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1.
Microbiol Spectr ; : e0125121, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851139

RESUMO

The type III secretion (T3S) injectisome is a syringe-like protein-delivery nanomachine widely utilized by Gram-negative bacteria. It can deliver effector proteins directly from bacteria into eukaryotic host cells, which is crucial for the bacterial-host interaction. Intracellular pathogen Salmonella enterica serovar Typhimurium encodes two sets of T3S injectisomes from Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2), which are critical for its host invasion and intracellular survival, respectively. The inner membrane export gate protein, SctV (InvA in SPI-1 and SsaV in SPI-2), is the largest component of the injectisome and is essential for assembly and function of T3SS. Here, we report the 2.11 Å cryo-EM structure of the SsaV cytoplasmic domain (SsaVC) in the context of a full-length SctV chimera consisting of the transmembrane region of InvA, the linker of SsaV (SsaVL) and SsaVC. The structural analysis shows that SsaVC exists in a semi-open state and SsaVL exhibits two major orientations, implying a highly dynamic process of SsaV for the substrate selection and secretion in a full-length context. A biochemical assay indicates that SsaVL plays an essential role in maintaining the nonameric state of SsaV. This study offers near atomic-level insights into how SsaVC and SsaVL facilitate the assembly and function of SsaV and may lead to the development of potential anti-virulence therapeutics against T3SS-mediated bacterial infection. IMPORTANCE Type III secretion system (T3SS) is a multicomponent nanomachine and a critical virulence factor for a wide range of Gram-negative bacterial pathogens. It can deliver numbers of effectors into the host cell to facilitate the bacterial host infection. Export gate protein SctV, as one of the engines of T3SS, is at the center of T3SS assembly and function. In this study, we show the high-resolution atomic structure of the cytosolic domain of SctV in the nonameric state with variable linker conformations. Our first observation of conformational changes of the linker region of SctV and the semi-open state of the cytosolic domain of SctV in the full-length context further support that the substrate selection and secretion process of SctV is highly dynamic. These findings have important implications for the development of therapeutic strategies targeting SctV to combat T3SS-mediated bacterial infection.

2.
J Agric Food Chem ; 69(45): 13416-13424, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34738463

RESUMO

Mandipropamid (MDP) is a widely used chiral fungicide to control oomycete pathogens with two enantiomers. In this study, the enantioselective bioactivity, toxicity, and degradation of MDP were investigated for the first time. The bioactivity of S-MDP was 118-592 times higher than that of R-MDP and 1.14-1.67 times higher than that of Rac-MDP against six phytopathogens. Molecular docking found that S-MDP formed a strong halogen bond with HIS 693 of cellulose synthase and possessed a lower binding energy, which validated the results of the bioactivity assay. S-MDP showed lower toxicity toward Spirodela polyrhiza, while it exhibited higher toxicity in Danio rerio embryo and larva. S-MDP preferentially degraded in cowpea and pepper, while R-MDP preferentially degraded in soil. There is no significant difference between the two enantiomers in the toxicity of adult D. rerio and in cucumber degradation. Therefore, the development of the S-enantiomer was considered as a better option to exhibit high efficiency, which could reduce the residual risk of the pesticide and ensure environmental safety.


Assuntos
Fungicidas Industriais , Poluentes do Solo , Amidas , Ácidos Carboxílicos , Fungicidas Industriais/análise , Fungicidas Industriais/toxicidade , Simulação de Acoplamento Molecular , Solo , Poluentes do Solo/análise , Estereoisomerismo , Verduras
3.
New Phytol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34761409

RESUMO

MicroRNAs (miRNAs) are a class of 21-24 nucleotides (nt) noncoding small RNAs ubiquitously distributed across the plant kingdom. miR482/2118, one of the conserved miRNA superfamilies originating from gymnosperms, has divergent main functions in core-angiosperms. It mainly regulates NUCLEOTIDE BINDING SITE-LEUCINE-RICH REPEAT (NBS-LRR) genes in eudicots, functioning as an essential component in plant disease resistance; in contrast, it predominantly targets numerous long noncoding RNAs (lncRNAs) in monocot grasses, which are vital for plant reproduction. Usually, miR482/2118 is 22-nt in length, which can trigger the production of phased small interfering RNAs (phasiRNAs) after directed cleavage. PhasiRNAs instigated from target genes of miR482/2118 enhance their roles in corresponding biological processes by cis-regulation on cognate genes and expands their function to other pathways via trans activity on different genes. This review summarizes the origin, biogenesis, conservation, and evolutionary characteristics of the miR482/2118 superfamily and delineates its diverse functions in disease resistance, plant development, stress responses, etc.

4.
Methods ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34748953

RESUMO

Accumulated studies have discovered that circular RNAs (CircRNAs) are closely related to many complex human diseases. Due to this close relationship, CircRNAs can be used as good biomarkers for disease diagnosis and therapeutic targets for treatments. However, the number of experimentally verified circRNA-disease associations are still fewer and also conducting wet-lab experiments are constrained by the small scale and cost of time and labour. Therefore, effective computational methods are required to predict associations between circRNAs and diseases which will be promising candidates for small scale biological and clinical experiments. In this paper, we propose novel computational models based on Graph Convolution Networks (GCN) for the potential circRNA-disease association prediction. Currently most of the existing prediction methods use shallow learning algorithms. Instead, the proposed models combine the strengths of deep learning and graphs for the computation. First, they integrate multi-source similarity information into the association network. Next, models predict potential associations using graph convolution which explore this important relational knowledge of that network structure. Two circRNA-disease association prediction models, GCN based Node Classification (GCN-NC) and GCN based Link Prediction (GCN-LP) are introduced in this work and they demonstrate promising results in various experiments and outperforms other existing methods. Further, a case study proves that some of the predicted results of the novel computational models were confirmed by published literature and all top results could be verified using gene-gene interaction networks.

5.
Biomark Med ; 15(16): 1541-1551, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34651511

RESUMO

Aim: Increased serum ferritin (SF) indicates an adverse prognosis in patients with hematologic malignancies. However, its prognostic significance in multiple myeloma (MM) remains unknown. Patients & methods: The impact of SF levels on outcomes in patients with MM was retrospectively analyzed and dynamically assessed. Results: At initial diagnosis, 188 out of 295 patients (63.7%) had high SF that correlated with poor prognosis factors including adverse overall survival and progression-free survival. SF expression was dynamically observed at different time points and SF levels significantly decreased after treatment induction. In addition, SF expression significantly increased at disease progression or relapse. Conclusion: SF can be used as a prognostic factor at initial diagnosis and relapse in patients with MM.

6.
Genomics ; 113(6): 3895-3906, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34555497

RESUMO

Persistent infections of high-risk human papillomaviruses (HPVs) are the leading cause of cervical cancers. We collected cervical exfoliated cell samples from females in Changsha city, Hunan Province and obtained 338 viral genomes of four major HPV types, including HPV 16 (n = 82), 18 (n = 35), 52 (n = 121) and 58 (n = 100). The lineage/sublineage distribution of the four HPVs confirmed previous epidemiological reports, with the predominant prevailing sublineage as A4 (50%), A1 (37%) and A3 (13%) for HPV16, A1 (83%) for HPV18, B2 (86%) for HPV52 and A1 (65%), A3 (19%) and A2 (12%) for HPV58. We also identified two potentially novel HPV18 sublineages, i.e. A6 and A7. Virus mutation analysis further revealed the presence of HPV16 and HPV58 sublineages associated with potentially high oncogenicity. These findings expanded our knowledge of the HPV genetic diversity in China, providing valuable evidence to facilitate HPV DNA screening, vaccine effectiveness evaluation and control strategy development.

7.
J Agric Food Chem ; 69(34): 9735-9742, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427095

RESUMO

Cyproconazole (CPZ), a representative chiral triazole fungicide, is widely used to control Fusarium head blight (FHB). In this study, the stereoselective efficiency of CPZ was investigated in vitro and in planta. Consistent results were observed between the in vitro bioassay and the in planta visual disease rating, with the control efficacy ordered RS-CPZ > RR-CPZ > SR-CPZ > SS-CPZ. Unexpectedly, the in planta deoxynivalenol level was in the order RR-CPZ > RS-CPZ > SS-CPZ > SR-CPZ, while RS-CPZ inhibited the deoxynivalenol production and ergosterol biosynthesis in Fusarium graminearum. We further investigated that the Tri genes were upregulated in Fusarium graminearum of the RS-CPZ group, and SR-CPZ preferentially degraded in wheat. An extra action mode of CPZ was inferred to stimulate the production of deoxynivalenol. These findings revealed the stereoselective efficiency of CPZ stereoisomers against FHB and provided new insights into the mechanism of action of triazole fungicides against FHB and deoxynivalenol.


Assuntos
Fusarium , Doenças das Plantas , Estereoisomerismo , Triazóis/farmacologia , Tricotecenos
8.
Nanotechnology ; 32(47)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34388741

RESUMO

The material, electrical and ultraviolet optoelectronic properties of few layers bottom molybdenum disulfide (MoS2) field effect transistors (FETs) device was investigated before and after 1 MeV electron irradiation. Due to the participation of SiO2in conduction, we discovered novel photoelectric properties and a relatively long photogenerated carrier lifetime (several tens of seconds). Electron irradiation causes lattice distortion, the decrease of carrier mobility, and the increase of interface state. It leads to the degradation of output characteristics, transfer characteristics and photocurrent of the MoS2FET.

9.
Front Public Health ; 9: 689021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368059

RESUMO

Background: To identify distinct trajectories of body mass index (BMI) in a large sample of Chinese children by urban-rural and sex disparities. Methods: Data for this study were obtained from the National Surveys on Chinese Students' Constitution and Health among 16,060 children aged 6-11 years. Weight and height data were used to calculate BMI. Group-based trajectory modeling (GBTM) was used to identify distinct BMI trajectories. Results: Seven distinct trajectories were identified, "sustained healthy weight" (46.01%), "sustained obesity" (17.26%), "sustained underweight" (4.50%), "obesity to overweight" (6.45%), "obesity to healthy weight" (11.75%), "healthy weight to overweight" (8.67%), and "healthy weight to obesity" (5.36%). The proportions of "sustained obesity," "healthy weight to obesity," and "healthy weight to overweight" trajectories were much higher among boys compared with girls (P < 0.001). Meanwhile, children living in rural areas were more represented in the "healthy weight to obesity" trajectory (P < 0.001). Conclusion: In this study, the proportions of BMI development trajectories among 6-11-year-old children varied by sex and urban-rural areas, which may require tailored interventions specifically toward these at-risk trajectories.


Assuntos
Obesidade , Sobrepeso , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , Obesidade/epidemiologia , População Rural , Magreza
10.
Sci Total Environ ; 792: 148381, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34146805

RESUMO

Manures, storages for antibiotic resistance genes (ARGs), pollute soil and water as well as endanger human health. Recently, we have been searching a better solution to remove antibiotics and ARGs during aerobic composting. Here, the dynamics of chitosan addition on the profiles of 71 ARGs, bacterial communities, chlortetracycline (CTC), ofloxacin (OFX) were investigated in chicken manure composting and compared with zeolite addition. Chitosan addition effectively reduces antibiotics contents (CTC under detection limit, OFX 90.96%), amounts (18) and abundance (56.7%, 11.1% higher than zeolite addition) of ARGs and mobile genetic elements (MGEs) after 42 days composting. Network analysis indicated that a total of 27 genera strains assigned into 4 phyla (Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes) were the potential hosts of ARGs. Redundancy analysis (RDA) demonstrated that bacterial community succession is the main contributor in the variation of ARGs. Overall, chitosan addition may effect bacterial composition by influencing physic-chemical properties and the concentration of antibiotics, Cu2+, Zn2+ to reduce the risk of ARG transmission. This study gives a new strategy about antibiotics and ARGs removal from composting on the basis of previous studies.


Assuntos
Quitosana , Compostagem , Animais , Antibacterianos , Galinhas , Genes Bacterianos , Humanos , Esterco
11.
Artigo em Inglês | MEDLINE | ID: mdl-33799380

RESUMO

Understanding the deposition and tracking the source of soil organic carbon (C) and nitrogen (N) within agricultural watersheds are critical for assessing soil C and N budgets and developing watershed-specific best management practices. Few studies have been conducted and reported on highly eroded hilly-gully watersheds. In this field study, a constructed dam-controlled hilly-gully watershed in northeastern China was selected to identify the sources of soil C and N losses. Soils at various land uses and landscape positions, and sediments near the constructed dam, were collected and analyzed for selected physiochemical properties, total organic carbon (TOC), total nitrogen (TN), and stable isotopes (13C and 15N). Soil C and N loss and deposition in the watershed were assessed and the relative contributions of each source quantified by a stable isotope mixing model (SIAR). Results indicated that soil C loss was primarily from cropland, accounting for 58.75%, followed by gully (25.49%), forest (9.2%), and grassland (6.49%). Soil N loss was similar to soil C, with cropland contribution of 80.58%, gully of 10.30%, grassland of 7.54%, and forest of 1.59%. The C and N deposition gradually decreased along the direction of the runoff pathway near the constructed dam, and the deposited C and N from cropland and gullies showed an order: middle-dam > bottom-dam > upper-dam and upper-dam > bottom-dam > middle-dam, respectively. A high correlation between soil TOC or TN and the sediment properties suggested that the deposition conditions could be the major factors affecting the C and N pools in the sedimentary zones. This study would provide a scientific insight to develop effective management practices for soil erosion and nutrient loss control in highly eroded agriculture watersheds.


Assuntos
Carbono , Solo , Agricultura , Carbono/análise , China , Nitrogênio/análise
12.
J Pediatr Endocrinol Metab ; 34(2): 163-169, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33544542

RESUMO

OBJECTIVES: The prevalence of general overweight and obesity defined by body mass index criteria has greatly increased in Chinese children and adolescents in recent decades. However, few studies have considered the trend in abdominal obesity in Chinese children and adolescents. This study aimed to examine the secular trends in waist circumference (WC), waist-to-height ratio (WHtR) and the prevalence of abdominal obesity among Chinese children and adolescents aged 6-17 years from 1993 to 2015. METHODS: A total of 11,985 children and adolescents aged 6-17 years participated in the China Health and Nutrition Survey, a continuous cross-sectional survey, conducted from 1993 to 2015. Abdominal obesity was defined as WC≥age- and sex-specific 90th percentile based on the reference from Chinese children and adolescents or WHtR≥0.50. RESULTS: After adjustment for age, sex and region, mean WC increased from 60.27 cm in 1993 to 64.31 cm in 2015 (p for trend <0.001), and mean WHtR increased from 0.430 to 0.434 (p for trend <0.05). The prevalence of abdominal obesity defined by WC reference increased from 5.0% in 1993 to 19.3% in 2015 and defined by WHtR reference increased from 6.4% in 1993 to 14.5% in 2015 (p for trend <0.001). CONCLUSIONS: The prevalence of abdominal obesity among Chinese children and adolescents aged 6-17 years has increased between 1993 and 2015.


Assuntos
Estatura , Índice de Massa Corporal , Obesidade Abdominal/epidemiologia , Razão Cintura-Estatura , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Inquéritos Nutricionais , Prevalência , Prognóstico , Fatores de Tempo
13.
Artigo em Inglês | MEDLINE | ID: mdl-33631424

RESUMO

Pseudouridine (Ψ) is the most prevalent post-transcriptional RNA modification and is widespread in small cellular RNAs and mRNAs. However, the functions, mechanisms and precise distribution of Ψs (especially in mRNAs) still remain largely unclear. The landscape of Ψs across the transcriptome has not yet been fully delineated. Here, we present a highly effective model based on a convolutional neural network (CNN), called PULSE, to analyze large-scale profiling data of Ψ sites and characterize the contextual sequence features of pseudouridylation. PULSE, consisting of two alternatively stacked convolution and pooling layers followed by a fully-connected neural network, can automatically learn the hidden patterns of pseudouridylation from the local sequence information. Extensive validation tests demonstrated that PULSE can outperform other state-of-the-art prediction methods and achieve high prediction accuracy, thus enabling us to further characterize the transcriptome-wide landscape of Ψ sites. We further showed that the prediction results derived from PULSE can provide novel insights into understanding the functional roles of pseudouridylation, such as the regulations of RNA secondary structure, codon usage, translation, and RNA stability, and the connection to single nucleotide variants.

14.
Nanomaterials (Basel) ; 11(2)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525597

RESUMO

Vanadium dioxide (VO2) is a typical metal-insulator transition (MIT) material, which changes from room-temperature monoclinic insulating phase to high-temperature rutile metallic phase. The phase transition of VO2 is accompanied by sudden changes in conductance and optical transmittance. Due to the excellent phase transition characteristics of VO2, it has been widely studied in the applications of electric and optical devices, smart windows, sensors, actuators, etc. In this review, we provide a summary about several phases of VO2 and their corresponding structural features, the typical fabrication methods of VO2 nanostructures (e.g., thin film and low-dimensional structures (LDSs)) and the properties and related applications of VO2. In addition, the challenges and opportunities for VO2 in future studies and applications are also discussed.

15.
Biosens Bioelectron ; 172: 112779, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33160235

RESUMO

The transient receptor potential vanilloid 1 (TRPV1) is a key target for the spicy taste sensor and analgesic drug development. However, the human TRPV1-associated signaling remains to be obscure. In this study, we overexpressed human TRPV1 (hTRPV1) in HEK293T cells and explored its signaling activated by spicy substances. A cell membrane biosensor was constructed by using the cells highly expressed hTRPV1 through a layer-by-layer assembly. Our results showed that the activation constants by capsaicin, allicin and sanshool, the active components of chili pepper, garlic and mountain pepper, were Ka, capsaicin = 3.5206 × 10-16 mol/L, Ka, allicin = 5.0227 × 10-15 mol/L, Ka, sanshool = 1.7832 × 10-15 mol/L. Obviously, the order of the sensitivity mediated by hTRPV1 was capsaicin > sanshool > allicin. The affinity values of the three spicy substances with hTRPV1 analyzed by molecular docking simulation also displayed the same law. Most importantly, some amide bonds and their similar groups and even benzene rings of spicy compounds were fund to be critical in the spicy sensing process. In addition, Glu570 in the active pocket of hTRPV1 plays an important role in identifying spicy substances. The elucidation of the detailed mechanism mediated by hTRPV1 in spicy sensing will lay a theoretical foundation to design rational strategies for screening of potential analgesics.


Assuntos
Técnicas Biossensoriais , Canais de Potencial de Receptor Transitório , Capsaicina , Membrana Celular , Células HEK293 , Humanos , Simulação de Acoplamento Molecular , Canais de Cátion TRPV/genética
16.
Cell Transplant ; 29: 963689720958655, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33086892

RESUMO

The transcription factor Pax4 plays an essential role in the development of insulin-producing ß cells in pancreatic islets. Ectopic Pax4 expression not only promotes ß cell survival but also induces α-to-ß cell transdifferentiation. This dual functionality of Pax4 makes it an appealing therapeutic target for the treatment of insulin-deficient type 1 diabetes (T1D). In this study, we demonstrated that Pax4 gene delivery by an adenoviral vector, Ad5.Pax4, improved ß cell function of mouse and human islets by promoting islet cell survival and α-to-ß cell transdifferentiation, as assessed by multiple viability assays and lineage-tracing analysis. We then explored the therapeutic benefits of Pax4 gene delivery in the context of islet transplantation using T1D mouse models. Both mouse-to-mouse and human-to-mouse islet transplantation, via either kidney capsule or portal vein, were examined. In all settings, Ad5.Pax4-treated donor islets (mouse or human) showed substantially better therapeutic outcomes. These results suggest that Pax4 gene delivery into donor islets may be considered as an adjunct therapy for islet transplantation, which can either improve the therapeutic outcome of islet transplantation using the same amount of donor islets or allow the use of fewer donor islets to achieve normoglycemia.


Assuntos
Transdiferenciação Celular , Técnicas de Transferência de Genes , Células Secretoras de Glucagon/citologia , Proteínas de Homeodomínio/genética , Células Secretoras de Insulina/citologia , Transplante das Ilhotas Pancreáticas , Fatores de Transcrição Box Pareados/genética , Animais , Linhagem da Célula , Sobrevivência Celular , Diabetes Mellitus Tipo 1/terapia , Feminino , Regulação da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Fatores de Transcrição Box Pareados/metabolismo , Resultado do Tratamento
17.
Artigo em Inglês | MEDLINE | ID: mdl-33127082

RESUMO

OBJECTIVES: Readmission within 30 days of discharge after coronary artery bypass grafting is a measure of quality and a driver of cost in health care. Traditional predictive models use time-independent variables. We developed a new model to predict time to readmission after coronary artery bypass grafting using both time-independent and time-dependent preoperative and perioperative data. METHODS: Adults surviving to discharge after isolated coronary artery bypass grafting at a multi-hospital academic health system from January 2017 to September 2018 were included in this study. Two distinct data sources were used: the institutional cardiac surgical database and the clinical data warehouse, which provided more granular data points for each patient. Patients were divided into training and validation sets in an 80:20 ratio. We evaluated 82 potential risk factors using Cox survival regression and machine learning techniques. The area under the receiver operating characteristic curve was used to estimate model predictive accuracy. RESULTS: We trained the model with 21 variables that scored a P value of less than .05 in the univariable analysis. The multivariable model determined 16 significant risk factors, and 6 of them were time-dependent. These included preoperative hemoglobin a1c level, preoperative creatinine, preoperative hematocrit, intraoperative hemoglobin, postoperative creatinine, and postoperative hemoglobin. Area under the receiver operating characteristic values were 0.906 and 0.868 for training and validation sets, respectively. CONCLUSIONS: Time-dependent perioperative variables in an isolated coronary artery bypass grafting cohort provided better predictive ability to a readmission model. This study was unique in the inclusion of time-dependent covariates in the predictive model for readmission after discharge after coronary artery bypass grafting.

18.
Medicine (Baltimore) ; 99(38): e22129, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957333

RESUMO

INTRODUCTION: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD. Patient concerns: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation. DIAGNOSIS: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy. INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-α receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out. OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before. CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD. RATIONALE: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD. PATIENT CONCERNS: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation. DIAGNOSES: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy. INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-a receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out. OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before. CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD. LESSONS: There is still a possibility of recurrence after the treatment of GvHD with capsule fecal microbiota transplantation. How to optimize the dosage and treatment course of fecal microbiota capsule administration needs further exploration.


Assuntos
Transplante de Microbiota Fecal , Doença Enxerto-Hospedeiro/terapia , Enteropatias/terapia , Adulto , Cápsulas , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Síndromes Mielodisplásicas/terapia , Doadores não Relacionados
19.
Int J Biol Macromol ; 163: 1393-1402, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32755709

RESUMO

In this study, the effect of Ziziphus jujuba Mill var. spinosa seeds (ZSS) polysaccharides on the bioavailability of spinosin in mice and its molecular mechanism were investigated. After continuously fed with ZSS polysaccharides 100 mg/kg·d-1 for 28 consecutive days, the C57BL/6 mice absorbed spinosin at an obvious lower level compared with the control group. The expression levels of P-gp, MRP2 and Occludin in the colon were significantly increased. ZSS polysaccharides significantly regulated the composition of the gut microbiota, reducing the abundance of Bacteroidetes, and increasing the richness of Firmicutes and Verrucomicrobia. Moreover, ZSS polysaccharides can significantly regulate the expression levels of tight junction proteins and efflux transporters in Caco-2 cells. However, the gut microbiota culture supernatant showed no obvious biological activity in this regard. Furthermore, histopathological analysis revealed ZSS polysaccharides can alleviate TNBS-induced colitis, reduced inflammatory cell infiltration in mice. This immune regulation was related to the NF-κB and MAPK pathways in RAW264.7 cells.


Assuntos
Colite/prevenção & controle , Flavonoides/metabolismo , Polissacarídeos/farmacologia , Sementes/química , Ziziphus/química , Animais , Bacteroidetes/efeitos dos fármacos , Disponibilidade Biológica , Células CACO-2 , Linhagem Celular Tumoral , Colite/microbiologia , Firmicutes/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Inflamação/microbiologia , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Verrucomicrobia/efeitos dos fármacos
20.
Diabetes ; 69(11): 2392-2399, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32855171

RESUMO

Testosterone (T) affects ß-cell function in men and women. T is a prohormone that undergoes intracrine conversion in target tissues to the potent androgen dihydrotestosterone (DHT) via the enzyme 5α-reductase (5α-R) or to the active estrogen 17ß-estradiol (E2) via the aromatase enzyme. Using male and female human pancreas sections, we show that the 5α-R type 1 isoform (SRD5A1) and aromatase are expressed in male and female ß-cells. We show that cultured male and female human islets exposed to T produce DHT and downstream metabolites. In these islets, exposure to the 5α-R inhibitors finasteride and dutasteride inhibited T conversion into DHT. We did not detect T conversion into E2 from female islets. However, we detected T conversion into E2 in islets from two out of four male donors. In these donors, exposure to the aromatase inhibitor anastrozole inhibited E2 production. Notably, in cultured male and female islets, T enhanced glucose-stimulated insulin secretion (GSIS). In these islets, exposure to 5α-R inhibitors or the aromatase inhibitor both inhibited T enhancement of GSIS. In conclusion, male and female human islets convert T into DHT and E2 via the intracrine activities of SRD5A1 and aromatase. This process is necessary for T enhancement of GSIS.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Aromatase/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Testosterona/farmacologia , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Aromatase/genética , Células Cultivadas , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Células Secretoras de Insulina/metabolismo , Masculino
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