[Total polyphenols of Cydonia oblonga inhibited proliferation and migration of renal cancer cells by PI3K/Akt/mTOR pathway].

The mechanism of total polyphenols of Cydonia oblonga Miller(TPCOM) against kidney cancer was elucidated through a combination of network pharmacology, bioinformatics, and experimental verification. The active polyphenolic compounds from C. oblonga were screened by network pharmacological techniques and kidney cancer-related targets were collected through the database. The differential gene expression analysis was performed on RNA sequencing data from tumor tissue and normal tissue of kidney cancer patients obtained from the Gene Expression Omnibus(GEO) database. The results of network pharmacology predictions and differential gene expression analysis were used to identify the core genes targeted by TPCOM in kidney cancer. Survival analysis was conducted to identify key targets that could impact patient survival, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) enrichment analyses. Cell proliferation and activity experiments(cell counting kit-8) were conducted using TPCOM at concentrations ranging from 20 to 640 µg·mL~(-1) on 786-O and Renca cells. Additionally, TPCOM at concentrations of 40, 80, and 160 µg·mL~(-1) was applied to kidney cancer cells to assess its effect on cell migration and its regulation of protein expression levels related to the protein kinase B(Akt), mammalian target of rapamycin(mTOR), and phosphoinositide 3-kinase(PI3K) signaling pathways. Network pharmacology predicted eight active polyphenolic compounds from C. oblonga. Survival analysis revealed 15 significantly differentially expressed genes in kidney cancer that were affected by TPCOM and had a significant impact on patient survival. KEGG and GO analysis results indicated that these 15 targets were primarily associated with the PI3K/Akt signaling pathway, cell migration, and proliferation. The results showed that TPCOM could inhibit the proliferation of 786-O and Renca cells, with IC_(50) values of 121.4 and 137.9 µg·mL~(-1), respectively. TPCOM was also found to inhibit the migration of these cells and suppress the PI3K/Akt/mTOR signaling pathway. TPCOM may exert its anti-kidney cancer effects by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway, thereby restraining the proliferation and migration of kidney cancer cells. This study provides a foundation for the research on the anti-tumor effects of natural product C. oblonga, particularly in Xinjiang, and holds significance for further promoting its development and utilization.

Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori.

BACKGROUND: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM: To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.

Linolenic acid-metronidazole inhibits the growth of Helicobacter pylori through oxidation.

BACKGROUND: Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori (H. pylori) infections. Therefore, there is an urgent need to develop new antimicrobial agents to replace antibiotics. Our previous study found that linolenic acid-metronidazole (Lla-Met) has a good antibacterial effect against H. pylori, both antibiotic-resistant and sensitive H. pylori. Also, H. pylori does not develop resistance to Lla-Met. Therefore, it could be used for preparing broad-spectrum antibacterial agents. However, since the antibacterial mechanism of Lla-Met is not well understood, we explored this phenomenon in the present study. AIM: To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections. METHODS: H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified. RESULTS: Lla-Met treatment induced several changes in H. pylori cells, including roughening and swelling. In vivo experiments revealed that Lla-Met induced oxidation, DNA fragmentation, and phosphatidylserine ectropionation in H. pylori cells. Inhibiting Lla-Met with L-cysteine abrogated the above phenomena. Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes, both anti-oxidation-related genes. CONCLUSION: Lla-Met kills H. pylori mainly by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology.

Impact factors of Blastocystis hominis infection in persons living with human immunodeficiency virus: a large-scale, multi-center observational study from China.

BACKGROUND: Blastocystis hominis (Bh) is zoonotic parasitic pathogen with a high prevalent globally, causing opportunistic infections and diarrhea disease. Human immunodeficiency virus (HIV) infection disrupts the immune system by depleting CD4+ T lymphocyte (CD4+ T) cell counts, thereby increasing Bh infection risk among persons living with HIV (PLWH). However, the precise association between Bh infection risk and HIV-related biological markers and treatment processes remains poorly understood. Hence, the purpose of the study was to explore the association between Bh infection risk and CD4+ T cell counts, HIV viral load (VL), and duration of interruption in antiviral therapy among PLWH. METHODS: A large-scale multi-center cross-sectional study was conducted in China from June 2020 to December 2022. The genetic presence of Bh in fecal samples was detected by real-time fluorescence quantitative polymerase chain reaction, the CD4+ T cell counts in venous blood was measured using flowcytometry, and the HIV VL in serum was quantified using fluorescence-based instruments. Restricted cubic spline (RCS) was applied to assess the non-linear association between Bh infection risk and CD4+ T cell counts, HIV VL, and duration of interruption in highly active antiretroviral therapy (HARRT). RESULTS: A total of 1245 PLWH were enrolled in the study, the average age of PLWH was 43 years [interquartile range (IQR): 33, 52], with 452 (36.3%) being female, 50.4% (n = 628) had no immunosuppression (CD4+ T cell counts > 500 cells/µl), and 78.1% (n = 972) achieved full virological suppression (HIV VL < 50 copies/ml). Approximately 10.5% (n = 131) of PLWH had interruption. The prevalence of Bh was found to be 4.9% [95% confidence interval (CI): 3.8-6.4%] among PLWH. Significant nonlinear associations were observed between the Bh infection risk and CD4+ T cell counts (Pfor nonlinearity < 0.001, L-shaped), HIV VL (Pfor nonlinearity < 0.001, inverted U-shaped), and duration of interruption in HARRT (Pfor nonlinearity < 0.001, inverted U-shaped). CONCLUSIONS: The study revealed that VL was a better predictor of Bh infection than CD4+ T cell counts. It is crucial to consider the simultaneous surveillance of HIV VL and CD4+ T cell counts in PLWH in the regions with high level of socioeconomic development. The integrated approach can offer more comprehensive and accurate understanding in the aspects of Bh infection and other opportunistic infections, the efficacy of therapeutic drugs, and the assessment of preventive and control strategies.

Underwater Oleophobic Electrospun Membrane with Spindle-Knotted Structured Fibers for Oil-in-Water Emulsion Separation.

The potential of spider silk as an intriguing biological prototype for collecting water from a humid environment has attracted wide attention, and various materials with suitable structures have been engineered. Here, inspired by this phenomenon, a kind of superwetting poly(vinylidene fluoride) (PVDF) membrane with spindle-knotted structured fibers was prepared by the electrospinning method followed by oxygen plasma etching treatment. The prepared membrane presented a satisfactory separation efficiency for various oil-in-water emulsions. The cooperative effect of the special wettability property and the spindle-knot structure stimulated the emulsified oil droplets to accumulate quickly on the membrane surface. A model that explains the accumulation of emulsified oil droplets has also been developed. Furthermore, an artificial fiber comprising a micron-sized spindle-knot structure was prepared by the dip-coating method to clearly illustrate the aggregation process of the emulsified oil droplets and to verify the theoretical explanation. We hope that this study will provide new inspiration for oil/water emulsion separation techniques.

Acute Atypical Endophthalmitis Following Intravitreal Sustained-release Dexamethasone Implant: A Case Series.

PURPOSE: To present three cases of acute endophthalmitis following intravitreal sustained-release dexamethasone (Ozurdex®) with atypical presentation and to discuss the management of these patients. METHODS: A retrospective case series of three patients with endophthalmitis following intravitreal sustained-release dexamethasone (Ozurdex®) implantation who presented between July 2020 to August 2020. RESULTS: Two out of three patients who were treated with topical steroid and antibiotic therapy alone showed favorable outcomes and were managed without the need for intravitreal antibiotics or implant removal. One patient who showed initial response to topical therapy subsequently required pars plana vitrectomy, implant removal and a single empirical dose of intra-vitreal antibiotics and anti-fungal agent due to persistent inflammation. CONCLUSION: Post intravitreal Ozurdex® endophthalmitis although a rare entity can present with atypical features of a painless white eye and a delayed onset intraocular inflammation. Although all cases of endophthalmitis should be treated as infective until proven otherwise, it is fair to consider a trial of conservative treatment with topical steroids and antibiotics initially with close monitoring. In cases with poor response to topical therapy, pars planar vitrectomy and implant removal should be strongly considered.

Recombinant SARS-CoV-2 RBD with a built in T helper epitope induces strong neutralization antibody response.

Without approved vaccines and specific treatments, COVID-19 is spreading around the world with above 26 million cases and approximately 864 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5) were expressed and renatured. The antigenicity and immunogenicity of S1-4 were evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency was measured preliminarily by microneutralization assay (MN50). The soluble S1-4 and S1-5 protein was prepared to high homogeneity and purity. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity supplemented with Th1-type immunity. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralizing antibody titer 256. Recombinant SARS-CoV-2 RBD with a built in T helper epitope could stimulate both strong humoral immunity supplemented with cellular immunity in mice, demonstrating that it could be a promising subunit vaccine candidate.

The Role of Leisure Satisfaction in Serious Leisure and Subjective Well-Being: Evidence From Chinese Marathon Runners.

The topics of serious leisure and subjective well-being have been discussed extensively in previous research. It is generally acknowledged that people prefer to experience deeper satisfaction and happiness through serious participation in leisure-time physical activities. However, it is essential to examine the relationship between serious leisure and subjective well-being in an urban setting as well as the mediating effect of leisure satisfaction. Data were collected from 447 recreational runners at the 2018 Wuxi International Marathon event in China. The study results showed that serious leisure was positively associated with leisure satisfaction and subjective well-being, that leisure satisfaction was positively associated with subjective well-being, and that leisure satisfaction completely mediated the relationship between serious leisure and subjective well-being. Running group membership significantly affected the path from serious leisure to leisure satisfaction, while other demographic variables (e.g., gender and education) did not moderate any paths. These results help explain the intricate relationship between serious leisure and subjective well-being and offer theoretical and managerial implications for serious leisure.

The biological characteristics of SARS-CoV-2 spike protein Pro330-Leu650.

SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.

[Association between DIO polymorphism and aerobic endurance].

OBJECTIVE: To study whether polymorphisms in the iodothyronine deiodinase (DIO) gene region contribute to endurance exercise capacity and to validate whether TSHR gene can be used as genetic marks associated with aerobic endurance performance. METHODS: Three SNPs (C785T in DIO1 gene regions, Thr92Ala and Gly3Asp in DIO2 gene regions) were selected. The genotypes of the 123 elite long running athletes(EEA) and 127 college students from northern China(CG) were analyzed using the matrix assisted laser desorption ionisation-time of flight mass spectrometry method(MALDI-TOF). The athletes were divided into different groups according to the sports level and the items, which are international masters and masters (43 vs 80), 5/10 km and marathon (92 vs 31). RESULTS: There was no significant difference of the C785T loci in DIO1 gene and the Thr92Ala loci in DIO2 gene between the EEA and the CG(P＞0.05), while at Gly3Asp loci, the frequency distributions of the 3 genotypes were remarkably different in the groups of control and international masters of sports, as well as in the groups of control and marathon athletes(P＜0.05). The genotype TT only existed in EEA not in CG, however, the frequency distribution was very low. The Thr92Ala and Gly3Asp loci of DIO2 gene were in strong linkage disequilibrium. The frequency distributions of the haplotype CT were significantly different in the male CG and the female CG, the male CG and the male EEA(P＜0.05), the male CG and the male masters of sports, as well as in the male CG and the male marathon athletes(P＜0.05). The frequency distributions of the haplotype TC were remarkably higher in the groups of female international masters of sports and female 5 000 m/10 000 m than those in the female CG(P＜0.05). CONCLUSION: The frequency distributions of the haplotype CT were different in male and female CG, and haplotype CT could be used as a genetic mark associated with aerobic endurance performance of the male EEA, especially for the long running athletes of masters of sports and marathon, while the haplotype CT was associated with the aerobic endurance performance of the female long running athletes of international masters of sports and 5 000 m/10 000 m.

Evolution and genetic characterization of hepatitis A virus isolates in China.

OBJECTIVES: Hepatitis A virus (HAV), transmitted mainly through the fecal-oral route, is one of the major causes of acute viral hepatitis worldwide. HAV is endemic in China. This study performed genetic and evolutionary analysis of HAV isolates circulated in the country. METHODS: Clinical samples were collected and HAV nucleotide and deduced amino acid sequences were analyzed. 70 representative sequences of HAV VP3-VP1-2A regions sampled from 1988 to 2014 were compared and characterized using the Bayesian Markov Chain Monte Carlo approach (BEAST software, Version1.7.5). RESULTS: All isolates from China in this study belonged to genotype I, with most of the samples clustering in subgenotype IA, while several unique amino acid variants were observed. The estimated mean substitution rate was 5.56×10(-4) substitutions / site / year, the time to the most recent common ancestor of genotype I isolates in China was calculated to be around 180 years ago. Skyline plots showed the incidence of HAV went down gradually from the mid-1990s. CONCLUSIONS: The evolution estimations were consistent with the laboratory and epidemiological results. Several isolates from China showed amino acid changes close to the immunodominant sites, which needs to be further analyzed. The study results have indicated the effectiveness of improving economic and sanitation levels together with HAV vaccination to control HAV-related infections in China.

[Anti-hypertensive Effect of Total Flavonoids of Cydonia oblonga Leaves and Its Mechanism Based on Anti-inflammatory Function].

OBJECTIVE: To study the anti-hypertensive effect of total flavonoids of Cydonia oblonga leaves in spontaneously hypertensive rats, then to preliminarily investigate the mechanism of action based on anti-inflammatory function. METHODS: Spontaneously hypertensive rats were divided into six groups as spontaneously hypertensive control group (SHR), captopril group (25 mg/kg), Eucommia ulmoides group (30 mg/kg), total flavonoids of Cydonia oblonga leaves low (40 mg/kg), middle (80 mg/kg) and high dose (160 mg/kg) groups. Eight Wistar-Kyoto (WKY) rats were given distilled water as the control. The drugs were given by intragastric administration for 16 weeks, then the contents of IL-1ß, IL-6, IL-10, TNF-α and CRP in rats serum were detected. The weight and the blood pressure of rats were measured at 0 min and 2, 4, 6, 8, 10, 12, 14, 16 weeks after drug administrated. RESULTS: Compared with control group, the contents of IL-1ß, IL-6, TNF-α and CRP were increased and IL-10 was decreased; Compared with SHR group, the contents of IL-1ß,IL-6, TNF-α and CRP were decreased in total flavonoids of Cydonia oblonga leaves groups. CONCLUSION: Total flavonoids of Cydonia oblonga leaves show an anti-hypertensive activity in spontaneously hypertensive rats and the mechanism is related to the function of anti-inflammatory.

Effect of Cydonia oblonga Mill. leaf extracts or captopril on blood pressure and related biomarkers in renal hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cydonia oblonga Mill. (COM) is used in traditional Uyghur medicine to treat or prevent cardiovascular disease. In a previous study COM leaf extracts were found to be active in renal hypertensive rats (RHR). The present study tests the dose-dependence of the effect of ethanol leaf extracts on hypertension and on biomarkers associated with blood pressure control, such as angiotensin-II (AII), plasma renin activity (PRA), apelin-12 (A), endothelin (ET) and nitric oxide (NO), compared to captopril. METHODS: Two-kidney one-clip (2K1C) Goldblatt model rats were divided randomly into six groups: sham, model, captopril 25 mg/kg, COM leaf extract 80, 160 and 320 mg/kg (n=10 each). Drugs were administered orally daily for eight weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before treatment and every 2 weeks. Blood and kidney samples were collected after the last treatment to measure AII, PRA, A, ET and NO. RESULTS: RHR had increased blood pressure, AII, A, PRA, ET and decreased NO. Treatment with captopril reduced blood pressure, AII, A, PRA, and ET, though not quite to normal values. COM leaf extracts significantly and dose-dependently reduced blood pressure, AII, A, RA and ET, whereas NO was increased. The highest dose of COM had the same effects as captopril. CONCLUSION: The effects of COM extracts on blood pressure and biomarkers were dose-dependent and at the highest dose similar to those of captopril. This suggests an action of COM on the renin-angiotensin system, which could explain its antihypertensive effect.

Pathological Changes in Internal Organs after Blocking Low Hydraulic Resistance Channels along the Stomach Meridian in Pigs.

Objective. The correlation between meridians and organs (Zang-fu) is an important aspect of meridian theory. The objective of this paper is to investigate the pathological changes in the organs resulting from blocking low hydraulic resistance channel (LHRC) along the stomach meridian by injecting gel in pigs so as to offer some insight into the correlation between meridians and internal organs. Methods. Four white piglets and twelve black minipigs were divided into four batches and were observed in different periods. Each batch included two pairs of pigs and each pair matched two pigs with similar conditions among which gel was injected into 6~8 low hydraulic resistance points along the the stomach meridian in the experimental pig and the same amount of saline was injected into the same points in the control pig. The state of stomach and intestine was observed 6~10 weeks after the blocking model was developed. Results. The results showed that there were bloated stomach or/and intestine in all the experimental pigs while there were normal states in seven control pigs except one dead during the experiment. Conclusion. The findings confirmed that the blockage of LHRC along the stomach meridian can influence the state of stomach and intestine, leading to a distension on stomach or/and intestine.

Study on the Formation of Novel Threadlike Structure through Intravenous Injection of Heparin in Rats and Refined Observation in Minipigs.

Objective. To study if the novel threadlike structure (NTS) was caused by coagulation during injecting urethane intraperitoneally and the source of NTS. Methods. Twenty-two SD rats were anaesthetized by urethane injected intraperitoneally. Heparin was injected at 5 minutes before the anaesthesia from femoral vein in 11 rats, and saline was given in the other 11 rats randomly. Six Chinese minipigs were carried to look for NTS. One sample was taken to be stained by DAPI/Phalloidin and observed by a laser scanning confocal microscope. Results. In the group of heparin, 10 rats were found to have NTS with appearance rate of 90.9%, and 9 rats were found to have NTS with the appearance rate of 80.1%. Both groups have 1.81 average numbers of NTS in each rat without significant difference (P > 0.05). In the observation of pigs, the NTS was found to prolong from the serous membranes of abdominal wall and organ surface. Histological observation showed elongated nuclei and alignment which is similar to the characteristics of PVS. Conclusion. There is no strong evidence to say that the NTS on organ surface was caused by coagulation of blood. The source of NTS might be a prolonged structure from serous membrane in abdominal cavity during the development and more or less retained after birth.

[Genetic susceptibility for acute high altitude disease].

Acute high altitude disease(AHAD), which can be divided into acute mountain disease (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE), is one of the special illnesses occurred at high altitude, commonly encountered by travelers to high altitudes (>2 500 m), which affects people's work capacity and health and could be even a life-threatening disease. Despite extensive investigations over the last century, the pathophysiology of AHAD remains elusive. Nevertheless, numerous researches have confirmed the existence of AHAD susceptibility differences. The aim of this paper was to review the epidemiological evidence for a genetic component to the various forms of AHAD so far, as well as to supply helpful reference to its epidemiological studies.

[Construction of recombinant CHO cell strain for high expression of HBsAg].

OBJECTIVE: To overexpress hepatitis B virus S gene in CHO cells cultured in serum-free media. METHOD: Plasmid was constructed by cloning of HBV S gene and then it was transfected into CHO cells. After cell screen, the positive clones were identified and isolated into a serum-free media followed by the serological and morphological characterization of the expression product. RESULT: CHO cell strains which can express HBsAg efficiently and stably were obtained. Spherical and filamentous HBsAg could be detected under electronic microscope. The titer of the expression product was up to 1:5000. CONCLUSION: Serum-free media cultured CHO cell strain for overexpression of HBsAg was successfully constructed and the expression product was high antigenic.

Electrical stimulation ameliorates light-induced photoreceptor degeneration in vitro via suppressing the proinflammatory effect of microglia and enhancing the neurotrophic potential of Müller cells.

Many types of electrical stimulation (ES) devices have been shown to promote the survival of degenerated neural cells, such as dopaminergic neurons in the medial forebrain bundle-transected rats, ischemic-injured cortical neurons and inner-and outer-nuclear-layer cells in degenerated retina. Using a rat photic injury model, our lab previously proved the neuroprotective effect of transcorneal electrical stimulation (TCES) on apoptotic photoreceptor cells. To delineate the mechanisms that might underlie this process, the effects of ES on light-damaged photoreceptor degeneration-induced microglia and Müller cell activation were investigated in the present in vitro study. Our data showed that ES (3 ms, 20 Hz, 300-1600 µA) increased survival among light-reared cone-derived cells (661W) cultured alongside microglia or Müller cells analyzed by LDH and TUNEL assays. The degree of rescue was found to depend on the different intensities of the ES current. The immunocytochemistry revealed that ES significantly decreased the numbers of activated microglia cells with ameboid shapes and increased the numbers of reactive gliotic Müller cells with larger soma when they were co-cultured with light-damaged 661W cells. Real-time RT-PCR and Western blotting indicated that ES which was applied to different co-cultures and 661W cell-conditioned media (661WCM)-treated glia cultures had a prominent inhibitive effect on the secretion of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in microglia and a positive regulative effect on the production of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in Müller cells. The death rate of light-exposed 661W cells cultured with microglia was decreased significantly by the addition of neutralizing antibodies against IL-1ß and TNF-α. On the other hand, the death rate of light-exposed 661W cells cultured with Müller cells was prominently increased when the co-culture was incubated in the presence of neutralizing antibody against BDNF while anti-CNTF neutralizing antibody did not induce additional exacerbation of the cell death among those 661W cells. These findings indicate the feasibility of using ES to create a nurturing environment for light-damaged photoreceptor cells. This environment is characterized by diminished microglial activation and fortified Müller cells reactive gliosis, which may have great potential in ameliorating photoreceptor damage. In this way, ES was here determined to be a novel, potent therapeutic option for delaying the progression of photoreceptor degeneration in patients suffering from retinitis pigmentosa (RP).

[Some potential candidate genes related to elite endurance diathesis].

Differences among individuals in exercise performance are multifactorial and determined by a range of environmental (physical training, nutrition, and technological aids) and genetic factors. So far, numerous gene polymorphisms involved in elite athletic capability have been studied. However, in recent years, the attempts to identify new genes or loci fell into a bottleneck and may limit the use of genetic information for talent search. We selected some potential endurance-related genes, reviewed their functions in physical performance, and studied on their polymorphisms. The results of this study will provide new ideas and references for future research.