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1.
Expert Rev Vaccines ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034224

RESUMO

BACKGROUND: The resurgence of Bordetella pertussis infections leading to whooping cough is a concern in many parts of the world. The number of pertussis cases in China has increased significantly since 2013. RESEARCH DESIGN AND METHODS: In this study, whole genome sequencing analysis was performed for 388 B. pertussis strains isolated in China from 1970s to 2018, combining 594 published strains from around the world. RESULTS: This study revealed that lineage V diverged about 50 years ago in China, while lineage IV is dominant in the other countries. It also revealed that the erythromycin-resistant sub-lineages Va, Vb and Vc with limited genomic variation emerged 11~12 years ago. These three sub-lineages were identified after the co-purified acellular vaccines (cp-ACVs) completely replaced the previous whole cell vaccines (WCVs) after the national immunization program of 2012. It suggests that the cp-ACVs cannot induce immunity that is potent enough to restrict the spread of the lineage V, antibiotic abuse further favors the spread of this lineage in China. CONCLUSIONS: These findings demand a reassessment of the immunization strategy and development of new vaccines in China to stop the resurgence and drug resistance of B. pertussis.

2.
Orphanet J Rare Dis ; 15(1): 248, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928263

RESUMO

OBJECTIVE: This study aimed to explore the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN). METHODS: A single-arm, open-label study was conducted. All subjects received pantethine during the 24-week period of treatment. The primary endpoints were change of the Unified Parkinson's Disease Rating Scale (UPDRS) I-III and Fahn-Marsden (FM) score from baseline to week 24 after treatment. RESULTS: Fifteen children with PKAN were enrolled, and all patients completed the study. After 24 weeks of treatment with pantethine at 60 mg/kg per day, there was no difference in either UPDRS I-III (t = 0.516, P = 0.614) or FM score (t = 0.353, P = 0.729) between the baseline and W24. Whereas the rates of increase in UPDRS I-III (Z = 2.614, p = 0.009) and FM scores (Z = 2.643, p = 0.008) were slowed. Four patients (26.7%) were evaluated as "slightly improved" by doctors through blinded video assessment. Patients with lower baseline UPDRS I-III or FM scores were more likely to be improved. The quality of life of family members improved after pantethine treatment, evaluated by PedsQL TM 2.0 FIM scores, whereas the quality of life of the patients was unchanged at W24, evaluated by PedsQL TM 4.0 and PedsQL TM 3.0 NMM. Serum level of CoA was comparable between baseline and W24. There was no drug related adverse event during the study. CONCLUSIONS: Pantethine could not significantly improve motor function in children with PKAN after 24 weeks treatment, but it may delay the progression of motor dysfunction in our study. Pantethine was well-tolerated at 60 mg/kg per day. TRIAL REGISTRATION: Clinical trial registration number at www.chictr.org.cn :ChiCTR1900021076, Registered 27 January2019, the first participant was enrolled 30 September 2018, and other 14 participants were enrolled after the trial was registered.

3.
Food Funct ; 11(9): 7817-7829, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32808642

RESUMO

It is widely believed that grape seed proanthocyanidin extract (GSPE) exerts antioxidant and anti-inflammatory effects. Dietary supplementation with GSPE has been reported to alleviate colitis signs in mice, but the mechanisms involved require further exploration. The present study investigated how the oral administration of GSPE ameliorates colitis signs and reduces colitis-associated inflammation. C57BL/6 mice were treated with GSPE for 21 days. During the final 7 days of treatment, the mice were administered dextran sulfate sodium (DSS) dissolved in drinking water to induce experimental colitis. We found that GSPE treatment improved DSS-induced colitis, which was evidenced by decreases in disease activity index (DAI) scores, pathological scores, and oxidative stress and increases in zonula occludens-1 (ZO-1), occludin, and claudin-1 mRNA levels of colon tissue. Notably, the proinflammatory cytokines TNF-α and IL-1ß were significantly downregulated as a result of GSPE treatment in colon tissues. GSPE treatment also reduced NLR family pyrin domain-containing 3 (NLRP3) inflammasome mRNA levels of colon tissue. Furthermore, an analysis of 16S rRNA sequences showed that GSPE rebalanced the DSS-damaged gut microbiota, including reducing Bacteroidetes, Dubosiella, and Veillonella, increasing Verrucomicrobia and Akkermansia, and elevating the Firmicutes to Bacteroidetes ratio. In conclusion, GSPE supplementation alleviates DSS-induced colitis by modulating inflammatory cytokines and oxidation stress, maintaining the intestinal barrier, and improving the microbial community. These results indicate that GSPE might be a new dietary strategy for the treatment of ulcerative colitis.

4.
J Sci Food Agric ; 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32767366

RESUMO

BACKGROUND: Sanghuang mushrooms are medicinal fungi widely used in eastern Asia. In this study, the antioxidant and anti-inflammatory activity of a novel extracellular polysaccharopeptide, sanghuang extracellular polysaccharopeptide (SePSP) was investigated. The SePSP was purified from the submerged fermentation broth of a sanghuang mycelium, Sanghuangporus lonicericola strain CBS17, which was isolated from a wild sanghuang fruiting body. RESULTS: The SePSP was extracted using an ethanol precipitation procedure, followed by diethylaminoethanol (DEAE) anion-exchange and size-exclusion chromatography. The mass ratio of the polysaccharide and peptide components in the purified SePSP was approximately 4.87:1. By determining its free radical scavenging abilities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), the hydroxyl free radical, and the superoxide anion free radical, as well as its total reducing power, SePSP was shown to have strong concentration-dependent antioxidant activity in vitro. Further, SePSP effectively alleviated dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice. Administration of 200 mg kg-1 SePSP by gavage for 7 days prevented body weight loss; significantly reduced the mRNA levels of proinflammatory cytokines, including TNF-α and IL-1ß; increased mRNA level of the anti-inflammatory cytokine IL-10 in the colon, and decreased the malondialdehyde concentration from 6.42 to 4.82 µmol L-1 in the blood in UC mice. CONCLUSION: The SePSP had strong concentration-dependent antioxidant activity in vitro and effectively alleviated DSS-induced UC in mice. The in vivo therapeutic efficacy in DSS-induced UC may be mediated by modulating the expression of inflammatory cytokines and inhibiting oxidative stress. The findings provide a scientific rationale for the use of bioactive nutraceuticals from sanghuang mushrooms to develop functional foods for the prevention and treatment of UC. © 2020 Society of Chemical Industry.

5.
J Youth Adolesc ; 49(8): 1674-1686, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32578000

RESUMO

With China's fast-growing economy, family dinners are often overlooked. However, family dinner, as an important routine family activity, provides an opportunity for interaction between adolescents and their parents, which promotes adolescents' happiness. Guided by the positive youth development perspective, the character strength theory of happiness and the family investment model, the current study simultaneously investigated the mediating role of adolescents' internal assets and the moderating role of parental educational level in the influence of family dinner on adolescents' happiness in Chinese families. A three-wave longitudinal study spanning approximately three years was conducted among 817 Chinese seventh graders (52.4% male; Mage = 12.62 years). The frequency of family dinner at the first year was significantly positively correlated with adolescents' happiness in the first and third years. The cross-sectional and longitudinal results showed that adolescents' internal assets mediated the relationship between family dinner frequency and happiness. Specifically, family dinner with higher-educated parents was a stronger predictor of internal assets than family dinner with lower-educated parents after one year. These findings from the Chinese cultural context complement the research in this field and inform practical endeavors to promote adolescents' happiness worldwide based on the strengths of different cultures.

6.
Food Funct ; 11(5): 3964-3974, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32400787

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory bowel disease whose prevalence is increasing globally. A synbiotic has probiotic and prebiotic components and is regarded as a promising candidate for alleviating UC-associated inflammation. The purpose of this study is to determine whether there is an additive efficacy between the probiotic Bifidobacterium infantis (B. infantis) and the prebiotic xylooligosaccharide (XOS) against UC. C57BL/6 mice were treated with B. infantis, XOS, or synbiotic (combination of B. infantis and XOS) for 21 d. During the final 7 d of treatment, the mice were administered dextran sulfate sodium (DSS) dissolved in drinking water to induce colitis. All treatments decreased the disease activity index (DAI) and pathological scores, and synbiotic treatment was more efficacious than either the probiotic or prebiotic alone. Compared with the DSS-induced colitis group, all treatment groups significantly downregulated the proinflammatory cytokines TNF-α and IL-1ß, and synbiotic treatment significantly upregulated the anti-inflammatory cytokine IL-10 in the colon tissues. Furthermore, all treatments significantly reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome mRNA level in the colon tissues. All treatments significantly inhibited oxidative stress and increased zonula occludens-1 (ZO-1), occludin, and claudin-1 tight junction (TJ) molecule mRNA levels in the colon tissues. Therefore, the observed efficacy of synbiotics against colitis may be explained by the additive combination of the direct anti-inflammatory effects of the probiotic and prebiotic components and their ability to fortify colonic epithelial barrier integrity. Our findings suggest that a synbiotic is a promising dietary supplement or functional food for the effective management of UC.

7.
J Neurol ; 267(9): 2612-2618, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32388833

RESUMO

BACKGROUND: Epilepsy might be one of the manifestations in children with leukodystrophies, but the incidence of epilepsy in different types of leukodystrophies is unclear yet. METHODS: A retrospective observational cohort study was performed on children diagnosed with leukodystrophies in Peking University First Hospital from January 2004 to June 2019, and the patients were followed for 5.5 years (0.4-14.2 years) after the first visit. RESULTS: A total of 333 patients were included. The overall incidence of epilepsy was 30.6% (102/333). Alexander disease had the highest incidence (77.3%, 51/66), followed by vanishing white matter disease (41.2%, 21/51), Canavan disease (33.3%, 1/3), megalencephalic leukoencephalopathy with subcortical cysts (32.1%, 9/28), X-linked adrenoleukodystrophy (23.1%, 3/13), Krabbe disease (18.8%, 3/16), metachromatic leukodystrophy (14.3%, 6/42), and Pelizaeus-Merzbacher disease (7.0%, 8/114). The incidence of epilepsy in leukodystrophies classified as astrocytopathies was higher than that in myelin disorders (55.9% vs. 11.2%, P < 0.001). Of the 102 patients with epilepsy, seizures were the chief complaint in 61.8% (63/102) and the initial symptom in 22.5% (23/102). The median age at seizure onset was 20.5 months (1 day-176 months). A total of 63.7% (65/102) of children were treated with antiepileptic drugs (AEDs), and the responder rate was 90.8% (59/65) at the last follow-up, including 71.2% (42/59) of children who were seizure free. CONCLUSIONS: Epilepsy was not uncommon in children with leukodystrophies. Children with Alexander disease had the highest incidence; whereas, children with Pelizaeus-Merzbacher disease had the lowest incidence. Children with leukodystrophies classified as astrocytopathies were more prone to have epilepsy than those classified as myelin disorders. Most children with leukodystrophies who presented with epilepsy showed a good response to antiepileptic drugs.

8.
Microb Cell Fact ; 19(1): 84, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252770

RESUMO

Phytases are widely utilized in feed industry to increase the utilization of phosphorus, minerals, and amino acids for improvement of animal and human nutrition. At present, all known ß-propeller phytases (BPP) have been generated from bacteria, particularly Bacillus. In this work we report for the first time a new fungal-derived BPP phytase. We identified a phytase highly differentially expressed only in the parasitic stage of a nematophagous fungus, Arhtrobotrys oliogospora, during the development of the 3D traps. We found that this phytase was homologous to the known bacterial BPP phytase, thus we referred the new phytase to Aophytase. The heterologous expression of codon-optimized Aophytase gene in Pichia pastoris was successfully investigated to yield recombinant Aophytase (r-Aophytase) with high specific enzyme activity of 74.71 U/mg, much higher than those of recombinant BPP phytases derived bacteria. The kinetic parameters of the r-Aophytase, the optimum pH and temperature, as well as the effects of surfactant, EDTA and different ions on its enzyme activity were further investigated. The potential utilization of r-Aophytase in feed processing was finally explored. We found that the optimal pH value was about 7.5, and the optimal temperature was 50 °C.; r-Aophytase significantly increased the release of inorganic phosphorus from soybean meal, and improved the release of soluble minerals from the durum wheat flour and finger millet flour. The findings indicate its potential utilization in the feed processing to ameliorate nutritional value of cereals and animal feed in the future.

9.
J Mater Chem B ; 8(13): 2598-2606, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32124889

RESUMO

Recently, graphene quantum dots (GQDs) have been extensively studied in biomedical areas such as bio-imaging, bio-sensing and photothermal therapy due to their superior optical and physiochemical properties compared to traditional organic biomarkers. Application of GQDs in photodynamic therapy (PDT) has been explored since 2014, but currently the main challenges are inadequate singlet oxygen (1O2) quantum yield (QY), poor solubility and biocompatibility. Herein, we report on the synthesis of a new class of fluorine-containing GQDs (F-GQDs) by an oxidative cutting method using fluorinated graphite as the raw material. The as-synthesized F-GQD sample demonstrates an average particle size of 2.1 nm with a fluorine doping content of 1.43%. The F-GQDs have a better water solubility and biocompatibility than the GQDs, and emit strong green fluorescence at 365 nm excitation with a relative fluorescence QY of 13.72%. Moreover, the fluorescence imaging effect as well as photodynamic activity was successfully tested in both an in vitro HepG2 cell line model and a 3D multicellular spheroid model, the latter of which mimics the tumour microenvironment. Further studies using UV-visible spectroscopy to monitor the degradation of water-soluble 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABDA) demonstrate that the F-GQD sample generates 1O2 efficiently (QY = 0.49) under visible light irradiation. Compared to non-fluorinated GQDs, the as-reported F-GQDs appear to be a more promising photosensitizer for image-guided PDT.

10.
Int J Biol Macromol ; 149: 1213-1221, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32035955

RESUMO

Lectins are the primary recognition macromolecules for various types of fucosylation, a common eukaryotic post-translational modification. In this study, we report the heterologous expression and molecular binding properties of a fucose-specific lectin, AofleA, isolated from Arthrobotrys oligospora. This is the first reported fucose-specific lectin found in nematophagous fungi. The recombinant AofleA (r-AofleA) was expressed in Escherichia coli with high efficiency, yielding at least 500 mg of soluble and functional r-AofleA per liter of broth. Using hemagglutination inhibition assay and glycan microarray analysis, r-AofleA was found to be broadly specific for fucosylated glycans or oligosaccharides including Fucα(1-2), Fucα(1-3), Fucα(1-4) and Fucα(1-6) linkages, similar to Aleuria aurantia lectin (AAL). Frontal affinity chromatography showed that r-AofleA has high affinity towards PA-L-fucose with an average Kd value of 15 nM. These findings provide a basis for improved understanding of the structure and functions of AofleA during recognition and capture of prey nematodes by nematophagous fungus A. oligospora.

11.
CNS Neurosci Ther ; 26(7): 754-761, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32043823

RESUMO

AIMS: To investigate the natural history and genotype-phenotype correlation of pantothenate kinase-associated neurodegeneration. METHODS: We collected data of patients with PKAN by searching from available publications in English and Chinese. Patients diagnosed in our center (Peking University First Hospital) were also included. The difference in natural history and genotype between early-onset (<10 year of age at onset) and late-onset patients (≥10 year of age at onset) with PKAN was compared. RESULTS: A total of 248 patients were included. The median age at onset was 3.0 years in the early-onset group and 18.0 years in the late-onset group. Dystonia in lower limbs was the most common initial symptom in both groups. In the early-onset group, the median interval between the disease onset and occurrence of oromandibular dystonia, generalized dystonia, loss of independent ambulance was 6.0 years, 5.0 years, and 5.0 years. The corresponding values in late-onset group were 1.0 year, 4.0 years, and 6.0 years. About 20.0% died at median age of 12.5 years and 9.5 years after the onset in early-onset group. About 2.0% of the late-onset patients died during the follow-up. A total of 176 mutations were identified. Patients carrying two null alleles in PANK2 showed significantly earlier age of disease onset and progressed more rapidly to loss of independent ambulance. CONCLUSIONS: This study provided a comprehensive review on the natural history and genotype of 248 patients with PKAN. The results will serve as a historical control data for future clinical trial on PKAN.

12.
J Coll Physicians Surg Pak ; 30(1): 13-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931925

RESUMO

OBJECTIVE: To evaluate the recovery influence of CO2 pneumoperitoneum pressure for transabdominal preperitoneal hernioplasty (TAPP). STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: General Department II, Zhongda Hospital, Southeast University, Nanjing, China, from August 2016 to October 2018. METHODOLOGY: Eighty cases were enrolled prospectively and divided into three groups in chronological order. A 14 mmHg CO2 pressure was used for negative control group while the pressure was controlled at 12 mmHg for observation group and 10 mmHg for intervention group. General information included the patients' age, gender, type of hernia, hernia defect size, dissection of inguinal area, type of patch, time of operation, and frequency of swelling of perineum. Postoperative recovery was compared among the three groups at 24 hours and 1 month after surgery, including pain scores, foreign body sensation, local complications, urinary retention, swelling of the perineum, sex life and mobility. RESULTS: Seventy-eight patients were included in the final analysis. There were no differences among the three groups in patients' age, gender, type of hernia, hernia defect size, dissection of inguinal area and type of patch. However, the time of operation of intervention group increased (p=0.015) and incidence of swelling of perineum decreased than other two groups (p<0.05). After 24 hours, there were no significant differences in pain, foreign body sensation, local complications and urinary retention. Perineal swelling remission rate of intervention group was better than other two groups (p<0.05). After one month, three groups had no differences in the all terms of pain, foreign body sensation, sexual life and perineal swelling residual rate. CONCLUSION: Low pneumoperitoneum pressure can relieve swelling of perineum perioperatively and improve recovery of TAPP.

13.
Sci Rep ; 9(1): 17909, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784560

RESUMO

CSNK2B, which encodes the beta subunit of casein kinase II (CK2), plays an important role in neuron morphology and synaptic transmission. Variants in CSNK2B associated with epilepsy and/or intellectual disability (ID)/developmental delay (DD) have been reported in five cases only. Among the 816 probands suspected hereditary epilepsy whose initial report of trio-based whole exome sequencing (WES) were negative, 10 de novo pathogenic or likely pathogenic variants of CSNK2B in nine probands were identified after reanalysis of their raw Trio-WES data. Six of the nine epileptic patients had ID/DD. The age of seizure onset of these nine patients with CSNK2B variants ranged from 2-12 months. Eight patients had age of seizure onset of less than 6 months. The epilepsy of most probands (8/9) was generalized tonic-clonic seizure and clustered (6/9). Most patients had normal electroencephalogram (5/9) and brain magnetic resonance image (7/9) results. Most patients (7/9) had easy-to-control seizures. Levetiracetam was the most commonly used drug in seizure-free patients (5/7). The variants detected in five patients (5/9, 55.6%) were located in the zinc-binding domain. In summary, our research provided evidence that variants in CSNK2B are associated with epilepsy with or without ID/DD. CSNK2B-related epilepsy is relatively easy to be controlled. The zinc-binding domain appears to be the hotspot region for mutation.

14.
Am J Hum Genet ; 105(5): 996-1004, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31587869

RESUMO

Mechanically activated (MA) ion channels convert physical forces into electrical signals. Despite the importance of this function, the involvement of mechanosensitive ion channels in human disease is poorly understood. Here we report heterozygous missense mutations in the gene encoding the MA ion channel TMEM63A that result in an infantile disorder resembling a hypomyelinating leukodystrophy. Four unrelated individuals presented with congenital nystagmus, motor delay, and deficient myelination on serial scans in infancy, prompting the diagnosis of Pelizaeus-Merzbacher (like) disease. Genomic sequencing revealed that all four individuals carry heterozygous missense variants in the pore-forming domain of TMEM63A. These variants were confirmed to have arisen de novo in three of the four individuals. While the physiological role of TMEM63A is incompletely understood, it is highly expressed in oligodendrocytes and it has recently been shown to be a MA ion channel. Using patch clamp electrophysiology, we demonstrated that each of the modeled variants result in strongly attenuated stretch-activated currents when expressed in naive cells. Unexpectedly, the clinical evolution of all four individuals has been surprisingly favorable, with substantial improvements in neurological signs and developmental progression. In the three individuals with follow-up scans after 4 years of age, the myelin deficit had almost completely resolved. Our results suggest a previously unappreciated role for mechanosensitive ion channels in myelin development.


Assuntos
Canais Iônicos/genética , Proteínas de Membrana/genética , Bainha de Mielina/genética , Doença de Pelizaeus-Merzbacher/genética , Adolescente , Adulto , Pré-Escolar , Feminino , Heterozigoto , Humanos , Masculino , Mutação de Sentido Incorreto/genética , Oligodendroglia/metabolismo , Adulto Jovem
15.
Inorg Chem ; 58(19): 13394-13402, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31556604

RESUMO

Carbon dots (CDs), as an effective bioimaging agent, have aroused widespread interest. With the increasing number of CDs used in photodynamic therapy (PDT), developing efficient CDs with multiple functions such as imaging and phototherapy has become a new challenge. Herein, a new type of copper-doped CDs (Cu-CDs) with a high fluorescence quantum yield of 24.4% was synthesized from a copper complex of poly(acrylic acid) through coordination between the carboxyl group and copper ions. Owing to their good solubility, bright fluorescence, and low cytotoxicity, the Cu-CDs can be used for fluorescence imaging in both the HeLa (human cervical cancer) cell line and SH-SY5Y (human neuroblastoma cells) multicellular spheroids (3D MCs). More importantly, the Cu-CDs show a high quantum yield of singlet oxygen (1O2; 36%), good photoinduced cytotoxicity, and effective inhibition of 3D MC growth. Therefore, the Cu-CDs can be used as a promising imaging-guided PDT agent. This study provides a new carbon-based nanomaterial for multifunctional photodiagnostic and therapeutic agents for biological applications.


Assuntos
Carbono/farmacologia , Cobre/farmacologia , Corantes Fluorescentes/farmacologia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Carbono/química , Linhagem Celular Tumoral , Cobre/química , Corantes Fluorescentes/química , Células HeLa , Humanos , Nanopartículas/química , Imagem Óptica , Fotoquimioterapia
16.
World J Pediatr ; 15(5): 454-464, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31372844

RESUMO

BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare neurological degenerative disorder caused by the mutations of MLC1 or GLIALCAM with autosomal recessive or autosomal dominant inheritance and a different prognosis, characterized by macrocephaly, delayed motor and cognitive development, and bilateral abnormal signals in cerebral white matter (WM) with or without cysts on magnetic resonance imaging (MRI). This study aimed to reveal the clinical and genetic features of MLC patients with GLIALCAM mutations and to explore the brain pathological characteristics and prognosis of mouse models with different modes of inheritance. METHODS: Clinical information and peripheral venous blood were collected from six families. Genetic analysis was performed by Sanger sequencing of GLIALCAM. GlialcamArg92Trp/+ and GlialcamLys68Met/Thr132Asn mouse models were generated based on mutations from patients (c.274C>T(p.Arg92Trp) (c.203A>T(p.Lys68Met), and c.395C>A (p.Thr132Asn))). Brain pathologies of the mouse models at different time points were analyzed. RESULTS: Six patients were clinically diagnosed with MLC. Of the six patients, five (Pt1-Pt5) presented with a heterozygous mutation in GLIALCAM (c.274C>T(p.Arg92Trp) or c.275G>C(p.Arg92Pro)) and were diagnosed with MLC2B; the remaining patient (Pt6) with two compound heterozygous mutations in GLIALCAM (c.203A>T (p.Lys68Met) and c.395C>A (p.Thr132Asn)) was diagnosed with MLC2A. The mutation c.275C>G (p.Arg92Pro) has not been reported before. Clinical manifestations of the patient with MLC2A (Pt6) progressed with regression, whereas the course of the five MLC2B patients remained stable or improved. The GlialcamArg92Trp/+ and GlialcamLys68Met/ Thr132Asn mouse models showed vacuolization in the anterior commissural WM at 1 month of age and vacuolization in the cerebellar WM at 3 and 6 months, respectively. At 9 months, the vacuolization of the GlialcamLys68Met/ Thr132Asn mouse model was heavier than that of the GlialcamArg92Trp/+ mouse model. Decreased expression of Glialcam in GlialcamArg92Trp/+ and GlialcamLys68Met/ Thr132Asn mice may contribute to the vacuolization. CONCLUSIONS: Clinical and genetic characterization of patients with MLC and GLIALCAM mutations revealed a novel mutation, expanding the spectrum of GLIALCAM mutations. The first Glialcam mouse model with autosomal recessive inheritance and a new Glialcam mouse model with autosomal dominant inheritance were generated. The two mouse models with different modes of inheritance showed different degrees of brain pathological features, which were consistent with the patients' phenotype and further confirmed the pathogenicity of the corresponding mutations.


Assuntos
Proteínas de Ciclo Celular/genética , Cistos/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Animais , Grupo com Ancestrais do Continente Asiático , Moléculas de Adesão Celular Neurônio-Glia/genética , Modelos Animais de Doenças , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Camundongos , Mutação , Proteínas do Tecido Nervoso/genética , Prognóstico
17.
Environ Sci Pollut Res Int ; 26(28): 28884-28897, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385246

RESUMO

Industrialization and urbanization process has brought both economic development and a series of environmental problems. Hebei Province is a high haze area and one of the key areas of China's "Blue Sky Defense" policy. As carbon emission is one of the most important factors causing haze, it is necessary to screen the influencing factors effectively to make quantitative analysis and predict carbon emissions in different degrees of coordination. Faced with the new situation of Beijing-Tianjin-Hebei coordinated development and more environmental constraints, this paper designs a system for predicting carbon emissions in Hebei Province innovatively using the data during 1990-2016. In the first step, 7 influence factors are determined by "graded screening." Then, this paper improved the traditional support vector machine (SVM) by improved gray wolf optimizer (IGWO), and established IGWO-SVM model. Finally, the carbon emissions in Hebei Province from 2017 to 2025 are predicted under three stages of different cooperative development speed of 7 influence factors by the improved intelligent algorithm model. Based on the forecasting results, this paper put forward some pertinent opinions to provide theoretical basis for formulating relevant policies on carbon emissions in Hebei Province to effectively control carbon emissions from the source.


Assuntos
Carbono/análise , Urbanização , Pequim , Carbono/química , China , Desenvolvimento Econômico , Previsões
18.
Inflammation ; 42(5): 1857-1868, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31332661

RESUMO

Pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, has been reported to have anti-inflammatory properties, but the effects of PF11 on acute lung inflammation were unknown. The present study aimed to investigate the protective effects and potential mechanisms of PF11 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in male BALB/c mice. After being treated with PF11 (3, 10, and 30 mg/kg, intravenous) once a day for 3 consecutive days, the mice were challenged by intratracheal instillation of LPS, and then their lung tissues and bronchoalveolar lavage fluid (BALF) were collected for further analysis. The results showed that PF11 attenuated LPS-induced ALI, with alleviated histopathological damage, decreased lung wet/dry weight ratio, and reduced protein concentration and inflammatory cells number in BALF. Moreover, PF11 reversed the LPS-induced increases of mRNA expression and protein levels of interleukin-6, tumor necrosis factor-α, and interleukin-1ß. Meanwhile, PF11 decreased LPS-induced myeloperoxidase activity and neutrophil infiltration in lung tissue by reducing the expression of macrophage inflammatory protein-2 and intercellular adhesion molecule-1, as well as enhanced neutrophil clearance by accelerating neutrophils apoptosis and their phagocytosis by alveolar macrophages. In conclusion, these results indicated that PF11 significantly attenuated LPS-induced ALI through suppressing neutrophil infiltration and accelerating neutrophil clearance, suggesting its potential in the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Movimento Celular/efeitos dos fármacos , Ginsenosídeos/farmacologia , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/metabolismo , Ginsenosídeos/uso terapêutico , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
19.
Clin Genet ; 96(3): 207-215, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31066047

RESUMO

Congenital muscular dystrophies (CMDs) are clinically and genetically heterogeneous conditions. We launched a nationwide study to determine the frequency of CMD in the Chinese population and assess the status of diagnosis and disease management for CMD in China. Cases were chosen from databases in 34 tertiary academic hospitals from 29 first-level administrative divisions (provinces, municipalities, autonomous regions, and special administrative regions), and medical records were reviewed to confirm the diagnoses. The study included 409 patients, of those patients who consented to genetic testing (n = 340), mutations were identified in 286 of them. The most common forms identified were LAMA2-related CMD (36.4%), followed by COL6-related CMD (23.2%) and α-dystroglycanopathy (21.0%). The forms of CMD related to mutations in LMNA and SEPN1 were less frequent (12.5% and 2.4%, respectively). We also recorded a significant difference in the diagnostic capabilities and disease management of CMD, with this being relatively backward in research centers from less developed regions. We provide, for the first time, comprehensive epidemiologic information of CMD in a large cohort of Chinese people. To our knowledge, this is the largest sample size of its kind so far highlighting the prevalence of CMD in China.

20.
BMC Med Genet ; 20(1): 76, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064337

RESUMO

BACKGROUND: Brown-Vialetto-Van Laere Syndrome (BVVLS), a rare neurological disorder characterized by motor, sensory, and cranial neuronopathies, is mainly associated with defective riboflavin transporters encoded by SLC52A2 and SLC52A3 genes. Clinical outcomes have been shown to be improved significantly by high-dose riboflavin supplementation. The aim of this study was to identify genetic causes and further evaluate the clinical course and response to riboflavin in a Chinese pedigree with BVVLS. CASE PRESENTATION: We report the novel compound heterozygous variants c.1328G>A p.(Cys443Tyr) and c.1022_1023insC p. (Leu341Profs*103) of SLC52A2 gene in a female proband who presented in our out-patient clinic at the age of one-year-old with progressive mental and motor regression, breath holding, and brain stem dysfunction including facial weakness, hearing loss, dysphagia. Following high-dose riboflavin supplementation, the respiratory insufficiency and mental, motor, and bulbar function improved. However, sensorineural hearing loss was not improved. The missense variant site was highly conserved. Both variants were not found in the population database gnomAD. The two variants were inherited from her mother and father, respectively. Both variants were predicted to be deleterious by Polyphen2, Mutation taster, and SIFT and were classified as likely pathogenic according to the ACMG guideline. CONCLUSIONS: Two novel pathogenic variations of SLC52A2 gene were firstly found from a Chinese pedigree with BVVLS. Clinical outcomes could be improved by early diagnosis and riboflavin supplementation.


Assuntos
Paralisia Bulbar Progressiva/genética , Perda Auditiva Neurossensorial/genética , Mutação , Receptores Acoplados a Proteínas-G/genética , Sequência de Aminoácidos , China , Feminino , Humanos , Lactente , Masculino , Linhagem , Receptores Acoplados a Proteínas-G/química , Homologia de Sequência de Aminoácidos
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