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1.
Front Immunol ; 12: 761981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858414

RESUMO

In inflammatory bowel disease (IBD), intestinal mucosa cell and intestinal epithelial cell are severely damaged, and then their susceptibility to bacteria increases, so many commensal bacteria become pathogenic. The pathogenic commensal bacteria can stimulate a series of compensatory immune responses in the intestine. However, the immune response prevents the intestinal tract from restoring homeostasis, which in turn produces an indispensable inflammatory response. On the contrary, in IBD, the fierce inflammatory response contributes to the development of IBD. However, the effect of commensal bacteria on inflammation in IBD has not been clearly studied. Therefore, we further summarize the changes brought about by the changes of commensal bacteria to the inflammation of the intestines and their mutual influence. This article reviews the protective mechanism of commensal bacteria in healthy people and the mechanism of commensal bacteria and immune response to the destruction of the intestinal barrier when IBD occurs. The treatment and prevention of IBD are also briefly summarized.

2.
Front Plant Sci ; 12: 713890, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484276

RESUMO

As an important component, 1,000 kernel weight (TKW) plays a significant role in the formation of yield traits of wheat. Kernel size is significantly positively correlated to TKW. Although numerous loci for kernel size in wheat have been reported, our knowledge on loci for kernel area (KA) and kernel circumference (KC) remains limited. In the present study, a recombinant inbred lines (RIL) population containing 371 lines genotyped using the Wheat55K SNP array was used to map quantitative trait loci (QTLs) controlling the KA and KC in multiple environments. A total of 54 and 44 QTLs were mapped by using the biparental population or multienvironment trial module of the inclusive composite interval mapping method, respectively. Twenty-two QTLs were considered major QTLs. BLAST analysis showed that major and stable QTLs QKc.sau-6A.1 (23.12-31.64 cM on 6A) for KC and QKa.sau-6A.2 (66.00-66.57 cM on 6A) for KA were likely novel QTLs, which explained 22.25 and 20.34% of the phenotypic variation on average in the 3 year experiments, respectively. Two Kompetitive allele-specific PCR (KASP) markers, KASP-AX-109894590 and KASP-AX-109380327, were developed and tightly linked to QKc.sau-6A.1 and QKa.sau-6A.2, respectively, and the genetic effects of the different genotypes in the RIL population were successfully confirmed. Furthermore, in the interval where QKa.sau-6A.2 was located on Chinese Spring and T. Turgidum ssp. dicoccoides reference genomes, only 11 genes were found. In addition, digenic epistatic QTLs also showed a significant influence on KC and KA. Altogether, the results revealed the genetic basis of KA and KC and will be useful for the marker-assisted selection of lines with different kernel sizes, laying the foundation for the fine mapping and cloning of the gene(s) underlying the stable QTLs detected in this study.

3.
Int J Nanomedicine ; 16: 4545-4557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34267512

RESUMO

Background: Shigella infection has always been a global burden, and it particularly threatens children between the ages of 1 and 5 years. Economically underdeveloped countries are dominated by Shigella flexneri infection. The most effective method to treat Shigella is antibiotics, but with the abuse of antibiotics and the prevalence of multidrug resistance, we urgently need a relatively safe non-antibiotic treatment to replace it. Ultrasmall Au nanoclusters (NCs) have special physical and chemical properties and can better interact with and be internalized by bacteria to disrupt the metabolic balance. The purpose of this study was to explore whether Au NCs may be a substitute for antibiotics to treat Shigella infections. Methods: Au NCs and Shigella Sf301, R2448, and RII-1 were cocultured in vitro to evaluate the bactericidal ability of Au NCs. The degree of damage and mode of action of Au NCs in Shigella were clearly observed in images of scanning electron microscopy (SEM). In vivo experiments were conducted to observe the changes in body weight, clinical disease activity index (DAI) and colon (including length and histopathological sections) of mice treated with Au NCs. The effect of Au NCs was analysed by measuring the content of lipocalin-2 (LCN2) and Shigella in faeces. Next, the changes in Shigella biofilm activity, the release of reactive oxygen species (ROS), the changes in metabolism-related and membrane-related genes, and the effect of Au NCs on the body weight of mice were determined to further analyse the mechanism of action and effect. Results: Au NCs (100 µM) interfered with oxidative metabolism genes, induced a substantial increase in ROS levels, interacted with the cell membrane to destroy it, significantly killed Shigella, and effectively alleviated the intestinal damage caused by Shigella in mice. The activity of the biofilm formed by Shigella was reduced. Conclusion: The effective antibacterial effect and good safety suggest that Au NCs represent a good potential alternative to antibiotics to treat Shigella infections.


Assuntos
Colite/metabolismo , Colite/microbiologia , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Shigella/fisiologia , Animais , Colite/tratamento farmacológico , Ouro/uso terapêutico , Humanos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Shigella/efeitos dos fármacos
4.
Acta Pharm Sin B ; 11(2): 442-455, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33643823

RESUMO

Although different types of drugs are available for postmenopausal osteoporosis, the limitations of the current therapies including drug resistances and adverse effects require identification of novel anti-osteoporosis agents. Here, we defined that norlichexanthone (NOR), a natural product, is a ligand of estrogen receptor-alpha (ERα) and revealed its therapeutic potential for postmenopausal osteoporosis. We used mammalian-one hybrid assay to screen for ERα modulators from crude extracts of several plant endophytes. As a result, NOR purified from the extract of endophyte ARL-13 was identified as a selective ERα modulator. NOR directly bound to ERα with an affinity in nanomolar range, revealing that it is a natural ligand of ERα. NOR induced osteoblast formation in MC3T3-E1 precursor cells. Conversely, NOR inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation in both RAW264.7 macrophages and mouse primary monocytes. Mechanistically, NOR inhibited RANKL-induced association of ERα and TRAF6 to prevent ERα-mediated TRAF6 activation via Lys63-linked ubiquitination. Importantly, NOR exhibited potent anti-osteoporosis efficacy in an ovariectomized mouse model. Comparing to estrogen, NOR was of much less capability in stimulating endometrial hyperplasia and promoting mammalian cancer cell proliferation. Taken together, our study identified NOR as a natural and high affinity ligand of ERα with substantial anti-osteoporosis but less estrogenic activity.

5.
Front Cell Dev Biol ; 9: 641831, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748132

RESUMO

Background: Neural tube defects (NTDs) are among the most common and severe congenital defects in humans. Their genetic etiology is complex and remains poorly understood. The Mediator complex (MED) plays a vital role in neural tube development in animal models. However, no studies have yet examined the role of its human homolog in the etiology of NTDs. Methods: In this study, 48 pairs of neural lesion site and umbilical cord tissues from NTD and 21 case-parent trios were involved in screening for NTD-related somatic and germline de novo variants. A series of functional cell assays were performed. We generated a Med12 p.Arg1784Cys knock-in mouse using CRISPR/Cas9 technology to validate the human findings. Results: One somatic variant, MED12 p.Arg1782Cys, was identified in the lesion site tissue from an NTD fetus. This variant was absent in any other normal tissue from different germ layers of the same case. In 21 case-parent trios, one de novo stop-gain variant, MED13L p.Arg1760∗, was identified. Cellular functional studies showed that MED12 p.Arg1782Cys decreased MED12 protein level and affected the regulation of MED12 on the canonical-WNT signaling pathway. The Med12 p.Arg1784Cys knock-in mouse exhibited exencephaly and spina bifida. Conclusion: These findings provide strong evidence that functional variants of MED genes are associated with the etiology of some NTDs. We demonstrated a potentially important role for somatic variants in the occurrence of NTDs. Our study is the first study in which an NTD-related variant identified in humans was validated in mice using CRISPR/Cas9 technology.

7.
Animals (Basel) ; 11(2)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525565

RESUMO

This study was conducted to evaluate the dietary supplemental effects of 2-nitroethanol (NEOH) in comparison with monensin on methane (CH4) emission, growth performance and carcass characteristics in female lambs. Sixty female, small-tailed Chinese Han lambs (3.5 ± 0.3 month) were randomly allotted into three dietary treatment groups: (1) Control group, a basal control diet, (2) monensin group, the basal diet added with 40 mg/kg monensin, (3) NEOH group, the basal diet added with 277 mg/kg nitroethanol, and the feedlotting trial lasted for 70 days. Although dietary addition of monensin and NEOH did not affect nutrient digestibility of lambs, both monensin and NEOH decreased the calculated CH4 production (12.7% vs. 17.4% decrease; p < 0.01). In addition, the CH4 production represents less dietary energy loss in the monensin and NEOH group than in the control, indicating that monensin and NEOH are potent CH4 inhibitors that can reduce dietary energy loss. Dietary addition of monensin and NEOH decreased dry matter intake (p < 0.01); however, they increased the ADG of female lambs (p < 0.01). As a result, both monensin and NEOH increased feed conversion efficiency of the feedlotting lambs (p < 0.01), suggesting that feed energy saved from CH4 production promoted the feed efficiency and ADG in the present study. Except for the fact that NEOH addition increased the net muscle percentage to carcass weight (p = 0.03), neither monensin nor NEOH had a significant influence on carcass characteristics of female lambs (p > 0.05). From an economic point of view, NEOH and monensin caused a reduction in feed consumption costs, therefore resulting in a higher net revenue and economic efficiency than the control. In summary, dietary supplementation of NEOH in comparison with monensin presented a more promoting effect on energy utilization in female lambs by inhibiting rumen methanogenesis more efficiently, and NEOH improved the net revenue and economic efficiency more significantly than monensin.

8.
Sci Total Environ ; 764: 144245, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33385660

RESUMO

Neural tube defects (NTDs) have a complex etiology. Few studies have assessed alkaline earth metals exposures and occurrence of NTDs. We examined the association between prenatal exposure to magnesium (Mg), calcium (Ca), strontium (Sr) and barium (Ba) and risk for NTDs in a case-control study, and assessed the teratogenic effects of Ba on mice. Placentas were collected from 408 women with NTD-affected pregnancies and 593 women who delivered healthy infants, and concentrations of these metals were determined as prenatal exposure markers. The single effect of individual exposure and joint effect of coexposure to these metals were evaluated with logistic regression and Bayesian kernel machine regression (BKMR), respectively. Barium chloride (BaCl2) was intragastrically administered to pregnant ICR mice and fetal mice were examined for NTDs. Median concentrations of Mg and Ba were higher in NTD cases than in controls (Pall < 0.001). In logistic regression, higher levels of Ba were associated with 1.6-fold increased risk for NTDs (95% confidence interval: 1.06-2.43). In BKMR, the joint effect of the four-metal mixture on NTD risk increased steadily with the levels of the mixture. A change in Ba concentration from the 25th to 75th percentile displayed a risk effect when the other three metals were fixed at the 25th, 50th or 75th percentile, while such a change in Ca concentration showed a protective effect when the other metals were held at the 25th or 50th percentile. No interactions among metals were found. In the mouse experiment, dams treated with 200 mg/kg BaCl2 showed 16.8% of NTDs in fetal mice, compared to 2.6% in the untreated control group (P < 0.01). Taken together, higher mixture levels of the four alkaline earth metals were associated with increased risk for NTDs, with Ba being the major contributor for the joint effect. Intragastric administration of Ba can induce NTDs in mice.


Assuntos
Defeitos do Tubo Neural , Efeitos Tardios da Exposição Pré-Natal , Animais , Bário/toxicidade , Teorema de Bayes , Estudos de Casos e Controles , Feminino , Camundongos , Camundongos Endogâmicos ICR , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , Gravidez
9.
Theor Appl Genet ; 134(3): 807-821, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33388883

RESUMO

KEY MESSAGE: This study mapped QTLs associated with kernel-related traits by high-density genetic map. Five new major and stable QTLs for KL, KDR, SN, and KWPS were mapped in multiple environments. In the present study, a recombinant inbred line population including 371 lines derived from the cross of Chuannong18 and T1208 was genotyped using the Wheat55K single nucleotide polymorphism array. A novel high-density genetic map consisting of 11,583 markers spanning 4192.62 cM and distributed across 21 wheat chromosomes was constructed. QTLs for important kernel-related traits were mapped in multiple environments. A total of 96 and 151 QTLs were mapped by using the ICIM method and the MET method, respectively. And a total of 114 digenic epistatic QTLs were also detected across 21 chromosomes, and the epistatic effects of each trait were analyzed. BLAST analysis showed that 23 QTLs for different kernel-related traits were first time mapped and five of them were major and stable QTLs for kernel diameter ratio (121.34-126.83 cM on 4BS), spike number per square meter (71.32-73.84 cM on 2DS), kernel weight per spike (71.32-75.26 cM on 2DS), and kernel length (16.78-31.64 cM on 6A and 51.63-58.40 cM on 3D), respectively. Fifteen QTL clusters that contained 58 QTLs were also detected, and all most stable QTLs were contained in these QTL clusters. Significant correlations between different traits were detected and discussed. These results lay the foundation for fine mapping and cloning of the gene(s) underlying the stable QTLs detected in this study.


Assuntos
Cromossomos de Plantas/genética , Marcadores Genéticos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sementes/genética , Triticum/genética , Mapeamento Cromossômico , Ligação Genética , Genótipo , Fenótipo , Sementes/crescimento & desenvolvimento , Triticum/crescimento & desenvolvimento
10.
Cell Mol Immunol ; 18(1): 57-72, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33041339

RESUMO

The liver is a lymphoid organ with unique immunological properties, particularly, its predominant innate immune system. The balance between immune tolerance and immune activity is critical to liver physiological functions and is responsible for the sensitivity of this organ to numerous diseases, including hepatotropic virus infection, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, and liver cancer, which are major health problems globally. In the past decade, with the discovery of liver-resident natural killer cells, the importance of innate lymphocytes with tissue residency has gradually become the focus of research. In this review, we address the current knowledge regarding hepatic innate lymphocytes with unique characteristics, including NK cells, ILC1/2/3s, NKT cells, γδ T cells, and MAIT cells, and their potential roles in liver homeostasis maintenance and the progression of liver diseases and cancer. A better understanding of the immunopathogenesis of hepatic innate lymphocytes will be helpful for proposing effective treatments for liver diseases and cancer.

11.
Cell Mol Immunol ; 18(1): 128-137, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31767976

RESUMO

Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is mediated by an inappropriate attack by HBV-specific T cells in patients. However, this immunopathogenic process has not been clarified because of the lack of a suitable animal model. Here, we used immunocompetent Fah-/- mice as the recipients in the adoptive transfer of HBsAg+ hepatocytes from HBs-Tg mice to replace the recipient hepatocytes (HBs-HepR). HBs-HepR mice exhibited persistent HBsAg expression with chronic hepatitis and eventually developed HCC with a prevalence of 100%. HBsAg-specific CD8+ T cells were generated and specifically and continuously induced hepatocyte apoptosis with progressive chronic inflammation, and the depletion of CD8+ T cells or their deficiency prevented HCC, which could then be reproduced by the transfer of HBsAg-specific CD8+ T cells. In summary, our results demonstrated that CD8+ T cells plays a critical role in HBsAg-driven inflammtion and HCC tumorigenesis.

12.
Sci Total Environ ; 750: 141735, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877786

RESUMO

The relationship between alkaline earth elements in utero exposure and the risk of cleft lip with or without cleft palate (CL ± P) remains unclear. We aimed to investigate the associations between the concentration of alkaline earth elements in umbilical cord and risk for CL ± P. A case-control study was carried out in this study, including 78 cases and 142 controls. Association between each metals and the risk of CL ± P were evaluated with conventional logistic regression, bayesian kernel machine regression and weighted quantile sum regression models. Logistic regression model indicated that in utero exposure to higher levels of Barium was associated with increasing risk for CL ± P (odds ratio = 2.79, 95% confidence interval, 1.22-6.38) and for cleft lip with cleft palate (odds ratio = 3.94, 95% confidence interval, 1.45-10.72). Bayesian kernel machine regression model showed the statistical association between the metals mixture and risk difference of CL ± P, and barium was associated with CL ± P risk when all other metals were held fixed at the 25th percentiles (risk difference = 1.07, 95% confidence interval, 1.01-1.14). In weighted quantile sum model, barium accounted for most of the weight index in the combined effect of the metals mixture. The weighted quantile sum index showed that a quartile increase in the index resulted in an increase odds of 1.69 (95% confidence interval, 1.16-2.46) for CL ± P and of 2.11 (95% confidence interval, 1.34-3.35) for CLP. No associations were found in the three statistical models between Calcium, Magnesium and Strontium and the risks of CL ± P. In conclusion, in utero exposure to mixtures of alkaline earth elements was associated with an increased risk for CL ± P, of which barium was likely to be important factors in the development.


Assuntos
Fenda Labial , Fissura Palatina , Teorema de Bayes , Estudos de Casos e Controles , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Humanos , Cordão Umbilical
13.
Ecotoxicol Environ Saf ; 207: 111284, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32942100

RESUMO

Questions remain about the effects of rare earth elements (REEs) on reproductive health, and no study has explored in utero exposure to REEs and risk of orofacial clefts (OFCs). We recruited subjects from a case-control study conducted in Shanxi Province, China. Concentrations of fifteen REEs were quantified in umbilical cord samples by means of Inductively Coupled Plasma Mass Spectrometry measurements. We employed logistic regression and weighted quantile sum (WQS) regression models to estimate the association between REEs exposures and OFCs. Of 226 subjects included in our study, 34 were cleft lip only, 44 were cleft lip with cleft palate and 6 were cleft palate only. In the logistic regression model, concentrations above the median of all subjects were associated with an increased OFCs risk of 2.35-fold (95% CI: 1.22, 4.53) for Lanthanum and 2.12-fold for Neodymium (95% CI: 1.10, 4.10) adjusting for maternal age, BMI, gestational weeks, sex of infants and passive smoking. In WQS model, a quartile increase in the index resulting in an increase of 3.10 (95% CI: 1.38, 6.96) in the odds of OFC. Lanthanum and Neodymium were suggested to be important factors. The results were largely consistent for OFC subtypes. In conclusion, in utero exposure to mixtures of REEs increased the risk of OFCs. Lanthanum and Neodymium were likely to be important factors in the development of OFCs.


Assuntos
Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Metais Terras Raras/análise , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Cordão Umbilical/química , Adulto , Estudos de Casos e Controles , China , Fenda Labial/metabolismo , Fissura Palatina/metabolismo , Feminino , Humanos , Lantânio/análise , Modelos Logísticos , Masculino , Neodímio/análise , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fatores de Risco , Poluição por Fumaça de Tabaco
14.
Cancer Biol Med ; 17(4): 1026-1038, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33299651

RESUMO

Objective: Natural killer (NK) cells have gained considerable attention due to their potential in treating "cold tumors," and are therefore considered as one of the new strategies for curing cancer, by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products. Methods: We constructed a trispecific killer engager (TriKE) consisting of anti-CD16, IL-15, and anti-CD19. This TriKE was designed to attract CD19+ tumor cells to CD16+ NK cells, whereas IL-15 sustained the proliferation, development, and survival of NK cells. Results: Treatment with 161519 TriKE in the presence of CD19+ targets upregulated expression of CD69, CD107a, TRAIL, IFN-γ, and TNF-α in NK cells, and significantly improved the proliferation and cytotoxicity of NK cells. NK cells "armed" with 161519 TriKE showed stronger cytolysis against CD19+ targets compared with that of "unarmed" NK cells. A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE, when compared with that in control mice or mice treated with 1619 BiKE. Combined use of IL-2 was a more effective treatment with 1619 BiKE, when compared with that using 161519 TriKE. Conclusions: The newly generated 161519 TriKE enhanced the proliferation, activation, cytokine secretion, and cytotoxicity of NK cells in the presence of CD19+ tumor cells. The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts, and could be used to treat CD19-positive cancers.

15.
Environ Res ; 189: 109919, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32980010

RESUMO

Ionic liquids (ILs) are commonly known as "green" solvents and have been widely used in various fields. However, the ecotoxicity of ILs in aquatic environment has received considerable attention from scientific researchers. This study investigated the toxic effects of different concentrations of 1-octyl-3-methylimidazolium hexafluorophosphate ([C8mim][PF6]) (0, 1.35, 2.70 and 5.40 mg/L) on intestinal physical barrier, immunological barrier, and intestinal microbiome in common carp on days 30 and 60. The results showed that ([C8mim][PF6]) exposure could reduce the intestinal villus height, decrease the mRNA expression of tight junction genes (occludin, claudin-2 and zonula occludens-1), and increase the levels of D-lactic and diamine oxidase, and reduce acid phosphatase and lysozyme activities, complement 3 and 4 contents, and anti-inflammatory cytokine TGF-ß protein level, while increase pro-inflammatory cytokines TNF-α and IL-1ß protein levels in common carp. Moreover, ([C8mim][PF6]) exposure was also found to significantly reduce gut microbial diversity and alter microbial community structure in common carp. Collectively, our study highlighted that exposure to ([C8mim][PF6]) could disrupt intestinal physical barrier, impair immunological barrier and alter intestinal microbiome in common carp, suggesting that ILs exert a negative effect on fish intestinal health status and may pose serious health risks in fish. The results of this study may be helpful to illuminate the toxicity mechanisms of the ILs on fish.


Assuntos
Carpas , Microbioma Gastrointestinal , Líquidos Iônicos , Animais , Citocinas/genética , Dieta , Proteínas de Peixes , Mucosa Intestinal , Intestinos , Líquidos Iônicos/toxicidade
17.
Int J Nanomedicine ; 15: 6401-6408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32904597

RESUMO

Background: Clostridium difficile infection (CDI) has become one of the most important factors threatening human health, and about 20-30% antibiotic-related diarrhea cases and almost all pseudomembranous enteritis cases are related to CDI. The high recurrence of Clostridium difficile (C. difficile) and the emergence of drug resistance make clinical treatment of CDI difficult. Therefore, there is an urgent need to develop a non-antibiotic-alternative therapy against CDI. Gold nanoclusters (AuNCs) can better interact with bacteria due to its ultrasmall size. The aim of the present study was to explore whether AuNCs could be used as an antibacterial agent to kill C. difficile. Methods: AuNCs and C. difficile were co-cultivated in an anaerobic atmosphere to evaluate the bactericidal effect of AuNCs. The bacterial growth rate was estimated by using two concentrations of AuNCs (50 and 100 µM). The damage of AuNCs to C. difficile is detected by SYTOX Green staining methods and SEM image analysis. The mechanism of AuNCs on C. difficile was explored by reactive oxygen species (ROS) detection. The toxic effect of AuNCs on human cells was evaluated by MTT method. Results: AuNCs (100 µM) killed C. difficile drastically. AuNCs increased the release of ROS by about 5 fold and destroyed the membrane integrity of C. difficile cells without causing significant toxic effect on human cells. Conclusion: AuNCs showed great potential as an alternative to traditional antibiotics in killing C. difficile and may prove to be an alternative to treat CDI.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Clostridioides difficile/efeitos dos fármacos , Ouro/farmacologia , Nanoestruturas/química , Linhagem Celular , Clostridioides difficile/crescimento & desenvolvimento , Clostridioides difficile/metabolismo , Clostridioides difficile/ultraestrutura , Ouro/química , Humanos , Testes de Sensibilidade Microbiana , Espécies Reativas de Oxigênio/metabolismo
18.
Front Immunol ; 11: 1500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765518

RESUMO

Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease (NAFLD), is accompanied by steatosis, hepatocyte injury and liver inflammation, which has been a health problem in the world as one of the major high risk factors of cirrhosis and hepatocellular carcinoma (HCC). Complex immune responses involving T cells, B cells, Kupffer cells, monocytes, neutrophils, DCs and other innate lymphocytes account for the pathogenesis of NASH; however, the underlying mechanisms have not been clearly elucidated in detail. In the liver, innate and innate-like lymphocytes account for more than two-thirds of total lymphocytes and play an important role in maintaining the immune homeostasis. Therefore, their roles in the progression of NASH deserves investigation. In this review, we summarized murine NASH models for immunological studies, including the diet-induced NASH, chemical-induced NASH and genetic-induced NASH. The role of innate and innate-like lymphocytes including NK cells, ILCs, NKT, γδT and MAIT cells in the progression of NASH were elucidated. Further, the metabolic regulation of the innate immune response was addressed in consideration to explain the molecular mechanisms. Based on the findings of the reviewed studies, strategies of immune intervention are proposed to control the progression of NASH.


Assuntos
Fígado/imunologia , Linfócitos/imunologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Animais , Modelos Animais de Doenças , Humanos , Imunidade Inata , Camundongos
19.
Emerg Microbes Infect ; 9(1): 1470-1473, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32608335

RESUMO

Since the first report of the coronavirus disease (COVID-19) in late December 2019, the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now widely spread to more than 187 countries and regions. However, it is unclear whether there has been cryptic transmission before these early officially confirmed cases, we therefore retrospectively screened for the SARS-CoV-2 RNA in 1271 nasopharyngeal swab samples, as well as the prevalence of IgM, IgG, and total antibodies against SARS-CoV-2 in 357 matched serum samples collected from hospitalized patients with influenza-like illness between 1 December 2018 and 31 March 2020 in Shanghai Ruijin Hospital. The onset date of the earliest COVID-19 case in this study was 25 January 2020. Before this time point, the presence of SARS-CoV-2 was not observed, which limited the possibility that SARS-CoV-2 has already spread among the population before the large-scale outbreak. Additionally, among 6662 patients with influenza-like illness from 1 December 2017 to 31 March 2020, the overall number of patients positive for influenza and other respiratory viruses during the COVID-19 period decreased significantly when compared with that in the same period of the last two years, reflecting that public health interventions can effectively control the spread of common respiratory viruses.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Diagnóstico Diferencial , Feminino , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/virologia , Pandemias , Pneumonia Viral/epidemiologia , RNA Viral/análise , Estudos Retrospectivos , SARS-CoV-2
20.
Hum Genet ; 139(10): 1299-1314, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32356230

RESUMO

Extensive studies that have sought causative mutation(s) for neural tube defects (NTDs) have yielded limited positive findings to date. One possible reason for this is that many studies have been confined to analyses of germline mutations and so may have missed other, non-germline mutations in NTD cases. We hypothesize that somatic mutations of planar polarity pathway (PCP) genes may play a role in the development of NTDs. Torrent™ Personal Genome Machine™ (PGM) sequencing was designed for selected PCP genes in paired DNA samples extracted from the tissues of lesion sites and umbilical cord from 48 cases. Sanger sequencing was used to validate the detected mutations. The source and distribution of the validated mutations in tissues from different germ layers were investigated. Subcellular location, western blotting, and luciferase assays were performed to better understand the effects of the mutations on protein localization, protein level, and pathway signaling. ix somatic mutations were identified and validated, which showed diverse distributions in different tissues. Three somatic mutations were novel/rare: CELSR1 p.Gln2125His, FZD6 p.Gln88Glu, and VANGL1 p.Arg374His. FZD6 p.Gln88Glu caused mislocalization of its protein from the cytoplasm to the nucleus, and disrupted the colocalization of CELSR1 and FZD6. This mutation affected non-canonical WNT signaling in luciferase assays. VANGL1 p.Arg374His impaired the co-localization of CELSR1 and VANGL1, increased the protein levels of VANGL1, and influenced cell migration. In all, 7/48 (14.5%) of the studied NTD cases contained somatic PCP mutations. Somatic mutations in PCP genes (e.g., FZD6 and VANGL1) are associated with human NTDs, and they may occur in different stages and regions during embryonic development, resulting in a varied distribution in fetal tissues/organs.


Assuntos
Caderinas/genética , Proteínas de Transporte/genética , Receptores Frizzled/genética , Proteínas de Membrana/genética , Mutação , Defeitos do Tubo Neural/genética , Tubo Neural/metabolismo , Transporte Ativo do Núcleo Celular/genética , Sequência de Aminoácidos , Animais , Caderinas/metabolismo , Proteínas de Transporte/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Feto , Receptores Frizzled/metabolismo , Expressão Gênica , Genoma Humano , Células HEK293 , Humanos , Masculino , Proteínas de Membrana/metabolismo , Tubo Neural/anormalidades , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/metabolismo , Defeitos do Tubo Neural/patologia , Gravidez , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Sequenciamento Completo do Genoma
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