Diabetic retinopathy ( DR ) is one of the main blinding eye diseases for people over the age of 50, and diabetic macular edema ( DME) is the leading cause of vision loss is DR patients. The early diagnosis and early treatment is important. As OCT and FFA, mfERG, especially the retinal thickness, volume, retinal edema index quantitative indicators such as objective evaluation of macular edema, embodies the new progress of retinal imaging technology in recent years. OCT is a non -contact clinical application in recent years, noninvasive, high resolution of ophthalmic imaging examination, can do it on retinal ultrastructure observation and quantitative analysis, and the technology is relatively mature, become a routine inspection diagnosis of macular edema. Laser photocoagulation, intravitreous injection with Ranibizumab and vitrectomy is nowadays the important means for the treatment of intractable macular edema.

Background Diabetes mellitus (DM) can provoke the apoptosis of retinal cells and downregulate the expression of calcitonin gene related peptide (CGRP) in the retina.Capsaicin promotes the release of CGRP and elicits protective effects on human organs.However,whether CGRP protects retinal cells in diabetic retinopathy (DR) is still unclear.Objective The study was designed to examine the effect of capsaicin on the apoptosis of retinal cells in diabetic rats and its relationship with CGRP.Methods Forty clean healthy adult male Sprague-Dawey rats were randomly divided into the diabetes group,capsaicin pretreated group,streptozocin (STZ)control group,capsaicin control group and plain control group,with 8 rats per group.The diabetic model was established by the intraperitoneal injection of 60 mg/kg in all rats except those of the plain control group.0.4 mL of a 1％ capsaicin injected at 20 mg/kg was subcutaneously injected for 3 consecutive days prior to model establishment in the capsaicin pretreated group,after which 1.2 mL of STZ was intraperitoneally injected on the fourth day.Rats from the STZ control group were administered intraperitoneally 1.2 mL of 0.1 mol/L,pH 4.5,citrate buffer.The capsaicin control group received subcutaneous injections of 0.4 mL of 1％ capsaicin at 20 mg/kg for 3 consecutive days,after which 1.2 mL of 0.1 mol/L,pH 4.5,citrate buffer was administered intraperitoneally.The rats were sacrificed at the tenth week after model establishment and retinal specimens were prepared for the apoptosis assay by TUNEL staining and the quantitative analysis of caspase-3 activity.Expression of CGRP in the retina and serum was detected using ELISA.The use of experimental animals followed the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results Retinal cell apoptosis was mainly localized to the retinal ganglion cell (RGC) layer.The apoptosis rate of RGCs was (43.4±5.0)％ in the DR model group and (30.0±5.1)％ in the capsaicin pretreated group,showing a significant difference (t =5.930,P＜0.01).Compared with the DR model group and capsaicin pretreated group,the apoptosis rates of the DR control group (12.4±9.9) ％ and the capsaicin control group (17.6-±6.1) ％ were significantly lower (t =8.800,t =4.925,P＜0.01).The apoptosis rate of the plain control group was (16.2±6.9)％,exhibiting significant differences in comparison with the DR control group and capsaicin control group (t =-0.989,t =0.951,P＞0.05).The specific activity of caspase-3 was (2.19±0.86) in the DR model group and (1.96±0.56) in the capsaicin pretreated group,presenting a significant difference (t =-0.515,P＜0.05).Those of the DR control group and capsaicin control group were (1.47±0.14) and (0.74±0.27),respectively,with considerable decline in comparison with the DR model group and capsaicin pretreated group (t=2.142,t=2.797,P＜0.05).The retinal and serum CGRP levels were (424.4±44.2)and (148.8±39.1) ng/L,respectively,displaying significantly lower levels than (543.2±74.4) and (237.5±78.7) ng/L (t =3.070,2.359,P＜0.05) from the capsaicin pretreated group.Conclusions Apoptosis of retinal ganglion cells occurs in the STZ-induced diabetic rats.Pretreatment of capsaicin reduces retinal cell apoptosis,which may be associated with an increase of CGRP in the retina.

Animals ; Animals, Newborn ; Cells, Cultured ; Corticotropin-Releasing Hormone ; pharmacology ; Interleukin-6 ; metabolism ; Microglia ; cytology ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

Animals ; Antioxidants ; metabolism ; Fatigue ; blood ; Female ; Hypericum ; chemistry ; Male ; Mice ; Mice, Inbred ICR ; Physical Conditioning, Animal ; Plant Extracts ; pharmacology

Objective To observe the lecithin's effect on membrane of African green monkey kidney cells (Vero) exposed to sodium arsenite(NaAsO2). Methods Vero cells cultured in vitro were divided into 4 groups:control group (saline), model group (2.20 mg/L NaAsO2), high eoncentration of lecithin and arsenic group (53.33mg/L lecithin + 2.20 mg/L NaAsO2), low eoncentration of lecithin and arsenic group( 13.32 mg/L lecithin + 2.20 mg/L NaAsO2), 6 bottles of cells in each group, medium was changed every 2 days, cultured for 120 h. Na+ ,K+-ATPase activities of membrane were measured by spectrophotometry, and membrane phospholipids composition including phosphatidylserine (PS), phosphatidylethano-lamine (PE), phosphatidylcholine (PC) and sphingmyelin (SM) were measured by high performance liquid chromatography (HPLC). Results The Na~, K+-ATPase activities of membrane of control group, model group, high concentration of lecithin and arsenic group, low concentration of lecithin and arsenic group were (0.962 ± 0.081) × 106, (0.544 ± 0.037) × 106, (0.647 ± 0.043) x 106, (0.550±Compared with control group, the Na+ ,K+-ATPase activities of other 3 groups were significantly reduced (all P < 0.05). Compared with model group, the Na+ ,K+-ATPase activity in high concentration of lecithin and arsenic group was significantly higher (P < 0.05),but in low concentration of lecithin and arsenic group did not change significantly (P > 0.05). Compared with control group[(0.087 ± 0.003), (0.127 ± 0.053), (0.588 ± 0.105),(0.071 ± 0.029)g/L], PS, PE, PC, SM levels in model group[(0.051 ± 0.018), (0.073 + 0.030), (0.240 ±0.038), (0.047 ± 0.121 )g/L] were significantly lower(all P < 0.05) ;PS, PE, PC in high concentration of lecithin and arsenic group[(0.084 ± 0.011), (0.109 ± 0.363), (0.591 ± 0.476)g/L] did not change significantly(all P > 0.05), but SM[(0.057 ± 0.004)g/L] significantly decreased(P < 0.05) ;PS, PE, SM levels of low concentration of lecithin and arsenic group[(0.058 ± 0.020), (0.086 ± 0.177), (0.048 ± 0.103)g/L] significantly reduced (all P < 0.05), the PC did not change significantly [(0.521±0.098 )g/L, P > 0.05]. Compared with model group,the levels of PS, PE, PC, SM in high concentration of lecithin and arsenic group were significantly higher(all P <0.05);PS, PE, SM levels in low concentration of lecithin and arsenic group did not change significantly(all P > 0.05), and PC was significantly higher(P < 0.05). Conclusions High concentration lecithin has certain protective effect on Vero cell membrane exposured to sodium arsenite.

Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC₅₀) was 13.8 μmol·L^-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC₅₀: 41.99 μmol·L^-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

Catheter Ablation ; Child ; Humans ; Male ; Tachycardia, Atrioventricular Nodal Reentry ; surgery