Publications by authors named "Fenghua Wang"

192 Publications

Retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGA1.

FASEB J 2021 09;35(9):e21859

Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cyclic nucleotide-gated (CNG) channels are important mediators in the transduction pathways of rod and cone photoreceptors. Native CNG channels are heterotetramers composed of homologous A and B subunits. Biallelic mutations in CNGA1 or CNGB1 genes result in autosomal recessive retinitis pigmentosa (RP). To investigate the pathogenic mechanism of CNG channel-associated retinal degeneration, we developed a mouse model of CNGA1 knock-out using CRISPR/Cas9 technology. We observed progressive retinal thinning and a concomitant functional deficit in vivo as typical phenotypes for RP. Immunofluorescence and TUNEL staining showed progressive degeneration in rods and cones. Moreover, microglial activation and oxidative stress damage occurred in parallel. RNA-sequencing analysis of the retinae suggested down-regulated synaptic transmission and phototransduction as early as 9 days postnatal, possibly inducing later photoreceptor degeneration. In addition, the down-regulated PI3K-AKT-mTOR pathway indicated upregulation of autophagic process, and chaperone-mediated autophagy was further shown to coincide with the time course of photoreceptor death. Taken together, our studies add to a growing body of research exploring the mechanisms of photoreceptor death during RP progression and provide a novel CNGA1 knockout mouse model for potential development of therapies.
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http://dx.doi.org/10.1096/fj.202101004RDOI Listing
September 2021

A versatile pH-responsive peptide based dynamic biointerface for tracking bacteria killing and infection resistance.

Biomater Sci 2021 Sep 5;9(17):5785-5790. Epub 2021 Aug 5.

Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, Zhenjiang, Jiangsu, China.

Herein we reported a versatile dynamic biointerface based on pH-responsive peptide self-assembly and disassembly to capture the bacteria to avoid bacteria further infected tissue around that can release peptides from the surface in a slightly acidic environment to kill the bacteria with the specificity. The exposed biointerface still presented infection resistance.
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http://dx.doi.org/10.1039/d1bm00950hDOI Listing
September 2021

A clinical observational study on the efficacy of subcutaneous etonogestrel implants for adenomyosis in 20 patients.

Gynecol Endocrinol 2021 Aug 23;37(8):735-739. Epub 2021 Jun 23.

Department of Gynecology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China.

To evaluate the efficacy of subcutaneous etonogestrel implants for adenomyosis. We conducted a clinical observational study of 20 patients suffering from adenomyosis treated with subcutaneous etonogestrel implants from August 2015 to July 2017 and followed up for 36 months. We evaluated the efficacy of subcutaneous etonogestrel implants primarily based on the following indicators: the pictorial blood loss assessment chart (PBAC) for menstrual blood volume, changes in bleeding patterns, the visual analog scale (VAS) pain score for dysmenorrhea, uterine volume, serum cancer antigen 125 (CA125) levels, hemoglobin levels and side effects. During the 3 years of follow-up, subcutaneous etonogestrel implants were removed from six patients, among whom one was diagnosed with endometrial cancer, four had an increased menstrual blood volume, and one entered menopause. In total, 14 patients were treated with subcutaneous etonogestrel implants for 3 years. Among these patients, the number of patients with heavy menstrual bleeding and high PBAC and VAS scores and serum CA125 levels was significantly decreased after implantation compared with that before implantation. In the eight patients with anemia, hemoglobin levels increased gradually. However, the uterine volumes did not significantly change. Bleeding patterns were changed but were tolerable. Subcutaneous etonogestrel implants represent a new option for the clinical treatment of adenomyosis for patients who refuse surgery.
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http://dx.doi.org/10.1080/09513590.2021.1922886DOI Listing
August 2021

Modeling Cone/Cone-Rod Dystrophy Pathology by AAV-Mediated Overexpression of Mutant CRX Protein in the Mouse Retina.

Transl Vis Sci Technol 2021 06;10(7):25

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: This study aims to evaluate the pathogenesis of cone/cone-rod dystrophy (CoD/CoRD) caused by a cone-rod homeobox (CRX) mutation, which was identified in a Chinese family, through adeno-associated virus (AAV)-mediated overexpression of mutant CRX protein in the mouse retina.

Methods: Comprehensive ophthalmologic examinations were performed for the pedigree members of a Chinese family with CoD/CoRD. Whole exome sequencing and Sanger sequencing were performed to determine the genetic cause of the disease. Furthermore, AAV vectors were used to construct AAV-CRX-mut-HA, which was transfected into mouse photoreceptor cells to clarify the pathogenesis of the mutant CRX.

Results: Fundus photography and optical coherence tomography images displayed features that were consistent with CoD/CoRD, including macular atrophy and photoreceptor layer thinning. Electroretinogram analysis indicated an obvious decrease in photopic responses or both scotopic and photopic responses in affected individuals. A frameshift variant c.611delC (p.S204fs) in CRX was cosegregated with the disease in this family. AAV-CRX-mut-HA that subretinally injected into the C57BL/6 mice generally transfected the outer nuclear layer, leading to the loss of cone and rod photoreceptor cells, abnormal expression of CRX target genes, and a decrease in electroretinogram responses.

Conclusions: AAV-mediated overexpression of CRX[S204fs] in the mouse retina led to a CoRD-like phenotype and showed the possible pathogenesis of the antimorphic CRX mutation.

Translational Relevance: This study provides a modeling method to evaluate the pathogenesis of CoD/CoRD and other inherited retinal dystrophies caused by distinct gain-of-function mutations.
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http://dx.doi.org/10.1167/tvst.10.7.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237110PMC
June 2021

Efficacy of calcium dobesilate in treating Chinese patients with mild-to-moderate non-proliferative diabetic retinopathy (CALM-DR): protocol for a single-blind, multicentre, 24-armed cluster-randomised, controlled trial.

BMJ Open 2021 05 28;11(5):e045256. Epub 2021 May 28.

Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, Jiangsu, China

Introduction: Calcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy (DR) due to its potential in protecting against retinal vascular damage. However, there is limited evidence exploring its efficacy in combating DR progression. This study is aimed at evaluating whether CaD could prevent DR progression into an advanced stage among Chinese patients with mild-to-moderate non-proliferative DR (NPDR).

Methods And Analysis: This study is a single-blind, multicentre, cluster-randomised, controlled superiority trial. A total of 1272 patients with mild-to-moderate NPDR will be enrolled and randomly assigned at a 1:1 ratio into the control group (conventional treatment group) and the intervention group (conventional treatment plus CaD (500 mg three times per day) for 12 months). Patients will be followed at 1, 3, 6 and 12 months after randomisation and receiving treatments, with the severity of DR assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. The primary endpoint is the progression of DR during follow-up, which is defined as an increase of two or more steps in the ETDRS scale. The secondary endpoints include the concomitant changes in visual acuity, presence, number, location and type of retinal lesions, and retinal blood vessel diameter as well as the arteriovenous ratio at different visits.

Ethics And Dissemination: Each local ethics committee (first Vote: Ethical Review Committees of Zhongda Hospital of Southeast University (2019ZDSYLL132-P01)) has approved the study. The results will be published in high impact peer-reviewed scientific journals aimed at the general reader.

Trial Registration Numbers: NCT04283162.
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http://dx.doi.org/10.1136/bmjopen-2020-045256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166613PMC
May 2021

The food additive fast green FCF inhibits α-synuclein aggregation, disassembles mature fibrils and protects against amyloid-induced neurotoxicity.

Food Funct 2021 Jun;12(12):5465-5477

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education; Tianjin Key Laboratory of Industrial Microbiology; College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, P. R. China.

α-Synuclein (α-syn) aggregates into cytotoxic amyloid fibrils, which are recognized as the defining neuropathological feature of Parkinson's disease (PD). Therefore, inhibiting α-syn fibrillogenesis and disrupting the preformed fibrils are both considered attractive strategies to cure PD. We discovered that a safe food additive, fast green FCF, is capable of inhibiting α-synuclein fibrillogenesis and reducing the related cytotoxicity. Thioflavin T fluorescence assays demonstrated that fast green FCF could inhibit the fibrillogenesis α-synuclein. In the presence of 100 μM fast green FCF, amorphous aggregates were formed and observed by atomic force microscopy. Toxicity assays in cell cultures revealed that fast green FCF significantly reduced the cytotoxicity of α-syn. Molecular dynamics simulations revealed the potential mechanism of the interactions between fast green FCF and α-synuclein. Fast green FCF greatly disrupted the α-synuclein pentamer and reduced the β-sheet content by reducing both nonpolar and polar interactions. Furthermore, two binding sites were identified, named region I (Y39-K45) and region II (H50-Q62). Our data reveal that electrostatic interactions, hydrogen bonds, and π-π interactions synergistically contribute to the binding of fast green FCF to the α-synuclein pentamer. These results indicate that fast green FCF is a candidate prototype for the development of drugs against the aggregation of amyloid fibrils in PD.
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http://dx.doi.org/10.1039/d0fo03301dDOI Listing
June 2021

The feasibility and safety of same-day surgery for diaphragmatic eventration by minithoracotomy in children.

Pediatr Surg Int 2021 Sep 17;37(9):1215-1220. Epub 2021 Apr 17.

Department of Pediatric Thoracic Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China.

Purpose: The diaphragmatic plication procedure by thoracoscopy has gradually become standard treatment for diaphragmatic eventration (DE). However, thoracoscopic diaphragmatic plication is difficult to manipulate and the surgical learning curve is long. This study aimed to demonstrate the feasibility and safety of same-day surgery for DE by minithoracotomy in children.

Methods: From December 2017 to December 2019, we included 22 patients who underwent diaphragmatic plication of DE in the Department of Pediatric Thoracic Surgery at the Guangzhou Women and Children's Medical Center. A total of 10 patients underwent diaphragmatic plication by minithoracotomy and 12 patients underwent thoracoscopic plication. The perioperative condition and postoperative follow-up were evaluated, respectively.

Results: The age, sex, and weight were no different in the minithoracotomy group versus the thoracoscopy group (P > 0.05). The intraoperative time, blood loss volume, and postoperative hospital stay of the minithoracotomy group were significantly less than that of the thoracoscopy group (31.10 ± 4.70 min vs. 72.08 ± 22.8 min; 1.20 ± 0.42 ml vs. 2.58 ± 1.67 ml; and 1.00 ± 0.00 days vs. 6.00 ± 2.95 days, respectively, all P < 0.05). The eventration levels in these two groups were significantly different in the perioperative and postoperative periods as detected by chest X-ray. No chest tubes were inserted and no recurrence of DE occurred in the thoracoscopy group through the postoperative follow-up of at least 6 months.

Conclusion: Same-day surgery by minithoracotomy as a treatment for DE was feasible and safe with less operative time, less blood loss, and low recurrence. Same-day surgery for DE was attributed to a quick recovery. More prospective studies are necessary to further explore the consequences of same-day surgery for DE by minithoracotomy.
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http://dx.doi.org/10.1007/s00383-021-04907-0DOI Listing
September 2021

Peripapillary Vessel Density in Eyes with Rhegmatogenous Retinal Detachment after Pars Plana Vitrectomy.

J Ophthalmol 2021 23;2021:6621820. Epub 2021 Mar 23.

Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: To investigate the vascular density of the optic nerve head (ONH) and macula using optical coherence tomography angiography (OCTA) in patients undergoing vitrectomy for rhegmatogenous retinal detachment (RRD) and to evaluate associations with visual outcomes.

Methods: Patients with RRD, successfully treated with a pars plana vitrectomy (PPV) and a minimum three-month follow-up were included in this study. The vessel density (VD) of the ONH and peripapillary regions, foveal avascular zone (FAZ), foveal flow density (FFD), and parafoveal flow density (PFD) were evaluated using OCTA and compared to the fellow eye. Multivariate linear regression analysis was performed to determine correlations with visual outcomes.

Results: Thirty-one patients with macula-off RRD were included in the study. Compared with the fellow eyes, eyes after RRD surgery had a lower peripapillary VD ( < 0.01). No significant difference in superficial and deep FFD, PFD, and FAZ area was found compared to the fellow eyes. Postoperative peripapillary VD and baseline BCVA were significantly associated with BCVA three months after PPV ( < 0.05).

Conclusion: Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower peripapillary vessel density than fellow healthy eyes. Postoperative BCVA was related to postoperative peripapillary VD.
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http://dx.doi.org/10.1155/2021/6621820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009721PMC
March 2021

Small dome-shaped pigment epithelium detachment in polypoidal choroidal vasculopathy: an under-recognized sign of polypoidal lesions on optical coherence tomography?

Eye (Lond) 2021 Apr 8. Epub 2021 Apr 8.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) and swept-source optical coherence tomographic angiography (SS-OCTA) to identify polypoidal lesions in serous or serosanguinous maculopathy.

Materials And Methods: A retrospective review of patients presenting pigment epithelial detachments (PEDs) with the diagnosis of polypoidal choroidal vasculopathy (PCV), neovascular age-related macular degeneration (nAMD), and central serous chorioretinopathy (CSC), all of which underwent SD-OCT, SS-OCTA, and indocyanine green angiography (ICGA). Typical features of polypoidal lesions on SD-OCT included sharply peaked PED, notched PED, and hyperreflective ring underneath PED. SS-OCTA feature was vascularized PEDs on cross-sectional images corresponding to cluster-like structures on en face images. The parameters of PEDs were measured for analysis.

Results: Of 72 eyes, 30 had PCV, 22 had nAMD, and 20 had CSC. A total of 128 localized PEDs were detected on SD-OCT. Typical features on SD-OCT had a high specificity (94.0%) but a limited sensitivity (73.8%). SS-OCTA features provided a higher sensitivity (96.7%). PEDs of the polypoidal lesions unrecognized by SD-OCT were dome-shaped, with smaller ratio of height to base diameter and less area, and almost had heterogeneous internal reflectivity and a connected double-layer sign. Some lesions misidentified by SS-OCTA developed into ICGA-proven polypoidal lesions at follow-up visits.

Conclusion: A small dome-shaped PED with heterogeneous internal reflectivity and a connected double-layer sign on SD-OCT may suggest a polypoidal lesion of PCV. SS-OCTA may be a helpful tool to investigate preclinical PCV and observe the formation of polypoidal lesions.
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http://dx.doi.org/10.1038/s41433-020-01390-0DOI Listing
April 2021

Replacement of polyps with type 1 macular neovascularization in polypoidal choroidal vasculopathy imaged with swept source OCT angiography.

Am J Ophthalmol Case Rep 2021 Jun 11;22:101057. Epub 2021 Mar 11.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

Purpose: To investigate the morphological changes of polyps in eyes with polypoidal choroidal vasculopathy (PCV) after treatment with vascular endothelial growth factor (VEGF) inhibitors using swept source optical coherence tomography angiography (SS-OCTA).

Observations: Following anti-VEGF therapy, polyps were found to evolve into typical type 1 macular neovascularization (MNV) in five eyes. In all of these five eyes, a polypoidal lesion was detected adjacent to a serous or hemorrhagic retinal pigment epithelial detachment (PED).

Conclusions And Importance: Polypoidal lesions in PCV can evolve into typical type 1 MNV. This morphological evolution suggests that these polyps are clusters of tangled vessels that can proliferate into a more typical neovascular pattern, and this evolution may be facilitated by being adjacent to a PED. Since this morphological appearance could be associated with a better prognosis, SS-OCTA might be helpful in identifying cases of transformed polyps that may be associated with a decreased risk for vision loss.
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http://dx.doi.org/10.1016/j.ajoc.2021.101057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995480PMC
June 2021

Real World First-Line Treatments and Outcomes of Nab-Paclitaxel Plus Gemcitabine, mFOLFIRINOX and GEMOX in Unresectable Pancreatic Cancer from a Chinese Single Institution.

Curr Oncol 2020 12 30;28(1):209-219. Epub 2020 Dec 30.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Background: There have not been any head-to-head prospective studies to compare the effects of different chemotherapy regimens as first-line treatments for unresectable pancreatic cancer (UPC). We aimed to compare the effectiveness of nab-paclitaxel plus gemcitabine, mFOLFIRINOX and gemcitabine plus oxaliplatin (GEMOX) as first-line treatments by using real-world data from Chinese patients.

Methods: We retrospectively included patients with UPC treated with nab-paclitaxel plus gemcitabine, mFOLFIRINOX or GEMOX as a first-line treatment at Sun Yat-sen University Cancer Center. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed.

Results: A total of 117 patients were administered nab-paclitaxel plus gemcitabine ( = 62), mFOLFIRINOX ( = 30) or GEMOX ( = 25) as first-line chemotherapy. The median OS was 11.1, 10.1 and 10.2 months ( = 0.75) in the nab-paclitaxel plus gemcitabine, mFOLFIRINOX and GEMOX, respectively. The ORR was similar among the three groups (24%, 23% and 32%, = 0.76) and the DCR was higher in the nab-paclitaxel-gemcitabine group (82%) than the other two groups (60% and 64%, = 0.04). The most common adverse events of grade 3 or 4 were neutropenia (32%, 28% and 5%), peripheral neuropathy (13%, 16% and 0) and fatigue (9%, 16% and 5%). Febrile neutropenia occurred in 2%, 4% and 5% of the patients in the three groups.

Conclusion: In the first line treatment of UPC, our results suggest that nab-paclitaxel plus gemcitabine was associated with a higher DCR than mFOLFIRINOX or GEMOX, while all groups demonstrated similar OS, PFS and ORR.
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http://dx.doi.org/10.3390/curroncol28010023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816170PMC
December 2020

Biochemical characterization of a tyrosinase from Bacillus aryabhattai and its application.

Int J Biol Macromol 2021 Apr 8;176:37-46. Epub 2021 Feb 8.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address:

Although lots of tyrosinases have been isolated from bacteria, few studies are focused on tyrosinases from Bacillus sp.. In this study, a tyrosinase from B. aryabhattai TCCC 111983 (TYR) was functionally expressed, purified, and then biochemically characterized. The recombinant tyrosinase (rTYR) presented a good catalytic activity in a broad temperature and pH range, retaining over 60% of the relative activity at 30 °C-90 °C and 45% at pH 3.0 to 10.0. Especially, rTYR exhibited 20% of its maximum activity at 0 °C, and it also showed a variable stability towards different effectors. It presented high tolerance towards salinity and chloride, retaining 81% of its original activity in 2 M NaCl. Kinetic parameters indicated that rTYR displayed a relatively good affinity for both l-tyrosine and l-DOPA. Additionally, rTYR demonstrated remarkable advantages on efficient decolorizing azo and anthraquinonic food dyes (carmine and erythrosin), and more five industrial dyes with or without mediators in acidic, neutral, and alkaline conditions. As the first report on the tyrosinase from B. aryabhattai, the aforementioned results indicated that rTYR would be potential for food industrial applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.042DOI Listing
April 2021

The role of dislocation-solute interactions on the creep behaviour of binary Mg-RE alloys.

Sci Rep 2021 Feb 3;11(1):2860. Epub 2021 Feb 3.

National Engineering Research Center of Light Alloy Net Forming and State Key Laboratory of Metal Matrix Composite, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

The effect of dislocation-RE atoms interactions on the creep behaviour has been studied via creep testing and HAADF-STEM analysis of two extruded alloys; Mg-0.5Ce and Mg-2Gd (wt%). Almost no Ce atoms are detected in the Mg matrix due to the low solid solubility and faster diffusion rate in as-extruded condition. However, Gd solute segregations are observed along dislocations and hexagonal dislocation patterns. Such segregations can not only pin the dislocation motion and enhance the creep strengthening via dislocation patterns, but also lead to dynamic precipitation. Thus, combing with the stress exponent values, the transition of creep mechanism between Mg-0.5Ce alloys and Mg-2Gd alloys has been found and dislocation-Gd atoms interactions are determined to be the main factor for superior creep resistance of Mg-2Gd alloys.
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http://dx.doi.org/10.1038/s41598-021-82517-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859206PMC
February 2021

Corrigendum to "Crystal structure of the NS3 helicase of tick-borne encephalitis virus" [Biochem. Biophys. Res. Commun. 528(3) (2020) 601-606].

Biochem Biophys Res Commun 2021 Feb 16;541:103. Epub 2021 Jan 16.

School of Life Sciences, Tianjin University, Tianjin, China; Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China.

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http://dx.doi.org/10.1016/j.bbrc.2021.01.003DOI Listing
February 2021

Pristimerin induces apoptosis and inhibits proliferation, migration in H1299 Lung Cancer Cells.

J Cancer 2020 2;11(21):6348-6355. Epub 2020 Sep 2.

Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P. R. China.

The natural occurring pristimerin, a quinonemethide triterpenoid, is extracted from a variety of species of the and family. This research investigated the anti-cancer potential of pristimerin on NSCLC cells NCI-H1299 and elucidated the molecular mechanism. Cell growth inhibition by pristimerin was assessed using the MTT assay. Apoptosis was detected using the Annexin V/propidium iodide (PI) test. The colony forming assay was used to investigate the anti-proliferative effects of pristimerin. Wound healing assay and the transwell cell migration assay were utilized to determine the inhibitory effects of migration and invasion, respectively. Western blot was used to detect the protein expression, and real-time-quantitative (RT-q) PCR was used to analyze the mRNA expression. The results showed that pristimerin inhibited the proliferation of H1299 cells with an IC value of 2.2 ± 0.34 µM and induced apoptosis in a dose-dependent manner. The colony formation ability was reduced in a dose-dependent manner. A marked inhibition of migration and invasion against H1299 cells was observed in a dose- or time-dependent manner. Moreover, the decreased protein levels of vimentin, F-actin, integrin β1, matrix metalloproteinase (MMP2) and Snail revealed the potential inhibition of epithelial-to-mesenchymal transition (EMT). The regulated mRNA levels of integrin β1, MMP2 and Snail indicated the great potential in the treatment of NSCLC. In conclusion, our study demonstrated that pristimerin suppressed NSCLC cells NCI-H1299 , exhibited potent activities of proliferation inhibition and apoptosis induction. Furthermore, the treatment of pristimerin decreased migration and invasion of H1299, which was correlated with EMT-related proteins and mRNA.
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http://dx.doi.org/10.7150/jca.44431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532514PMC
September 2020

Time dependence of susceptible-infected-susceptible epidemics on networks with nodal self-infections.

Phys Rev E 2020 May;101(5-1):052310

Delft University of Technology, Faculty of Electrical Engineering, Mathematics and Computer Science, P.O Box 5031, 2600 GA Delft, The Netherlands.

The average fraction of infected nodes, in short the prevalence, of the Markovian ɛ-SIS (susceptible-infected-susceptible) process with small self-infection rate ɛ>0 exhibits, as a function of time, a typical "two-plateau" behavior, which was first discovered in the complete graph K_{N}. Although the complete graph is often dismissed as an unacceptably simplistic approximation, its analytic tractability allows to unravel deeper details, that are surprisingly also observed in other graphs as demonstrated by simulations. The time-dependent mean-field approximation for K_{N} performs only reasonably well for relatively large self-infection rates, but completely fails to mimic the typical Markovian ɛ-SIS process with small self-infection rates. While self-infections, particularly when their rate is small, are usually ignored, the interplay of nodal self-infection and spread over links may explain why absorbing processes are hardly observed in reality, even over long time intervals.
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http://dx.doi.org/10.1103/PhysRevE.101.052310DOI Listing
May 2020

3-Methyladenine Alleviates Experimental Subretinal Fibrosis by Inhibiting Macrophages and M2 Polarization Through the PI3K/Akt Pathway.

J Ocul Pharmacol Ther 2020 10 18;36(8):618-628. Epub 2020 Jun 18.

Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To explore the effects of 3-methyladenine (3-MA), a selective inhibitor of phosphatidylinositol-3-kinase (PI3K), on experimental subretinal fibrosis (SRF) in mice. The SRF mouse model was established by 532 nm laser photocoagulation at each fundus of mice on day 0. 3-MA was administered every 2 days from day 0 to 35. Immunofluorescence of choroidal flat mounts was performed to evaluate the size of SRF area, local macrophages, and polarization, respectively. Besides, Western blot analysis was carried out to assess the expression levels of macrophage polarization-related genes, Arg-1, Ym-1, and transforming growth factor-β (TGF-β). Co-culture and migration experiments were used to demonstrate the inhibitory effect of 3-MA on fibroblasts. The gene knockout and Western blot analysis were used to explore the signal pathways related to macrophage polarization. Compared with the control group, the 3-MA-treated group showed significantly less size of SRF area. 3-MA treatment reduced both circulating and local macrophages, and counteracted M2 polarization. Moreover, 3-MA inhibited fibroblast recruitment. Mechanistically, we proved that 3-MA inhibits macrophage M2 polarization by suppressing PI3K/Akt signal pathway rather than the PI3K-autophagy-related signal pathway. 3-MA exerts antifibrotic effects on experimental SRF by targeting circulating and local macrophages and M2 polarization, through PI3K/Akt signal pathway. These results support the potential use of 3-MA as a new therapeutic modality for SRF associated with neovascular age-related macular degeneration.
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http://dx.doi.org/10.1089/jop.2019.0112DOI Listing
October 2020

Crystal structure of the NS3 helicase of tick-borne encephalitis virus.

Biochem Biophys Res Commun 2020 07 4;528(3):601-606. Epub 2020 Jun 4.

School of Life Sciences, Tianjin University, Tianjin, China; Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China. Electronic address:

Tick-borne encephalitis virus (TBEV) is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus in Flaviviridae. It can cause the server infectious diseases named tick-borne encephalitis (TBE), which is characterized by paralysis and epilepsy. However, no effective treatment for TBE has been developed targeting TBEV. The NS3 helicase from TBEV plays an essential role in viral replication, which makes it an important target for drug design. In this study, the crystal structure of TBEV NS3 helicase has been determined to the resolution of 2.14 Å. Subsequent alignment with homologous structures reveals that the NTP binding site and RNA-binding sites are located in motifs Ⅱ and Ⅵ of NS3 and the critical residues for binding are conserved across species in the genus, while the distinct conformation transition implies that the TBEV helicase need a different local rearrangement. This study demonstrates the key atomic-level features of TBEV helicase and provides basis for the design of antiviral drugs targeting TBEV helicase.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.138DOI Listing
July 2020

Epidemiology of Coronavirus Disease 2019 (COVID-19) Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Disaster Med Public Health Prep 2020 12 18;14(6):796-804. Epub 2020 May 18.

TEDA International Cardiovascular Hospital, TianJin, China.

In December, 2019, an infectious outbreak of unknown cause occurred in Wuhan, which attracted intense attention. Shortly after the virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the epidemic of coronavirus disease 2019 (COVID-19) broke out, and an information storm occurred. At that time, 2 important aspects, that is, the stages of spread and the components of the epidemic, were unclear. Answers to the questions (1) what are the sources, (2) how do infections occur, and (3) who will be affected should be clarified as the outbreak continues to evolve. Furthermore, components of the epidemic and the stages of spread should be explored and discussed. Based on information of SARS, Middle East respiratory syndrome (MERS), and COVID-19, the components of the epidemic (the sources, the routes of infection, and the susceptible population) will be discussed, as well as the role of natural and social factors involved. Epidemiologic characteristics of patients will be traced based on current information.
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http://dx.doi.org/10.1017/dmp.2020.155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399147PMC
December 2020

Surface Topography Index: An Ignored Trait of Pectus Excavatum for Deformity Severity Assessment.

Ann Thorac Surg 2020 11 4;110(5):1784. Epub 2020 May 4.

Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Rd, 510180 Guangzhou, PR China.

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http://dx.doi.org/10.1016/j.athoracsur.2020.03.092DOI Listing
November 2020

Evaluation of the association of macular ganglion cell-inner plexiform layer thickness and myopia in Chinese young adults.

Eye (Lond) 2021 02 14;35(2):393-399. Epub 2020 Apr 14.

Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: To describe the distribution of ganglion cell-inner plexiform layer (GCIPL) thickness among Chinese young adults and report whether the decreased GCIPL thickness is associated with myopia.

Methods: In this study, we included Chinese young adults who underwent Cirrus spectral domain-optical coherence tomography (SD-OCT). SD-OCT was used to measure average and minimum GCIPL thickness, and GCIPL thickness at all sectors. Subfoveal choroidal thickness (CT), axial length (AL), and spherical equivalents (SE) were also measured.

Results: A total of 348 eyes were included in the analysis. Average GCIPL thickness showed a significant difference between myopes and emmetropes, with 87.89 ± 3.65 μm for emmetropic groups and 82.65 ± 4.96 μm for myopic groups. The GCIPL thickness was significantly thinner in myopia than in emmetropia at all locations (P < 0.05), affirming that myopia was associated with thinner GCIPL thickness (P = 0.001). The mean subfoveal CT also showed a significant difference between myopes and emmetropes, with 330.57 ± 9.43 μm for emmetropic groups and 265.98 ± 4.12 μm for myopic groups. GCIPL (OR 0.863, 95% CI, 0.785-0.949), AL (OR 2.499, 95% CI, 1.532-4.075) and intraocular pressure (IOP) (OR 1.250, 95% CI, 1.086-1.438) revealed significant associations with myopia. When adjusting for AL, IOP, and anterior chamber depth (ACD) in the myopia subgroup, the GCIPL thickness remained positively associated.

Conclusions: In a specific Chinese young population, myopic eyes have measurably less macular GCIPL thickness than normal eyes. Decreasing GCIPL thickness may be associated with the progression of myopia.
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http://dx.doi.org/10.1038/s41433-020-0847-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026982PMC
February 2021

Exosome-based targeted RNA delivery for immune tolerance induction in skin transplantation.

J Biomed Mater Res A 2020 05 20;108(7):1493-1500. Epub 2020 Mar 20.

Department of Pathology, The 8th Medical Center of Chinese PLA General Hospital, Beijing, China.

Exosomes have been widely applied to the delivery of RNA and small molecules currently. However, the low targeting and specificity greatly limited the effect of exosome delivery. Here we designed an exosome that can perform the targeted delivery of two different types of RNA. Based on the mesenchymal stem cells (MSCs) derived exosomes, the RNA delivery system of targeted dendritic cells (DC-Exosome) was constructed, using the layer by layer self-assembly. DC-Exosomes can specifically bind to DCs, while guiding the endocytosis of chimeras and exosome. Then aptamer/siRNA chimera was cut into mTOR siRNA by Dicer, and microRNA was released from exosome under lysosomal digestion. SIGN aptamer performed the rapid induction of immune tolerance, and later mTOR siRNA was formed to inhibit mTOR pathway and suppress immune responses. Exosomes could maintain long time-stability after PEG-PEI polyplexes modification and promote HLA-G expression in DCs continuously. Animal experiments showed that DC-Exosomes could induce immune tolerance at 3, 7, and 14 days after skin transplantation. Compared with the microRNA-Exosome group, the number of CD11c+ DCs in DC-Exosome group decreased, while the proportion of HLA-G+ DCs increased remarkably. In conclusion, we constructed a new exosome-based targeted delivery system which could effectively induce the immune tolerance in transplantation.
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http://dx.doi.org/10.1002/jbm.a.36919DOI Listing
May 2020

Renal Hemodynamic Changes and Postsurgical Recovery in Children Treated for Ureteropelvic Junction Obstruction.

Ultrasound Q 2020 Mar;36(1):20-23

Department of Pediatric Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Objective: The aims of the study were to measure renal hemodynamic indexes and to evaluate postsurgical recovery in children diagnosed with obstructive hydronephrosis using color Doppler ultrasound.

Methods: This study enrolled 36 patients with ureteropelvic junction obstruction who underwent Anderson-Hynes pyeloplasty. The peak systolic velocity (PSV) and the resistive index (RI) of the main renal arteries (MRAs) and interlobar renal arteries (IRAs) were measured using color Doppler ultrasound. Renal hemodynamic indexes were measured before surgery and 2, 4, 6, 8, 10, 12, 14, and 16 weeks after surgery.

Results: Split renal function and renal parenchymal thickness were positively correlated with PSV and negatively correlated with RI. Anterior-posterior diameter had no significant correlation with PSV or RI. The PSV in MRAs and IRAs were lower than those of the contralateral kidneys but increased after surgery. Anderson-Hynes pyeloplasty was successfully performed in all patients, including one patient whose kidney was removed 16 weeks after surgery. The RI in the MRAs and IRAs were higher than those of the contralateral kidneys but decreased within 2 weeks after surgery. Peak systolic velocity and RI were still atypical 16 weeks after surgery. The hemodynamic index of the nonfunctional kidney did not show improvement after surgery.

Conclusions: Peak systolic velocity and RI were correlated with renal function and renal parenchymal thickness but were not correlated with dilatation of the renal pelvis. Peak systolic velocity increased whereas RI decreased after surgery and were stable at 8 weeks, but remained abnormal 16 weeks after surgery. Hemodynamic measurements may be a useful and convenient method to evaluate surgical outcomes after Anderson-Hynes pyeloplasty.
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http://dx.doi.org/10.1097/RUQ.0000000000000477DOI Listing
March 2020

Fifteen-Year Application of Manure and Chemical Fertilizers Differently Impacts Soil ARGs and Microbial Community Structure.

Front Microbiol 2020 6;11:62. Epub 2020 Feb 6.

Key Laboratory of Agricultural Water Resources, Hebei Key Laboratory of Soil Ecology, Center for Agricultural Resources Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Shijiazhuang, China.

Manure, which contains large amounts of antibiotics and antibiotic resistance genes (ARGs), is widely used in agricultural soils and may lead to the evolution and dispersal of ARGs in the soil environment. In the present study, soils that received manure or chemical fertilizers for 15 years were sampled on the North China Plain (NCP), which is one of the primary areas of intensive agriculture in China. High-throughput quantitative PCR and sequencing technologies were employed to assess the effects of long-term manure or chemical fertilizer application on the distribution of ARGs and microbial communities. A total of 114 unique ARGs were successfully amplified from all soil samples. Manure application markedly increased the relative abundance and detectable numbers of ARGs, with up to 0.23 copies/16S rRNA gene and 81 unique ARGs. The increased abundance of ARGs in manure-fertilized soil was mainly due to the manure increasing the abundance of indigenous soil ARGs. In contrast, chemical fertilizers only moderately affected the diversity of ARGs and had no significant effect on the relative abundance of the total ARGs. In addition, manure application increased the abundance of mobile genetic elements (MGEs), which were significantly and positively correlated with most types of ARGs, indicating that horizontal gene transfer via MGEs may play an important role in the spread of ARGs. Furthermore, the application of manure and chemical fertilizers significantly affected microbial community structure, and variation partitioning analysis showed that microbial community shifts represented the major driver shaping the antibiotic resistome. Taken together, our results provide insight into the long-term effects of manure and chemical fertilization on the dissemination of ARGs in intensive agricultural ecosystems.
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http://dx.doi.org/10.3389/fmicb.2020.00062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015874PMC
February 2020

Quantification of Diabetic Retinopathy Lesions in DME Patients With Intravitreal Conbercept Treatment Using Deep Learning.

Ophthalmic Surg Lasers Imaging Retina 2020 02;51(2):95-100

Background And Objectives: To quantitatively evaluate diabetic retinopathy (DR) lesions using the authors' validated machine learning algorithms and provide physicians with an automated and precise method to follow the progression of DR and outcome of interventions.

Patients And Methods: Retrospective analyses were conducted of 3,496 color fundus photography images from 19 patients with clinically significant diabetic macular edema receiving conbercept treatment. The modified seven-field fundus images were obtained at baseline and at the third, sixth, and twelfth month visit, whereas the modified two-field fundus images were obtained at the other monthly visits. The area of intraretinal hemorrhage and hard exudate lesions was traced by the authors' validated algorithms.

Results: The mean central foveal thickness at baseline was 459.9 μm ± 127.5 μm. Mean central foveal thickness was 316.5 μm ± 53.0 μm at the twelfth month visit, which decreased by 143.4 μm when compared with the baseline optical coherence tomography. The mean total area of intraretinal hemorrhage in the study eye in seven fields was 5.656 ± 1.176 mm at baseline, 2.438 ± 0.976 mm at the third month, 2.901 ± 0.521 mm at the sixth month, and 2.122 ± 0.582 mm at the end of the study. The area of intraretinal hemorrhage was reduced by 62.49% from baseline to the end of study (P < .0001). The mean total area of hard exudates in the study eye was 2.549 ± 0.776 mm at baseline, 2.233 ± 0.576 mm at the third month, 2.710 ± 0.621 mm at the sixth month, and 1.473 ± 0.564 mm at the end of the study. The mean total area of hard exudates decreased by 41.1% at the twelfth month (P < .0001) compared with the first visit. Significant decrease was observed in the area of intraretinal hemorrhage during conbercept treatment. The hard exudates area fluctuated during loading then subsequently decreased at the twelfth month.

Conclusions: The present study quantitatively analyzed the change in the area change of intraretinal hemorrhage and hard exudate lesions during the course of conbercept treatment. The automated system is promising to be a precise and objective method for monitoring the progression of DR and outcomes of interventions in clinical settings. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:95-100.].
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http://dx.doi.org/10.3928/23258160-20200129-05DOI Listing
February 2020

Pediatric primary diffuse leptomeningeal melanomatosis: Case report and review of the literature.

Medicine (Baltimore) 2020 Feb;99(8):e19178

Department of Neurosurgery.

Rationale: Primary melanocytic tumors of central nerve system (CNS) are rare, primary diffuse leptomeningeal melanomatosis (PDLM), a subtype of malignant melanomas of CNS, is extremely rare,especially in pediatrics. As the clinical manifestation of PDLM is not characteristic, It is often misdiagnosed as tubercular meningitis and hemorrhage.

Patient Concerns: A 13-year-old boy was admitted to our department with symptoms of recurrent headache and vomiting twice. As the brain imaging revealed a lesion located in the left temporal lobe mimicked hemorrhage, so there was a misdiagnosis of hemorrhage in first hospitalization. He was admitted again for the recurrence of the headache and vomiting. Detailed physical examination showed multiple melanin changes in the skin of the whole body which were ignored in last hospitalization. Brain imaging showed the significantly enlarged lesion in the left temporal lobe and several smaller lesions in the left parietal lobe and cerebellum which indicated metastasis.

Diagnosis: According to the history,physical examination and the radiological finding, the patient was diagnosed with malignant melanoma of central never system possibly.

Interventions: The patient underwent left temporal and parietal lesions total resection with a craniotomy.

Outcomes: The diagnosis of PDLM was established according to pathological characteristics and the negative finding of positron emission tomography (PET)-computed tomography (CT) outside CNS. The patient got no further treatment for economic reasons and experienced the progression and died 5 months after operation.

Lessons: PDLM is extremely rare in CNS, as the clinical manifestation, radiological changes are not special, early diagnosis is difficult. The confirmed diagnosis is established by leptomeningeal biospy or surgical tissue. PET-CT can help differential diagnosis with metastastic leptomeningeal melanomas. The prognosis is dismal due to the inefficiency of chemotherapy or radiotherapy.
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http://dx.doi.org/10.1097/MD.0000000000019178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034675PMC
February 2020

T-cadherin inhibits invasion and migration of endometrial stromal cells in endometriosis.

Hum Reprod 2020 01;35(1):145-156

Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, P.R. China.

Study Question: What is the expression level of T-cadherin in endometriosis, and does T-cadherin play a role in regulating invasion and migration of endometrial stromal cells?

Summary Answer: T-cadherin expression was reduced in ectopic endometriotic lesions compared to eutopic endometrium, and T-cadherin overexpression inhibited the invasion and migration of endometrial stromal cells.

What Is Known Already: Endometriosis is a disease that involves active cell invasion and migration. T-cadherin can inhibit cell invasion, migration and proliferation in various cancer cells, but its role in endometriosis has not been investigated.

Study Design, Size, Duration: We explored the expression status of T-cadherin in 40 patients with and 24 without endometriosis. We also isolated endometrial stromal cells to study the invasion, migration and signaling pathway regulation of T-cadherin overexpression.

Participants/materials, Setting, Methods: Patients were recruited at the Guangzhou Women and Children's Medical Center to study the expression levels of T-cadherin. The expression of T-cadherin was detected by immunohistochemistry staining and western blot. H-score was used to evaluate the staining intensity of T-cadherin. The correlation between T-cadherin expression levels (H-score) and endometriosis patients' age, stage, lesion size and adhesion was analyzed. Endometrial stromal cells from patients with and without endometriosis were isolated, and cell invasion and migration were detected by transwell assays after T-cadherin overexpression. The expression of vimentin in T-cadherin-overexpressed cells was detected by western blot. After T-cadherin overexpression, the phosphorylation profile of signaling pathway proteins was detected with the Proteome Profiler Human Phospho-Kinase Array Kit.

Main Results And The Role Of Chance: There was no difference in the expression of T-cadherin in the normal endometrium of control patients and the eutopic endometrium of endometriotic patients, but it was significantly decreased in the ectopic endometrium of endometriotic patients, compared with control endometrium and eutopic endometrium of endometriosis patients (P < 0.0001, for both). Western blot analysis also showed that the expression of T-cadherin was decreased in ectopic endometriotic lesions, but not the normal control endometrium or the endometriotic eutopic endometrium. The results of transwell assays indicated that T-cadherin overexpression inhibited the invasion and migration of endometrial stromal cells. In addition, T-cadherin overexpression promoted the phosphorylation of HSP27 (S78/S82) and JNK 1/2/3 (T183/Y185, T221/Y223) and decreased the expression of vimentin, MMP2 and MMP9 in eutopic endometriosis stromal cells.

Large-scale Data: N/A.

Limitations, Reasons For Caution: The control group were patients with benign gynecological conditions (e.g. uterus myoma, endometrial or cervical polyp), which may have genetic or epigenetic variations associated with T-cadherin expression and signaling pathways. The case numbers of involved endometriosis and control patients were limited. This study only used endometrial stromal cells from patients with or without endometriosis. Ideally, ectopic endometrial stromal cells of the ovarian endometriotic lesions should also be utilized to explore the function of T-cadherin.

Wider Implications Of The Findings: Further investigation of the role of T-cadherin in endometriosis may generate new potential therapeutic targets for this complex disorder.

Study Funding And Competing Interest(s): This study was supported by the Natural Science Foundation of Guangdong Province (2016A030313495), National Natural Science Foundation of China (81702567, 81671406, 31871412), the Science and Technology Programs of Guangdong (2017A050501021), Medical Science Technology Research Fund of Guangdong Province (A2018075), the Science and Technology Programs of Guangzhou City (201704030103), Internal Project of Family Planning Research Institute of Guangdong Province (S2018004), Post-doc initiation fund of Guangzhou (3302) and Post-doc science research initiation fund of Guangzhou Women and Children's Medical Center (20160322). There are no conflicts of interest.
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http://dx.doi.org/10.1093/humrep/dez252DOI Listing
January 2020

One-Year Outcomes of 1 Dose versus 3 Loading Doses Followed by Pro Re Nata Regimen Using Ranibizumab for Neovascular Age-Related Macular Degeneration: The ARTIS Trial.

J Ophthalmol 2019 10;2019:7530458. Epub 2019 Oct 10.

Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

. To compare the functional and anatomical outcomes of one dose and three loading doses followed by the pro re nata (PRN) regimen in Chinese neovascular age-related macular degeneration (nvAMD) (including polypoidal choroidal vasculopathy (PCV)) patients. . In this multicenter, prospective, open-label, controlled, 12-month study (ClinicalTrials.gov: NCT02810808), patients were randomized (1 : 1) to 1 dose + PRN (PRN group) or 3 loading doses + PRN (LD group) using intravitreal ranibizumab treatment. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated. The main outcome was the change in BCVA. The noninferiority limit was 5 letters. . Forty-five patients in the PRN group and 49 patients in the LD group finished 12-month follow-up. Each group included 4 PCV patients. The mean change in BCVA from baseline was 7.8 letters in the PRN group, compared with 10.9 letters in the LD group (=0.344). There were no significant differences between two groups in the mean change of CRT (-159.3 m vs. -120.5 m) at month 12. The mean number of injections during the 12-month follow-up was 6.0 in the PRN group and 6.8 in the LD group. The proportion of patients who gained an improvement in visual acuity by 15 or more letters was 28.9% in the PRN group and 44.9% in the LD group (=0.066). . One dose + PRN showed noninferior visual gains than 3 loading doses + PRN regimen using ranibizumab in Chinese nvAMD and PCV patients. Number of injections in the PRN group was similar as that in the LD group but remained a potential risk of vision instability during one-year follow-up using OCT-guided retreatment criteria. This trial is registered with NCT02810808.
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http://dx.doi.org/10.1155/2019/7530458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811781PMC
October 2019

Nonadditive and Asymmetric Allelic Expression of Growth Hormone in Hybrid Tilapia.

Front Genet 2019 15;10:961. Epub 2019 Oct 15.

Tilapia Genetics and Breeding Center, Guangxi Academy of Fishery Sciences, Nanning, China.

Hybridization is a common breeding technique that can improve germplasm through heterosis in aquaculture. However, the regulation of key gene expression, including the details of transcriptional level changes at the beginning of hybridization events, remains largely undefined, especially in teleosts. In this study, by interspecies crossing between two pure lines of Nile tilapia and blue tilapia, we obtained a hybrid tilapia population as a model to elucidate heterosis, and we traced the molecular outcomes of growth hormone (GH) expression and allele-specific expression (ASE) in hybrids. The hybrids display growth vigor compared to their parents in the 120-day growth trial. GH mRNA expression was uniquely expressed in the pituitary. Higher GH expression was found in the hybrid than the midparent value, in both males and females, showing a nonadditive pattern. We identified four single-nucleotide polymorphism sites between Nile tilapia and blue tilapia. Subsequently, by pyrosequencing, we found asymmetric allelic expression in hybrids with higher maternal allelic transcript ratios in both males and females. Fasting significantly increased GH expression in hybrids, but asymmetric allelic expression was not affected by feeding or fasting conditions. Finally, we identified and effects overall expression and ASE values in the hybrid, which showed that the and effects promoted the expression of maternal subgenome in the hybrid, contributing to the expression superiority of GH in hybrid tilapia. Taken together, the results of our study first illustrated the concept of GH expression superiority and its formation mechanism in hybrid fish with growth vigor.
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http://dx.doi.org/10.3389/fgene.2019.00961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803431PMC
October 2019

Chitinase-3-Like-1 Promotes M2 Macrophage Differentiation and Induces Choroidal Neovascularization in Neovascular Age-Related Macular Degeneration.

Invest Ophthalmol Vis Sci 2019 11;60(14):4596-4605

Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Purpose: Choroidal neovascularization (CNV) is the principal pathological factor contributing to blindness in neovascular age-related macular degeneration (nAMD). Infiltration of M2 macrophage is thought to contribute to CNV progress, although the way that regulates its differentiation remains unclear. Here, we investigate the role of CHI3L1 in M2 differentiation and angiogenesis in CNV.

Methods: Serums from nAMD patients were tested for CHI3L1 expression. Mice were subjected to laser injury to induce CNV, and lesion expansion were tracked using fundus fluorescence angiography (FFA) and immunofluorescence analysis. Several strategies were taken to verify the contribution of M2 macrophage and CHI3L1: macrophage depletion by clodrosome, local CHI3L1 inhibition using intravitreally injection neutralize antibody (mAY), and depletion of CHI3L1 receptor (IL13-Ra2) by small-interfering RNA (siRNA). Tuber analysis was used to further determine angiogenetic effect of CHI3L1. Anti-VEGFA was used as positive control for mAY.

Results: Serum levels of CHI3L1 were highly elevated in nAMD patients. CHI3L1 was expressed by infiltrating M2 macrophages and was elevated as CNV progress in a mice model. System macrophage depletion and local suppression of CHI3L1 alleviated CNV formation while enhancing anti-VEGFA therapeutic effect. Stimulation of macrophage with recombinant CHI3L1 activated MAPK signaling cascade and induced transition to M2, while siRNA knockdown of IL13-Ra2 abolished it. In an in vitro coculture system, supernatants from CHI3L1-stimulated M2 macrophages and promoted tube vascularization.

Conclusions: These results unveil novel angiogenic regulation of CHI3L1 and M2 polarized macrophages in CNV development. These mechanistic insights may point to CHI3L1 as a new therapeutic target for treatment for nAMD.
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http://dx.doi.org/10.1167/iovs.19-27493DOI Listing
November 2019
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