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1.
Sci Rep ; 14(1): 2709, 2024 02 01.
Article in English | MEDLINE | ID: mdl-38302636

ABSTRACT

With the aging of the population, sarcopenia has become more common. Studies have shown a broad association between liver disease and sarcopenia. However, this link remains unclear. Our study explored the link between NAFLD and sarcopenia and predicting the pathogenesis. To begin, we investigated the causal relationship and genetic correlation between them using MR and LDSC. Second, each GWAS was annotated by MAGMA. The annotated genes were analyzed for pleiotropy using the PLACO approach. Finally, functional analysis was conducted on the identified pleiotropic genes. We observed a significant genetic correlation between NAFLD and sarcopenia. Subsequently, we conducted gene-level pleiotropy analysis using PLACO and identified a total of 153 genes with pleiotropic effects. Functional analysis revealed enrichment of these genes in various tissues, including pancreas, liver, heart, blood, brain, and muscle, with involvement in cellular regulation, intracellular function, and antigen response. Moreover, our MR analysis provided evidence of a causal relationship between NAFLD and sarcopenia. Our study has discovered the genetic and causal relationships between NAFLD and sarcopenia, providing further insights into their pathophysiological mechanisms. The identification of pleiotropic genes also offers potential targets for future drug therapies aimed at controlling or treating NAFLD and sarcopenia.


Subject(s)
Non-alcoholic Fatty Liver Disease , Sarcopenia , Humans , Non-alcoholic Fatty Liver Disease/complications , Sarcopenia/pathology , Muscle, Skeletal/pathology , Aging
2.
Sci Rep ; 13(1): 22643, 2023 12 19.
Article in English | MEDLINE | ID: mdl-38114510

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a major disease that threatens the life and health of neonates. Vitamin A (VA) can participate in early fetal lung development and affect lung immune function. Researches revealed that the serum VA level in premature infants with ARDS was lower than that in premature infants without ARDS of the same gestational age, and premature infants with VA deficiency (VAD) were more likely to develop ARDS. Moreover, the VA levels can be used as a predictor of the development and severity of neonatal ARDS. However, the critical question here is; Does ARDS develop due to VAD in these systemic diseases? Or does ARDS develop because these diseases cause VAD? We hypothesize that VAD may aggravate neonatal ARDS by affecting immunity, metabolism, barriers and other pathways. In this article, we used multiomics analysis to find that VAD may aggravate ARDS mainly through the Fc epsilon RI signaling pathway, the HIF-1 signaling pathway, glutathione metabolism, and valine, leucine and isoleucine degradation signaling pathways, which may provide the molecular pathogenic mechanism behind the pathology of VAD-aggravated ARDS and can also provide potential molecular targets for subsequent research on ARDS.


Subject(s)
Respiratory Distress Syndrome, Newborn , Respiratory Distress Syndrome , Vitamin A Deficiency , Humans , Infant, Newborn , Rats , Animals , Vitamin A Deficiency/complications , Animals, Newborn , Multiomics , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome, Newborn/genetics , Vitamin A
3.
Front Nutr ; 10: 1111950, 2023.
Article in English | MEDLINE | ID: mdl-37006939

ABSTRACT

Aim: Observational studies have reported that levels of vitamin D were associated with the incidence of chronic obstructive pulmonary disease (COPD), but the relationship between them may have been confounded in previous studies. In this study, we aimed to determine the relationship between the levels of 25-hydroxyvitamin D (25OHD) and the risk of COPD by two-sample Mendelian randomization (MR) analysis. Methods: Summary statistics for 25OHD and COPD in this study were obtained from the EBI (n = 496,946) consortium and Finn (n = 187,754) consortium. MR was adopted to explore the effect of the genetically predicted levels of 25OHD on the risk of COPD. Based on three assumptions of MR analysis, inverse variance weighting was used as the main analysis. To make our results more robust and reliable, MR Egger's intercept test, Cochran's Q test, funnel plot, and "leave-one-out" sensitivity analysis were used to assess the potential pleiotropy and heterogeneity in this study. Then, colocalization analysis and MR Steiger approaches were used to estimate the possible directions of estimates between them. Finally, we analyzed the causal associations between the four core genes (DHCR7, GC, CYP2R1, and CYP24A1) of vitamin D and the levels of 25OHD or the risk of COPD. Results: Our results showed that each 1 standard deviation (SD) increase in the genetically predicted 25OHD level was associated with a 57.2% lower relative risk of COPD [odds ratio (OR): 0.428, 95% Cl: 0.279-0.657, p = 1.041 × 10-4], and the above association was also verified by maximum likelihood (OR: 0.427, 95% Cl: 0.277-0.657, p = 1.084 × 10-4), MR-Egger (OR: 0.271, 95% CI: 0.176-0.416, p = 2.466 × 10-4), MR-PRESSO (OR: 0.428, 95% Cl: 0.281-0.652, p = 1.421 × 10-4) and MR-RAPS (OR: 0.457, 95% Cl: 0.293-0.712, p = 5.450 × 10-4). Furthermore, colocalization analyses (rs3829251, PP.H4 = 0.99) and MR Steiger ("TRUE") also showed a reverse association between them. Besides, the core genes of vitamin D also showed similar results except for CYP24A1. Conclusion: Our findings provide evidence for a reverse association between genetically predicted 25OHD levels and COPD risk. Taking measures to supplement 25OHD may help reduce the incidence of COPD.

5.
Eat Weight Disord ; 28(1): 11, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36790552

ABSTRACT

OBJECTIVES: To determine the causal association between genetically predicted obesity and the risk of hip osteoarthritis. METHODS: We performed two-sample Mendelian randomization (MR) analysis to analyze the association between body mass index (BMI) and hip osteoarthritis using pooled-level genome-wide association study (GWAS) data. The inverse variance weighted (IVW), MR‒Egger, and weighted median methods were used to estimate the causal association. In addition, we applied the MR Steiger filtering method, MR robust adjusted profile score (MR.RAPS) methods, and the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test to examine and address potential horizontal pleiotropy. RESULTS: We found a causal relationship between genetically predicted BMI and the risk of hip osteoarthritis by the IVW method [OR = 1.45, 95% confidence interval (CI) = 1.04-2.00, P = 0.02]. In the sensitivity analysis, the results of the MR‒Egger and weighted median methods revealed similar estimations but with a wide CI with lower precision. The funnel plot, MR-Egger intercept, and MR-PRESSO all indicated the absence of a directional pleiotropic effect. In addition, no heterogeneity was observed in the present analysis. Therefore, the result of IVW is most suitable and reliable for the present MR analysis. CONCLUSION: There is a causal relationship between obesity and a higher risk of hip osteoarthritis, suggesting that weight management may be an intervention for the prevention and management of hip osteoarthritis. LEVEL OF EVIDENCE: Bioinformatics, Basic science.


Subject(s)
Genome-Wide Association Study , Osteoarthritis, Hip , Humans , Osteoarthritis, Hip/genetics , Body Mass Index , Nonoxynol , Obesity/complications , Obesity/genetics , Polymorphism, Single Nucleotide
6.
Front Microbiol ; 13: 993052, 2022.
Article in English | MEDLINE | ID: mdl-36147858

ABSTRACT

Galacto-oligosaccharides (GOS) are oligosaccharides formed by ß-galactosidase transgalactosylation. GOS is an indigestible food component that can pass through the upper gastrointestinal tract relatively intact and ferment in the colon to produce short-chain fatty acids (SCFAs) that further regulate the body's intestinal flora. GOS and other prebiotics are increasingly recognized as useful food tools for regulating the balance of colonic microbiota-human health. GOS performed well compared to other oligosaccharides in regulating gut microbiota, body immunity, and food function. This review summarizes the sources, classification, preparation methods, and biological activities of GOS, focusing on the introduction and summary of the effects of GOS on ulcerative colitis (UC), to gain a comprehensive understanding of the application of GOS.

7.
Front Genet ; 13: 849206, 2022.
Article in English | MEDLINE | ID: mdl-35646051

ABSTRACT

Objectives: Although it has long been reported that high levels of cystatin C could contribute to the development of osteoporosis in some studies, no evidence has established a causal association between them thus far. Methods: A Mendelian randomization (MR) study was conducted to determine the causal effect of cystatin C on osteoporosis based on public databases obtained from separately published genome-wide association studies (GWASs). The single-nucleotide polymorphisms (SNPs) for cystatin C were extracted from the MR-Base (CKDGen, 33,152 participants), and the SNPs for osteoporosis were extracted from the United Kingdom Biobank project (United Kingdom Biobank, including 5,266 osteoporosis cases and 331,893 controls). We defined the odds ratio (OR) of IVW methods as the primary outcome. In addition, weighted median and MR-Egger regressions were used in the sensitivity analysis. Results: In IVW, we found that genetically predicted cystatin C was causally associated with the risk of osteoporosis with an OR of 1.02 [95% confidence interval (CI) = 1.003-1.025, p = 0.01]. In the further sensitivity analysis, weighted median regression also showed directionally similar estimates (OR = 1.02, 95% CI = 1.005-1.03, p = 0.005), and MR-Egger regression (OR = 1.02, 95% CI = 1.000-1.036, p = 0.15) revealed similar estimates but with lower precision. The funnel plot, MR-Egger intercept, and MR-PRESSO all indicate that no directional pleiotropic effect was observed. Conclusion: In conclusion, our MR study showed evidence of a causal association between serum cystatin C levels and osteoporosis, which also needs to be verified by studies with larger sample sizes in the future. Early monitoring of cystatin C may enable us to prevent osteoporosis-related diseases.

8.
J Vis Exp ; (181)2022 03 11.
Article in English | MEDLINE | ID: mdl-35343961

ABSTRACT

Berberine (BBR) is an isoquinoline alkaloid isolated from Coptis chinensis and possesses valuable pharmacological activities, including anti-inflammatory, anti-tumor, and alleviating several complications of type 2 diabetes mellitus (T2DM). However, the role of BBR in regulating diabetic tendon injury remains poorly understood. In this study, a rat model of T2DM was constructed, and cell apoptosis and autophagy were assessed in tendon tissues after BBR treatment through TdT-Mediated dUTP nick-end labeling (TUNEL) assay and immunohistochemical analysis. Tendon fibroblasts were obtained from the rat Achilles tendon, and the role of BBR in regulating cell apoptosis, the production of inflammatory cytokines, and autophagy activation were assessed using flow cytometry, quantitative real-time PCR (qRT-PCR), and western blot analysis. We demonstrated that BBR treatment significantly increased autophagy activation and decreased cell apoptosis in tendon tissues of T2DM rats. In tendon fibroblasts, BBR repressed High glucose (HG)-induced cell apoptosis and production of proinflammatory cytokines. HG treatment resulted in a decrease of autophagy activation in tendon fibroblasts, whereas BBR restored autophagy activation. More important, pharmacological inhibition of autophagy by 3-MA weakened the protective effects of BBR against HG-induced tendon fibroblasts injury. Taken together, the current results demonstrate that BBR helps relieve diabetic tendon injury by activating autophagy of tendon fibroblasts.


Subject(s)
Berberine , Diabetes Mellitus, Type 2 , Tendon Injuries , Animals , Apoptosis , Autophagy , Berberine/pharmacology , Fibroblasts , Rats , Tendons
9.
Biosci Rep ; 42(3)2022 03 31.
Article in English | MEDLINE | ID: mdl-35293974

ABSTRACT

Diabetic foot ulcer (DFU) is a kind of common and disabling complication of Diabetes Mellitus (DM). Emerging studies have demonstrated that tendon fibroblasts play a crucial role in remodeling phase of wound healing. However, little is known about the mechanism underlying high glucose (HG)-induced decrease in tendon fibroblasts viability. In the present study, the rat models of DFU were established, and collagen deposition, autophagy activation and cell apoptosis in tendon tissues were assessed using Hematoxylin-Eosin (HE) staining, immunohistochemistry (IHC), and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay, respectively. Tendon fibroblasts were isolated from Achilles tendon of the both limbs, and the effect of HG on autophagy activation in tendon fibroblasts was assessed using Western blot analysis, Cell Counting Kit-8 (CCK-8) assay, and flow cytometry. We found that cell apoptosis was increased significantly and autophagy activation was decreased in foot tendon tissues of DFU rats compared with normal tissues. The role of HG in regulating tendon fibroblasts viability was then investigated in vitro, and data showed that HG repressed cell viability and increased cell apoptosis. Furthermore, HG treatment reduced LC3-II expression and increased p62 expression, indicating that HG repressed autophagy activation of tendon fibroblasts. The autophagy activator rapamycin reversed the effect. More importantly, rapamycin alleviated the suppressive role of HG in tendon fibroblasts viability. Taken together, our data demonstrate that HG represses tendon fibroblasts proliferation by inhibiting autophagy activation in tendon injury.


Subject(s)
Diabetic Foot , Tendon Injuries , Animals , Apoptosis , Autophagy , Cell Proliferation , Diabetic Foot/metabolism , Fibroblasts/metabolism , Glucose/metabolism , Rats , Sirolimus/pharmacology , Tendon Injuries/metabolism , Tendons/metabolism
10.
Front Endocrinol (Lausanne) ; 13: 1054206, 2022.
Article in English | MEDLINE | ID: mdl-36589832

ABSTRACT

Objective: Investigating the causal relationship between rheumatoid arthritis (RA) and atlantoaxial subluxation (AAS) and identifying and quantifying the role of C-reactive protein (CRP) as a potential mediator. Methods: Using summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of genetically predicted rheumatoid arthritis (14,361 cases, and 43,923 controls) and AAS (141 cases, 227,388 controls) was performed. Furthermore, we used two-step MR to quantitate the proportion of the effect of c-reactive protein-mediated RA on AAS. Results: MR analysis identified higher genetically predicted rheumatoid arthritis (primary MR analysis odds ratio (OR) 0.61/SD increase, 95% confidence interval (CI) 1.36-1.90) increased risk of AAS. There was no strong evidence that genetically predicted AAS had an effect on rheumatoid arthritis risk (OR 1.001, 95% CI 0.97-1.03). The proportion of genetically predicted rheumatoid arthritis mediated by C-reactive protein was 3.7% (95%CI 0.1%-7.3%). Conclusion: In conclusion, our study identified a causal relationship between RA and AAS, with a small proportion of the effect mediated by CRP, but a majority of the effect of RA on AAS remains unclear. Further research is needed on additional risk factors as potential mediators. In clinical practice, lesions of the upper cervical spine in RA patients need to be given more attention.


Subject(s)
Arthritis, Rheumatoid , Atlanto-Axial Joint , C-Reactive Protein , Joint Dislocations , Humans , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/genetics , Atlanto-Axial Joint/metabolism , Atlanto-Axial Joint/pathology , C-Reactive Protein/genetics , C-Reactive Protein/metabolism , Cervical Vertebrae/pathology , Genome-Wide Association Study , Joint Dislocations/genetics , Joint Instability/complications , Joint Instability/pathology
11.
Pharm Biol ; 58(1): 785-795, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33073642

ABSTRACT

CONTEXT: Qing-Mai-Yin (QMY) is a clinically used herbal formula for treating arteriosclerosis obliterans (ASO). OBJECTIVE: To evaluate the chemical constituents and effects of QMY on ASO rabbit model. MATERIALS AND METHODS: Forty-eight New Zealand rabbits were divided into six groups (n = 8): normal (normal rabbits treated with 0.5% CMC-Na), vehicle (ASO rabbits treated with 0.5% CMC-Na), positive (simvastatin, 1.53 mg/kg), and QMY treatment (300, 600, and 1200 mg/kg). ASO rabbit model was prepared by high fatty feeding, roundly shortening artery, and bovine serum albumin immune injury. QMY (300, 600 and 1200 mg/kg) was orally administered for 8 weeks. The effects and possible mechanisms of QMY on ASO rabbits were evaluated by pathological examination, biochemical assays, and immunohistochemical assays. The compositions of QMY were analysed using HPLC-Q-TOF-MS/MS analysis. RESULTS: Compared to the vehicle rabbit, QMY treatment suppressed plaque formation and intima thickness in aorta, and decreased intima thickness, whereas increased lumen area of femoral artery. Additionally, QMY treatment decreased TC, TG and LDL, decreased CRP and ET, and increased NO and 6-K-PGF1α in serum. Furthermore, the potential mechanisms studied revealed that QMY treatment could suppress expression of TNF-α, IL-6, ICAM-1 and NF-κB in endothelial tissues, and increase IκB. In addition, HPLC analysis showed QMY had abundant anthraquinones, stilbenes, and flavonoids. CONCLUSION: QMY has ameliorative effects on ASO rabbit, and the potential mechanisms are correlated to reducing inflammation and down-regulating NF-κB. Our study provides a scientific basis for the future application and investigation of QMY.


Subject(s)
Arteriosclerosis Obliterans/drug therapy , Drugs, Chinese Herbal/pharmacology , Inflammation/drug therapy , Medicine, Chinese Traditional , Animals , Arteriosclerosis Obliterans/pathology , Chromatography, High Pressure Liquid , Disease Models, Animal , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/administration & dosage , Inflammation/pathology , Male , NF-kappa B/metabolism , Rabbits , Simvastatin/pharmacology , Tandem Mass Spectrometry
12.
Zhonghua Yan Ke Za Zhi ; 47(5): 436-42, 2011 May.
Article in Chinese | MEDLINE | ID: mdl-21756747

ABSTRACT

OBJECTIVE: To observe the changes of retinal thickness during critical period plasticity in rat, and to investigate whether apoptosis participates in the structural forming of retina. METHODS: Experimental research. 50 normal newborn pups of SD rat were randomly selected in the experiment. In vivo consecutive scanning of retinal image was taken and the retinal thickness from RPE to ILM was recorded in 10 pups (20 eyes) with spectral domain optical coherence tomography (OCT) at postnatal day 14 (P14), P18, P21, P24 and P42. Bcl-2, Bax, Caspase-3 mRNA was assessed with fluorescent quantitative real-time polymerase chain reaction after total RNA extracted from 4 retinas of 2 pups at each time point from P14 to P42. Histological measurement of retinal thickness of sections with HE staining from 4 pups (8 eyes) at each time point was compared with the results of OCT scanning. TUNEL staining was used to detect the apoptotic cells in retinal cryosections of 2 pups (4 eyes) at the same time point. The data were analyzed by One-way ANOVA and Linear Regression through SPSS 11.5 software. RESULTS: There was significant difference between the retinal thickness measured through OCT in pups from P14 to P42 (F = 15.425, P = 0.001). And the values were (243.42 ± 13.83) µm at P14, (218.78 ± 8.21) µm at P18, (195.42 ± 8.02) µm at P21, (195.74 ± 14.85) µm at P24, (190.79 ± 11.70) um at P42. The retinal thickness measured through OCT decreased significantly during the first 3 weeks after birth. The results of OCT measurement had linear correlation with histology measurement (R = 0.794, P = 0.000). There was significant difference between mRNA expression of Bcl-2, Bax and Caspase-3 in pups from P14 to P42 (F = 18.684, F = 47.307, F = 49.611; P = 0.000). The relative expression of Bax and Caspase-3 peaked at P24 while Bcl-2 was much more stable. There were a lot of apoptotic cells in the ganglion cells layer, the inner nuclear layer and the outer nuclear layer during P18 to P24 by TUNEL staining. And the apoptosis alleviated at P42. CONCLUSIONS: The retinal thickness decreases when the retina continues to develop during critical period plasticity. Cirrus HD-OCT can be used as an effective instrument to show the layers of retina in rat in vivo. Apoptosis participates in the course of retinal development which possibly leads to the thinning of retina.


Subject(s)
Apoptosis , Retina/cytology , Tomography, Optical Coherence , Animals , Caspase 3/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Retina/metabolism , bcl-2-Associated X Protein/metabolism
13.
Int J Ophthalmol ; 3(2): 141-4, 2010.
Article in English | MEDLINE | ID: mdl-22553538

ABSTRACT

AIM: In order to improve the biocompatibility of intraocular lenses (IOL), the polymethylmethacrylate (PMMA) IOL was modified with F-heparin. METHODS: The PMMA IOL was modified with F ions and heparin by the technique of ion beam combined with low temperature and low pressure plasma. The monkeys (20 eyes) with cataract partly were randomly classified into 2 groups and implanted with PMMA IOL and modified IOL respectively for 180 days. All of the eyes were examined by slit-lamp microscope at postoperative 15, 30, 60, 90, 180 days. The extracted IOL was analyzed with computer image analysis, light microscope (LM) and scanning electron microscope (SEM) at postoperative 180 days. RESULTS: The early inflammatory reactions postoperatively include anterior chamber exudation and aqueous cell count. The modified IOL group showed less than the non-modified IOL group. The late foreign body cell reaction that adhered to the surface of non-modified IOL was more predominant. The morphologic and pathological changes of posterior capsule opacification (PCO) in monkeys' eyes included fibrosis-type, pearl-type and soemmerring's ring. There was a significant difference between the two groups. CONCLUSION: F-heparin modified IOL has good uveal and capsular biocompatibility.

14.
Zhonghua Yan Ke Za Zhi ; 45(6): 550-5, 2009 Jun.
Article in Chinese | MEDLINE | ID: mdl-19957680

ABSTRACT

OBJECTIVE: To evaluate the combined effect of topical rapamycin (RAPA) eye drop in nanometer vector and poly (lactic acid) (PLA) wafers of cyclosporine A (CsA) in the prevention of acute allograft rejection after rabbit corneal transplantation. Methods It was an experimental study. RAPA was incorporated into the nanometer particles and CsA was incorporated into PLA wafers. A was syngeneic control whose both donor and recipient are New Zealand rabbit. Gray donor corneas were implanted into the 102 recipients of New Zealand albino rabbits with corneal neovascularization who were randomly divided into B, C, D, E, F, G 6 groups to receive the different types of therapy: B was no therapy control; C was eye drop of nanometer vector but no RAPA twice a day, 28 days; D was PLA wafers in the anterior chamber of rabbit eyes but no drugs; E was 0.5% RAPA eye drop of nanometer vector twice a day, 28 days; F was PLA wafers of CsA in the anterior chamber of rabbit eyes; G was PLA wafers of CsA in the anterior chamber of rabbit eyes and 0.5% RAPA eye drop of nanometer vector eye drop twice a day for 28 days together. Postoperative evaluation included slit-lamp biomicroscopy, histopathology and immunohistology, Cytokines related with neovascularization and immunosuppression in the corneal tissue by RT-PCR. The graft survival was assessed by One-Way ANOVA and q test. RESULTS: Corneal allograft survival time: A (100.00 +/- 0.00), B (8.44 +/- 1.24), C (8.89 +/- 2.57), D (8.56 +/- 2.30), E (43.11 +/- 5.58), F (43.67 +/- 9.54), G (72.00 +/- 15.34) d. Group G led to a statistically significant prolongation of transplant survival and was superior than group E and F which was a statistical prolongation compared with group B, C and D (qGE = 11.42, qGF = 11.24, qEB = 13.64, qEC = 13.38, qED = 13.46, qFB = 13.82, qFC = 13.56, qFD = 13.64; P < 0.01). Immunohistopathologically, the grafts were subjected to an immune response contained a dense infiltrate of neutrophils, CD4+ and CD8+ T lymphocytes in the group B, C and D. This cellular infiltrate was a significant reduction in group E,F,G. RT-PCR showed that the gene expression of IL-2 was inhibited earlier (3 days) in group F, G and VEGF gene expression being suppressed later (14 days) in group E, G. CONCLUSIONS: Combined therapy with topical application of RAPA eye drop of nanometer vector and CsA PLA wafers can significantly prolong the survival of allograft at high-risk. Moreover, topical combined treatment of them is more effective, lower dosage, less side-effects and cheaper than the treatment with topical individual immunosuppressive drug.


Subject(s)
Cyclosporine/therapeutic use , Graft Rejection/drug therapy , Immunosuppressive Agents/therapeutic use , Sirolimus/therapeutic use , Animals , Corneal Transplantation , Drug Delivery Systems , Lactic Acid/therapeutic use , Nanoparticles/therapeutic use , Polyesters , Polymers/therapeutic use , Rabbits
15.
Graefes Arch Clin Exp Ophthalmol ; 247(4): 503-14, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19084985

ABSTRACT

OBJECTIVE: To examine the survival, migration, integration, differentiation and the expression of various neurotrophic factors of bone-marrow mesenchymal stem cells (BMSCs) transplanted into the vitreous cavity of rats injured by ischemia/reperfusion(I/R). METHODS: The BMSCs were separated from rat marrow using the wall-sticking method, and cultured in vitro to expand. Flow cytometry detected the surface antigens of BMSCs. Ninety-six rats were randomly divided into four groups: normal control injected PBS(C+P), normal control injected BMSCs (C+B), ischemic/reperfusion injected PBS(I/R+P)and ischemic/reperfusion injected BMSCs(I/R+B). After retinal I/R injury was induced in each group by increasing intraocular pressure, 10 microl PBS and BMSC suspensions labeled by red fluorescence CM-Dil were immediately injected into the vitreous cavity. We observed the survival, migration and integration of BMSCs using confocal microscopy. The differentiation and expression of basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) of CM-Dil-labeled BMSCs were detected by immunofluorescent labeling and reserved by confocal microscopy. The expression of mRNA and proteins of bFGF, BDNF and CNTF were assayed by RT-PCR and Western Blot respectively. RESULTS: After transplantation to normal eyes, BMSCs labeled by CM-Dil were mostly present in the vitreous cavity, and did not migrate. After transplantation to I/R eyes, BMSCs labeled by CM-Dil were mostly present along with the inner limiting membrane. Only a few cells were integrated into the ganglion cell layer. Two or 4 weeks after transplantation, a few BMSCs labeled by CM-Dil were observed to express markers of neuron- neurone specific enolase (NSE), neurofilament (NF) and various neurotrophic factors. The BMSC-injected I/R model eyes showed less reduction in the number of RGCs than that of the I/R eyes with PBS injection. CONCLUSIONS: BMSC transplantation is a valuable neuroprotection tool for the treatment of retina and optic nerve diseases.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Reperfusion Injury/therapy , Vitreous Body/surgery , Animals , Blotting, Western , Cell Count , Cell Differentiation/physiology , Cell Movement/physiology , Cell Survival/physiology , Flow Cytometry , Fluorescent Antibody Technique, Indirect , Male , Mesenchymal Stem Cells/metabolism , Microscopy, Confocal , Nerve Growth Factors/genetics , Neurons/cytology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Retinal Ganglion Cells/cytology , Reverse Transcriptase Polymerase Chain Reaction
16.
Zhonghua Yan Ke Za Zhi ; 43(8): 688-93, 2007 Aug.
Article in Chinese | MEDLINE | ID: mdl-18001564

ABSTRACT

OBJECTIVE: To study the characteristics of spherical aberrations (SA) of the traditional intraocular lenses (IOLs) produced by different materials and designs. METHODS: A special optical metrical system was established in the laboratory to measure the SA of IOLs by using the Hartmann-Shack aberrometer. Eight different types of IOLs were divided into two Groups. Group 1 consisted of 4 types of IOLs made by different materials, Group 2 consisted of 4 types of IOLs made by different designs. SA of these IOLs was measured at 3, 4, 5, 6 and 7 mm apertures separately. All data was analyzed statistically. RESULTS: With the size of aperture increased, SA in these two groups was both increased. There were positive correlations between the size of aperture and the SA (r = 0.6465, 0.7872; P < 0.01). The numbers of IOLs fitted with Rayleigh criterion at apertures of 3, 4, 5, 6, and 7 mm were 8, 5, 3, 2 and 2, respectively. In Group 1, the acrylic IOL (SA60AT) with high refractive index showed the greatest SA, and the acrylic IOL (AR40e) with low refractive index showed the smallest SA. The difference of SA between these two IOLs was statistically significant (P < 0.01). SA of the silicon IOL (SI40NB) and PMMA IOL (PC330UV) lied between these two extremities. In Group 2, the convexo-convex IOL with the posterior surface more curved than the anterior surface had the greatest SA. The convex-plano IOL had the smallest spherical aberration. The difference of SA between these two IOLs was statistically significant (P < 0.01). SA of convexo-convex IOL with the anterior surface more curved and the epuiconvex IOL was lied between these two extremities. CONCLUSIONS: IOLs made by different materials and designs under different apertures show significant difference of SA, which is useful for the improvement of optic quality of IOLs. Further studies on the exact mechanism of these differences are required.


Subject(s)
Lenses, Intraocular , Materials Testing , Prosthesis Design
17.
Zhonghua Yan Ke Za Zhi ; 43(12): 1082-4, 2007 Dec.
Article in Chinese | MEDLINE | ID: mdl-18331676

ABSTRACT

OBJECTIVE: To analyze the results of bimanual microphacoemulsification combined with rollable intraocular lens (IOL), to evaluate the feasibility and safety of this procedure and to compare the clinical results of two different types of rollable intraocular lens. METHODS: Thirty-five cases (35 eyes) were divided into 2 groups. Group 1 included 15 eyes used Thinoptx IOL, Group 2 included 20 eyes used Acri. Smart IOL. The data included best corrected visual acuity (BCVA) and intraocular pressure (IOP) (pre-, 1 day, 1 week and 1 month post-operatively); corneal curvature (pre- and 1 month post-operatively); target refraction and post-operation refraction (1 month after the operation). RESULTS: A significant difference was found between pre-operative and 1 month post-operative BCVA (P<0.01). No significant different was found between pre-operative and post-operative IOP, astigmatism, target refraction and refraction. There was no significant difference in pre-operative and post-operative astigmatism, target refraction and post-operation 1-month refraction between these two groups. CONCLUSIONS: Bimanual microphacoemulsification with rollable intraocular lens (IOL) is a feasible and safe procedure for the cataract surgery.


Subject(s)
Cataract/therapy , Lens Implantation, Intraocular/instrumentation , Lens Implantation, Intraocular/methods , Phacoemulsification/methods , Aged , Female , Humans , Lenses, Intraocular , Male , Middle Aged
18.
Zhonghua Yan Ke Za Zhi ; 42(8): 744-50, 2006 Aug.
Article in Chinese | MEDLINE | ID: mdl-17081449

ABSTRACT

OBJECTIVE: To construct pGEX-DT(389)-hbFGF plasmid, express and identify the cytotoxicity to human lens epithelial cells (HLECs). METHODS: Extracting DNA of dead diphtheria bacillus and RNA of 12-week fetal brain cortex. The fragments of truncated diphtheria toxin (containing 389 amino acids of N-terminus, DT(389)) and full length human bFGF gene (encoding 18kd protein) were amplified by PCR technique respectively. The two fragments were inserted into prokaryotic expression vector pGEX-4T-1. After testing sequence, the expressing plasmid was transformed into E.Coli BL21 strain and induced expression under IPTG. The expressed fusion protein was purified and identified. MTT experiment tested cytotoxicity of the fusion protein to HLECs in vitro. The way of HLECs death under different dosage was identified by flow cytometry. RESULTS: The gene fragments of DT(389) and human bFGF were accurately amplified. The expression vector including DT(389)-hbFGF fused gene was constructed and expressed successfully. DT(389)-hbFGF fusion protein can induce HLECs apoptosis in a dosage dependence manner during certain range. The LD(50) was about 3.8 x 10(-11) mol/L. CONCLUSION: The successful cloning and expression of DT(389)-hbFGF immunotoxin lay a foundation for accelerating lens epithelial cells apoptosis and the targeting therapy toward posterior capsule opacification.


Subject(s)
Diphtheria Toxin/biosynthesis , Epithelial Cells/pathology , Fibroblast Growth Factor 2/biosynthesis , Lens, Crystalline/cytology , Cells, Cultured , Cloning, Molecular , Cytotoxicity, Immunologic , Diphtheria Toxin/genetics , Diphtheria Toxin/toxicity , Fibroblast Growth Factor 2/genetics , Humans , Plasmids/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/toxicity
19.
Zhonghua Yan Ke Za Zhi ; 42(10): 896-900, 2006 Oct.
Article in Chinese | MEDLINE | ID: mdl-17217782

ABSTRACT

OBJECTIVE: To evaluate corneal nerve distribution and morphological changes in subjects with type 2 diabetes. METHODS: Sixty-five eyes of 59 patients with type 2 diabetes (26 males, 39 females) and 26 eyes (10 males, 16 females) of control subjects were included in the present study. Based on the indirect ophthalmoscopic examination and fluorescein angiography, the diabetic group was divided into three sub-groups according to the stage of retinopathy: without diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). The central cornea was scanned with Confoscan 3.0. The images of subbasal nerve plexus and stromal nerves were analyzed. RESULTS: Corneal branch nerve fiber density of subbasal nerve plexus decreased in diabetic group as compared with control group, the difference was statistically significant. The decrease of nerve fiber density appeared only in the PDR sub-group, while the decrease was not significant in NDR and NPDR sub-groups. No obviously difference was found among control group, NDR and NPDR sub-groups. The proportion of patients with an abnormal morphologic nerve fibers in mid-stroma in diabetes group was greater than that in the control group and the difference was statistically significant (chi(2) = 46.613, P = 0.000). CONCLUSIONS: Corneal confocal microscope allows rapid and noninvasive in vivo evaluation of corneal nerves. The subbasal and stromal nerves of subjects with type 2 diabetes were abnormal in morphology.


Subject(s)
Cornea/innervation , Diabetes Mellitus, Type 2/pathology , Ophthalmic Nerve/pathology , Aged , Female , Humans , Male , Microscopy, Confocal , Middle Aged , Nerve Fibers/pathology
20.
Zhonghua Yan Ke Za Zhi ; 41(3): 285-8, 2005 Mar.
Article in Chinese | MEDLINE | ID: mdl-15840380

ABSTRACT

Modern cataract surgery is routinely combined with the implantation of an intraocular lens (IOL). Although surgical technique as well as IOL materials and designs have been improved dramatically, the problems related postoperative visual acuity still occur, such as glare disability, low visual acuity at night, and so on. Wavefront aberration technique can be used to help us revealing the real reasons of such postoperative visual problems. We reviewed the relative study outcome of the application of wavefront aberration technique in phakic eyes, and summarized the current opinions on the study of pseudophakic eyes.


Subject(s)
Lenses, Intraocular , Refraction, Ocular/physiology , Cataract Extraction , Diagnostic Techniques, Ophthalmological , Humans , Lens Implantation, Intraocular
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