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1.
Neural Regen Res ; 17(3): 682-689, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34380910

RESUMO

SNCA, GBA, and VPS35 are three common genes associated with Parkinson's disease. Previous studies have shown that these three genes may be associated with Alzheimer's disease (AD). However, it is unclear whether these genes increase the risk of AD in Chinese populations. In this study, we used a targeted gene sequencing panel to screen all the exon regions and the nearby sequences of GBA, SNCA, and VPS35 in a cohort including 721 AD patients and 365 healthy controls from China. The results revealed that neither common variants nor rare variants of these three genes were associated with AD in a Chinese population. These findings suggest that the mutations in GBA, SNCA, and VPS35 are not likely to play an important role in the genetic susceptibility to AD in Chinese populations. The study was approved by the Ethics Committee of Xiangya Hospital, Central South University, China on March 9, 2016 (approval No. 201603198).

2.
Artigo em Inglês | MEDLINE | ID: mdl-34729814

RESUMO

BACKGROUND: Marital status may have an impact on the elderly population's health, but few studies in China discussed about the association between marital status and cognitive impairment. OBJECTIVE: To investigate the relationship between marital status and cognitive impairment. To compare the influences of marital status on dementia between men and women. METHODS: This study was based on a representative national cross-sectional epidemiological survey in China. We randomly selected 13 provinces and municipalities and included 19,276 participants aged 65 years or older in our study. Data was collected by interviewing the participants about their sociodemographic characteristics, and neuropsychological testing was administered to the participants by neurologists. To analyze the association between marital status and cognitive impairment, multiple logistic regression was based on a series of models. RESULTS: Among the 19,276 subjects, about 77.2% were married, 1.6% were single, 21.2% were divorced/separated or widowed. The odds ratios (OR) of dementia were higher in single (OR: 2.13, CI: 1.53-2.97; p < 0.001), divorced/separated/widowed when they were ≤55 years old (OR: 1.75, CI: 1.30-2.35; p < 0.001), and divorced/separated/widowed when they were >55 years old (OR: 1.16, CI: 1.03-1.31; p < 0.001) participants than in married ones. Divorced/separated/widowed ≤55 men had about 2.75 times increase in dementia risk than married men. CONCLUSION: People with long-term divorced/separated/widowed status would be associated to cognitive impairment more than those with short-term divorced/separated/widowed status. Men may be affected by marriage disruption more than women in terms of increasing the risk of dementia.

3.
Environ Pollut ; : 118540, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801619

RESUMO

As part of the leap development of high-tech, REEs have become emerging pollutants that have attracted more and more attention in our production and life. This article summarizes and discusses the distribution and detection rate of REEs in the world's soil and water, and briefly introduces the top five countries with rare earth reserves in the world. The focus is on the impact of REEs on plant, including the distribution of REEs in plant tissue and their bioavailability; the effect of REEs on seed germination and growth; the role of REEs in plant resistance, including abiotic stresses such as low temperature, salt stress, drought, and heavy metal stress; the response of REEs in plant physiology and biochemistry, including mineral absorption, photosynthesis, as well as the description of the substitution mechanism of REEs competing for Ca in plant cells. Summarized the possible mechanism of REEs to activate endocytosis in plants, and provided some reference and insights for revealing the mechanism of REEs affecting endocytosis from the perspective of cell and molecular biology. Finally, it points out the future development direction of rare earth and the problems considered in its application. The purpose is to provide reliable reference materials for the effective use of rare earth resources and the protection of the ecological environment.

4.
Curr Opin Biotechnol ; 74: 55-60, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34794111

RESUMO

To move towards a circular bioeconomy, sustainable strategies for the utilization of renewable, non-food biomass wastes such as lignocellulose, are needed. To this end, an efficient bioconversion of d-xylose - after d-glucose the most abundant sugar in lignocellulose - is highly desirable. Most standard organisms used in biotechnology are limited in metabolising d-xylose, and also in vitro enzymatic strategies for its conversion have not been very successful. We herein discuss that bioconversion of d-xylose is mostly hampered by missing knowledge on the kinetic properties of the enzymes involved in its metabolism. We propose a combination of classical enzyme characterizations and mathematical modelling approaches as a workflow for rational, model-based design to optimize enzyme cascades and/or whole cell biocatalysts for efficient d-xylose metabolism.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(10): 987-993, 2021 Oct 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34719412

RESUMO

OBJECTIVES: To study the association of amplitude-integrated electroencephalogram (aEEG) and the quantitative indices biparietal width (BPW) and interhemispheric distance (IHD) of cranial magnetic resonance imaging (cMRI) with short-term neurodevelopment in moderately and late preterm infants. METHODS: A total of 104 moderately and late preterm infants who were admitted to the neonatal intensive care unit from September 2018 to April 2020 were selected as the subjects for this prospective study. The Naqeeb method and sleep-wake cycling (SWC) were used for aEEG assessment within 72 hours after birth. cMRI was performed at the corrected gestational age of 37 weeks. BPW and IHD were measured at the T2 coronal position. At the corrected age of 6 months, the Developmental Screening Test for Child Under Six (DST) was used to follow up neurodevelopment. According to developmental quotient (DQ), the infants were divided into a normal DST group (78 infants with DQ≥85) and an abnormal DST group (26 infants with DQ<85). Related indices were compared between the two groups. The association between aEEG and cMRI was evaluated. RESULTS: Compared with the normal DST group, the abnormal DST group had significantly lower aEEG normal rate and SWC maturation rate (P<0.05), as well as a significantly larger IHD and a significantly smaller BPW (P<0.05). Immature SWC, aEEG abnormality, and a relatively large IHD were the risk factors for abnormal DST (P<0.05), and a relatively large BPW was a protective factor against abnormal DST (P<0.05). CONCLUSIONS: For moderately and late preterm infants, aEEG within 72 hours after birth and the quantitative indices BPW and IHD of cMRI at the corrected gestational age of 37 weeks may affect their neurodevelopmental outcome at the corrected age of 6 months.


Assuntos
Eletroencefalografia , Recém-Nascido Prematuro , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Estudos Prospectivos
6.
Front Aging Neurosci ; 13: 749649, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776933

RESUMO

Background: Alzheimer's disease (AD) is the most common type of dementia and has no effective treatment to date. It is essential to develop a minimally invasive blood-based biomarker as a tool for screening the general population, but the efficacy remains controversial. This cross-sectional study aimed to evaluate the ability of plasma biomarkers, including amyloid ß (Aß), total tau (t-tau), and neurofilament light chain (NfL), to detect probable AD in the South Chinese population. Methods: A total of 277 patients with a clinical diagnosis of probable AD and 153 healthy controls with normal cognitive function (CN) were enrolled in this study. The levels of plasma Aß42, Aß40, t-tau, and NfL were detected using ultra-sensitive immune-based assays (SIMOA). Lumbar puncture was conducted in 89 patients with AD to detect Aß42, Aß40, t-tau, and phosphorylated (p)-tau levels in the cerebrospinal fluid (CSF) and to evaluate the consistency between plasma and CSF biomarkers through correlation analysis. Finally, the diagnostic value of plasma biomarkers was further assessed by constructing a receiver operating characteristic (ROC) curve. Results: After adjusting for age, sex, and the apolipoprotein E (APOE) alleles, compared to the CN group, the plasma t-tau, and NfL were significantly increased in the AD group (p < 0.01, Bonferroni correction). Correlation analysis showed that only the plasma t-tau level was positively correlated with the CSF t-tau levels (r = 0.319, p = 0.003). The diagnostic model combining plasma t-tau and NfL levels, and age, sex, and APOE alleles, showed the best performance for the identification of probable AD [area under the curve (AUC) = 0.89, sensitivity = 82.31%, specificity = 83.66%]. Conclusion: Blood biomarkers can effectively distinguish patients with probable AD from controls and may be a non-invasive and efficient method for AD pre-screening.

7.
Comput Math Methods Med ; 2021: 6486452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840597

RESUMO

Aim: To explore the relationship between the quantitative indicators (biparietal width, interhemispheric distance) of the cranial MRI for preterm infants at 37 weeks of postmenstrual age (PMA) and neurodevelopment at 6 months of corrected age. Methods: A total of 113 preterm infants (gestational age < 37 weeks) delivered in the Obstetrics Department of the First People's Hospital of Lianyungang from September 2018 to February 2020 and directly transferred to the Neonatology Department for treatment were enrolled in this study. Based on their development quotient (DQ), the patients were divided into the normal (DQ ≥ 85, n = 76) group and the abnormal (DQ < 85, n = 37) group. Routine cranial MRI (cMRI) was performed at 37 weeks of PMA to measure the biparietal width (BPW) and interhemispheric distance (IHD). At the corrected age of 6 months, Development Screening Test (for children under six) was used to assess the participants' neurodevelopment. Results: Univariate analysis showed statistically significant differences in BPW, IHD, and the incidence of bronchopulmonary dysplasia between the normal and the abnormal groups (P < 0.05), while no statistically significant differences were found in maternal complications and other clinical conditions between the two groups (P > 0.05). Binary logistic regression analysis demonstrated statistically significant differences in IHD and BPW between the normal and the abnormal groups (95% CI: 1.629-12.651 and 0.570-0.805, respectively; P = 0.004 and P < 0.001, respectively), while no significant differences were found in the incidence of bronchopulmonary dysplasia between the two groups (95% CI: 0.669-77.227, P = 0.104). Receiver operating characteristic curve revealed that the area under the curve of BPW, IHD, and the joint predictor (BPW + IHD) were 0.867, 0.805, and 0.881, respectively (95% CI: 0.800-0.933, 0.710-0.900, and 0.819-0.943, respectively; all P values < 0.001). Conclusion: BPW and IHD, the two quantitative indicators acquired by cMRI, could predict the neurodevelopmental outcome of preterm infants at the corrected age of 6 months. The combination of the two indicators showed an even higher predictive value.

8.
Aging Dis ; 12(7): 1741-1752, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34631218

RESUMO

Progranulin (GRN) mutations are a major cause of frontotemporal dementia (FTD); the spectrum of clinical phenotypes of FTD is much more extensive than previously reported. The frequency and locations of GRN mutations in Chinese patients with FTD remain uncertain. We performed cDNA sequencing in one sporadic male patient who initially presented FTD symptoms. Brain magnetic resonance imaging (MRI) and positron emission computed tomography/computed tomography (PET/CT) were applied to further confirm the diagnosis of FTD from this patient. Cellular apoptosis and survival test were performed to identify the function of GRN. We identified one novel missense GRN mutation (c.1498G>A, p.V500I) in this patient, who initially presented typical behavioral-variant frontotemporal dementia (bvFTD) features but then presented progressive supranuclear palsy (PSP) clinical characteristics 5 years after onset. Besides, WT GRN protein showed an adequate trophic stimulus to preserve the survival of SH-SY5Y cells in the medium free of serum, while GRN mutation (c.1498G>A, p.V500I) may impair the ability of supporting cell survival. This study owns significant implications for genetic counseling and clinical heterogeneity. We illustrate the fact that FTD presenting features of bvFTD and PSP in one patient could be considered as a specific phenotype in patients with GRN mutations. GRN p.V500I led to the neuronal degeneration in vitro; this finding provides a significant evidence that this mutation may be a new causative mutation in patients with FTD.

9.
EBioMedicine ; 72: 103609, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34628353

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a severe psychiatric disorder that affects approximately 0.75% of the global population. Both genetic and environmental factors contribute to development of SCZ. SCZ tends to run in family while both genetic and environmental factor contribute to its etiology. Much evidence suggested that alterations in DNA methylations occurred in SCZ patients. METHODS: To investigate potential inheritable pattern of DNA methylation in SCZ family, we performed a genome-wide analysis of DNA methylation of peripheral blood samples from 106 Chinese SCZ family trios. Genome-wide DNA methylations were quantified by Agilent 1 × 244 k Human Methylation Microarray. FINDINGS: In this study, we proposed a loci inheritance frequency model that allows characterization of differential methylated regions as SCZ biomarkers. Based on this model, 112 hypermethylated and 125 hypomethylated regions were identified. Additionally, 121 hypermethylated and 139 hypomethylated genes were annotated. The results of functional enrichment analysis indicated that multiple differentially methylated genes (DMGs) involved in Notch/HH/Wnt signaling, MAPK signaling, GPCR signaling, immune response signaling. Notably, a number of hypomethylated genes were significantly enriched in cerebral cortex and functionally enriched in nervous system development. INTERPRETATION: Our findings not only validated previously discovered risk genes of SCZ but also identified novel candidate DMGs in SCZ. These results may further the understanding of altered DNA methylations in SCZ. FUNDING: None.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34709801

RESUMO

Most chronic wounds suffer from infections, and their treatment is challenging. The usage of antibiotics may lead to bacterial resistance and adverse side effects. Positively charged substances have shown promise, but their applications are usually limited by certain cytotoxicity or complex synthesis. Doped polyaniline that carries a high density of positive charges would be a promising candidate due to its good biocompatibility and easy availability, but its interaction with bacteria has not been elucidated. Herein, the distinct bactericidal effect of polyaniline against Gram-positive bacteria has been verified. The antibacterial activity may result from the specific interaction with lipoteichoic acid to destroy the Gram-positive bacterial cell wall. Polyaniline and a macromolecular dopant (sulfonated hyaluronic acid) are used to construct a flexible hydrogel with skin-mimic electrical conductivity. The in vivo results demonstrate that electrical stimulation (ES) through this hydrogel is superior to ES via separated electrodes (the ES strategy used clinically) for promoting infected chronic wound healing.

11.
Mov Disord ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519102

RESUMO

BACKGROUND: No comprehensive meta-analysis has ever been performed to assess the value of neurofilament light chain (NfL) as a biomarker in genetic ataxia. OBJECTIVE: We conducted a meta-analysis to summarize NfL concentration and evaluate its utility as a biomarker in genetic ataxia. METHODS: Studies were included if they reported NfL concentration of genetic ataxia. We used log (mean ± SD) NfL to describe mean raw value of NfL. The effect size of NfL between genetic ataxia and healthy controls (HC) was expressed by mean difference. Correlation between NfL and disease severity was calculated. RESULTS: We identified 11 studies of 624 HC and 1006 patients, here referred to as spinocerebellar ataxia (SCA1, 2, 3, 6, and 7), Friedreich ataxia (FRDA), and ataxia telangiectasia (A-T). The concentration of blood NfL (bNfL) elevated with proximity to expected onset, and progressively increased from asymptomatic to preclinical to clinical stage in SCA3. Compared with HC, bNfL levels were significantly higher in SCA1, 2, 3, and 7, FRDA, as well as A-T, and the difference increased with the advancing disease in SCA3. bNfL levels correlated with disease severity in SCA3. There was a significant correlation between bNfL and longitudinal progression in SCA3. Additionally, bNfL increased with age in HC, yet this is probably masked by higher disease-related effects on bNfL in genetic ataxia. CONCLUSIONS: bNfL can be used as a potential biomarker to predict disease onset, severity, and progression of genetic ataxia. Reference-value setting of bNfL should be divided according to age. © 2021 International Parkinson and Movement Disorder Society.

12.
J Psychiatr Res ; 143: 113-122, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34487988

RESUMO

NRXN1 is involved in synaptogenesis and have been implicated in Autism spectrum disorders. However, many rare inherited missense variants of NRXN1 have not been thoroughly evaluated. Here, functional analyses in vitro and in Drosophila of three NRXN1 missense mutations, Y282H, L893V, and I1135V identified in ASD patients in our previous study were performed. Our results showed these three mutations interfered protein degradation compared with NRXN1-WT protein. Expressing human NRXN1 in Drosophila could lead to abnormal circadian rhythm and sleep behavior, and three mutated proteins caused milder phenotypes, indicating the mutations may change the function of NRXN1 slightly. These findings highlight the functional role of rare NRXN1 missense variants identified in autism patients, and provide clues for us to better understand the pathogenesis of abnormal circadian rhythm and sleep behavior of other organisms, including humans.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Animais , Transtorno do Espectro Autista/genética , Proteínas de Ligação ao Cálcio/genética , Drosophila/genética , Humanos , Mutação de Sentido Incorreto , Moléculas de Adesão de Célula Nervosa/genética , Proteólise , Sono/genética
13.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(8): 793-799, 2021 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34565721

RESUMO

OBJECTIVES: Spinocerebellar ataxia type 2 (SCA2) is one of the most common autosomal dominant ataxias in the world. Several reports revealed that CAG repeats in some polyQ-containing genes may affect the age at onset (AAO) of patients with SCA2, however, little studies were conducted among Chinese patients with SCA2. Thus, the aim of this study is to evaluate the effect of CAG repeats on the AAO of patients with SCA2 in China. METHODS: A total of 119 patients with SCA2 were enrolled and were divided into 2 groups according to their major phenotype: 17 patients from 9 families with Parkinson's syndrome were grouped as the Parkinson's disease-SCA2 (PD-SAC2); 91 patients from 66 SCA2 families and 11 sporadic SCA2 patients were grouped as the ataxia-SCA2 (A-SCA2). Blood samples were obtained from the subjects, and the CAG repeat length in ATXN2 and other (CAG)n-containing genes was screened using fluorescent PCR. The Spearman's rank correlation between the CAG repeat length in (CAG)n-containing genes and AAO was analyzed. Regression analysis was performed to investigate whether the CAG repeat length could explain the variant of AAO. A t-test was used to compare the difference of CAG repeat length in (CAG)n-containing genes between the PD-SAC2 and A-SCA2 groups. RESULTS: The CAG repeat length in the longer allele of ATXN2 was negatively correlated with AAO of SCA2 (R=-0.251, P<0.05), and the CAG repeat length could explain 41.7% of the variation of AAO. AAO negatively correlated with the CAG repeat length in the shorter allele of ATXN7 (R=-0.251, P=0.006) or in the longer allele of TBP gene (R=-0.197, P=0.034). A tendency of delay in the AAO was also observed in patients with SCA2 carrying the CAG repeat within the ATXN3, CACNA1A, ATXN7, TBP, and RAI1. In addition, we found that the CAG repeat length in ATXN7 and ATXN2 between the A-SCA2 and the PD-SCA2 groups was significantly different (both P<0.05). CONCLUSIONS: The CAG repeat in ATXN2 is a major genetic factor for the AAO of patients with SCA2 in China. The CAG repeat length in ATXN3, CACNA1A, ATXN7, TBP, and RAI1 genes might be a potential factor associated with the AAO of SCA2. The CAG repeat in ATXN7 might be a potential factor affecting the Parkinson's syndrome in SCA2.


Assuntos
Proteínas do Tecido Nervoso , Ataxias Espinocerebelares , Idade de Início , Alelos , China/epidemiologia , Humanos , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética
14.
CNS Neurosci Ther ; 27(12): 1531-1539, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34551193

RESUMO

AIM: The role of vascular dementia (VaD)-associated genes in Alzheimer's disease (AD) remains elusive despite similar clinical and pathological features. We aimed to explore the relationship between these genes and AD in the Chinese population. METHODS: Eight VaD-associated genes were screened by a targeted sequencing panel in a sample of 3604 individuals comprising 1192 AD patients and 2412 cognitively normal controls. Variants were categorized into common variants and rare variants according to minor allele frequency (MAF). Common variant (MAF ≥ 0.01)-based association analysis was conducted by PLINK 1.9. Rare variant (MAF < 0.01) association study and gene-based aggregation testing of rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal (SKAT-O test), respectively. Age at onset (AAO) and Mini-Mental State Examination (MMSE) association studies were performed with PLINK 1.9. Analyses were adjusted for age, gender, and APOE ε4 status. RESULTS: Four common COL4A1 variants, including rs874203, rs874204, rs16975492, and rs1373744, exhibited suggestive associations with AD. Five rare variants, NOTCH3 rs201436750, COL4A1 rs747972545, COL4A1 rs201481886, CST3 rs765692764, and CST3 rs140837441, showed nominal association with AD risk. Gene-based aggregation testing revealed that HTRA1 was nominally associated with AD. In the AAO and MMSE association studies, variants in GSN, ITM2B, and COL4A1 reached suggestive significance. CONCLUSION: Common variants in COL4A1 and rare variants in HTRA1, NOTCH3, COL4A1, and CST3 may be implicated in AD pathogenesis. Besides, GSN, ITM2B, and COL4A1 are probably involved in the development of AD endophenotypes.

15.
NPJ Genom Med ; 6(1): 69, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389718

RESUMO

Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and complicated etiology. There exist potential genetic component overlaps between different neurodegenerative dementias. Here, 1795 patients with neurodegenerative dementias from South China were enrolled, including 1592 with Alzheimer's disease (AD), 110 with frontotemporal dementia (FTD), and 93 with dementia with Lewy bodies (DLB). Genes targeted sequencing analysis were performed. According to the American College of Medical Genetics (ACMG) guidelines, 39 pathogenic/likely pathogenic (P/LP) variants were identified in 47 unrelated patients in 14 different genes, including PSEN1, PSEN2, APP, MAPT, GRN, CHCHD10, TBK1, VCP, HTRA1, OPTN, SQSTM1, SIGMAR1, and abnormal repeat expansions in C9orf72 and HTT. Overall, 33.3% (13/39) of the variants were novel, the identified P/LP variants were seen in 2.2% (35/1592) and 10.9% (12/110) of AD and FTD cases, respectively. The overall molecular diagnostic rate was 2.6%. Among them, PSEN1 was the most frequently mutated gene (46.8%, 22/47), followed by PSEN2 and APP. Additionally, the age at onset of patients with P/LP variants (51.4 years), ranging from 30 to 83 years, was ~10 years earlier than those without P/LP variants (p < 0.05). This study sheds insight into the genetic spectrum and clinical manifestations of neurodegenerative dementias in South China, further expands the existing repertoire of P/LP variants involved in known dementia-associated genes. It provides a new perspective for basic research on genetic pathogenesis and novel guiding for clinical practice of neurodegenerative dementia.

16.
iScience ; 24(8): 102894, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34401673

RESUMO

Schizophrenia (SCZ) is a severe neuropsychiatric disorder that affects 1% of the global population. Copy number variations (CNVs) have been shown to play a critical role in its pathophysiology; however, only case-control studies on SCZ susceptibility CNVs have been conducted in Han Chinese. Here, we performed an array comparative genomic hybridization-based genome-wide CNV analysis in 100 Chinese family trios with SCZ. Burden test suggested that the SCZ probands carried more duplications than their healthy parents and unrelated healthy controls. Besides, five CNV loci were firstly reported to be associated with SCZ here, including both unbalanced transmitted CNVs and enriched de novo CNVs. Moreover, two genes (CTDSPL and MGAM) in these CNVs showed significant SCZ relevance in the expression level. Our findings support the crucial role of CNVs in the etiology of SCZ and provide new insights into the underlying mechanism of SCZ pathogenesis.

17.
Neurochem Res ; 46(12): 3213-3221, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34406548

RESUMO

In numerous studies, microRNAs (miRNAs) have been authenticated to play vital roles in the pathophysiology of neuropathic pain and other neurological diseases. In our study, we focused on evaluating miR-378 and its potential effects in neuropathic pain development, as well as the underlying molecular mechanisms. Primarily, a chronic sciatic nerve injury (CCI) rat model was established. Next, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure the expression levels of miR-378 and EZH2 mRNA; the EZH2 protein expression levels were detected by western blot. A luciferase activity assay monitored the interaction of miR-378 and EZH2. Mechanical and thermal hyperalgesia was also performed to quantitate the effects of overexpression of miR-378 or EZH2 on the CCI rats. We found that miR-378 was down-regulated in the CCI rats, and the overexpression of miR-378 produced significant relief in their pain management. EZH2 was the downstream gene of miR-378 and was negatively regulated by miR-378. The up-regulation of EZH2 reduced the inhibitory effects of miR-378 on the development of neuropathic pain in the CCI rats. miR-378 acts as an inhibitor in the progression of neuropathic pain via targeting EZH2; the miR-378/EZH2 axis may be a novel target for the diagnosis and therapy of neuropathic pain in clinical treatment.

18.
Front Neurol ; 12: 628710, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248812

RESUMO

Accumulating evidence has revealed that immunity plays an important role in amyotrophic lateral sclerosis (ALS) progression. However, the results regarding the serum levels of immunoglobulin and complement are inconsistent in patients with ALS. Although immune dysfunctions have also been reported in patients with other neurodegenerative diseases, few studies have explored whether immune dysfunction in ALS is similar to that in other neurodegenerative diseases. Therefore, we performed this study to address these gaps. In the present study, serum levels of immunoglobulin and complement were measured in 245 patients with ALS, 65 patients with multiple system atrophy (MSA), 60 patients with Parkinson's disease (PD), and 82 healthy controls (HCs). Multiple comparisons revealed that no significant differences existed between patients with ALS and other neurodegenerative diseases in immunoglobulin and complement levels. Meta-analysis based on data from our cohort and eight published articles was performed to evaluate the serum immunoglobulin and complement between patients with ALS and HCs. The pooled results showed that patients with ALS had higher C4 levels than HCs. In addition, we found that the IgG levels were lower in early-onset ALS patients than in late-onset ALS patients and HCs, and the correlations between age at onset of ALS and IgG or IgA levels were significant positive. In conclusion, our data supplement existing literature on understanding the role of peripheral immunity in ALS.

19.
Front Endocrinol (Lausanne) ; 12: 696121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326815

RESUMO

Currently, the molecular mechanisms underlining male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are downregulated in seminal plasma of infertile patients and can serve as molecular biomarkers for male infertility. However, the source and mechanism for the dysregulation of piRNAs remain obscure. In this study, we found that exosomes are present in high concentrations in human seminal plasma and confirmed that piRNAs are predominantly present in the exosomal fraction of seminal plasma. Moreover, we showed that piRNAs were significantly decreased in exosomes of asthenozoospermia patients compared with normozoospermic men. By systematically screening piRNA profiles in sperms of normozoospermic men and asthenozoospermia patients, we found that piRNAs were parallelly reduced during infertility. At last, we investigated the expression of some proteins that are essential for piRNAs biogenesis in sperms and therefore identified a tight correlation between the levels of spermatozoa piRNA and MitoPLD protein, suggesting that the loss-of-function of MitoPLD could cause a severe defect of piRNA accumulation in sperms. In summary, this study identified a parallel reduction of piRNAs and MitoPLD protein in sperms of asthenozoospermia patients, which may provide pathophysiological clues about sperm motility.

20.
Sci Transl Med ; 13(603)2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290057

RESUMO

Inflammatory bowel disease (IBD) affects 0.3% of the global population, yet the etiology remains poorly understood. Anti-inflammation therapy has shown great success, but only 60% of patients with IBD benefit from it, indicating that new targets are needed. Here, we report the discovery of an intrinsic counter regulatory mechanism in colitis pathogenesis that may be targeted for IBD treatment. In response to microbial invasion, resident Vimentin+ stromal cells, connective tissue cells genetically marked by Twist2, are activated during the propagation phase of the disease, but not during initiation and resolution phases, and become a primary source of prostaglandin E2 (PGE2). PGE2 induction requires a nuclear factor κB-independent, TLR4-p38MAPK-Cox2 pathway activation. Ablation of each of the pathway genes, but not Rela or Tgfb1, in Twist2 cells enhanced M1 macrophage polarization and granulocyte/T helper 1 (TH1)/TH17 infiltration and aggravated colitis development. PGE2 administration ameliorated colitis in mouse models with defective PGE2 production but not in animals with normal PGE2 induction. Analysis of clinical samples and public domain data revealed increased expression of Cox2, the rate-limiting enzyme of PGE2 biosynthesis, in inflamed tissues, and especially in colon Vimentin+Twist2+ stromal cells, in about 60% of patients with active Crohn's disease or ulcerative colitis. Moreover, Cox2 protein expression was negatively correlated with disease severity, suggesting an involvement of stromal cells in IBD pathogenesis. Thus, the study uncovers an active immune pathway in colitic inflammation that may be targeted to treat patients with IBD with defects in PGE2 production.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Colo , Humanos , Imunidade Inata , Camundongos , Células Estromais
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