Publications by authors named "Yu Meng Wang"

37 Publications

Association of foveal avascular zone area withstructural and functional progression in glaucoma patients.

Br J Ophthalmol 2021 Apr 7. Epub 2021 Apr 7.

Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, La Jolla, California, USA.

Background: To investigate whether quantitative optical coherence tomography angiography (OCTA) metrics of the superficial/deep macular retina and optic disc are associated with glaucoma progression risk.

Methods: A total of 238 eyes from 119 patients with open angle glaucoma or ocular hypertension, and no history of systemic hypertension or diabetes mellitus were included. All participants underwent OCTA imaging with a swept-source OCT (DRI-OCT 1, Topcon, Japan). OCTA metrics of superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the macular region, and radial peripapillary capillary network of the optic disc were measured by a customised MATLAB program to obtain foveal avascular zone (FAZ) area, FAZ circularity and capillary density of SCP/DCP, and capillary density of the peripapillary region. Relationships between baseline OCTA metrics, visual field (VF) metrics, intraocular pressure fluctuation and risk of glaucoma progression were analysed with the Cox proportional hazards model. A frailty model was used to adjust for intereye correlation.

Results: During a mean follow-up duration of 29.39 months (range 12-56 months), 50, 48 and 16 eyes were determined to have retinal nerve fibre layer (RNFL), ganglion cell-inner plexiform layer (GC-IPL) and VF progression respectively. FAZ area per SD increase at baseline were significantly associated with both RNFL thinning (HR 1.73 95% CI 1.04 to 2.90); p=0.036) and GC-IPL thinning (HR 2.62, 95% CI 1.59 to 4.31; p<0.001), after adjusting for age, axial length and other potential confounding factors. VF progression was associated with age (HR 1.05, 95% CI 1.02 to 1.08; p<0.001) and mean deviation value (HR 0.91, 95% CI 0.84 to 0.98; p=0.010), but not with any OCTA metrics.

Conclusion: Enlarged FAZ area measured by OCTA was associated with a higher risk of RNFL and GC-IPL thinning associated with glaucoma, but not with functional deterioration in glaucoma.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318065DOI Listing
April 2021

Combined Phacoemulsification-Endoscopic Cyclophotocoagulation versus Phacoemulsification Alone in Primary Angle-Closure Glaucoma: A Pilot Randomized Controlled Trial.

Ophthalmol Glaucoma 2021 Mar 13. Epub 2021 Mar 13.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Hong Kong Eye Hospital, Kowloon, Hong Kong SAR, China; Prince of Wales Hospital, Shatin, Hong Kong SAR, China. Electronic address:

Purpose: To compare combined phacoemulsification plus endoscopic cyclophotocoagulation (ECP) versus phacoemulsification alone in primary angle-closure glaucoma (PACG) with coexisting cataract.

Design: Prospective randomized controlled clinical trial-a pilot study.

Participants: Forty-eight PACG eyes of 48 patients with coexisting cataract.

Intervention: Recruited patients were randomized into undergoing phacoemulsification plus ECP or phacoemulsification alone. After surgery, patients were followed up every 3 months for 2 years.

Main Outcome Measures: Intraocular pressure (IOP) and requirement for topical glaucoma drugs.

Results: Twenty-seven PACG eyes were randomized to receive combined phacoemulsification plus ECP, and 21 PACG eyes underwent phacoemulsification alone. There was no statistically significant difference in mean preoperative IOP between combined phacoemulsification plus ECP and phacoemulsification groups (20.0 mmHg vs. 20.7 mmHg; P = 0.71). Phacoemulsification plus ECP resulted in lower mean postoperative IOP than phacoemulsification alone at all follow-up visits, but the differences only reached statistical significance at 1 month (P = 0.01), 12 months (P = 0.01), and 24 months (P = 0.04) postoperatively. There was no statistically significant difference in mean preoperative number of topical glaucoma drugs between combined phacoemulsification plus ECP and phacoemulsification groups (3.3 vs 3.1, P = 0.71). Combined phacoemulsification plus ECP resulted in lower glaucoma drug requirement than phacoemulsification alone at all follow-up visits, but the differences did not reach statistical significance at any time points postoperatively (P ≥ 0.05). Both groups were comparable in visual improvement, complication rate, need for additional surgical intervention, and visual field changes.

Conclusions: Combined phacoemulsification plus ECP is noninferior to phacoemulsification alone in controlling IOP in PACG eyes with cataract. Combined phacoemulsification plus ECP resulted in lower mean IOP and glaucoma drug requirement than phacoemulsification alone at all follow-up visits in this pilot study, but the differences did not reach statistical significance at the majority of time points. A large-scale randomized controlled trial is in progress to evaluate these differences.
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http://dx.doi.org/10.1016/j.ogla.2021.03.007DOI Listing
March 2021

Characterization of macular choroid in normal-tension glaucoma: a swept-source optical coherence tomography study.

Acta Ophthalmol 2021 Mar 6. Epub 2021 Mar 6.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.

Purpose: To investigate the features of the small-to-medium (choriocapillaris and Sattler's layer) and large (Haller's layer) sized vessel layers of the macular choroid in normal-tension glaucoma (NTG) patients using swept-source optical coherence tomography (SS-OCT).

Methods: We conducted an observational cross-sectional study in 234 NTG eyes from 134 patients, and 203 normal eyes from 109 non-glaucomatous control subjects. We used Image J to segment the choroidal layer and then a Python script to measure the average macular choroidal thickness (MCT) and choroidal vascular index (CVI) of two vessel layers at five different locations. Quantitative optical coherence tomography angiography (OCTA) metrics for the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at macular region were also measured by a customized MATLAB program. Generalized estimating equations (GEE) models were performed to determine ocular and demographic factors associated with the choroidal metrics, adjusting for inter-eye correlation.

Results: Significant average MCT thinning was found in NTG eyes at all five locations of the two layers, in comparison with controls (all p ≤ 0.05). In addition, compared with control eyes, significant decrease in CVI was found in NTG eyes at all five sections of the large sized vessel layer: 500 µm nasal and temporal to macula (p = 0.002), 1500 µm nasal (p < 0.001), 2500 µm nasal (p = 0.001), 1500 µm temporal (p < 0.001) and 2500 µm temporal (p = 0.004). In contrast, no significant CVI difference was detected in the small-to-medium sized vessel layer. In the comparison of OCTA metrics of SCP and DCP at macular region between NTG and normal eyes, there were no significant difference of parafoveal vessel density (VD), foveal avascular zone (FAZ) area, FAZ circularity and fractal dimension (FD) in both layers.

Conclusion: We found significant alterations in macular choroidal vascularity (reduced CVI and thinner layer) in NTG patients. Such alterations are more pronounced in the Haller's layer, rather than the choriocapillaris & Sattler's layer, in NTG. Choroidal layer may be more related to vasculature changes at macular region in NTG.
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http://dx.doi.org/10.1111/aos.14829DOI Listing
March 2021

Resorcylic Acid Lactones Produced by an Endophytic Penicillium ochrochloron Strain from Kadsura angustifolia.

Planta Med 2021 Mar 21;87(3):225-235. Epub 2020 Dec 21.

Key Laboratory of Eco-environments in Three Gorges Reservoir Region of Ministry of Education, School of Life Sciences, Southwest University, Chongqing, People's Republic of China.

Four new -resorcylic acid lactones, including penochrochlactone A (2: ), 4-O-desmethyl-aigialomycin B (4: ), and penochrochlactones C and D (5: and 6: ), two compounds isolated from a natural source for the first time, 5, 6-acetonide-aigialomycin B (1: ) and penochrochlactone B (3: ), together with six known compounds, aigialomycin F (7: ), aigialomycins A, B, and D (8: -10: ), zeaenol (11: ), and oxozeaenol (12: ), were isolated from a mycelial solid culture of the endophytic fungus SWUKD4.1850 from the medicinal plant by sequential purification over silica gel, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and chemical conversions. In addition, all the new compounds were evaluated for their cytotoxic and antibacterial activities . Penochrochlactone C (5: ) displayed moderate cytotoxicity against the HeLa tumor cell line with an IC value of 9.70 µM. In the antibacterial assays, compounds 4:  - 6: exhibited moderate activities against , and with MIC values between 9.7 and 32.0 µg/mL.
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http://dx.doi.org/10.1055/a-1326-2600DOI Listing
March 2021

Serum Metabolomic Indicates Potential Biomarkers and Metabolic Pathways of Pediatric Kashin-Beck Disease.

Biomed Environ Sci 2020 Oct;33(10):750-759

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health, Harbin 150081, Heilongjiang China.

Objective: To explore potential serum biomarkers of children with Kashin-Beck Disease (KBD) and the metabolic pathways to which the biomarkers belong.

Methods: A two-stage metabolomic study was employed. The discovery cohort included 56 patients, 51 internal controls, and 50 external controls. The metabolites were determined by HPLC-(Q-TOF)-MS and confirmed by Human Metabolome Databases (HMDB) and Metlin databases. MetaboAnalyst 3.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to analyze the metabolic pathways of the candidate metabolites. The use of HPLC-(Q-TRAP)-MS enabled quantitative detection of the target metabolites which were chosen using the discovery study and verified in another independent verification cohort of 31 patients, 41 internal controls, and 50 external controls.

Results: Eight candidate metabolites were identified out in the discovery study, namely kynurenic acid, N-α-acetylarginine, 6-hydroxymelatonin, sphinganine, ceramide, sphingosine-1P, spermidine, and glycine. These metabolites exist in sphingolipid, glutathione, and tryptophan metabolic pathways. In the second-stage study, five candidate metabolites were validated, including kynurenic acid, N-α-acetylarginine, sphinganine, spermidine, and sphingosine-1P. Except for spermidine, all substances exhibited low expression in the case group compared with the external control group, and the difference in levels of sphinganine, spermidine, and sphingosine-1P was statistically significant.

Conclusion: The direction of change of levels of sphinganine, spermidine, and sphingosine-1P in the two-stage study cohorts was completely consistent, and the differences were statistically significant. Therefore, these substances can be used as potential biomarkers of KBD. Furthermore, these results raise the possibility that sphingolipid metabolic pathways may be closely related to KBD.
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http://dx.doi.org/10.3967/bes2020.100DOI Listing
October 2020

Global assessment of arteriolar, venular and capillary changes in normal tension glaucoma.

Sci Rep 2020 11 5;10(1):19222. Epub 2020 Nov 5.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Microcirculatory insufficiency has been hypothesized in glaucoma pathogenesis. There is a scarcity of data to comprehensively examine the changes in retinal microvasculature and its role in normal tension glaucoma (NTG). We conducted a cross-sectional case-control study and included 168 eyes from 100 NTG patients and 68 healthy subjects. Quantitative retinal arteriolar and venular metrics were measured from retinal photographs using a computer-assisted program. Radial peripapillary capillary network was imaged with OCT-A and quantitative capillary metrics (circumpapillary vessel density (cpVD) and circumpapillary fractal dimension (cpFD)) were measured with a customized MATLAB program. We found that NTG was associated with decreased arteriolar and venular tortuosity, arteriolar branching angle, cpVD and cpFD. Decreased venular caliber, arteriolar and venular branching angles, cpVD and cpFD were associated with thinner average RNFL thickness. Decreased arteriolar and venular branching angles, cpVD and cpFD were also associated with worse standard automated perimetry measurements (mean deviation and visual field index). Compared with retinal arteriolar and venular metrics, regression models based on OCT-A capillary metrics consistently showed stronger associations with NTG and structural and functional measurements in NTG. We concluded that NTG eyes showed generalized microvascular attenuations, in which OCT-A capillary metrics attenuations were more prominent and strongly associated with NTG.
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http://dx.doi.org/10.1038/s41598-020-75784-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644687PMC
November 2020

Effect of weight loss on the retinochoroidal structural alterations among patients with exogenous obesity.

PLoS One 2020 9;15(7):e0235926. Epub 2020 Jul 9.

Department of Ophthalmology, Advanced Eye Center, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Purpose: To evaluate the changes in the retinochoroidal vasculature in patients with exogenous obesity using swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA).

Methods: In this prospective study, 60 patients diagnosed with obesity (47 males) (mean age: 46.47±10.9 years) were included, of which 30 patients underwent bariatric surgery (Group A), and 30 patients underwent conservative management (exercise/diet) (Group B). Parameters including choroidal thickness (CT), choroidal vascularity index (CVI) and retinal capillary density index (CDI) and arteriovenous ratio (AVR) were measured at the baseline and three months follow up. 30 eyes (30 age and gender-matched) of normal participants were included for comparison.

Results: Baseline CT was lower in 60 participants with obesity compared to controls. Compared with normal subjects, subjects with obesity had higher mean CVI (0.66±0.02 versus 0.63±0.04; p<0.01), smaller FAZ area (0.26±0.07 versus 0.45±0.32; p<0.01), higher CDI (superficial plexus: 0.7±0.04 versus 0.68±0.06; p = 0.04, deep plexus: 0.38±0.02 versus 0.35±0.06; p = 0.01), and lower AVR (0.68±0.05 versus 0.70±0.03 versus; p<0.01). At 3-month after intervention, CT showed a significant increase in participants from Group A (329.27±79μm; p<0.01) but not in Group B from baseline. No significant change was noted in CVI or CDI at 3-month in either group compared to baseline. AVR significantly increased in Group B (p = 0.03).

Conclusion: Subclinical changes in retinochoroidal vasculature occurs in participants with exogenous obesity compared to healthy subjects. Surgical intervention (bariatric surgery) may have a favorable outcome on the choroidal thickness in these patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235926PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347179PMC
September 2020

A plant DNA virus replicates in the salivary glands of its insect vector via recruitment of host DNA synthesis machinery.

Proc Natl Acad Sci U S A 2020 07 7;117(29):16928-16937. Epub 2020 Jul 7.

Ministry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Insect Sciences, Zhejiang University, 310058 Hangzhou, China;

Whereas most of the arthropod-borne animal viruses replicate in their vectors, this is less common for plant viruses. So far, only some plant RNA viruses have been demonstrated to replicate in insect vectors and plant hosts. How plant viruses evolved to replicate in the animal kingdom remains largely unknown. Geminiviruses comprise a large family of plant-infecting, single-stranded DNA viruses that cause serious crop losses worldwide. Here, we report evidence and insight into the replication of the geminivirus tomato yellow leaf curl virus (TYLCV) in the whitefly () vector and that replication is mainly in the salivary glands. We found that TYLCV induces DNA synthesis machinery, proliferating cell nuclear antigen (PCNA) and DNA polymerase δ (Polδ), to establish a replication-competent environment in whiteflies. TYLCV replication-associated protein (Rep) interacts with whitefly PCNA, which recruits DNA Polδ for virus replication. In contrast, another geminivirus, papaya leaf curl China virus (PaLCuCNV), does not replicate in the whitefly vector. PaLCuCNV does not induce DNA-synthesis machinery, and the Rep does not interact with whitefly PCNA. Our findings reveal important mechanisms by which a plant DNA virus replicates across the kingdom barrier in an insect and may help to explain the global spread of this devastating pathogen.
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http://dx.doi.org/10.1073/pnas.1820132117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382290PMC
July 2020

Whitefly HES1 binds to the intergenic region of Tomato yellow leaf curl China virus and promotes viral gene transcription.

Virology 2020 03 21;542:54-62. Epub 2020 Jan 21.

Ministry of Agriculture Key Laboratory of Molecular Biology of Crops Pathogens and Insects, Institute of Insect Sciences, Zhejiang University, Hangzhou, China. Electronic address:

Intergenic region of begomovirus genome is vital to virus replication and viral gene transcription in plants. Previous studies have reported that Tomato yellow leaf curl China virus (TYLCCNV), a begomovirus, is able to accumulate and transcribe in its whitefly vector. However, the viral and host components that participate in begomovirus transcription in whiteflies are hitherto unknown. Using a yeast one-hybrid system, we identified >50 whitefly proteins that interacted with TYLCCNV intergenic region. Dual luciferase analysis revealed that one of the identified proteins, the hairy and enhancer of split homolog-1 (HES1), specifically bound to CACGTG motif in TYLCCNV intergenic region. Silencing HES1 decreased viral transcription, accumulation and transmission. These results demonstrate that the interactions between whitefly proteins and the intergenic region of TYLCCNV may contribute to viral transcription in the whitefly vector. Our findings offer valuable clues for the research and development of novel strategies to interfere with begomovirus transmission.
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http://dx.doi.org/10.1016/j.virol.2020.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031692PMC
March 2020

High prevalence of myopia in children and their parents in Hong Kong Chinese Population: the Hong Kong Children Eye Study.

Acta Ophthalmol 2020 Jan 24. Epub 2020 Jan 24.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong.

Purpose: To determine the myopia prevalence in Hong Kong Chinese children and their parents.

Methods: It was a population-based cross-sectional study. A total of 4257 children aged 6-8 years, and 5880 parents were recruited in the Hong Kong Children Eye Study. Cycloplegic autorefraction was measured for children; and non-cycloplegic autorefraction for parents. Parental educational level, children's outdoor time, and near work were collected by validated questionnaires.

Results: In children aged 6-8 years, 25.0% were myopic, and among them, 12.7% for the 6-year-olds, 24.4% for the 7-year-olds and 36.1% for the 8-year-old. About 0.7% of children aged 8 years were high myopia. In all age groups, boys (their myopia rate: 13.9% at 6 years, 26.7% at 7 years, and 38.3% at 8 years) were more myopic than girls (11.3% at 6 years, 22.0% at 7 years, 33.4% at 8 years). Among parents, 72.2% were myopic (mother, 73.2%; father, 70.7%) and 13.5% high myopia (mother, 12.8%; father, 14.5%). It was observed that prevalence decreased with ages and increased with education level.

Conclusion: There is a strikingly high prevalence of myopia in Hong Kong children aged 6-8, much higher than that of other regions of China. Of note, the prevalence of children was similar to that in 15 years ago. Furthermore, the myopia prevalence of parents is high, and it had already increased in this cohort. Prevention of childhood myopia is important, likewise for visual complications from high myopia in adults.
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http://dx.doi.org/10.1111/aos.14350DOI Listing
January 2020

Isoquinolines from national herb Corydalis tomentella and neuroprotective effect against lipopolysaccharide-induced BV2 microglia cells.

Bioorg Chem 2020 01 9;95:103489. Epub 2019 Dec 9.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address:

Five new isoquinolines (1-5) were isolated from national herb Corydalis tomentella. Their structures were elucidated by extensive analysis of the 1D and 2D NMR spectra and from the HRESIMS. Absolute configurations of 1-3 were determined by comparing their experimental and computed ECD data. Since plants from Corydalis have been reported to protect against Alzheimer's disease, all compounds were evaluated for their neuroprotective effect against lipopolysaccharide-induced BV2 microglia cells. Compound 2 and 3 showed well anti-neuroinflammatory activity at low concentration (25 μM).
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http://dx.doi.org/10.1016/j.bioorg.2019.103489DOI Listing
January 2020

Chemical Constituents of Stems and Leaves of L. and Its Fingerprint.

Molecules 2019 Oct 30;24(21). Epub 2019 Oct 30.

Dalian Wuzhou Holy Herb Scientific and Techonological Co. Ltd., Dalian 116600, China.

L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (, ) and fourteen known metabolites (-) were isolated from the stems and leaves of (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds and were determined by ECD calculations. Compounds and exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC values of 41.20 μmol/L and 30.43 μmol/L, respectively. The fingerprint profiles of stems and leaves of with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.
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http://dx.doi.org/10.3390/molecules24213911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864839PMC
October 2019

Corneal Biomechanical Evaluation After Conventional Corneal Crosslinking With Oxygen Enrichment.

Eye Contact Lens 2020 Sep;46(5):306-309

Department of Ophthalmology (J.W., L.W., Z.L., K.Z., G.M.), Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China; Aier Eye Hospital Group (J.W.), Liaocheng Aier Eye Hospital, Liaocheng, Shandong, China; Department of Ophthalmology (L.W.), Binzhou Medical University Hospital, Binzhou, Shandong, China; and Department of Ophthalmology and Visual Sciences (Y.M.W.), The Chinese University of Hong Kong, Hong Kong, China.

Purpose: To assess corneal biomechanical changes after conventional corneal crosslinking (CXL), with and without oxygen enrichment.

Methods: Sixty fresh porcine corneas were randomly divided into group 1 (control), group 2 (conventional CXL), and group 3 (conventional CXL in a high-oxygen environment during ultraviolet A [UVA] irradiation). After crosslinking, a 5-mm wide corneal strip was extracted using a double-bladed knife from 12 to 6'o clock. The Young's modulus of each strip was determined by stress-strain measurements. A comparison between the three groups was performed with a one-way analysis of variance.

Results: At 4% strain, the Young's modulus of the corneas in groups 1, 2, and 3 were: 0.68±0.20 megapascal (MPa), 1.01±0.23 MPa, and 1.12±0.24 MPa, respectively. The Young's modulus values for groups 2 and 3 showed no statistical significance (P>0.05), However, both groups 2 and 3 were significantly higher than group 1 (P<0.05). At 6% strain, the Young's modulus of the corneas in groups 1, 2, and 3 were: 0.97±0.21, 1.35±0.25, and 1.64±0.44 MPa, respectively, and at 8% strain, the Young's modulus was: 1.29±0.26, 1.72±0.45, 2.20±0.74 MPa, respectively. At 6% and 8% strain, the Young's modulus for the corneas in group 3 was significantly higher than those in both group 1 and group 2 (P<0.05).

Conclusions: Increasing oxygen concentration during UVA irradiation may improve the efficacy of conventional CXL.
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http://dx.doi.org/10.1097/ICL.0000000000000645DOI Listing
September 2020

Rosmarinic acid treatment during porcine oocyte maturation attenuates oxidative stress and improves subsequent embryo development .

PeerJ 2019 18;7:e6930. Epub 2019 Jun 18.

College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.

Background: maturation (IVM) of oocytes has been widely used in the field of assisted reproductive technology. However, oocytes can be injured by oxidative stress during the process of IVM.

Methods: The present study was designed to evaluate the influences of rosmarinic acid (RA) on the IVM of porcine oocytes and the subsequent development of early-stage embryos as well as its underlying mechanisms. Various concentrations of RA (5 µM, 10 µM, and 25 µM) were treated with porcine oocyte maturation medium during the period of IVM.

Results And Discussion: The results showed that 5 µM RA treatment during the period of porcine oocyte IVM improves blastocyst quality and hatching ability after parthenogenetic activation. Furthermore, the presence of RA during the period of IVM dramatically improved the total number of cells after somatic cell nuclear transfer compared to the number of cells in the control group. Notably, RA treatment during the period of porcine oocyte IVM decreased intracellular reactive oxygen species generation not only in oocytes but also in cumulus cells. Further analysis showed that the intracellular free thiols levels in the oocytes were enhanced by treatment with RA during the period of porcine oocyte IVM compared to the free thiols levels in the control groups. These results indicate that RA improves the developmental competence of porcine oocytes during the IVM period by attenuating oxidative stress.
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http://dx.doi.org/10.7717/peerj.6930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587974PMC
June 2019

Virtual screening of active compounds from Artemisia argyi and potential targets against gastric ulcer based on Network pharmacology.

Bioorg Chem 2019 07 13;88:102924. Epub 2019 Apr 13.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Beijing Shijitan Hospital, Capital Medical University, Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing 100038, PR China. Electronic address:

Artemisia argyi (AA) is one of the renowned herbs in China often used in the treatment of gastric ulcer (GU). Aiming to predict the active compounds and systematically investigate the mechanisms of Artemisia argyi for GU treatment, the approach of network pharmacology, molecular docking, gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were adopted, respectively, in present study. A total of 13 predicted targets of the 103 compounds in Artemisia argyi were obtained. Sorted by pathogenic mechanisms of targets and structure types of compounds, it was revealed that flavonoids and sesquiterpenes had better performance than monoterpenes. The network analysis showed that Phospholipase a2 (PA21B), Sulfotransferase family cytosolic 2b member 1 (ST2B1), Nitric-oxide synthase, endothelial (NOS3), Gastrin (GAST), neutrophil collagenase (MMP-8), Leukotriene A-4 hydrolase (LKHA4), Urease maturation factor HypB (HYPB), and Periplasmic serine endoprotease DegP (HtrA) were the key targets with intensely interaction. The functional enrichment analysis indicated that AA probably produced the gastric mucosa protection effects by synergistically regulating many biological pathways, such as NF-κB signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, VEGF signaling pathway, and Toll-like receptor signaling pathway, etc. In addition, C73 and C15 might be promising leading compounds with good molecular docking score. As a consequence, this study holistically illuminates the active constituents and mechanisms based on data analysis, which contributes to searching for leading compounds and the development of new drugs for gastric ulcer.
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http://dx.doi.org/10.1016/j.bioorg.2019.102924DOI Listing
July 2019

Repeatability and Agreement of a Swept-Source Optical Coherence Tomography-Based Biometer IOLMaster 700 Versus a Scheimpflug Imaging-Based Biometer AL-Scan in Cataract Patients.

Eye Contact Lens 2020 Jan;46(1):35-45

Department of Ophthalmology and Visual Sciences (T.C.Y.C., K.H.W., F.Y.T., Y.M.W., and C.C.), The Chinese University of Hong Kong, Kowloon, Hong Kong; Hong Kong Eye Hospital (T.C.Y.C.), Kowloon, Hong Kong; and Department of Mathematics and Statistics (M.Y.), Hang Seng Management College, New Territories, Hong Kong.

Purpose: To compare the repeatability and agreement between a swept-source biometer and a Scheimpflug biometer in cataract patients.

Methods: Three consecutive measurements were obtained using a swept-source biometer (IOLMaster 700) and a Scheimpflug biometer (AL-Scan) in 52 eyes of 52 patients. Keratometry, central corneal thickness (CCT), anterior chamber depth (ACD), axial length, and white-to-white (WTW) distance were recorded. Astigmatism values were transformed into vector components of J0 and J45. Intraoperator repeatability was analyzed using intraclass correlation coefficients (ICCs) and reproducibility coefficients (RCs). Agreement of measurements between the two devices was evaluated using the Bland-Altman method.

Results: The IOLMaster 700 showed higher ICCs and lower RCs for the mean keratometry (Km) (P≤0.018), CCT (P≤0.027), and ACD (P≤0.001) measurements, whereas the AL-Scan showed higher ICC and lower RC for the J45 vector component of astigmatism at the 2.4-mm zone (P≤0.034). Both the devices had excellent repeatability (ICC=0.999) in axial length measurement. Systematic differences were found in Km, CCT, ACD, and WTW (P≤0.018) between the devices. The mean difference for Km was -0.196 and -0.144 D measured at the 2.4-mm zone and 3.3-mm zone, respectively. The corresponding mean difference for CCT, ACD, and WTW distance was 14.92 μm, -0.017 mm, and 0.283 mm, respectively. These differences led to a statistically significant but clinically insignificant difference in the prediction of intraocular lens power.

Conclusions: This study showed significant differences in anterior segment measurement repeatability and agreement between a swept-source biometer and a Scheimpflug biometer in eyes with cataract.
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http://dx.doi.org/10.1097/ICL.0000000000000603DOI Listing
January 2020

Perturbations in Amino Acid Metabolism in Children with Kaschin-Beck Disease: A Study of Urinary Target Metabolomics.

Biomed Environ Sci 2019 Jan;32(1):34-37

The Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang, China.

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http://dx.doi.org/10.3967/bes2019.004DOI Listing
January 2019

MicroRNA-197 controls ADAM10 expression to mediate MeCP2's role in the differentiation of neuronal progenitors.

Cell Death Differ 2019 10 18;26(10):1863-1879. Epub 2018 Dec 18.

Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, 200011, Shanghai, China.

Duplication of MECP2 (Methyl-CpG-binding protein 2) causes severe mental illness called MECP2 duplication syndrome (MDS), yet the underlying mechanism remains elusive. Here we show, in Tg(MECP2) transgenic mouse brain or cultured neural progenitor cells (NPCs), that elevated MeCP2 expression promotes NPC differentiation into neurons. Ectopic expression of MeCP2 inhibits ADAM10 and thus the NOTCH pathway during NPC differentiation. In human cells, this downregulation on ADAM10 was mediated by miRNA-197, which is upregulated by MeCP2. Surprisingly, miR-197 binds to the ADAM10 3'-UTR via its 3' side, not the canonical seed sequence on the 5' side. In mouse cells, a noncoding RNA Gm28836 is used to replace the function of miR-197 between MeCP2 and ADAM10. Similar to MeCP2, overexpressing miR-197 also promotes NPCs differentiation into neurons. Interestingly, three rare missense mutations (H371R, E394K, and G428S) in MECP2, which we identified in a Han Chinese autism spectrum disorders (ASD) cohort showed loss-of-function effects in NPC differentiation assay. These mutations cannot upregulate miR-197. Overexpressing miR-197 together with these MeCP2 mutations could rescue the downregulation on ADAM10. Not only the inhibitor of miR-197 could reverse the effect of overexpressed MeCP2 on NPCs differentiation, but also overexpression of miR-197 could reverse the NPCs differentiation defects caused by MECP2 mutations. Our results revealed that a regulatory axis involving MeCP2, miR-197, ADAM10, and NOTCH signaling is critical for NPC differentiation, which is affected by both MeCP2 duplication and mutation.
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http://dx.doi.org/10.1038/s41418-018-0257-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748079PMC
October 2019

Comparison of Corneal Tomography and a New Combined Tomographic Biomechanical Index in Subclinical Keratoconus.

J Refract Surg 2018 Sep;34(9):616-621

Purpose: To investigate and compare the diagnostic ability of corneal tomography and biomechanical and combined parameters for detection of corneal ectasia.

Methods: Consecutive patients with subclinical keratoconus (SCKC) and age-matched controls were included. Only one eye from each patient was selected for analysis. The final D value from the Belin/Ambrósio Enhanced Ectasia Display (BAD) was obtained from the Pentacam (Oculus Optikgeräte, Wetzlar, Germany). The tomographic biomechanical index (TBI) was derived from the Pentacam and Corvis ST (Oculus Optikgeräte). Classification analysis between normal and subclinical keratoconus (SCKC) was evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) and partial AUC (pAUC) with specificity of 80% or greater were compared.

Results: Twenty-three eyes with SCKC and 37 normal eyes were included. All Pentacam-derived parameters (P < .001) and all but two Corvis ST-derived parameters (P < .020) were significantly different between normal and SCKC eyes. A significant difference was found in the final D value (P ≤ .020) and TBI (P ≤ .040) between normal and SCKC eyes. For differentiating normal and SCKC eyes, TBI and BAD final D value demonstrated the highest AUC (0.925 and 0.786, respectively) and pAUC (0.150 and 0.088, respectively). TBI demonstrated 84.4% sensitivity and 82.4% specificity using a cut-off of 0.16. Comparative analysis between these parameters showed that AUC and pAUC of TBI were significantly higher than all parameters from Pentacam (P ≤ .032).

Conclusions: In the current study, combined use of tomographic and biomechanical parameters demonstrated a higher capability in differentiating normal and SCKC eyes when compared to tomographic analysis alone. [J Refract Surg. 2018;34(9):616-621.].
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http://dx.doi.org/10.3928/1081597X-20180705-02DOI Listing
September 2018

Analysis of multiple genetic loci reveals rs1324183 as a putative genetic marker for keratoconus.

Br J Ophthalmol 2018 12 12;102(12):1736-1741. Epub 2018 Jul 12.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

Objective: To investigate the associations between 16 single-nucleotide polymorphisms (SNPs) in 14 genetic loci and keratoconus in an independent Chinese cohort.

Methods: This cross-sectional, case-control association study included a Chinese cohort of 133 patients with keratoconus and 371 control subjects. In a recent meta-analysis study, we identified association of 16 SNPs in 14 gene loci with keratoconus. In this study, we genotyped these 16 SNPs in all the patients and controls and analysed their association with keratoconus, its clinical severities and progression profiles. We also analysed the genotype-phenotype correlation between individual SNPs and steep keratometry, flat keratometry (Kf), average keratometry (Avg K) and best-fit sphere diameter (BFS) of the anterior and posterior corneal surface.

Results: Among the 16 selected SNPs, rs1324183 in the locus showed a significant association with keratoconus (OR=2.22; 95% CI 1.42 to 3.45, p=4.30×10), especially severe keratoconus (OR=5.10, 95% CI 1.63 to 15.93, p=0.005). The rs1324183 A allele was positively associated with anterior Kf (p=0.008), anterior Avg K (p=0.017), posterior Kf (p=0.01) and negatively associated with apex pachymetry (p=0.007) and anterior BFS (p=0.023) in keratoconus. The other 15 SNPs had no significant association with keratoconus or genotype-phenotype correlations.

Conclusions: This study confirmed the association of SNP rs1324183 in with keratoconus and revealed the association of this SNP with keratoconus severity and corneal parameters. It is thus a putative genetic marker for monitoring the progression of keratoconus to a severe form and facilitating early intervention.
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http://dx.doi.org/10.1136/bjophthalmol-2018-312218DOI Listing
December 2018

Survival Analysis of Corneal Densitometry After Collagen Cross-Linking for Progressive Keratoconus.

Cornea 2018 Nov;37(11):1449-1456

Cornea Service, Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.

Purpose: To evaluate the history of densitometric data in patients with keratoconus undergoing corneal cross-linking.

Methods: Twenty-two eyes of 22 patients with keratoconus were included. Corneal tomography and densitometry measurements were performed before and after accelerated corneal cross-linking. The duration of corneal haze was defined as the time between cross-linking and densitometry measurements returning to the preoperative value. Survival analysis of corneal haze after cross-linking was performed. Preoperative and postoperative corneal densitometry, maximum keratometry (Kmax), and central corneal thickness were compared.

Results: The duration of corneal haze was 18.2 ± 3.8 months at the first zone of 0 to 2 mm and 10.9 ± 2.5 months at the second zone of 2 to 6 mm. There was no change in Kmax between the preoperative period and the time at which corneal haze resolved (P = 0.394 at the first zone; P = 0.658 at the second zone). Compared with the measurement taken at resolution of corneal haze, Kmax at 1 year after haze resolution was lower (62.0 ± 9.9 D to 61.2 ± 9.9 D, P = 0.008 at the first zone; 63.6 ± 10.9 D to 62.5 ± 10.1 D, P = 0.016 at the second zone). There was a decrease of central corneal thickness between the preoperative period and the time at which corneal haze resolved (470.8 ± 34.1 μm to 464.8 ± 34.5 μm, P = 0.047 at the first zone; 465.0 ± 35.3 μm to 454.7 ± 37.2 μm, P = 0.001 at the second zone), but it remained unchanged after haze resolution (P = 0.146 at the first zone; P = 0.067 at the second zone).

Conclusions: Corneal cross-linking halted keratoconus progression when detectable haze was present. There was continuous corneal flattening measured at 1 year after haze resolution. Thinning of the cornea was seen only when haze was detectable after cross-linking.
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http://dx.doi.org/10.1097/ICO.0000000000001686DOI Listing
November 2018

Factors Associated With Long-term Intraocular Pressure Fluctuation in Primary Angle Closure Disease: The CUHK PACG Longitudinal (CUPAL) Study.

J Glaucoma 2018 08;27(8):703-710

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong.

Purpose: To determine the demographic, ocular, and systemic factors associated with long-term intraocular pressure (IOP) fluctuation in primary angle closure disease (PACD).

Methods: This prospective cohort study included 422 PACD eyes from 269 Chinese patients, including 274 primary angle closure glaucoma (PACG) eyes and 152 primary angle closure/primary angle closure suspect (PAC/PACS) eyes. Long-term IOP fluctuation defined as the SD of all IOP measurements over 2 years (at least 5 measurements in total). Chinese patients with PACD were recruited and followed up 3 monthly. Eyes with IOP-lowering surgery or lens extraction performed within the 2-year study period were excluded. Patient demographics, received treatments, ocular biometry, retinal nerve fiber layer thickness, and systemic factors (eg, hypertension, smoking) were evaluated. Generalized estimating equations adjusting for inter-eye correlation were used to determine the associations.

Results: Eyes with PACG had significantly higher IOP fluctuation than PAC/PACS (2.4±1.2 versus 2.1±0.9 mm Hg; P=0.04). In the multivariate analysis with PACG eyes, higher baseline IOP (P<0.001), greater number of IOP-lowering medications (P<0.001), previous trabeculectomy (P=0.002), and current smoking (P=0.03) were significantly associated with larger IOP fluctuation, whereas diabetes mellitus was associated with lower IOP fluctuation (P=0.03). Among PAC/PACS eyes, younger age group (P<0.001), male sex (P=0.002), and higher baseline IOP (P<0.001) were significantly associated with larger IOP fluctuation.

Conclusions: PACG eyes have greater IOP fluctuation than PAC/PACS eyes. Certain demographic, ocular, and systemic factors are associated with IOP fluctuation in PACD eyes.
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http://dx.doi.org/10.1097/IJG.0000000000000996DOI Listing
August 2018

Glycine treatment enhances developmental potential of porcine oocytes and early embryos by inhibiting apoptosis.

J Anim Sci 2018 Jun;96(6):2427-2437

College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.

Glycine, a component of glutathione (GSH), plays an important role in protection from reactive oxygen species (ROS) and inhibition of apoptosis. The aim of this study was to determine the effect of glycine on in vitro maturation (IVM) of porcine oocytes and their developmental competence after parthenogenetic activation (PA). We examined nuclear maturation, ROS levels, apoptosis, mitochondrial membrane potential (ΔΨm), and ATP concentration, as well as the expression of several genes related to oocyte maturation and development. Our studies found that treatment with glycine in IVM culture medium increased nuclear maturation rate, but varying the concentrations of glycine (0.6, 6, or 12 mM) had no significant effect. Furthermore, 6 mM glycine supported greater blastocyst formation rates and lesser apoptosis after PA than the other concentrations (P < 0.05). All the glycine treatment groups had decreased levels of ROS in both matured oocytes and at the 2-cell stage (P < 0.05). At the 2-cell stage, the 6 mM glycine group had ROS levels that were lesser than the other 2 glycine treatment groups (0.6 and 12 mM). From this, we deemed 6 mM to be the optimal condition, and we then investigated the effects of 6 mM glycine on gene expression. The expression of both FGFR2 and Hsf1 were greater than the control group in mature oocytes. The glycine treatment group had greater levels of expression of an antiapoptotic gene (Bcl2) in mature oocytes and cumulus cells and lesser levels of expression of a proapoptotic gene (Bax) in PA blastocysts (P < 0.05). In addition, mitochondrial ΔΨm and ATP concentration were increased in 6 mM glycine group compared with the control group. In conclusion, our results suggest that glycine plays an important role in oocyte maturation and later development by reducing ROS levels and increasing mitochondrial function to reduce apoptosis.
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http://dx.doi.org/10.1093/jas/sky154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095358PMC
June 2018

Histological and microRNA Signatures of Corneal Epithelium in Keratoconus.

J Refract Surg 2018 Mar;34(3):201-211

Purpose: To illustrate the histopathology of keratoconic corneal epithelia and its micro-ribonucleic acid (miRNA) regulation.

Methods: Corneal epithelia were collected from 27 patients with keratoconus and 26 normal patients after surgery or by impression cytology. The miRNA profile was determined using miRNA microarray. The biological roles of miRNA target genes were delineated by gene ontology and pathway analyses. The expressions of significant miRNAs were validated using TaqMan polymerase chain reaction (PCR), whereas protein localization and expression of the miRNA target genes were examined by immunofluorescence and immunoblotting analyses.

Results: Histological assessment showed that corneal epithelia in patients with keratoconus were thinner with loosely packed cells compared to normal patients. Microarray analysis revealed that 12 miRNAs were significantly downregulated in keratoconic corneal epithelia. Gene ontology analysis demonstrated that the predicted miRNA target genes participated in cell junction, cell division, and motor activity, whereas pathway analysis highlighted the involvement of syndecan-mediated signaling pathway. TaqMan PCR validated the altered expression of six miRNAs in corneal epithelia from surgery (hsa-miR-151a-3p, hsa-miR-138-5p, hsa-miR-146b-5p, hsa-miR-194-5p, hsa-miR-28-5p, and hsa-miR-181a-2-3p) and four miRNAs in squamous corneal epithelial samples collected from impression cytology (hsa-miR-151a-3p, hsa-miR-195-5p, hsa-miR-185-5p, and hsa-miR-194-5p). In addition, higher S100A2 expression was found in the epithelial basal cell layer of keratoconic corneal epithelia.

Conclusions: The miRNA and histological analyses in this study demonstrated structural and biological changes in keratoconic corneal epithelia, broadening the understanding of keratoconus pathology. In addition, impression cytology is useful to collect corneal epithelial tissues for gene expression analysis. [J Refract Surg. 2018;34(3):201-211.].
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http://dx.doi.org/10.3928/1081597X-20171215-02DOI Listing
March 2018

Association of the gene with extreme myopia rather than lower grade myopias.

Br J Ophthalmol 2018 04 7;102(4):570-574. Epub 2018 Feb 7.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Aims: To investigate the association of the () with different severities of myopia.

Methods: A total of four haplotype-tagging single-nucleotide polymorphisms (SNPs; rs2071754, rs3026354, rs3026390 and rs628224) and two previously reported SNPs (rs644242 and rs662702) in the gene were analysed in a Hong Kong Chinese cohort of 1288 myopia subjects (including 252 extreme myopia, 277 high myopia, 393 moderate myopia and 366 mild myopia) and 791 no myopia controls. Allelic association analyses were performed for individual SNPs in different subgroups of myopia and in combined myopia, followed by a meta-analysis of our current data with reported data on in myopia.

Results: The association of tagging SNPs rs2071754 and rs644242 with extreme myopia could not withstand multiple correction (rs2071754: OR=1.25, P value=0.031; rs644242: OR=1.33, P value=0.032). In the meta-analysis, rs644242 showed an enhanced, significant association with extreme myopia (OR=1.27, 95% CI 1.10 to 1.46, P value=0.001; I=0%). In contrast, there was no significant association between the SNPs and high, moderate or mild myopia. No linear correlation was found between the SNPs and axial length.

Conclusion: This study provides additional evidence suggesting that the SNP rs644242 is associated with extreme myopia but not lower grade myopia. Thus, may be implicated in the development or progression into severe myopia. Further longitudinal studies are warranted.
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http://dx.doi.org/10.1136/bjophthalmol-2017-311327DOI Listing
April 2018

Downregulation of β1,4-galactosyltransferase 5 improves insulin resistance by promoting adipocyte commitment and reducing inflammation.

Cell Death Dis 2018 02 7;9(2):196. Epub 2018 Feb 7.

Key Laboratory of Metabolic Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, 200032, China.

Protein glycosylation is an important post-translational modification. Aberrant glycosylation has been implicated in many diseases because of associated changes in protein distribution and biological function. We showed that the expression of β1, 4-galactosyltransferase 5 (B4GalT5) was positively correlated with diabetes and obesity. In vivo, B4GalT5 knockdown in subcutaneous adipose tissue alleviated insulin resistance and adipose tissue inflammation, and increased adipogenesis in high-fat diet (HFD)-fed mice and ob/ob mice. Downregulation of B4GalT5 in preadipocyte cells induced commitment to the adipocyte lineage in the absence of bone morphogenetic protein (BMP) 2/4 treatment, which is typically essential for adipogenic commitment. RNAi silencing experiments showed B4GalT5 knockdown activated Smad and p38 MPAK signaling pathways through both type 1A and 2 BMP receptors. Remarkably, B4GalT5 knockdown decreased BMPRIA glycosylation but increased BMPRIA stability and cellular location, thus leading to redistribution of BMPRIA and activation of the BMP signaling pathway. Meanwhile, downregulation of B4GalT5 decreased the infiltration of macrophages and the markers of M1 macrophages in subcutaneous adipose tissue of HFD mice and ob/ob mice. In bone marrow-derived macrophages (BMDMs) and RAW264.7cells, B4GalT5 knockdown also repressed the markers of M1 by reducing NFκB and JNK signaling. These results demonstrated B4GalT5 downregulation improved insulin resistance by promoting adipogenic commitment and decreasing M1 macrophage infiltration.
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http://dx.doi.org/10.1038/s41419-017-0239-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833706PMC
February 2018

Comparative evaluation of progression rate in keratoconus before and after collagen crosslinking.

Br J Ophthalmol 2018 08 9;102(8):1109-1113. Epub 2017 Nov 9.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Purpose: To compare the rate of disease progression in keratoconus before and after corneal collagen crosslinking (CXL).

Methods: 145 eyes were followed without CXL (no-CXL group) for a median duration of 31 months whereas 45 eyes were followed up for 41 months before (pre-CXL) and after (post-CXL) accelerated, epithelium-off crosslinking. Progression was defined based on significant slope found in linear mixed effect models against time. Swept-source optical coherence tomography was used for measurement of anterior steep keratometry, anterior flat keratometry (Ant Kf), anterior average keratometry (Ant Avg K); posterior steep keratometry, posteriorflat keratometry (Post Kf), posterior average keratometry (Post Avg K) and corneal thickness.

Results: The patients in pre-CXL group were significantly younger (26.3±5.48 years) compared with the patients in no-CXL group (32.7±10.24 years) (P=0.004). Significant differences were observed during baseline examination for all parameters (P≤0.035) between pre-CXL and no-CXL groups except Ant Cyl and Post Cyl. During observation period, statistically significant differences were noted between pre-CXL and no-CXL groups in the progression rate of Ant Kf, Ant Avg K, Post Kf and Post Avg K (P≤0.045). After CXL, the progression rate in post-CXL group was comparable to that in no-CXL group. All corneal parameters remained stable in no-CXL group throughout the follow-up period.

Conclusions: Serial tomographic examination is useful to document disease progression before and after CXL. In our study, a decrease in progression rate of corneal parameters was noted after CXL. In cases with stable corneal parameters over time, careful monitoring can be considered instead of collagen crosslinking.
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http://dx.doi.org/10.1136/bjophthalmol-2017-311017DOI Listing
August 2018

Comparison of Corneal Dynamic and Tomographic Analysis in Normal, Forme Fruste Keratoconic, and Keratoconic Eyes.

J Refract Surg 2017 Sep;33(9):632-638

Purpose: To investigate and compare the diagnostic ability of corneal tomography and dynamic corneal response to differentiate between normal eyes and those with forme fruste keratoconus and keratoconus.

Methods: Corneal tomography was performed using Pentacam (Pentacam HR; Oculus Optikgeräte, Wetzlar, Germany). Corneal deformation response was captured via Corvis ST (Optikgeräte) using a beta version of Corvis software. Classification analysis between normal eyes and eyes with forme fruste keratoconus and between normal and keratoconic eyes was evaluated using receiver operating characteristic curves. The area under the ROC curve (AUC) and partial AUC (pAUC) for each classifying parameter were compared.

Results: Twenty-one patients with forme fruste keratoconus in one eye and clinically evident keratoconus in the fellow eye and 38 normal individuals were recruited. Overall, 21 eyes with forme fruste keratoconus and 18 eyes with keratoconus were compared with 73 normal eyes. The mean age of the participants was comparable between groups. Comparative analysis between Pentacam and Corvis ST parameters showed significantly lower AUC and pAUC for Corvis ST parameters in differentiating keratoconic from normal eyes (P ≥ .049). However, comparable AUC and pAUC was observed between the Corvis Biomechanical Index (AUC = 0.785; pAUC = 0.079) and D value of the Belin/Ambrósio Enhanced Ectasia Display (AUC = 0.757; pAUC = 0.068) (P ≥ .477) for detection of forme fruste keratoconus with sensitivities of 63.2% and 52.6%, given a common specificity of 80.3%.

Conclusions: The current study showed the feasibility of use of non-tomographical parameters obtained from the Corvis ST for differentiating normal eyes and those with forme fruste keratoconus and keratoconus. The diagnostic ability of the Corvis ST was comparable to that of the Pentacam for differentiating normal eyes and eyes with forme fruste keratoconus. [J Refract Surg. 2017;33(9):632-638.].
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http://dx.doi.org/10.3928/1081597X-20170621-09DOI Listing
September 2017

Shift in progression rate of keratoconus before and after epithelium-off accelerated corneal collagen crosslinking.

J Cataract Refract Surg 2017 07;43(7):929-936

From the Department of Ophthalmology and Visual Sciences (Wang, Chan, Jhanji), the Chinese University of Hong Kong, Hong Kong Eye Hospital (Chan), and the Department of Mathematics and Statistics (Yu), Hang Seng Management College, Hong Kong, China; Department of Ophthalmology (Jhanji), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. Electronic address:

Purpose: To evaluate the shift in keratoconus progression rate after corneal collagen crosslinking (CXL).

Setting: Chinese University of Hong Kong Eye Centre, Hong Kong, China.

Design: Prospective case series.

Method: Accelerated epithelium-off CXL was performed in patients with progressive keratoconus. Optical coherence tomography-based corneal measurements were recorded. The data collected after the first postoperative month were used for analysis. The main outcome measure was the rate of progression of steep keratometry (K), flat K, average K, and best-fit sphere (BFS) using linear mixed-effects models. Progression was defined based on a significant slope against time in these models.

Results: Forty-seven eyes (38 patients; mean age 27.6 years ± 6.5 [SD]) were included. The median number of preoperative visits and postoperative visits was 3 and 5, respectively. A significant reduction in the progression rate of the anterior average K (0.063 ± 0.138 diopter [D]/mo to -0.022 ± 0.029 D/mo) and posterior average K (-0.011 ± 0.025 D/mo to 0.000 ± 0.009 D/mo) occurred (both P < .001). On univariate analysis, the baseline anterior average K had the strongest association with the progression rate of the anterior average K after CXL. On multivariate analysis, the preoperative progression rate of the posterior BFS was significantly associated with postoperative progression rate of the anterior (P < .001) and posterior average K (P ≤ .05).

Conclusions: A significant reduction in the progression rate of average K occurred after accelerated epithelium-off CXL. The reduction was associated with the baseline anterior average K and preoperative progression of posterior BFS.
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http://dx.doi.org/10.1016/j.jcrs.2017.04.033DOI Listing
July 2017

Genetic associations for keratoconus: a systematic review and meta-analysis.

Sci Rep 2017 07 4;7(1):4620. Epub 2017 Jul 4.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Genetic associations for keratoconus could be useful for understanding disease pathogenesis and discovering biomarkers for early detection of the disease. We conducted a systematic review and meta-analysis to summarize all reported genetic associations for the disease. We searched in the MEDLINE, Embase, Web of Science, and HuGENET databases for genetic studies of keratoconus published from 1950 to June 2016. The summary odds ratio and 95% confidence intervals of all polymorphisms were estimated using the random-effect model. Among 639 reports that were retrieved, 24 fulfilled required criteria as eligible studies for meta-analysis, involving a total of 53 polymorphisms in 28 genes/loci. Results of our meta-analysis lead to the prioritization of 8 single-nucleotide polymorphisms (SNPs) in 6 genes/loci for keratoconus in Whites. Of them 5 genes/loci were originally detected in genome-wide association studies, including FOXO1 (rs2721051, P = 5.6 × 10), RXRA-COL5A1 (rs1536482, P = 2.5 × 10), FNDC3B (rs4894535, P = 1.4 × 10), IMMP2L (rs757219, P = 6.1 × 10; rs214884, P = 2.3 × 10), and BANP-ZNF469 (rs9938149, P = 1.3 × 10). The gene COL4A4 (rs2229813, P = 1.3 × 10; rs2228557, P = 4.5 × 10) was identified in previous candidate gene studies. We also found SNPs in 10 genes/loci that had a summary P value < 0.05. Sensitivity analysis indicated that the results were robust. Replication studies and understanding the roles of these genes in keratoconus are warranted.
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http://dx.doi.org/10.1038/s41598-017-04393-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496893PMC
July 2017