Correlation analysis of epicardial adipose tissue thickness, C-reactive protein, interleukin-6, visfatin, juxtaposed with another zinc finger protein 1, and type 2 diabetic macroangiopathy.

BACKGROUND: To investigate the correlation between the thickness of epicardial adipose tissue (EAT), C-reactive protein (CRP), interleukin (IL) -6, visfatin, juxtaposed with another zinc finger protein 1 (JAZF1) and type 2 diabetic mellitus (T2DM) macroangiopathy. METHODS: The study enrolled 82 patients with T2DM with macroangiopathy (the Complication Group), and 85 patients with T2DM (the Diabetes Group) who were admitted to Shandong Provincial Third Hospital from February 2018 to February 2020. In addition, 90 healthy people who underwent physical examination at the same hospital during the same period were enrolled (the Healthy Control Group). Age, gender, height, weight, waist circumference (WC), hip circumference (HC), diabetic course and therapeutic drugs, waist hip ratio (WHR), and body mass index (BMI) were recorded and calculated. RESULTS: The baseline characteristics of the three groups were comparable, and the diabetic course of the Complication Group and the Diabetes Group was not significantly different (P > 0.05). The WHR of the Complication Group was higher than that of the Diabetes Group and the Healthy Control Group, with statistical significance (P < 0.05). The FPG, 2hPG, HbA1C, CRP, IL-6, Visfatin, JAZF1, HOMA-IR, EAT thickness, and baPWV of the Complication Group were all higher than those of the Diabetes Group and the Healthy Control Group (P < 0.05, respectively). The JAZF1 and FIns of the Complication Group and Diabetes Group were lower than those of the Healthy Control Group, and JAZF1 of the Complication Group was lower than the Diabetes Group with statistical significance (P<0.05, respectively). Pearson correlation analysis showed that the EAT thickness was positively correlated with CRP, IL-6, visfatin, and JAZF1 (r = 0.387, 0.451, 0.283, 0.301, respectively, all P<0.001). Pearson correlation analysis showed that baPWV was positively correlated with EAT thickness, CRP, IL-6, visfatin, and JAZF1 (r = 0.293, 0.382, 0.473, 0.286, respectively, all P < 0.001). Multivariate stepwise regression analysis showed that FPG, 2hPG, HbA1C, CRP, IL-6, visfatin, JAZF1, and EAT thickness were independent risk factors that affected T2DM macroangiopathy. CONCLUSIONS: Clinical monitoring and treatment of T2DM macroangiopathy can use CRP, IL-6, Visfatin, JAZF1, and EAT thickness as new targets to delay the progression of the disease. Further research on the relationship between the above factors and the pathogenesis of T2DM macroangiopathy may be helpful provide new treatment strategies.

Quercetin protects retina external barrier from oxidative stress injury by promoting autophagy.

Purpose: This study aimed to investigate the protective effects of quercetin on the tight junction proteins of human retinal pigment epithelial cells (ARPE-19 cells) suffering from oxidative stress injury and explore the possible mechanism.Methods: H2O2 (300 µM) was used to establish an oxidative stress model of ARPE-19 cells. ARPE-19 cells were pretreated with different concentrations (0-80 µM) of quercetin before H2O2 exposure. The expression and distribution of tight junction proteins and autophagy-related proteins were detected by Western blot and immunostaining. ARPE-19 cells were pretreated with 5 mM 3-methyladenine (3-MA).Results: The cell viability weakened in the H2O2 group compared with the control group. However, it was preserved after pretreatment with quercetin. It was observed that the expression levels of occludin, claudin-1 were decreased in the H2O2 group. Quercetin treatment significantly enhanced the expression levels of them as compared to the H2O2 group. H2O2 alone strongly decreased the Zonula occludens protein 1 (ZO-1) expression in the cytomembrane. Quercetin supplementation enhanced the accumulation of ZO-1 in ARPE-19 cells. The expression levels of Beclin-1 and Microtubule associated protein light chain 3 II (LC-3II) increased, and that of P62 decreased in the quercetin protection group. The appearance of LC-3II, which examined by immunofluorescence experiments, enhanced in the quercetin protection group as compared with the control group. The expression levels of beclin-1 and LC-3II increased, and that of P62 increased in the autophagy-inhibited group compared with the quercetin protection group. The levels of occludin and claudin-1 also decreased.Conclusion: Quercetin prevents the loss of tight junction proteins by upregulating autophagy after oxidative stress in ARPE-19 cells.

A rodent model of anterior ischemic optic neuropathy (AION) based on laser photoactivation of verteporfin.

BACKGROUND: A rodent model of photodynamic AION resulting from intravenous verteporfin is presented. The analysis of the morphological function, the pathological changes and the potential mechanism of action were further investigated. METHODS: Photodynamic treatment was conducted on the optic nerve head (ONH) following administration of the photosensitizer. The fellow eye was considered as sham control. Fundus Fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT) and Flash-visual evoked potential (F-VEP) recordings were conducted at different time points. Immunohistochemistry was used to observe apoptotic cell death (TUNEL) and macrophage infiltration (ED-1/Iba-1). Retrograde labeling of retinal ganglion cells (RGCs) was used to evaluate the loss of RGCs. RESULTS: After laser treatment, SD-OCT indicated optic nerve edema, while FFA indicated late leakage of the ONH. F-VEPs were distinctly reduced compared to control eyes. The number of apoptotic RGCs peaked on day 14 (5.71 ± 0.76, p < 0.01). The infiltration of ED-1 and Iba-1 increased on the 3rd day following PDT, while it peaked on day 14 (67.5 ± 9.57 and 77.5 ± 12.58 respectively, p < 0.01). Following 3 weeks of AION, the densities of RGCs in the central retinas of the normal and AION eyes were 3075 ± 298/mm2 and 2078 ± 141/mm2 (p < 0.01), respectively. CONCLUSIONS: Verteporfin photodynamic treatment on rodents ONH can lead to functional, histological, and pathological changes. This type of animal model of AION is easy to establish and stable. It can be used for studying the mechanism and neuroprotective medicine of AION injury.

Microvasculature dropout detected by the optical coherence tomography angiography in nonarteritic anterior ischemic optic neuropathy.

OBJECTIVE: To investigate microcirculation characteristics of peripapillary superficial retina and optic disc in eyes with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography angiography (OCTA). METHODS: Forty-one eyes of 30 NAION patients and 30 eyes of 30 normal subjects were evaluated with OCTA (AngioVue, Optovue). The whole vessel density, inside disc vessel density, peripapillary vessel density, and vessel densities based on the sectorial division in the nerve head mode peripapillary superficial retina and RPC mode optic disc were measured respectively. RESULTS: In the NAION group, vessel densities in both the peripapillary superficial retina and optic disc were significant reduced (P < 0.01), as compared with the control group. The whole vessel density of the optic disc in chronic NAION group were significantly lower than that in acute NAION group (P < 0.01). The whole and temporal vessel density of the peripapillary superficial retina was significantly correlated with log MAR VA (r = -0.381 and r = -0.337, both P < 0.05). Vessel densities in both the peripapillary superficial retina and optic disc were reduced (P < 0.05) in unilateral involved eyes, as compared to the unaffected fellow eyes, except for the inside disc (P = 0.270) and SN (P = 0.054) vessel density in the optic disc, while there was no difference in the fellow eyes compared to the normal eyes. CONCLUSION: In NAION patients, a dropout of microvasculature in peripapillary superficial retina and optic disc could be detected by OCTA directly. OCTA might become a useful tool for detection and monitoring of NAION. Lasers Surg. Med. 50:194-201, 2018. © 2017 Wiley Periodicals, Inc.

Findings of OCT-angiography compared to fluorescein and indocyanine green angiography in central serous chorioretinopathy.

PURPOSE: The present study analyzed the appearances of optical coherence tomography angiography (OCTA) in patients with central serous chorioretinopathy (CSC) based on fluorescein angiography (FA) and indocyanine green angiography (ICGA). METHOD: In the current case series, 54 eyes of 50 patients diagnosed as CSC were evaluated retrospectively. OCTA, FA, and ICGA were performed on each patient. Two trained observers examined the OCTA images independently to confirm and compare the choriocapillary appearance with that on FA/ICGA. Also, the leakage of vessels on FA, perfusion of choroidal blood flow on ICGA, blood flow density, and vascular morphology on OCTA, as well as, the effect of serous retinal detachment (SRD) on imaging were observed. Furthermore, the image findings of contralateral eyes were included. RESULTS: 47/54 eyes (corresponding to 43 patients in 50 patients) were finally diagnosed with CSC that presented a leakage on FA and dilated vessels on ICGA, and the corresponding areas could be recognized on OCTA. However, in some of the cases (15 eyes, 31.9%), a portion of the leakage lesion on FA did not overlap completely with that on OCTA. On the OCTA B-scan, six eyes did not show a choriocapillary flow signal under subretinal fluid (SRF) with a median SRD height of 485 µm, despite the dilated vessels on ICGA. Approximately, 21 contralateral eyes without SRD and leakage presented dilated vessels on ICGA; however, only 13 eyes could be recognized on OCTA. In addition, seven eyes presented CSC on FA/ICGA but manifested explicit abnormal vascularization beneath the retinal pigment epithelium (RPE) on OCTA. CONCLUSION: FA/ICGA remains the gold standard for the diagnosis of CSC and cannot be completely replaced by OCTA. However, in some cases displaying hot-spots CNV, OCTA can contribute toward a definite diagnosis. The SRD height may exert a shielding effect on the choriocapillary flow signals on OCTA. Lasers Surg. Med. 50:987-993, 2018. © 2018 Wiley Periodicals, Inc.

Optical coherence tomography angiography of macular telangiectasia type 1: Comparison with mild diabetic macular edema.

OBJECTIVE: The present study aimed to investigate the characteristics of macular telangiectasia type 1 (Mac tel type 1) using spectral-domain optical coherence tomography angiography (OCTA) and compare them with the characteristics of mild diabetic macular edema (DME), to provide a new objective method for quick clinical diagnosis and treatment. METHODS: A retrospective comparative analysis of 9 Mac tel type 1, 15 DME, and 15 normal eyes was performed using fluorescein angiography, spectral-domain optical coherence tomography, and OCTA. The morphological changes, retinal vessel density, and nonperfused areas were evaluated using split-spectrum amplitude-decorrelation angiography algorithm. RESULTS: OCTA revealed obvious saccular capillary telangiectasia and loss of parafoveal vascular density of Mac tel type 1. However, a number of line segment hyperreflective signals around the macula and more distinct nonperfusion in DME were observed. The quantitative foveal avascular zone mean area in Mac tel type 1 was larger than that in the normal eyes (0.40 ± 0.06 mm2 vs. 0.88 ± 0.19 mm2 , P < 0.001). However, the area in DME (1.52 ± 0.38 mm2 ) was larger than that in Mac tel type 1 (P < 0.001), and the foveal zone area in DME (1.127 ± 0.05 mm2 ) was also lager than it in Mac tel (P < 0.05). The vascular density of the superficial layer reduced in both Mac tel type 1 and DME (compared with normal eyes). The difference between Mac tel type 1 (49.56 ± 5.23)% and DME(44.58 ± 3.82)% was significant in the superficial capillary layer (P < 0.01). The vascular density of the retinal deep layer also reduced in both Mac tel type 1 and DME (compared with normal eyes). The difference between Mac tel type 1 (53.78 ± 7.36)% and DME (53.64 ± 4.96)% was no significant in this layer (P > 0.05). CONCLUSION: Morphological differences between Mac tel 1 and DME can be observed on OCTA. Superficial vascular density and non-perfusion area may serve as a quantitative method to identify them. Lasers Surg. Med. 49:225-232, 2017. © 2017 Wiley Periodicals, Inc.

Suppression of GLUT1; a new strategy to prevent diabetic complications.

High blood glucose results in high glucose levels in retina, because GLUT1, the sole glucose transporter between blood and retina, transports more glucose when blood glucose is high. This is the ultimate cause of diabetic retinopathy. Knockdown of GLUT1 by intraocular injections of a pool of siRNAs directed against SLC2A1 mRNA which codes for GLUT1 significantly reduced mean retinal glucose levels in diabetic mice. Systemic treatment of diabetic mice with forskolin or genistein, which bind GLUT1 and inhibit glucose transport, significantly reduced retinal glucose to the same levels seen in non-diabetics. 1,9-Dideoxyforskolin, which binds GLUT1 but does not stimulate adenylate cyclase had an equivalent effect to that of forskolin regarding lowering retinal glucose in diabetics indicating that cyclic AMP is noncontributory. GLUT1 inhibitors also reduced glucose and glycohemoglobin levels in red blood cells providing a peripheral biomarker for the effect. In contrast, brain glucose levels were not increased in diabetics and not reduced by forskolin. Treatment of diabetics with forskolin prevented early biomarkers of diabetic retinopathy, including elevation of superoxide radicals, increased expression of the chaperone protein ß2 crystallin, and increased expression of vascular endothelial growth factor (VEGF). These data identify GLUT1 as a promising therapeutic target for prevention of diabetic retinopathy.

Long-term expression of glial cell line-derived neurotrophic factor slows, but does not stop retinal degeneration in a model of retinitis pigmentosa.

Retinitis pigmentosa is a group of diseases in which one of hundreds of mutations causes death of rod photoreceptor cells and then cones gradually die from oxidative damage. As different mutations cause rod cell death by different mechanisms, mutation-specific treatments are needed. Another approach is to use a neurotrophic factor to promote photoreceptor survival regardless of the mechanism of cell death, and previous studies have demonstrated encouraging short-term results with gene transfer of glial cell line-derived neurotrophic factor (GDNF). We generated rd10 mice with doxycycline-inducible expression of GDNF in photoreceptors (Tet/IRBP/GDNF-rd10 mice) or retinal pigmented epithelial cells (Tet/VMD2/GDNF-rd10 mice). In doxycycline-treated Tet/IRBP/GDNF-rd10 mice, there was a 9.3 × 10(4) -fold increase in Gdnf mRNA at P35 and although it decreased over time, it was still increased by 9.4 × 10(3) -fold at P70. Gdnf mRNA was increased 4.5 × 10(2) -fold in doxycycline-treated Tet/VMD2/GDMF-rd10 mice at P35 and was not significantly decreased at P70. GDNF protein levels were increased about 2.3-fold at P35 and 30% at P70 in Tet/IRBP/GDNF-rd10 mice, and in Tet/VMD2/GDNF-rd10 mice they were increased 30% at P35 and not significantly increased at P70. Despite the difference in expression, Tet/IRBP/GDNF-rd10 and Tet/VMD2/GDNF-rd10 mice had comparable significant increases in outer nuclear layer thickness and mean photopic and scotopic ERG b-wave amplitudes compared with rd10 mice at P35 which decreased, but was still significant at P70. Compared with rd10 mice, Tet/IRBP/GDNF-rd10 and Tet/VMD2/GDNF-rd10 mice had comparable significant improvements in cone density at P50 that decreased, but were still significant at P70. These data indicate that despite a large difference in expression of GDNF, Tet/IRBP/GDNF-rd10 and Tet/VMD2/GDNF-rd10 provide comparable slowing of photoreceptor degeneration, but cannot stop the degeneration.

[Protective effect of valproic acid on ischemia-reperfusion induced injury in retina of rat].

OBJECTIVE: To study the protective effects and the related mechanism of valproic acid (VPA) on ischemia-reperfusion-induced injury in retina of rat. METHODS: Experimental study. Ninety Wistar rats were divided randomly into three groups: normal (blank) control group, retinal ischemia-reperfusion (experimental control) group treated with PBS, retinal ischemia-reperfusion (experimental) group treated with VPA. Retinal ischemia was induced by acute high intraocular pressure. Rats were executed at 6, 12, 24, 48 h and 7 d after reperfusion. The eyeballs were enucleated for retinal histopathological examination. The fluoro-gold retrograde labeling was performed and the survival of retinal ganglion cells was analyzed by calculating the densities in fluoro-gold labeled retinal ganglion cell. The protein expression of heat shock protein 70 (Hsp70) and the acetylation of transcription factor Sp1 were analyzed by Western blot assay. The levels of bcl-2 and bax mRNA were analyzed by RT-PCR assay. To determine the significance of differences, analysis of paired-samples t-test was carried out. RESULTS: (1) The HE staining of retinal histological section showed that the edema of retina were attenuated significantly by VPA in experimental group, the difference between the experimental group and the experimental control group was statistically significant (t = 7.491, P < 0.05). The fluoro-gold retrograde labeling showed that the survival of retinal ganglion cells in experimental group [(1629 ± 63)/mm(2)] was significantly higher than experimental group [(908 ± 65)/mm(2)], the difference between the two groups was statistically significant (t = 7.248, P < 0.05). (2) The immuno-blot analysis showed that VPA resulted in significant increase in expression of Hsp70 protein in ischemic retinas, the difference between experimental group and experimental control group was statistically significant (t = 6.176, P < 0.05). The acetylation of Sp1 was significantly higher in experimental group than experimental control group, the difference between the two groups was statistically significant (t = 11.264, P < 0.05). The RT-PCR analysis showed that VPA increased the expression of bcl-2 mRNA in experimental group (0.403 ± 0.009), the difference between experimental group and experimental control group (0.314 ± 0.012) was statistically significant (t = 5.489, P < 0.05). VPA attenuated the expression of bax mRNA in experimental group (0.383 ± 0.009), the difference between experimental group and experimental control group (0.492 ± 0.016) was statistically significant (t = 5.723, P < 0.05). CONCLUSIONS: (1) VPA protected retina from ischemic injury. (2) The upregulation of Hsp70 and bcl-2, downregulation of bax maybe involved in the mechanism of the protection.

[Chinese herbal medicine Lingqi Huangban Granule protects retinal pigment epithelial cells against oxidative stress-induced injury in vitro].

OBJECTIVE: To observe the protective effects of drug-contained serum of Lingqi Huangban Granule (LQHBG), a compound traditional Chinese herbal medicine, on oxidative stress-induced injury in rabbit retinal pigment epithelial (RPE) cells in vitro. METHODS: The oxidative stress of rabbit RPE cells in vitro was induced with hydrogen peroxide (500µmol/L) and different concentrations of LQHBG were administered to rats to prepare medicated serum. RPE cells were randomized into normal control group (no hydrogen peroxide), model group (hydrogen peroxide), model plus serum group (hydrogen peroxide and 10% control serum), model plus low-dose LQHBG group (hydrogen peroxide and low-dose LQHBG-medicated serum) and model plus high-dose LQHBG group (hydrogen peroxide and high-dose LQHBG-medicated serum). Teminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and flow cytometry (FCM) were used to measure apoptosis of cultured rabbit RPE cells. Protein expressions of caspase-3 and Bcl-X(L) were observed by Western blot method. RESULTS: FCM results showed that the apoptotic rates of the normal control group, model group, control serum group and serum containing low- and high-dose LQHBG groups were (4.85±0.26)%, (20.02±1.37)%, (21.84±0.94)%, (13.56±0.55)%, and (8.58±0.39)%, respectively; compared with the model group, the apoptotic rates of RPE cells in the low- and high-dose LQHBG groups were obviously reduced in a dose-related manner (P<0.05). TUNEL results showed that nuclei of apoptotic cells were stained brown; the number of apoptotic cells in the low- and high-dose LQHBG groups was obviously less than that in the model group. The protein expression of caspase-3 was up-regulated in the model and control serum groups, which was higher than that in the high-dose LQHBG group (P<0.05). The protein expression of Bcl-X(L) was down-regulated in the model and control serum groups, which was lower than that in the low- and high-dose LQHBG groups (P<0.01). CONCLUSION: Drug-contained serum of LQHBG obviously reduces apoptosis and partly protects rabbit RPE cells from oxidative stress-induced injury. The protective function is due to an improvement in antioxidant abilities, down-regulation of the expression of caspase-3 and up-regulation of the expression of Bcl-X(L).

Gastric cancer cell-derived extracellular vesicles disrupt endothelial integrity and promote metastasis.

The endothelium is the critical barrier that controls transendothelial communications. Blood vessels in cancer tissue are poorly developed and highly permeable. However, it is poorly understood how circulating cancer cells released through these "leaky" vessels break the intact vasculature of remote organs to metastasize. We investigated the roles of cancer cell-derived extracellular vesicles (CEVs) in regulating cancer metastasis by analyzing samples from gastric cancer patients, performing in vitro experiments, and studying mouse models. We made several novel observations. First, the rate of metastasis was closely associated with plasma levels of CEVs in patients with gastric cancer. Second, cultured endothelial cells endocytosed CEVs, resulting in cytoskeletal rearrangement, low expression of the junction proteins cadherin and CD31, and forming large intercellular gaps to allow the transendothelial migration of cancer cells. The dynamin inhibitor Dynasore prevented these CEV-induced changes of endothelial cells by blocking CEVs endocytosis. Third, CEVs disrupted the endothelial barrier of cancer-bearing mice to promote cancer metastasis. Finally, lactadherin promoted the clearance of circulating CEVs to reduce metastasis. These results demonstrate the essential role of CEVs in promoting the metastasis of gastric cancer.

3-[1-(4-Chloro-phen-yl)eth-yl]-1,3-thia-zinane-2-thione.

In the title compound, C(12)H(14)ClNS(2), the thia-zole ring adopts an envelope conformation; the basal plane is nearly perpendicular to the benzene ring at a dihedral angle of 85.72 (5)°. Weak inter-molecular C-H⋯S hydrogen bonding is present in the crystal structure.

Analysis of the effect of probucol-mecobalamin tablets combination on oxidative stress in patients with diabetic peripheral neuropathy.

OBJECTIVE: This research aimed to observe the effect of probucol combined with mecobalamin tablets on oxidative stress in patients with diabetic peripheral neuropathy (DPN). METHODS: In this prospective study, 104 patients with DPN who were treated in our hospital were included, from August 2018 to January 2020. They were divided into groups of combination (n = 52) and control (n = 52) by using a random number table. All patients took mecobalamin tablets after meals for 3 months (1 tablet/time, 3 times/d). On this basis, patients in the combination group took probucol for 3 months (4 tablets/time, 2 times/d). The observation indicators were the Toronto Clinical Scoring System (TCSS)(symptom, sensory, and reflex scores), nerve conduction velocity[sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity(MNCV) of the common peroneal nerve and median nerve], oxidative stress indicators[superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px) and catalase(CAT)], clinical efficacy and adverse reactions. RESULTS: There was no significant difference in the symptom scores, sensory scores, reflex scores, and total scores between the two groups before treatment (p > 0.05), while these four indicators of the combination group were significantly lower than that in the control group after treatment (p < 0.05). These four indicators of the two groups after treatment were significantly lower than before treatment (p < 0.05). There was no significant difference in the SNCV and NMCV of the common peroneal nerve and median nerve between the two groups before treatment (p > 0.05), while the indicators of the combination group were significantly higher than that of the control group (p < 0.05) after treatment, and these indicators of the two groups after treatment were significantly higher than that before treatment (p < 0.05). There was no significant difference in SOD, MDA, GSH-Px, and CAT between the two groups before treatment (p > 0.05). After treatment, the SOD, GSH-Px, and CAT in the combination group were significantly higher than that in the control group (p < 0.05), while the MDA in the combination group was significantly lower than that in the control group (p < 0.05). After treatment, the SOD, GSH-Px, and CAT in the two groups were significantly higher than that before treatment (p < 0.05), while the MDA was lower (p < 0.05). The clinical efficacy of the combination group was significantly better than that of the control group (94.23 % vs 78.85 %, p＜0.05) after treatment. There was no significant difference in the incidence of total adverse reactions between the two groups (3.85 % vs 5.77 %, p > 0.05). CONCLUSION: The therapeutic effect of probucol combined with mecobalamin tablets for patients with DPN was significant, which could effectively improve the oxidative stress response of patients and was worthy of clinical promotion.

The Prevalence of Müllerian Anomalies in Women with a Diagnosed Renal Anomaly.

STUDY OBJECTIVE: To characterize the prevalence of Müllerian anomalies (MAs) among patients with renal anomalies (RAs). DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A retrospective chart review of female patients with RAs who presented to an academic pediatric hospital between 2007 and 2019 was performed. Patients were identified using International Classification of Diseases 9th and 10th revision codes. Data collected included the type of RA, presence and type of MA, method of diagnosis, and associated anomalies. RA subtype analysis was performed. RESULTS: We identified 5590 cases of RA for the years 2007 through 2019. A random, retrospective chart review was performed resulting in a study population of 363 RA patients. The prevalence of any MA in the overall RA population was 104/363 (29%) (95% confidence interval, 24% - 33%). The prevalence of MA for patients with renal agenesis was 59/182 (32%) compared with 45/181 (25%) for patients with renal dysgenesis. The most common MA were failures of Müllerian duct fusion. Only 73/352 (21%) of patients received screening for a MA at the time of RA diagnosis. Of patients without a diagnosed MA 187/259 (72%) were unscreened and either not yet menarchal or had unknown menarchal status. CONCLUSIONS: Of all RA patients, 29% (n = 104/363) had an underlying MA. No difference was found in the prevalence of MA in patients with renal agenesis vs dysgenesis. Limitations noted are that some patients might be of an age at which assessment of the Müllerian structures is suboptimal or who might not have been screened. These results suggest the need for a prospective study to determine evidence-based guidelines for screening for MA among patients diagnosed with any RA to avoid complications from an unrecognized MA.

PARP1 as a prognostic biomarker for human cancers: a meta-analysis.

Aim: A comprehensive meta-analysis was carried out to evaluate the association between high PARP1 expression and clinical outcomes in diverse types of cancers. Materials & methods: The electronic databases for all articles about PARP1 expression and cancers were searched. Additionally, bioinformatics analysis was utilized to validate the results of the meta-analysis. Results: Fifty-two studies with a total of 7140 patients were included in the current meta-analysis. High PARP1 expression was found to be significantly associated with poor overall survival and recurrence in various cancers, which were further strengthened and complemented by the results of bioinformatic analysis. Furthermore, increased PAPR1 expression was also related to clinicopathological features. Conclusion: Our findings confirmed that PARP1 might be a promising biomarker for prognosis in human cancers.

Agents that bind annexin A2 suppress ocular neovascularization.

TM601 is a synthetic polypeptide with sequence derived from the venom of the scorpion Leiurus quinquestriatus that has anti-neoplastic activity. It has recently been demonstrated to bind annexin A2 on cultured tumor and vascular endothelial cells and to suppress blood vessel growth on chick chorioallantoic membrane. In this study, we investigated the effects of TM601 in models of ocular neovascularization (NV). When administered by intraocular injection, intravenous injections, or periocular injections, TM601 significantly suppressed the development of choroidal NV at rupture sites in Bruch's membrane. Treatment of established choroidal NV with TM601 caused apoptosis of endothelial cells and regression of the NV. TM601 suppressed ischemia-induced and vascular endothelial growth factor-induced retinal NV and reduced excess vascular permeability induced by vascular endothelial growth factor. Immunostaining with an antibody directed against TM601 showed that after intraocular or periocular injection, TM601 selectively bound to choroidal or retinal NV and co-localized with annexin A2, which is undetectable in normal retinal and choroidal vessels, but is upregulated in endothelial cells participating in choroidal or retinal NV. Intraocular injection of plasminogen or tissue plasminogen activator, which like TM601 bind to annexin A2, also suppressed retinal NV. This study supports the hypothesis that annexin A2 is an important target for treatment of neovascular diseases and suggests that TM601, through its interaction with annexin A2, causes suppression and regression of ocular NV and reduces vascular leakage and thus may provide a new treatment for blinding diseases such as neovascular age-related macular degeneration and diabetic retinopathy.

[Be cautious of using anti-vascular endothelial growth factor therapy for treatment of macular edema secondary to retinal vein occlusion].

There are various therapies for the treatment of macular edema secondary to retinal vein occlusion (RVO). Intravitreous injection of anti-vascular endothelial growth factor (VEGF) is a new procedure. The efficacy and safety of this therapy have been widely proved in short term clinical observations. However, the relapse of macular edema and the requirement for multi-injections are still remaining problems. It requires more evidences to prove that a better long term prognosis could be obtained from this procedure as compared with traditional laser coagulation. The optimizing therapies should include a combination of anti-VEGF therapy with other drugs and laser treatment to decrease the risk of multi-injections and to obtain the best results. Selection of appropriate therapeutic procedure (based on the evidence based medicine) to protect and improve visual function are the important project of clinicians and require further exploration and investigation.

The SDF-1/CXCR4 ligand/receptor pair is an important contributor to several types of ocular neovascularization.

Hypoxia causes increased expression of several proteins that have the potential to promote neovascularization. Vascular endothelial growth factor (VEGF) is up-regulated by hypoxia in the retina and plays a central role in the development of several types of ocular neovascularization, but the effects of other hypoxia-regulated proteins are less clear. Stromal-derived factor-1 (SDF-1) and its receptor, CXCR4, have hypoxia response elements in the promoter regions of their genes and are increased in hypoxic liver and heart. In this study, we found that SDF-1 and CXCR4 are increased in hypoxic retina, with SDF-1 localized in glial cells primarily near the surface of the retina and CXCR4 localized in bone marrow-derived cells. Glial cells also expressed CXCR4, which suggested the possibility of autocrine stimulation, but influx of bone marrow-derived cells is the major source of increased levels of CXCR4. High levels of VEGF in the retina in the absence of hypoxia also increased levels of Cxcr4 and Sdf1 mRNA. CXCR4 antagonists reduced influx of bone marrow-derived cells into ischemic retina and strongly suppressed retinal neovascularization, VEGF-induced subretinal neovascularization, and choroidal neovascularization. These data suggest that SDF-1 and CXCR4 contribute to the involvement of bone marrow-derived cells and collaborate with VEGF in the development of several types of ocular neovascularization. They provide new targets for therapeutic intervention that may help to bolster and supplement effects obtained with VEGF antagonists.

Edaravone (MCI-186), a free radical scavenger, attenuates retinal ischemia/reperfusion injury in rats.

AIM: To investigate the effect of edaravone (MCI-186), a free radical scavenger, against ischemia/reperfusion (I/R) injury in the rat retina. METHODS: Retinal ischemia was induced in male Sprague-Dawley rats by elevating intraocular pressure to 110 mmHg for 60 min. The rats were intraperitoneally injected with edaravone at a dose of 3 mg/kg at 30 min before ischemia, and then treated with edaravone (3 mg/kg, ip) twice daily for 1 or 5 d after I/R. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the retinal tissues were determined on d 1 after I/R injury. The apoptosis of retinal neurons was detected on d 1 after I/R injury by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling staining. The electroretinogram (ERG) was recorded on d 5 after reperfusion. RESULTS: Edaravone lowered MDA levels, raised SOD activity, and attenuated I/R-induced apoptosis of retinal neurons within the inner nuclear, ganglion cell, and outer nuclear layers of the rat retina. Moreover, edaravone suppressed I/R-induced reduction in a- and b-wave amplitudes of ERG. CONCLUSION: Edaravone can protect the retina from I/R injury in rats through reducing oxidative stress and inhibiting apoptosis of retinal neurons, which suggests that edaravone might be a potential choice for the treatment of I/R-induced eye disorders.

[Protective effect of Huangban Granule against light-induced retinal damage in rats].

OBJECTIVE: To observe the protective effect of Huangban Granule, a compound of traditional Chinese herbal medicine, on rats with retinal damage induced by light. METHODS: A total of 24 male Sprague-Dawley (SD) rats were randomly divided into normal control group, untreated group and Huangban Granule group. Retinal light damage was induced by exposure to constant white fluorescent light for 5 hours at an illumination of 2,800 Lux. The Huangban Granule was given 10 days before light exposure until the animals were sacrificed in Huangban Granule group, and an equal volume of distilled water for the rats in untreated group. Electroretinogram (ERG) was recorded in all animals 2 weeks after light exposure and the animals were sacrificed for histopathological examination of retina. The outer nuclear layers (ONLs) on the superior and inferior retina were counted. RESULTS: Fourteen days after light exposure, the ONLs on the superior retina were 3 to 6 in the untreated group and 7 to 9 in treatment group. There were 9 to 11 layers in normal group. The mean number of ONLs in the untreated group (4.68+/-1.64) was less than that in the treatment group (8.23+/-1.35) (P<0.01). B-wave amplitudes were (319.38+/-71.96) muV and (135.16+/-42.30) muV in Huangban Granule group and the untreated group respectively (P<0.01). A-wave amplitudes were (184.63+/-47.23) muV and (83.35+/-27.75) muV (P<0.01), and oscillatory potential amplitudes were (239.38+/-20.19) muV and (125.44+/-26.23) muV (P<0.01) respectively in the two group. There was no significant difference in implicit times of a-wave and b-wave among the three groups. CONCLUSION: Huangban Granule obviously protects both function and morphology of the retina from light-induced retinal damage in rats.