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1.
Biosens Bioelectron ; 265: 116648, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39178718

RESUMO

Subcellularly amperometric analysis in situ is crucial for understanding intracellular redox biochemistry and subcellular heterogeneity. Unfortunately, the ultra-small size and complex microenvironment inside the cell pose a great challenge to achieve this goal. To address the challenge, a minimized living microbial sensor has been fabricated in this work for amperometric analysis. Here, by fabricating the dimidiate microelectrode as the working electrode, while fitting a living electroactive bacterium (EAB) as the transducer, outward extracellular electron transfer (EET) of the sensory EAB is correlated with the concentration of lactic acid, which is electrochemically recorded and thus displays an electrical signal output for detection. In specific, the S. oneidensis modified dimidiate microelectrode (S.O.@GNE-NPE) acts as an integrated electroanalytical device to generate the electrical signal in situ. The established microcircuit provides unprecedented precision and sensitivity, contributing to subcellular amperometric measurement. The microbial sensor shows a linear response in the concentration range of 0-60 mM, with a limit of detection (LOD) at 0.3 mM. The microsensor also demonstrates good selectivity against interferences. Additionally, intracellular analysis of lactic acid provides direct evidence of enhanced lactic metabolism in cancer cells as a result of "Warburg Effect". This work shows an example of nano-, bio- and electric technologies that have been integrated on the EAB-modified dimidiate microelectrode, and achieves intracellular biosensing application through such integration. It may give a new strategy on the combination of micro/nanotechnologies with sensory EAB for the necessary development of bioelectronic devices.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Ácido Láctico , Microeletrodos , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Humanos , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Ácido Láctico/análise , Ácido Láctico/metabolismo , Desenho de Equipamento , Limite de Detecção , Shewanella
2.
World J Gastrointest Surg ; 16(7): 2047-2053, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39087105

RESUMO

BACKGROUND: The optimal approach for managing hepatic hemangioma is controversial. AIM: To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience. METHODS: A clinical grading system was retrospectively applied to 1171 patients with hepatic hemangioma from January 2002 to December 2018. Patients were classified into four groups based on the clinical grading system and treatment: (1) Observation group with score < 4 (Obs score < 4); (2) Surgical group with score < 4 (Sur score < 4); (3) Observation group with score ≥ 4 (Obs score ≥ 4); and (4) Surgical group with score ≥ 4 (Sur score ≥ 4). The clinico-pathological index and outcomes were evaluated. RESULTS: There were significantly fewer symptomatic patients in surgical groups (Sur score ≥ 4 vs Obs score ≥ 4, P < 0.001; Sur score < 4 vs Obs score < 4, χ² = 8.60, P = 0.004; Sur score ≥ 4 vs Obs score < 4, P < 0.001). The patients in Sur score ≥ 4 had a lower rate of in need for intervention and total patients with adverse event than in Obs score ≥ 4 (P < 0.001; P < 0.001). Nevertheless, there was no significant difference in need for intervention and total patients with adverse event between the Sur score < 4 and Obs score < 4 (P > 0.05; χ² = 1.68, P > 0.05). CONCLUSION: This clinical grading system appeared as a practical tool for hepatic hemangioma. Surgery can be suggested for patients with a score ≥ 4. For those with < 4, follow-up should be proposed.

3.
Nat Commun ; 15(1): 5818, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987265

RESUMO

A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety of cell death and survival pathways, yet the understanding of mitochondria and their dysfunction in primary human cells and in specific disease states, including asthma, is modest. Ferroptosis is traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic and mitochondrial damage to drive programmed cell death. However, in this report we identify a lipoxygenase orchestrated, compartmentally-targeted ferroptosis-associated peroxidation process which occurs in a subpopulation of dysfunctional mitochondria, without promoting cell death. Rather, this mitochondrial peroxidation process tightly couples with PTEN-induced kinase (PINK)-1(PINK1)-Parkin-Optineurin mediated mitophagy in an effort to preserve the pool of functional mitochondria and prevent cell death. These combined peroxidation processes lead to altered epithelial cell phenotypes and loss of ciliated cells which associate with worsened asthma severity. Ferroptosis-targeted interventions of this process could preserve healthy mitochondria, reverse cell phenotypic changes and improve disease outcomes.


Assuntos
Asma , Proteínas de Ciclo Celular , Células Epiteliais , Ferroptose , Proteínas de Membrana Transportadoras , Mitocôndrias , Mitofagia , Fenótipo , Fator de Transcrição TFIIIA , Humanos , Mitocôndrias/metabolismo , Asma/metabolismo , Asma/patologia , Células Epiteliais/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Fator de Transcrição TFIIIA/metabolismo , Fator de Transcrição TFIIIA/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Masculino , Proteínas Quinases/metabolismo , Feminino , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Animais , Peroxidação de Lipídeos , Camundongos , Pessoa de Meia-Idade
4.
BJS Open ; 8(3)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38935425

RESUMO

BACKGROUND: Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related biomarker. The aim of the study was to assess soluble suppression of tumourigenicity 2 elevation after hepatectomy and whether it can predict posthepatectomy liver failure. METHODS: This was a single-centre retrospective study including all patients who underwent a liver resection between 2015 and 2019. Plasma concentrations of soluble suppression of tumourigenicity 2 were measured before surgery and at postoperative days 1, 2, 5 and 7. Posthepatectomy liver failure was defined according to the International Study Group of Liver Surgery and the morbidity rate was graded according to the Clavien-Dindo classification. RESULTS: A total of 173 patients were included (75 underwent major and 98 minor resection); plasma levels of soluble suppression of tumourigenicity 2 increased from 43.42 (range 18.69-119.96) pg/ml to 2622.23 (range 1354.18-4178.27) pg/ml on postoperative day 1 (P < 0.001). Postoperative day 1 soluble suppression of tumourigenicity 2 concentration accurately predicted posthepatectomy liver failure ≥ grade B (area under curve = 0.916, P < 0.001) and its outstanding performance was not affected by underlying disease, liver pathological status and extent of resection. The cut-off value, sensitivity, specificity, positive predictive value and negative predictive value of postoperative day 1 soluble suppression of tumourigenicity 2 in predicting posthepatectomy liver failure ≥ grade B were 3700, 92%, 85%, 64% and 97% respectively. Soluble suppression of tumourigenicity 2high patients more frequently experienced posthepatectomy liver failure ≥ grade B (64.3% (n = 36) versus 2.6% (n = 3)) and Clavien-Dindo IIIa higher morbidity rate (23.2% (n = 13) versus 5.1% (n = 6)) compared with soluble suppression of tumourigenicity 2low patients. CONCLUSIONS: Soluble suppression of tumourigenicity 2 may be a reliable predictor of posthepatectomy liver failure ≥ grade B as early as postoperative day 1 for patients undergoing liver resection. Its role in controlling hepatic injury/regeneration needs further investigation. Registration number: ChiCTR-OOC-15007210 (www.chictr.org.cn/).


Assuntos
Biomarcadores , Hepatectomia , Falência Hepática , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Hepatectomia/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Falência Hepática/etiologia , Falência Hepática/sangue , Falência Hepática/prevenção & controle , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Idoso , Biomarcadores/sangue , Adulto , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/sangue , Valor Preditivo dos Testes
5.
Int J Oncol ; 64(6)2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38695241

RESUMO

Cancer remains a formidable adversary, challenging medical advancements with its dismal prognosis, low cure rates and high mortality rates. Within this intricate landscape, long non­coding RNAs (lncRNAs) emerge as pivotal players, orchestrating proliferation and migration of cancer cells. Harnessing the potential of lncRNAs as therapeutic targets and prognostic markers holds immense promise. The present comprehensive review delved into the molecular mechanisms underlying the involvement of lncRNAs in the onset and progression of the top five types of cancer. By meticulously examining lncRNAs across diverse types of cancer, it also uncovered their distinctive roles, highlighting their exclusive oncogenic effects or tumor suppressor properties. Notably, certain lncRNAs demonstrate diverse functions across different cancers, confounding the conventional understanding of their roles. Furthermore, the present study identified lncRNAs exhibiting aberrant expression patterns in numerous types of cancer, presenting them as potential indicators for cancer screening and diagnosis. Conversely, a subset of lncRNAs manifests tissue­specific expression, hinting at their specialized nature and untapped significance in diagnosing and treating specific types of cancer. The present comprehensive review not only shed light on the intricate network of lncRNAs but also paved the way for further research and clinical applications. The unraveled molecular mechanisms offer a promising avenue for targeted therapeutics and personalized medicine, combating cancer proliferation, invasion and metastasis.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias , RNA Longo não Codificante , RNA Longo não Codificante/genética , Humanos , Neoplasias/genética , Neoplasias/patologia , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Prognóstico , Progressão da Doença
6.
Obes Surg ; 34(4): 1138-1151, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38351200

RESUMO

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are the two most frequently performed techniques in treating obesity and its related comorbidities. We aimed to compare the clinical efficacy and safety of LSG with LRYGB in terms of short- and mid-term outcomes of weight loss, obesity-related comorbidities, and post-operative complications via a meta-analysis of RCTs. METHODS: Clinical comparative RCTs on LSG and LRYGB were searched through PubMed, MEDLINE, and Web of Science databases from inception to August 2022. Pooled outcomes from the selected studies were discussed by the random-effect meta-analysis method. Quality assessment and risk of bias for selected RCTs were implemented, and all the statistical analyses were performed. RESULTS: Twenty studies, including 1270 patients, were enrolled. Meta-analysis results indicated the great superior efficacy of LRYGB to LSG in BMI loss at 6 (MD -1.35 kg/m2, 95% CI: -2.07 to -0.62, p = 0.0003), 12 months (MD -1.09 kg/m2, 95% CI: -1.86 to -0.33, p = 0.005), and 36 months (MD -1.47 kg/m2, 95% CI: -2.77 to -0.16, p = 0.03) as well as %EWL gaining at 36 months. Significantly higher remission rates of T2DM and dyslipidemia were achieved by LRYGB at 12 months. Besides, better improvements for T2DM-related and lipid biochemical parameters were found favoring LRYGB. However, LSG resulted in a lower post-operative complication rate and shorter operating time. CONCLUSIONS: Present meta-analysis results suggested that LRYGB was superior to LSG concerning short- and mid-term weight loss, short-term T2DM remission efficacy, and related biochemical parameters. LSG is favored for obviously fewer complications and shorter operating time.


Assuntos
Gastrectomia , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Ensaios Clínicos Controlados Aleatórios como Assunto , Redução de Peso , Humanos , Obesidade Mórbida/cirurgia , Gastrectomia/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade
7.
ACS Omega ; 8(43): 40242-40250, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37929105

RESUMO

In this paper, through the establishment of a blockage analysis process, multistage weight loss method, and FT-IR, GC-MS, SEM, EDS, XRD and other characterization test means, it is clear that the scale sample is mainly organic material covered with complex and diverse sulfur and iron compounds, and the mechanism of sulfur-containing gas well blockage is revealed by tracing into the well material, formation minerals, acid gas corrosion, and other substances. Through the selection of chelating agent, cleaning agent, and acid concentration, as well as the optimization of different process parameters, the "dispersion-chelation-dissolution" composite unblocking technology is proposed, and a set of unblocking formula systems for complex sulfur and iron scale is clarified. Finally, XRD and SEM characterization tests of the scale samples before and after dissolution were conducted to study the declogging mechanism and confirm the acid-insoluble nature of FeS2 and its stability in a weak acidic environment.

8.
Ann Med ; 55(2): 2279748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37983519

RESUMO

The intricate web of cancer biology is governed by the active participation of long non-coding RNAs (lncRNAs), playing crucial roles in cancer cells' proliferation, migration, and drug resistance. Pioneering research driven by machine learning algorithms has unveiled the profound ability of specific combinations of lncRNAs to predict the prognosis of cancer patients. These findings highlight the transformative potential of lncRNAs as powerful therapeutic targets and prognostic markers. In this comprehensive review, we meticulously examined the landscape of lncRNAs in predicting the prognosis of the top five cancers and other malignancies, aiming to provide a compelling reference for future research endeavours. Leveraging the power of machine learning techniques, we explored the predictive capabilities of diverse lncRNA combinations, revealing their unprecedented potential to accurately determine patient outcomes.


lncRNAs play crucial roles in cancer biology, regulating proliferation, migration, and drug resistance.Emerging evidence suggests that machine learning can predict cancer prognosis using specific lncRNA combinations.Comprehensive information on the predictive abilities of lncRNA combinations in oncology concerning machine learning is lacking.This review offers up-to-date vital references on diverse lncRNA combinations pertinent to future research and clinical trials.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Neoplasias/diagnóstico , Neoplasias/genética , Prognóstico , Aprendizado de Máquina
9.
Nat Commun ; 13(1): 6107, 2022 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-36245043

RESUMO

Acute myeloid leukemia (AML) is maintained by self-renewing leukemic stem cells (LSCs). A fundamental problem in treating AML is that conventional therapy fails to eliminate LSCs, which can reinitiate leukemia. Heat shock transcription factor 1 (HSF1), a central regulator of the stress response, has emerged as an important target in cancer therapy. Using genetic Hsf1 deletion and a direct HSF1 small molecule inhibitor, we show that HSF1 is specifically required for the maintenance of AML, while sparing steady-state and stressed hematopoiesis. Mechanistically, deletion of Hsf1 dysregulates multifaceted genes involved in LSC stemness and suppresses mitochondrial oxidative phosphorylation through downregulation of succinate dehydrogenase C (SDHC), a direct HSF1 target. Forced expression of SDHC largely restores the Hsf1 ablation-induced AML developmental defect. Importantly, the growth and engraftment of human AML cells are suppressed by HSF1 inhibition. Our data provide a rationale for developing efficacious small molecules to specifically target HSF1 in AML.


Assuntos
Autorrenovação Celular , Leucemia Mieloide Aguda , Humanos , Autorrenovação Celular/genética , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Células-Tronco Neoplásicas/metabolismo , Succinato Desidrogenase/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
World Allergy Organ J ; 15(10): 100702, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36254182

RESUMO

Background: Clinical studies on the effectiveness of omalizumab in patients with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are scarce in China. Moreover, identifying potential biomarkers predicting its efficacy remains a great challenge. Methods: In this prospective trial, all enrolled patients underwent endoscopic examination, computed tomography, blood tests, etc, and they completed a 22-item sino-nasal outcome test (SNOT-22), visual analogue scale (VAS), and asthma control test (ACT) evaluation, at baseline and after 24-week omalizumab therapy. Results: Twenty-two patients were finally recruited. Their VAS scores were significantly better including nasal congestion, anterior rhinorrhea, postnasal drip, and loss of smell (P < 0.01). Seventeen patients reported a reduction in SNOT-22 scores of ≥8.9 and 19 patients achieved ACT scores >20. The median change in the Lund-MacKay score (LMS) was 6. Both the Lund-Kennedy score (LKS) and nasal polyp score showed significant improvement (P < 0.01). Only 3 parameters in the pulmonary function test showed evident amelioration (P < 0.05). The eosinophilic CRSwNP and the male subgroups showed better improvements in subjective and objective evaluation. A receiver operating characteristic curve indicated a cutoff value of 17.5 and 16.5 in LMS had the moderate predictive value (AUC = 0.706) for the decline in the SNOT-22 (more than 8.9 points) and reduction in anterior rhinorrhea VAS (more than 2 cm), respectively. A cutoff value of 18.5 in ACT could provide the moderate predictive value (AUC = 0.771) for the reduction of loss of smell VAS (more than 2 cm). Conclusions: The beneficial effectiveness of omalizumab in the patients with difficult-to-treat CRSwNP and asthma was confirmed. ECRSwNP and male patients were more likely to have positive responses. The multiple cutoff values for the LMS and ACT may serve as useful predictors for improvement acceptable to difficult-to-treat CRSwNP patients.

11.
J Chromatogr A ; 1683: 463547, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36228572

RESUMO

Barium sulfate (BaSO4) content is used to evaluate the grade of barite ore. In the present study, we report a method to determine the BaSO4 content in barite ore by phase conversion-headspace gas chromatography with partial pressure correction. In this method, the ore sample is roasted with sodium carbonate and potassium carbonate after pretreatment with hydrochloric acid. The roasted product is subsequently placed in a closed headspace bottle to react with hydrochloric acid. The ratio of CO2 to O2 signals is detected by a thermal conductivity detector for gas chromatography. Finally, the BaSO4 content in barite ore is calculated using this ratio. The method demonstrates good precision (relative standard deviation < 0.84%) and accuracy (relative error < 3.40%), with the uncertainty at 95% confidence interval at approximately +/- 0.57%. Moreover, this approach is expected to be used for the batch testing of BaSO4 content in barite ores in industrial applications.


Assuntos
Sulfato de Bário , Dióxido de Carbono , Sulfato de Bário/química , Pressão Parcial , Ácido Clorídrico , Cromatografia Gasosa/métodos
12.
Int J Mol Sci ; 23(19)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36233329

RESUMO

NAC transcription factors (TFs) could regulate drought stresses in plants; however, the function of NAC TFs in soybeans remains unclear. To unravel NAC TF function, we established that GmNAC12, a NAC TF from soybean (Glycine max), was involved in the manipulation of stress tolerance. The expression of GmNAC12 was significantly upregulated more than 10-fold under drought stress and more than threefold under abscisic acid (ABA) and ethylene (ETH) treatment. In order to determine the function of GmNAC12 under drought stress conditions, we generated GmNAC12 overexpression and knockout lines. The present findings showed that under drought stress, the survival rate of GmNAC12 overexpression lines increased by more than 57% compared with wild-type plants, while the survival rate of GmNAC12 knockout lines decreased by at least 46%. Furthermore, a subcellular localisation analysis showed that the GmNAC12 protein is concentrated in the nucleus of the tobacco cell. In addition, we used a yeast two-hybrid assay to identify 185 proteins that interact with GmNAC12. Gene ontology (GO) and KEGG analysis showed that GmNAC12 interaction proteins are related to chitin, chlorophyll, ubiquitin-protein transferase, and peroxidase activity. Hence, we have inferred that GmNAC12, as a key gene, could positively regulate soybean tolerance to drought stress.


Assuntos
Secas , Glycine max , Ácido Abscísico/metabolismo , Quitina/metabolismo , Clorofila , Etilenos , Regulação da Expressão Gênica de Plantas , Peroxidases/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Glycine max/metabolismo , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transferases/metabolismo , Ubiquitinas/metabolismo
13.
Medicine (Baltimore) ; 101(22): e29326, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35665732

RESUMO

OBJECTIVES: Leiomyosarcoma of inferior vena cava (IVC) is a rare clinical entity with severe vascular involvement. Surgical management of leiomyosarcoma is still challenging. METHODS: This a retrospective study of consecutive patients referred to our hospital from January 2017 to June 2019. Depending on the anatomical site of affected IVC, leiomyosarcomas were categorized into zone I-II. The clinical data including baseline information, surgical parameters, peri-operative management, short- and mid-term outcomes were observed. RESULTS: Four patients with leiomyosarcoma of zone I-III underwent radical resection without intraoperative mortality. Prosthetic grafts were interpositioned in all patients to instruct vena cava. Renal vein reconstruction was perfumed in two patients due to involvement to renal veins. Median blood loss was 450 mL (200-600 mL), median operative time was 215 minutes (150-240 minutes). No Clavien-Dindo IIIa or higher complication was observed. No organ dysfunction and recurrence were observed with median follow-up of 25.5 months. CONCLUSIONS: Curative resection of zone I-II leiomyosarcoma is associated with longer survival in selected cases, en-bloc resection with complex vascular reconstruction could be considered.


Assuntos
Leiomiossarcoma , Neoplasias Vasculares , Humanos , Leiomiossarcoma/cirurgia , Veias Renais , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Vasculares/cirurgia , Veia Cava Inferior/cirurgia
14.
Transpl Immunol ; 71: 101525, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34990790

RESUMO

BACKGROUND: As an early complication after liver transplantation, early allograft dysfunction (EAD) indicates a poor prognosis. This study analyzes the risk factors related to early allograft dysfunction (EAD) after liver transplantation using grafts from donation after citizen death (DCD) to provide a reference for the prevention of EAD after DCD liver transplantation. METHODS: A total of 32 patients who underwent DCD liver transplantation in the organ transplantation center of our hospital from September 2013 to January 2021 were enrolled in this study. The patients were divided into the EAD group and non-EAD group according to whether they developed EAD after transplantation. The general data of the donors and recipients before transplantation, intraoperative conditions, and clinical data within one week after transplantation were compared between the two groups, and related complications were statistically analyzed. The follow-up time was one week postoperatively or, if they died within the first week postoperatively, until the patient died. RESULTS: The subjects included 10 females and 22 males, and the incidence of postoperative EAD was 25% (8/32). Four patients (12%) had primary malignant tumors (primary liver cancer and cholangiocarcinoma), and five donors (15%) had fatty liver. The univariate analysis revealed that the donor BMI (P = 0.005), degree of fatty liver (P = 0.025), aspartate aminotransferase (P = 0.001), alanine aminotransferase (P < 0.001), and total bilirubin (P = 0.009) were related to the occurrence of EAD after DCD liver transplantation. By analyzing the correlation between the incidence EAD and postoperative complications after liver transplantation using grafts from DCD donors, it was shown that the incidence of primary nonfunction (PNF) is related to EAD (P = 0.024). CONCLUSION: Donor BMI, the degree of fatty liver, and preoperative liver function are risk factors for EAD after DCD liver transplantation, and the occurrence of EAD after DCD liver transplantation significantly increases the probability of PNF.


Assuntos
Fígado Gorduroso , Hepatopatias , Transplante de Fígado , Fígado Gorduroso/etiologia , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Resultado do Tratamento
15.
J Clin Invest ; 132(1)2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34762602

RESUMO

Altered redox biology challenges all cells, with compensatory responses often determining a cell's fate. When 15 lipoxygenase 1 (15LO1), a lipid-peroxidizing enzyme abundant in asthmatic human airway epithelial cells (HAECs), binds phosphatidylethanolamine-binding protein 1 (PEBP1), hydroperoxy-phospholipids, which drive ferroptotic cell death, are generated. Peroxidases, including glutathione peroxidase 4 (GPX4), metabolize hydroperoxy-phospholipids to hydroxy derivatives to prevent ferroptotic death, but consume reduced glutathione (GSH). The cystine transporter SLC7A11 critically restores/maintains intracellular GSH. We hypothesized that high 15LO1, PEBP1, and GPX4 activity drives abnormal asthmatic redox biology, evidenced by lower bronchoalveolar lavage (BAL) fluid and intraepithelial cell GSH:oxidized GSH (GSSG) ratios, to enhance type 2 (T2) inflammatory responses. GSH, GSSG (enzymatic assays), 15LO1, GPX4, SLC7A11, and T2 biomarkers (Western blot and RNA-Seq) were measured in asthmatic and healthy control (HC) cells and fluids, with siRNA knockdown as appropriate. GSSG was higher and GSH:GSSG lower in asthmatic compared with HC BAL fluid, while intracellular GSH was lower in asthma. In vitro, a T2 cytokine (IL-13) induced 15LO1 generation of hydroperoxy-phospholipids, which lowered intracellular GSH and increased extracellular GSSG. Lowering GSH further by inhibiting SLC7A11 enhanced T2 inflammatory protein expression and ferroptosis. Ex vivo, redox imbalances corresponded to 15LO1 and SLC7A11 expression, T2 biomarkers, and worsened clinical outcomes. Thus, 15LO1 pathway-induced redox biology perturbations worsen T2 inflammation and asthma control, supporting 15LO1 as a therapeutic target.


Assuntos
Araquidonato 15-Lipoxigenase/metabolismo , Asma/enzimologia , Células Epiteliais/enzimologia , Ferroptose , Glutationa/metabolismo , Mucosa Respiratória/enzimologia , Transdução de Sinais , Linhagem Celular , Células Epiteliais/patologia , Regulação da Expressão Gênica , Humanos , Inflamação/enzimologia , Inflamação/patologia , Oxirredução , Mucosa Respiratória/patologia
16.
Allergy ; 77(2): 540-549, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34735742

RESUMO

BACKGROUND: Recent studies have revealed that the nasal microbiota in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is profoundly altered and is correlated with systemic inflammation. However, little is known regarding whether the microbiota can be utilized to predict nasal polyp recurrence. This study is aimed to determine whether altered nasal microbiota constituents could be used as biomarkers to predict CRSwNP recurrence. METHODS: Nasal microbiota constituents were quantified and characterized using bacterial 16S ribosomal RNA gene sequencing. Selected features for least absolute shrinkage and selection operator regression-based predictors were the nasal microbiota community composition and CRSwNP patient clinical characteristics. The primary outcome was recurrence, which was determined post-admission. RESULTS: By distinguishing recurrence-associated nasal microbiota taxa and exploiting the distinct nasal microbiota abundance between patients with recurrent and non-recurrent CRSwNP, we developed a predictive classifier for the diagnosis of nasal polyps' recurrence with 91.4% accuracy. CONCLUSIONS: Key taxonomical features of the nasal microbiome could predict recurrence in CRSwNP patients. The nasal microbiome is an understudied source of clinical variation in CRSwNP and represents a novel therapeutic target for future prevention and treatment.


Assuntos
Microbiota , Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Humanos , Microbiota/genética , Pólipos Nasais/diagnóstico , RNA Ribossômico 16S/genética , Rinite/diagnóstico , Rinite/microbiologia , Sinusite/diagnóstico , Sinusite/microbiologia
17.
J Allergy Clin Immunol ; 149(2): 579-588, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34547368

RESUMO

BACKGROUND: The epithelium is increasingly recognized as a pathologic contributor to asthma and its phenotypes. Although delayed wound closure by asthmatic epithelial cells is consistently observed, underlying mechanisms remain poorly understood, partly due to difficulties in studying dynamic physiologic processes involving polarized multilayered cell systems. Although type-2 immunity has been suggested to play a role, the mechanisms by which repair is diminished are unclear. OBJECTIVES: This study sought to develop and utilize primary multilayered polarized epithelial cell systems, derived from patients with asthma, to evaluate cell migration in response to wounding under type-2 and untreated conditions. METHODS: A novel wounding device for multilayered polarized cells, along with time-lapse live cell/real-time confocal imaging were evaluated under IL-13 and untreated conditions. The influence of inhibition of 15 lipoxygenase (15LO1), a type-2 enzyme, on the process was also addressed. Cell migration patterns were analyzed by high-dimensional frequency modulated Möbius for statistical comparisons. RESULTS: IL-13 stimulation negatively impacts wound healing by altering the total speed, directionality, and acceleration of individual cells. Inhibition 15LO1 partially improved the wound repair through improving total speed. CONCLUSIONS: Migration abnormalities contributed to markedly slower wound closure of IL-13 treated cells, which was modestly reversed by 15LO1 inhibition, suggesting its potential as an asthma therapeutic target. These novel methodologies offer new ways to dynamically study cell movements and identify contributing pathologic processes.


Assuntos
Asma/etiologia , Araquidonato 15-Lipoxigenase/fisiologia , Asma/diagnóstico por imagem , Asma/tratamento farmacológico , Asma/imunologia , Movimento Celular , Células Cultivadas , Células Epiteliais/fisiologia , Humanos , Interleucina-13/farmacologia , Inibidores de Lipoxigenase/farmacologia , Cicatrização/efeitos dos fármacos
18.
Minim Invasive Ther Allied Technol ; 31(3): 332-341, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33143517

RESUMO

BACKGROUND: This paper evaluates the efficacy and safety of repeat hepatic resection and radiofrequency ablation in the treatment of recurrent hepatocellular carcinoma. MATERIAL AND METHODS: We retrieved and collected all relevant articles from the inception to 8 March 2020. After data extraction, we conducted meta-analysis and carried out the heterogeneity test, sensitivity analysis, and publication bias test to evaluate reliability. RESULTS: A total of 12 studies with 1746 patients (rHR 837, RFA 909) were included. rHR was similar to RFA in a one-year overall survival rate (OS), while rHR was superior to RFA in 3- and 5-year OS and 1-, 3-, and 5-year disease-free survival rates (DFS), but the procedure-related complications of RFA were significantly less than those of rHR. Among the subgroups with Milan criteria, rHR was similar to RFA in 1-, 3-, and 5-year OS and 1-year DFS, but superior to RFA in 3- and 5-year DFS. CONCLUSIONS: RFA is the first choice for recurrent HCC meeting Milan criteria. When it does not meet the Milan criteria, minimally invasive treatment should not be carried out at the cost of survival, and rHR should be the first choice.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/efeitos adversos , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento
19.
iScience ; 24(12): 103425, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34877491

RESUMO

We previously showed stabilization of NIK-induced activation of NF-κB non-canonical signaling suppresses MLL-AF9-induced AML. In the current study, we demonstrate that deletion of NF-κB non-canonical RelB prevents the inhibitory effect of NIK stabilization in MLL-AF9 AML. Mechanistically, RelB suppresses its direct target, TIFAB, which is upregulated in human AML and correlates negatively with the survival of AML patients. Forced expression of TIFAB reverses NIK-induced impaired AML development through downregulation of RelB and upregulation of HOXA9. Consistent with upregulation of HOXA9, gene set enrichment analysis shows that forced expression of TIFAB blocks myeloid cell development, upregulates leukemia stem cell signature and induces similar gene expression patterns to those of HOXA9-MEIS1 and HOXA9-NUP98, and upregulates oxidative phosphorylation. Accordingly, forced expression of HOXA9 also largely releases the inhibitory impact of NIK stabilization via downregulation of RelB and upregulation of RelA. Our data suggest that NIK/RelB suppresses MLL-AF9-induced AML mainly through downregulation of TIFAB/HOXA9.

20.
Artigo em Chinês | MEDLINE | ID: mdl-34304525

RESUMO

Objective:To observe the effect of endoscopic dacryocystorhinostomy on different lacrimal duct obstruction. Methods:Eighty eyes with the lacrimal passage obstruction were collected, and treated with endoscopic dacryocystorhinostomy. Meanwhile, the abnormal structures of the nasal cavity were corrected and the pathological changes of the nasal cavity and sinuses were treated. The patients were followed up and the curative effect was observed. Follow-up period ranged from 10 months to 8 years. Results:The first operation cure rate was 78.8%, the effective rate was 17.5%, the ineffective rate was 3.8%, and the success rate was 96.2%. Two of the 3 eyes failed in first operation were cured by reoperation. The total success rate was 98.8%. Conclusion:Endoscopic dacryocystorhinostomy can be used as a routine operation in the treatment of different lacrimal duct obstruction. The structural abnormalities and pathological changes of the nasal cavity and paranasal sinuses can be treated simultaneously. Combined with postoperative treatment and follow-up, long-term curative effect can be obtained.


Assuntos
Dacriocistorinostomia , Aparelho Lacrimal , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Endoscopia , Humanos , Aparelho Lacrimal/cirurgia , Ducto Nasolacrimal/cirurgia , Resultado do Tratamento
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