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1.
Adv Sci (Weinh) ; : e2103845, 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35001541

RESUMO

The propensity of sodium anode to form uniform electrodeposit is bound up with the nature of electrode surface and regulation of Na-ion flux, as well as distribution of electronic field, which is quite crucial for high-areal-capacity sodium metal batteries (SMBs). Herein, a novel metallic sodium/sodium-tin alloy foil anode (Na/NaSn) with 3D interpenetrated network and porous structure is prepared through facile alloy reaction. The strong sodiophilic properties of sodium-tin alloy can lower the nucleation energy, resulting in smaller depositing potential and strong adsorption of Na+ , while synergistic effect of porous skeleton and additional potential difference (≈0.1 V) between Na and Na-Sn alloy (Na15 Sn4 ) can alleviate volume expansion, redistribute the Na-ion flux and regulate electronic field, which favors and improves homogeneous Na deposition. The as-fabricated Na/NaSn electrode can endow excellent plating/stripping reversibility at high areal capacity (over 1600 h for 4 mAh cm-2 at 1 mA cm-2 and 2 mAh cm-2 at 2 mA cm-2 ), fast electrochemical kinetics (500 h under 4 mAh cm-2 at 4 mA cm-2 ) and superior rate performances. A novel strategy in the design of high-performance Na anodes for large-scale energy storage is provided.

2.
Int J Infect Dis ; 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35017110

RESUMO

OBJECTIVE: The mortality rate for critically ill coronavirus disease 2019 (COVID-19) cases was more than 80%. Nonetheless, research about the effect of common respiratory diseases on critically ill COVID-19 expression and outcomes is scarce. DESIGN: We performed proteomic analyses on airway mucus obtained by bronchoscopy from severe COVID-19 patients, or induced sputum from patients with chronic obstructive pulmonary disease (COPD), asthma, and healthy controls. RESULTS: Out of the total identified and quantified proteins, 445 differentially expressed proteins (DEPs) were found in different comparison groups. In comparison to COPD, asthma, and controls, 11 proteins were uniquely present in COVID-19 patients. Apart from DEPs associated with COPD vs controls and asthma vs controls, there were a total of 59 DEPs specific to COVID-19 patients. Finally, the findings revealed that there were 8 overlapping proteins in COVID-19 patients, including C9, FGB, FGG, PRTN3, HBB, HBA1, IGLV3-19, and COTL1. Functional analyses revealed that the majority of them were associated with complement and coagulation cascades, platelet activation, or iron metabolism, and anemia-related pathways. CONCLUSIONS: This study provides fundamental data for identifying COVID-19-specific proteomic changes in comparison to COPD and asthma, which may suggest molecular targets for specialized therapy.

4.
J Surg Oncol ; 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34918842

RESUMO

BACKGROUND AND OBJECTIVES: Previous studies have concluded that colorectal cancer patients with deficient mismatch repair (dMMR) usually have a good prognosis. However, some studies have suggested that the prognosis of rectal cancer patients with dMMR appears to be worse. Our aim was to investigate chemoradiotherapy resistance in dMMR rectal tumors. METHODS: A retrospective study of 217 patients with locally advanced rectal adenocarcinoma treated with chemoradiotherapy and total mesorectal excision surgery was conducted using immunohistochemistry to determine MMR status and propensity score matching models to reduce potential confounders. Kaplan-Meier analysis, log-rank test, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups. RESULTS: The 3-year DFS rates were 77.1% and 56.7% in the pMMR and dMMR groups, respectively. The pMMR group had significantly better DFS than the dMMR group (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.10-3.91; p = 0.019). However, there was no significant difference in OS between the two groups (45.7 [interquartile range, IQR], 39.3-72.1] vs. 47.5 [IQR, 29.5-72.1]) (HR, 1.39; 95% CI, 0.70-2.77; p = 0.35). Neither OS nor DFS was significantly different between the neoadjuvant chemoradiotherapy and postoperative chemoradiotherapy groups. CONCLUSION: Locally advanced dMMR rectal adenocarcinoma exhibits greater chemoradiotherapy resistance than pMMR.

5.
Front Immunol ; 12: 782731, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956212

RESUMO

The SARS-CoV-2 and its variants are still hitting the world. Ever since the outbreak, neurological involvements as headache, ageusia, and anosmia in COVID-19 patients have been emphasized and reported. But the pathogenesis of these new-onset neurological manifestations in COVID-19 patients is still obscure and controversial. As difficulty always lay in the diagnosis of neurological infection, current reports to validate the presence of SARS-CoV-2 in cerebrospinal fluid (CSF) almost relied on the basic methods and warranted improvement. Here we reported a case series of 8 patients with prominent new-onset neurological manifestations, who were screened out from a patch of 304 COVID-19 confirmed patients. Next-generation sequencing (NGS) and proteomics were conducted in the simultaneously obtained CSF and serum samples of the selected patients, with three non-COVID-19 patients with matched demographic features used as the controls for proteomic analysis. SARS-CoV-2 RNA was detected in the CSF of four COVID-19 patients and was suspicious in the rest four remaining patients by NGS, but was negative in all serum samples. Proteomic analysis revealed that 185 and 59 proteins were differentially expressed in CSF and serum samples, respectively, and that only 20 proteins were shared, indicating that the proteomic changes in CSF were highly specific. Further proteomic annotation highlighted the involvement of complement system, PI3K-Akt signaling pathway, enhanced cellular interaction, and macrophages in the CSF proteomic alterations. This study, equipped with NGS and proteomics, reported a high detection rate of SARS-CoV-2 in the CSF of COVID-19 patients and the proteomic alteration of CSF, which would provide insights into understanding the pathological mechanism of SARS-CoV-2 CNS infection.


Assuntos
COVID-19/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/virologia , Líquido Cefalorraquidiano/metabolismo , Líquido Cefalorraquidiano/virologia , RNA Viral/líquido cefalorraquidiano , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica , SARS-CoV-2 , Análise de Sequência de RNA
6.
Oxid Med Cell Longev ; 2021: 3456725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925691

RESUMO

Relevant researches have recognized the vital role of inducing ferroptosis in the treatment of tumor. The latest findings indicate that PEBP1/15-LO can play an essential role in the process of cell death. However, its role in regulating ferroptosis in hepatocellular carcinoma (simplified by HCC) remains unclear. The previous research of our team has proved that DHA can induce ferroptosis of hepatic stellate cells. In this study, we found that DHA could also induce ferroptosis in HCC cells. Interestingly, DHA induced ferroptosis by promoting the formation of PEBP1/15-LO and promoting cell membrane lipid peroxidation. In addition, we also found that DHA had no obvious regulatory effect on 15-LO, but it could promote PEBP1 protein expression. Importantly, we discovered the upregulation of PEBP1 induced by DHA was related to the inhibition of its ubiquitination degradation. In vivo experiments have also obtained consistent results that DHA can inhibit tumor growth and affect the expression of ferroptosis markers in tumor tissues, which would be partially offset by interference with PEBP1.

7.
Opt Express ; 29(23): 38737-38757, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808920

RESUMO

Computer-Controlled Optical Surfacing (CCOS) has been greatly developed and widely used for precision optical fabrication in the past three decades. It relies on robust dwell time solutions to determine how long the polishing tools must dwell at certain points over the surfaces to achieve the expected forms. However, as dwell time calculations are modeled as ill-posed deconvolution, it is always non-trivial to reach a reliable solution that 1) is non-negative, since CCOS systems are not capable of adding materials, 2) minimizes the residual in the clear aperture 3) minimizes the total dwell time to guarantee the stability and efficiency of CCOS processes, 4) can be flexibly adapted to different tool paths, 5) the parameter tuning of the algorithm is simple, and 6) the computational cost is reasonable. In this study, we propose a novel Universal Dwell time Optimization (UDO) model that universally satisfies these criteria. First, the matrix-based discretization of the convolutional polishing model is employed so that dwell time can be flexibly calculated for arbitrary dwell points. Second, UDO simplifies the inverse deconvolution as a forward scalar optimization for the first time, which drastically increases the solution stability and the computational efficiency. Finally, the dwell time solution is improved by a robust iterative refinement and a total dwell time reduction scheme. The superiority and general applicability of the proposed algorithm are verified on the simulations of different CCOS processes. A real application of UDO in improving a synchrotron X-ray mirror using Ion Beam Figuring (IBF) is then demonstrated. The simulation indicates that the estimated residual in the 92.3 mm × 15.7 mm CA can be reduced from 6.32 nm Root Mean Square (RMS) to 0.20 nm RMS in 3.37 min. After one IBF process, the measured residual in the CA converges to 0.19 nm RMS, which coincides with the simulation.

8.
ACS Appl Mater Interfaces ; 13(45): 53915-53924, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34726379

RESUMO

Owing to the scarcity of Pt, low-cost, stable, and efficient nonprecious metal-based electrocatalysts that can be applied in a wide pH range for the hydrogen evolution reaction (HER) are urgently required. Herein, a highly efficient and robust HER catalyst that is applicable at all pH values is fabricated, containing isolated Co-single atomic sites anchored in the self-supported WO3 arrays grown on Cu foam. At a current density of 10 mA cm-2, the HER overpotentials are 117, 105, and 149 mV at pH values of 0, 7, and 14, respectively, which are significantly lower than those of the undoped WO3, suggesting superior electrocatalytic H2-evolution activity at all pH values. The catalyst also exhibits long-term stability over a wide pH range, particularly in an acidic medium over 24 h, owing to the excellent anticorrosion properties of WO3. Density functional theory calculations prove that the enhanced HER activity is attributed to the isolated Co sites because these optimize the adsorption energy of H* species on WO3. Moreover, the high electrical conductivity of Co-doped WO3 and the three-dimensional array structure supported on the porous metal support afford a catalyst with suitable HER kinetics to enhance the catalytic performance.

9.
Redox Biol ; 47: 102151, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34607160

RESUMO

Ferroptosis is a recently identified non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation. However, the underlying exact mechanisms remain poorly understood. Here, we report that the total levels of N6-methyladenosine (m6A) modification are evidently increased upon exposure to ferroptosis-inducing compounds due to the upregulation of methylase METTL4 and the downregulation of demethylase FTO. Interestingly, RNA-seq shows that m6A modification appears to trigger autophagy activation by stabilizing BECN1 mRNA, which may be the potential mechanism for m6A modification-enhanced HSC ferroptosis. Importantly, YTHDF1 is identified as a key m6A reader protein for BECN1 mRNA stability, and knockdown of YTHDF1 could prevent BECN1 plasmid-induced HSC ferroptosis. Noteworthy, YTHDF1 promotes BECN1 mRNA stability and autophagy activation via recognizing the m6A binding site within BECN1 coding regions. In mice, erastin treatment alleviates liver fibrosis by inducing HSC ferroptosis. HSC-specific inhibition of m6A modification could impair erastin-induced HSC ferroptosis in murine liver fibrosis. Moreover, we retrospectively analyzed the effect of sorafenib on HSC ferroptosis and m6A modification in advanced fibrotic patients with hepatocellular carcinoma (HCC) receiving sorafenib monotherapy. Attractively, the m6A modification upregulation, autophagy activation, and ferroptosis induction occur in human HSCs. Overall, these findings reveal novel signaling pathways and molecular mechanisms of ferroptosis, and also identify m6A modification-dependent ferroptosis as a potential target for the treatment of liver fibrosis.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Adenosina/análogos & derivados , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Animais , Autofagia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Células Estreladas do Fígado , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Camundongos , Estudos Retrospectivos , Transdução de Sinais
10.
Front Pharmacol ; 12: 729062, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566651

RESUMO

Evidence of the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of chronic obstructive pulmonary disease (COPD) is growing but still largely unknown. This study aims to explore the expression, functions and molecular mechanisms of Fantom3_F830212L20, a lncRNA that transcribes in an antisense orientation to Nqo1.We name this lncRNA as Nqo1 antisense transcript 1 (Nqo1-AS1). The distribution, expression level and protein coding potential of Nqo1-AS1 were determined. The effects of Nqo1-AS1 on cigarette smoke (CS)-induced oxidative stress were also evaluated. The results showed that Nqo1-AS1 were mainly located in the cytoplasm of mouse alveolar epithelium and had a very low protein coding potential. Nqo1-AS1 (or its human homologue) was increased with the increase of CS exposure. Nqo1-AS1 overexpression enhanced the mRNA and protein levels of Nqo1 and Serpina1 mRNA expression, and attenuated CS-induced oxidative stress, whereas knockdown of Nqo1-AS1 significantly decreased Nqo1 and Serpina1 mRNA expressions, and aggravated CS-induced oxidative stress. Nqo1-AS1 increased Nqo1 mRNA stability and upregulated Nqo1 expression through antisense pairing with Nqo1 3'UTR. In conclusion, these results suggest that Nqo1-AS1 attenuates CS-induced oxidative stress by increasing Nqo1 mRNA stability and upregulating Nqo1 expression, which might serve as a novel approach for the treatment of COPD.

11.
Biochem Pharmacol ; 192: 114730, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34400125

RESUMO

Activation of hepatic stellate cells (HSCs) is a central event in the pathogenesis of liver fibrosis and is often accompanied by the disappearance of lipid droplets (LDs). Although interference with LD metabolism can effectively reverse the activation of HSCs, there is currently no effective therapy for liver fibrosis. Our previous evidence indicates that long non-coding RNA (lncRNA)-H19 plays an essential role in LD metabolism of HSC. In this study, we investigated the potential molecular mechanism of dihydroartemisinin (DHA) inhibits LD metabolism and liver fibrosis by regulating H19-AMPK pathway. We found that DHA restores LDs content in activated HSCs via reducing the transcription of H19 driven by hypoxia inducible factor 1 subunit alpha (HIF1α) and inhibiting the lipid oxidation signal mediated by AMP-activated protein kinase (AMPK) phosphorylation. In vivo experiments, we have proved that DHA reduced the deposition of extracellular matrix (ECM) and reduce the level of liver fibrosis in CCl4-induced liver fibrosis of mice. In summary, our results emphasize the importance of H19 in liver fibrosis and the potential of DHA to regulate H19 to treat liver fibrosis, providing a new direction for the prevention and treatment of liver fibrosis.


Assuntos
Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Artemisininas/uso terapêutico , Células Estreladas do Fígado/efeitos dos fármacos , Gotículas Lipídicas/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , RNA Longo não Codificante/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Artemisininas/farmacologia , Linhagem Celular , Células Estreladas do Fígado/metabolismo , Humanos , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/fisiologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , RNA Longo não Codificante/metabolismo
12.
J Ethnopharmacol ; 280: 114411, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34265380

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Acute-on-chronic liver failure (ACLF) is a key complication of chronic hepatitis, with a relatively high mortality rate and limited treatment options, which dramatically threatens human lives. Yi-Qi-Jian-Pi formula (YQJPF) is a herbal compound commonly used to treat liver failure. AIM OF THE STUDY: The purpose of this research is to discuss the potential molecular biological effect and mechanism of YQJPF in ACLF. MATERIALS AND METHODS: In this study, we created a rat model of ACLF by CCl4-, LPS- and D-Galactosamine (D-Gal) and an in vitro model of LPS-induced hepatocyte damage. The specific components of YQJPF and potential mechanism were explored based on bioinformatics analyses. Furthermore, we verified the effect of YQJPF on ACLF using immunohistochemistry, RT-qPCR, western blotting, and flow cytometry. RESULTS: Our research demonstrated that, after YQJPF treatment, hepatocyte injury in rats was relieved. Bioinformatics analysis showed that PI3K/AKT, HIF-1, mitochondrial apoptosis pathways played prominent roles. YQJPF promoted HIF-1α protein expression and exerted protective effects against hypoxic injury, simultaneously reducing mitochondrial ROS production, suppressing hepatocyte apoptosis. Furthermore, we showed that YQJPF accelerates PI3K/AKT pathway activation, a known broad-spectrum inhibitor of PI3K. LY294002, which was used for reverse verification, suppressed the effect of YQJPF on hypoxic injury and ROS-mediated hepatocyte apoptosis. CONCLUSIONS: YQJPF ameliorates liver injury by suppressing hypoxic injury and ROS-mediated hepatocyte apoptosis by modulating the PI3K/AKT pathway.

13.
Psychopharmacology (Berl) ; 238(9): 2535-2542, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34189597

RESUMO

RATIONALE: Forgetting of fear memory is a current medical therapy for posttraumatic stress disorder (PTSD), and hippocampal long-term depression (LTD) may be the underlying mechanism. Neuregulin 1 (NRG1), a trophic factor, reportedly modulates memory consolidation and synaptic plasticity. METHODS: Fear memory was assessed using contextual fear conditioning. Electrophysiology was used to measure LTD and GABAergic transmission in the hippocampus. OBJECTIVES: To determine the contribution of hippocampal NRG1 to fear memory forgetting and low-frequency stimulation (LFS)-induced LTD. RESULTS: Administration of NRG1 in the hippocampus accelerated forgetting of contextual fear memories. Furthermore, NRG1 had no effect on low-frequency stimulation-induced LTD in young mice but significantly facilitated the induction of LTD and GABAergic transmission in adult animals. More importantly, NRG1-facilitated LTD induction in adult mice could be blocked by inhibition of GABAA receptors and NMDAR activation. CONCLUSION: These findings suggest a role for NRG1 in fear memory forgetting and hippocampal LTD, providing a potential target for the development of drug-assisted PTSD therapy.


Assuntos
Depressão , Neuregulina-1 , Animais , Medo , Hipocampo , Depressão Sináptica de Longo Prazo , Camundongos , Plasticidade Neuronal
14.
Acta Radiol ; : 2841851211024002, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134527

RESUMO

BACKGROUND: The value of combined dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and apparent diffusion coefficient (ADC) histogram analysis for the diagnosis of breast cancer has not been evaluated in previous studies. PURPOSE: To investigate the diagnostic value of DCE-MRI combined with ADC in benign and malignant breast lesions. MATERIAL AND METHODS: The clinicopathological imaging data included 168 patients (177 lesions) with breast lesions who underwent convention breast MRI, DCE-MRI, and diffusion-weighted imaging (DWI); they were divided into the benign lesion group (n = 39) and malignant lesion group (n = 129) based on pathology. RESULTS: Using the type III outflow curve as a diagnostic criterion for malignant breast lesions, the diagnostic sensitivity was 76.9%, the specificity was 80%, the correct rate was 72.2%, and its area under the curve (AUC) was 0.823. Using an enhancement ratio > 100% as a diagnostic criterion for malignant breast lesions, the sensitivity was 61.5%, specificity was 80%, and AUC was 0.723. Using > 3 ipsilateral vessels as a diagnostic criterion for malignant lesions in the breast resulted in a diagnostic sensitivity of 81.6%, a specificity of 80.8%, and an AUC of 0.805. CONCLUSION: The type of time intensity curve DCE-MRI, the early enhancement rate in the first phase, the number of ipsilateral vessels, and the ADC full volume histogram of the blood supply score and DWI are valuable in the diagnosis of benign and malignant breast lesions.

15.
Biofactors ; 47(5): 801-818, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34129254

RESUMO

Targeting the elimination of activated hepatic stellate cells (HSCs) and blocking excessive deposition of extracellular matrix are recognized as an effective strategy for the treatment of hepatic fibrosis. As a newly discovered programmed cell death mode, the regulatory mechanism of ferroptosis in the clearance of activated HSCs has not been fully elucidated. In the present study, we reported that the induction of ferroptosis in activated HSCs was required for dihydroartemisinin (DHA) to alleviate hepatic fibrosis. Treatment with DHA could improve the damage of hepatic fibrosis in vivo and inhibit the activation of HSCs in vitro. Interestingly, DHA treatment could trigger ferroptosis to eliminate activated HSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Specific ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 could impair DHA-induced ferroptosis and also damage DHA-mediated the inhibition of activated HSCs. Importantly, autophagy activation may be closely related to DHA-induced ferroptosis. ATG5 siRNA could prevent DHA-mediated autophagy activation and ferroptosis induction, whereas ATG5 plasmid could promote the effect of DHA on autophagy and ferroptosis. Of note, the upregulation of nuclear receptor coactivator 4 (NCOA4) may play a critical role in the molecular mechanism. NCOA4 siRNA could impair DHA-induced ferroptosis, whereas NCOA4 plasmid could enhance the promoting effect of DHA on ferroptosis. Overall, our study revealed the potential mechanism of DHA against hepatic fibrosis and showed that ferroptosis could be a new way to eliminate activated HSCs.

16.
IUBMB Life ; 73(9): 1166-1179, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34173707

RESUMO

AIMS: This study was designated to illustrate the underlying mechanisms of emodin anti-liver fibrosis via network pharmacology and experiment. METHODS: The TSMCP and Genecards database were applied to screen the relevant targets of emodin or liver fibrosis. The essential target was selected by using Cytoscape to analyze the topological network of potential targets. Furthermore, we constructed a preliminary molecule docking study to explore the binding site by Surflex-Dock suite SYBYL X 2.0. The DAVID database was selected for gene functional annotations and KEGG enrichment analysis. Moreover, we demonstrated the ameliorating effect of emodin on carbon tetrachloride (CCl4 )-induced liver injury in mice. We also verified the network predictions in vitro via various techniques. RESULTS: The collected results showed that 35 targets were related to emodin, and 6,198 targets were associated with liver fibrosis. The Venn analysis revealed that 17 intersection targets were correlated with emodin anti-liver fibrosis. The topological network analysis suggested that the p53 was the remarkable crucial target. Besides, the molecule docking results showed that emodin could directly interact with p53 by binding the active site residues ASN345, GLN331, and TYR347. Finally, KEGG pathway enrichment results indicated that essential genes were mainly enriched in mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, our study confirmed that emodin alleviated CCl4 -induced liver injury in mice, inducing hepatic stellate cells (HSCs) apoptosis via regulating the p53/ERK/p38 axis. CONCLUSIONS: This study partially verified the network pharmacological prediction of emodin inducing HSCs cell apoptosis through the p53/ERK/p38 axis.

17.
Clin Respir J ; 15(8): 915-924, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33942518

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving pandemic, hypertension is one of the most common co-existing chronic conditions and a risk factor for mortality. Nearly one-third of the adult population is hypertensive worldwide, it is urgent to identify the factors that determine the clinical course and outcomes of COVID-19 patients with hypertension. METHODS AND RESULTS: 148 COVID-19 patients with pre-existing hypertension with clarified outcomes (discharge or deceased) from a national cohort in China were included in this study, of whom 103 were discharged and 45 died in hospital. Multivariate regression showed higher odds of in-hospital death associated with high-sensitivity cardiac troponin (hs-cTn) > 28 pg/ml (hazard ratio [HR]: 3.27, 95% confidence interval [CI]: 1.55-6.91) and interleukin-6 (IL-6) > 7 pg/ml (HR: 3.63, 95% CI:1.54-8.55) at admission. Patients with uncontrolled blood pressure (BP) (n = 52) which were defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg for more than once (≥2 times) during hospitalization, were more likely to have ICU admission (p = 0.037), invasive mechanical ventilation (p = 0.028), and renal injury (p = 0.005). A stricter BP control with the threshold of 130/80 mm Hg was associated with lower mortality. Treatment with renin-angiotensin-aldosterone system (RAAS) suppressors, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and spironolactone, was associated with a lower rate of ICU admission compared to other types of anti-hypertensive medications (8 (22.9%) vs. 25 (43.1%), p = 0.048). CONCLUSION: Among COVID-19 patients with pre-existing hypertension, elevated hs-cTn and IL-6 could help clinicians to identify patients with fatal outcomes at an early stage, blood pressure control is associated with better clinical outcomes, and RAAS suppressors do not increase mortality and may decrease the need for ICU admission.


Assuntos
COVID-19 , Hipertensão , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , China/epidemiologia , Mortalidade Hospitalar , Humanos , Hipertensão/epidemiologia , Estudos Retrospectivos , SARS-CoV-2
18.
Front Pharmacol ; 12: 658811, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967802

RESUMO

Acute-on-chronic liver failure (ACLF) is described as a characteristic of acute jaundice and coagulation dysfunction. Effective treatments for ACLF are unavailable and hence are urgently required. We aimed to define the effect of Yi-Qi-Jian-Pi Formula (YQJPF) on liver injury and further examine the molecular mechanisms. In this study, we established CCl4-, LPS-, and d-galactosamine (D-Gal)-induced ACLF rat models in vivo and LPS- and D-Gal-induced hepatocyte injury models in vitro. We found that YQJPF significantly ameliorates liver injury in vivo and in vitro that is associated with the regulation of hepatocyte necroptosis. Specifically, YQJPF decreased expression of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3) and pseudokinase mixed lineage kinase domain-like (MLKL) to inhibit the migration of RIPK1 and RIPK3 into necrosome. YQJPF also reduces the expression of inflammatory cytokines IL-6, IL-8, IL-1ß, and TNF-α, which were regulated by RIPK3 mediates cell death. RIPK1 depletion was found to enhance the protective effect of YQJPF. Furthermore, we showed that YQJPF significantly downregulates the mitochondrial reactive oxygen species (ROS) production and mitochondrial depolarization, with ROS scavenger, 4-hydroxy-TEMPO treatment recovering impaired RIPK1-mediated necroptosis and reducing the expression of IL-6, IL-8, IL-1ß, and TNF-α. In summary, our study revealed the molecular mechanism of protective effect of YQJPF on hepatocyte necroptosis, targeting RIPK1/RIPK3-complex-dependent necroptosis via ROS signaling. Overall, our results provided a novel perspective to indicate the positive role of YQJPF in ACLF.

19.
Tob Induc Dis ; 19: 16, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679283

RESUMO

INTRODUCTION: There is relatively little research on the impact of government cash subsidies on health risk behaviors of the elderly in China. We thus analyzed the effect of pension subsidies on the smoking and drinking behaviors of rural elderly using a pension scheme introduced in rural China in 2009. METHODS: Based on panel data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2008 and 2011, a Difference-in-Differences (DID) method was applied to comprehensively analyze the impact of the new agricultural insurance on the health risk behaviors of the rural elderly. In order to solve possible sample selection biases, the Propensity Score Matching with Difference-in-Differences (PSM-DID) approach was used. RESULTS: We found that the implementation of the government cash subsidies clearly promoted smoking rather than drinking behavior among rural older adults. Specifically, the government cash subsidies facilitated smokers to smoke an additional 2.9 cigarettes/day, and the impact of government cash subsidies on the average cigarettes/day among smokers was more pronounced among the male elderly, lower age elderly, higher income elderly, and elderly with intact instrumental activities of daily living (IADL). CONCLUSIONS: In order to reduce the negative externalities of old-age subsidies, the government should place some restrictions on the use of cash subsidies for tobacco purchase by the elderly.

20.
Toxicology ; 452: 152707, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33549628

RESUMO

Liver pathological angiogenesis is considered to be one of the key events in the development of liver fibrosis. Autophagy is a defense and stress regulation mechanism. However, whether autophagy regulates pathological angiogenesis in liver fibrosis is still questionable. Here, we aimed to study how curcumol regulated liver sinusoidal endothelial cells (LSECs) angiogenesis through autophagy. We found that curcumol (10, 20 and 40 µM) could inhibit the expression of angiogenesis markers in the LSECs. Importantly, we showed that curcumol might influence LSEC pathological angiogenesis by regulating autophagy level. Furthermore, we indicated that the transcription factor Krüppel-like factor 5 (KLF5) was considered as a key target for curcumol to regulate LSEC angiogenesis. Interestingly, we also suggested that autophagy was as a potential mechanism for curcumol to restrain KLF5 expression. Increased autophagy level could impair the suppression effect of curcumol on KLF5. Fascinatingly, our results indicated that curcumol inhibited autophagy and led to p62 accumulation, which might be a regulation mechanism of KLF5 degradation. Finally, in mice liver fibrosis model, we unanimously showed that curcumol (30 mg/kg) inhibited pathological angiogenesis by reducing LSEC autophagy level and suppressing KLF5 expression. Collectively, these results provided a deeper insight into the molecular mechanism of curcumol to inhibit LSEC pathological angiogenesis during liver fibrosis.


Assuntos
Autofagia/efeitos dos fármacos , Células Endoteliais/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Neovascularização Patológica/metabolismo , Proteínas de Ligação a RNA/metabolismo , Sesquiterpenos/uso terapêutico , Animais , Autofagia/fisiologia , Capilares/efeitos dos fármacos , Capilares/metabolismo , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neovascularização Patológica/prevenção & controle , Sesquiterpenos/farmacologia
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