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1.
Artigo em Inglês | MEDLINE | ID: mdl-38683273

RESUMO

Phthalate acid esters (PAEs) and their metabolites, such as di-n-butyl phthalate (DBP) and mono-n-butyl phthalate (MBP), are known to cause male reproductive damage. Lactiplantibacillus plantarum RS20D has demonstrated the ability to remove both DBP and MBP in vitro, suggesting its potential as a detoxifying agent against these compounds. This study aimed to investigate the protective effects of RS20D on DBP or MBP-induced male reproductive toxicity in adolescent rats. Oral administration of RS20D significantly mitigated the histological damage to the testes caused by MBP or DBP, restored sperm concentration, morphological abnormalities, and the proliferation index in MBP-exposed rats, and partially reversed spermatogenic damage in DBP-exposed rats. Furthermore, RS20D restored serum levels of estradiol (E2) and testosterone, and superoxide dismutase (SOD) activity in DBP-exposed rats, significantly increased testosterone levels in MBP-exposed rats, and restored copper (Cu) concentrations in the testes after exposure to DBP or MBP. Additionally, RS20D effectively modulated the intestinal microbiota in DBP-exposed rats and partially ameliorated dysbiosis induced by MBP, which may be associated with the alleviation of reproductive toxic effects induced by DBP or MBP. In conclusion, this study demonstrates that RS20D administration can alleviate male reproductive toxicity and gut dysbacteriosis induced by DBP or MBP exposure, providing a dietary strategy for the bioremediation of PAEs and their metabolites.

2.
Prev Med Rep ; 41: 102703, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38595729

RESUMO

Objective: This study aims to systematically assess the rehabilitative effects of Baduanjin in stroke patients. Methods: Ten electronic databases were systematically searched using MeSH and free terms for relevant studies written in the English or Chinese language, and published on or before 15 February 2023. Studies in which Baduanjin was the only difference in treatment administered to experimental and control groups were included in the review. The studies' risk of bias was evaluated using the Cochrane criteria. Results: Twenty one studies that involved 1,649 participants were included. Compared to the control group, Baduanjin increased the scores for the Fugl-Meyer Assessment (including both upper and lower extremity components), Berg Balance Scale, Trunk Impairment Scale, Functional Ambulation Categories, 6-minute Walking Distance, Modified Barthel Index, Barthel Index, and total effective rate, but reduced the scores for the Pk254 balance function detection system, National Institutes of Health Stroke Scale and neurological deficit scale (P < 0.05, for all). Conclusion: The present study findings revealed the potential benefits of Baduanjin in improving movement, balance, trunk, ambulation and neurological functions, and the ability to perform activities of daily living in stroke patients. Larger randomized controlled trials with more standardized intervention protocols are required to obtain more robust evidence.

3.
Int J Biol Macromol ; 257(Pt 1): 128649, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38065452

RESUMO

Okra polysaccharides exhibits a range of biological activities. To date, its processing using microbial fermentation has not been explored. This study investigated the fermentation of okra juice with various lactic acid bacteria, followed by the extraction and characterization of crude polysaccharides (termed OPS-F), in contrast to their non-fermented counterpart (OPS). Changes in physicochemical properties, antioxidant activity and immunomodulatory ability were noted. The results demonstrated that OPS-F had a 7.42-12.53 % increase in total polysaccharides content compared to OPS. However, high-performance size-exclusion chromatography indicated a reduction in the molecular weight of OPS-F (7.9-9.5 × 105 Da) relative to OPS (1.66 × 106 Da). Compared to OPS, OPS-F had reduced levels of mannose, glucose, glucuronic acid and arabinose, but increased rhamnose, galacturonic acid and galactose, exhibiting enhanced solubility and lower apparent viscosity. Fourier transform infrared spectroscopy and nuclear magnetic resonance analysis showed minimal changes in polysaccharide structure post-fermentation. Moreover, despite a decrease in antioxidant activity post-fermentation, OPS-F exhibited superior immunomodulatory potential. In conclusion, fermenting okra juice with lactic acid bacteria alters the physicochemical properties of crude polysaccharides and enhances their immunomodulatory activity, offering a promising approach for developing new functional food resources.


Assuntos
Abelmoschus , Antioxidantes , Antioxidantes/farmacologia , Antioxidantes/química , Abelmoschus/química , Fermentação , Polissacarídeos/farmacologia , Polissacarídeos/química , Peso Molecular
4.
Appl Microbiol Biotechnol ; 107(22): 6985-6998, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37702791

RESUMO

The presence of cypermethrin in the environment and food poses a significant threat to human health. Lactic acid bacteria have shown promise as effective absorbents for xenobiotics and well behaved in wide range of applications. This study aimed to characterize the biosorption behavior of cypermethrin by Lactiplantibacillus plantarum RS60, focusing on cellular components, functional groups, kinetics, and isotherms. Results indicated that RS60 exopolysaccharides played a crucial role removing cypermethrin, with the cell wall and protoplast contributing 71.50% and 30.29% to the overall removal, respectively. Notably, peptidoglycans exhibited a high affinity for cypermethrin binding. The presence of various cellular surface groups including -OH, -NH, -CH3, -CH2, -CH, -P = O, and -CO was responsible for the efficient removal of pollutants. Additionally, the biosorption process demonstrated a good fit with pseudo-second-order and Langmuir-Freundlich isotherm. The biosorption of cypermethrin by L. plantarum RS60 involved complex chemical and physical interactions, as well as intraparticle diffusion and film diffusion. RS60 also effectively reduced cypermethrin residues in a fecal fermentation model, highlighting its potential in mitigating cypermethrin exposure in humans and animals. These findings provided valuable insights into the mechanisms underlying cypermethrin biosorption by lactic acid bacteria and supported the advancement of their application in environmental and health-related contexts. KEY POINTS: • Cypermethrin adsorption by L. plantarum was clarified. • Cell wall and protoplast showed cypermethrin binding ability. • L. plantarum can reduce cypermethrin in a fecal fermentation model.

5.
Int J Food Microbiol ; 394: 110167, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-36913840

RESUMO

To understand the deterioration of vinegar that has frequently occurred in China recently and to address such a concern, the physicochemical indicators and bacterial structure of the spoiled vinegar collected from Sichuan were preliminarily investigated. Results showed that Lactobacillaceae was most likely responsible for the decrease of vinegar total sugar and furfural, through which total acid and furfuryl alcohol were generated. Then, an unreported difficult-to-cultivate gas-producing bacterium named Z-1 was isolated using a modified MRS medium. Strain Z-1 was identified as Acetilactobacillus jinshanensis subsp. aerogenes on the basis of physiological, biochemical, molecular biological and whole genome analyses. According to the investigation, such species was present throughout the fermentation process and not limited in Sichuan. The analysis of genetic diversity indicated that all the obtained A. jinshanensis isolates displayed high sequence similarity and an absence of recombination. Although it demonstrated acid resistance, Z-1 could be completely deactivated through heating (60 °C). Based on the above results, suggestions for safe production are made for vinegar enterprises.


Assuntos
Ácido Acético , Bactérias , Ácido Acético/farmacologia , Ácido Acético/análise , Bactérias/genética , Fermentação , Lactobacillaceae , China
6.
Materials (Basel) ; 17(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38203862

RESUMO

In this study, we address the challenge of surface roughness in CoCrMo alloys, typically used in artificial knee joints, which can initiate a cascade of biological responses causing inflammation, osteolysis, joint instability, and increased susceptibility to infection. We propose the application of a chemical mechanical polishing (CMP) technique, using an ecologically responsible slurry composed of 4 wt% SiO2, 0.3 wt% H2O2, 1.0 wt% glycine, and 0.05 wt% benzotriazole. Our innovative approach demonstrated significant improvements, achieving a material removal rate of 30.9 nm/min and reducing the arithmetic mean roughness from 20.76 nm to 0.25 nm, thereby enhancing the nanoscale surface quality of the artificial knee joint alloy. The smoother surface is attributed to a decrease in corrosion potential to 0.18 V and a reduction in corrosion current density from 9.55 µA/cm2 to 4.49 µA/cm2 with the addition of BTA, evidenced by electrochemical tests. Furthermore, the preservation of the phase structure of the CoCrMo alloy, as confirmed by XRD analysis and elemental mapping, ensures the structural integrity of the treated surfaces. These outcomes and our simulation results demonstrate the effectiveness of our CMP method in engineering surface treatments for artificial knee joints to optimize friction behavior and potentially extend their lifespans.

7.
BMJ Open ; 12(11): e067280, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379643

RESUMO

OBJECTIVE: This study aims to systematically evaluate the effects of Baduanjin on motor function, balance and gait in patients with Parkinson's disease (PD). DESIGN: Systematic review and meta-analysis. STUDY SELECTION: All eligible randomised controlled trials (RCTs) published in the English and Chinese language were included. DATA SOURCES: Ten electronic databases were systematically searched, from inception to 17 March 2022: PubMed, Web of Science, Cochrane Library, Embase, EBSCOhost, OVID, SinoMed, China National Knowledge Infrastructure, Wanfang Data and China Science Journal Database (VIP). REVIEW METHODS: Methodological quality assessment and meta-analysis were performed for the included studies using the Cochrane Review Manager V.5.4 software. RESULTS: Ten RCTs with 804 participants were included. The results revealed the following: (1) Baduanjin significantly improved the motor function of patients with PD, based on the Unified Parkinson's Disease Rating Scale Part III (mean difference, MD -5.37, 95% CI -8.96 to -1.78, p=0.003) and Fugl-Meyer Assessment of Lower Extremity (MD 5.39, 95% CI 2.71 to 8.07, p<0.0001); (2) Baduanjin significantly improved the ability of balance of patients with PD, based on the Berg Balance Scale (MD 4.40, 95% CI 3.08 to 5.73, p<0.00001); (3) Baduanjin significantly improved the gait of patients with PD, based on the 6 min walk distance (MD 21.62, 95% CI 11.14 to 32.10, p<0.0001). After the further subgroup and sensitivity analyses, the heterogeneity was identified to be potentially due to the different degrees of disease severity in patients with PD and the difference in Baduanjin intervention durations. CONCLUSIONS: The analysis of this systematic evaluation indicates that Baduanjin might have a positive effect in improving the motor function, balance and gait of patients with PD. However, due to the quantity and clinical heterogeneity limitations of the included studies, this conclusion still warrants more high-quality and multicentre RCTs for further verification.


Assuntos
Doença de Parkinson , Qigong , Humanos , Doença de Parkinson/complicações , Marcha , Exercício Físico , Qigong/métodos , Caminhada
8.
J Appl Microbiol ; 132(4): 2968-2979, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35025132

RESUMO

AIMS: The current study aimed to evaluate the capacity of two Lactiplantibacillus plantarum strains to remove Bisphenol A (BPA) and to determine the preliminary removal mechanisms underlying this process. METHODS AND RESULTS: The BPA removal capacity of L. plantarum RS20D and DL7X was assessed by HPLC analysis. The effect of various treatments (physical, chemical and enzymatic) on two strains were studied to understand which interaction types worked. The different cellular components of them were also subjected to binding assays. Additionally, Fourier-transform infrared spectroscopy (FTIR) was performed to identify the functional groups related to the BPA-binding process. Results show that various treatments enhanced the binding capacity of two strains, the effect of sodium dodecyl sulphate was the most outstanding (p < 0.05). Hydrogen bonding and hydrophobic interactions likely occurred. Peptidoglycans showed the highest binding capability, protoplasts and teichoic acids might also exert a binding effect. -OH, C=O, -CH, -NH, C-N, C-O and P=O participated in BPA binding by the two L. plantarum lines. CONCLUSIONS: Peptidoglycans, protoplasts and teichoic acid played a vital role in the binding of BPA. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provided a theoretical foundation for developing effective dietary strategies with foodborne L. plantarum to remove food contaminants.


Assuntos
Compostos Benzidrílicos , Fenóis , Compostos Benzidrílicos/química , Interações Hidrofóbicas e Hidrofílicas , Fenóis/química , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Front Microbiol ; 13: 1113705, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36713200

RESUMO

Petro-plastic wastes cause serious environmental contamination that require effective solutions. Developing alternatives to petro-plastics and exploring feasible degrading methods are two solving routes. Bio-plastics like polyhydroxyalkanoates (PHAs), polylactic acid (PLA), polycaprolactone (PCL), poly (butylene succinate) (PBS), poly (ethylene furanoate) s (PEFs) and poly (ethylene succinate) (PES) have emerged as promising alternatives. Meanwhile, biodegradation plays important roles in recycling plastics (e.g., bio-plastics PHAs, PLA, PCL, PBS, PEFs and PES) and petro-plastics poly (ethylene terephthalate) (PET) and plasticizers in plastics (e.g., phthalate esters, PAEs). All these bio- and petro-materials show structure similarity by connecting monomers through ester bond. Thus, this review focused on bio-plastics and summarized the sequences and structures of the microbial enzymes catalyzing ester-bond synthesis. Most of these synthetic enzymes belonged to α/ß-hydrolases with conserved serine catalytic active site and catalyzed the polymerization of monomers by forming ester bond. For enzymatic plastic degradation, enzymes about PHAs, PBS, PCL, PEFs, PES and PET were discussed, and most of the enzymes also belonged to the α/ß hydrolases with a catalytic active residue serine, and nucleophilically attacked the ester bond of substrate to generate the cleavage of plastic backbone. Enzymes hydrolysis of the representative plasticizer PAEs were divided into three types (I, II, and III). Type I enzymes hydrolyzed only one ester-bond of PAEs, type II enzymes catalyzed the ester-bond of mono-ester phthalates, and type III enzymes hydrolyzed di-ester bonds of PAEs. Divergences of catalytic mechanisms among these enzymes were still unclear. This review provided references for producing bio-plastics, and degrading or recycling of bio- and petro-plastics from an enzymatic point of view.

10.
J Appl Microbiol ; 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36626738

RESUMO

AIMS: Beads containing heat-inactivated bacterial biomaterial (BBBs) were prepared for removal of cypermethrin (CPM) and the conditions for this removal were evaluated and optimized via orthogonal experiments. The adsorption characteristics of BBBs and the binding mechanism were then explored. METHODS AND RESULTS: Single-factor and orthogonal experiments were carried out to optimize five factors affecting the production and effectivity of the beads. The adsorption rate of CPM could reach 98% with beads prepared under optimized conditions: equal volumes of Lactobacillus cell debris derived from 1 × 1011 CFU; 2% hydroxypropyl-ß-cyclodextrin and 2.5% activated carbon concentration, were mixed to give mixture TM, and this and SA, was mixed 1:4 with sodium alginate (SA) and beads were prepared using a 26-Gauge needle). The best adsorption conditions were initial CPM concentration of 10 mg l-1, incubation time of 24 h, and rotational speed of 180 rpm. BBBs have a well-formed structure and abundant surface functional groups, such as -COOH, -OH, -NH, -CH, -CO, -C = C. The adsorption process conformed to pseudo-second-order kinetic, and it was also a Freundlich monolayer adsorption, and the calculated maximum adsorption capacity was 9.69 mg g-1 under optimized conditions. CONCLUSIONS: BBBs showed the highest CPM removal capacity and a good tolerance ability.

11.
J Appl Microbiol ; 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36626792

RESUMO

AIMS: Beads containing heat-inactivated bacterial biomaterial (BBBs) were prepared for removal of cypermethrin (CPM) and the conditions for this removal were evaluated and optimized via single-factor coupled orthogonal experiments based on five factors. The adsorption characteristics of BBBs and the binding mechanism were then explored. METHODS AND RESULTS: Results showed that the adsorption rate of CPM could reach 98% with beads prepared under optimized conditions: equal volumes of Lactobacillus cell debris derived from 1×1011 CFU; 2% hydroxypropyl-ß-cyclodextrin and 2.5% activated carbon concentration, were mixed to give mixture TM, and this and SA, was mixed 1:4 with sodium alginate (SA) and beads were prepared using a 26-Gauge needle). The best adsorption conditions were initial CPM concentration of 10 mg l-1, incubation time of 24 h, and rotational speed of 180 rpm. BBBs have a well-formed structure and abundant surface functional groups, such as -COOH, -OH, -NH, -CH, -CO, -C=C. The adsorption process conformed to pseudo-second-order kinetic, and it was also a Freundlich monolayer adsorption, and the calculated maximum adsorption capacity was 9.69 mg g-1 under optimized conditions. CONCLUSIONS: BBBs showed the highest CPM removal capacity and a good tolerance ability. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provided a theoretical foundation for developing an adsorbent with heat-inactivated Lactobacillus plantarum (L. plantarum) RS60 for removing CPM in wastewater or drinks.

12.
Hum Mutat ; 40(4): 392-403, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30609140

RESUMO

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.


Assuntos
Encefalopatias/genética , Calcinose/genética , Predisposição Genética para Doença , Mutação , Doenças Neurodegenerativas/genética , Adulto , Idoso , Alelos , Transporte Biológico , Biomarcadores , Encefalopatias/diagnóstico , Encefalopatias/metabolismo , Calcinose/diagnóstico , Calcinose/metabolismo , Linhagem Celular Tumoral , China , Feminino , Genes sis , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/metabolismo , Neuroimagem , Fenótipo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptores Acoplados a Proteínas G/genética , Receptores Virais/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Tomografia Computadorizada por Raios X , Receptor do Retrovírus Politrópico e Xenotrópico
13.
Int J Nurs Stud ; 82: 129-138, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29631145

RESUMO

BACKGROUND: Spasticity is a common post-stroke complication, and it results in substantial deterioration in the quality of life of patients. Although potential positive effects of warm-needle moxibustion on spasticity after stroke have been observed, evidence on its definitive effect remains uncertain. OBJECTIVES: This study aimed to summarize clinical evidence pertaining to therapeutic effects and safety of warm-needle moxibustion for treating spasticity after stroke. DESIGN: Randomized controlled trials were reviewed systematically on the basis of the Cochrane Handbook for Systematic Reviews of Interventions. The report follows the PRISMA statement. METHODS: Ten electronic databases (PubMed, CENTRAL, EMBASE, AMED, CINAHL, Web of Science, CBM, CNKI, WanFang, and VIP) were explored, and articles were retrieved manually from two Chinese journals (The Journal of Traditional Chinese Medicine and Zhong Guo Zhen Jiu) through retrospective search. Randomized controlled trials with warm-needle moxibustion as treatment intervention for patients with limb spasm after stroke were included in this review. The risk of bias assessment tool was utilized in accordance with Cochrane Handbook 5.1.0. All included studies reported spasm effect as primary outcome. Effect size was estimated using relative risk, standardized mean difference, or mean difference with a corresponding 95% confidence interval. Review Manager 5.3 was utilized for meta-analysis. RESULTS: Twelve randomized controlled trials with certain methodological flaws and risk of bias were included, and they involved a total of 878 participants. Warm-needle moxibustion was found to be superior to electroacupuncture or acupuncture in reducing spasm and in promoting motor function and daily living activities. Pooled results for spasm effect and motor function were significant when warm-needle moxibustion was compared with electroacupuncture or acupuncture. A comparison of daily living activities indicated significant differences between warm-needle moxibustion and electroacupuncture. However, no difference was observed between warm-needle moxibustion and acupuncture. CONCLUSIONS: Warm-needle moxibustion may be a promising intervention to reduce limb spasm as well as improve motor function and daily living activities for stroke patients with spasticity. However, evidence was not conclusive. Rigorously designed randomized controlled trials with sample sizes larger than that in the included trials should be conducted for verification.


Assuntos
Moxibustão/métodos , Espasticidade Muscular/terapia , Acidente Vascular Cerebral/complicações , Atividades Cotidianas , Humanos , Espasticidade Muscular/etiologia , Espasticidade Muscular/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/fisiopatologia
14.
Cell Tissue Res ; 370(2): 267-273, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28766044

RESUMO

Primary familial brain calcification (PFBC) is a neuropsychiatric disorder characterized by bilateral cerebral calcification with diverse neurologic or psychiatric symptoms. Recently, XPR1 variation has accounted for PFBC as another new causative gene. However, little is known about the distribution and basic function of XPR1 and its interaction with the other three pathogenic genes for PFBC (SLC20A2, PDGFRB and PDGFB). The aim of this study was to further clarify the role of XPR1 in PFBC brain pathology. As a result, gene expression profiles showed that XPR1 mRNA was widely expressed throughout the mouse brain. Cerebellum and striatum, most commonly affected in PFBC, contained a higher level of XPR1 protein than other brain regions. Additionally, XPR1 deficiency seriously affected Pi efflux and XPR1 mutations seemed to have an effect through haploinsufficiency mechanism. The immunoprecipitation and immunohistochemical studies demonstrated that XPR1 could interact with PDGFRB and might form a complex on the cell membrane. These results suggested that XPR1 played a fundamental role in the maintenance of cellular phosphate balance in the brain. This provided us with a novel perspective on understanding the pathophysiology of PFBC. The expression networks and interaction with the known pathogenic genes could shed new light on additional candidate genes for PFBC.


Assuntos
Encefalopatias/genética , Encéfalo/metabolismo , Calcinose/genética , Receptores Acoplados a Proteínas G/genética , Receptores Virais/genética , Transcriptoma , Animais , Encéfalo/patologia , Encefalopatias/metabolismo , Encefalopatias/patologia , Calcinose/metabolismo , Calcinose/patologia , Expressão Gênica , Predisposição Genética para Doença , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mapas de Interação de Proteínas , RNA Mensageiro/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/análise , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores Acoplados a Proteínas G/análise , Receptores Acoplados a Proteínas G/metabolismo , Receptores Virais/análise , Receptores Virais/metabolismo , Regulação para Cima , Receptor do Retrovírus Politrópico e Xenotrópico
15.
J Hum Genet ; 62(7): 697-701, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28298627

RESUMO

Four causative genes, including solute carrier family 20 member 2 (SLC20A2), platelet-derived growth factor receptor b (PDGFRB), platelet-derived growth factor b (PDGFB)and xenotropic and polytropic retrovirus receptor 1 (XPR1), have been identified to cause primary familial brain calcification (PFBC). However, PDGFRB mutations seem to be quite rare and no PDGFRB mutations have been reported in Chinese PFBC patients. A total of 146 PFBC patients including 12 families and 134 sporadic patients were recruited in this study. All of them were previously tested negative for the SLC20A2. Mutational analyses of the entire exons and exon-intron boundaries of PDGFRB were carried out by direct gene sequencing. In silico analyses of the identified variants were conducted using Mutation Taster, PolyPhen-2 and Sorts Intolerant From Tolerant. Two heterozygous variants, c.3G>A and c.2209G>A, of the PDGFRB gene were revealed in two PFBC families, respectively. These two variants were not observed in 200 healthy controls. The variant c.3G>A was located in exon 2 and affected the initiation codon of the PDGFRB gene. The variant c.2209G>A resulted in amino-acid substitutions of aspartic acid to asparagine at position 737. Both of these two variants co-segregated with the disease phenotype (variant carriers in Family 1: I1, II2 and II3; variant carriers in Family 2: I2 and II8), suggesting a pathogenic impact of these variants. The prevalence of PDGFRB mutations in Chinese PFBC patients seems to be quite low, indicating that PDGFRB is not a major causative gene of PFBC in Chinese population.


Assuntos
Povo Asiático/genética , Encéfalo/patologia , Calcinose/genética , Mutação/genética , Proteínas Proto-Oncogênicas c-sis/genética , Sequência de Aminoácidos , Sequência de Bases , Encéfalo/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Família , Feminino , Humanos , Masculino , Linhagem , Proteínas Proto-Oncogênicas c-sis/química , Receptor do Retrovírus Politrópico e Xenotrópico
16.
Gene ; 2016 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-27984190

RESUMO

BACKGROUND: Until recently, primary familial brain calcification (PFBC) has been determined by four genes, SLC20A2, PDGFRB, PDGFB and XPR1. No studies have been carried out to analyze the gene mutation of PDGFB in Chinese population. OBJECTIVE: To screen mutations of PDGFB gene in a large cohort of Chinese PFBC patients with no SLC20A2 mutations. METHODS: We recruited 192 PFBC patients, including 21 index cases and 171 sporadic cases, in our study. Peripheral venous blood samples of all included participants were collected for genomic DNA extraction. The coding sequence of PDGFB was amplified by polymerase chain reaction (PCR) followed by direct sequencing. The potential effects of the identified variants on protein function were assessed by bioinformatics analysis. RESULTS: Three missense variants (c.35G>T, c.232C>T, and c.610C>A) and one nonsense variant (c.220G>T) of PDGFB were identified in five sporadic PFBC patients. The variant c.35G>T was found in 2 healthy controls from the same ethnic background, whereas c.220G>T, c.232C>T and c.610C>A were absent from 500 controls. c.220G>T (p.E74*) produced a stop codon in the place of the glutamicacid residue number 74. c.232C>T (p.R78C) occurred at highly conserved regions and were predicted as damaging by at least two computational predictive programs, suggesting that this variant were likely to have a causal role in PFBC. Although variant c.610C>A (p.P204T) also occurred at a highly conserved region, it was predicted to be most likely benign by two computational predictive programs, suggesting an uncertain role of this variant on PFBC. CONCLUSIONS: The present study identified one likely pathogenic variant (p.E74*) and two variants of uncertain significance (p.R78C and p.P204T) in PDGFB. Further studies of PDGF-B functional expression for these variants are still required to confirm the pathogenic effect.

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