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1.
Hepatology ; 77(5): 1612-1629, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36098707

RESUMO

BACKGROUND AND AIMS: Monocyte-derived macrophages (MoMFs), a dominant population of hepatic macrophages under inflammation, play a crucial role in liver fibrosis progression. The spleen serves as an extra monocyte reservoir in inflammatory conditions; however, the precise mechanisms of involvement of the spleen in the pathogenesis of liver fibrosis remain unclear. APPROACH AND RESULTS: By splenectomy and splenocyte transfusion, it was observed that splenic CD11b + cells accumulated intrahepatically as Ly6C lo MoMFs to exacerbate CCl 4 -induced liver fibrosis. The splenocyte migration into the fibrotic liver was further directly visualized by spleen-specific photoconversion with KikGR mice and confirmed by CD45.1 + /CD45.2 + spleen transplantation. Spleen-derived CD11b + cells purified from fibrotic livers were then annotated by single-cell RNA sequencing, and a subtype of CD11b + CD43 hi Ly6C lo splenic monocytes (sM-1s) was identified, which was markedly expanded in both spleens and livers of mice with liver fibrosis. sM-1s exhibited mature feature with high expressions of F4/80, produced much ROS, and manifested preferential migration into livers. Once recruited, sM-1s underwent sequential transformation to sM-2s (highly expressed Mif , Msr1 , Clec4d , and Cstb ) and then to spleen-derived macrophages (sMφs) with macrophage features of higher expressions of CX 3 CR1, F4/80, MHC class II, and CD64 in the fibrotic hepatic milieu. Furthermore, sM-2s and sMφs were demonstrated capable of activating hepatic stellate cells and thus exacerbating liver fibrosis. CONCLUSIONS: CD11b + CD43 hi Ly6C lo splenic monocytes migrate into the liver and shift to macrophages, which account for the exacerbation of liver fibrosis. These findings reveal precise mechanisms of spleen-liver axis in hepatic pathogenesis and shed light on the potential of sM-1 as candidate target for controlling liver diseases.


Assuntos
Macrófagos , Baço , Camundongos , Animais , Baço/patologia , Macrófagos/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Monócitos/metabolismo , Camundongos Endogâmicos C57BL
2.
J Asthma ; 61(3): 212-221, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37738216

RESUMO

OBJECTIVE: While linear regression and LASSO models have been established for predicting in-hospital mortality, there is currently no validated clinical prediction algorithm to predict in-hospital mortality for patients with chronic obstructive pulmonary disease (COPD) exacerbations using machine learning. Thus, we will evaluate the BAP-65 and CURB-65, and construct a novel prediction model using the random forest (RF) technique. METHODS: A dataset of 1,418 patients with COPD exacerbations was collected. Age, gender, mental status, vital signs, and laboratory results were all taken into account for predictors. The categorical outcome variable was hospital-based mortality of people over 65 years. The dataset was divided randomly into a training dataset (70%) and a testing dataset (30%). We trained three prediction models, BAP-65, CURB-65, and the RF model, estimated the area under the receiver operating characteristic curve (AUROC) for the entire dataset. We also conducted a comparison of the AUROC values using the Delong test. RESULTS: A total of 658 individuals with COPD acute exacerbations were enrolled. Our analysis using the receiver operating characteristic curve demonstrated that the RF model exhibited excellent performance, with an AUROC of 0.80 (95% confidence interval: 0.75-0.84). In comparison, the BAP-65 prediction model yielded an AUROC of 0.72 (0.68-0.75), while the CURB-65 prediction model achieved an AUROC of 0.69 (0.67-0.73). CONCLUSIONS: The RF model demonstrated superior predictive capabilities than the BAP-65 and CURB-65 models in predicting in-hospital mortality. The results further highlighted significant factors for predicting in-hospital mortality, including blood eosinophil count, systolic blood pressure, and prior history of asthma.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Mortalidade Hospitalar , Curva ROC , Aprendizado de Máquina
3.
Oncologist ; 28(8): e591-e599, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-36929946

RESUMO

BACKGROUND: For patients with cN0 and T1-2 breast cancer, sentinel lymph node biopsy (SLNB) can provide survival results equivalent to axillary lymph node dissection (ALND). However, whether it can be performed on T3-4c patients is still controversial. MATERIALS AND METHODS: Female patients diagnosed with cN0, T3-4c, and M0 breast cancer from 2004 to 2019 were identified using the surveillance, epidemiology and end results (SEER) database and divided into 2 groups, the SLNB group (1-5 regional lymph nodes examined) and the ALND group (≥10 regional lymph nodes examined). Finally, only those with pN0 disease were included in the SLNB group. The baseline differences in clinicopathological characteristics between groups were eliminated by propensity score matching (PSM). We also conducted subgroup analyses according to age, overall TNM stage, breast cancer subtypes, surgical approaches, radiation therapy, and chemotherapy. The primary endpoint was survival. RESULTS: With a mean follow-up of 75 months, a total of 186 deaths were reported among 864 patients. The overall survival (OS) and breast cancer-specific survival (BCSS) in the SLNB group were 78.2% and 87.5%, respectively, and that in the ALND group were 78.7% and 87.3%, respectively. The unadjusted hazard ratio (HR) for OS and BCSS in the SLNB group (vs. the ALND group) was 0.922 (95% CI, 0.691-1.230, P = .580) and 0.874 (95% CI, 0.600-1.273, P = .481), respectively. Besides, the OS and BCSS between the 2 groups were also similar in all subgroup analyses. CONCLUSIONS: SLNB may be performed on female patients with cN0, T3-4c, and M0 breast cancer.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Biópsia de Linfonodo Sentinela/métodos , Neoplasias da Mama/patologia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Excisão de Linfonodo/métodos , Linfonodos/patologia , Axila/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia
4.
Small ; 19(25): e2301579, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36919785

RESUMO

A highly efficient g-C3 N4 photocatalyst is developed by a novel one-pot thermal polymerization method under a salt fog environment generated by heating the aqueous solution of urea and mixed metal salts of NaCl/KCl, namely SF-CN. Thanks to the synergistic effect of the oxygenation and chemical etching of the salt fog, the obtained SF-CN is an oxygenated ultrathin porous carbon nitride with an intermolecular triazine-heptazine heterostructure, meanwhile, shows enlarged specific surface area, greatly enhanced absorption of visible light, narrowed band gap with a lower conduction band, and an increased photocurrent response due to the effective separation of photogenerated holes and electrons, comparing to those of pristine g-C3 N4 . The theoretical simulations further reveal that the triazine-heptazine heterostructure possesses better photocatalytic hydrogen evolution (PHE) capability than pure triazine and heptazine carbon nitrides. In turn, SF-CN demonstrates an excellent visible light PHE rate of 18.13 mmol h-1  g-1 , up to 259.00 times of that of pristine g-C3 N4 .

5.
Microb Pathog ; 182: 106252, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37454943

RESUMO

The type VI secretion system (T6SS) has been regarded as a late-model virulence factor widely distributed in Acinetobacter baumannii (A. baumannii). This study aimed to elucidate the clinical manifestations, the genetic background and microbiological characteristics of A. baumannii isolates causing bloodstream infection (BSI), and assessed the impact of T6SS carrying state on the clinical course. In this study, Clinical samples of A. baumannii causing BSI were collected from a teaching hospital in China from 2016 to 2020 and a retrospective cohort was conducted. Experimental strains were categorized into T6SS positive and negative groups through PCR targeting on hcp gene. The antimicrobials sensitivity test, virulence genes, biofilm formation ability, serum resistance of A. baumannii strains and Galleria mellonella infection model were investigated. Independent risk factors for T6SS+ A. baumannii BSI and Kaplan-Meier curve through follow-up survey were analyzed. A total of 182 A. baumannii strains were isolated from patients with BSI during 5 years and the medical records of all patients were retrospectively reviewed. The proportion of T6SS+ isolates was 62.64% (114/182), which exhibited significantly higher resistance rates of commonly used antibacterial drugs compared to T6SS- group. We found that T6SS+ A. baumannii strains had significantly weaker biofilm formation ability compared to T6SS- A. baumannii. Despite no difference in the positivity rate of tested virulence genes in two groups, T6SS+ strains exhibited higher resistance to the serum and increased virulence in vivo compared to T6SS- strains, indicating that T6SS is likely to enhance the survival and invasive capabilities of A. baumannii in vivo. Indwelling catheter, respiratory diseases, ICU history, white blood cell count and percentage of neutrophils increasing were independent risk factors for T6SS+ A. baumannii BSI. At last, the Kaplan-Meier curve confirmed a higher mortality rate associated with T6SS+ A. baumannii BSI, suggesting that the presence of T6SS may serve as a prognostic factor for mortality. In conclusion, our study revealed that T6SS+ A. baumannii exhibited distinct clinical features, characterized by high antimicrobial resistance and enhanced virulence, providing valuable insights for clinical treatment considerations.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Sepse , Sistemas de Secreção Tipo VI , Humanos , Virulência/genética , Sistemas de Secreção Tipo VI/genética , Estudos Retrospectivos , Infecções por Acinetobacter/microbiologia , Antibacterianos/farmacologia , Prognóstico
6.
BMC Pregnancy Childbirth ; 23(1): 235, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37038114

RESUMO

INTRODUCTION: Our previous study has proofed the glucose sensitive gene-thioredoxin-interacting protein (TXNIP) expression was up in the placenta of the patients with gestational diabetes mellitus (GDM), but the pathological mechanisms underlying abnormal TXNIP expression in the placenta of patients with GDM is completely unclear and additional investigations are required to explain the findings we have observed. In the present study, we simulated the high TXNIP expression via introducing the Tet-On "switch" in vitro, approximate to its expression level in the real world, to explore the following consequence of the abnormal TXNIP. METHODS: The expression and localization of TXNIP in the placenta of GDM patients and the health control was investigated via immunofluorescent staining, western blot and RT-qPCR. Overexpression of TXNIP was achieved through transfecting Tet-on system to the human trophoblastic cell line-HTR-8/Svneo cell. TXNIP knockout was obtained via CRISPR-Cas9 method. The cell phenotype was observed via IncuCyte Imaging System and flow cytometry. The mechanism was explored via western blot and RT-qPCR. RESULTS: The expression level of TXNIP in the GDM placenta was nearly 2-3 times higher than that in the control. The TXNIP located at trophoblastic cells of the placenta. When the expression of TXNIP was upregulated, the migration and invasion of the cells accelerated, but cell apoptosis and proliferation did not changed compared with the control group. Furthermore, the size of the TetTXNIP cells became larger, and the expression level of Vimentin and p-STAT3 increased in the TetTXNIP cells. All the changes mentioned above were opposite in the TXNIP-KO cells. CONCLUSIONS: Abnormal expression of TXNIP might be related to the impairment of the GDM placental function, affecting the migration and invasion of the placental trophoblast cells through STAT3 and Vimentin related pathway; thus, TXNIP might be the potential therapeutic target for repairing the placental dysfunction deficient in GDM patients.


Assuntos
Proteínas de Transporte , Diabetes Gestacional , Placenta , Humanos , Feminino , Gravidez , Adulto , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Proteínas de Transporte/metabolismo , Placenta/metabolismo , Placenta/patologia , Trofoblastos/metabolismo , Trofoblastos/patologia , Fosforilação , Fator de Transcrição STAT3/metabolismo
7.
Biochem Genet ; 61(4): 1282-1299, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36550211

RESUMO

Autophagy is closely related to breast cancer and has the dual role of promoting and inhibiting the progression of breast cancer. In this study, we aimed to establish an autophagy-related gene signature for the prognosis of breast cancer. A gene signature composed of the eight most survival-relevant autophagy-associated genes was identified by least absolute shrinkage and selection operator (LASSO) regression analysis. A risk score was calculated based on the gene signature, which divided breast cancer patients into low- or high-risk groups and showed good and poor prognosis, respectively. The risk score displayed good prognostic performance in both the training cohort (TCGA, 1-10-year AUC > 0.63) and the validation cohort (GEO, 1-10-year AUC > 0.66). The multivariate Cox regression and stratified analysis revealed that the risk score was an independent prognostic factor for breast cancer patients. Moreover, the high-risk score was associated with higher infiltration of neutrophils and M2-polarized macrophages, and lower infiltration of resting memory CD4+ T cells, CD8+ T cells, and NK cells. Finally, the high-risk score was associated with myc target, glycolysis, and mTORC1 signaling. The risk score developed based on the autophagy-associated gene signature was an independent prognostic biomarker for breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Linfócitos T CD8-Positivos , Prognóstico , Autofagia/genética , Glicólise
8.
Mikrochim Acta ; 190(12): 479, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-37994918

RESUMO

A novel peroxidase-like nanozyme has been constructed by decorating two-dimensional Ti3C2Tx nanosheets (Ti3C2Tx NSs) with gold nanoparticles (AuNPs) to develop a colorimetric and photothermal dual-mode immunosensor. The Ti3C2Tx/AuNPs nanocomposite-catalyzed 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2 reaction system produces the one-electron oxidation product of TMB (oxTMB), which exhibits color change and strong near-infrared (NIR) laser-driven photothermal effect at 808 nm laser irradiation. Given these characteristics, the developed immunosensor achieves ultrasensitive dual-mode detection of zearalenone (ZEN) by measuring colorimetric and photothermal signals with a microplate reader and a portable infrared thermometer, respectively. Under optimal working conditions, the limit of detection (LOD) of ZEN is 0.15 pg mL-1 for the colorimetric mode and 0.48 pg mL-1 for the photothermal mode. In the analysis of actual contaminated cereals samples, the test result of this method was consistent with that of UPLC-MS/MS. The proposed colorimetric and photothermal dual-mode immunosensor offers a new strategy for the low-cost detection of hazardous substances. The application of a widely used household infrared thermometer makes the signal readout more convenient, which provides great prospects in food safety and environment inspection applications.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Nanocompostos , Zearalenona , Colorimetria/métodos , Ouro , Grão Comestível , Peróxido de Hidrogênio , Cromatografia Líquida , Imunoensaio , Espectrometria de Massas em Tandem , Titânio , Peroxidase
9.
J Environ Manage ; 326(Pt B): 116760, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36427368

RESUMO

Silicates have been used as soil heavy metal passivators, but low remediation efficiency limited their development. In order to solve this problem, in this paper, an economical and environmentally friendly amorphous iron silicate was prepared by a simple co-precipitation method. It could be proved from the passivation experiments that the remediation efficiency of amorphous iron silicate (AIS) on Cd-contaminated soil was better than that of natural silicates (montmorillonite and diatomite), which reflected the superiority of amorphous materials. Plant experiments showed that AIS could effectively inhibit the absorption and accumulation of Cd2+ in the edible parts of garlic. In addition, it may effectively reduce the potential ecological risk assessment of soil, and its immobilization mechanism of Cd2+ includes electrostatic adsorption, co-precipitation, ion exchange, and complexation of surface functional groups. This study demonstrates the advantages of amorphous iron silicate as a new functional material in the remediation of Cd-contaminated soil and provides a reference for the development and application of environment-friendly passivators.


Assuntos
Recuperação e Remediação Ambiental , Poluentes do Solo , Cádmio/química , Adsorção , Poluentes do Solo/análise , Solo/química , Silicatos , Ferro
10.
Int Wound J ; 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37905575

RESUMO

Breast remodelling is a major therapeutic choice in radical mastectomy. Breast reconstruction is regarded as a promising option for the treatment of breast cancer. The purpose of this meta-analysis was to investigate the effect of Post mastectomy radiotherapy (PMRT) on postoperative wound complications in breast carcinoma. A comprehensive review of documents was conducted between the date of establishment and the 28th of August 2023. In all of the trials, patients were treated with breast cancer. The researchers chose 11 publications out of 8068 related studies. Two researchers examined these publications to satisfy the inclusion criteria. Among the 516 patients who had received radiation therapy in the course of the operation, 1772 had not received radiation therapy. The impact of radiation therapy and non-radiation therapy in breast cancer patients after breast reconstruction was reported in 8 studies, and the incidence of postoperative wound infection in non-radiation group was significantly lower (OR, 1.95; 95% CI, 1.26-3.02 p = 0.003). In nine studies, There is not considered to have achieved statistical significance between radiation therapy and non-radiation treatment for post-operation wound dehiscence in breast cancer patients who had received chemotherapy (OR, 1.61; 95% CI, 0.70-3.72 p = 0.27). The results of six trials demonstrated that radiation therapy and non-radiation therapy had no statistical significance on post-operation haemorrhage in breast cancer patients (OR, 1.02; 95% CI, 0.42-2.47 p = 0.96). The results of 7 trials demonstrated that radiation therapy and non-radiation therapy had no significant impact on the post-operation of skin necrosis (OR, 1.22; 95% CI, 0.66-2.28 p = 0.53). Two trials demonstrated that those without radiation therapy were less likely than those who received radiation therapy in skin contracture in patients (OR, 7.24; 95% CI, 1.80-29.10 p = 0.005). Regarding the incidence of wound infection and cutaneous contraction was higher in the radiation group.

11.
Zhongguo Zhong Yao Za Zhi ; 48(18): 5024-5031, 2023 Sep.
Artigo em Zh | MEDLINE | ID: mdl-37802844

RESUMO

Chemical constituents were isolated and purified from ethyl acetate fraction of Arctium lappa leaves by silica gel, ODS, MCI, and Sephadex LH-20 column chromatography. Their structures were identified with multiple spectroscopical methods including NMR, MS, IR, UV, and X-ray diffraction combined with literature data. Twenty compounds(1-20) were identified and their structures were determined as arctanol(1), citroside A(2), melitensin 15-O-ß-D-glucoside(3), 11ß,13-dihydroonopordopicrin(4), 11ß,13-dihydrosalonitenolide(5), 8α-hydroxy-ß-eudesmol(6), syringin(7), dihydrosyringin(8), 3,4,3',4'-tetrahydroxy-δ-truxinate(9),(+)-pinoresinol(10), phillygenin(11), syringaresinol(12), kaeperferol(13), quercetin(14), luteolin(15), hyperin(16), 4,5-O-dicaffeoylquinic acid(17), 1H-indole-3-carboxaldehyde(18), benzyl-ß-D-glucopyranoside(19), and N-(2'-phenylethyl) isobutyramide(20). Among them, compound 1 is a new norsesquiterpenoid, and compounds 2-5, 7-8, and 18-20 are isolated from this plant for the first time.


Assuntos
Arctium , Arctium/química , Espectroscopia de Ressonância Magnética , Luteolina/análise , Folhas de Planta/química
12.
BMC Infect Dis ; 22(1): 662, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35907785

RESUMO

BACKGROUND: We aimed to explore the prognostic utilities of C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD64 (nCD64) index, in combination or alone, in septic patients. METHODS: We retrospectively included 349 septic patients (based on Sepsis 3.0 definition). The primary outcome was 28-day all-cause mortality. Cox regression model, receiver-operating characteristic (ROC) curve, reclassification analysis, Kaplan-Meier survival curves were performed to evaluate the predictive efficacy of the above parameters. RESULTS: CRP, nCD64 index were independent predictors of 28-day mortality for sepsis in the Cox regression model [CRP, HR 1.004 (95% CI 1.002-1.006), P < 0.001; nCD64 index, HR 1.263 (95% CI 1.187-1.345, P < 0.001]. Area under the ROC curve (AUC) of CRP, PCT, nCD64 index, nCD64 index plus PCT, nCD64 index plus CRP, were 0.798 (95% CI 0.752-0.839), 0.833 (95% CI 0.790-0.871), 0.906 (95% CI 0.870-0.935), 0.910 (95% CI 0.875-0.938), 0.916 (95% CI 0.881-0.943), respectively. nCD64 plus CRP performed best in prediction, discrimination, and reclassification of the 28-day mortality risk in sepsis. The risk of 28-day mortality increased stepwise as the number of data exceeding optimal cut-off values increased. CONCLUSIONS: nCD64 index combined with CRP was superior to CRP, PCT, nCD64 index and nCD64 index plus PCT in predicting 28-day mortality in sepsis. Multi-marker approach could improve the predictive accuracy and be beneficial for septic patients.


Assuntos
Pró-Calcitonina , Receptores de IgG/sangue , Sepse , Biomarcadores/metabolismo , Proteína C-Reativa/análise , Humanos , Unidades de Terapia Intensiva , Neutrófilos/metabolismo , Prognóstico , Curva ROC , Receptores de IgG/metabolismo , Estudos Retrospectivos , Sepse/diagnóstico , Sepse/metabolismo
13.
Nano Lett ; 21(17): 7166-7174, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34448590

RESUMO

Critical challenges remain in trauma emergency and surgical procedures involving liver bleeding, particularly in perforating wounds that cannot be pressed and large wounds that cannot be sewn. Self-assembling peptide hydrogels are particularly attractive due to their intrinsic biocompatibility and programmability. Herein, we develop a nano-band-aid (NBA) through a three-stage self-assembly strategy of two functionalized peptides, which were first coassembled into nanofibers and then woven to a meshlike network driven by Ca2+. Then, catalyzed by blood coagulation factor XIIIa (FXIIIa), NBA underwent a third stage, self-assembly into a densely compacted physical barrier to stop and control the bleeding. As expected, NBA rapidly and efficiently stopped the bleeding in rat liver scratches while effectively reducing the inflammation around the wound and promoting the wound healing. This bionic self-assembly strategy will provide a clinically potential peptide-based treatment for fatal liver bleeding and reinvigorate efforts to develop self-assembling peptide hydrogels as hemostatic agents.


Assuntos
Biônica , Hemostasia , Animais , Hidrogéis , Fígado , Peptídeos , Ratos
14.
Zhongguo Zhong Yao Za Zhi ; 47(9): 2409-2418, 2022 May.
Artigo em Zh | MEDLINE | ID: mdl-35531688

RESUMO

In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1ß and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.


Assuntos
Inflamassomos , MicroRNAs , Animais , Proteínas Hedgehog , Inflamassomos/genética , Inflamassomos/metabolismo , Interleucina-6 , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Medicina Tradicional Chinesa , Camundongos , MicroRNAs/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais
15.
J Transl Med ; 19(1): 381, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496872

RESUMO

BACKGROUND: Tumor-derived exosomes (TEXs) are involved in tumor progression and the immune modulation process and mediate intercellular communication in the tumor microenvironment. Although exosomes are considered promising liquid biomarkers for disease diagnosis, it is difficult to discriminate TEXs and to develop TEX-based predictive biomarkers. METHODS: In this study, the gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database, IMvigor210 cohorts, and six independent Gene Expression Omnibus datasets. A TEXs-associated signature named TEXscore was established to predict overall survival in multiple cancer types and in patients undergoing immune checkpoint blockade therapies. RESULTS: Based on exosome-associated genes, we first constructed a tumor-derived exosome signature named TEXscore using a principal component analysis algorithm. In single-cell RNA-sequencing data analysis, ascending TEXscore was associated with disease progression and poor clinical outcomes. In the TCGA Pan-Cancer cohort, TEXscore was elevated in tumor samples rather than in normal tissues, thereby serving as a reliable biomarker to distinguish cancer from non-cancer sources. Moreover, high TEXscore was associated with shorter overall survival across 12 cancer types. TEXscore showed great potential in predicting immunotherapy response in melanoma, urothelial cancer, and renal cancer. The immunosuppressive microenvironment characterized by macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells was associated with high TEXscore in the TCGA and immunotherapy cohorts. Besides, TEXscore-associated miRNAs and gene mutations were also identified. Further experimental research will facilitate the extending of TEXscore in tumor-associated exosomes. CONCLUSIONS: TEXscore capturing tumor-derived exosome features might be a robust biomarker for prognosis and treatment responses in independent cohorts.


Assuntos
Exossomos , Melanoma , Biomarcadores Tumorais/genética , Humanos , Imunoterapia , Melanoma/genética , Melanoma/terapia , Prognóstico , Análise de Célula Única , Microambiente Tumoral
16.
BMC Microbiol ; 21(1): 208, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238225

RESUMO

BACKGROUND: The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. RESULTS: This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. CONCLUSIONS: This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/genética , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Genes Bacterianos/genética , Plasmídeos/genética
17.
Sensors (Basel) ; 22(1)2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-35009550

RESUMO

A competitive fluorescence immunoassay for the quantitative detection of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) in pan-fried meat patties was developed, using magnetic nanoparticles coupled with coating antigen as the capture probe and anti-IQ antibody coupled with NaYF4: Yb, Er upconversion nanoparticles as the signal probe. Under optimal conditionals, the wide detection range for IQ in phosphate buffer saline is from 0.01 to 100 µg·L-1 (R2 = 0.991) with a detection limit of 0.007 µg·L-1. This proposed method has been applied to detect IQ in two different types of pan-fried meat patties at varying frying times, and the IQ content in chicken patties and fish patties are 2.11-3.47 µg·kg-1 and 1.35-2.85 µg·kg-1, respectively. These results are consistent with that of the ultraperformance liquid chromatography-tandem mass spectrometry. In summary, this method can serve as a sensitive and specific test tool for the determination of IQ in processed meat.


Assuntos
Nanopartículas , Quinolinas , Animais , Temperatura Alta , Imunoensaio , Carne/análise
18.
Entropy (Basel) ; 23(2)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33514034

RESUMO

It is widely accepted that the frictional pressure drop is impossible to be negative for pipe flow. However, the negative frictional pressure drops were observed for some cases of two-phase slug and churn flows in pipes, challenging the general sense of thermodynamic irreversibility. In order to solve this puzzling problem, theoretical investigations were performed for the entropy generation in slug and churn flows. It is found that the frictional pressure drop along with a buoyancy-like term contributes to the entropy generation due to mechanical energy loss for steady, incompressible slug and churn flows in vertical and inclined pipes. Experiments were conducted in a vertical pipe with diameter as 0.04 m for slug and churn flows. Most of the experimental data obtained for frictional pressure drop are negative at high gas-liquid ratios from 100 to 10,000. Entropy generation rates were calculated from experimental data. The results show that the buoyancy-like term is positive and responsible for a major part of entropy generation rate while the frictional pressure drop is responsible for a little part of entropy generation rate, because of which the overall entropy generation due to mechanical energy loss is still positive even if the frictional pressure drop is negative in vertical slug and churn flows. It is clear that the negative frictional pressure drops observed in slug and churn flows are not against the thermodynamics irreversibility.

19.
Biochem Biophys Res Commun ; 525(4): 895-901, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171530

RESUMO

Liraglutide, a glucagon-like peptide 1 (GLP-1) analogue, could reverse NAFLD-induced liver damage by improving metabolic profiles, but the exact molecular mechanism has not been elucidated. Sestrin2 is a novel antioxidant protein, essential for regulating metabolic homeostasis. However, whether sestrin2-mediated redox balance participated in the protective effects of liraglutide against NAFLD is still elusive. The aim of the study was to determine whether liraglutide could ameliorate NAFLD by increasing Sestrin2-mediated signaling in obese mice. Following a normal diet or high fat diet (HFD) for 8 weeks, male C57BL/6 mice were treated with or without liraglutide for 4 weeks. Function and histopathology of liver were conducted to evaluate liver injury. Sestrin2-related AMPK and Nrf2/HO-1 pathway were examined. Antioxidative and inflammatory genes and were determined. HFD mice displayed significantly increased body weight, fat mass, lipids levels and impaired glucose homeostasis with reduced glucose tolerance and insulin sensitivity. Metabolic profiles, hepatic injury, and hepatic lipid accumulation from HFD mice were improved by liraglutide treatment. Liraglutide enhanced Sestrin2, phosphorylated AMPK, Nrf2, and HO-1 protein levels. Additionally, Liraglutide treatment increased mRNA levels of Sestrin2, Nrf2, HO-1 and down-stream genes catalase, GCLM and NQO1, but reduced malondialdehyde and TNF-α levels. Our findings indicated that liraglutide ameliorated obesity-related NAFLD through upregulating Sestrin2-mediated Nrf2/HO-1 pathway.


Assuntos
Heme Oxigenase-1/metabolismo , Liraglutida/farmacologia , Proteínas de Membrana/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/complicações , Peroxidases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Fibrose , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/etiologia , Peroxidases/genética
20.
BMC Infect Dis ; 20(1): 36, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931740

RESUMO

BACKGROUND: Hantavirus infection is worldwide epidemic and can cause life-threatening consequences. With more and more cases reported in countries with atypical morbidity, it is necessarily urgent to know some atypical symptoms and signs of Hantavirus infection. CASE PRESENTATION: Here we report the case of a 44-year old male with a complaint of fever and diffuse abdominal pain, initially suspiciously diagnosed with acute peritonitis. The patient was eventually diagnosed as hemorrhagic fever with renal syndrome and enhanced CT scan showed peritonitis. The clinical condition of the patient was relatively mild and he was recovered 9 days later. CONCLUSION: Peritonitis secondary to hemorrhagic fever with renal syndrome is rare in clinically practice. When confronted with atypical celialgia, it is important to make differential diagnosis of hantavirus infection.


Assuntos
Febre Hemorrágica com Síndrome Renal/complicações , Febre Hemorrágica com Síndrome Renal/diagnóstico , Orthohantavírus/imunologia , Peritonite/diagnóstico , Peritonite/etiologia , Adulto , Antibacterianos/uso terapêutico , China , Diagnóstico Diferencial , Técnica Direta de Fluorescência para Anticorpo/métodos , Febre Hemorrágica com Síndrome Renal/tratamento farmacológico , Febre Hemorrágica com Síndrome Renal/virologia , Humanos , Masculino , Resultado do Tratamento
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