Publications by authors named "Mingming Ma"

124 Publications

A Higher Serum Calcium Level is an Independent Risk Factor for Vision-Threatening Diabetic Retinopathy in Patients with Type 2 Diabetes: Cross-Sectional and Longitudinal Analyses.

Endocr Pract 2021 May 14. Epub 2021 May 14.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai engineering center for precise diagnosis and treatment of eye diseases, Shanghai, China. Electronic address: https://orcid.org/0000-0001-8435-0240.

Objective: An elevated serum calcium level is associated with a higher risk of type 2 diabetes (T2D), but its role in microvascular complications remains unclear. This study was conducted to investigate the association between serum calcium levels and vision-threatening diabetic retinopathy (VTDR).

Methods: This study employed a cross-sectional and longitudinal design. The cross-sectional part included all patients treated for T2D at Shanghai General Hospital between 2007 and 2016, while the longitudinal part involved an overlapping cohort of diabetic patients without VTDR who were followed from their admission until December 2019. VTDR was defined as severe nonproliferative, proliferative diabetic retinopathy, or clinically significant macular edema. Multivariable logistic and Cox proportional hazard regression analyses were performed respectively.

Results: A total of 3269 patients were included in the cross-sectional analysis, and 649 patients were included in the longitudinal analysis. In the cross-sectional analysis, the following factors were independently associated with VTDR: higher corrected serum calcium (odds ratio 1.31 per 0.1 mmol/L, 95% confidence interval [CI] 1.16-1.49), younger age, longer diabetes duration, albuminuria, impaired renal function, and lower serum magnesium. In the longitudinal analysis, 95 subjects developed VTDR during follow-up (9.7 years, interquartile range 7.4-10.9 years). The following variables were identified as independent risk factors for VTDR: higher corrected serum calcium (hazard ratio 1.38 per 0.1 mmol/L, 95% CI 1.10-1.72), younger age, longer diabetes duration, sub-VTDR, albuminuria, lower serum magnesium, and higher HbA1c.

Conclusions: A higher serum calcium level may be an independent risk factor for VTDR in patients with T2D.
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http://dx.doi.org/10.1016/j.eprac.2021.05.003DOI Listing
May 2021

Adult child socio-economic status disadvantage and cognitive decline among older parents in Mexico.

Soc Sci Med 2021 Jun 24;279:113910. Epub 2021 Apr 24.

Leonard Davis School of Gerontology, University of Southern California, USA.

There is growing interest in the contribution of offspring educational attainment to parents' health outcomes. However, less is known about the impacts of offspring socio-economic status (SES) on parents' cognitive decline or about the role of offspring SES disadvantage. We used data from the Mexican Health and Aging Study (n = 10,426) to evaluate the impact of adult child SES disadvantage on parents' verbal memory trajectories over fourteen years (2001-2015). We estimated linear mixed models and used measures of adult child SES (educational, financial, and employment) disadvantage. Our most robust finding was that having an adult child with less than secondary education was associated with faster decline in verbal memory z-scores for older women (β: -0.009 [95% CI: -0.01, -0.001]) and men (β: -0.01 [95% CI: -0.02, -0.01]). Although poor adult child financial well-being was associated with a faster decline in parents' verbal memory z-scores, this finding was less consistent across model specifications. Additional analyses also suggested some evidence of heterogeneity by parents' own educational attainment and gender. These findings highlight the potential importance of children's socio-economic status for the cognitive aging of their older parents.
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http://dx.doi.org/10.1016/j.socscimed.2021.113910DOI Listing
June 2021

Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy.

Orphanet J Rare Dis 2021 Apr 28;16(1):188. Epub 2021 Apr 28.

Department of Neurology, First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.

Background: Duchenne muscular dystrophy (DMD) is the most common genetic muscle disease in human. We aimed to describe the genotype distribution in a large cohort of Chinese DMD patients and their delayed loss of ambulation by glucocorticoid (GC) treatments. This is to facilitate protocol designs and outcome measures for the emerging DMD clinical trials.

Results: A total of 1163 patients with DMD were recruited and genotyped. Genotype variations were categorized as large deletions, large duplications, and small mutations. Large deletions were further analyzed for those amenable to exon-skipping therapies. Participants aged 5 years or older were grouped into GC-treated and GC-naïve groups. Clinical progression among different genotypes and their responses to GC treatments were measured by age at loss of ambulation (LOA). Among the mutation genotypes, large deletions, large duplications, and small mutations accounted for 68.79%, 7.14%, and 24.07%, respectively. The mean age at diagnosis was 4.59 years; the median ages at LOA for the GC-naïve, prednisone/prednisolone-treated, and deflazacort-treated groups were 10.23, 12.02, and 13.95 years, respectively. The "deletion amenable to skipping exon 44" subgroup and the nonsense-mutation subgroup had older ages at LOA than the "other deletions" subgroup. Subgroups were further analyzed by both genotypes and GC status. All genotypes showed significant beneficial responses to GC treatment. Deletions amenable to skipping exon 44 showed a lower hazard ratio (0.155). The mean age at death was 18.57 years in this DMD group.

Conclusion: Genotype variation influences clinical progression in certain DMD groups. Beneficial responses to GC treatment were observed among all DMD genotypes. Compared with other genotypes, deletions amenable to skipping exon 44 had a lower hazard ratio, which may indicate a stronger protective effect of GC treatments on this subgroup. These data are valuable for designing future clinical trials, as clinical outcomes may be influenced by the genotypes.
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http://dx.doi.org/10.1186/s13023-021-01837-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082961PMC
April 2021

Changes in the Morphology, Number, and Protein Levels of Plasma Exosomes in CADASIL Patients.

J Alzheimers Dis 2021 ;81(1):221-229

Department of Neurology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan, China.

Background: Exosomes are nano-sized extracellular vesicles which are secreted by cells and usually found in body fluids. Previous research has shown that exosomal secretion and autophagy-lysosomal pathway synergistically participates in intracellular abnormal protein elimination. The main pathological manifestations of Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is abnormal accumulation of mutant NOTCH3, and CADASIL vascular smooth muscle cells have been found with autophagy-lysosomal dysfunction. However, whether plasma exosomes change in CADASIL patients is still unclear.

Objective: We are aimed to investigate the differences of plasma exosomes between CADASIL patients and healthy controls.

Methods: The subjects included 30 CADASIL patients and 30 healthy controls without NOTCH3 mutation. The severity of white matter lesions (WMLs) of CADASIL patients was quantified by Fazekas score. Transmission electron microscopy and nanoparticle tracking analysis were performed to characterize plasma exosomes. In addition, NOTCH3, Neurofilament light and Aβ42 levels in plasma exosomes were quantified by enzyme-linked immunosorbent assays.

Results: We found that exosomes from CADASIL patients were lower in quantity. In addition, CADASIL plasma exosomes had significantly lower levels of NOTCH3 and significantly increased levels of NFL than those of matched healthy subjects. Interestingly, plasma exosome NOTCH3 levels of CADASIL patients significantly correlated with severity of WMLs.

Conclusion: The exosome NOTCH3 may be related to the pathological changes of CADASIL, which provides a basis for the pathogenesis research of CADASIL. In addition, plasma exosome NOTCH3 and NFL levels may act as biomarkers to monitor and predict disease progression and measure therapeutic effectiveness in the future clinical trials.
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http://dx.doi.org/10.3233/JAD-210101DOI Listing
January 2021

Protective effects of peptide FK18 against neuro-excitotoxicity in SH-SY5Y cells.

Exp Ther Med 2021 May 1;21(5):451. Epub 2021 Mar 1.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.

Excitotoxic neuronal injury is associated with numerous acute and chronic neurological disorders, such as Alzheimer's disease and glaucoma. Neuroprotection is a direct and effective therapeutic approach, with small-molecule bioactive peptides displaying certain advantages, including high membrane permeability, low immunogenicity and convenient synthesis and modification. FK18 is a novel peptide derived from basic fibroblast growth factor, which is a protein with neuroprotective effects. The present study aims to evaluate the neuroprotective effect of FK18 against excitotoxic injury. For this purpose, cell viability was determined by the MTS assay, cell apoptosis was assessed by flow cytometry and the TUNEL assay; expression of antiapoptotic proteins Bcl-2, proapoptotic protein Bax and caspase-3 as well as the phosphorylation of Akt and Erk was estimated by western blotting. The results of the present study demonstrated that FK18 effectively increased the viability of, and attenuated glutamate-induced apoptosis of SH-SY5Y cells. In addition, FK18 significantly increased Akt phosphorylation and decreased Erk phosphorylation in SH-SY5Y cells. FK18 also increased the Bcl-2/Bax ratio and decreased the level of cleaved-caspase-3 in SY5Y cells, which was reversed by the Akt pathway inhibitor LY294002, but not by the Erk pathway inhibitor U0126. The findings of the present study suggested that FK18 may be a promising therapeutic agent for the inhibition of neuronal cell death in multiple neurological diseases involving excitotoxicity.
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http://dx.doi.org/10.3892/etm.2021.9880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967878PMC
May 2021

Current Situation and Key Parameters for Improving Wheat Quality in China.

Front Plant Sci 2021 15;12:638525. Epub 2021 Feb 15.

Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences, Beijing, China.

Processing quality of winter-wheat is affected by genotype, environmental conditions, and crop husbandry practices. In the present study, a data set of 17 quality-related traits for 211 main winter-wheat varieties in China during 2006 to 2018 was extracted from China Wheat Quality Report. Analysis was carried out to evaluate the quality status and variations, to reveal correlation between quality-related traits, as well as to identify key influencing factors. Results indicated that the quality indicators of medium-gluten or medium-strong-gluten wheat varieties were acceptable, whereas those of weak- and strong-gluten wheat varieties were far below national standard, especially hardness index (HI), crude protein content (CPC), wet gluten content (WG), and water absorption for weak-gluten wheat and sedimentation value (SV), stability time (ST), and stretch area (SA) for strong-gluten wheat, respectively. Correlation analysis showed that WA, WG, development time, HI, CPC, falling number, ST, and tractility directly affected the overall quality of winter-wheat. CPC, SV, and WG in medium-gluten wheat had no significant correlation with the processing quality of noodles score, whereas gluten index significantly correlated with noodle score ( < 0.001). This implied that protein quality might play a more important role than protein quantity in determining medium-gluten wheat quality. Furthermore, analysis of variance showed that genetic characteristics (cultivars) had significant influences on the restriction indexes (SV, ST, and SA) of strong-gluten wheat, whereas genetic characteristics, environment conditions, and crop growing practices (cultivars, locations, and years) significantly affected the restriction indexes (HI, CPC, WG, and WA) of weak-gluten wheat. The results suggest that improvement of Chinese strong-gluten wheat should mainly focus on cultivating new varieties. As to weak-gluten wheat, cultivation and husbandry practices should be paid more attention to limit undesired high grain protein content.
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http://dx.doi.org/10.3389/fpls.2021.638525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917211PMC
February 2021

Offspring Educational Attainment and Older Parents' Cognition in Mexico.

Demography 2021 Feb 18;58(1):75-109. Epub 2021 Jan 18.

T. Denny Sanford School of Social and Family Dynamics, Arizona State University, P.O. Box 873701, Tempe, AZ 85287, USA.

Population-level disparities in later-life cognitive health point to the importance of family resources. Although the bulk of prior work establishes the directional flow of resources from parents to offspring, the "linked lives" perspective raises the question of how offspring resources could affect parental health as well. This paper examines whether adult children's education influences older parents' (aged 50+) cognitive health in Mexico, where schooling reforms have contributed to significant gains in the educational achievements of recent birth cohorts. Harnessing a change in compulsory school laws and applying an instrumental variables approach, we found that each year of offspring schooling was associated with higher overall cognition among parents, but was less predictive across different cognitive functioning domains. More offspring schooling improved parents' cognitive abilities in verbal learning, verbal fluency, and orientation, but not in visual scanning, visuo-spatial ability, or visual memory. The beneficial effects of offspring schooling on those cognitive domains are more salient for mothers compared to fathers, suggesting potential gendered effects in the influence of offspring schooling. The results remained robust to controls for parent-child contact and geographic proximity, suggesting other avenues through which offspring education could affect parental health and a pathway for future research. Our findings contribute to growing research which stresses the causal influence of familial educational attainment on population health.
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http://dx.doi.org/10.1215/00703370-8931725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894606PMC
February 2021

The silent occurrence of cerebral small vessel disease in nonelderly patients with type 2 diabetes mellitus.

J Diabetes 2021 Feb 9. Epub 2021 Feb 9.

Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: The prevalence of cerebral small vessel disease (SVD) increases in elderly patients with type 2 diabetes (T2DM), exacerbating cognitive decline. However, the prevalence and the severity of SVD in dementia-free nonelderly T2DM patients were largely unknown. Our primary aim is to investigate SVD in such patients, with a specific focus on the correlation between SVD and diabetic peripheral sensorimotor polyneuropathy (DSP).

Methods: We recruited 180 young and middle-aged subjects without cognitive impairment (106 with T2DM, 74 controls). Signs of cerebral SVD on magnetic resonance image were investigated, and the overall SVD burden was evaluated by a combined score. Patients with T2DM underwent further detailed DSP assessment. Regression models were used to investigate the association of SVD with the presence of T2DM, and the associations of the prevalence and severity of SVD and DSP were also explored in patients with T2DM.

Results: The prevalence of microbleeds and overall burden of SVD were significantly higher in T2DM patients than in the controls. Further, the presence of DSP related to an increased risk of SVD after adjustment in diabetic group. Moreover, Toronto Clinical Scoring System values were positively associated with the increased SVD scores, and bilateral sural sensory nerve conduction velocities were negatively associated with increasingly severity of SVD scores.

Conclusion: The current findings extended the increasing prevalence of SVD to dementia-free nonelderly patients with T2DM, suggesting that the time for cognitive screening and prevention might be moved forward in T2DM patients, especially for those with DSP.
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http://dx.doi.org/10.1111/1753-0407.13164DOI Listing
February 2021

Spreading of TDP-43 pathology via pyramidal tract induces ALS-like phenotypes in TDP-43 transgenic mice.

Acta Neuropathol Commun 2021 01 18;9(1):15. Epub 2021 Jan 18.

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

Transactive response DNA-binding protein 43 kDa (TDP-43) has been identified as the major component of ubiquitinated inclusions found in patients with sporadic amyotrophic lateral sclerosis (ALS). Increasing evidence suggests prion-like transmission of TDP-43 aggregates via neuroanatomic connection in vitro and pyramidal tract in vivo. However, it is still unknown whether the spreading of pathological TDP-43 sequentially via pyramidal tract can initiate ALS-like pathology and phenotypes. In this study, we reported that injection of TDP-43 preformed fibrils (PFFs) into the primary motor cortex (M1) of Thy1-e (IRES-TARDBP) 1 mice induced the spreading of pathological TDP-43 along pyramidal tract axons anterogradely. Moreover, TDP-43 PFFs-injected Thy1-e (IRES-TARDBP) 1 mice displayed ALS-like neuropathological features and symptoms, including motor dysfunctions and electrophysiological abnormalities. These findings provide direct evidence that transmission of pathological TDP-43 along pyramidal tract induces ALS-like phenotypes, which further suggest the potential mechanism for TDP-43 proteinopathy.
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http://dx.doi.org/10.1186/s40478-020-01112-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814549PMC
January 2021

Magnetohydrodynamic Interface-Rearranged Lithium Ions Distribution for Uniform Lithium Deposition and Stable Lithium Metal Anode.

Chemphyschem 2021 May 28;22(10):1027-1033. Epub 2021 Apr 28.

Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.

Uneven lithium (Li) electrodeposition hinders the wide application of high-energy-density Li metal batteries (LMBs). Current efforts mainly focus on the side-reaction suppression between Li and electrolyte, neglecting the determinant factor of mass transport in affecting Li deposition. Herein, guided Li mass transport under the action of a local electric field near magnetic nanoparticles or structures at the Li metal interface, known as the magnetohydrodynamic (MHD) effect, are proposed to promote uniform Li deposition. The modified Li trajectories are revealed by COMSOL Multiphysics simulations, and verified by the compact and disc-like Li depositions on a model Fe O substrate. Furthermore, a patterned mesh with the magnetic Fe-Cr O core-shell skeleton is used as a facile and efficient protective structure for Li metal anodes, enabling Li metal batteries to achieve a Coulombic efficiency of 99.5 % over 300 cycles at a high cathode loading of 5.0 mAh cm . The Li protection strategy based on the MHD interface design might open a new opportunity to develop high-energy-density LMBs.
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http://dx.doi.org/10.1002/cphc.202000897DOI Listing
May 2021

Comparison of left atrial and left atrial appendage mechanics in the risk stratification of stroke in patients with atrial fibrillation.

Cardiovasc Ultrasound 2021 Jan 9;19(1). Epub 2021 Jan 9.

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, People's Republic of China.

Background: Left atrial (LA) and left atrial appendage (LAA) dysfunction has been demonstrated to contribute to atrial fibrillation (AF)-related stroke. However, usefulness of LA and LAA mechanics has not been fully compared. We sought to investigate the association of LA and LAA mechanics with stroke and to compare their diagnostic values in the risk stratification of stroke in patients with nonvalvular AF.

Methods: A total of 208 consecutive patients with AF (63.58 ± 10.37 years, 63.9% male,57.7% persistent AF) who underwent echocardiography before catheter ablation were prospectively enrolled. Speckle-tracking was used to measure LA and LAA global longitudinal strain (GLS). LA and LAA mechanical dispersions (MD) were defined as the standard deviation (SD) of time to peak positive strain corrected by the R-R interval.

Results: Patients with prior stroke/ transient ischemic attack (TIA) (n = 31) had significantly higher LA and LAA MD than those without (n = 177) (11.56 ± 4.38% vs. 8.43 ± 3.44%, 15.15 ± 5.46% vs. 10.94 ± 4.40%, both P < 0.01). In multivariable analysis, LA and LAA MD were independently associated with stroke/TIA (odds ratio, 1.18-1.29, 1.19-1.22, respectively, both P < 0.01), providing incremental values over clinical and standard echocardiographic parameters. In a subgroup analysis, LA MD was more useful than LAA MD in patients with normal LA volumes, while LAA MD was superior to LA MD in patients with LA enlargement.

Conclusions: Higher LA and LAA mechanical dispersion are independently associated with stroke/TIA in AF patients and had incremental values over clinical and conventional echocardiographic parameters. What's more, priorities of dispersion assessment are different depending on patients' LA size.
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http://dx.doi.org/10.1186/s12947-020-00232-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797160PMC
January 2021

Solvent-Directed Transition Metal-Free C-C Bond Cleavage by Azido-1,3,5-triazines and Their Stability-Reactivity Paradox.

J Org Chem 2021 Jan 2;86(1):762-769. Epub 2020 Dec 2.

CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China.

We report a solvent-directed and regioselective carbon-carbon bond cleavage of aryl ketones by azido-1,3,5-triazines (ATs), which is typically completed within 10 min in DMSO at room temperature, without using transition metal catalysts. The cleavage is driven by the steric hindrance in the adducts of aryl ketones and ATs, which is substantiated by DFT calculation. Our recent results showed that ATs present high reactivity in solution and high stability in solid state. This "stability-reactivity paradox" has been explained in light of the molecular and crystal structures of ATs.
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http://dx.doi.org/10.1021/acs.joc.0c02342DOI Listing
January 2021

[Identification of SPAST gene variant in a pedigree affected with hereditary spastic paraplegia type 4].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Nov;37(11):1261-1264

Institute of Medical Genetics, Henan Provincial People's Hospital, Department of Neurology, Henan Provincial People's Hospital, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory for Birth Defect Prevention, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, [email protected] qq.com.

Objective: To explore the genetic basis for a pedigree affected with hereditary spastic paraplegia type 4 (HSP4).

Methods: Peripheral venous blood samples were taken from members of the four-generation pedigree and 50 healthy controls for the extraction of genomic DNA. Genes associated with peripheral neuropathy and hereditary spastic paraplegia were captured and subjected to targeted capture and next-generation sequencing. The results were confirmed by Sanger sequencing.

Results: DNA sequencing suggested that the proband has carried a heterozygous c.1196C>G variant in exon 9 of the SPAST gene, which can cause substitution of serine by threonine at position 399 (p.Ser399Trp) and lead to change in the protein function. The same variant was also detected in other patients from the pedigree but not among unaffected individuals or the 50 healthy controls. Based on the ACMG 2015 guidelines, the variant was predicted to be possibly pathogenic.

Conclusion: The c.1196C>G variant of the SPAST gene probably underlay the HSP4 in this pedigree.
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http://dx.doi.org/10.3760/cma.j.cn511374-20191120-00592DOI Listing
November 2020

IGFBP‑rP1‑silencing promotes hypoxia‑induced angiogenic potential of choroidal endothelial cells via the RAF/MEK/ERK signaling pathway.

Mol Med Rep 2020 Dec 11;22(6):4837-4847. Epub 2020 Oct 11.

Department of Ophthalmology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.

Insulin‑like growth factor binding protein‑related protein 1 (IGFBP‑rP1) has been reported to have various functions in different cellular contexts. Our previous investigation discovered that IGFBP‑rP1 inhibited retinal angiogenesis in vitro and in vivo by inhibiting the pro‑angiogenic effect of VEGF and downregulating VEGF expression. Recently, IGFBP‑rP1 was confirmed to be downregulated in the aqueous humor of patients with neovascular age‑related macular degeneration compared with controls; however, its specific role remains unknown. The present study applied the technique of gene silencing, reverse transcription‑quantitative PCR, western blotting, cell viability assays, cell motility assays and tube formation assays. Chemical hypoxic conditions and choroidal endothelial (RF/6A) cells were used to explore the effect of IGFBP‑rP1‑silencing on the phenotype activation of RF/6A cells under hypoxic conditions and to elucidate the underlying mechanisms. siRNA achieved IGFBP‑rP1‑silencing in RF/6A cells without cytotoxicity. IGFBP‑rP1‑silencing significantly restored the viability of RF/6A cells in hypoxia and enhanced hypoxia‑induced migration and capillary‑like tube formation of RF/6A cells. Furthermore, IGFBP‑rP1‑silencing significantly upregulated the expression of B‑RAF, phosphorylated (p)‑MEK, p‑ERK and VEGF in RF/6A cells under hypoxic conditions; however, these upregulations were inhibited by exogenous IGFBP‑rP1. These data indicated that silencing IGFBP‑rP1 expression in RF/6A cells effectively promoted the hypoxia‑induced angiogenic potential of choroidal endothelial cells by upregulating RAF/MEK/ERK signaling pathway activation and VEGF expression.
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http://dx.doi.org/10.3892/mmr.2020.11578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646924PMC
December 2020

Nickel nanocrystal/nitrogen-doped carbon composites as efficient and carbon monoxide-resistant electrocatalysts for methanol oxidation reactions.

Nanoscale 2020 Nov;12(42):21687-21694

Department of Chemistry, College of Science, North University of China, Taiyuan, Shanxi 030051, China.

High-performance electrocatalysts for the methanol oxidation reaction (MOR) are the key to advance the application of direct methanol fuel cells. Pt-Based electrocatalysts for the MOR are limited due to their high cost, low stability and poor resistance to carbon monoxide (CO) poisoning. The development of non-noble metal-based electrocatalysts for the MOR with high activity and good stability is desired, but it remains a challenge. Herein, we report a simple strategy to prepare nickel nanocrystals embedded in a nitrogen-doped carbon matrix (Ni/N-C composite) by pyrolysis of Ni-coordinated polyaniline-poly(vinyl alcohol) hydrogels. These in situ generated Ni nanocrystals serve as active electrocatalysts for the MOR, while the nitrogen-doped carbon matrix serves as a conductive support to facilitate electron transfer and also to protect the active Ni nanocrystals. The optimal Ni/[email protected] electrocatalyst shows a high MOR activity of 147 mA cm-2 at 1.66 V vs. the RHE in alkaline methanol solution, which is outstanding among Ni-based MOR electrocatalysts. Ni/[email protected] also shows better stability than the Pt/C catalyst in the long-term MOR test at high current densities. Upon CO poisoning, Ni/[email protected] retains 85% of its MOR activity, far exceeding the performance of the Pt/C catalyst (61% retention). Owing to its facile synthesis, outstanding activity and high stability, the Ni/[email protected] composite is promising as a low-cost, efficient and CO-resistant electrocatalyst for the MOR.
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http://dx.doi.org/10.1039/d0nr04822dDOI Listing
November 2020

A preliminary study on the prenatal diagnosis of fetal conotruncal defects using intelligent navigation echocardiography.

Int J Gynaecol Obstet 2021 Apr 5;153(1):138-145. Epub 2021 Jan 5.

Department of Diagnostic Ultrasound and Echocardiography, Sir Run Run Shaw Hospital of Clinical Medicine of Zhejiang University, Zhejiang, China.

Objective: To compare the accuracy, efficiency, and consistency between experienced and less-experienced professionals using intelligent navigation echocardiography.

Methods: In this prospective study, we enrolled 93 second- and third-trimester fetuses with conotruncal defects (CTD) from July 2017 to February 2018. One or more spatiotemporal image correlation volume data sets were collected per case. The fetuses with CTD were diagnosed by the following two groups of professionals (n = 20 in each) with different experience levels using intelligent navigation echocardiography and two-dimensional ultrasound: group A with 15 years of experience and group B with 1 year of experience. The diagnostic consistency and accuracy of the technologies between the two groups were analyzed.

Results: Satisfactory consistency was noted in the two groups (group A, τ = 0.855, P < 0.05, and group B, τ = 0.821, P < 0.05), and no significant difference in accuracy (χ = 3.218, P > 0.05) in using intelligent navigation echocardiography was reported between the two groups. However, there a significant difference in accuracy (χ = 0.021, P < 0.05) when using two-dimensional ultrasound was observed between the two groups.

Conclusion: Intelligent navigation echocardiography was found to be efficient and accurate for the diagnosis of CTD and good consistency existed in the experienced and less-experienced professionals.
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http://dx.doi.org/10.1002/ijgo.13429DOI Listing
April 2021

Cu-Catalyzed Site-Selective and Enantioselective Ring Opening of Cyclic Diaryliodoniums with 1,2,3-Triazoles.

Org Lett 2020 08 7;22(16):6441-6446. Epub 2020 Aug 7.

Hefei National Laboratory for Physical Sciences at the Microscale, and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.

A Cu-catalyzed enantioselective ring-opening/triazolylation reaction is reported. The reaction shows excellent chemoselectivity regarding the three different nitrogen atoms of 1,2,3-triazoles. The optically enriched axially chiral aryl iodides thus obtained were readily derivatized to different types of chiral phosphine ligands and their corresponding copper or palladium complexes.
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http://dx.doi.org/10.1021/acs.orglett.0c02256DOI Listing
August 2020

Is Ross Syndrome a New Type of Synucleinopathy? A Brief Research Report.

Front Neurosci 2020 8;14:635. Epub 2020 Jul 8.

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Ross syndrome (RS) is a rare peripheral autonomic system disorder characterized by tonic pupil, hyporeflexia, and segmental anhidrosis. Neuropathological studies show that RS results from the selective cholinergic nerve degeneration. However, the cause and underlying mechanisms are largely unknown. Here, we show α-synuclein accumulation in the autonomic nerve terminals in the lesser curvature of stomach of patients with RS. In addition, immunohistochemical findings demonstrate that a dominant degeneration of cholinergic fibers is exhibited in patients with RS, while main degeneration of adrenergic fibers is demonstrated in patients with pure autonomic failure in their gastrointestinal and urinary system. Our study suggests that RS belongs to α-synucleinopathies. Moreover, our findings indicate that adrenergic nerves and cholinergic nerves are not equally damaged in different types of pure autonomic dysfunctions.
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http://dx.doi.org/10.3389/fnins.2020.00635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361646PMC
July 2020

Diagnostic performance of fetal intelligent navigation echocardiography (FINE) in fetuses with double-outlet right ventricle (DORV).

Int J Cardiovasc Imaging 2020 Nov 8;36(11):2165-2172. Epub 2020 Jul 8.

Department of Diagnostic Ultrasound and Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, Hangzhou, People's Republic of China.

The main objective of this study was to investigate the diagnostic performance of FINE in generating and displaying 3 specific abnormal fetal echocardiography views such as left ventricular outflow tract (LVOT) view, right ventricular outflow tract (RVOT) view, and 3-vessels and trachea (3VT) view in fetuses with double-outlet right ventricle (DORV). In this prospective study, thirty fetuses diagnosed with DORV by fetal echocardiography in the second and third trimesters were enrolled. One or more STIC volume data-sets were collected from the 4-chamber view as initial view for each fetus, one optimal volume per fetus was selected for on-line analysis using FINE, and the diagnosis plane image was optimized using the Virtual Intelligent Sonographer Assistance (VIS-assistance).The visualization rates of 3 specific abnormal fetal echocardiography views of DORV and key diagnostic elements were calculated. One or more STIC volumes (n = 30 total) were obtained in 25 patients. A single STIC volume per patient was analyzed using the FINE method. FINE was able to successfully generate and display 3 specific abnormal fetal echocardiography views. The display rates of the 3 specific abnormal fetal echocardiography views (3VT, LVOT, RVOT) were 84.0%, 76.0% and 84.0%, respectively. By applying intelligent navigation technology to STIC volume data-sets, the FINE method can successfully generate three specific abnormal cardiac fetal echocardiography diagnostic views in fetuses with DORV, the FINE method can be used for screening and remote consultation of fetal DORV.
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http://dx.doi.org/10.1007/s10554-020-01932-3DOI Listing
November 2020

High impact polytriazole resins for advanced composites.

Des Monomers Polym 2020 5;23(1):50-58. Epub 2020 May 5.

Key Laboratory of Specially Functional Polymeric Materials and Related Technology of the Ministry of Education, East China University of Science and Technology, Shanghai, China.

Three azido-terminated poly(ethylene glycol) macromonomers (ATPEGs) were synthesized from poly(ethylene glycol)s (PEGs) and characterized. The extended polytriazole (EPTA) resins were prepared from the macromonomers, azide and alkyne monomers. Toughening effect of PEGs on polytriazole resins was analyzed by means of mechanical, thermal and electronic microscope characterization. The results show that molecular weight and content of ATPEGs have great influence on the thermal and mechanical properties of cured EPTA resins. The impact strength of cured EPTA resins increases with the increase of the amount and molecular weight of ATPEGs. The flexural strength and heat resistance of cured EPTA resins decrease with the increase of addition amount and molecular weight of ATPEGs. High impact EPTA resins were obtained.
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http://dx.doi.org/10.1080/15685551.2020.1761584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241543PMC
May 2020

Propagation of Pathological α-Synuclein from the Urogenital Tract to the Brain Initiates MSA-like Syndrome.

iScience 2020 Jun 15;23(6):101166. Epub 2020 May 15.

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Institute of Parkinson and Movement Disorder, Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address:

The neuropathological feature of multiple system atrophy (MSA), a fatal adult-onset disorder without effective therapy, is the accumulation of pathological α-synuclein (α-Syn) in the central nervous system (CNS). Here we show that pathological α-Syn exists in nerve terminals in detrusor and external urethral sphincter (EUS) of patients with MSA. Furthermore, α-Syn-preformed fibrils (PFFs) injected in the EUS or detrusor in TgM83 mice initiated the transmission of pathological α-Syn from the urogenital tract to brain via micturition reflex pathways, and these mice developed widespread phosphorylated α-Syn inclusion pathology together with phenotypes. In addition, urinary dysfunction and denervation-reinnervation of external anal sphincter were detected earlier in the mouse models with α-Syn PFFs inoculation before the behavioral manifestations. These results suggest that pathological α-Syn spreading through the micturition reflex pathways retrogradely from the urogenital tract to CNS may lead to urinary dysfunction in patients with MSA, which is different from the etiology of idiopathic Parkinson disease.
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http://dx.doi.org/10.1016/j.isci.2020.101166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260590PMC
June 2020

Author Correction: p66Shc: A novel biomarker of tubular oxidative injury in patients with diabetic nephropathy.

Sci Rep 2020 Apr 8;10(1):6288. Epub 2020 Apr 8.

Department of Nephrology, 2nd Xiangya Hospital, Central South University, Changsha, Hunan, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-62787-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142087PMC
April 2020

PRESnovo: Prescreening Prior to Sequencing to Improve Accuracy and Sensitivity of Neuropeptide Identification.

J Am Soc Mass Spectrom 2020 Jul 26;31(7):1358-1371. Epub 2020 Apr 26.

Identification of peptides in species lacking fully sequenced genomes is challenging due to the lack of prior knowledge. sequencing is the method of choice, but its performance is less than satisfactory due to algorithmic bias and interference in complex MS/MS spectra. The task becomes even more challenging for endogenous peptides that do not involve an enzymatic digestion step, such as neuropeptides. However, many neuropeptides possess common sequence motifs that are conserved across members of the same family. Taking advantage of this feature to improve sequencing of neuropeptides, we have developed a method named PRESnovo (prescreening precursors prior to sequencing) to predict the motif from a MS/MS spectrum. A neuropeptide sequence is broken into a motif with conserved amino acid residues and the remaining partial sequence. By searching against a predefined motif database constructed from known homologous sequences, PRESnovo assigns the most probable motif to each precursor via a sophisticated scoring function. Performance analysis was conducted with 15 neuropeptide standards, and 11 neuropeptides were correctly identified with PRESnovo compared to 1 identification by PEAKS only. We applied PRESnovo to assign motifs to peptide sequences in conjunction with PEAKS for assigning the rest of the peptide sequence in order to discover neuropeptides in tissue samples of green crab, , and Jonah crab, . Collectively, a large number of neuropeptides were identified, including 13 putative neuropeptides identified in green crab brain, 77 in Jonah crab brain, and 47 in Jonah crab sinus glands for the first time. This PRESnovo strategy greatly simplifies sequencing and enhances the accuracy and sensitivity of neuropeptide identification when common motifs are present.
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http://dx.doi.org/10.1021/jasms.0c00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332408PMC
July 2020

Height shrinkage, health and mortality among older adults: Evidence from Indonesia.

Econ Hum Biol 2020 05 21;37:100863. Epub 2020 Feb 21.

Institute for Advanced Research, Shanghai University of Finance and Economics, Shanghai 200433, China; Key Laboratory of Mathematical Economics (SUFE), Ministry of Education, Shanghai 200433, China. Electronic address:

In this paper, we analyze the correlates of height shrinkage and the association of height shrinkage and late-life health among mid-aged and older adults from the Indonesian Family Life Survey. We first document the extent of height shrinkage based on measured height over 17 years. Height shrinkage is higher among older age groups, taller individuals, and women. Socioeconomic and initial health correlates of shrinkage are found to be different for men and women. Higher education, marital status, household consumption, urban birth and poor self-reported health in adulthood and childhood are found to be significant correlates for men. Ethnicity, working in the agricultural sector and availability of local health infrastructure are key correlates of height shrinkage for women. Height shrinkage of 1 cm is associated with a 0.02 s.d. decrease in cognition scores for Indonesian men and a 0.01 s.d. decrease for women, and 4% increase in index of mobility difficulties for both men and women. Extreme height loss, defined as height loss greater than 3 cm is associated with 8-10 percent lower lung function and grip strength among both men and women. Extreme height loss among Indonesian older women is also associated with a 7-percentage-point increase in the likelihood of death in the most recent wave. Our results emphasize the importance of taking into account age related height loss as a significant covariate for health and mortality of older adults, independent of baseline height and health.
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http://dx.doi.org/10.1016/j.ehb.2020.100863DOI Listing
May 2020

Efficient Cascade Resonance Energy Transfer in Dynamic Nanoassembly for Intensive and Long-Lasting Multicolor Chemiluminescence.

ACS Nano 2020 03 11;14(3):3696-3702. Epub 2020 Mar 11.

CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China.

Light emission induced by chemical reactions, known as chemiluminescence (CL), has been widely used for bioassays, biosensors, imaging, and illumination applications. Most known CL systems exhibit flash-type single-color light emissions, which limit their applications. Long-lasting multicolor CL in aqueous solutions is highly desirable, especially for biological applications, but remains a challenge. Herein, we report a simple strategy of achieving highly efficient cascade Förster resonance energy transfer (FRET) in the dynamic nanoassembly of β-cyclodextrin (β-CD), CL reagents, and fluorophores in aqueous solution, which emits intensive multicolor CL with adjustable wavelength within 410-610 nm. β-CD can bind CL reagents and fluorophores to form a dynamic nanoassembly. These nanoassemblies can bring the included luminescent intermediate and fluorophores into close proximity and proper alignment, which should greatly enhance the FRET efficiency between luminescent intermediate and fluorophores. Indeed, the cascade FRET efficiency in this supramolecular nanoassembly reaches up to 92%, which is comparable with the cascade FRET systems based on covalently linked donors and acceptors. By using hydroxypropyl methylcellulose as the thickener to slow the diffusion (to elongate the CL emission), and using Ca(OH) solid (a low solubility strong base) as buffer to maintain the pH in the optimal range for the CL reaction, this nanoassembly system has been further developed to achieve slow-diffusion-controlled catalytic CL reactions, which enables long-lasting multicolor CL in aqueous solution that is visible to naked eyes and lasts for more than 20 h. The multicolor CL systems can be used to prepare transformable two-dimensional multicolor codes for encryption application.
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http://dx.doi.org/10.1021/acsnano.0c00847DOI Listing
March 2020

High Glucose-Induced TRPC6 Channel Activation Decreases Glutamate Uptake in Rat Retinal Müller Cells.

Front Pharmacol 2019 14;10:1668. Epub 2020 Feb 14.

Department of Ophthalmology, Shanghai General Hospital, Shanghai, China.

High glucose (HG) increases the production of reactive oxygen species (ROS), leading to decreased glutamate uptake in Müller cells. The transient receptor potential cation channel 6 (TRPC6) channel, an oxidative stress-sensitive Ca-permeable cationic channel, is readily detected in Müller cells and highly expressed under HG conditions. Yet, the effect of high glucose-induced TRPC6 channel activation in Müller cells is poorly understood. We hypothesized that TRPC6 channel activation mediates high glucose-induced decreases in Müller cell glutamate uptake. We found RNA interference (RNAi) of the TRPC6 channel abolished HG-induced decreases in glutamate uptake and cell death. HG also decreased the expression of the glutamate-aspartate transporter (GLAST), which is the most important transporter involved in glutamate uptake. The mRNA level of ciliary neurotrophic factor (CNTF) in rMC-1 cells and the release of CNTF in the culture media was decreased, but the mRNA levels of IL-6 and vascular endothelial growth factor (VEGF) were increased under HG conditions. After RNAi silencing in rMC-1 cells, the mRNA levels of CNTF increased, but IL-6 and VEGF levels decreased. Furthermore, TRPC6 knockdown (KD) decreased expression of glial fibrillary acidic protein (GFAP) and increased expression of Kir4.1, pointing to inhibition of HG-induced gliosis in rMC-1 cells. ROS and intracellular Ca levels decreased after TRPC6 knockdown. Exposure to Hyp9 (10 μM), a highly selective TRPC6 channel agonist, can aggravate HG-induced pathological changes. Collectively, our results suggest TRPC6 channel activation is involved in HG-induced decreases in glutamate uptake in rMC-1 cells. These findings provide novel insights into the role of TRPC6 in HG-induced retinal neurovasculopathy and suggest TRPC6 is a promising target for drug development for diabetic retinopathy (DR).
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http://dx.doi.org/10.3389/fphar.2019.01668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033573PMC
February 2020

Left atrial appendage mechanical dispersion provides incremental value for thromboembolic risk stratification over CHADS-VASc Score in nonvalvular atrial fibrillation.

Int J Cardiol 2020 May 13;307:41-47. Epub 2020 Feb 13.

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Background: Left atrial appendage (LAA) dysfunction is associated with increased risk of thromboembolic events. However, little is known about LAA mechanical dispersion (MD) would provide additional information toward thromboembolism over the CHA2DS2-VASc score. The aim of this study was to determine the association of LAA mechanics as assessed by speckle-tracking imaging with thromboembolic events in patients with nonvalvular atrial fbrillation (AF).

Methods: A total of 116 consecutive patients with AF referred for transesophageal echocardiography (TEE) were prospectively enrolled. Of these, 17(14.7%) patients had prior embolic events. Using speckle-tracking echocardiography (STE), we measured the LAA strain in each of 24 segments in mid-esophageal TEE views obtained at 0°, 45°, 90° and 135°. LAA MD was defined as the standard deviation (SD) of time to peak positive strain corrected by the R-R interval.

Results: Patients with embolism had lower LAA global longitudinal strain (GLS) (8.56 ± 2.62% vs 11.37 ± 5.54%, p = 0.002) and higher LAA MD (16.90 ± 6.67% vs 12.10 ± 3.94%; P = 0.010) than those without embolism. LAA MD >13.1% differentiated patients with embolism from controls, with an area under the curve (AUC) of 0.709(p = 0.004). LAA MD was independently associated with the presence of thromboembolism in multivariate analysis (odds ratio, 1.24; 95% confidence interval, 1.08-1.42; P = 0.002). The model based on CHADS-VASc score for discrimination of patients with embolism was significantly improved by adding LAA MD (P < 0.01).

Conclusion: LAA MD obtained from strain echocardiography was significantly associated with a prior history of embolic events and had incremental diagnostic value over CHA2DS2VASc score, suggesting that LAA MD may be useful in refining thromboembolic risk stratification in patients with AF.
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http://dx.doi.org/10.1016/j.ijcard.2020.02.031DOI Listing
May 2020

Lower limb muscle magnetic resonance imaging in Chinese patients with myotonic dystrophy type 1.

Neurol Res 2020 Feb 17;42(2):170-177. Epub 2020 Jan 17.

Department of Neurology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Henan, China.

: Muscle magnetic resonance imaging (MRI) is a reliable noninvasion tool for detecting muscle abnormalities of myopathies. This study aimed to investigate the MRI features of lower limb muscles in Chinese patients with myotonic dystrophy type 1 (DM1) and to evaluate the correlation between clinical factors and muscle MRI.: We retrospectively reviewed the medical records and lower limb muscle MRI in 24 Chinese DM1 patients. Muscular Impairment Rating Scale (MIRS) was used to assess the clinical muscular impairment. Modified Mercuri's scale was used to assess the degree of fatty infiltration. Spearman rank correlation test was used to analyze the relationship between fatty degeneration score with age, age of onset, disease duration, MIRS grading and creatinine kinase (CK) level.: Fatty infiltration was found in 22 of 24 DM1 patients and 8 patients were asymmetrically affected. The medial gastrocnemius was the most affected muscle, followed by soleus and tibialis anterior muscles in lower legs. At thigh level, the anterior compartment was usually the most affected region with the rectus femoris relatively spared. 79.2% of DM1 patients had edema in lower limb muscles. The total mean score of fatty infiltration correlated with MIRS grading, age and disease duration but did not correlate with the age of onset or CK level.: Here, we found fatty infiltration present in most Chinese DM1 patients with a selective involvement pattern. There is a correlation between the total mean score of fatty infiltration and MIRS grading, age and disease duration.
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http://dx.doi.org/10.1080/01616412.2020.1716494DOI Listing
February 2020

Therapeutic effects of mesenchymal stem cell-derived exosomes on retinal detachment.

Exp Eye Res 2020 02 19;191:107899. Epub 2019 Dec 19.

Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, 251 Fukang Road, Tianjin, 300384, China. Electronic address:

Retinal detachment (RD) induces ischemia and oxygen deficiency in the retina and results in multiple pathological events; photoreceptor cell degeneration and death is the eventual cause of vision decline. In this study, we investigated the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Exos) in a rat retinal detachment (RD) model. The model was developed using a subretinal injection of 1% hyaluronic acid in male Sprague-Dawley rats. MSC-Exos were sub-retinally injected at the time of retinal separation to study their therapeutic function. The retinal expression levels of inflammatory cytokines TNF-α, IL-1β, and MCP-1 were detected by RT-PCR, the autophagy-related protein 5 (Atg5) and microtubule-associated protein 1 light chain 3 beta (LC3) were detected by Western blot, and apoptosis was examined using TUNEL assays at 3 days following RD. Retinal structure was observed at 7 days post-RD. Proteomic analysis was also performed to detect proteins carried by MSC-Exos using iTRAQ-based technology combined with one-dimensional nano LC-nano-ESI- MS/MS. We found that expression of TNF-α and IL-1β were significantly reduced, the LC3-II to LC3-I ratio was enhanced and cleavage of Atg5 was decreased after MSC-Exo treatment. Treatment with MSC-Exos also suppressed photoreceptor cell apoptosis and maintained normal retinal structure when compared to control groups. Proteomic analysis revealed that MSC-Exos contained proteins with anti-inflammatory, neuroprotective and anti-apoptotic effects. These results suggest that MSC-Exos have therapeutic effects on RD-induced retinal injury and can be used to reduce effects of retinal detachment on photoreceptor cell degeneration in patients.
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http://dx.doi.org/10.1016/j.exer.2019.107899DOI Listing
February 2020

BAG3 p.Pro209Ser mutation identified in a Chinese family with Charcot-Marie-Tooth disease.

J Neurol 2020 Apr 18;267(4):1080-1085. Epub 2019 Dec 18.

Department of Neurology, Henan Provincial People's Hospital, People's Hospital of Henan University, No. 7, Weiwu Road, Zhengzhou, 450003, Henan, China.

Bcl2-associated athanogene 3 (BAG3) gene mutations cause dilated cardiomyopathy and myofibrillar myopathy. Recently, a novel c.625C>T (p.Pro209Ser) mutation in BAG3 was reported to cause axonal Charcot-Marie-Tooth (CMT) disease in three families. Here, we describe two patients with adult-onset and moderate CMT in a Chinese family. Nerve conduction velocity studies revealed an axonal sensorimotor neuropathy, which was supported by sural nerve biopsy. Lower limb magnetic resonance imaging (MRI) revealed fatty infiltration more severe in the soleus and deep posterior compartment muscles than in the medial gastrocnemius and anterior compartment muscles. Whole exome sequencing identified the same c.625C>T (p.Pro209Ser) mutation in BAG3, which co-segregated with the CMT disease in this family. This study further enforces the association between BAG3 gene and CMT disease, indicating that BAG3 should be considered in the genetic testing for CMT. The p.Pro209Ser mutation with different ethnic origins might be another hotspot mutation of BAG3. MRI is helpful to detect accurate extent of muscle involvement.
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http://dx.doi.org/10.1007/s00415-019-09680-8DOI Listing
April 2020