syndecan-1 was detected by ELISA, and potential correlations between syndecan-1 and triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein a, apolipoprotein (apo) B, apoA1 and apoB/apoA1 were analyzed. Forty-one patients with type 2 diabetes and 31 age-matched, non-diabetic healthy subjects (controls) were enrolled. Syndecan-1 in patients with diabetes (26.15 ± 2.42 ng/ml) was significantly higher than that of the controls (16.85 ± 1.98 ng/ml, t = -2.98, P = 0.005). Serum syndecan-1 level correlated negatively with apoA1 (r = -0.46, P = 0.003). Multiple regression analysis showed that apoA1 (b = -0.43, P = 0.003) was a predictor of serum syndecan-1 levels in subjects with type 2 diabetes.

Frosted branch angiitis in a woman with Mycobacterium tuberculosis infection.

PURPOSE: To describe a case of frosted branch angiitis in a patient with tuberculous meningitis. METHODS: Case report. RESULTS: A 27-year-old woman of tuberculous meningitis was referred to us complaining of blurred vision for 2 days. Prominent white sheathing of the retinal venules and, to a much lesser extent, arterioles, consistent with frosted branch angiitis were also observed in both eyes. And after treatment with systemic anti-tuberculosis medications and steroid, frosted branch angiitis showed resolution. CONCLUSIONS: Frosted branch angiitis can be caused by Mycobacterium tuberculosis. Systemic anti-tubercular therapy and steroids were effective.

Enhanced syndecan-1 expression on neutrophils in patients with type 2 diabetes mellitus.

The peripheral neutrophils are one of the main inflammatory cells and significantly influence the damage of endothelium. Type 2 diabetes is a manifestation of an ongoing low-grade inflammation. In diabetes, impairment of neutrophil adhesion to the endothelium and migration to the site of inflammation were detected, which associated closely with adhesion molecules expressed on neutrophils and endothelial cells. To detect the expression of syndecan-1 on neutrophils in patients with type 2 diabetes mellitus, we recruited 29 patients with type 2 diabetes mellitus without any diabetic complication and 24 healthy subjects (controls). Expression of syndecan-1 was determined by flow cytometry, and potential correlations between syndecan-1 and clinical characteristics were analyzed. On neutrophils, percentage of positive syndecan-1 cells was significantly higher in subjects with diabetes (10.363 ± 1.689%) than that of the controls (3.775 ± 0.634%, P = 0.001). An association between body mass index (BMI) and percentage of positive syndecan-1 neutrophils was detected (r = 0.415, P = 0.025). When BMI was categorized into subgroups of ≤25 kg/m(2) (n = 10) and >25 kg/m(2) (n = 19), the average percentages of positive syndecan-1 neutrophils in patients with diabetes were 5.733 ± 1.842% and 12.642 ± 2.251%, respectively (t = -2.137, P = 0.042). A multiple regression analysis showed that BMI (ß = 0.783, P < 0.000) was a significant predictor of positive syndecan-1 neutrophils in subjects with type 2 diabetes.

Insulin increases shedding of syndecan-1 in the serum of patients with type 2 diabetes mellitus.

AIMS: To detect the level of serum syndecan-1 of patients with type 2 diabetes. METHODS: Subjects with diabetes were categorized into 4 subgroups, oral-agents, insulin therapy for 12 months. Serum syndecan-1 was detected by ELISA, and potential correlation between syndecan-1 levels and clinical characteristics was analyzed. RESULTS: Sixty-two diabetic patients and 20 healthy subjects (controls) were enrolled. Syndecan-1 in diabetic patients (24.616+/-1.993 ng/ml) was higher than that of the controls (18.907+/-2.638 ng/ml). The average concentration of syndecan-1 in the group of oral-agents, insulin therapy for 12 months was 19.157+/-2.556 ng/ml (n=20), 24.447+/-3.173 ng/ml (n=23), 35.005+/-4.749 ng/ml (n=11), and 27.593+/-8.304 ng/ml (n=8), respectively. An association between serum syndecan-1 and intake of exogenous insulin was found (r=0.266, p=0.035). Serum syndecan-1 of insulin-therapy group (27.811+/-2.669 ng/ml) enhanced significantly compared to that of the controls (p=0.030) and that of the oral-agents group (p=0.035). Syndecan-1 of the insulin therapy for 1-12 months group enhanced predominantly compared to that of the controls (p=0.005) and the oral-agents group (p=0.005). CONCLUSIONS: Chronic inflammation and exogenous insulin usage increases serum syndecan-1 level. Exogenous insulin can promote shedding of syndecan-1 ectodomains to the serum in a time-dependent manner.