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1.
BMC Bioinformatics ; 22(1): 12, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407074

RESUMO

BACKGROUND: Multi-locus genotype data are widely used in population genetics and disease studies. In evaluating the utility of multi-locus data, the independence of markers is commonly considered in many genomic assessments. Generally, pairwise non-random associations are tested by linkage disequilibrium; however, the dependence of one panel might be triplet, quartet, or other. Therefore, a compatible and user-friendly software is necessary for testing and assessing the global linkage disequilibrium among mixed genetic data. RESULTS: This study describes a software package for testing the mutual independence of mixed genetic datasets. Mutual independence is defined as no non-random associations among all subsets of the tested panel. The new R package "mixIndependR" calculates basic genetic parameters like allele frequency, genotype frequency, heterozygosity, Hardy-Weinberg equilibrium, and linkage disequilibrium (LD) by mutual independence from population data, regardless of the type of markers, such as simple nucleotide polymorphisms, short tandem repeats, insertions and deletions, and any other genetic markers. A novel method of assessing the dependence of mixed genetic panels is developed in this study and functionally analyzed in the software package. By comparing the observed distribution of two common summary statistics (the number of heterozygous loci [K] and the number of share alleles [X]) with their expected distributions under the assumption of mutual independence, the overall independence is tested. CONCLUSION: The package "mixIndependR" is compatible to all categories of genetic markers and detects the overall non-random associations. Compared to pairwise disequilibrium, the approach described herein tends to have higher power, especially when number of markers is large. With this package, more multi-functional or stronger genetic panels can be developed, like mixed panels with different kinds of markers. In population genetics, the package "mixIndependR" makes it possible to discover more about admixture of populations, natural selection, genetic drift, and population demographics, as a more powerful method of detecting LD. Moreover, this new approach can optimize variants selection in disease studies and contribute to panel combination for treatments in multimorbidity. Application of this approach in real data is expected in the future, and this might bring a leap in the field of genetic technology. AVAILABILITY: The R package mixIndependR, is available on the Comprehensive R Archive Network (CRAN) at: https://cran.r-project.org/web/packages/mixIndependR/index.html .


Assuntos
Loci Gênicos/genética , Genômica/métodos , Software , Bases de Dados Genéticas , Genótipo , Desequilíbrio de Ligação/genética
2.
Food Sci Nutr ; 8(11): 6037-6046, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33282256

RESUMO

In this study, the color of the dry fruiting bodies, fresh weight (FW): dry weight (DW) ratio, amino acids, and total phenolics, which are of nutritional or commercial interest, were compared among different drying temperature treatments. The effect of rehydration methods and color protection reagents on the fruiting body color, polyphenol oxidase (PPO) activity, and browning inhibition rate were evaluated. The results showed that drying with hot air at 65℃ was quickest and resulted in a better color without compromising the FW:DW ratio and rehydration ratio of the fruiting bodies. Furthermore, some reactions that occurred under high temperatures increased the content of protein, amino acids, and total phenolics. Soaking after boiling was the most suitable rehydration method, leading to the lowest PPO activity (39.87 ± 1.35 U/g). All of the four analyzed color protection reagents could significantly inhibit the browning of Yu Muer fruiting bodies under room temperature water rehydration conditions, with a citric acid content of 6 g/L showing the best performance. These results provide technical support for the development of the Yu Muer industry and for promoting the commercial processing of Yu Muer fruiting bodies slices.

3.
Chemosphere ; : 128992, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33303228

RESUMO

FeAl-layered double hydroxide (FeAl-LDH) supported by char was synthesized using the hydrothermal method in order to activate hydrogen peroxide (H2O2) to degrade phenol. The effects of char type, char synthesis amount, and several important parameters on the degradation were investigated. In addition, the physicochemical properties of FeAl-LDH@BC were revealed by instruments including the transmission electron microscope (TEM), X-ray diffraction (XRD), and Fourier-transform infrared (FT-IR). The results showed that the degradation efficiency of phenol (80 mg/L) by FeAl-LDH@BC0.25 was 85.28% at a pH of 3 and H2O2 concentration of 400 mg/L, and exhibited good reusability with a small amount of iron leaching. Electron paramagnetic resonance (EPR) and radical quenching results indicated that ·OH radicals were the main participant during the degradation process, and XRD and FTIR spectra showed that FeAl-LDH was dissolved and rebuilt during the degradation process, and a small amount of iron was leached out resulting in the homogeneous catalysis. Hence, both homogeneous and heterogeneous processes occurred in the phenol oxidation process. Further soil remediation experiments showed that FeAl-LDH@BC0.25 could also effectively degrade phenol in soil, although the efficiency was lower than that in solution.

4.
Aging (Albany NY) ; 122020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33298623

RESUMO

Background and aims Advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE), are associated with cognition decline. We aim to investigate the effect of liraglutide on cognitive function in diabetic mice. Results Diabetic mice showed decreased cognitive function. Moreover, lower glucagon like peptide-1 (GLP-1) levels in plasma were detected in db/db mice. Additionally, up-regulated RAGE and down-regulated glucagon like peptide-1 (GLP-1R) levels were observed in db/db mice. However, decreased GLP-1R and increased RAGE were reversed by liraglutide. We also found decreased cellular activity in cells with AGEs. Moreover, AGEs up-regulated RAGE in PC12 and HT22 cells. However, liraglutide improved the cell activity damaged by AGEs. Although we did not discover the direct-interaction between RAGE and GLP-1R, elevated RAGE levels induced by AGEs were restored by liraglutide. Conclusion We demonstrated that the cognitive function of diabetic mice was improved by liraglutide via the down-regulation of RAGE. Methods db/db mice and db/m mice were used in this study. Liraglutide was used to remedy diabetic mice. Neurons and RAGE in hippocampus were shown by immunofluorescence. And then, PC12 cells or HT22 cells with AGEs were treated with liraglutide. GLP-1R and RAGE were measured by western blotting.

5.
Stem Cell Res ; 49: 102053, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33212352

RESUMO

Hemophilia A (HA), is a X-linked recessive congenital bleeding disorder, caused by deficiency of the coagulation factorVIII (FVIII) which is encoded by coagulation factor 8 (F8). HA affects 1 of every 5,000 males worldwide. The intron 22 inversion (Inv22) mutation of F8 causes about 45% of severeHA cases.Here, we generated induced pluripotent stem cells (iPSCs) from a HA patient with Inv22 mutation by electroporation of urine-derived cells (UCs) with episomal plasmids under feeder-free, virus-free, serum-free condition and without oncogene c-MYC. This iPSCs line could facilitate future applications of human iPSCs by provide a valuable cell model.

6.
Front Cell Infect Microbiol ; 10: 553648, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194796

RESUMO

Background: Invasive fungal infection (IFI) is one of the most common nosocomial infections. However, data on the epidemiology of IFI and susceptibility to antifungal agents in China are quite limited, and in particular, no current data exist on the microbiological, and clinical characteristics of IFI patients in Northeast China. Objectives: The purpose of this study was to provide a retrospective review of the clinical characteristics, laboratory test results, and risk factor predictions of inpatients diagnosed with IFI. Multivariate regression analysis was used to assess prognostic factors associated with the mortality of these patients. Methods: We retrospectively analyzed the results from 509 patients with IFI extracted from the First Hospital of China Medical University from January 2013 to January 2018. Results: Neutrophil numbers, total bilirubin, length of stay in the ICU, renal failure, use of immunosuppressants within the past 30 days, stomach tube placement and septic shock were risk factors for death from IFI. Recent surgery (within 2 weeks) and drainage tube placement did not increase mortality in these IFI patients. Increased serum levels of PCT (AUC 0.601, 95% CI 0.536-0.665, P = 0.003) and CRP (AUC 0.578, 95% CI 0.512-0.644, P = 0.020) provided effective predictors of 30-day mortality rates. Conclusions: We report for the first time epidemiological data on invasive fungal infections in Northeast China over the past 5 years. Despite the limited available clinical data, these findings will greatly aid clinical health care workers with regard to the identification, prevention, and treatment of IFI in hospitalized patients.

7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(10): 877-883, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33148381

RESUMO

Objective To investigate the expression levels of microRNA-186-5p (miR-186-5p) and Toll-like receptor 3 (TLR3) and their relationships with the apoptosis in high-glucose (HG)-treated AC16 cardiomyocytes. Methods Target Scan7.1 database predicted that miR-186-5p could act directly on TLR3. Diabetic cardiomyopathy model was established in cardiomyocytes stimulated by HG. The expression of miR-186-5p was detected by real-time quantitative PCR and the expression of TLR3 was detected by Western blot analysis. The expression of miR-186-5p or TLR3 was enhanced or reduced by cell transfection. The apoptosis of cardiomyocytes was detected by flow cytometry. The expression of cleaved caspase-3(c-caspase-3) was detected by Western blot analysis, and the interaction between miR-186-5p and TLR3 was analyzed by luciferase activity assay. Results The bioinformatics analysis and luciferase activity assay showed that TLR3 was a direct target gene of miR-186-5p. The expression of miR-186-5p was down-regulated in HG-treated cardiomyocytes, and the over-expression of miR-186-5p reversed HG-induced cardiomyocyte apoptosis and reduced the protein level of c-caspase-3. Down-regulation of TLR3 inhibited HG-induced apoptosis and reduced protein level of c-caspase-3 in cardiomyocytes. Over-expression of TLR3 increased HG-induced cardiomyocyte apoptosis and reversed the effect of miR-186-5p. Conclusion The miR-186-5p can inhibit the apoptosis of cardiomyocytes induced by HG via down-regulating TLR3 expression.


Assuntos
Apoptose , MicroRNAs/genética , Miócitos Cardíacos/citologia , Receptor 3 Toll-Like/genética , Caspase 3/metabolismo , Linhagem Celular , Glucose/efeitos adversos , Humanos , Miócitos Cardíacos/efeitos dos fármacos
9.
Front Oncol ; 10: 544956, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123466

RESUMO

Background: Sarcomas are heterogeneous rare malignancies constituting approximately 1% of all solid cancers in adults and including more than 70 histological and molecular subtypes with different pathological and clinical development characteristics. Method: We identified prognostic biomarkers of sarcomas by integrating clinical information and RNA-seq data from TCGA and GEO databases. In addition, results obtained from cell cycle, cell migration, and invasion assays were used to assess the capacity for Tanespimycin to inhibit the proliferation and metastasis of sarcoma. Results: Sarcoma samples (N = 536) were divided into four pathological subtypes including DL (dedifferentiated liposarcoma), LMS (leiomyosarcoma), UPS (undifferentiated pleomorphic sarcomas), and MFS (myxofibrosarcoma). RNA-seq expression profile data from the TCGA dataset were used to analyze differentially expressed genes (DEGs) within metastatic and non-metastatic samples of these four sarcoma pathological subtypes with DEGs defined as metastatic-related signatures (MRS). Prognostic analysis of MRS identified a group of genes significantly associated with prognosis in three pathological subtypes: DL, LMS, and UPS. ISG15, NUP50, PTTG1, SERPINE1, and TSR1 were found to be more likely associated with adverse prognosis. We also identified Tanespimycin as a drug exerting inhibitory effects on metastatic LMS subtype and therefore can serve a potential treatment for this type of sarcoma. Conclusions: These results provide new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provide new directions for further study of sarcoma.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33113060

RESUMO

Biomass-derived carbon-attapulgite adsorbent was developed for organic pollutants removal. All the batch assays were performed to evaluate the effects of organic components, contact time, and initial concentration of organic pollutants on the adsorption performance of the as-prepared adsorbent. The samples were characterized via Brunauer-Emmett-Teller (BET), Fourier transform infrared (FTIR), X-ray diffractometer (XRD), and scanning electron microscopy (SEM). The results demonstrated that the acid-treated carbon-attapulgite adsorbent (H-ATP/BC) showed a large specific surface area (237 m2 g-1) and possessed abundant oxygen-containing functional groups and silicon-oxygen bonds (i.e., O-Si-O and O-Si), which provided more active sites and conduced to the adhesive of organic pollutants. Both physical adsorption and chemical adsorption were involved in the adsorption process, and competitive adsorption occurred when two or more target pollutants coexist. Especially, phenol and/or aniline with an aromatic ring were much more likely to adhere to the H-ATP/BC surface than pyridine, and the selectivity order of H-ATP/BC for these pollutants was phenol > aniline > pyridine. From the model fitting, it was observed that the adsorption data could be described well by a pseudo-second-order model and Freundlich isotherms. The theoretical maximum phenol, aniline, and pyridine adsorption capacities of the H-ATP/BC were 14.31 mg g-1, 15.21 mg g-1, and 20.74 mg g-1, respectively. Comparison among the commercial adsorbents price also illustrated that H-ATP/BC could be a promising material for efficient treatment of organic pollutants.Graphical abstract.

11.
J Dent ; 103: 103501, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33068710

RESUMO

OBJECTIVES: This study investigated whether novel liposome formulations loaded with transforming growth factor ß1 (TGF-ß1) could promote the odontogenic differentiation of human dental pulp stem cells (hDPSCs) for dentine-pulp regeneration. METHODS: 0-100 ng/mL of liposomal TGF-ß1 was prepared using the thin-film hydration method. Release of TGF-ß1 from the liposomes was quantified by an enzyme-linked immunosorbent assay (ELISA). The hDPSCs were treated with different concentrations of liposomal TGF-ß1 and cell viability was tested using an MTT assay. "Osteodentine" differentiation capacity was assessed by RT-qPCR, ELISA and Alizarin red S staining. RESULTS: The ELISA results showed that liposomal TGF-ß1 achieved a controlled and prolonged release over time. The MTT results demonstrated that the liposomes (100 µg/mL) were not cytotoxic to the cells. Liposomal TGF-ß1 up-regulated the expression of "osteodentine" markers, RUNX-2, DMP-1 and DSPP, in hDPSCs after 7 days of treatment and resulted in the accumulation of mineralised nodules. CONCLUSION: This study indicated that liposomes are an effective carrier for delivering TGF-ß1 over time. Liposomal TGF-ß1 promoted dentinogenesis and increased mineralisation in hDPSCs. This highlights the potential of liposomal TGF-ß1 for future use in dentine-pulp regeneration. CLINICAL SIGNIFICANCE: Liposomal TGF-ß1 may be used as a synergist for promoting dentine-pulp regeneration of immature permanent teeth or as a pulp capping agent for inducing reparative dentine formation.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32875595

RESUMO

BACKGROUND AND AIM: This study aimed to clarify health-related quality of life (HRQoL) of patients with colorectal precancer and colorectal cancer (CRC) in China and to better understand related utility scores. METHODS: A hospital-based cross-sectional survey was conducted in precancer and CRC patients from 2012 to 2014, covering 12 provinces in China. HRQoL was assessed with EuroQol 5-Dimensions 3-Levels. Utility scores were derived using Chinese value set. A multivariate regression model was established to explore potential predictors of utility scores. RESULTS: A total of 376 precancer (mean age 58.7 years, 61.2% men) and 2470 CRC patients (mean age 58.6 years, 57.6% men) were included. In five dimensions, there was a certain percentage of problem reported among precancer (range: 12.0% to 36.7%) and CRC (range: 32.4% to 50.3%) patients, with pain/discomfort being the most serious dimension. Utility scores of precancer and CRC patients were 0.870 (95% confidence interval [CI], 0.855-0.886) and 0.751 (95% CI, 0.742-0.759), both of which were lower than those of general Chinese population (0.960 [95% CI, 0.960-0.960]). Utilities for patients at stage I to stage IV were 0.742 (95% CI, 0.715-0.769), 0.722 (95% CI, 0.705-0.740), 0.756 (95% CI, 0.741-0.772), and 0.745 (95% CI, 0.742-0.767), respectively. Multivariate analysis showed that therapeutic regimen, time point of the interview, education, occupation, annual household income, and geographic region were associated with utilities of CRC patients. CONCLUSION: Health-related quality of life of both precancer and CRC patients in China declined considerably. Utility scores differed by sociodemographic and clinical characteristics, and findings of these utilities may facilitate implementation of further cost-utility evaluations.

13.
Thorac Cardiovasc Surg Rep ; 9(1): e40-e43, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32963931

RESUMO

Background Intravenous leiomyomatosis is a rare disease. Histologically, intravenous leiomyomatosis is a benign tumor, but its biological behavior can be malignant. The development of intracardiac extensions leads to congestive heart failure and occasionally sudden fatalities. Case Description The cases of three patients treated at our university between 2017 and 2018 were studied retrospectively. Intravenous tumors extending into the right heart system were fully removed without perioperative complications or death. Only one tumor recurrence was observed during the followed-up period. Conclusion The gold standard for the treatment of intravenous leiomyomatosis with intracardiac extension is complete and successful surgical resection.

14.
Ann Transl Med ; 8(14): 860, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32793704

RESUMO

Background: Tumor mutation burden (TMB) has an important association with immunotherapy responses. TMB in the Chinese population has not been well established. Finding differences between the Chinese and Caucasian populations and elucidating the underlying biological mechanisms of high TMB might help develop more precise and effective means for TMB and immunotherapy response prediction. Methods: Chinese cancer patients fresh tissue (n=2,177), formalin-fixed, paraffin-embed (FFPE) specimens (n=3,294), and pleural fluid (n=189) were profiled using a 295- or 520-gene next-generation sequencing (NGS) panel. The association of the TMB status with a series of molecular features and biological pathways was determined using bootstrapping. Results: TMB, measured by 295- or 520-cancer-related gene panels, was correlated with whole-exome sequencing (WES) TMB based on the in silico simulation in The Cancer Genome Atlas cohort. The median TMB of our data was slightly higher than that from the Foundation Medicine Inc. (FMI) dataset. TMB was also slightly different within the same cancer type between the Chinese and Caucasian population. We discovered that the underlying pathways of TMB status varied greatly and sometimes had an opposite association with TMB across different cancer types. Moreover, we developed a 23-gene and a 16-gene signature to predict TMB prediction for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively, indicating a histology-specific mechanism for driving high-TMB in lung cancer. Conclusions: TMB varies among different ethnic populations. Our findings extend the knowledge of the underlying biological mechanisms for high TMB and might be helpful for developing more precise and accessible TMB assessment panels and algorithms in more cancer types.

15.
Bioresour Technol ; 317: 124016, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32822892

RESUMO

In this study, batch experiments were conducted to compare the effect of temperature and substrate source on microbial communities in the anaerobic digestion of kitchen waste. The results showed that the microbial communities of anaerobic digestion were not sensitive to varied sources of waste, but shifted with the change in operating temperatures. In the reactors operated at mesophilic conditions, Levilinea, Syntrophomonas, Methanothrix, and Methanosphaerula, etc. were the dominant microbes during the process. While in thermophilic reactors, Levilinea, Ornatilinea, Methanosphaerula and Methanomassiliicoccus, etc. prevailed. Meanwhile, an enrichment in Coprothermobacter, Defluviitoga, Defluviitalea, Tepidimicrobium, Lutispora and Fonticella were observed as the temperature changed from mesophilic to thermophilic, suggesting these genera could be selectively enriched at thermophilic conditions. The results provided fundamental understanding of the microbiology that could support the scale up of food waste anaerobic digestion.


Assuntos
Microbiota , Eliminação de Resíduos , Anaerobiose , Reatores Biológicos , Alimentos , Metano , Esgotos , Temperatura
16.
Arch Virol ; 165(11): 2689-2693, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32812093

RESUMO

Here, we describe a novel mycovirus, Auricularia heimuer fusarivirus 1 (AhFV1), isolated from the edible fungus Auricularia heimuer strain CCMJ1296. The virus has a single-stranded positive-sense [+ssRNA] genome of 7,127 nucleotides containing two overlapping open reading frames (ORFs) and a poly(A) tail. The large ORF1 encodes a polyprotein of 1,637 amino acids (aa) with conserved RNA-dependent RNA polymerase (RdRp) and DEAD-like helicase superfamily (DEXDc) domains. ORF2 encodes a putative 633-aa protein with unknown function. A BLAST search showed that the nucleotide sequence of the AhFV1 genome is 41.28% identical to that of Sclerotium rolfsii fusarivirus 2 and 40.49% identical to that of Sclerotium rolfsii fusarivirus 1. Phylogenetic analysis based on RdRp and helicase (Hel) sequences indicated that AhFV1 is related to unclassified mycoviruses and other fusariviruses. Our data suggest that AhFV1 should be classified as a member of the newly proposed family "Fusariviridae". This is the second virus and the first full genome sequence of a fusarivirus from A. heimuer.


Assuntos
Basidiomycota/virologia , Micovírus/classificação , Filogenia , Vírus de RNA/classificação , Sequência de Aminoácidos , China , Micovírus/isolamento & purificação , Genoma Viral , Fases de Leitura Aberta , RNA Helicases/genética , RNA Replicase/genética , Vírus de RNA/isolamento & purificação , RNA Viral , Proteínas Virais/genética
17.
Heart Lung Circ ; 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32830033

RESUMO

Intravenous-cardiac leiomyomatosis (IVCL) is a rare, histologically benign but biologically aggressive tumour. Accurate diagnosis and appropriate treatment choices are important for prognosis. The best surgical approach remains unclear owing to limited evidence. This study aimed to assess surgical strategies for treating IVCL and to propose individualised surgical strategies. We searched PubMed, Web of Science, and the Cochrane Library to identify case reports and case series published in English over the last 10 years. Two (2) reviewers independently screened the literature according to the inclusion and exclusion criteria, and subsequently extracted data. One hundred and ten (110) cases were included. According to our analysis, IV cardiac leiomyomatosis is most common in the fifth decade, and the mean age at detection is 45.71±7.67 years. Most patients had undergone previous hysterectomy/myomectomy, or had a co-existing uterine leiomyoma when admitted. The most common clinical presentations were dyspnoea, palpitation, pelvic mass, and leg oedema. More patients benefited more from one-stage surgery. Seventy-eight per cent (78%) of cases experienced a surgical approach of thoracic and abdominal incisions. Extractions of IVCL were varied. Eighty-seven (87) patients experienced cardiopulmonary bypass and deep hypothermic circulatory arrest was performed on 64.4% of them. Total hysterectomy and bilateral oophorectomy, together with pelvic leiomyoma excision, were done in 76.0% of patients. Overall, surgical strategies for IVCL are varied; the optimal strategy required consideration of multiple factors. Complete resection is recommended for both single- and two-stage operations. Once complete resection is achieved, recurrence is rare.

18.
Am J Hum Genet ; 107(3): 514-526, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32791035

RESUMO

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenoteratozoospermia. Although recent studies have revealed several MMAF-associated genes and demonstrated MMAF to be a genetically heterogeneous disease, at least one-third of the cases are still not well understood for their etiology. Here, we identified bi-allelic loss-of-function variants in CFAP58 by using whole-exome sequencing in five (5.6%) unrelated individuals from a cohort of 90 MMAF-affected Chinese men. Each of the men harboring bi-allelic CFAP58 variants presented typical MMAF phenotypes. Transmission electron microscopy demonstrated striking flagellar defects with axonemal and mitochondrial sheath malformations. CFAP58 is predominantly expressed in the testis and encodes a cilia- and flagella-associated protein. Immunofluorescence assays showed that CFAP58 localized at the entire flagella of control sperm and predominantly concentrated in the mid-piece. Immunoblotting and immunofluorescence assays showed that the abundances of axoneme ultrastructure markers SPAG6 and SPEF2 and a mitochondrial sheath protein, HSP60, were significantly reduced in the spermatozoa from men harboring bi-allelic CFAP58 variants. We generated Cfap58-knockout mice via CRISPR/Cas9 technology. The male mice were infertile and presented with severe flagellar defects, consistent with the sperm phenotypes in MMAF-affected men. Overall, our findings in humans and mice strongly suggest that CFAP58 plays a vital role in sperm flagellogenesis and demonstrate that bi-allelic loss-of-function variants in CFAP58 can cause axoneme and peri-axoneme malformations leading to male infertility. This study provides crucial insights for understanding and counseling of MMAF-associated asthenoteratozoospermia.


Assuntos
Anormalidades Múltiplas/genética , Astenozoospermia/genética , Axonema/genética , Infertilidade Masculina/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Anormalidades Múltiplas/patologia , Alelos , Animais , Astenozoospermia/fisiopatologia , Axonema/patologia , Sistemas CRISPR-Cas/genética , Proteínas de Ciclo Celular/genética , Homozigoto , Humanos , Infertilidade Masculina/patologia , Mutação com Perda de Função/genética , Perda de Heterozigosidade/genética , Masculino , Camundongos , Camundongos Knockout , Proteínas dos Microtúbulos/genética , Mitocôndrias/genética , Cauda do Espermatozoide/metabolismo , Cauda do Espermatozoide/patologia , Testículo/metabolismo , Testículo/patologia , Sequenciamento Completo do Exoma
19.
Biomed Res Int ; 2020: 2315230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733933

RESUMO

Objective: High-fat-diet- (HFD-) induced hepatic cell apoptosis is common in mice with nonalcoholic fatty liver disease (NAFLD). We aim to investigate the effect of Ginsenoside Rb1 (GRb1) on hepatocyte apoptosis. Methods: C57BL/6J mice with HFD were used to induce a liver-injured model with cell apoptosis. In addition, GRb1 was used to treat HFD-induced apoptosis in a liver with or without inhibitor of peroxisome proliferator-activated receptor γ (PPAR-γ). Results: Compared with C57BL/6J mice with common chow, there are downregulated PPAR-γ but upregulated cell apoptosis in the liver of mice with HFD. Furthermore, GRb1 elevated the hepatic PPAR-γ level and suppressed hepatocytic apoptosis. However, GW9662 abolished the effects of GRb1 on apoptosis in the liver. Conclusions: GRb1 alleviated HFD-induced apoptosis of hepatocytes of mice via PPAR-γ.

20.
Jpn J Infect Dis ; 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32741931

RESUMO

To analyze clinical characteristics and potential predictors of disease severity in patients with COVID-19.Clinical data from 64 patients with COVID-19 were retrospectively analyzed. Of the 64 patients, 37 were male and 27 were female. Their mean age was 47.8 years, 43 (67.2%) cases were non-severe, 21 (32.8%) were severe, and 2 patients (3.1%) died. Age and serum ferritin were significantly associated with COVID-19 severity. Repeated monitoring of ferritin, interleukin-6, C-reactive protein, lactic acid dehydrogenase, and erythrocyte sedimentation rate during COVID-19 treatment may assist the prediction of disease severity and evaluation of treatment effects. There were no significant differences in the duration of severe illness or the number of days on high-level respiratory support between a low-dose methylprednisolone group and a high-dose methylprednisolone group. The mean number of days in hospital in the high dose group was higher than that in the low-dose group. Repeated monitoring of ferritin, interleukin-6, C-reactive protein, lactic acid dehydrogenase, and erythrocyte sedimentation rate during COVID-19 treatment may assist the prediction of disease severity and evaluation of treatment effects.

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