Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization.

Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization.

Highly Expressed Amyloid Beta-42 Of Aqueous Humor In Patients With Neovascular Macular Degeneration.

Background: Age-related macular degeneration (AMD) is a type of macular degeneration disease, and amyloid beta (aß) is the main component of vitreous warts in AMD patients. Neovascular AMD (nAMD) is the most serious type of AMD, but its pathogenesis remains unclear. The aim of this study was to detect the expression of aß42 in the aqueous humor of nAMD patients and to evaluate whether aß42 expression of aqueous humor is correlated with cognitive function in these patients.Methods: A total of 70 patients were enrolled in this study, including 50 nAMD patients (nAMD group) and 20 patients with cataract (control group). The cognitive function of the patients was assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment Scale, and based on their scores, 50 patients with nAMD were divided into two subgroups: the p-nAMD group (18 nAMD patients with normal cognition) and the ci-nAMD group (32 nAMD patients with cognitive impairment). An immunofluorescence microsphere probe technique was used to detect the aß42 expression of aqueous humor in all patients. Pearson correlation analysis was used.Results: The aß42 expression of aqueous humor was significantly higher in the nAMD group (124.56 ± 41.93 pg/mL) as compared with the control group (82.94 ± 33.75 pg/mL; P < .01). There was no significant difference in aß42 expression of aqueous humor between the p-nAMD group (136.42 ± 51.68 pg/mL) and ci-nAMD group (117.90 ± 34.46 pg/mL; P = .14).Conclusion: In nAMD patients, aß42 was highly expressed in the aqueous humor but was not correlated with cognitive function.

Assessment of three successive treatments of ranibizumab on neovascular macular degeneration by OCT angiography.

In the present study, the efficacy of three consecutive anti-VEGF treatments in patients with neovascular macular degeneration (nAMD) was assessed by optical coherence tomography angiography (OCT-A). A total of 23 eyes with nAMD were treated with intravitreal injections (IVIs) of ranibizumab once a month for three consecutive months. There were eight follow-up time-points: Prior to the initial IVI and on days 1, 3, 7, 14, 30, 60 and 90 after the first IVI. The follow-up examinations consisted of measurements of the best-corrected visual acuity (BCVA), the height of retinal pigmented epithelium detachment (RPED), the greatest linear dimension (GLD), choroidal neovascularization (CNV) flow area, whole retinal thickness and four-quadrant retinal thickness. The results indicated that, when compared with the baseline, the BCVA gradually improved after IVI and improved significantly on days 60 and 90 (P<0.05); the RPED and GLD improved after IVI, with a significant improvement on days 30, 60 and 90 (all, P<0.05); the CNV flow area was gradually shortened in the early stage after IVI but rebounded on day 30, while the difference was statistically significant on day 14 (P<0.05). The temporal retinal thickness was statistically significant on day 30 (P<0.05) and there were statistically significant differences in nasal and inferior retinal thickness on days 14 and 30 compared with prior to IVI (all, P<0.05). The BCVA was positively correlated with the RPED, GLD, CNV flow area and nasal retinal thickness (all, P<0.05). In conclusion, OCT-A may provide an effective reference to guide the evaluation, treatment and monitoring of nAMD. The present study was registered in the Chinese Clinical Trial Registry (CChiTR; no. ChiCTR1900023607; http://www.chictr.org.cn/listbycreater.aspx).

Effects of imipenem combined with low-dose cyclophosphamide on the intestinal barrier in septic rats.

Anti-infection therapy combined with immunotherapy is one of the important research approaches for treating sepsis. However, the combination of anti-infection and immunotherapy therapeutic agents may have an adverse effect on intestinal barrier function. In the present study, it was hypothesized that imipenem combined with low-dose cyclophosphamide (CTX) could improve the sepsis survival rate compared with imipenem treatment alone. In addition, the alterations in the intestinal barrier were investigated and the possible mechanisms of altering intestinal barrier function in septic rats treated with imipenem combined with low-dose CTX or imipenem alone were explored. To investigate the effect of imipenem combined with low-dose CTX on the intestinal barrier, the markers of histopathology, intestinal permeability, intestinal epithelial apoptosis, cytokines interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α, and tight junction proteins zonula occludens (ZO)-1, occludin and claudin-2, were quantitatively and qualitatively evaluated. The results indicated that imipenem combined with low-dose CTX significantly improved the survival rate of rats compared with imipenem alone (P<0.05). However, no significantly difference between the treatment with imipenem combined with low-dose CTX and imipenem treatment alone was indicated with regard to histopathology, intestinal permeability, intestinal epithelial apoptosis and the expression of claudin-2, ZO-1 and TNF-α. However, imipenem combined with low-dose CTX significantly reduced IL-6 and IL-10 expression and significantly increased occludin expression compared with imipenem alone (P<0.05). It was concluded that imipenem combined with low-dose CTX could improve the survival rate of rats with sepsis compared with rats treated with imipenem alone. The present findings suggest that imipenem combined with low-dose CTX may cause damage to the intestinal barrier function and the mechanism may be associated with a reduction in IL-10 expression.

Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death.

It is known that oxidative stress plays a pivotal role in age-related macular degeneration (AMD) pathogenesis. Alpha-mangostin is the main xanthone purified from mangosteen known as anti-oxidative properties. The aim of the study was to test the protective effect of alpha-mangostin against oxidative stress both in retina of light-damaged mice model and in hydrogen peroxide (H2O2)-stressed RPE cells. We observed that alpha-mangostin significantly inhibited light-induced degeneration of photoreceptors and 200 µM H2O2-induced apoptosis of RPE cells. 200 µM H2O2-induced generation of reactive oxygen species (ROS) and light-induced generation of malondialdehyde (MDA) were suppressed by alpha-mangostin. Alpha-mangostin stimulation resulted in an increase of superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity and glutathione (GSH) content both in vivo and vitro. Furthermore, the mechanism of retinal protection against oxidative stress by alpha-mangostin involves accumulation and the nuclear translocation of the NF-E2-related factor (Nrf2) along with up-regulation the expression of heme oxygenas-1 (HO-1). Meanwhile, alpha-mangostin can activate the expression of PKC-δ and down-regulate the expression of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, P38. The results suggest that alpha-mangostin could be a new approach to suspend the onset and development of AMD.

Changes of serum TOS and TAS levels and their association with apolipoprotein(a) in patients with polycystic ovary syndrome and infertility / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate changes of serum total oxidation status (TOS) and total antioxidant status (TAS) and their association with apolipoprotein (a) [Apo(a)] in patients with polycystic ovary syndrome (PCOS) combined with infertility.</p><p><b>MWTHODS</b>Ninety patients with PCOS and infertility were selected as the study group, including 45 patients treated with antioxidants combined with Diane-35(group A) and 45 with Diane-35 therapy only (group B), with 45 healthy volunteers with normal menstruation and normal dual phase basic body temperatures as the control group. Serum TOS of the participants was determined by dual xylenol orange method, and serum TAS was determined with ABTS method; plasma Apo(a) level was determined by dual wavelength immune transmission turbidity method.</p><p><b>RESULTS</b>Before treatment, serum TOS, OSI, and Apo(a) levels were significantly higher and TAS level was significantly lower in the study group than in the control group (P<0.05). Serum TOS, OSI, and Apo (a) were significantly lowered and TAS was significantly increased in group A after the therapy as compared with the levels before therapy and the levels in group B. The rate of natural recovery of menstruation was significantly higher and the incidence of cardiovascular disease was significantly lower in group A than in group B (P<0.05). Pearson correlation analysis showed that serum TOS and OSI were positively correlated with plasma Apo(a) (r=0.524 and 0.531, P<0.05), and serum TAS was negatively correlated with plasma Apo(a) (r=-0.519, P<0.05).</p><p><b>CONCLUSION</b>Antioxidant therapy can lower TOS, OSI and Apo(a) levels and increase TAS level to lessen oxidative stress, improve the prognosis, and reduce the risks of cardiovascular disease in patients with PCOS and infertility.</p>

Retinal Neurodegeneration in db/db Mice at the Early Period of Diabetes.

Purpose. To describe both the functional and pathological alternations in neurosensory retina in a murine model of spontaneous type 2 diabetes (db/db mouse). Methods. db/db (BKS/DB-/-) mice and heterozygous littermates (as control group) at various ages (12, 16, 20, 24, and 28 weeks) were inspected with pattern electroretinogram (PERG), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Histological markers of neuroinflammation (IBA-1 and F4/80) were evaluated by immunohistochemistry. In addition, levels of retinal ganglion cell death were measured by terminal dUTP nick-end labeling (TUNEL). Results. Significant alternations of PERG responses and increased retinal ganglion cells (RGCs) apoptosis were observed in diabetic db/db mice for 20-week period when compared with control group. IBA-1 and F4/80 expression in microglia/macrophages became evidently for 24-week period, thus supporting the PERG findings. Furthermore, obvious thinning of nasal and dorsal retina in 28-week-old db/db mice was also revealed by OCT. No visible retinal microvascular changes were detected by FFA throughout the experiments on db/db mice. Conclusions. Diabetic retina underwent neurodegenerative changes in db/db mice, which happened at retinal ganglion cell layer and inner nuclear layer. But there was no obvious abnormality in retinal vasculature on db/db mice.

Contras-enhanced ultrasound-directed nose-intestinal feeding tube placement / 中华超声影像学杂志

Objective To investigate the feasibility of contrast-enhanced ultrasound-directed nosejujunium tube placement.Methods Twenty-four patients hospitalized in ICU who need support from enteral feeding were collected for this study.Flocare spiral nose-jejunium tube was placed into stomach with guide wire.Real-time ultrasound was used after injection of SonoVue for monitoring the passage of feeding tube from pylorus to duodenum-jejunum segment which was pushed down if without strong resistant force.Finnally,the guide wire was drawed out and enteral feeding was conducted with ascertainment of abdominal X-ray photograph for suitable site in intestinal tract.Results Contrast ultrasound -directed nose-jejunum tube placement procedure was conducted in 24 cases.Twenty-one cases (87.5%) was accomplished successfully,and 3 cases (12.5%) was failed.No special change was observed in the procedure of all patients.Conclusions Contrast ultrasound -directed nose-jejunum tube placement procedure can be regarded as a convenient,safe,and reliable insertion technology,which provide an effective means for early enteral nutrition for critical patients.