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1.
Front Immunol ; 12: 594330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33828547

RESUMO

Cigarette smoke (CS)-induced macrophage activation and airway epithelial injury are both critical for the development of chronic obstructive pulmonary disease (COPD), while the eventual functions of autophagy in these processes remain controversial. We have recently developed a novel COPD mouse model which is based on the autoimmune response sensitized by CS and facilitated by elastin. In the current study, we therefore utilized this model to investigate the roles of autophagy in different stages of the development of bronchitis-like airway inflammation. Autophagic markers were increased in airway epithelium and lung tissues, and Becn+/- or Lc3b-/ - mice exhibited reduced neutrophilic airway inflammation and mucus hyperproduction in this COPD mouse model. Moreover, treatment of an autophagic inhibitor 3-methyladenine (3-MA) either during CS-initiated sensitization or during elastin provocation significantly inhibited the bronchitis-like phenotypes in mice. Short CS exposure rapidly induced expression of matrix metallopeptidase 12 (MMP12) in alveolar macrophages, and treatment of doxycycline, a pan metalloproteinase inhibitor, during CS exposure effectively attenuated the ensuing elastin-induced airway inflammation in mice. CS extract triggered MMP12 expression in cultured macrophages, which was attenuated by autophagy impairment (Becn+/- or Lc3b-/ -) or inhibition (3-MA or Spautin-1). These data, taken together, demonstrate that autophagy mediates both the CS-initiated MMP12 activation in macrophages and subsequent airway epithelial injury, eventually contributing to development COPD-like airway inflammation. This study reemphasizes that inhibition of autophagy as a novel therapeutic strategy for CS-induced COPD.

3.
J Invasive Cardiol ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33833128

RESUMO

OBJECTIVE: The study sought to assess the effectiveness and safety of the novel P60 Vivolight frequency-domain optical coherence tomography (OCT) system (Shenzhen Vivolight Medical Device & Technology). METHODS: A total of 90 patients were enrolled from 3 institutions. The pullbacks were performed with both the P60 Vivolight OCT system and the Ilumien Optis OCT system (Abbott Vascular). The primary endpoint was the clear stent length (CSL). Device safety was assessed by the record of serious procedure-related or postprocedure adverse events. The secondary endpoints were the average lumen area of stent, clear image length (CIL), system stability, and imaging catheter operability. RESULTS: The mean relative errors of CSL were 3.30% (95% confidence interval [CI], -0.71 to 7.31) in the full analysis set (FAS) and 0.83% (95% CI, -1.79 to 3.45) in the per-protocol set (PPS). The mean relative errors of the average lumen area of stent were 2.20% (95% CI, 0.70 to 3.80) in the FAS and 1.55% (95% CI, 0.30 to 2.80) in the PPS. No difference was observed in the percentage of obtaining >24 mm of CIL (93.18% in the P60 Vivolight group vs 95.45% in the Ilumien Optis group; P=.48). There were no serious procedure-related or postprocedure adverse events. CONCLUSIONS: The feasibility and safety of the novel Vivolight OCT system is equivalent to that of the Ilumien Optis OCT system.

4.
Cell Immunol ; 364: 104341, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33798909

RESUMO

Asthma is a chronic inflammatory disease of the lungs that poses a considerable health and socioeconomic burden. Several risk factors work synergistically to affect the progression of asthma. Lipid metabolism, especially in distinct cells such as T cells, macrophages, granulocytes, and non-immune cells, plays an essential role in the pathogenesis of asthma, as lipids are potent signaling molecules that regulate a multitude of cellular response. In this review, we focused on the metabolic pathways of lipid molecules, especially fatty acids and their derivatives, and summarized their roles in various cells during the pathogenesis of asthma along with the current pharmacological agents targeting lipid metabolism.

5.
Hum Mutat ; 42(5): 577-591, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33644933

RESUMO

Xia-Gibbs syndrome (XGS) is a rare Mendelian disease typically caused by de novo stop-gain or frameshift mutations in the AT-hook DNA binding motif containing 1 (AHDC1) gene. Patients usually present in early infancy with hypotonia and developmental delay and later exhibit intellectual disability (ID). The overall presentation is variable, however, and the emerging clinical picture is still evolving. A detailed phenotypic analysis of 34 XGS individuals revealed five core phenotypes (delayed motor milestones, speech delay, low muscle tone, ID, and hypotonia) in more than 80% of individuals and an additional 12 features that occurred more variably. Seizures and scoliosis were more frequently associated with truncations that arise before the midpoint of the protein although the occurrence of most features could not be predicted by the mutation position. Transient expression of wild type and different patient truncated AHDC1 protein forms in human cell lines revealed abnormal patterns of nuclear localization including a diffuse distribution of a short truncated form and nucleolar aggregation in mid-protein truncated forms. Overall, both the occurrence of variable phenotypes and the different distribution of the expressed protein reflect the heterogeneity of this syndrome.

6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(1): 28-32, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33565396

RESUMO

OBJECTIVE: To investigate the predictive value of different glycemic variability indexes within 6 hours on the short-term prognosis of septic shock patients. METHODS: A retrospective study was conducted. The 133 patients with septic shock admitted to intensive care unit (ICU) of Nanjing Hospital Affiliated to Nanjing Medical University from December 2014 to December 2019 were enrolled. Patients with septic shock admitted to ICU died during hospitalization were enrolled in the death group and others in the survival group. General data of the patients including gender, age, underlying disease, site of infection, duration of mechanical ventilation, length of ICU stay, whether to use continuous renal replacement therapy (CRRT) and acute physiology and chronic health evaluation II (APACHE II) scores within 24 hours were collected. The blood glucose (GLUadm), mean arterial pressure (MAP), serum creatinine (SCr) and procalcitonin (PCT) were recorded at ICU admission. The patients admitted to ICU received bundle therapy within 6 hours and blood glucose was observed every 2 hours. The blood glucose difference (GLUdif), average blood glucose (GLUave), blood glucose standard deviation (GLUsd) and blood glucose variation coefficient (GLUcv) within 6 hours were calculated. Multivariate Logistic regression analysis was used to analyze the prognostic factors of short-term prognosis of patients with septic shock, and receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficacy of glycemic parameters for short-term prognosis of septic shock patients. RESULTS: A total of 133 patients with septic shock were admitted to ICU, among them 87 patients survived and 46 patients died during the ICU hospitalization. Compared with the survival group, the SCr at ICU admission and APACHE II score within 24 hours were significantly higher in the death group [SCr (µmol/L): 208.5 (143.0, 286.5) vs. 172.0 (91.0, 234.0), APACHE II score: 30.28±6.67 vs. 24.03±5.90, both P < 0.05], the length of ICU stay was shorter [days: 4.00 (2.00, 10.25) vs. 9.00 (4.00, 13.00), P < 0.01]. However, there were no significant differences in the baseline data of gender, age, underlying disease, infection site, CRRT ratio, MAP or PCT at ICU admission between the two groups. Compared with the survival group, the GLUsd and GLUcv within 6 hours in the death group were higher [GLUsd (mmol/L): 2.33 (1.95, 3.14) vs. 2.02 (1.66, 2.52), GLUcv: (31.00±7.06)% vs. (23.31±10.51)%, both P < 0.05]. There were no statistically significant differences in the levels of GLUadm, GLUdif or GLUave within 6 hours between the two groups. Multivariate Logistic regression analysis showed that APACHE II score within 24 hours and GLUsd and GLUcv within 6 hours were independent risk factors of the short-term prognosis of septic shock patients [APACHE II score: odds ratio (OR) = 1.173, 95% confidence interval (95%CI) was 1.095-1.256, P = 0.000; GLUsd: OR = 1.465, 95%CI was 1.038-2.067, P = 0.030; GLUcv: OR = 1.089, 95%CI was 1.043-1.138, P = 0.000]. ROC curve analysis showed that GLUsd and GLUcv within 6 hours both had certain predictive value for the short-term prognosis of septic shock patients, the area under ROC curve (AUC) of GLUcv within 6 hours was higher than that of APACHE II score (0.765 vs. 0.753), and AUC of GLUsd within 6 hours was close to APACHE II score (0.629 vs. 0.753); and the diagnostic value of GLUsd combined with GLUcv within 6 hours was higher than the two respectively (AUC: 0.809 vs. 0.629, 0.765), the sensitivity was 97.8%, and the specificity was 66.7%. CONCLUSIONS: GLUsd combined with GLUcv within 6 hours can be used to estimate the short-term prognosis of septic shock patients.


Assuntos
Sepse , Choque Séptico , APACHE , Glicemia , Humanos , Unidades de Terapia Intensiva , Prognóstico , Curva ROC , Estudos Retrospectivos , Choque Séptico/diagnóstico , Choque Séptico/terapia
7.
Angiology ; 72(5): 451-458, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33401931

RESUMO

We investigated the association between plasma microRNA (miR)-204 and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus (T2DM). We consecutively enrolled 179 individuals with T2DM who underwent coronary computed tomography at Anzhen Hospital from January 2015 to September 2016. The CAC score (CACS) was expressed in Agatston units and >10 Hounsfield units were defined as CAC-positive status. Significant CAC was observed in 98 (54.7%) patients. Plasma miR-204 levels (relative expression) were significantly lower in patients with significant CAC than controls (1.001 ± 0.100 vs 0.634 ± 0.211, P < .001). Plasma miR-204 levels were also negatively correlated with the glycosylated hemoglobin A1c (HbA1c) level (r = -0.702, P < .001), CACS (r = -0.710, P < .001), and the United Kingdom Prospective Diabetes Study (UKPDS) score (r = -0.355, P < .001). After multivariate logistic analyses, plasma miR-204 levels were still significantly and independently associated with the presence of CAC (odds ratio = 0.103, CI = 0.018-0.583, P < .001) after adjustment for conventional risk factors. Receiver operating characteristic curve analysis showed that plasma miR-204 levels can predict the severity and extent of CAC, and the specificity was higher than that of the traditional risk factors UKPDS score and HbA1c. In conclusion, the downregulation of miR-204 was independently associated with CAC in patients with T2DM.

8.
J Bone Joint Surg Am ; 103(9): e36, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33475308

RESUMO

BACKGROUND: Environmental conditions strongly influence the healing capacity of connective tissues. Well-vascularized extrasynovial tendons typically undergo a robust wound-healing process following transection and repair. In contrast, avascular intrasynovial tendons do not mount an effective repair response. The current study tests the hypothesis that flexor tendons, as a function of their synovial environment, exhibit unique inflammatory, angiogenic, and metabolic responses to injury and repair. METHODS: Flexor tendons present a distinct opportunity to test the study hypothesis, as they have proximal regions that are extrasynovial and distal regions that are intrasynovial. In an internally controlled study design, the second and fifth forepaw flexor tendons were transected and repaired in either the extrasynovial or the intrasynovial anatomical region. Histological, gene expression, and proteomics analyses were performed at 3 and 7 days to define the early biological events that drive synovial environment-dependent healing responses. RESULTS: Uninjured intrasynovial tendons were avascular, contained high levels of proteoglycans, and expressed inflammatory factors, complement proteins, and glycolytic enzymes. In contrast, extrasynovial tendons were well vascularized, contained low levels of proteoglycans, and were enriched in inflammation inhibitors and oxidative phosphorylation enzymes. The response to injury and repair was markedly different between the 2 tendon regions. Extrasynovial tendons displayed a robust and rapid neovascularization response, increased expression levels of complement proteins, and an acute shift in metabolism to glycolysis, whereas intrasynovial tendons showed minimal vascularity and muted inflammatory and metabolic responses. CONCLUSIONS: The regional molecular profiles of intact and healing flexor tendons revealed extensive early differences in innate immune response, metabolism, vascularization, and expression of extracellular matrix as a function of the synovial environment. These differences reveal mechanisms through which extrasynovial tendons heal more effectively than do intrasynovial tendons. CLINICAL RELEVANCE: To improve outcomes after operative repair, future treatment strategies should promote features of extrasynovial healing, such as enhanced vascularization and modulation of the complement system and/or glucose metabolism.

9.
Methods Mol Biol ; 2158: 23-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32857362

RESUMO

Neonatal mouse hearts have a regenerative capacity similar to adult zebrafish. Different cardiac injury models have been established to investigate the regenerative capacity of neonatal mouse hearts, including ventricular amputation, cryoinjury, and ligation of a major coronary artery. While the ventricular resection model can be utilized to study how tissue forms and regenerates de novo, cryoinjury and coronary artery ligation are methods that might better mimic myocardial infarction by creating tissue damage and necrosis as opposed to the removal of healthy tissue in the ventricular amputation model. Here we describe methods of creating ventricular resection and cardiac cryoinjury in newborn mice.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criocirurgia/efeitos adversos , Traumatismos Cardíacos/patologia , Coração/fisiologia , Regeneração , Remodelação Ventricular , Animais , Animais Recém-Nascidos , Proliferação de Células , Feminino , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/reabilitação , Masculino , Camundongos
10.
J Hazard Mater ; 406: 124758, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33321313

RESUMO

Cellulose aerogels achieve excellent absorption of waste oil and organic pollutant, which has received lots of attention recently. It is still a big challenge to obtain aerogels with both high cost-effectiveness and advanced oil absorption performance, since it is a time-consuming, and environmentally unfriendly process to obtain cellulose, compared with direct usage of natural fibers. In this manuscript, we develop highly porous and hydrophobic kapok/microfibrillated cellulose (MFC) aerogels with a dual-scale hierarchically porous structure at micro-level as cost-effective, sustainable, and floating superabsorbents via simple vacuum freeze-drying and surface modification. Kapok, a natural hollow fiber, has been recently considered as a new sustainable resource for oil cleanup. By partially replacing MFC with chopped kapok fibers in MFC aerogels (MMAs), the resultant kapok/MFC aerogels (KCAs) exhibit ultralow density (5.1 mg/cm-3), ultrahigh porosity (99.58%) and hydrophobicity (140.1°) leading to advanced oil sorption (130.1 g/g) that is 25.3% higher than that of MMAs. In addition, these KCAs can rapidly and selectively absorb waste oil from oil-water mixture with ultrahigh absorption ability of 104-190.1 g/g, which is comparable to other environmentally unfriendly and high-cost aerogels. Furthermore, the KCAs own excellent reusability and sustainability. These benefits enable the KCAs a suitable alternative to clean oil spills.

11.
Cells ; 9(11)2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33187367

RESUMO

Molecular and functional characterization of alveolar epithelial type I (AT1) cells has been challenging due to difficulty in isolating sufficient numbers of viable cells. Here we performed single-cell RNA-sequencing (scRNA-seq) of tdTomato+ cells from lungs of AT1 cell-specific Aqp5-Cre-IRES-DsRed (ACID);R26tdTomato reporter mice. Following enzymatic digestion, CD31-CD45-E-cadherin+tdTomato+ cells were subjected to fluorescence-activated cell sorting (FACS) followed by scRNA-seq. Cell identity was confirmed by immunofluorescence using cell type-specific antibodies. After quality control, 92 cells were analyzed. Most cells expressed 'conventional' AT1 cell markers (Aqp5, Pdpn, Hopx, Ager), with heterogeneous expression within this population. The remaining cells expressed AT2, club, basal or ciliated cell markers. Integration with public datasets identified three robust AT1 cell- and lung-enriched genes, Ager, Rtkn2 and Gprc5a, that were conserved across species. GPRC5A co-localized with HOPX and was not expressed in AT2 or airway cells in mouse, rat and human lung. GPRC5A co-localized with AQP5 but not pro-SPC or CC10 in mouse lung epithelial cell cytospins. We enriched mouse AT1 cells to perform molecular phenotyping using scRNA-seq. Further characterization of putative AT1 cell-enriched genes revealed GPRC5A as a conserved AT1 cell surface marker that may be useful for AT1 cell isolation.

12.
Lipids Health Dis ; 19(1): 240, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198752

RESUMO

BACKGROUND: The association of the atherogenic index of plasma (AIP), an emerging lipid index that can predict the risk for cardiovascular disease, with adverse outcomes in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not been determined. Therefore, the aim of this study was to investigate whether the AIP could independently predict adverse cardiovascular events in T2DM patients with ACS undergoing PCI. METHODS: This study was a retrospective analysis of a single-centre prospective registry involving 826 consecutive T2DM patients who underwent primary or elective PCI for ACS from June 2016 to November 2017. This study ultimately included 798 patients (age, 61 ± 10 years; male, 72.7%). The AIP was calculated as the base 10 logarithm of the ratio of the plasma concentration of triglycerides to high-density lipoprotein-cholesterol (HDL-C). All the patients were divided into 4 groups based on the AIP quartiles. The primary endpoint was a composite of death from any cause, non-fatal spontaneous myocardial infarction (MI), non-fatal ischaemic stroke, and unplanned repeat revascularization. The key secondary endpoint was a composite of cardiovascular death, non-fatal MI, and non-fatal ischaemic stroke. RESULTS: During a median follow-up period of 927 days, 198 patients developed at least one event. An unadjusted Kaplan-Meier analysis showed that the incidence of the primary endpoint increased gradually with rising AIP quartiles (log-rank test, P = 0.001). A multivariate Cox proportional hazards analysis revealed that compared with the lowest AIP quartile, the top AIP quartile was associated with significantly increased risk for the primary and key secondary endpoints (hazard ratio [HR]: 2.249, 95% confidence interval [CI]: 1.438 to 3.517, P < 0.001; and HR: 2.571, 95% CI: 1.027 to 6.440, P = 0.044, respectively). CONCLUSIONS: A higher AIP value on admission was independently and strongly associated with adverse cardiovascular events in T2DM patients with ACS undergoing PCI.

13.
Onco Targets Ther ; 13: 11529-11535, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204107

RESUMO

Background: Lung squamous-cell carcinoma (SqCC) is the second most common histology in non-small-cell lung carcinomas (NSCLCs). The treatment options for advanced lung SqCC are still an unmet medical need. Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), is beneficial in the therapy of advanced NSCLC patients. This study aimed to preliminarily assess the efficacy and safety of low-dosage apatinib in patients with advanced lung SqCC. Methods: In this single-arm, open-label, investigator-initiated phase II prospective study (ChiCTR1800019808), we enrolled patients aged 54-80 years with platinum-refractory or chemotherapy rejected advanced lung squamous-cell carcinoma. Key exclusion criteria included major blood vessel involvement and gross hemoptysis with an amount of more than 20 mL. Apatinib at an initial dose of 250 mg was administered to patients once daily until disease progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was progression-free survival (PFS) in all patients. We assessed the adverse events according to the treatment received. Results: Thirty-eight patients were enrolled between June 11, 2015 and August 29, 2018. Two patients failed to evaluate treatment efficacy for personal reasons, and thus 36 patients were eligible for evaluation of tumor response to apatinib. Median PFS was 4.9 months (95% CI: 3.0-6.8 months). Six patients achieved partial response (PR); the objective response rate (ORR) was 16.7% (6/36), and the total disease control rate (DCR) was 77.8% (28/36). Followed up to March 2020, 35 of the 38 patients were dead, and the 1-year survival rate was 21.1% (8/38). The median overall survival (OS) was 6.9 months (95% CI: 5.2-8.5 months). The most common adverse events included fatigue (50.0%), hypertension (42.1%), proteinuria (23.7%), loss of appetite (23.1%) and hand-foot reaction (21.1%). No grade 4 adverse effect or drug-related mortality occurred. Conclusions: Low-dose apatinib monotherapy might be an option for patients with advanced lung squamous-cell carcinoma.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33165141

RESUMO

Hydrogen sulfide (H2S), generally known as a new gas signal molecule after nitric oxide (NO) and carbon monoxide (CO), in the last few decades has been found as an important endogenous gasotransmitter, playing a significant role in the cardiovascular system both pathologically and physiologically. In recent years, there is growing evidence that H2S provides myocardial protection against myocardial ischemia-reperfusion injury (MIRI), which resulted in an ongoing focus on the possible mechanisms of action accounting for the H2S cardioprotective effect. At present, lots of mechanisms of action have been verified through in vitro and in vivo models of ischemia-reperfusion (I/R) injury, such as S-sulfhydrated modification, anti-apoptosis, effects on miRNA, bidirectional effect on autophagy, anti-oxidant stress, or interaction with NO and CO. With advances in understanding of the molecular pathogenesis of MIRI and pharmacology studies, the design, the development and the pharmacological characterization of H2S-donor drugs have been made great important progress. This review summarizes the latest research progress on the role of H2S in MIRI, systematically explains the molecular mechanism of H2S affecting MIRI, and provides a new idea for the formulation of a myocardial protection strategy in the future.

15.
J Clin Lab Anal ; : e23657, 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33225517

RESUMO

BACKGROUND: To evaluate the ability of peripheral blood inflammatory markers in predicating the typing of COVID-19, prognosis, and some differences between COVID-19 and influenza A patients. METHODS: Clinical data on 285 cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. Additional 446 Influenza A outpatients' hematologic data were enrolled for comparison. RESULTS: NLR, SII, RLR, PLR, HsCRP, and IL-6 were significant higher and LMR was lower in severe COVID-19 patients than in mild COVID-19 patients (p < .001). PLR and LMR were lower in the individuals with influenza A than those with COVID-19 (p < .01). COVID-19 patients with higher levels of NLR, SII, RLR, PLR, HsCRP, and IL-6 and lower LMR were significantly associated with the severe type. AUC of NLR (0.76) was larger while the specificity of IL-6 (86%) and sensitivity of HsCRP (89%) were higher than other inflammatory markers in predicating the typing of COVID-19. PT had obvious correlation with all the inflammatory markers except RPR. NLR showed positive correlations with AST, TP, BUN, CREA, PT, and D-dimer. Patients with high IL-6 levels have a relatively worse prognosis (HR = 2.30). CONCLUSION: Peripheral blood inflammatory markers reflected the intensity of inflammation and associated with severity of COVID-19.NLR was more useful to predict severity as well as IL-6 to predict prognosis of COVID-19. PLR and LMR were initially found to be higher in SARS-CoV-2 virus-infected group than in influenza A.

16.
Oncogene ; 39(49): 7181-7195, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33037411

RESUMO

The development of resistance to EGFR Tyrosine kinase inhibitors (TKIs) in NSCLC with activating EGFR mutations is a critical limitation of this therapy. In addition to genetic alterations such as EGFR secondary mutation causing EGFR-TKI resistance, compensatory activation of signaling pathways without interruption of genome integrity remains to be defined. In this study, we identified S6K1/MDM2 signaling axis as a novel bypass mechanism for the development of EGFR-TKI resistance. The observation of S6K1 as a candidate mechanism for resistance to EGFR TKI therapy was investigated by interrogation of public databases and a clinical cohort to establish S6K1 expression as a prognostic/predictive biomarker. The role of S6K1 in TKI resistance was determined in in vitro gain-and-loss of function studies and confirmed in subcutaneous and orthotopic mouse lung cancer models. Blockade of S6K1 by a specific inhibitor PF-4708671 synergistically enhanced the efficacy of TKI without showing toxicity. The mechanistic study showed the inhibition of EGFR caused nuclear translocation of S6K1 for binding with MDM2 in resistant cells. MDM2 is a downstream effector of S6K1-mediated TKI resistance. Taken together, we present evidence for the reversal of resistance to EGFR TKI by the addition of small molecule S6K1/MDM2 antagonists that could have clinical benefit.

17.
Sheng Li Xue Bao ; 72(5): 575-585, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33106828

RESUMO

Ferroptosis is a novel form of regulated cell death which is dependent on iron and reactive oxygen species (ROS) and associated with the accumulation of lipid peroxides. It is obviously different from other cell death types in terms of morphology, biochemistry, genetics, etc. Also, it is related to the production of iron catalyzed lipid peroxides which is triggered by non-enzymatic or enzymatic reactions. Ferroptosis has been proved to be involved in hematological diseases, cardio-cerebrovascular diseases, liver and kidney diseases. This paper will review the definition, mechanism, inducers of ferroptosis, as well as the function of ferroptosis in respiratory system. We expect to present a new concept for respiratory research and suggest potential targets for clinical prevention and treatment of respiratory diseases.


Assuntos
Ferroptose , Transtornos Respiratórios , Morte Celular , Humanos , Ferro , Espécies Reativas de Oxigênio
18.
Sheng Li Xue Bao ; 72(5): 617-630, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33106832

RESUMO

Corona virus disease 2019 (COVID-19) is a new type of coronavirus pneumonia, which is caused by infection of a novel coronavirus, SARS-CoV-2. The virus infects lung cells by binding angiotensin-converting enzyme 2 (ACE2) of cell surface, which leads to leukocyte infiltration, increased permeability of blood vessels and alveolar walls, and decreased surfactant in the lung, causing respiratory symptoms. The aggravation of local inflammation causes cytokine storm, resulting in systemic inflammatory response syndrome. In December 2019, a number of new pneumonia cases were reported by Wuhan Municipal Health Commission, after then a novel coronavirus was isolated and identified as SARS-CoV-2. To the date of Sep. 13th, 2020, COVID-19 is affecting 216 countries or regions, causing 28 637 952 cases, 917 417 deaths, and the mortality rate is 3.20%. This review will summarize the structure of SARS-CoV-2 and the pharmaceutical treatment of COVID-19, and their potential relationships.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Vírus da SARS , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos
19.
J Geriatr Cardiol ; 17(9): 554-560, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33117419

RESUMO

Objective: To evaluate the effects and mechanisms of glucose-insulin-potassium (GIK) on post-procedural myocardial injury (PMI) after percutaneous coronary intervention (PCI). Methods: A total of 200 non-diabetic patients with documented coronary heart disease (CHD) were divided into the Group GIK and Group G, with 100 patients in each group. Patients in Group G were given intravenous infusion of glucose solution 2 hours before PCI. As compared, patients in Group GIK were given GIK. Results: Both post-procedural creatine phosphokinase isoenzyme MB (CK-MB; 62.1 ± 47.8 vs. 48.8 ± 52.6 U/L, P = 0.007) and cTnI (0.68 ± 0.83 vs. 0.19 ± 0.24 ng/mL, P < 0.001) in Group GIK were significantly higher than those in Group G. In Group G, 9.0% and 4.0% of patients had post-procedural increases in CK-MB 1-3 times and > 3 times, which were significantly lower than those in Group GIK (14.0% and 7.0%, respectively; all P values < 0.01); 13.0% and 7.0% of patients had post-procedural increases in cTnI 1-3 times and > 3 times, which were also significantly lower than those in Group GIK (21.0% and 13.0%, respectively; all P < 0.001). Pre-procedural (10.2 ± 4.5 vs. 5.1 ± 6.3, P < 0.001) and post-procedural rapid blood glucose (RBG) levels (8.9 ± 3.9 vs. 5.3 ± 5.6, P < 0.001) in Group G were higher than those in Group GIK. In adjusted logistic models, usage of GIK (compared with glucose solution) remained significantly and independently associated with higher risk of post-procedural increases in both CK-MB and cTnI levels > 3 times. Furthermore, pre-procedural RBG levels < 5.0mmol/L were significantly associated with higher risk of post-procedural increases in both CK-MB and cTnI levels. Conclusions: In non-diabetic patients with CHD, the administration of GIK may increase the risk of PMI due to hypoglycemia induced by GIK.

20.
Biomed Res Int ; 2020: 4598462, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908890

RESUMO

Background: Anion gap (AG) has been proved to be associated with prognosis of many cardiovascular diseases. This study is aimed at exploring the association of AG with inhospital all-cause mortality and adverse clinical outcomes in coronary care unit (CCU) patients. Method: All data of this study was extracted from Medical Information Mart for Intensive Care III (MIMIC-III, version 1.4) database. All patients were divided into four groups according to AG quartiles. Primary outcome was inhospital all-cause mortality. Lowess smoothing curve was drawn to describe the overall trend of inhospital mortality. Binary logistic regression analysis was performed to determine the independent effect of AG on inhospital mortality. Result: A total of 3593 patients were enrolled in this study. In unadjusted model, as AG quartiles increased, inhospital mortality increased significantly, OR increased stepwise from quartile 2 (OR, 95% CI: 1.01, 0.74-1.38, P = 0.958) to quartile 4 (OR, 95% CI: 2.72, 2.08-3.55, P < 0.001). After adjusting for possible confounding variables, this association was attenuated, but still remained statistically significant (quartile 1 vs. quartile 4: OR, 95% CI: 1.02, 0.72-1.45 vs. 1.49, 1.07-2.09, P = 0.019). Moreover, CCU mortality (P < 0.001) and rate of acute kidney injury (P < 0.001) were proved to be higher in the highest AG quartiles. Length of CCU (P < 0.001) and hospital stay (P < 0.001) prolonged significantly in higher AG quartiles. Maximum sequential organ failure assessment score (SOFA) (P < 0.001) and simplified acute physiology score II (SAPSII) (P < 0.001) increased significantly as AG quartiles increased. Moderate predictive ability of AG on inhospital (AUC: 0.6291), CCU mortality (AUC: 0.6355), and acute kidney injury (AUC: 0.6096) was confirmed. The interactions were proved to be significant in hypercholesterolemia, congestive heart failure, chronic lung disease, respiratory failure, oral anticoagulants, Beta-blocks, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), and vasopressin treatment subgroups. Conclusion: AG was an independent risk factor of inhospital all-cause mortality and was associated with adverse clinical outcomes in CCU patients.

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