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1.
J Autoimmun ; 132: 102867, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35932662

RESUMO

Gut commensals help shape and mold host immune system and deeply influence human health. The disease spectrum of mankind that gut microbiome may associate with is ever-growing, but the mechanisms are still enigmas. Characterized by loss of self-tolerance and sustained self-attack, systemic lupus erythematosus (SLE) is labeled with chronic inflammation, production of autoantibodies and multisystem injury, which so far are mostly incurable. Gut microbiota and their metabolites, now known as important environmental triggers of local/systemic immune responses, have been proposed to be involved in SLE development and progression probably through the following mechanisms: translocation beyond their niches; molecular mimicry to cross-activate immune response targeting self-antigens; epitope spreading to expand autoantibodies spectrum; and bystander activation to promote systemic inflammation. Gut microbiota which varies between individuals may also influence the metabolism and bio-transformation of disease-modifying anti-rheumatic drugs, thus associated with the efficacy and toxicity of these drugs, adding another explanation for heterogenic therapeutic responses. Modulation of gut microbiota via diet, probiotics/prebiotics, antibiotics/phages, fecal microbiota transplantation, or helminth to restore immune tolerance and homeostasis is expected to be a promising neoadjuvant therapy for SLE. We reviewed the advances in this territory and discussed the application prospect of modulating gut microbiota in controlling SLE.

2.
PLoS One ; 17(7): e0269102, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35900973

RESUMO

Avian pathogenic Escherichia coli (APEC), which has potential zoonotic risk, can cause severe systemic infections such as septicemia and meningitis in poultry. Colibactin is a hybrid non-ribosomal peptide/polyketide secondary metabolite produced by bacteria, which induces double-strand DNA breaks and chromosome instability in eukaryotic cells. ClbA is a 4'-phosphopantetheinyl transferase (PPTase) that is essential for colibactin and plays a role in siderophore synthesis. However, whether ClbA is associated with meningitis development in APEC is unclear. In this study, we abolished the clbA gene in the APEC XM strain, investigated the effect of clbA on colibactin synthesis and evaluated the pathogenic capacity of colibactin on meningitis development. Deletion of clbA reduced DNA damage to cells and hindered the normal synthesis of colibactin. Compared with the mice infected by wild-type APEC XM, the clbA deletion mutant infected mice had significant reduction in a series of characteristics associated with meningitis including clinical symptoms, bacterial loads of blood and brain, disruption of the blood brain barrier and the expression of inflammatory factors in the brain tissue. Complementation of ClbA recovered some APEC XM virulence. We conclude that ClbA is obligatory for the synthesis of colibactin and is responsible for the development of meningitis in mice infected by APEC.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Meningite , Doenças das Aves Domésticas , Animais , Proteínas de Bactérias , Aves/metabolismo , Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/metabolismo , Camundongos , Doenças das Aves Domésticas/microbiologia , Transferases (Outros Grupos de Fosfato Substituídos) , Virulência/genética , Fatores de Virulência/metabolismo
3.
Front Neurol ; 13: 864563, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756925

RESUMO

Objective: This study was conducted to determine the safety and efficacy of the Esperance® Distal Access Catheter (0.071"), a novel large bore aspiration catheter in treating acute ischemic stroke (AIS) with large vessel occlusion (LVO). Methods: A prospective multicenter clinical trial involving 15 stroke centers was performed. Baseline characteristics, procedural data, and angiographic and clinical outcomes of all acute stroke procedures (from May 2020 to March 2021) using the novel large bore aspiration catheter were analyzed. Results: During the study period, 160 consecutive patients were recruited. The mean age and median baseline NIHSS were 65.4 years and 16, respectively. Successful reperfusion was achieved in 147 (91.9%) cases [at least modified Thrombolysis in Cerebral Infarction (mTICI) 2b] with aspiration alone, with complete reperfusion (mTICI 3) in 94 (58.8%) cases. Successful/complete first pass reperfusion was achieved in 104 (64.60%) cases, including mTICI 2b in 34 (21.1%) cases and mTICI 3 in 70 (43.5%) cases. The time from groin puncture to successful reperfusion was 44 (33, 62) min. There were 16 (9.9%) cases requiring rescue therapy using stent-retriever. Procedure-related complications included 2 (1.3%) cases of arterial perforation, 2 (1.3%) cases of arterial dissection, 12 (7.5%) cases of distal embolization, and 1(0.6%) case of puncture site infection. The rate of symptomatic intracranial hemorrhage (sICH) was 3.8% and mortality rate was 13.8%. A total of 99 (62.3%) cases had a favorable outcome (mRS 0-2) at 90 days. Conclusions: In current practice, the first-line aspiration approach with the Esperance® Distal Access Catheter is safe and efficacious. This device may achieve high reperfusion rates with lower instances of rescue stent retriever therapy.

4.
Transl Stroke Res ; 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35759064

RESUMO

The relevance of impaired microvascular tissue reperfusion despite successful macrovascular angiographic reperfusion (no-reflow) in acute ischemic stroke (AIS) remains controversial. In this study, we aimed to investigate the impact of tissue optimal reperfusion (TOR) and its influencing factors. From December 1, 2020 to December 1, 2021, AIS patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score [mTICI] ≥ 2b) after mechanical thrombectomy (MT) were retrospectively reviewed. Computed tomography perfusion was performed before and after MT. Successful reperfusion was assessed by TOR, defined as > 90% reduction of the Tmax > 6 s lesion volumes between baseline and early follow-up perfusion profiles. The impact of TOR on functional outcomes after successful recanalization and influencing factors for TOR were both investigated. Sixty-three patients were included, including 44 cases in the TOR group and 19 cases in the non-TOR group. The TOR group had a higher rate of favorable outcome (aOR 4.366, 95%CI 1.159-16.445, p = 0.030) and NIHSS improvement (aOR 5.089, 95%CI 1.340-19.322, p = 0.017) than the non-TOR group. Multivariable logistic regression showed baseline glucose (OR 0.648, 95%CI 0.492-0.854, p = 0.002) and mTICI 2c/3 (OR 10.984, 95%CI 2.220-54.343, p = 0.003) predicted TOR in model 1; in model 2, postoperative glucose (OR 0.468, 95%CI 0.278-0.787, p = 0.004) and mTICI 2c/3 (OR 9.436, 95%CI 1.889-47.144, p = 0.006) were predictive. TOR was strongly associated with good functional outcomes after successful recanalization of MT. Higher mTICI grade and lower perioperative glucose level may predict microvascular tissue reperfusion.

5.
Front Pharmacol ; 13: 813682, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517815

RESUMO

Background: Tuberculosis drug-induced liver injury (TB-DILI) is a common and potentially severe adverse drug reaction leading to treatment interruption and treatment failure. The real-world preventive effectiveness of hepatoprotective agents for DILI is not well described. The aim of the study was to evaluate the patterns of prophylactic therapies in real-world settings and risks of DILI among adult TB patients without known risk factors for DILI. Methods: This is a population-based retrospective cohort study of patients receiving first-line anti-tuberculosis drugs in the Chinese Center for Disease Control and Prevention (CDC) TB registry linked to the Ningbo Regional Health Care Database (NRHCD) between 2015 and 2020. The primary exposure was any use of chemopreventive agents including silymarin and/or glycyrrhetinic acid during the 30-day period prior to TB diagnosis (index date). The main outcome measure was the occurrence of newly onset DILI following TB treatment. Eligible patients were followed until the earliest of any DILI, treatment discontinuation, death, or end of the study period (30 June 2020). Marginal structural competing risk models and Cox models via inverse probability treatment weights using high-dimensional propensity scores were used to estimate subdistribution hazard risks (SHR) and 95% confidence intervals (CIs) for DILI risks, with adjustment for age, sex, TB-related characteristics, and comorbidities. Results: We identified a cohort of 6,743 adult patients with TB (mean age of 47.1 [SD 18.7] years; 65.80% male), of whom 2,886 (42.8%) patients received hepatoprotective agents. A total of 895 DILI events and 111 all-cause death events without DILI were observed over a median follow-up of 367 days post-TB diagnosis. The incidence rates of composite outcomes combining DILI and all-cause mortality were 248.9 and 222.3 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.35, 95% CI 1.11-1.64), respectively. The incidence rates of DILI were 223.7 and 196.1 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.38, 95% CI 1.12-1.71), respectively. Patients with any chemopreventive agent use had comparable liver function changes as evidenced by laboratory tests. Conclusion: A non-trivial number of adult patients received chemopreventive agents for TB-DILI. However, prophylactic utilization of hepatoprotective agents was not associated with a reduction in TB-DILI risks.

6.
Front Cell Infect Microbiol ; 12: 853212, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493744

RESUMO

Background: SARS-CoV-2 is highly contagious and poses a great threat to epidemic control and prevention. The possibility of fecal-oral transmission has attracted increasing concern. However, viral shedding in feces has not been completely investigated. Methods: This study retrospectively reviewed 97 confirmed coronavirus disease 2019 (COVID-19) patients hospitalized at the First Affiliated Hospital, School of Medicine, Zhejiang University, from January 19 to February 17, 2020. SARS-CoV-2 RNA in samples of sputum, nasopharyngeal or throat swabs, bronchoalveolar lavage and feces was detected by real-time reverse transcription polymerase chain reaction (RT-PCR). Clinical characteristics and parameters were compared between groups to determine whether fecal RNA was positive. Results: Thirty-four (35.1%) of the patients showed detectable SARS-CoV-2 RNA in feces, and 63 (64.9%) had negative detection results. The median time of viral shedding in feces was approximately 25 days, with the maximum time reaching 33 days. Prolonged fecal-shedding patients showed longer hospital stays. Those patients for whom fecal viral positivity persisted longer than 3 weeks also had lower plasma B-cell counts than those patients in the non-prolonged group [70.5 (47.3-121.5) per µL vs. 186.5 (129.3-376.0) per µL, P = 0.023]. Correlation analysis found that the duration of fecal shedding was positively related to the duration of respiratory viral shedding (R = 0.70, P < 0.001) and negatively related to peripheral B-cell counts (R = -0.44, P < 0.05). Conclusions: COVID-19 patients who shed SARS-CoV-2 RNA in feces presented similar clinical characteristics and outcomes as those who did not shed SARS-CoV-2 RNA in feces. The prolonged presence of SARS-CoV-2 nucleic acids in feces was highly correlated with the prolonged shedding of SARS-CoV-2 RNA in the respiratory tract and with lower plasma B-cell counts.


Assuntos
COVID-19 , RNA Viral , COVID-19/diagnóstico , Fezes/química , Humanos , RNA Viral/genética , Estudos Retrospectivos , SARS-CoV-2/genética
7.
Front Neurol ; 13: 803224, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493822

RESUMO

Introduction: Intracranial atherosclerotic disease (ICAD) is one of the most important etiologies of ischemic stroke, especially in Asia. Although medical treatment was recommended as the first-line therapy for ICAD, the recurrent stroke rate was still high in severe stenosis of ICAD despite aggressive medical treatment. Traditionally, the degree of luminal stenosis is used as the principal index for stroke risk stratification in patients with ICAD, while recent evidence suggested that symptomatic atherosclerotic plaques were characterized by plaque features and hemodynamics. This prospective, longitudinal, and nested case-control study aims to identify multimodal imaging predictors of high-risk patients with ICAD refractory to medical treatment and explore a refined risk stratification model based on the above multimodal imaging predictors. Methods: This prospective, longitudinal, and nested case-control study includes 400 symptomatic patients with ICAD with 50-99% of stenosis treated with aggressive medical therapy. All patients who meet the eligibility criteria are assessed by multimodal imaging examination from three aspects, including lumen stenosis, plaque characteristics, and hemodynamic features. The enrolled patients receive aggressive medical management, including antiplatelet therapy and cardiovascular risk control. The primary outcome is ischemic stroke or death attributable to the lesion of the target vessel within 1 year. The secondary endpoints are (1) any stroke or death; (2) all-cause mortality; (3) any stroke out of the territory of the responsible lesion; (4) functional outcome with the modified Rankin Scale (mRS). Ethics and Dissemination: This study has been approved by the ethics committee of our center ([2021]083) and has been prospectively registered (Registration No: ChiCTR2100048832). Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings.

8.
Food Chem ; 387: 132742, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35398677

RESUMO

In this study, free phytosterols and phytosterol glycosides in rice bran were successfully separated and analyzed using solid-phase extraction (SPE) combined with gas chromatography-mass spectrometry (GC-MS). The results showed that free phytosterols in rice bran included ergosterol (129 ± 8 µg/g rice bran), campesterol (126 ± 9 µg/g rice bran), stigmasterol (106 ± 9 µg/g rice bran), ß-sitosterol (305 ± 10 µg/g rice bran), cycloartenol (80.5 ± 3.9 µg/g rice bran) and 24-methylenecycloartenol (87.1 ± 2.2 µg/g rice bran), while phytosterol glycosides included campesterol glucoside (16.0 ± 1.3 µg/g rice bran), stigmasterol glucoside (99.0 ± 4.9 µg/g rice bran) and ß-sitosterol glucoside (133 ± 7 µg/g rice bran). The methodological validation indicated that this method could accurately quantify free phytosterols and phytosterol glycosides in rice bran. This study provided a new direction to establish a rapid and simple method for the simultaneous determination of different forms of phytosterols in foods.


Assuntos
Oryza , Fitosteróis , Cromatografia Gasosa-Espectrometria de Massas , Glicosídeos , Oryza/química , Fitosteróis/análise , Extração em Fase Sólida
9.
Artigo em Inglês | MEDLINE | ID: mdl-35469706

RESUMO

OBJECTIVES: Although the cause of Meniere's disease (MD) is not fully understood, endolymphatic hydrops is widely believed to be responsible for MD. Previous studies have used Air-Conducted Sound (ACS)-induced Vestibular Evoked Myogenic Potentials (VEMPs) to evaluate otolithic function in patients with MD. However, the use of Galvanic Vestibular Stimulation-VEMPs (GVS-VEMPs) with other vestibular tests in MD has been rare. This study aimed to explore the application of galvanic VEMPs in assessing MD. METHODS: Normal individuals and patients with unilateral definite MD were included in this retrospective study. All participants underwent pure tone audiometry. Ocular and cervical VEMPs induced by GVS, and ACS were recorded. The characteristic parameters of VEMPs (n1 latency, p1 latency, amplitude, and AR) were analyzed. RESULTS: The provocation rates of GVS-VEMPs did not differ between MD patients and control individuals. Compared with ACS, GVS could evoke potentials with longer latencies. MD patients presented GVS-VEMPs with lower amplitudes and ACS-cVEMP with shorter latencies and had a higher response rate in GVS-oVEMP. However, no differences or correlations were found in the characteristic parameters of GVS-VEMPs among the different stages of MD. CONCLUSIONS: GVS is as effective as ACS for inducing VEMP, and GVS-VEMP recording can detect retrolabyrinthine degeneration in MD. Further research is needed to assess the utility of GVS-VEMP in the evaluation of MD severity. LEVEL OF EVIDENCE: Level 4.

10.
Polymers (Basel) ; 14(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35458344

RESUMO

In the past few years, biomass carbon materials have gained wide attention from many scholars as TiO2 carrier materials to improve photocatalytic activity due to their renewable, green, low-cost, and high-efficiency advantages. In this study, TiO2/carbonized waste rabbit fibers (TiO2/CRFs) nanocomposites with the hierarchical microporous/mesoporous structure were fabricated by a combination of carbonization, immersion, and calcination methods using tetrabutyl titanate as the titanium source and waste rabbit hair as the carbon source. The properties and catalytic activity of TiO2/CRFs composite were evaluated based on several characterization techniques and methylene blue (MB) photodegradation studies. The results showed that the degradation of MB by TiO2/CRFs could reach 98.1% after 80 min of solar irradiation. Moreover, TiO2/CRFs still maintained high photocatalytic activity after five cycles of degradation tests, exhibiting good stability and reusability. The improved photocatalytic performance of TiO2/CRFs materials is attributed to the natural carbon and nitrogen element doping of TiO2/CRFs and its morphology, which reduces the compounding of photogenerated electron-hole pairs and narrows the TiO2 band gap, while the multiple reflections of visible light in the pore channels enhance the visible light absorption of the materials. Furthermore, the large specific surface area provides abundant reaction sites for adsorbed reactants. This paper provides the experimental basis for the application of waste rabbit biomass carbon composites in photocatalytic degradation field.

11.
Br J Anaesth ; 128(5): 785-795, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35249707

RESUMO

BACKGROUND: The pathophysiological mechanisms by which venous congestion and hypotension lead to acute adverse kidney events after cardiac surgery with cardiopulmonary bypass have not been elucidated. We tested the hypothesis that intraoperative hypotension and venous congestion are associated with acute kidney injury and acute kidney disease. METHODS: Primary exposures were venous congestion and intraoperative hypotension defined by central venous pressure ≥12, 16, or 20 mm Hg or mean arterial pressure ≤55, 65, or 75 mm Hg. The primary outcomes were acute kidney injury and acute kidney disease. Multivariable logistic regression and Cox proportional hazard models were used, adjusted for relevant confounding factors and multiple comparisons. RESULTS: Of 5127 eligible subjects, 1070 (20.9%) and 327 (7.2%) developed acute kidney injury and acute kidney disease, respectively. The occurrence of acute kidney injury was statistically associated with both venous congestion and intraoperative hypotension. The cumulative incidence rate for new onset acute kidney disease was 1.34 (95% confidence interval [CI], 1.21-1.60) per 100 person-days. Acute kidney disease was significantly associated with each 10 min epoch of central venous pressure ≥12 mm Hg (hazard ratio [HR]=1.03; 99% CI, 1.01-1.06; P<0.001), ≥16 mm Hg (HR=1.04; 99% CI, 1.01-1.07; P<0.001), and ≥20 mm Hg (HR=1.07; 99% CI, 1.02-1.13; P<0.001). Venous congestion was associated with an 8-17% increased risk for de novo renal replacement therapy. In contrast, intraoperative hypotension was not associated with development of acute kidney disease. CONCLUSION: Although both venous congestion and intraoperative hypotension are associated with acute kidney injury, only venous congestion correlates with acute kidney disease among patients undergoing cardiac surgery requiring cardiopulmonary bypass. The reported associations are suggestive of a pathophysiological role of venous congestion in acute kidney disease.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Hiperemia , Hipotensão , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Feminino , Humanos , Hiperemia/etiologia , Rim , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco
12.
Front Oncol ; 12: 775238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251963

RESUMO

Radiotherapy exerts a crucial role in curing cancer, however, its treatment efficiency is mostly limited due to the presence of radioresistance. Epithelial-to-mesenchymal transition (EMT) is a biological process that endows the cancer cells with invasive and metastatic properties, as well as radioresistance. Many potential mechanisms of EMT-related radioresistance being reported have broaden our cognition, and hint us the importance of an overall understanding of the relationship between EMT and radioresistance. This review focuses on the recent progresses involved in EMT-related mechanisms in regulating radioresistance, irradiation-mediated EMT program, and the intervention strategies to increase tumor radiosensitivity, in order to improve radiotherapy efficiency and clinical outcomes of cancer patients.

13.
Endocr Connect ; 11(4)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35258485

RESUMO

Objective: The objective of this study is to investigate the role of serum irisin level in diagnosis of central precocious puberty (CPP) in girls and its major determinants. Methods: This study was conducted in 67 girls with CPP, 19 girls with premature thelarche (PT) and 59 normal controls. The major determinants of irisin were assessed by multivariate linear regression (MLR) analysis. Propensity score matching (PSM) analysis was performed to minimize the bias that can result from BMI. A receiver operating characteristic curve was used to obtain the optimal threshold value of irisin. Results: The girls with CPP and PT had higher irisin levels than controls (P < 0.05). The optimal cutoff value of irisin levels for predicting CPP was 91.88 ng/mL, with a sensitivity of 70.1% and a specificity of 72.9%. MLR analysis showed that BMI was a predictor of irisin (P < 0.05). Serum irisin levels remained higher in the CPP girls than the controls with adjustment for BMI (P < 0.05). Conclusions: Increased serum irisin levels with CPP suggest that irisin is involved in puberty. However, due to low sensitivity and specificity, irisin level can only be used as an auxiliary indicator rather than a single diagnostic indicator of CPP.

14.
Arch Insect Biochem Physiol ; 110(1): e21876, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35220618

RESUMO

A G-quadruplex (G4) was identified in the promoter of transcription factor BmPOUM2 in Bombyx mori. This G4 structure contains three loops and is bound by transcription factor BmLARK, facilitating the transcription of BmPOUM2. However, the relationship between the structure and function of the BmPOUM2 G4 remains to be clarified. In this study, loop mutants of the BmPOUM2 G4 structure were generated to study the function of the structure in transcription regulation. The results revealed that mutations of Loops A and B could not completely suppress G4 formation, but affected the binding of the G4 structure with BmLARK and the promoter activity. The mutation (C-to-T) of the one-nucleotide-loop, Loop C, enhanced the G4 formation, its binding with BmLARK and the transcription activity of the BmPOUM2 promoter. It is speculated that the binding site of BmLARK probably is on the G-quartet planes, rather than on the loops, which may assist the maintenance and modification of the G4 structure and its protein binding activity.


Assuntos
Bombyx , Animais , Bombyx/metabolismo , Proteínas de Insetos/metabolismo , Mutação , Ligação Proteica , Fatores de Transcrição/genética
15.
Stem Cell Res Ther ; 13(1): 57, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-35123555

RESUMO

BACKGROUND: Cholestatic liver injury can lead to serious symptoms and prognoses in the clinic. Currently, an effective medical treatment is not available for cholestatic liver injury. Human menstrual blood-derived stem cells (MenSCs) are considered as an emerging treatment in various diseases. This study aimed to explore the treatment effect of MenSCs in cholestatic liver injury. METHODS: The treatment effect of MenSCs on chronic cholestatic liver injury was verified in 3,5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC)-induced C57/BL6 mice. Pathological, fibrosis area in the liver tissue and serum liver enzymes were tested. Proteomics and western blot were used to explore the related targets and molecular mechanisms. Adeno-associated virus (AAV) 9-infected mice were applied for verification. RESULTS: MenSCs markedly improved the survival rate of the DDC-treated mice (60% vs. 100%), and decreased the mouse serum aspartate aminotransferase (AST) (169.4 vs. 108.0 U/L, p < 0.001), alanine aminotransferase (ALT) (279.0 vs. 228.9 U/L, p < 0.01), alkaline phosphatase (ALP) (45.6 vs. 10.6 U/L, p < 0.0001), direct bilirubin (DBIL) (108.3 vs. 14.0 µmol/L, p < 0.0001) and total bilirubin (TBIL) (179.2 vs. 43.3 µmol/L, p < 0.0001) levels as well as intrahepatic cholestasis, bile duct dilation and fibrotic areas (16.12 vs. 6.57%, p < 0.05). The results further indicated that MenSCs repaired the DDC-induced liver tight junction (TJ) pathway and bile transporter (OATP2, BSEP and NTCP1) injury, thereby inhibiting COL1A1, α-SMA and TGF-ß1 activation by upregulating liver ß-catenin expression. CONCLUSIONS: MenSC transplantation could be an effective treatment method for cholestatic liver injury in mice. MenSCs may exhibit therapeutic effects by regulating ß-catenin expression.


Assuntos
Colestase , Fígado , Animais , Ductos Biliares , Células Sanguíneas , Colestase/terapia , Humanos , Fígado/metabolismo , Menstruação , Camundongos , Transplante de Células-Tronco
16.
Cancer Cell Int ; 22(1): 38, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35078458

RESUMO

BACKGROUND: The tumour heterogeneous make-up of immune cell infiltrates is a key factor for the therapy response and prognosis of hepatocellular carcinoma (HCC). However, it is still a major challenge to comprehensively understand the tumour immune microenvironment (TIME) at the genetic and cellular levels. METHODS: HCC single-cell RNA sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database, and gene expression data were retrieved from The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was performed to evaluate the abundance of immune infiltrating cells. We employed weighted gene coexpression network analysis (WGCNA) to construct a gene coexpression network. Univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were further used to construct a risk model. Moreover, the expression levels of model genes were assessed by qPCR. RESULTS: We defined 25 cell clusters based on the scRNA-seq dataset (GSE149614), and the clusters were labelled as various cell types by marker genes. Then, we constructed a weighted coexpression network and identified a total of 6 modules, among which the brown module was most highly correlated with tumours. Moreover, we found that the brown module was most closely related to monocytes (cluster 21). Through univariate Cox and LASSO analyses, we constructed a 3-gene risk model (RiskScore = 0.257*Expression CSTB + 0.263* Expression TALDO1 + 0.313* Expression CLTA). This risk model showed excellent predictive efficacy for prognosis in the TCGA-LIHC and ICGC cohorts. Additionally, patients with high risk scores were found to be less likely to benefit from immunotherapy. CONCLUSIONS: We developed a 3-gene signature (including CLTA, TALDO1 and CSTB) based on the heterogeneity of the TIME to predict the survival outcome and immunotherapy response.

18.
Mol Ther Nucleic Acids ; 26: 927-944, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760337

RESUMO

The circRNAs, a new subclass of non-coding RNAs that are catalyzed by RNA-binding proteins (RBPs), have been reported to be associated with the progression of multiple types of cancer. We previously discovered that heterogeneous nuclear ribonucleoprotein L (HnRNP-L), a multi-functional RBP, is associated with pro-proliferation and anti-apoptosis activities in prostate tumor cells. In this study, we aim to establish the biological relevance of circCSPP1 (a newly discovered signature circRNA in prostate cancer [PCa]) and HnRNP-L to prostate cancer progression. First, we demonstrated that circCSPP1 expression was higher in prostate cancer tissues than in benign tissues and higher in prostate cancer cells than in benign cells. Then, the in vitro gain- and loss-of-function experiments showed that the circCSPP1 expression in prostate cancer cells was regulated by HnRNP-L, and the increased circCSPP1 significantly induced autophagy, which led to an enhanced potential in proliferation, migration, and invasion of prostate cancer cells. These results were consistent with the in vivo experiment where increased or decreased circCSPP1 was associated with higher or slower growth rate in grafted tumors. Finally, we demonstrated the potential competing endogenous RNA network, involving circCSPP1, miR-520h, and early growth response factor 1 (EGR1), in prostate cancer cells, which may play an important role in prostate cancer progression. Our study indicated that the increase in circCSPP1 in prostate cancer, which may be catalyzed by HnRNP-L, can induce cellular autophagy through the circCSPP1-miR-520h-EGR1 axis, leading to the progression of prostate tumor. This newly discovered circRNA biomarker may be used for clinical prognosis of prostate cancer as well as for development of novel therapy plans.

19.
Materials (Basel) ; 14(21)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34772208

RESUMO

Since the commercial applications of rare earth magnesium alloys are increasing gradually, there are considerable advantages to developing lower cost and higher performance magnesium alloys with high abundance rare earth (RE) elements. However, the alloying order of a matrix magnesium alloy is completely changed with the addition of RE elements. Therefore, further study of the strengthening mechanism of Ce element in magnesium alloys is required. In this work, the thermodynamic stability of the possible second phases in a Mg-Al-Mn-Ce multicomponent magnesium alloy were analyzed, based on first-principle calculations, and the precipitation sequence of the key RE phases was deduced as a consequence. Combined with Scanning Electron Microscope (SEM), X-ray Diffractometer (XRD), Energy Dispersive Spectrometer (EDS), and other experimental methods, it was investigated whether the preferentially precipitated second phases were the nucleation core of primary α-Mg. The complex alloying problem and strengthening mechanism in a multi-elemental magnesium alloy system were simplified with the aid of electronegativity theory. The results showed that the preferentially precipitated Al11Ce3 and Al10Ce2Mn7 phases could not be the nucleation core of primary α-Mg, and the grain refinement mechanism was such that the second phases at the grain boundary prevented the growth of magnesium grains. Moreover, the tensile test results showed that the reinforced structure, in which the Al-Ce phase was mixed with Mg-Al phase, was beneficial for improving the mechanical properties of magnesium alloys, at both ambient temperature and high temperature.

20.
Vet Microbiol ; 263: 109273, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763144

RESUMO

Meningitis associated with avian pathogenic Escherichia coli (APEC) is an infectious disease of poultry that has gained significant attention because of its potential to infect humans. APEC can utilize two type Ⅵ secretion systems (T6SSs) to efficiently transport toxin effectors into hosts. ClpV1 is one of the core components of the T6SS1. To our knowledge, it has not been clarified how the clpV1 gene contributes to the pathogenicity of meningitis-associated APEC. To investigate the function of the clpV1 gene in the process of Escherichia coli meningitis, a mutant TW-XMΔclpV1 strain was constructed and characterized. In this study, the clpV1 deleted strain displayed a significant decrease in both motility and biofilm formation as well as a reduction in the expression of virulence genes fliC, luxS and ibeA. In vivo studies using mouse and duck models found that the clpV1 deleted groups showed decreased proliferation, fewer lesions and lower expression of inflammatory cytokines in the brain suggesting that clpV1 is involved in the pathogenicity of TWXM. Besides, the decreased quantity of Evans Blue (EB) and the down-regulation of tight junctions (TJs) proteins in the mouse clpV1 deleted group demonstrating a more intact blood-brain barrier (BBB). In conclusion, these results suggest that the clpV1 gene is associated with motility and biofilm formation of TWXM strain and contributes to meningitis by damaging the BBB and brain tissues.


Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli , Meningite , Doenças das Aves Domésticas , Fatores de Virulência , Animais , Galinhas , Modelos Animais de Doenças , Escherichia coli/genética , Escherichia coli/patogenicidade , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Meningite/microbiologia , Meningite/veterinária , Camundongos , Doenças das Aves Domésticas/microbiologia , Fatores de Virulência/genética
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