Publications by authors named "Wenyi Tang"

38 Publications

Ferrostatin-1 attenuates ferroptosis and protects the retina against light-induced retinal degeneration.

Biochem Biophys Res Commun 2021 Apr 22;548:27-34. Epub 2021 Feb 22.

Eye Institute and Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China; Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China; Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, National Health Commission, Shanghai, China. Electronic address:

Degenerative retinal diseases, including age-related macular degeneration, are serious diseases that may lead to irreversible retinal neuron damage and permanent vision impairment. There are currently no effective treatments for these diseases due to our incomplete understanding of the underlying pathological mechanisms. Ferroptosis, a newly identified iron-dependent mode of cell death, is implicated in various diseases. However, it is unknown whether ferroptosis is involved in light-induced retinal degeneration. In this study, we found that light exposure significantly reduced the viability of photoreceptor cells in vitro and induced pro-ferroptotic changes, including iron accumulation, mitochondrial shrinkage, glutathione depletion, increased malondialdehyde (MDA), and decreased protein expression of SLC7A11 and GPX4. The effects of light exposure on ferroptosis were attenuated by ferrostatin-1. Consistently, the results of in vivo studies demonstrated that ferrostatin-1 protected against light-induced ferroptosis. And it exerted therapeutic effects by inhibiting neuroinflammation and prevented the effects of light exposure on the structure and function of the retina. The findings reveal an important role of ferroptosis in the pathogenesis of light-induced retinal degeneration and suggest that ferroptosis may be a novel treatment target for preventing retinal degeneration.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.055DOI Listing
April 2021

SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs.

Front Physiol 2020 23;11:555006. Epub 2020 Nov 23.

Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China.

: Aberrant neovascularization resulting from inappropriate angiogenic signaling is closely related to many diseases, such as cancer, cardiovascular disease, and proliferative retinopathy. Although some factors involved in regulating pathogenic angiogenesis have been identified, the molecular mechanisms of proliferative retinopathy remain largely unknown. In the present study, we determined the role of platelet-derived growth factor-B (PDGF-B), one of the HIF-1-responsive gene products, in cell proliferation and angiogenesis in retinal microvascular endothelial cells (RMECs) and explored its regulatory mechanism. : Cell counting kit-8 (CCK-8), bromodeoxyuridine (BrdU) incorporation, tube formation, cell migration, and Western blot assays were used in our study. : Our results showed that PDGF-B promoted cell proliferation and angiogenesis by increasing the activity of Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2) in RMECs, which was attenuated by the inhibition of PDGF receptor (PDGFR) or SHP-2 knockdown. Moreover, activation of c-Myc was involved in the processes of PDGF-B/SHP-2-driven cell proliferation in RMECs. The promoting effects of PDGF-B/SHP-2 on c-Myc expression were mediated by the Erk pathway. : These results indicate that PDGF-B facilitates cell proliferation and angiogenesis, at least in part, the SHP-2/Erk/c-Myc pathway in RMECs, implying new potential treatment candidates for retinal microangiopathy.
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http://dx.doi.org/10.3389/fphys.2020.555006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719712PMC
November 2020

OCTA evaluation of treatment-naïve flat irregular PED (FIPED)-associated CNV in chronic central serous chorioretinopathy before and after half-dose PDT.

Eye (Lond) 2020 Dec 15. Epub 2020 Dec 15.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

Background: To qualitatively and quantitatively evaluate the features of treatment-naïve flat irregular pigment epithelial detachment (FIPED)-associated choroidal neovascularization (CNV) in chronic central serous chorioretinopathy (CSC) using swept-source (SS) optical coherence tomography angiography (OCTA) before and after half-dose photodynamic therapy (PDT).

Methods: Retrospective case series. The multimodal imaging data of the eyes with FIPED-associated CNV in chronic CSC were reviewed. The features of FIPED-associated CNVs were evaluated by SS-OCTA.

Results: Records of twenty-one patients (21 eyes) were reviewed. The mean age was 56.62 ± 6.87 years. After half-dose PDT, all patients have improved best spectacle-corrected visual acuity from 0.49 at baseline to 0.25 at 6-month visit, and subfoveal choroidal thickness decreased with subretinal fluids absorbed. By OCTA, the features of CNV at baseline included long filamentous linear vessels (21/21), branching into other large mature vessels with rare anastomoses (21/21); and/or a 'dead tree' appearance at the vessel's termini (20/21); and no perilesional hypointense halo (21/21). Compared to those at baseline, the mean vessel density of CNV showed no significant change at 1-,3-,6-month follow-up, while the mean area of CNV was significantly larger at the 6-month follow-up (p = 0.013).

Conclusions: OCT angiography allows to qualitatively and quantitatively evaluate CNV in chronic CSC. The features of FIPED-associated CNV on OCTA illustrated its quiescent characteristic and further guided therapy. Half-dose PDT showed favorable effects on chronic CSC complicated with FIPED-associated CNV.
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http://dx.doi.org/10.1038/s41433-020-01345-5DOI Listing
December 2020

A case report of ultrasonographic findings in bilateral diffuse Uveal melanocytic proliferation.

BMC Ophthalmol 2020 Dec 4;20(1):476. Epub 2020 Dec 4.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, 200031, China.

Background: To report undescribed characteristics of patients with bilateral diffuse uveal melanocytic proliferation (BDUMP) on ultrasound biomicroscopy (UBM) and high-frequency B-scan ultrasonography.

Case Presentation: Two of four participants presented with worsening bilateral vision after previously diagnosed primary pulmonary or ovarian carcinoma. The other two patients were diagnosed with lung carcinoma after presentation with BDUMP. All patients had ciliary body nevi-like lesion in combination with iris or ciliary body cysts, and uveal thickening on UBM. Focally elevated choroidal nevi-like lesion and exudative retinal detachment with choroidal thickening were detected with B-scan ultrasonography.

Conclusions: Our case series demonstrates the uveal characteristics of patients with BDUMP based on high-frequency B-scan ultrasonography and UBM. Ultrasonographic findings are crucial in the diagnosis of BDUMP because it is occult in nature.
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http://dx.doi.org/10.1186/s12886-020-01720-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716585PMC
December 2020

Acute cardiac injury in adult hospitalized COVID-19 patients in Zhuhai, China.

Cardiovasc Diagn Ther 2020 Oct;10(5):1303-1312

Department of Cardiovascular Medicine, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

Background: Coronavirus disease 2019 (COVID-19) has already became a public health emergency of international concern. COVID-19 related cardiac injury remains largely unclear.

Methods: We retrospectively analyzed demographic, clinical, laboratory and cardiovascular imaging data of all consecutively admitted adult COVID-19 patients in Zhuhai, China from January 17th, 2020 to February 18th, 2020.

Results: A total of 93 patients were included in the study. Acute cardiac injury was found in 9 (9.7%) COVID-19 patients with median level of hypersensitive cardiac troponin I (hs-cTnI) to be 0.085 µg/L (IQR 0.027-0.560 µg/L). Compared with patients without cardiac injury, the median age of patients with cardiac injury was significantly older (65.0 44.0, P<0.05), hypertension was significantly more common (44.4% 14.3%, P<0.05), and the proportion of severe-critical cases were greater (77.8% 17.9%, P<0.05). Patients with cardiac injury were more likely have elevation of N-terminal proBNP (NT-proBNP) in comparison (66.7% 10.0%, P<0.05). There was no significant difference in echocardiographic parameters between patients with and without cardiac injury. Multivariable logistic regression analysis indicated that older age (OR: 1.093, 95% CI: 1.011-1.182) and increased NT-proBNP (OR: 10.979, 95% CI: 2.024-59.555) were independent risk factors for cardiac injury. Cardiac magnetic resonance (CMR) imaging performed on three patients at around one month after they underwent significant hs-cTnI elevation showed that they had underlying cardiovascular comorbidities.

Conclusions: Acute cardiac injury was seen in the minority of hospitalized COVID-19 patients in Zhuhai, China. Older age and increased NT-proBNP were associated with acute cardiac injury.

Registration Number: ChiCTR2000030952.
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http://dx.doi.org/10.21037/cdt-20-607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666934PMC
October 2020

Susceptible user search for defending opinion manipulation.

Future Gener Comput Syst 2021 Feb 5;115:531-541. Epub 2020 Oct 5.

Department of Computer Science and Software Engineering, Miami University, Oxford, OH, 45056, USA.

The development of cyberspace offers unprecedentedly convenient access to online communication, thus inducing malicious individuals to subtly manipulate user opinions for benefits. Such malicious manipulations usually target those influential and susceptible users to mislead and control public opinion, posing a bunch of threats to public security. Therefore, an intelligent and efficient searching strategy for targeted users is one prominent and critical approach to defend malicious manipulations. However, the major body of current studies either provide solutions under ideal scenarios or offer inefficient solutions without guaranteed performance. As a result, this work adopts the combination of unsupervised learning and heuristic search to discover susceptible and key users for defense. We first propose a greedy algorithm fully considering the susceptibilities of different users, then adopt unsupervised learning and utilize the community property to design an accelerated algorithm. Moreover, the approximation guarantees of both greedy and community-based algorithms are systematically analyzed for some practical circumstances. Extensive experiments on real-world datasets demonstrate that our algorithms significantly outperform the state-of-the-art algorithm.
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http://dx.doi.org/10.1016/j.future.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534853PMC
February 2021

Two dimensional CdS/ZnO type-II heterostructure used for photocatalytic water-splitting.

Nanotechnology 2020 Nov;31(48):485701

School of Electronic Information Engineering, Key Laboratory of Extraordinary Bond Engineering and Advanced Materials Technology of Chongqing, Yangtze Normal University, Chongqing 408100, People's Republic of China. Those authors contributed equally to this work.

The electronic structures of two dimensional (2D) CdS/ZnO heterostructure (CdZnHT) consisting of CdS singlelayer (SL) and ZnO SL are explored based on hybrid density functional calculation. The negative interface formation energies suggest the formation of CdZnHT is exothermic. The bandgap of CdZnHT is favorable for absorbing visible light, and the decent band edge position makes it thermodynamically feasible for spontaneous generation of oxygen and hydrogen. The formed electric field across the interface induced by charge transfer will reduce photogenerated carrier recombination and promote carrier migration. Particularly, CdZnHT is a type-II heterostructure. Oxygen generation takes place at ZnO layer and hydrogen production occurs at CdS layer, which will also promote the effective separation and migration of phogogenerated carriers and enhance photocatalytic performance. These findings suggest that 2D CdZnHTs are possible candidates as water-splitting photocatalysts.
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http://dx.doi.org/10.1088/1361-6528/abb15aDOI Listing
November 2020

Baicalin down-regulating hepatitis B virus transcription depends on the liver-specific HNF4α-HNF1α axis.

Toxicol Appl Pharmacol 2020 09 17;403:115131. Epub 2020 Jul 17.

Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai 201203, PR China. Electronic address:

Baicalin (BA) inhibits hepatitis B virus (HBV) RNAs production and reduces levels of the related hepatocyte nuclear factors (HNFs), although the underlying mechanism is unclear. In this study, we investigated the specific pathway by which BA regulates HBV transcription through the HBV-related HNFs. Following transfection of HepG2 cells with pHBV1.2, we observed that BA inhibited the production of HBV RNAs and viral proteins in a time- and dose-dependent manner. These effects were consistent with the downregulation of HNF1α, which was abolished by HNF1α-shRNA. The shRNA of HNF4α, the upstream gene of HNF1α, also remarkedly reduced HNF1α expression and impaired the anti-HBV efficacy of BA, indicating that this function of BA depended on HNF4α/HNF1α axis. Furthermore, chromatin immunoprecipitation assay showed that BA significantly reduced HNF4α-HNF1α transactivation activity. The similar effects of BA were observed in entecavir (ETV)-resistant HBV transfected HepG2 cells. Thus, we proposed a mechanism for the anti-HBV activity of BA in an HNF4α-HNF1α-dependent manner, which impaired HNF4α and HNF1α transactivation, and effectively inhibited HBV transcription and viral replication.
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http://dx.doi.org/10.1016/j.taap.2020.115131DOI Listing
September 2020

Optical Coherence Tomography Angiography of Inflammatory Choroidal Neovascularization Early Response after Anti-VEGF Treatment.

Curr Eye Res 2020 12 22;45(12):1556-1562. Epub 2020 May 22.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University , Shanghai, China.

: To describe the optical coherence tomography angiography (OCTA) features of active inflammatory choroidal neovascularization (CNV) and characterize the early responses of anti-vascular endothelial growth factor (VEGF) treatment for inflammatory CNV. : OCT angiography images of inflammatory CNV were acquired and analyzed using the RTVue XR Avanti with AngioVue at baseline as well as fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT). OCTA scans were sequentially obtained 1 day before treatment, 1 day, 7 days, 14 days, and 30 days after anti-VEGF injection. Changes of the selected area and flow area of CNV on OCTA were measured along with those of the central macular thickness (CMT) on corresponding SD-OCT. : 19 eyes of 18 uveitic patients (mean age: 36.83 ± 10.05 years) presenting with active CNV were included in the prospective case series. The OCTA showed a 100% sensitivity for inflammatory CNV detection in 23 of 23 CNV lesions, revealing prevailing two neovascular phenotypes: vascular loops and intertwined nets. After anti-VEGF injection, as early as the 1-day follow-up, the mean selected area and the mean flow area of inflammatory CNV on OCTA were significantly reduced (both < .05) while the average CMT on SD-OCT did not change until the 7-day follow-up. OCTA was able to detect the reincrease of capillary density and vessel size predominantly in the second phenotype 14-30 days after anti-VEGF injection. : OCTA not only allows for noninvasive detection of inflammatory CNV with a high sensitivity but also facilitates its sequential observation after anti-VEGF treatment. The treatment outcomes are observable at day 1 post treatment. OCTA may be a useful tool for diagnosing inflammatory CNV and evaluating the early response to anti-VEGF treatment.
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http://dx.doi.org/10.1080/02713683.2020.1767790DOI Listing
December 2020

Physiological effects of the combined stresses of freezing-thawing, acid precipitation and deicing salt on alfalfa seedlings.

BMC Plant Biol 2020 May 11;20(1):204. Epub 2020 May 11.

Laboratory of Groundwater Resources and Environment of the Ministry of Education, College of New Energy and Environment, Jilin University, Changchun, 130012, China.

Background: Frequent freeze-thaw phenomena, together with widely used deicing salt and intense acid precipitation, often occur in northeastern China, causing damage to various aspects of plants, such as the permeability of biological membranes, osmotic adjustment, and photosystems. Aiming to explore the resistance of alfalfa to freezing-thawing (F), acid precipitation (A) and deicing salt (D), this study used Medicago sativa cv. Dongmu-70 as the experimental material, and the contents of malondialdehyde (MDA), soluble protein, soluble sugars, proline and chlorophyll were evaluated.

Results: As the temperature decreased, the MDA content in the seedlings of the group under combined stress (A-D-F) increased and was significantly higher than that of group F (by 69.48 ~ 136.40%). Compared with those in the control (CK) group, osmotic substances such as soluble sugars and proline in the treatment groups were higher, while the soluble protein content was lower. The chlorophyll contents in the seedlings of the treatment groups were lower than those of the CK group; however, the chlorophyll content displayed a non-significant change during the free-thaw cycle.

Conclusion: Injury to the permeability of the biological membranes and photosystems of alfalfa results from stress. Moreover, alfalfa maintains osmotic balance by adaptively increasing the potential of osmotic substances such as soluble sugars and proline. Furthermore, the influence of stress from freezing-thawing and deicing salt is highly substantial, but the combined stresses of acid precipitation with the two factors mentioned above had little effect on the plants.
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http://dx.doi.org/10.1186/s12870-020-02413-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216480PMC
May 2020

Quantitative analysis of retinal and choriocapillary vascular density of multiple evanescent white dot syndrome by optical coherence tomography angiography.

Graefes Arch Clin Exp Ophthalmol 2020 Aug 29;258(8):1697-1707. Epub 2020 Apr 29.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

Purpose: To describe optical coherence tomography angiography (OCTA) and other multimodal imaging features of multiple evanescent white dot syndrome (MEWDS).

Methods: The retinal and choriocapillary vascular density of MEWDS patients were measured by OCTA (OptoVue Inc.) in the acute and recovery phases. And other multimodal imaging data were also retrospectively reviewed.

Results: Sixteen patients with a mean age of 26.5 ± 6.99 years were included. Three patients were complicated with choroidal neovascularization (CNV). The mean baseline logMAR BCVA of the affected eyes was 0.52 ± 0.36 (Snellen equivalent 20/50). OCTA revealed significant reductions in vascular densities of deep capillary plexus (45.72 ± 3.70%, P = 0.0007), and choriocapillaris (46.08 ± 3.22%, P < 0.0001) of the affected eyes compared with the contralateral eyes (50.23 ± 4.06% and 52.28 ± 4.19%, respectively) in the acute phase. During the recovery phases, vascular densities of deep capillary plexus (49.50 ± 3.15%, P < 0.0001) and choriocapillaris (53.67 ± 2.58%, P < 0.0001) increased significantly in the affected eyes while those of the superficial capillary plexus remained stable. SD-OCT revealed an increase of the subfoveal choroidal thickness and disruption of the outer retinal layer, including ellipsoid zone discontinuities and the accumulation of hyperreflective material, corresponding to the hypofluorescent spots and dots on ICGA, respectively. BCVA increased to normal values after recovery, together with restoration of the structural morphology and choroidal thickness on SD-OCT, except in eyes with CNV.

Conclusion: The inner retinal layer and choroid can be secondarily transiently compromised in MEWDS. MEWDS complicated with CNV is associated with worse visual outcomes.
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http://dx.doi.org/10.1007/s00417-020-04687-8DOI Listing
August 2020

CLINICAL FEATURES OF FLAT IRREGULAR PIGMENT EPITHELIAL DETACHMENT ASSOCIATED WITH CHOROIDAL NEOVASCULARIZATION IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

Retina 2021 Jan;41(1):199-207

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China; and.

Purpose: To describe the multimodal imaging characteristics of flat irregular pigment epithelial detachment (FIPED) in patients with chronic central serous chorioretinopathy and determine the risk factors for vascularized FIPED and to explore the activity of vascularized FIPED before and after half-dose photodynamic therapy.

Methods: Multimodal imaging data of 185 eyes of 155 consecutive patients with chronic central serous chorioretinopathy included spectral domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography. Optical coherence tomography angiography was available for 56 eyes. Flat irregular PED was classified into two types based on indocyanine green angiography or optical coherence tomography angiography findings: avascular FIPED and vascularized FIPED.

Results: The avascular FIPED and vascularized FIPED were detected in 127 (68.6%) and 42 (22.7%) eyes, respectively. Age (P = 0.001), visual acuity (P = 0.048), subfoveal choroidal thickness (P = 0.032), height (P < 0.001) and width (P < 0.001) of FIPED, choriocapillary thickness (P = 0.015), and maximum vessel diameter (P = 0.009) beneath the FIPED were significantly different between avascular and vascularized FIPEDs. Old age was an independent risk factor for vascularized FIPED. On optical coherence tomography angiography, all vascularized FIPEDs manifested the pattern of mature choroidal neovascularization (CNV). After half-dose photodynamic therapy, vascularized FIPED remained stable without the reaccumulation of subretinal fluid at the last follow-up.

Conclusion: In chronic central serous chorioretinopathy, vascularized FIPED was closely associated with Type I CNV. Old age was an independent risk factor for vascularized FIPED. Vascularized FIPED is suggested as "quiescent" CNV, and half-dose photodynamic therapy may be recommended as the first-line therapy in chronic central serous chorioretinopathy complicated with quiescent CNV, except when the activity of CNV becomes evident.
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http://dx.doi.org/10.1097/IAE.0000000000002791DOI Listing
January 2021

MicroRNA-29b-3p inhibits cell proliferation and angiogenesis by targeting VEGFA and PDGFB in retinal microvascular endothelial cells.

Mol Vis 2020 24;26:64-75. Epub 2020 Feb 24.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

Purpose: Excessive angiogenesis, also known as neovascularization, has considerable pathophysiologic roles in several retinal diseases, including retinopathy of prematurity, diabetic retinopathy, and exudative age-related macular degeneration. Accumulated evidence has revealed that miRNAs play important roles in endothelial cell dysfunction and angiogenesis. However, the role of microRNA-29b-3p (miR-29b-3p) in retinal angiogenesis is still unclear. Therefore, we investigated whether and how miR-29b-3p affects the function of retinal microvascular endothelial cells (RMECs).

Methods: The overexpression and inhibition of miR-29b-3p were achieved by transfecting rat RMECs with an miR-29b-3p mimic and inhibitor, respectively. The proliferation, migration, and angiogenesis of RMECs were evaluated using a Cell Counting Kit-8 assay, Ki67 staining, western blotting (of proliferating cell nuclear antigen, cyclin A2, cyclin D1, and cyclin E1), wound healing test, and tube formation assay. The expression levels of vascular endothelial growth factor A (VEGFA) and platelet-derived growth factor B (PDGFB) were examined with quantitative real-time PCR and western blotting, respectively.

Results: Overexpression of miR-29b-3p statistically significantly inhibited the function of RMECs in cell proliferation and angiogenesis, while inhibition of miR-29b-3p increased the proliferative and angiogenic activities of RMECs. Moreover, VEGFA and PDGFB, as the targets of miR-29b-3p, were statistically significantly downregulated by the miR-29b mimic, whereas the miR-29b-3p inhibitor had the opposite effects.

Conclusions: miR-29b-3p negatively regulates RMEC proliferation and angiogenesis, at least partly by targeting VEGFA and PDGFB. These data may provide a potential therapeutic strategy for treating ocular neovascular diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043642PMC
February 2021

Effect of alkaline phosphatase on sepsis-associated acute kidney injury patients: A systematic review and meta-analysis.

Medicine (Baltimore) 2020 Jan;99(4):e18788

Department of Critical Care Medicine, Chinese Medicine Hospital of Hainan Province, Haikou, China.

Background: This systematic review and meta-analysis were performed to evaluate kidney function in patients with sepsis-associated acute kidney injury (SA-AKI) on alkaline phosphatase (AP) therapy.

Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched electronically from inception until May 4, 2019 and randomized controlled studies assessing AP treatment in patients with SA-AKI were included. Pool analyses with fixed effects or random effects models calculated pooled mean, standard deviation, and odds ratio (OR) with 95% confidence interval (CI).

Results: Four randomized controlled trials involving AP therapy for 392 patients with SA-AKI were included. AP had a positive effect on endogenous creatinine clearance (ECC) in patients with SA-AKI at day 14 (random effects: mean difference = 10.56, 95% CI = 2.27-18.84, P = .01) and day 28 (random effects: mean difference = 14.30, 95% CI = 6.27-22.33, P = .0005). All-cause mortality at day 28 (fixed effects: OR = 0.62, 95% CI = 0.40-0.97, P = .04) and day 90 (fixed effects: OR = 0.61, 95% CI = 0.39-0.96, P = .03) improved. Plasma creatinine level (fixed effects: mean difference = -76.83, 95% CI = -146.92 to -6.74, P = .03) and biomarkers level (random effects: mean difference = -6.57, 95% CI = -10.74 to -2.40, P < .00001) also improved in the therapy group compared with placebo.

Conclusion: In patients with SA-AKI, AP showed a relatively late protective effect by improving ECC at days 7, 14, and 28. ECC level improved when patients received AP dose of 0.212 mg/kg. Mortality improved at days 28 and 90, respectively, when patients received AP dose of 1.6 mg/kg. Levels of overall AKI biomarkers were improved in short term.
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http://dx.doi.org/10.1097/MD.0000000000018788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004577PMC
January 2020

Lentivirus vector-mediated knockdown of Sox9 shows neuroprotective effects on light damage in rat retinas.

Mol Vis 2019 14;25:703-713. Epub 2019 Nov 14.

Department of Ophthalmology and Vision Sciences, Eye and ENT Hospital, Fudan University, Shanghai, China.

Purpose: To investigate whether reduced Sox9 function exerts neuroprotection in light-induced retinal damage in rats and to explore the potential mechanism behind it.

Methods: Retinal light damage was used as a model for retinal degeneration. Two weeks before light damage in adult Sprague Dawley (SD) rats, the Sox9-shRNA lentiviral vector was intravitreally injected. On days 3, 7, and 14, retinal function was assessed using electroretinography (ERG), and the thickness of the outer nuclear layer (ONL) was measured in hematoxylin and eosin (HE) stained sections. The protein levels of glial fibrillary acidic protein (GFAP), vimentin, nestin, and chondroitin sulfate proteoglycans (Cspgs), which are related to gliosis and extracellular matrix (ECM) remodeling, were observed using western blot analysis. The expression of GFAP was further evaluated by immunohistochemistry.

Results: On days 3, 7, and 14 after light damage, the thickness of the ONL and the amplitudes of the ERG waves were significantly better preserved in the Sox9-shRNA group when compared with the control group. The protein levels of GFAP, vimentin, nestin, and Cspgs were significantly downregulated in the Sox9-shRNA group. Furthermore, the staining intensity and the spatial distribution of GFAP in the retinas were also obviously attenuated at every studied time point.

Conclusions: Intravitreal injection of the Sox9-shRNA lentiviral vector preserved rat retinal morphology and function after light damage and downregulated GFAP, vimentin, nestin, and Cspgs, which are related to Müller cell gliosis and ECM remodeling. The results indicate that Sox9 might be a potential therapeutic target for retinal degenerative diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857779PMC
June 2020

Physiological response in the leaf and stolon of white clover under acid precipitation and freeze-thaw stress.

Funct Plant Biol 2019 01;47(1):50-57

College of Animal Science, Jilin University, Changchun 130023, China.

Freeze-thaw (FT) in northern China is a common event in spring and autumn, and the release of sulfur dioxide from coal-burning in winter is apt to trigger acid precipitation. Both these stresses can aggravate the wintering ability of white clover (Trifolium repens L.). Acid precipitation and FT simulation experiments were carried out in the field and an indoor alternation refrigerator, respectively. The contents of soluble protein, soluble sugar, malondialdehyde (MDA), proline and antioxidant activity were tested under acid precipitation and FT stress. The results showed that under acid precipitation stress, the content of MDA, peroxidase and superoxide dismutase increased in both leaves and stolons, whereas soluble protein and soluble sugar content declined compared with the control groups. During the freezing period, the content of antioxidant enzyme activity, soluble protein and proline increased at first and then dropped, whereas MDA and soluble sugar content both increased. As a conclusion, the stolon of white clover is more sensitive than the leaf to short-term stress, either as the single FT stress or the combined stress of FT and acid precipitation, suggesting that maintaining more leaves can contribute to the resistance of white clover to these stresses.
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http://dx.doi.org/10.1071/FP19072DOI Listing
January 2019

Myocardial infarction and ''dye brushes'' sign from an atrial myxoma.

Int J Cardiovasc Imaging 2020 Jan 20;36(1):1-2. Epub 2019 Aug 20.

Department of Cardiology, Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52 Meihua East Rd., Zhuhai, 519000, People's Republic of China.

We report a case of a 25-year-old man present with acute ST-segment elevation myocardial infarction caused by a large left atrial myxoma. Nutrient vessels of the atrial mass showed a unique ''dye brushes'' sign on coronary angiography.
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http://dx.doi.org/10.1007/s10554-019-01685-8DOI Listing
January 2020

Bilateral methamphetamine-induced ischemic retinopathy.

Am J Ophthalmol Case Rep 2019 Sep 22;15:100473. Epub 2019 May 22.

Dept. of Ophthalmology, Eye and ENT Hospital of Fudan University, NHC Key Laboratory of Myopia (Fudan University), Shanghai, China.

Purpose: To describe the multimodal imaging and treatment of a 37-year-old male presenting with bilateral ischemic retinopathy induced by methamphetamine abuse.

Observations: A 37-year-old male presented with progressively deteriorating vision and was found to have branch retinal artery occlusion and central retinal vein occlusion in both eyes along with secondary vitreous hemorrhage in the left eye following seven years of intermittent intranasal methamphetamine abuse. Fundus fluorescein angiography and optical coherence tomography angiography revealed large areas of non-perfusion in the peripheral retina along with peripapillary neovascularization. Systemic evaluation revealed ischemic foci scattered in the deep brain on magnetic resonance angiography scanning. Based on the retinal findings, the patient was diagnosed with methamphetamine-induced ischemic retinopathy. He received panretinal photocoagulation, which improved the vision in the right eye and vitreous hemorrhage in the left eye. The vision in the left eye remained stable.

Conclusions And Importance: This case highlights that intranasal methamphetamine abuse is associated with bilateral simultaneous central retinal vein occlusion and branch retinal artery occlusion. To our knowledge, extensive bilateral ischemic retinopathy has not been documented previously with newer modalities. In addition, PRP may be considered for the treatment of ischemic retinopathy induced by methamphetamine abuse.
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http://dx.doi.org/10.1016/j.ajoc.2019.100473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551529PMC
September 2019

Comparative Analysis of Three-Dimensional Heads-Up Vitrectomy and Traditional Microscopic Vitrectomy for Vitreoretinal Diseases.

Curr Eye Res 2019 10 15;44(10):1080-1086. Epub 2019 May 15.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University , Shanghai , China.

: To investigate the visual outcomes and occurrences of perioperative complications after three-dimensional (3D) heads-up vitrectomy compared with traditional microscopic (TM) surgery for vitreoretinal diseases. : A retrospective case series comparison of 3D and TM vitrectomy performed on 124 and 202 eyes with a minimum follow-up of 6 months, respectively, by the same surgeon. Changes in visual acuity, primary anatomical success, operation time, and perioperative complications were evaluated. : There were no significant differences in age, gender, axial length, ocular and surgical history, surgical indication, and visual acuity between the two groups at baseline. Both groups showed a significant improvement in visual acuity at the final visit (both < .05) and experienced comparable anatomical recoveries regarding epiretinal membranes, vitreous hemorrhage, macular holes, retinal detachment, and pathological myopic foveoschisis. The mean overall operation time was not significantly longer in the 3D group (31.0 ± 17.6 min) than the TM (31.0 ± 15.9 min) group ( = .994). The incidence rates of postoperative complications during the follow-up were similar between the 3D (30.6%) and TM groups (30.2%) ( = .932). : The 3D and TM vitrectomy surgeries yielded comparable visual and anatomical outcomes for treatment of vitreoretinal diseases without a significant difference in the rate of complications. The 3D heads-up vitrectomy may be considered the treatment of choice for patients with various vitreoretinal diseases.
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http://dx.doi.org/10.1080/02713683.2019.1612443DOI Listing
October 2019

Light-Induced Lipocalin 2 Facilitates Cellular Apoptosis by Positively Regulating Reactive Oxygen Species/Bim Signaling in Retinal Degeneration.

Invest Ophthalmol Vis Sci 2018 12;59(15):6014-6025

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

Purpose: Lipocalin 2 (LCN2) is reported to be one of the key regulators of cell survival and death; however, its effect on retinal degeneration is unclear. Therefore, we aimed to investigate the role of LCN2 and its underlying mechanisms in light-induced retinal degeneration.

Methods: A recombinant lentivirus expressing a short hairpin RNA targeting LCN2 mRNA and a recombinant lentivirus overexpressing LCN2 were used to downregulate and upregulate retinal LCN2, respectively. Seven days after intravitreal injection of the lentiviruses, rats were exposed to blue light (2500 lux) for 24 hours. Retinal function and morphology were evaluated with ERG and hematoxylin-eosin staining, respectively. TUNEL staining was used to detect apoptotic cells. The levels of reactive oxygen species (ROS) were evaluated with dihydroethidium labeling. Western blotting and real-time PCR were used to examine protein and mRNA expression levels, respectively.

Results: Retinal LCN2 expression was significantly upregulated after light exposure. Light exposure reduced the amplitudes of a- and b-waves on the ERG and the thickness of the outer nuclear layer and promoted photoreceptor apoptosis. These phenomena were clearly attenuated by LCN2 knockdown, whereas LCN2 overexpression had the opposite effects. The overexpression of LCN2 facilitated photoreceptor apoptosis by increasing ROS generation and Bim expression. On the opposite, LCN2 knockdown mitigated the generation of light-exposure-induced ROS and the activation of the Bim-mediated mitochondrial apoptotic pathway.

Conclusions: Light-induced LCN2 is a proapoptotic factor in the retina, and LCN2 knockdown protects photoreceptors from apoptosis by inhibiting ROS production and Bim expression. LCN2 is a potential therapeutic target for light-induced retinal degeneration.
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http://dx.doi.org/10.1167/iovs.18-25213DOI Listing
December 2018

Synthesized glucocorticoid-induced leucine zipper peptide inhibits photoreceptor apoptosis and protects retinal function in light-induced retinal degeneration model.

Clin Exp Ophthalmol 2019 07 2;47(5):646-657. Epub 2019 Jan 2.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

Background: This study aimed to investigate the neuroprotective function of a synthesized glucocorticoid-induced leucine zipper peptide (GILZ-p) in a light-induced retinal degeneration model.

Methods: The GILZ peptide was synthesized and injected intravitreally into Sprague Dawley rats. Retinal injury was then induced in the rats by exposing their eyes to constant white light (5000 lux) for 24 h. The activation of retinal caspases-9/3 and the release of cytochrome c from the mitochondria to the cytosol were measured at 1, 3, 5 and 7 d after light injury. Photoreceptor apoptosis was evaluated with terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) staining at 3 d after injury. Haematoxylin and eosin staining and electroretinography were used to observe the changes in the retinal morphology and function, respectively, at 7 and 14 d after light injury.

Results: The intravitreally injected synthesized GILZ-p successfully penetrated to the retina and significantly inhibited the activation of retinal caspase-3 and caspase-9 at 1, 3, 5 and 7 d after light injury, and reduced the number of TUNEL-positive photoreceptors at 3 d after light injury. GILZ-p pre-treatment also alleviated cytochrome c release and rescued mitochondria-mediated apoptosis after injury. Simultaneously, GILZ-p pre-treatment also mitigated the light-induced thinning of the outer nuclear layer and the loss of retinal function at 7 and 14 d after light injury, respectively.

Conclusions: The synthesized GILZ-p prevented light-induced photoreceptor apoptosis and protected retinal function from degeneration, and is therefore a potential therapeutic option for degenerative retinal diseases.
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http://dx.doi.org/10.1111/ceo.13452DOI Listing
July 2019

NOVEL BEST1 MUTATIONS DETECTED BY NEXT-GENERATION SEQUENCING IN A CHINESE POPULATION WITH VITELLIFORM MACULAR DYSTROPHY.

Retina 2019 Aug;39(8):1613-1622

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

Purpose: To characterize novel BEST1 mutations and the phenotype-genotype correlations in vitelliform macular dystrophy in a Chinese population.

Methods: Seventeen individuals affected by vitelliform macular dystrophy underwent detailed ophthalmic examinations, including a best-corrected visual acuity test, slit-lamp biomicroscopy, fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and optical coherence tomography angiography. Next-generation sequencing was used to screen 790 genes frequently involved in common inherited nonsyndromic eye diseases in all participants. Sanger sequencing was used to identify possible disease-causing variants.

Results: The mean ± SD age of the patients was 44.20 ± 15.09 (range: 16-69) years. Seven novel BEST1 mutations were identified: six heterozygous missense (p.Thr307Asn, p.Ile295The, p.Leu75Pro, p.Thr2Ser, p.Ser79Tyr, and p.Val81Leu) and one frameshift (p.Glu115GlufsX120) mutation. Choroidal neovascularization was detected in two probands. One individual presented with subfoveal focal choroidal excavation. Arden ratios obtained by electrooculography were less than the 1.5 cutoff value in 7 patients. No mutations were identified in 2 patients, one of whom had a fundus appearance typical of vitelliform macular dystrophy and a decreased Arden ratio (1.2/1.2).

Conclusion: Patients with the same heterozygous BEST1 mutations exhibited varying phenotypes. Our results have expanded the BEST1 mutation spectrum in a Chinese population with vitelliform macular dystrophy.
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http://dx.doi.org/10.1097/IAE.0000000000002183DOI Listing
August 2019

A Synthesized Glucocorticoid- Induced Leucine Zipper Peptide Inhibits Retinal Müller Cell Gliosis.

Front Pharmacol 2018 6;9:331. Epub 2018 Apr 6.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

The anti-inflammatory activities of protein glucocorticoid-induced leucine zipper (GILZ) have been demonstrated and . Here, we examined the potential effect of a synthetic peptide derived from the leucine zipper motif and proline-rich region of GILZ on suppressing inflammatory responses in primary cultured rat Müller cells. Peptides were selected from amino acids 98-134 of the GILZ protein (GILZ-p). Solid-phase peptide synthesis was used to generate the cell-penetrating peptide TAT, which was bound to the amino terminus of GILZ-p. Primary cultured retinal Müller cells were stimulated with lipopolysaccharide (LPS) alone or in combination with different concentrations of GILZ-p, and the interaction of GILZ-p with nuclear factor (NF)-κB p65 in Müller cells was investigated by western blotting, immunoprecipitation, and immunofluorescence. The expression of the Müller cell gliosis marker glial fibrillary acidic protein (GFAP), functional protein aquaporin (AQP)-4, and the inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF) α, intercellular adhesion molecule (ICAM)-1, and monocyte chemoattractant protein (MCP)-1 was measured by Western Blotting. The concentration of those cytokines in culture medium was measured by using Enzyme-Linked Immunosorbent Assay. The synthesized GILZ-p, which was water-soluble, entered cells and bound with NF-κB p65, inhibiting p65 nuclear translocation. GILZ-p inhibited the LPS-induced expression of GFAP, IL-1β, TNFα, ICAM-1, and MCP-1 in Müller cells and prevented the LPS-induced downregulation of AQP4. These results indicate that GILZ-p interacted with NF-κB p65 and suppressed p65 nuclear translocation, thereby inhibiting inflammatory cytokine release and Müller cell gliosis.
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http://dx.doi.org/10.3389/fphar.2018.00331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897418PMC
April 2018

Lipocalin 2 Suppresses Ocular Inflammation by Inhibiting the Activation of NF-κβ Pathway in Endotoxin-Induced Uveitis.

Cell Physiol Biochem 2018 23;46(1):375-388. Epub 2018 Mar 23.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

Background/aims: Lipocalin 2 (LCN2), an important mediator of a variety of cellular processes, is involved in regulating the inflammatory response, but its roles in different inflammatory diseases are controversial. Because the role of LCN2 in ocular inflammation has been unclear until now, we explored the function of LCN2 in lipopolysaccharide (LPS)-induced ocular inflammation in vivo and in vitro.

Methods: Endotoxin-induced uveitis (EIU) was induced in male Sprague Dawley rats by the intravitreal injection of LPS. The expression and location of LCN2 in the retina were detected with western blotting and immunohistochemistry, respectively. We determined the clinical scores for anterior inflammation, quantified the infiltrated inflammatory cells, and measured the pro-inflammatory factors to determine the anti-inflammatory effects of LCN2 in EIU eyes. Cultured primary rat Müller cells were stimulated with LPS and the expression and secretion of LCN2 were measured with real-time PCR, western blotting, and an ELISA. After Müller cells were cotreated with LPS and LCN2 or PBS, the expression and secretion of TNF-α, IL-6, and MCP-1 were examined with realtime PCR, western blotting, and ELISAs. Western blotting and immunofluorescence were used to detect the phosphorylation and cellular distribution of nuclear factor kappaB (NF-κB) subunit p65.

Results: In EIU, the expression of LCN2 was significantly upregulated in the retina, especially in the outer nuclear layer (mainly composed of Müller cells). LPS stimulation of cultured Müller cells also markedly elevated LCN2 expression. Intravitreal injection of LCN2 significantly reduced the clinical scores, inflammatory infiltration, and protein leakage in EIU, which correlated with the reduced levels of proinflammatory factors in the aqueous humor and retina. LCN2 treatment also reduced the expression and secretion of TNF-α, IL-6, and MCP-1 in LPS-stimulated Müller cells. LCN2 inhibited the inflammatory response by inhibiting the phosphorylation and translocation of NF-κB p65.

Conclusions: LCN2 protects against ocular inflammation, at least in part, by negatively regulating the activation of the NF-κB signaling pathway. LCN2 may be a promising anti-inflammatory therapy for ocular diseases, such as uveitis.
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http://dx.doi.org/10.1159/000488472DOI Listing
June 2018

A white membrane beneath the inner limiting membrane of the retina in a 4-year-old child with ultrastructural evidence: a case report.

BMC Ophthalmol 2018 Mar 20;18(1):79. Epub 2018 Mar 20.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

Background: Epiretinal membranes (ERMs), secondary to retinal cell proliferation on the retinal surface, usually affect patients over 50 years of age but occur rarely in children. Here we report the case of a 4-year-old patient with a unilateral sub-inner limiting membrane (sub-ILM) membrane mimicking epiretinal membrane with notable ultrastructural features indicating its possible origin from old sub-ILM hemorrhage.

Case Presentation: A 4-year-old boy was admitted with the complaint of poor vision in his right eye, which had been detected at school vision screening performed 6 months earlier. Fundal examination showed a feather-shaped white membrane in the macula of the right eye, and optical coherence tomography (OCT) revealed a thickened retina with a hyper-reflective band on the retinal nerve fiber layer. We suspected epiretinal membrane in the right eye, and pars plana vitrectomy with membrane peeling was performed to improve the patient's vision. Surprisingly, the membrane was found intraoperatively to be located beneath the intact ILM; it was lifted carefully from the underlying retina as it was strongly adhered to a retinal artery of the superotemporal arcade. Postoperative scanning electron microscopy showed that the membrane consisted of hemosiderin, collagenous fibre and fibrinoid deposits. At follow-up visits, fundal examination and OCT revealed improvement in the retinal structure with disappearance of the hyper-reflective band and reduced retinal thickness. The patient's visual acuity in the right eye was stable at 20/100 at 1 year post operation.

Conclusions: The white membrane presented here was found to lie between the intact ILM and the rest of the retina, adhering firmly to the superotemporal vessel arch. Given the ultrastructural findings of the membrane and the medical history, we speculate that the sub-ILM membrane probably developed secondary to a sub-ILM hemorrhage.
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http://dx.doi.org/10.1186/s12886-018-0748-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859535PMC
March 2018

Predictive multi-imaging biomarkers relevant for visual acuity in idiopathic macular telangiectasis type 1.

BMC Ophthalmol 2018 Mar 5;18(1):69. Epub 2018 Mar 5.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China.

Background: To evaluate the structural changes associated with visual acuity (VA) in patients with idiopathic macular telangiectasia (MT) type 1 using multimodal imaging modalities.

Methods: A retrospective study of 14 patients with MT type 1 and of 10 eyes from 10 healthy individuals as age-matched controls was conducted. The medical records of patients who had undergone colour fundus photography, spectral domain optical coherence tomography (OCT), fluorescein angiography and OCT angiography were reviewed. Central macular thickness (CMT), the areas of macular oedema and ellipsoid zone (EZ) disruption, EZ length, disorganization of the retinal inner layers (DRIL) and external limiting membrane (ELM) disruption, as measured by spectral domain OCT; and vascular density and the foveal avascular zones (FAZ) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as measured by OCT angiography, were assessed in MT type 1 eyes and correlated with VA.

Results: The mean baseline best-corrected VA of MT type 1 eyes was 0.45 ± 0.28. The mean CMT was 385.19 ± 75.21 μm in MT type 1 eyes and 252.43 ± 15.77 μm in contralateral eyes (Z = - 4.113, p < 0.001). The mean vessel density of the DCP was lower in MT type 1 eyes (47.25 ± 4.69%) than in contralateral eyes (53.93 ± 2.94%) and normal eyes (59.37 ± 2.50%) (Z = - 3.492, - 4.099; p < 0.001, < 0.001). The baseline logMAR VA was correlated with CMT (r = 0.682, p = 0.007), SCP density (r = - 0.652, p = 0.012), DCP density (r = - 0.700, p = 0.005), total area of EZ disruption (r = 0.649, p = 0.012); and total lengths of EZ (r = 0.681, p = 0.007), ELM (r = 0.699, p = 0.005) and DRIL (r = 0.707, p = 0.005) disruption in the 1-mm-diameter foveal region in MT type 1 eyes.

Conclusions: Decreased DCP density and the presence of DRIL may be predictive biomarkers of VA in MT type 1. CMT, SCP density, total area of EZ disruption, and lengths of EZ and ELM disruption within the 1-mm-diameter central region were strongly associated with VA.
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http://dx.doi.org/10.1186/s12886-018-0737-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836363PMC
March 2018

Glucocorticoid-Induced Leucine Zipper Protects the Retina From Light-Induced Retinal Degeneration by Inducing Bcl-xL in Rats.

Invest Ophthalmol Vis Sci 2017 07;58(9):3656-3668

Department of Ophthalmology, Eye and Ear Nose Throat Hospital of Fudan University, Shanghai, China 2Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China.

Purpose: The aim of the present study was to investigate the neuroprotective effects of glucocorticoid-induced leucine zipper (GILZ) in a light-induced retinal degeneration model and to explore the underlying mechanisms.

Methods: Intravitreal injection of recombinant GILZ-overexpressing lentivirus (OE-GILZ-rLV) and short hairpin RNA targeting GILZ recombinant lentivirus (shRNA-GILZ-rLV) was performed to up- and downregulate retinal GILZ, respectively. Three days after stable transduction, rats were exposed to continuous bright light (5000 lux) for 2 days. Retinal function was assessed by full-field electroretinography (ERG), and the retinal structure was examined for photoreceptor survival and death in rats kept under a 12-hour light:2-hour dark cycle following light exposure. The expression levels of retinal Bcl-xL, caspase-9, and caspase-3 were examined by Western blotting or real-time PCR at 1, 3, 5, and 7 days after light exposure.

Results: Exposure to bright light downregulated retinal GILZ in parallel with the downregulation of Bcl-xL and the upregulation of active caspase-3. Overexpression of retinal GILZ attenuated the decrease of Bcl-xL and the activation of caspase-9 and caspase-3 at 1, 3, 5, and 7 days after bright light exposure, respectively. GILZ silencing aggravated the downregulation of Bcl-xL induced by bright light exposure. Bright light exposure reduced the amplitude of ERG, increased the number of apoptotic photoreceptor cells, and decreased retinal thickness; and GILZ overexpression could attenuate all these effects.

Conclusions: Overexpression of GILZ by OE-GILZ-rLV transduction protected the retina from light-induced cellular damage by activating antiapoptotic pathways.
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http://dx.doi.org/10.1167/iovs.17-22116DOI Listing
July 2017

EFFECT OF TRIPTOLIDE ON PROLIFERATION AND APOPTOSIS OF ANGIOTENSIN II-INDUCED CARDIAC FIBROBLASTS A PRELIMINARY STUDY.

Afr J Tradit Complement Altern Med 2017 23;14(1):145-154. Epub 2016 Nov 23.

National Heart and Lung Institute, Imperial College London, London SW3 6NP, United Kingdom.

Background: The effect of triptolide (TPL) on cardiac fibroblasts (CFbs) and cardiac fibrosis remain unknown till now. This study was conducted to explore the effects of TPL on proliferation and apoptosis of angiotensin II (Ang II)-induced CFbs.

Materials And Methods: Ang II was used to promote proliferation of CFbs. Two dosages of TPL (10ng/ml and 100ng/ml) were chosen. MTT assay was used to detect cell survival rate . Flow cytometer was performed to analyze apoptosis of CFbs. Hydroxyproline concentration was detected with hydroxyproline assay kit. Quantitative real-time PCR was used to detect the expression of TGF-β1 and Smad3 mRNA.

Results: Ang II promoted CFbs proliferation significantly. Compared to Ang II group, TPL markedly reduced the viability of CFbs and its Hydroxyproline concentration (P<0.05). Besides, TPL can significantly promote apoptosis of CFbs (P<0.05). Furthermore, TPL reduced the expressions of TGF-βΙ and Smad3 mRNA in Ang II-induced CFbs (P<0.05).

Conclusion: TPL can inhibit the proliferation of CFbs in rats by down-regulating TGF-β1/Smad3 signaling pathway. TPL might be a promising therapeutic drug for myocardial fibrosis.
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http://dx.doi.org/10.21010/ajtcam.v14i1.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411865PMC
June 2017

High Hepsin expression predicts poor prognosis in Gastric Cancer.

Sci Rep 2016 11 14;6:36902. Epub 2016 Nov 14.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

Hepsin, a membrane-associated serine protease, is frequently upregulated in epithelial cancers and involved in cancer progression. Our study aims to describe the expression pattern and evaluate the clinical implication of hepsin in gastric cancer patients. The mRNA expression of hepsin was analyzed in 50 gastric cancer and matched non-tumor tissues, which was downregulated in 78% (39/50) of gastric cancer. By searching and analyzing four independent datasets from Oncomine, we obtained the similar results. Furthermore, we evaluated the hepsin expression by IHC in tissue microarray (TMA) containing 220 Gastric Cancer specimens. More importantly, Kaplan-Meier survival and Cox regression analyses were taken to access the prognosis of gastric cancer and predicted that hepsin protein expression was one of the significant and independent prognostic factors for overall survival of Gastric Cancer.
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http://dx.doi.org/10.1038/srep36902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107942PMC
November 2016