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1.
Chem Sci ; 15(15): 5482-5495, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38638208

RESUMO

In quantum dot-sensitized solar cells (QDSCs), optimized quantum dot (QD) loading mode and high QD loading amount are prerequisites for great device performance. Capping ligand-induced self-assembly (CLIS) mode represents the mainstream QD loading strategy in the fabrication of high-efficiency QDSCs. However, there remain limitations in CLIS that constrain further enhancement of QD loading levels. This review illustrates the development of various QD loading methods in QDSCs, with an emphasis on the outstanding merits and bottlenecks of CLIS. Subsequently, thermodynamic and kinetic factors dominating QD loading behaviors in CLIS are analyzed theoretically. Upon understanding driving forces, resistances, and energy effects in a QD assembly process, various novel strategies for improving the QD loading amount in CLIS are summarized, and the related functional mechanism is established. Finally, the article concludes and outlooks some remaining academic issues to be solved, so that higher QD loading amount and efficiencies of QDSCs can be anticipated in the future.

2.
Brain Res Bull ; 207: 110876, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38215950

RESUMO

Numb is an evolutionarily conserved protein that regulates the differentiation of neuronal progenitor cells through unknown mechanisms. Numb has four alternative splice variants with different lengths of phosphotyrosine-binding (PTB) and proline-rich regions (PRR) domains. In this study, we demonstrated that Numb expression was increased in the primary cultures of rat cortical and hippocampal neurons over time in vitro, and Numb antisense inhibited neurite outgrowth. We verified that cells overexpressing short PTB (SPTB) or long PTB (LPTB) domains exhibited differentiation or proliferation, respectively. SPTB-mediated differentiation was related to the PRR domains, as cells expressing SPTB/LPRR had longer dendrites and more branched dendrites than cells expressing SPTB/SPRR. The differentiation of both cell types was completely blocked by the Ca2+ chelator. Western blot analysis revealed the increased total protein expression of voltage-gated calcium channel (VGCC) subunit α1C and α1D in cells expressing SPTB and LPTB Numb. The increased expression of the VGCC ß3 subunit was only observed in cells expressing SPTB Numb. Immunocytochemistry further showed that SPTB-mediated cell differentiation was associated with increased membrane expression of VGCC subunits α1C, α1D and ß3, which corresponded to the higher Ca2+ current (ICa) densities. Furthermore, we found that VGCC of cells transfected with SPTB/SPRR or SPTB/LPRR Numb isoforms exhibit steady-state inactivation (SSI) in both differentiated and undifferentiated phenotypes. A similar SSI of VGCC was observed in the differentiated cells transfected with SPTB/SPRR or SPTB/LPRR Numb isoforms, whereas a left shift SSI of VGCC in cells expressing SPTB/LPRR was detected in the undifferentiated cells. Collectively, these data indicate that SPTB domain is essential for neurite outgrowth involving in membrane expression of VGCC subunits, and LPRR plays a role in neuronal branching and the regulation of VGCC inactivation kinetics.


Assuntos
Proteínas de Membrana , Neurônios , Ratos , Animais , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Canais de Cálcio/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacologia , Crescimento Neuronal , Cálcio/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
3.
Molecules ; 28(19)2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37836761

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a liver disease syndrome. The prevalence of NAFLD has continued to increase globally, and NAFLD has become a worldwide public health problem. Glucosamine (GLC) is an amino monosaccharide derivative of glucose. GLC has been proven to not only be effective in anti-inflammation applications, but also to modulate the gut microbiota effectively. Therefore, in this study, the therapeutic effect of GLC in the NAFLD context and the mechanisms underlying these effects were explored. Specifically, an NAFLD model was established by feeding mice a high-fat and high-sugar diet (HFHSD), and the HFHSD-fed NAFLD mice were treated with GLC. First, we investigated the effect of treating NAFLD mice with GLC by analyzing serum- and liver-related indicator levels. We found that GLC attenuated insulin resistance and inflammation, increased antioxidant function, and attenuated serum and liver lipid metabolism in the mice. Then, we investigated the mechanism underlying liver lipid metabolism, inflammation, and intestinal barrier function in these mice. We found that GLC can improve liver lipid metabolism and relieve insulin resistance and oxidative stress levels. In addition, GLC treatment increased intestinal barrier function, reduced LPS translocation, and reduced liver inflammation by inhibiting the activation of the LPS/TLR4/NF-κB pathway, thereby effectively ameliorating liver lesions in NAFLD mice.


Assuntos
Hepatite , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metabolismo dos Lipídeos , Glucosamina/farmacologia , Lipopolissacarídeos/farmacologia , Fígado , Inflamação/metabolismo , Hepatite/metabolismo , Açúcares/metabolismo , Dieta , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL
4.
Nature ; 619(7970): 572-584, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37468586

RESUMO

The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease.


Assuntos
Intestinos , Análise de Célula Única , Humanos , Diferenciação Celular/genética , Cromatina/genética , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Mucosa Intestinal/citologia , Intestinos/citologia , Intestinos/imunologia , Análise da Expressão Gênica de Célula Única
5.
Phys Rev E ; 107(5-1): 054603, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37328991

RESUMO

Colloidal spheres in weakly conductive fluids roll back and forth across the surface of a plane electrode when subject to strong electric fields. The so-called Quincke oscillators provide a basis for active matter based on self-oscillating units that can move, align, and synchronize within dynamic particle assemblies. Here, we develop a dynamical model for oscillations of a spherical particle and investigate the coupled dynamics of two such oscillators in the plane normal to the field. Building on existing descriptions of Quincke rotation, the model describes the dynamics of the charge, dipole, and quadrupole moments due to charge accumulation at the particle-fluid interface and particle rotation in the external field. The dynamics of the charge moments are coupled by the addition of a conductivity gradient, which describes asymmetries in the rates of charging near the electrode. We study the behavior of this model as a function of the field strength and gradient magnitude to identify the conditions required for sustained oscillations. We investigate the dynamics of two neighboring oscillators coupled by far field electric and hydrodynamic interactions in an unbounded fluid. Particles prefer to align and synchronize their rotary oscillations along the line of centers. The numerical results are reproduced and explained by accurate low-order approximations of the system dynamics based on weakly coupled oscillator theory. The coarse-grained dynamics of the oscillator phase and angle can be used to investigate collective behaviors within ensembles of many self-oscillating colloids.


Assuntos
Coloides , Hidrodinâmica , Rotação
6.
Cell Oncol (Dordr) ; 46(6): 1645-1658, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37261698

RESUMO

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited therapeutic options. The diversity and composition of the intratumoral microbiota are associated with PDAC outcomes, and modulating the tumor microbiota has the potential to influence tumor growth and the host immune response. Here, we explore whether intervention with butyrate-producing probiotics can limit PDAC progression. METHODS: Based on the TCGA (PAAD) database, we analyzed the differential communities of intratumoral microbiota in PDAC patients with long survival and short survival and explored the relevant mechanisms of Clostridium butyricum and its metabolite butyrate in the treatment of PDAC. Treatment with Clostridium butyricum or butyrate in combination with the ferroptosis inducer RSL3 in a PDAC mouse model has an inhibitory effect on PDAC progression. The potential molecular mechanisms were verified by flow cytometry, RNA-seq, Western blotting, qRT‒PCR and immunofluorescence. RESULTS: We found that the tumoral butyrate-producing microbiota was linked to a better prognosis and less aggressive features of PDAC. Intervention with Clostridium butyricum or its metabolite butyrate triggered superoxidative stress and intracellular lipid accumulation, which enhanced ferroptosis susceptibility in PDAC. CONCLUSION: Our study reveals a novel antitumor mechanism of butyrate and suggests the therapeutic potential of butyrate-producing probiotics in PDAC.


Assuntos
Carcinoma Ductal Pancreático , Clostridium butyricum , Ferroptose , Neoplasias Pancreáticas , Camundongos , Animais , Humanos , Butiratos/farmacologia , Butiratos/metabolismo , Clostridium butyricum/metabolismo , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas
7.
Cancer Lett ; 562: 216153, 2023 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-37023939

RESUMO

IFNγ signaling is mainly mediated through the activation of the canonical JAK-STAT signaling pathway, transcription factors, and epigenetic modifications. The activation of IFNγ signaling pathway may provide a novel option for tumor immunotherapy, but the outcomes remain controversial. In fact, recent studies suggest that the resistance to IFNγ-dependent immunotherapies is commonly derived from the tumor cell-intrinsic heterogeneity, the molecular mechanism of which remains elusive. Therefore, elucidating the tumor cell-intrinsic heterogeneity in response to IFNγ would be beneficial to improve the efficacy of immunotherapy. Here, we first delineated the epigenetic redistribution and transcriptome alteration in response to IFNγ stimulation, and demonstrated that ectopic gain of H3K4me3 and H3K27Ac at the promoter region mainly contributed to the enhancement of IFNγ-mediated transcriptional activity of interferon-stimulated genes (ISGs). Furthermore, we found that the cellular heterogeneity of PD-L1 expression in response to IFNγ was mainly attributed to cell-intrinsic H3K27me3 levels. Enhancement of H3K27me3 by GSK-J4 limited PD-L1hi tumor growth by salvaging the intratumoral cytotoxicity of CD8+ T cells, which may provide therapeutic strategies to overcome immune escape and resistance to IFNγ-based immunotherapies in pancreatic cancer.


Assuntos
Histonas , Neoplasias Pancreáticas , Humanos , Histonas/metabolismo , Antígeno B7-H1 , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Interferon gama , Epigênese Genética
8.
J Pers Med ; 13(3)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36983718

RESUMO

Pulmonary embolism (PE) is a common and potentially fatal condition in the emergency department, and early identification of modifiable risk factors for prevention and management is highly desirable. Although gut dysbiosis is associated with a high incidence of venous thromboembolism, the role and mechanisms of the gut microbiome in the pathogenesis of venous thromboembolism, especially PE, remain unexplored. Here, we attempted to elucidate the benefits of the gut microbiome in the pathogenesis of PE using multiple antibiotics and fecal microbiota transplantation (FMT) for early intervention in a classical mouse model of PE. The results showed that early administration of various antibiotics (except ampicillin) could inhibit pulmonary thrombosis to a certain extent and reduced mortality in young and old mice with PE. Among them, vancomycin has the best inhibitory effect on PE. With the help of gut microbiota sequencing analysis, we found that antibiotic treatment can reshape the gut microbiota; especially vancomycin can significantly improve the gut microbiota structure in PE mice. Furthermore, FMT could transfer vancomycin-modified gut microbes into mice and inhibit the pathogenesis of PE, possibly due to increased intestinal colonization by Parasutterella. These data elucidate the underlying molecular mechanism by which early administration of vancomycin can remodel the gut microbiota to suppress PE, providing new clues for clinical optimization and development of PE prevention strategies.

9.
Pharmacol Res ; 188: 106633, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36574857

RESUMO

The changes in gut microbiota have been implicated in colorectal cancer (CRC). The interplays between the host and gut microbiota remain largely unclear, and few studies have investigated these interplays using integrative multi-omics data. In this study, large-scale multi-comic datasets, including microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing of CRC patients, were analyzed individually and integrated through advanced bioinformatics methods. We further examined the clinical relevance of these findings in the mice recolonized with microbiota from human. We found that CRC patients had distinct microbiota compositions compared to healthy controls. A machine-learning model was developed with 28 biomarkers for detection of CRC, which had high accuracy and clinical applicability. We identified multiple significant correlations between genera and well-characterized genes, suggesting the potential role of gut microbiota in tumor immunity. Further analysis showed that specific metabolites worked as profound communicators between these genera and tumor immunity. Integrating microbiota and metabolome perspectives, we cataloged gut taxonomic and metabolomic features that represented the key multi-omics signature of CRC. Furthermore, gut microbiota transplanted from CRC patients compromised the response of CRC to immunotherapy. These phenotypes were strongly associated with the alterations in gut microbiota, immune cell infiltration as well as multiple metabolic pathways. The comprehensive interplays across multi-comic data of CRC might explain how gut microbiota influenced tumor immunity. Hence, we proposed that modifying the CRC microbiota using healthy donors might serve as a promising strategy to improve response to immunotherapy.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Humanos , Camundongos , Animais , Microbioma Gastrointestinal/genética , Neoplasias Colorretais/metabolismo , Multiômica , Fezes , Microbiota/genética
10.
Materials (Basel) ; 15(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36500016

RESUMO

Laser Powder Bed Fusion (LPBF) presents a more extensive allowable design complexity and manufacturability compared with the traditional manufacturing processes by depositing materials in a layer-wised manner. However, the process variability in the LPBF process induces quality uncertainty and inconsistency. Specifically, the mechanical properties, e.g., tensile strength, are hard to be predicted and controlled in the LPBF process. Much research has recently been reported exploring the qualitative influence of single/two process parameters on tensile strength. In fact, mechanical properties are comprehensively affected by multiple correlated process parameters with unclear and complex interactions. Thus, the study on the quantitative process-quality model of the metal LPBF process is urgently needed to provide an enough-strength component via the metal LPBF process. Recent progress in artificial intelligence (AI) and machine learning (ML) provides new insight into quality prediction in terms of computational accuracy and speed. However, the predictive model quality through the traditional AL/ML is heavily determined by the training data size, and the experimental analysis can be expansive on LPBF. This paper explores the comprehensive effect of the tensile strength of 316L stainless-steel parts on LPBF and proposes a valid quantitative predictive model through a novel self-growing machine-learning framework. The self-growing framework can autonomously expand and classify the growing dataset to provide a high-accuracy prediction with fewer input data. To verify this predictive model of tensile strength, specimens manufactured by the LPBF process with different group process parameters (laser power, scanning speed, and hatch spacing) are collected. The experimental results validate the predicted tensile strengths within a less than 3% deviation.

11.
IEEE Trans Vis Comput Graph ; 28(12): 4980-4994, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35724276

RESUMO

The rapid development of deep natural language processing (NLP) models for text classification has led to an urgent need for a unified understanding of these models proposed individually. Existing methods cannot meet the need for understanding different models in one framework due to the lack of a unified measure for explaining both low-level (e.g., words) and high-level (e.g., phrases) features. We have developed a visual analysis tool, DeepNLPVis, to enable a unified understanding of NLP models for text classification. The key idea is a mutual information-based measure, which provides quantitative explanations on how each layer of a model maintains the information of input words in a sample. We model the intra- and inter-word information at each layer measuring the importance of a word to the final prediction as well as the relationships between words, such as the formation of phrases. A multi-level visualization, which consists of a corpus-level, a sample-level, and a word-level visualization, supports the analysis from the overall training set to individual samples. Two case studies on classification tasks and comparison between models demonstrate that DeepNLPVis can help users effectively identify potential problems caused by samples and model architectures and then make informed improvements.


Assuntos
Gráficos por Computador , Processamento de Linguagem Natural
12.
Gut Microbes ; 14(1): 2046246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35259052

RESUMO

The gut microbiota was emerging as critical regulatory elements in shaping the outcome of cancer immunotherapy. However, the underlying mechanisms by which the gut commensal species enhance antitumor immunity remain largely unexplored. Here, we show that the gut microbiota from healthy individuals conferred considerable sensitivity to anti-PD-1 in the colorectal cancer (CRC) tumor-bearing mice, whereas gut microbiota from CRC patients failed to do so. By 16S rRNA gene sequencing, we identified Lactobacillus that was significantly increased in the mice with good response to anti-PD-1, and significantly correlated with anti-tumor immunity. After a series of screening, we isolated a novel Lacticaseibacillus strain, named L. paracasei sh2020. L. paracasei sh2020 showed the most notable anti-tumor immunity in the mice with gut dysbiosis. Mechanistically, the antitumor immune response elicited by L. paracasei sh2020 was dependent on CD8+ T cell. In vitro and in vivo studies revealed that L. paracasei sh2020 stimulation triggered the upregulated expression of CXCL10 in the tumors and subsequently enhanced CD8+ T cell recruitment. Meanwhile, the modulation of gut microbiota caused by L. paracasei sh2020 enhanced its antitumor effect and gut barrier function. Overall, our study offered novel insights into the mechanism by which gut microbiota shaped the outcome of cancer immunotherapy and, more importantly, the novel strain L. paracasei sh2020 might serve as an easy and effective way to promote anti-PD-1 effect in clinical practice.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Lacticaseibacillus paracasei , Probióticos , Animais , Neoplasias Colorretais/tratamento farmacológico , Humanos , Lacticaseibacillus paracasei/genética , Camundongos , Probióticos/farmacologia , Probióticos/uso terapêutico , RNA Ribossômico 16S/genética , Carga Tumoral
13.
Clin Exp Hypertens ; 44(4): 306-312, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35129024

RESUMO

OBJECTIVE: The patient of hypertension and its complication increase fast in the past years. Obesity is thought to be a risk factor for hypertension, and BMI (body mass index) is widely used to evaluate the obesity and hypertension risk. However, the abdominal obesity and visceral fat accumulation are more obvious in the East Asian population. The aim of this study was to evaluate the predictive value of fatty liver for hypertension in the Chinese population. METHOD: We compared the predictive value of BMI and fatty liver for the hypertension and its complication in 1386 patients with hypertension in Shanghai China. RESULTS: In the analysis of 1386 patients with hypertension in Shanghai China, we found that the prevalence and risk of hypertension and its complications were higher in the fatty liver group than that in the group of BMI≥24. Furthermore, the areas under the ROC curve of fatty liver for hypertension and its complications were superior to that of BMI. CONCLUSION: These results suggested that fatty liver is a more sensitive early warning for hypertension and its complication than BMI in Chinese population.


Assuntos
Fígado Gorduroso , Hipertensão , Humanos , População do Leste Asiático , China/epidemiologia , Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Fatores de Risco , Obesidade/complicações , Obesidade/epidemiologia , Índice de Massa Corporal , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia
14.
Front Pharmacol ; 13: 829796, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35153797

RESUMO

Mesoporous silica nanocarrier (MSN) preparations have a wide range of medical applications. Studying the biocompatibility of MSN is an important part of clinical transformation. Scientists have developed different types of mesoporous silica nanocarriers (MSNs) for different applications to realize the great potential of MSNs in the field of biomedicine, especially in tumor treatment. MSNs have achieved good results in diagnostic bioimaging, tissue engineering, cancer treatment, vaccine development, biomaterial application and diagnostics. MSNs can improve the therapeutic efficiency of drugs, introduce new drug delivery strategies, and provide advantages that traditional drugs lack. It is necessary not only to innovate MSNs but also to comprehensively understand their biological distribution. In this review, we summarize the various medical uses of MSN preparations and explore the factors that affect their distribution and biocompatibility in the body based on metabolism. Designing more reasonable therapeutic nanomedicine is an important task for the further development of the potential clinical applications of MSNs.

15.
Transplantation ; 106(1): 37-47, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577253

RESUMO

BACKGROUND: Toward the goal of using more livers for transplantation, transplant centers are looking to increase the use of organs from "marginal" donors. Livers from these donors, however, have been shown to be more susceptible to preservation and reperfusion injury. METHODS: Using a porcine model of donation after circulatory death, we studied the use of antibody-mediated CD47 blockade to further improve liver graft function undergoing normothermic machine perfusion. Livers from 20 pigs (5 per group) were brought under either 30 or 60 min of warm ischemia time followed by the administration of CD47 monoclonal antibody (CD47mAb) treatment or immunoglobulin G control antibodies and 6 h of normothermic extracorporeal liver perfusion. RESULTS: After 6 h of normothermic extracorporeal liver perfusion, CD47mAb-treated livers with 30 or 60 min warm ischemia time had significantly lower alanine transaminase levels and higher bile production compared with their respective control groups. Blockade of the CD47 signaling pathway resulted in significantly lower thrombospondin-1 protein levels, lower expression of caspase-3, and higher expression of phosphorylated extracellular signal-regulated kinase. CONCLUSIONS: These findings suggested that CD47mAb treatment decreases ischemia/reperfusion injury through CD47/thrombospondin-1 signaling downregulation and the presence of necrosis/apoptosis after reperfusion and could increase liver regeneration during normothermic perfusion of the liver.


Assuntos
Transplante de Fígado , Traumatismo por Reperfusão , Animais , Antígeno CD47 , Fígado , Transplante de Fígado/efeitos adversos , Preservação de Órgãos/métodos , Perfusão/efeitos adversos , Perfusão/métodos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Suínos , Isquemia Quente/efeitos adversos
16.
J Inflamm Res ; 14: 6175-6190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34853526

RESUMO

BACKGROUND: Psoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis. OBJECTIVE: We sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response. METHODS: By using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice. RESULTS: Here, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis. CONCLUSION: Our results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.

17.
Pathol Res Pract ; 228: 153666, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34749216

RESUMO

Clear cell renal cell carcinoma (ccRCC) is resistant to conventional therapy due to the deletion of the von Hippel-Lindau (VHL) gene, and novel treatment options are urgently needed. Here, using tissue microarray analysis of 445 cancer tissues and 326 adjacent normal renal tissues obtained from patients with ccRCC, we present the early growth response-1 (EGR1) protein levels are significantly decreased in ccRCC cancer tissues. Consistently, the EGR1 mRNA expression also decreased in cancer tissues based on the transcriptomic data for 599 tumor and normal samples from The Cancer Genome Atlas. Moreover, Patients with ccRCC presenting low EGR1 expression are more prone to exhibit metastasis and a poor prognosis than those with high EGR1 expression. By multivariate Cox regression analysis, EGR1 is determined to serve as an independent prognostic factor for patients with ccRCC. Further cellular biochemical function analyses show that EGR1 may inhibit proliferation, invasion and metastasis of ccRCC. These findings will deepen our understanding of EGR1 function and shed light on precise treatment for ccRCC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Proteína 1 de Resposta de Crescimento Precoce/biossíntese , Neoplasias Renais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/metabolismo , Feminino , Humanos , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
18.
Int J Biol Sci ; 17(11): 2853-2870, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34345212

RESUMO

In mammals, thermogenic organs exist in the body that increase heat production and enhance energy regulation. Because brown adipose tissue (BAT) consumes energy and generates heat, increasing energy expenditure via BAT might be a potential strategy for new treatments for obesity and obesity-related diseases. Thermogenic differentiation affects normal adipose tissue generation, emphasizing the critical role that common transcriptional regulation factors might play in common characteristics and sources. An understanding of thermogenic differentiation and related factors could help in developing ways to improve obesity indirectly or directly through targeting of specific signalling pathways. Many studies have shown that the active components of various natural products promote thermogenesis through various signalling pathways. This article reviews recent major advances in this field, including those in the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA), cyclic guanosine monophosphate-GMP-dependent protein kinase G (cGMP-AKT), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), transforming growth factor-ß/bone morphogenic protein (TGF-ß/BMP), transient receptor potential (TRP), Wnt, nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κΒ), Notch and Hedgehog (Hh) signalling pathways in brown and brown-like adipose tissue. To provide effective information for future research on weight-loss nutraceuticals or drugs, this review also highlights the natural products and their active ingredients that have been reported in recent years to affect thermogenesis and thus contribute to weight loss via the above signalling pathways.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiologia , Transdução de Sinais/fisiologia , Termogênese/fisiologia , Animais , Peso Corporal , Metabolismo Energético , Humanos , Obesidade
19.
Materials (Basel) ; 14(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361469

RESUMO

Cu-bearing age-hardening steel has significant potential in shipbuilding applications due to its excellent weldability as compared to conventional NiCrMoV steel. Not much research has been carried out to analyze the differences in the mechanisms of strength and toughness between Cu-bearing age-hardening and NiCrMoV steel. Both steels were heat treated under the same conditions: they were austenized at 900 °C and then quenched to room temperature, followed by tempering at 630 °C for 2 h. The uniaxial tensile test reveals that the Cu-bearing age-hardening steel exhibits relatively lower strength but larger plasticity than NiCrMoV steel. The lower contents of Carbon and other alloying elements is one of possible reasons for these differences in mechanical properties. Transmission Electron Microscope observations show that two types of precipitates, Cr carbides and Cu-rich particles, exist in tempered Cu-bearing age-hardening steel. Cu-rich particles with sizes of 20-40 nm can inhibit the dislocation motion during deformation, which then results in dislocation pile ups and multiplication; this makes up the strength loss of Cu-bearing age-hardening steel and simultaneously improves its plasticity.

20.
Gut Microbes ; 13(1): 1949095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34313539

RESUMO

Farnesoid X receptor (FXR) is a nuclear receptor for bile acids (BAs) that is widely expressed in the intestine, liver and kidney. FXR has important regulatory impacts on a wide variety of metabolic pathways (such as glucose, lipid, and sterol metabolism) and has been recognized to ameliorate obesity, liver damage, cholestasis and chronic inflammatory diseases. The types of BAs are complex and diverse. BAs link the intestine with the liver through the enterohepatic circulation. BAs derivatives have entered clinical trials for liver disease. In addition to the liver, the intestine is also targeted by BAs. This article reviews the effects of different BAs on the intestinal tract through the enterohepatic circulation from the perspective of FXR, aiming to elucidate the effects of different BAs on the intestinal tract and lay a foundation for new treatment methods.


Assuntos
Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/farmacocinética , Ácidos e Sais Biliares/uso terapêutico , Circulação Êntero-Hepática/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Enteropatias/tratamento farmacológico , Intestinos/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Humanos
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