Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 222
Filtrar
1.
Genes Dis ; 9(1): 41-50, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35005106

RESUMO

Ubiquitin-specific protease (USP7), also known as Herpesvirus-associated ubiquitin-specific protease (HAUSP), is a deubiquitinase. There has been significant recent attention on USP7 following the discovery that USP7 is a key regulator of the p53-MDM2 pathway. The USP7 protein is 130 kDa in size and has multiple domains which bind to a diverse set of proteins. These interactions mediate key developmental and homeostatic processes including the cell cycle, immune response, and modulation of transcription factor and epigenetic regulator activity and localization. USP7 also promotes carcinogenesis through aberrant activation of the Wnt signalling pathway and stabilization of HIF-1α. These findings have shown that USP7 may induce tumour progression and be a therapeutic target. Together with interest in developing USP7 as a target, several studies have defined new protein interactions and the regulatory networks within which USP7 functions. In this review, we focus on the protein interactions of USP7 that are most important for its cancer-associated roles.

2.
Toxicology ; 466: 153066, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34919984

RESUMO

In order to overcome the weakness of conventional approaches for cell culture, and provide cells with more in vivo-like microenvironment for studying hepatotoxicity of drugs, "multiple-in-one" strategy was adopted to fabricate a 3D scaffold of silk fibroin/hydroxyapatite/poly lacticco-glycolic acid (SF/HA/PLGA), where HepG2 cells were cultivated and the toxicity of drugs to the cells was investigated. The prepared 3D scaffold proves to bear proper porosity, excellent mechanical property, steady pH environment and good biocompatibility for cell culture. Furthermore, the validity of the developed 3D-SF/HA/PLGA-scaffold based platform was verified by probing the toxicity of a known drug-induced liver injury (DILI) concern acetaminophen (APAP) to HepG2 cells. Eventually, an application of the platform to dioscin (a medicinal plant extract) reveals the hepatotoxicity of dioscin, which involves the inhibition of the expression of CYP3A4 mRNA in the cells. The developed 3D-SF/HA/PLGA-scaffold platform may become a universal avenue for safety evaluation of drugs.

3.
Front Genet ; 12: 770134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790230

RESUMO

Background: Although ribosomal protein S6 kinases, 90 kDa, polypeptide 3 (RSK2, RPS6KA3) has been reported to play an important role in cancer cell proliferation, invasion, and migration, including breast cancer, its clinical implication in primary breast cancer patients is not well understood, and there were not many studies to explore the relationship between RSK2 and breast cancer on a clinical level. Methods: A systematic series matrix file search uploaded from January 1, 2008 to November 31, 2017 was undertaken using ArrayExpress and Gene Expression Omnibus (GEO) databases. Search filters were breast cancer, RNA assay, and array assay. Files eligible for inclusion met the following criteria: a) sample capacity is over 100, b) tumor sample comes from unselected patient's primary breast tumor tissue, and c) expression of RSK2 and any clinical parameters of patients were available from the files. We use median as the cutoff value to assess the association between the expression of RSK2 and the clinical indexes of breast cancer patients. Finding: The meta-analysis identified 13 series matrix files from GEO database involving 3,122 samples that come from patients' primary breast cancer tissue or normal tissue. The expression of RSK2 in tumor tissues is lower than that in normal tissues [odds ratio (OR), 0.54; 95% credible interval (CI), 0.44-0.67; Cochran's Q test p = 0.14; I 2 = 41.7%]. Patients with a high expression of RSK2 showed more favorable overall survival [hazard ratio (HR), 0.71; 95% CI, 0.49-0.94; Cochran's Q test p = 0.95; I 2 = 0.0%] and less potential of distant metastasis (OR, 0.59; 95% CI, 0.41-0.87; Cochran's Q test p = 0.88; I 2 = 0.0%) and lymph node infiltration (OR, 0.81; 95% CI, 0.65-0.998; Cochran's Q test p = 0.09; I 2 = 42.8%). Besides, the expression of RSK2 in luminal breast cancer is lower than Cochran's Q test p = 0.06; I 2 = 63.5%). RSK2 overexpression corresponded with higher histological grade (OR, 1.329; 95% CI, 1.03-1.721; Cochran's Q test p = 0.69; I 2 = 0.0%). RSK2 expression is also associated with estrogen receptor (ER) and age. Conclusion: The meta-analysis provides evidence that RSK2 is a potential biomarker in breast cancer patients. The expression of RSK2 is distinctive in different intrinsic subtypes of breast cancer, indicating that it may play an important role in specific breast cancer. Further study is needed to uncover the mechanism of RSK2 in breast cancer. Systematic Review Registration: (website), identifier (registration number).

4.
Mater Horiz ; 8(4): 1314-1322, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821924

RESUMO

Acute kidney injury (AKI) is frequently associated with reactive oxygen species (ROS) and causes high mortality in clinics annually, and nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for AKI treatment. Herein, four kinds of natural antioxidants are able to coordinate with iron (Fe) ions to form ultra-small coordination polymer nanodots (CPNs) with good water dispersibility and strong ROS scavenging ability. In particular, Fe-curcumin CPNs (Fe-Cur CPNs) are applied for cellular ROS scavenging and rhabdomyolysis-induced AKI relief.

5.
Physiol Mol Biol Plants ; 27(10): 2283-2296, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34744366

RESUMO

RNA helicase catalyzes the denaturation of DNA or the unwinding of double-stranded RNA. It is vital to RNA splicing, transport, editing, degradation and the initiation of protein translation. However, the function of RNA helicase in Medicago truncatula has rarely been reported. In this study, 170 putative RNA helicase genes were identified in the M. truncatula genome, and classified into three subfamilies based on the presence of either a DEAD-box (52 genes), DEAH-box (38 genes), or DExD/H-box (80 genes) in their coding regions. Additionally, conserved helicase_C domains and other functional domains (e.g., the HA2, DUF, and ZnF domains) were also present in these genes. Chromosomal mapping and synteny analyses showed that there were tandem and segment duplications of RNA helicase genes. Furthermore, transcriptome and real-time PCR analysis showed that the expression of 35 RNA helicase genes was affected by abiotic stress. To be specific, 17, 12 and 19 genes were regulated by salt, drought and cold stress, respectively. It is worth noting that MtDEAD8, MtDEAH3, MtDExD/H18 and MtDExD/H23 responded to all three types of stress. These results provide valuable information for understanding the RNA helicase genes in M. truncatula and their abiotic stress-related functions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-021-01087-y.

6.
Arterioscler Thromb Vasc Biol ; : ATVBAHA121317071, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34758633

RESUMO

OBJECTIVE: Animal models of atherosclerosis are used extensively to interrogate molecular mechanisms in serial fashion. We tested whether a novel systems biology approach to integration of preclinical data identifies novel pathways and regulators in human disease. Approach and Results: Of 716 articles published in ATVB from 1995 to 2019 using the apolipoprotein E knockout mouse to study atherosclerosis, data were extracted from 360 unique studies in which a gene was experimentally perturbed to impact plaque size or composition and analyzed using Ingenuity Pathway Analysis software. TREM1 (triggering receptor expressed on myeloid cells) signaling and liver×receptor/retinoid×receptor activation were identified as the top atherosclerosis-associated pathways in mice (both P<1.93×10-4, TREM1 implicated early and liver×receptor/retinoid×receptor in late atherogenesis). The top upstream regulatory network in mice (sc-58125, a COX2 inhibitor) linked 64.0% of the genes into a single network. The pathways and networks identified in mice were interrogated by testing for associations between the genetically predicted gene expression of each mouse pathway-identified human homolog with clinical atherosclerosis in a cohort of 88 660 human subjects. Homologous human pathways and networks were significantly enriched for gene-atherosclerosis associations (empirical P<0.01 for TREM1 and liver×receptor/retinoid×receptor pathways and COX2 network). This included 12(60.0%) TREM1 pathway genes, 15(53.6%) liver×receptor/retinoid×receptor pathway genes, and 67(49.3%) COX2 network genes. Mouse analyses predicted, and human study validated, the strong association of COX2 expression (PTGS2) with increased likelihood of atherosclerosis (odds ratio, 1.68 per SD of genetically predicted gene expression; P=1.07×10-6). CONCLUSIONS: Preclinical Science Integration and Translation leverages published preclinical investigations to identify high-confidence pathways, networks, and regulators of human disease.

7.
Cancer Med ; 10(23): 8288-8299, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34725960

RESUMO

Now solid renal tumors ≤4 cm is the most common, especially the subtype of clear cell renal cell carcinoma (ccRCC) of malignant kidney tumors in clinical. However, there is not specific characteristics of contrast-enhanced ultrasound (CEUS) be recommended by the EFSUMB Guidelines in distinguish the essence of the kidney tumor with different sizes. Therefore, this meta-analysis aimed to assess the ability of CEUS to diagnose solid ccRCC (sccRCC) ≤4 cm. We comprehensively searched the Cochrane Library, Embase, PubMed, and Web of Science databases from their inception to 28 July 2020, for studies reporting the CEUS features of sccRCC lesions ≤4 cm. Additional articles were identified through the Chinese National Knowledge Infrastructure database. Studies were selected independently by two investigators and the relevant data were extracted. Discrepancies were resolved via discussion with the senior author. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, and the sensitivity and specificity of each study were determined and plotted as a receiver operating characteristic curve. Ten studies were included in this meta-analysis. Hyperenhancement showed medium sensitivity (67%-89%) and specificity (42%-75%) for diagnosing sccRCC ≤4 cm, fast-in contrast agent and heterogeneous enhancement showed high diagnostic abilities (area under curve (AUC) 0.74-0.84), but the presence of a pseudocapsule and fast-out contrast agent had poor diagnostic ability (AUC <0.70). The combination of hyperenhancement and iso-enhancement showed high sensitivity (98%) for diagnosing sccRCC ≤4 cm. Hyperenhancement, fast-in contrast agent, and heterogeneous enhancement may be specific features that could help to identify sccRCC ≤4 cm, while the presence of a pseudocapsule and fast-out of contrast agent may have low diagnostic values. The combination of multiple indexes may improve the diagnostic value of CEUS for sccRCC ≤4 cm.

8.
PLoS One ; 16(11): e0246707, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34739494

RESUMO

Glycogen-specific kinase (GSK3ß) is an integral regulator of the Wnt signalling pathway as well as many other diverse signalling pathways and processes. Dys-regulation of GSK3ß is implicated in many different pathologies, including neurodegenerative disorders as well as many different tumour types. In the context of tumour development, GSK3ß has been shown to play both oncogenic and tumour suppressor roles, depending upon tissue, signalling environment or disease progression. Although multiple substrates of the GSK3ß kinase have been identified, the wider protein networks within which GSK3ß participates are not well known, and the consequences of these interactions not well understood. In this study, LC-MS/MS expression analysis was performed using knockout GSK3ß colorectal cancer cells and isogenic controls in colorectal cancer cell lines carrying dominant stabilizing mutations of ß-catenin. Consistent with the role of GSK3ß, we found that ß-catenin levels and canonical Wnt activity are unaffected by knockout of GSK3ß and therefore used this knockout cell model to identify other processes in which GSK3ß is implicated. Quantitative proteomic analysis revealed perturbation of proteins involved in cell-cell adhesion, and we characterized the phenotype and altered proteomic profiles associated with this. We also characterized the perturbation of metabolic pathways resulting from GSK3ß knockout and identified defects in glycogen metabolism. In summary, using a precision colorectal cancer cell-line knockout model with constitutively activated ß-catenin we identified several of the diverse pathways and processes associated with GSK3ß function.

9.
Front Nutr ; 8: 743492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660667

RESUMO

Chitosan oligosaccharides (COS) play a prebiotic role in many ways, whereas its function on microbiota is not fully understood. In this study, the effects of COS on metabolic syndrome were initially investigated by testing changes in the physiological indicators after adding COS to the diet of mice with high fat (group H) and low fat (group L). The results showed that COS markedly inhibited the accumulation of body weight and liver fat induced by high-fat diet, as well as restored the elevated concentration of blood glucose and fasting insulin to normal levels. Next, changes of the murine intestinal microbiota were examined. The results exhibited that COS reduced with-in-sample diversity, while the between-sample microbial diversity enhanced. Specifically, COS enriched Clostridium paraputrificum and Clostridium ramosum in the mice on a high-fat diet, while the abundance of Clostridium cocleatum was reduced. As a comparison, Parabacteroides goldsteinii and Bacteroides uniformis increased their abundance in response to COS in the low-fat diet group. Noticeably, a large amount of Akkermansia muciniphila was enriched in both high-fat or low-fat diet groups. Among the differential fecal bacteria, Clostridium ramosume was found to be positively interacted with Faecalibacterim prausnitzii and Clostridium paraputrificum; Clostridium paraputrificum had a positive interactions with Lactococcus chungangensis and Bifidobacterium mongoliense, suggesting that COS probably ameliorate metabolic syndrome through the microbiota in view of the lipid-lowering effects of these interacted bacteria. Furthermore, the gene expression data revealed that COS improved the functions related to intestinal barrier and glucose transport, which could be the trigger and consequence of the variations in gut microbiota induced by COS. Additionally, correlation analysis found that intestinal bacteria are related to physiological parameters, which further supports the mediating role of gut microbiota in the beneficial effect of COS. In summary, our research results provide new evidence for the prebiotic effects of COS.

10.
Nat Commun ; 12(1): 5926, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635672

RESUMO

Enormous enhancement of superconducting pairing temperature (Tg) to 65 K in FeSe/SrTiO3 has made it a spotlight. Despite the effort of interfacial engineering, FeSe interfaced with TiOx remains the unique case in hosting high Tg, hindering a decisive understanding on the general mechanism and ways to further improving Tg. Here we constructed a new high-Tg interface, single-layer FeSe interfaced with FeOx-terminated LaFeO3. Large superconducting gap and diamagnetic response evidence that the superconducting pairing can emerge near 80 K, highest amongst all-known interfacial superconductors. Combining various techniques, we reveal interfacial charge transfer and strong interfacial electron-phonon coupling (EPC) in FeSe/LaFeO3, showing that the cooperative pairing mechanism works beyond FeSe-TiOx. Intriguingly, the stronger interfacial EPC than that in FeSe/SrTiO3 is likely induced by the stronger interfacial bonding in FeSe/LaFeO3, and can explain the higher Tg according to recent theoretical calculations, pointing out a workable route in designing new interfaces to achieve higher Tg.

11.
Plant Biotechnol J ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655511

RESUMO

Starch accounts for over 80% of the total dry weight in cereal endosperm and determines the kernel texture and nutritional quality. Amyloplasts, terminally differentiated plastids, are responsible for starch biosynthesis and storage. We screened a series of rice mutants with floury endosperm to clarify the mechanism underlying amyloplast development and starch synthesis. We identified the floury endosperm19 (flo19) mutant which shows opaque of the interior endosperm. Abnormal compound starch grains (SGs) were present in the endosperm cells of the mutant. Molecular cloning revealed that the FLO19 allele encodes a plastid-localized pyruvate dehydrogenase complex E1 component subunit α1 (ptPDC-E1-α1) that is expressed in all rice tissues. In vivo enzyme assays demonstrated that the flo19 mutant showed decreased activity of the plastidic pyruvate dehydrogenase complex. In addition, the amounts of monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) were much lower in the developing flo19 mutant endosperm, suggesting that FLO19 participates in fatty acid supply for galactolipid biosynthesis in amyloplasts. FLO19 overexpression significantly increased seed size and weight, but did not affect other important agronomic traits, such as panicle length, tiller number and seed setting rate. An analysis of single nucleotide polymorphism data from a panel of rice accessions identified that the pFLO19L haplotype was positively associated with grain length, implying a potential application in rice breeding. In summary, our study demonstrates that FLO19 is involved in galactolipid biosynthesis which is essential for amyloplast development and starch biosynthesis in rice.

12.
Front Mol Biosci ; 8: 750558, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692771

RESUMO

Background: To determine the respiratory outcomes in patients following COVID-19-related hospitalization. Methods: Systematic review and meta-analysis of the literature. Results: Forced vital capacity (FVC, % of predicted): 0-3 months post discharge: 96.1, 95% CI [82.1-110.0]; 3-6 months post discharge: 99.9, 95% CI [84.8, 115.0]; >6 months post discharge: 97.4, 95% CI [76.8-118.0]. Diffusing capacity of the lungs for carbon monoxide (DLCO, % of predicted): 0-3 months post discharge: 83.9, 95% CI [68.9-98.9]; 3-6 months post discharge: 91.2, 95% CI [74.8-107.7]; >6 months post discharge: 97.3, 95% CI [76.7-117.9]. Percentage of patients with FVC less than 80% of predicted: 0-3 months post discharge: 10%, 95% CI [6-14%]; 3-6 months post discharge: 10%, 95% CI [2-18%]; >6 months post discharge: 13%, 95% CI [8-18%]. Percentage of patients with DLCO less than 80% of predicted: 0-3 months post discharge: 48%, 95% CI [41-56%]; 3-6 months post discharge: 33%, 95% CI [23-44%]; >6 months post discharge: 43%, 95% CI [22-65%]. Conclusion: The meta-analysis confirms a high prevalence of persistent lung diffusion impairment in patients following COVID-19-related hospitalization. Routine respiratory follow-up is thus strongly recommended.

13.
Medicine (Baltimore) ; 100(43): e27570, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713831

RESUMO

RATIONALE: Astroblastoma is a rare tumor of the central nervous system with uncertain biological behavior and origin. Its histopathological features have been well established, while, to our knowledge, astroblastoma with oligodendroglial-like cells have not been reported. PATIENT CONCERNS: A 15-year-old girl presented with nausea, vomiting, headache, and visual disturbance. DIAGNOSIS: Magnetic resonance imaging revealed a large neoplasm in the left temporal. Histologically, the tumor showed solid and pseudopapillary structure. Immunohistochemical staining showed that the tumor cells were positive for glial fibrillary acidic protein and vimentin. The oligodendroglial-like cells were positive for glial fibrillary acidic protein, vimentin, and oligodendrocyte transcription factor 2. The antigen KI67 labeling index was about 4%. Sequencing for isocitrate dehydrogenase (IDH) 1 codon 132 and IDH2 codon 172 gene mutations showed negative results. Furthermore, fluorescent analysis revealed neither 1p nor 19q deletion in the lesion. Based on these findings, the girl was finally diagnosed as astroblastoma. INTERVENTIONS: A craniotomy with total excision of the tumor was performed. OUTCOMES: The follow-up time was 1 year, no evidence of disease recurrence was found in magnetic resonance imaging. LESSONS: Cerebral astroblastoma with oligodendroglial-like cells is a clinically rare tumor of central nervous system. Clear distinction and diagnosis are critical.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Neuroepiteliomatosas/patologia , Adolescente , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Craniotomia/métodos , Feminino , Humanos , Neoplasias Neuroepiteliomatosas/diagnóstico , Neoplasias Neuroepiteliomatosas/cirurgia
14.
Bioresour Technol ; 341: 125909, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34523547

RESUMO

A novel electrochemical system of microbial fuel cell (MFC) coupled solid-phase denitrification biofilm reactor (DBR) system was established to explore the effect of simultaneous power generation and pollutant removal under different HRTs (Ⅰ:48 h; Ⅱ :24 h). The average removal rates of methyl orange, Cr (VI) and NO3--N in test group were 93.0, 98.6 and 95.5% within 60 days, while those were 53.1, 72.1 and 72.7% in control. The maximum power density was 61.2 (Ⅰ) and 16.1 mW/m2 (Ⅱ), while average output voltage was 122 (Ⅰ) and 83.6 mV (Ⅱ). Components 1 and 2 in soluble microbial products were identified, and the humic-like and fulvic acid-like substances varied through different layers. Pseudomonas produced electricity in anode, while denitrified in denitrification layer. Importantly, symbiotic cooperation was absolutely dominant in network analysis of both anodic and denitrifying biofilms. MFC significantly improved DBR's ability to treatment co-polluted wastewater.


Assuntos
Fontes de Energia Bioelétrica , Poluentes Ambientais , Microbiota , Desnitrificação , Eletricidade , Eletrodos , Águas Residuárias
15.
Transplantation ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34534191

RESUMO

BACKGROUND: Hepatic ischemia/reperfusion injury (IRI) is an unavoidable outcome of liver transplantation, during which neutrophil extracellular traps (NETs) may play a critical role in the IRI-induced immune response to inflammation. The purpose of this study was to identify the function of recombinant human thrombomodulin (rTM) in the remission of hepatic IRI after liver transplantation and elucidate the specific mechanism. METHODS: NET formation was detected in the serum of liver transplantation patients and rats following liver transplantation. Hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining, immunohistochemistry and immunofluorescence were used to assess the effect of rTM on NET formation in vitro and in vivo. RESULTS: We found that rTM markedly inhibited neutrophil formation in NETs, reduced apoptosis in hepatocytes, alleviated rat hepatic IRI and improved liver function. In vitro, rTM inhibited neutrophil formation in NETs, and lipopolysaccharide (LPS) (a Toll-like receptor (TLR)-4 agonist) reversed the inhibitory effect of rTM on NET formation. rTM blocked TLR-4 and the downstream extracellular signal-regulated kinase (ERK)/c-Jun NH2 terminal kinase (JNK) and nicotinamide adenine dinucleotide phosphate (NADPH)/ROS/peptidylarginine deiminase 4 (PAD4) signaling pathways to protect against hepatic IRI and inhibit NET formation. In addition, we demonstrated that combined treatment with rTM and an NADPH oxidative inhibitor had a better effect than either treatment alone. CONCLUSIONS: NETs are a potential therapeutic target in hepatic IRI, and rTM could be used to prevent IR-induced hepatic injury. In addition, cotargeting NETosis-related signaling pathways might be a novel therapeutic strategy for hepatic IRI treatment.

16.
Front Cell Infect Microbiol ; 11: 696186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485176

RESUMO

Objective: Frailty is a common geriatric syndrome that is diagnosed and staged based mainly on symptoms. We aimed to evaluate frailty-related alterations of the intestinal permeability and profile fecal microbiota of healthy and frail older adults to identify microbial biomarkers of this syndrome. Methods: We collected serum and fecal samples from 94 community-dwelling older adults, along with anthropometric, medical, mental health, and lifestyle data. Serum inflammatory cytokines IL-6 and HGMB1 and the intestinal permeability biomarker zonulin were measured using enzyme-linked immunosorbent assays. The 16S rRNA amplicon sequencing method was performed to determine the fecal composition of fecal microbiota. We analyzed the diversity and composition differences of the gut microbiota in the two groups and assessed the relationship between the changes in microbiota structure and clinical biomarkers. Results: Older adults with frailty showed higher concentrations of IL-6, HGMB1, and zonulin. Although there were no statistically significant differences in the diversity index and evenness indices or species richness of fecal microbiota between the two groups, we found significant microbiota structure differences. Compared with the control group, fecal samples from the frail group had higher levels of Akkermansia, Parabacteroides, and Klebsiella and lower levels of the commensal genera Faecalibacterium, Prevotella, Roseburia, Megamonas, and Blautia. Spearman's correlation analysis showed that the intergenus interactions were more common in healthy controls than older adults with frailty. Escherichia/Shigella, Pyramidobacter, Alistipes, and Akkermansia were positively correlated with IL-6, while Faecalibacterium, Prevotella, and Roseburia were negatively correlated with IL-6. Alistipes were found to be positively correlated with HGMB1. Akkermansia and Alistipes were linked to the increased serum level of inflammatory factors and intestinal permeability. Conclusions: Frailty is associated with differences in the composition of fecal microbiota. These findings might aid in the development of probiotics or microbial-based therapies for frailty.


Assuntos
Fragilidade , Microbioma Gastrointestinal , Microbiota , Idoso , Fezes , Humanos , RNA Ribossômico 16S/genética
17.
J Biol Chem ; 297(3): 101096, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34418430

RESUMO

Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic lung disease with a median survival of 2 to 4 years. Injury to and/or dysfunction of the alveolar epithelium is strongly implicated in IPF disease initiation, but the factors that determine whether fibrosis progresses rather than normal tissue repair occurs remain poorly understood. We previously demonstrated that zinc finger E-box-binding homeobox 1-mediated epithelial-mesenchymal transition in human alveolar epithelial type II (ATII) cells augments transforming growth factor-ß-induced profibrogenic responses in underlying lung fibroblasts via paracrine signaling. Here, we investigated bidirectional epithelial-mesenchymal crosstalk and its potential to drive fibrosis progression. RNA-Seq of lung fibroblasts exposed to conditioned media from ATII cells undergoing RAS-induced epithelial-mesenchymal transition identified many differentially expressed genes including those involved in cell migration and extracellular matrix regulation. We confirmed that paracrine signaling between RAS-activated ATII cells and fibroblasts augmented fibroblast recruitment and demonstrated that this involved a zinc finger E-box-binding homeobox 1-tissue plasminogen activator axis. In a reciprocal fashion, paracrine signaling from transforming growth factor-ß-activated lung fibroblasts or IPF fibroblasts induced RAS activation in ATII cells, at least partially through the secreted protein acidic and rich in cysteine, which may signal via the epithelial growth factor receptor via epithelial growth factor-like repeats. Together, these data identify that aberrant bidirectional epithelial-mesenchymal crosstalk in IPF drives a chronic feedback loop that maintains a wound-healing phenotype and provides self-sustaining profibrotic signals.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Fibrose Pulmonar Idiopática/fisiopatologia , Movimento Celular , Células Epiteliais/metabolismo , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Fibrose/fisiopatologia , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/patologia , Masculino , Cultura Primária de Células , Fibrose Pulmonar/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
18.
Materials (Basel) ; 14(16)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34443107

RESUMO

The phenomenon of oxygen incorporation-induced superconductivity in iron telluride (Fe1+yTe, with antiferromagnetic (AFM) orders) is intriguing and quite different from the case of FeSe. Until now, the microscopic origin of the induced superconductivity and the role of oxygen are far from clear. Here, by combining in situ scanning tunneling microscopy/spectroscopy (STM/STS) and X-ray photoemission spectroscopy (XPS) on oxygenated FeTe, we found physically adsorbed O2 molecules crystallized into c (2/3 × 2) structure as an oxygen overlayer at low temperature, which was vital for superconductivity. The O2 overlayer were not epitaxial on the FeTe lattice, which implied weak O2 -FeTe interaction but strong molecular interactions. The energy shift observed in the STS and XPS measurements indicated a hole doping effect from the O2 overlayer to the FeTe layer, leading to a superconducting gap of 4.5 meV opened across the Fermi level. Our direct microscopic probe clarified the role of oxygen on FeTe and emphasized the importance of charge transfer effect to induce superconductivity in iron-chalcogenide thin films.

19.
Oncol Rep ; 46(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34296290

RESUMO

Following the publication of this article, the authors realized that the published version of Fig. 4A contained an erroneous label; essentially, the information purported to relate to experiments having been performed with docetaxel should not have been included in this figure. The correctly labelled version of Fig. 4 is shown with the remainder of Fig. 4 on the next page. This change does not affect the data shown in the paper, and the text in the published article did accurately describe the information shown in this figure. The authors sincerely apologize for the error that was introduced during the preparation of this figure, and thank the Editor for allowing them the opportunity to publish a Corrigendum. Furthermore, they regret any inconvenience caused. [the original article was published in Oncology Reports 46: Article no. 138, 2021; DOI: 10.3892/or.2021.8089].

20.
Front Oncol ; 11: 668610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235079

RESUMO

Purpose: The aim of this study was to assess the prognostic influence of Ki67 index changes in patients with primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), and to evaluate whether the combination of Ki67 index changes and residual disease (RD) tumor-infiltrating lymphocytes (TILs) provides additional prognostic information for this group. Materials and Methods: Data from 109 patients with primary TNBC and RD after NAC were analyzed retrospectively. Ki67 changes and RD TIL levels were investigated for associations with recurrence-free survival (RFS) and overall survival (OS) using Kaplan-Meier and Cox analyses. Results: Ki67 index decreased after NAC in 53 patients (48.6%) and high RD TIL levels (≥30%) were observed in 54 patients (49.5%). In multivariate Cox analyses, no Ki67 decrease status and low RD TIL levels were significantly associated with reduced RFS (hazard ratio (HR): 2.038, 95% confidence interval (CI): 1.135-3.658, P = 0.017; HR: 2.493, 95% CI: 1.335-4.653, P = 0.004), and OS (HR: 2.187, 95% CI: 1.173-4.077, P = 0.014; HR: 2.499, 95% CI: 1.285-4.858, P = 0.007), respectively. Notably, low RD TIL levels were significantly associated with reduced RFS (HR: 3.567, 95% CI: 1.475-8.624, P = 0.005) and reduced OS (HR: 3.873, 95% CI: 1.512-9.918, P = 0.005) in only the no Ki67 decrease group. The differences in 3-year RFS and OS between patients with no Ki67 decrease and low or high RD TIL levels were 24.4% vs 79.1% (P = 0.0001) and 33.1% vs 87.5% (P = 0.0001), respectively. Conclusion: Ki67 index changes and RD TIL levels were associated with the prognosis of patients with primary TNBC with RD after NAC. RD TIL levels had greater prognostic significance in the no Ki67 decrease group.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...