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1.
Biomed Eng Online ; 23(1): 30, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454458

RESUMO

BACKGROUND: Critically ill patients undergoing liberation often encounter various physiological and clinical complexities and challenges. However, whether the combination of hyperbaric oxygen and in-cabin ventilator therapy could offer a comprehensive approach that may simultaneously address respiratory and potentially improve outcomes in this challenging patient population remain unclear. METHODS: This retrospective study involved 148 patients experiencing difficulty in liberation after tracheotomy. Inclusion criteria comprised ongoing mechanical ventilation need, lung inflammation on computed tomography (CT) scans, and Glasgow Coma Scale (GCS) scores of ≤ 9. Exclusion criteria excluded patients with active bleeding, untreated pneumothorax, cerebrospinal fluid leakage, and a heart rate below 50 beats per minute. Following exclusions, 111 cases were treated with hyperbaric oxygen combined cabin ventilator, of which 72 cases were successfully liberated (SL group) and 28 cases (NSL group) were not successfully liberated. The hyperbaric oxygen chamber group received pressurization to 0.20 MPa (2.0 ATA) for 20 min, followed by 60 min of ventilator oxygen inhalation. Successful liberation was determined by a strict process, including subjective and objective criteria, with a prolonged spontaneous breathing trial. GCS assessments were conducted to evaluate consciousness levels, with scores categorized as normal, mildly impaired, moderately impaired, or severely impaired. RESULTS: Patients who underwent treatment exhibited improved GCS, blood gas indicators, and cardiac function indexes. The improvement of GCS, partial pressure of oxygen (PaO2), oxygen saturation of blood (SaO2), oxygenation index (OI) in the SL group was significantly higher than that of the NSL group. However, there was no significant difference in the improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and stroke volume (SV) between the SL group and the NSL group after treatment. CONCLUSIONS: Hyperbaric oxygen combined with in-cabin ventilator therapy effectively enhances respiratory function, cardiopulmonary function, and various indicators of critically ill patients with liberation difficulty after tracheostomy.


Assuntos
Oxigenoterapia Hiperbárica , Traqueostomia , Humanos , Estudos Retrospectivos , Oxigenoterapia Hiperbárica/métodos , Volume Sistólico , Função Ventricular Esquerda , Estado Terminal/terapia , Oxigênio , Ventiladores Mecânicos
2.
Acta Pharmacol Sin ; 44(7): 1416-1428, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36721007

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a major health concern worldwide, and the incidence of metabolic disorders associated with NAFLD is rapidly increasing because of the obesity epidemic. There are currently no approved drugs that prevent or treat NAFLD. Recent evidence shows that bavachin, a flavonoid isolated from the seeds and fruits of Psoralea corylifolia L., increases the transcriptional activity of PPARγ and insulin sensitivity during preadipocyte differentiation, but the effect of bavachin on glucose and lipid metabolism remains unclear. In the current study we investigated the effects of bavachin on obesity-associated NAFLD in vivo and in vitro. In mouse primary hepatocytes and Huh7 cells, treatment with bavachin (20 µM) significantly suppressed PA/OA or high glucose/high insulin-induced increases in the expression of fatty acid synthesis-related genes and the number and size of lipid droplets. Furthermore, bavachin treatment markedly elevated the phosphorylation levels of AKT and GSK-3ß, improving the insulin signaling activity in the cells. In HFD-induced obese mice, administration of bavachin (30 mg/kg, i.p. every other day for 8 weeks) efficiently attenuated the increases in body weight, liver weight, blood glucose, and liver and serum triglyceride contents. Moreover, bavachin administration significantly alleviated hepatic inflammation and ameliorated HFD-induced glucose intolerance and insulin resistance. We demonstrated that bavachin protected against HFD-induced obesity by inducing fat thermogenesis and browning subcutaneous white adipose tissue (subWAT). We revealed that bavachin repressed the expression of lipid synthesis genes in the liver of obese mice, while promoting the expression of thermogenesis, browning, and mitochondrial respiration-related genes in subWAT and brown adipose tissue (BAT) in the mice. In conclusion, bavachin attenuates hepatic steatosis and obesity by repressing de novo lipogenesis, inducing fat thermogenesis and browning subWAT, suggesting that bavachin is a potential drug for NAFLD therapy.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Camundongos Obesos , Glicogênio Sintase Quinase 3 beta/metabolismo , Fígado/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/genética , Flavonoides/farmacologia , Dieta , Glucose/metabolismo , Insulina/metabolismo , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL
3.
Neurocrit Care ; 38(2): 279-287, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35982267

RESUMO

BACKGROUND: Long-term bed rest in neurointensive care (NIC) patients leads to skeletal muscle atrophy and cognitive dysfunction, which seriously affects the physical fitness and final prognosis of critically ill patients. Exercise therapy plays an increasingly important role in the treatment and rehabilitation of patients with sarcopenia. However, the therapeutic effect and mechanism of exercise therapy for patients with neurological impairment remain unclear. METHODS: Serum samples of NIC patients before and after exercise therapy and normal people were collected to detect interleukin-6 (IL-6) and interleukin-1ß levels by enzyme-linked immunosorbent assay (ELISA). Middle cerebral artery occlusion (MCAO) was used for the construction of a rat model. The Morris water maze test, exploration test, and open-field test were used to assess neurological function in rats. Western blot and quantitative real-time polymerase chain reaction were performed to evaluate the activation of IL-6/adenosine-monophosphate-activated protein kinase (AMPK) signaling. RESULTS: Exercise therapy attenuated IL-6 expression in NIC patients. Exercise therapy alleviated cognitive dysfunctions and decreased IL-6 expression in MCAO rats. Exercise therapy alleviated gastrocnemius muscle injury in rats after MCAO by modulating IL-6/AMPK signaling. CONCLUSIONS: Treadmill exercise decreases inflammation in MCAO rats via modulating IL-6/AMPK signaling.


Assuntos
Isquemia Encefálica , Infarto da Artéria Cerebral Média , Ratos , Animais , Interleucina-6 , Isquemia Encefálica/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Inflamação
4.
BMC Gastroenterol ; 22(1): 440, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36284270

RESUMO

OBJECTIVE: To establish a prediction model for acute gastrointestinal injury (AGI) in patients with prolonged disorder of consciousness (pDOC) and to evaluate and apply the prediction model.  METHODS: The clinical data of 165 patients with pDOC admitted to the hyperbaric oxygen department from January 2021 to December 2021 were retrospectively reviewed, and the patients were divided into an AGI group (n = 91) and an N-AGI group (n = 74) according to whether AGI occurred. A prediction model was built by fitting multiple independent influencing factors through logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the model, the Hosmer-Lemeshow (H-L) test was used to evaluate the goodness-of-fit of the model, and the ROC curve and calibration curve were drawn to evaluate the predictive performance. A nomogram was plotted to visualize the prediction model. RESULTS: According to the multivariate logistic regression analysis results, the prediction model was finally constructed with the CRS-R score, DAO, PCT, ALB, and I-FABP, and a nomogram was generated. The area under the ROC curve (AUC) of the prediction model was 0.931, the sensitivity was 83.5%, and the specificity was 93.2%. The data were divided into 5 groups for the H-L test (χ2 = 2.54, P = 0.468 > 0.05) and into 10 groups for the H-L test (χ2 = 9.98, P = 0.267 > 0.05). A calibration curve was drawn based on the test results, indicating that the prediction model has a good goodness-of-fit and good prediction stability. CONCLUSION: The prediction model for AGI in pDOC patients constructed in this study can be used in clinical practice and is helpful to predict the occurrence of AGI in pDOC patients.


Assuntos
Traumatismos Abdominais , Estado de Consciência , Humanos , Estudos Retrospectivos , Prognóstico , Curva ROC , Nomogramas
5.
Oral Dis ; 27(5): 1073-1089, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32390250

RESUMO

OBJECTIVES: This systematic review was to evaluate the change of oral microbiome based on next-generation sequencing (NGS)-metagenomic analysis following periodontal interventions among systematically healthy subjects. MATERIALS AND METHODS: A structured search strategy consisting of "metagenomics" and "oral diseases" was applied to PubMed, EMBASE, and Web of Science to identify effective papers. The included studies were original studies published in English, using metagenomic approach to analyze the effectiveness of periodontal intervention on oral microbiome among systematically healthy human subjects with periodontitis. RESULTS: A total of 12 papers were included in this review. Due to the heterogeneity of selected study, quantitative analysis was not performed. The findings as to how alpha diversity changed after interventions were not consistent across studies. Six studies illustrated clear separation of microbial composition between dental plaque samples collected before and after intervention using principal coordinates/component analysis. The most commonly detected genera before intervention were Porphyromonas, Treponema, Tannerella, and Prevotella, while Streptococcus and Actinomyces usually increased and became the dominant genera after intervention. Correlation network analysis revealed that after intervention, the topology of network was different compared to the corresponding pre-interventional samples. CONCLUSION: Existing evidence of metagenomic studies depicts a complex change in oral microbiome after periodontal intervention.


Assuntos
Microbiota , Periodontite , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenoma , Metagenômica , Microbiota/genética
6.
Dermatol Ther ; 33(6): e14305, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32926496

RESUMO

Mevalonate pathway plays a key role in skin physiological process in human. Recently, it has been reported that mutation of some genes in the mevalonate pathway cause disseminated superficial actinic porokeratosis (DSAP). But the pathogenesis is still unknown. Pravastatin (PRA), one of HMG-CoA reductase (HMGCR) inhibitors, has been found to inhibit cells proliferation, including keratinocytes (KCs). In this study, we use PRA to block the mevalonate pathway in KCs with or without the down-stream intermediate products replenishment. The results demonstrated that PRA strongly inhibited proliferation of KCs and caused the G0 /G1 arrest. When some down-stream intermediate products were added, only cholesterol (CH) could partially rescue the inhibition effect of PRA on KCs proliferation, but not other products, such as mevalonic acid, farnesyl pyrophosphate or geranylgeranyl pyrophosphate. Mechanistic analysis revealed that PRA down-regulated expression of cyclin B1, but up-regulated cyclin E and p21 expression. And PRA increased the phosphorylation level of Protein Kinase B (AKT) but decreased the phosphorylation level of Extracellular Signal Regulated Kinase (ERK1/2). CH could attenuate the elevated cyclin E and activated AKT induced by PRA. These results indicated that CH could rescue the proliferation inhibition of KCs caused by PRA, which laid a foundation for elucidating the pathogenesis of DSAP clearly.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Pravastatina , Ciclo Celular , Proteínas de Ciclo Celular , Proliferação de Células , Colesterol , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Pravastatina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo
7.
J Cell Biochem ; 120(6): 9781-9786, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30537334

RESUMO

The recurrence and metastasis is one of the major reasons for malignant tumor treatment failure. Melatonin, a naturally occuring hormone, could reduce the recurrence and metastasis of various tumors. However, the underlying molecular mechanisms of melatonin on tumor metastasis inhibition have not been fully elucidated. In the present study, we explored the impact of melatonin on the migratory capability of human gastric carcinoma cells using wound healing assay, and further investigated if the inhibition on migration ability of melatonin was embodied by relocating tight junction proteins zo-1 and occludin onto the cells surface to remodel tight junction structure. Immunofluorescence assay and Western blot analysis were performed to detect the expression and cell location of the tight junction proteins. The migration distance was decreased as the cells were treated with melatonin. And melatonin increased the membrane location of tight junction proteins, zo-1 and occludin, showed by immunofluorescence staining and Western blot analysis. The results we got show that melatonin makes tight junction proteins anchored more on the cells membrane to remodel cells tight junction, which increase cells adhesion and decrease motility, resulting in the inhibition of gastric cancer cells migration and metastasis ability.


Assuntos
Movimento Celular/efeitos dos fármacos , Melatonina/farmacologia , Neoplasias Gástricas/metabolismo , Junções Íntimas/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Gástricas/patologia , Junções Íntimas/patologia
8.
Bioorg Med Chem Lett ; 29(23): 126747, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31668973

RESUMO

A series of novel biaryloxazolidinone derivatives containing amide and acrylamide structure were designed, synthesized and evaluated for their antibacterial activity. Most compounds generally exhibited potent antibacterial activity with MIC values of 1 µg/mL against S. aureus, MRSA, MSSA, LREF and VRE pathogens, using linezolid and radezolid as positive controls. Compound 17 exhibited good antibacterial activity with MIC values of 0.5 µg/mL against S. aureus, MRSA, MSSA and VRE and 0.25 µg/mL against LREF. The results indicated that compound 17 might serve as a potential hit-compound for further investigation.


Assuntos
Acrilamida/síntese química , Amidas/síntese química , Antibacterianos/uso terapêutico , Bactérias Gram-Positivas/efeitos dos fármacos , Antibacterianos/farmacologia , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
9.
J Cell Biochem ; 119(8): 6723-6731, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29665051

RESUMO

Although extensive efforts have been made in recent decades to treat advanced gastric cancer with comprehensive therapy based on chemotherapy, effective anti-gastric cancer therapeutics are still lacking in the clinics. Therefore, potent novel anti-gastric cancer ways are greatly needed. Here, we explored hyperbaric oxygen treatment as a novel and effective adjuvant treatment method which has anti-gastric cancer effects when used together with melatonin. When performed together with MLT, HBO effectively inhibited tumorigenicity of gastric cancer through selectively inducing a robust tumor suppressive apoptosis response. Mechanistic studies revealed that the sensitizing effect of hyperbaric oxygen is due to decreased ratio of Bcl-2/Bax, increased level of p53, cleaved Caspase3, GRP78, CHOP, and LC3. These results give a vivid picture that classic apoptosis pathways including mitochondrial pathway, tumor suppressive endoplasmic reticulum stress (ERS), and autophagy are all involved in the process. From the preliminary results got from the current study, we identified that HBO sensitizes human gastric cancer cells to MLT-induced apoptosis through a variety of complicated molecular mechanisms. HBO may provide a novel candidate supplemental treatment method for further development of potential anti-gastric cancer therapeutics. The combination of HBO and MLT could be a promising treatment for advanced gastric cancer.


Assuntos
Apoptose/efeitos dos fármacos , Oxigenoterapia Hiperbárica , Melatonina/farmacologia , Oxigênio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/terapia , Linhagem Celular Tumoral , Chaperona BiP do Retículo Endoplasmático , Humanos , Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
10.
Exp Lung Res ; 44(8-9): 417-423, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30739528

RESUMO

Hypoxia induces vigorous growth and a higher malignant phenotype in solid tumors. Hyperoxic treatment using hyperbaric oxygen (HBO) has previously been shown as a highly effective method to attenuate hypoxia. We aimed to investigate the effect of HBO on hypoxia-induced malignancy of lung cancer cells. Cobalt chloride (CoCl2) was used to induce chemical hypoxia in lung cancer cell line A549. Hypoxic inducible factor-1α (HIF-1α) expression, lactate dehydrogenase (LDH) activity, migration and invasion capacity, expression profiles of epithelial-mesenchymal transition (EMT) markers and apoptotic markers were assessed in CoCl2-treated A549 cells, with or without HBO treatment. Chemical hypoxia caused by CoCl2 resulted in high LDH activity, increased migration and invasion, decreased E-cadherin/N-cadherin ratio, enhanced EMT phenotype, higher Bcl-2/Bax ratio and elevated GRP78 expression. HBO treatment could significantly attenuate hypoxia-induced LDH activity, migration and invasion, restore hypoxia-reduced E-cadherin/N-cadherin ratio and EMT phenotype, as well as hypoxia-induced Bcl-2/Bax ratio, and repress GRP78 expression. HBO could serve as a reliable adjuvant treatment targeting the hypoxia microenvironment in solid tumors.


Assuntos
Apoptose , Diferenciação Celular , Oxigenoterapia Hiperbárica , Hipóxia/terapia , Neoplasias Pulmonares/terapia , Células A549 , Movimento Celular , Cobalto/farmacologia , Chaperona BiP do Retículo Endoplasmático , Transição Epitelial-Mesenquimal , Humanos , Hipóxia/induzido quimicamente , L-Lactato Desidrogenase/metabolismo , Neoplasias Pulmonares/patologia
11.
Clin Exp Pharmacol Physiol ; 43(10): 1004-12, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27314562

RESUMO

Protein tyrosine-phosphatases (PTPs) play important roles in various biological processes. Deregulation in PTP function has been implicated in carcinogenesis and tumour progression in many cancer types. However, the role of protein tyrosine phosphatase receptor type B (PTPRB) in non-small-cell lung cancer (NSCLC) tumorigenesis has not been investigated. Lentiviral vector expressing PTPRB cDNA or shRNA was infected into A549 and H1299 cell lines, followed by cell proliferation, colony formation, soft agar and invasion assays. A549 xenograft mouse model was used to evaluate in vivo function of PTPRB. Quantitative polymerase chain reaction (PCR) was used to measure PTPRB expression in NSCLC patient samples. Kaplan Meier analysis was performed to assess association between PTPRB expression and patient overall survival (OS). Multivariate analysis was performed to evaluate prognostic significance of PTPRB. Overexpression of PTPRB reduced cell proliferation rate, colony formation efficiency, soft agar growth and cell invasion in A549 and H1299 cells, as well as tumour growth rate in A549 xenograft. Knockdown of PTPRB increased Src phosphorylation and cell invasion, which was reversed by Src inhibitor PP2. Additionally, PTPRB was down-regulated in NSCLC patient and was associated with patient OS. PTPRB regulates Src phosphorylation and tumorigenesis in NSCLC. PTPRB may serve as an independent prognostic biomarker for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Progressão da Doença , Neoplasias Pulmonares/metabolismo , Proteína Oncogênica pp60(v-src)/metabolismo , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/fisiologia , Células A549 , Adulto , Animais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Fosforilação/fisiologia , Taxa de Sobrevida/tendências , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
12.
Oral Dis ; 26(6): 1349-1350, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32475038
13.
Eur J Med Chem ; 273: 116493, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38761790

RESUMO

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents to treat drug-resistant bacteria. We previously discovered compound OB-158 with potent antibacterial activity but exhibited poor oral bioavailability. Herein, a systematic structural optimization of OB-158 to improve pharmacokinetic profiles yielded 26 novel biaryloxazolidinone analogues, and their activities against Gram-positive S. aureus, multidrug resistant S. aureus and Enterococcus faecalis were evaluated. Remarkably, compound 8b was identified with potent antibacterial activity against S. aureus (MIC = 0.06 µg/mL), MSSA (MIC = 0.125 µg/mL), MRSA (MIC = 0.06 µg/mL), LRSA (MIC = 0.125 µg/mL) and LREFa (MIC = 0.5 µg/mL). Compound 8b was demonstrated as a promising candidate through druglikeness evaluation including metabolism in microsomes and plasma, Caco-2 cell permeability, plasma protein binding, cytotoxicity, and inhibition of CYP450 and human monoamine oxidase. Notably, compound 8b displayed excellent PK profile with appropriate T1/2 of 1.49 h, high peak plasma concentration (Cmax = 2320 ng/mL), high plasma exposure (AUC0-t = 8310 h ng/mL), and superior oral bioavailability (F = 68.1 %) in Sprague-Dawley rats. Ultimately, in vivo efficacy of compound 8b in a mouse model of LRSA systemic infection was also demonstrated. Taken together, compound 8b represents a promising drug candidate for the treatment of linezolid-resistant Gram-positive bacterial strains infection.


Assuntos
Antibacterianos , Linezolida , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Humanos , Animais , Linezolida/farmacologia , Relação Estrutura-Atividade , Células CACO-2 , Camundongos , Estrutura Molecular , Relação Dose-Resposta a Droga , Staphylococcus aureus/efeitos dos fármacos , Ratos , Farmacorresistência Bacteriana/efeitos dos fármacos , Masculino , Enterococcus faecalis/efeitos dos fármacos , Oxazolidinonas/farmacologia , Oxazolidinonas/química , Oxazolidinonas/síntese química , Ratos Sprague-Dawley
14.
Eur J Med Res ; 28(1): 122, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36918990

RESUMO

BACKGROUNDS: The association between obesity and asthma has been of interest, but whether the duration of asthma has an effect on obesity is still limitedly studied. AIM: The purpose of this study was to investigate the association between asthma duration and obesity-related indexes, where obesity-related indexes include Body mass index (BMI) and Weight-adjusted-waist index (WWI). METHODS: Data from National Health and Nutrition Examination Survey (NHANES) 2009-2018 were obtained to conduct this cross-sectional study. Duration of asthma was used as the independent variable and obesity-related indexes as the response variables. Multiple linear regression was used to assess the association between the independent variable and the response variables, and subsequently smoothed curve fitting and threshold effect analysis were performed to clarify whether there was a nonlinear correlation between the independent variable and the response variables. Finally, subgroup analysis was conducted to find sensitive populations. RESULTS: A total of 9170 participants were included in the analysis. Asthma duration was statistically different between the two groups when all participants were grouped by median WWI (Q1 < 11.65, Q2 ≥ 11.65) (P < 0.001), but not by median BMI (Q1 < 31.8, Q2 ≥ 31.8) (P = 0.130). There was a positive association between asthma duration and WWI [ß = 0.016, 95% CI (0.016, 0.017)], but a negative one with BMI [ß = - 0.098, 95% CI (- 0.112, - 0.085)], and the correlations between the independent and response variables became more pronounced with increasing asthma duration (P for trend < 0.01). In addition, there were nonlinear relationships between asthma duration with BMI and WWI (log likelihood ratio < 0.001), with the best valid inflection points for asthma duration being 2 years (with WWI as the response variable) and 3 years (with BMI as the response variable), respectively. In the subgroup analysis, the positive association between asthma duration and WWI was more pronounced in the participants who were male, aged less than 40 years, and had asthma onset before 12 years of age. In contrast, when BMI was used as the response variable, the negative association between it and asthma duration was more pronounced among participants of female, aged 60 years or older, and with asthma onset less than 12 years of age. CONCLUSIONS: In US adults, asthma duration might cause changes in obesity-related indexes. Longer asthma duration might cause weight loss, but might increase the risk of abdominal obesity.


Assuntos
Asma , Obesidade , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Índice de Massa Corporal , Inquéritos Nutricionais , Estudos Transversais , Obesidade/epidemiologia , Obesidade/complicações , Asma/epidemiologia , Asma/complicações
15.
Eur J Med Chem ; 246: 114945, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36462444

RESUMO

ATR kinase is essential to the viability of replicating cells responding to the accumulation of single-strand breaks in DNA, which is an attractive anticancer drug target based on synthetic lethality. Herein we design, synthesize, and evaluate a novel series of fused pyrimidine derivatives as ATR inhibitors. As a result, compound 48f, with an IC50 value of 0.0030 µM against ATR, displayed strong monotherapy efficacy in ataxia-telangiectasia mutated (ATM) kinase-deficient tumor cells LoVo, SW620, OVCAR-3 cell lines with IC50 values of 0.040 µM, 0.095 µM, 0.098 µM, respectively. More importantly, the combination of 48f with AZD-1390, cisplatin, oxaliplatin, and olaparib respectively resulted in synergistic activity against HT-29, HCT116, A549, MCF-7, MDA-MB-231 cells. Moreover, 48f showed a favorable pharmacokinetic profile with a bioavailability of 30.0% in SD rats, acceptable PPB, high permeability (Papp A to B = 8.23 cm s-1 × 10-6), and low risk of drug-drug interactions. Collectively, compound 48f could be a promising compound for further investigation.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Humanos , Ratos , Animais , Feminino , Apoptose , Linhagem Celular Tumoral , Pirimidinas/farmacologia , Ratos Sprague-Dawley , Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
16.
Front Surg ; 9: 877114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669250

RESUMO

Objective: This study aims to explore the effect of adjuvant hyperbaric oxygen therapy on ovarian function after laparoscopic ovarian cystectomy. Methods: A total of 60 patients with ovarian cysts treated at our hospital from January 2018 to August 2020 were enrolled. According to the different treatment modalities, the patients were divided into the control and observation groups. Patients in both groups underwent laparoscopic ovarian cystectomy with oral administration of Chinese patent medicine Kuntai capsules after surgery. Hyperbaric oxygen therapy was added to patients in the observation group in addition to the treatment in the control group. The anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and antral follicle count (AFC) serum levels were detected in both groups before the operation and at the first and third menstrual cycles postoperatively to evaluate ovarian function. Results: At the first and third menstrual cycles after surgery, the AMH, E2, and AFC serum levels in the two groups were significantly lower than before surgery, and the FSH and LH serum levels were higher than before surgery. The differences were statistically significant (P < 0.05). After the operation, AMH, E2, and AFC serum levels in the observation group were significantly higher than in the control group. FSH and LH serum levels were significantly lower than in the control group, and the differences were statistically significant (P < 0.05). Conclusion: For patients undergoing laparoscopic ovarian cystectomy, the adjuvant hyperbaric oxygen therapy could significantly improve the postoperative ovarian reserve function with remarkable effects.

17.
Int J Oncol ; 59(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34195850

RESUMO

Pancreatic cancer ranks seventh in terms of cancer­related mortality in men and women worldwide, where the most common subtype is pancreatic ductal adenocarcinoma (PDAC). To date, the pathogenesis of PDAC remains incompletely understood and the prognosis of PDAC is poor. In the present study, the expression of interleukin­28 receptor α subunit (IL­28RA) in PDAC tissues was detected using immunofluorescence staining and western blotting. IL­28RA recombinant plasmids and control pCMV6­entrymammalian expression plasmid, short hairpin (sh)IL­28RA plasmids and control pRS scrambled shRNA vector purchased were used to produce stably transfected PANC­1 cells overexpressing IL­28RA or with IL­28RA expression knocked down. MTS assays were used to measure cell viability and wound healing assay was used to assess the cell migratory ability in vitro. Flow cytometry analysis was performed to determine the proportion of cells in each phase of the cell cycle whereas total protein and phosphorylated protein levels were assessed using western blotting. Xenograft models of subcutaneous tumors were established by injecting PANC­1 cells hypodermically into nude mice to investigate the effect of IL­28RA on tumorigenesis and tumor growth. The results showed that the expression of IL­28RA in PDAC tissues was lower compared with that in normal tissues. IL­28RA overexpression in vitro resulted in the activation of the IL­28RA pathway, which reduced cell viability and decreased the proportion of cells in the G2/M phase by reducing cyclin B1 expression. In addition, IL­28RA overexpression inhibited migration of PDAC cells. By contrast, an increased proportion of cells in G2/M phase, upregulated cyclin B1 expression and enhanced cell viability and migratory ability along with inhibition of the IL­28RA pathway were observed in PANC­1 cells following IL­28RA knockdown. The inhibitory effect of IL­28RA was observed by tumor size in a nude mouse model induced by PANC­1 cells with stable IL­28RA overexpression or knockdown. The tumor size induced by PANC­1 cells with stable IL­28RA overexpression were smaller, whilst larger tumors induced by PANC­1 cells were observed following stable IL­28RA knockdown, when compared to control. Further studies showed that the effect of IL­28RA on PDAC cells was exerted by regulating the phosphorylation levels of STAT1 and AKT. In conclusion, lower IL­28RA expression may contribute to the pathogenesis of PDAC, where results from the present may provide further insights into the progression of PDAC, in addition to highlighting potentially novel therapeutic targets for this disease.


Assuntos
Carcinoma Ductal Pancreático/patologia , Regulação para Baixo , Neoplasias Pancreáticas/patologia , Receptores de Interferon/genética , Receptores de Interferon/metabolismo , Idoso , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico
18.
Trials ; 21(1): 634, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650814

RESUMO

BACKGROUND: The prevalence of pneumonia complicating stroke in acute phase has a poor prognosis and higher risk for death. Oral opportunistic pathogens have been reported to be associated with pneumonia among people with compromised health. Oral health promotion is effective in reducing dental plaque among patients with stroke, which is considered as reservoirs for oral opportunistic pathogens. This study evaluates the effectiveness of oral health promotions in reducing the prevalence of pneumonia via its effects on composition and relative abundance of oral opportunistic pathogens. METHODS/DESIGN: This study is a randomized, single-blind, parallel trial of 6 months duration. The study is being conducted at one of the largest medical teaching hospitals in Hefei, China. A total of 166 patients with stroke and free from any post-stroke complication will be recruited. After enrollment, patients will be randomized to one of the following groups: (1) oral hygiene instruction (OHI) or (2) OHI, 6-month use of powered tooth brushing, and 0.2% chlorhexidine gluconate mouth rinse (10 ml twice daily). The primary outcome is the prevalence of pneumonia complicating stroke. Patients will be monitored closely for any occurrence of pneumonia over the entire period of this trial. Oral rinse samples will be collected at baseline and multiple follow-up reviews (3, 5, 7 days, and 1, 3, 6 months after baseline). Next-generation sequencing will be employed to detect composition and relative abundances of the microorganism in the oral rinse samples. Questionnaire interviews and clinical oral examinations will be conducted at baseline and 1, 3, and 6 months after baseline. DISCUSSION: The findings of this trial will provide evidence whether oral health promotion intervention is effective in reducing the prevalence of pneumonia complicating stroke via its effect on the oral microbiome. The analysis of the outcomes of this trial is empowered by metagenomic analysis at 16S rRNA level, which is more sensitive and comprehensive to help us detect how oral health promotion inventions affect the oral microbiome in terms of its composition, relative abundance, and interactions between species, which all may contribute to the occurrence of pneumonia complicating stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT04095780 . Registered on 19 September 2019.


Assuntos
Promoção da Saúde , Metagenômica , Saúde Bucal , Pneumonia/prevenção & controle , Acidente Vascular Cerebral/complicações , China , Humanos , Microbiota , Boca/microbiologia , Higiene Bucal , RNA Ribossômico 16S , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego
19.
Eur J Med Chem ; 185: 111781, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31654879

RESUMO

We previously discovered a series of novel biaryloxazolidinone analogues bearing a hydrazone moiety with potent antibacterial activity. However, the most potent compound OB-104 exhibited undesirable chemical and metabolic instability. Herein, novel biaryloxazolidinone analogues were designed and synthesized to improve the chemical and metabolic stability. Compounds 6a-1, 6a-3, 14a-1, 14a-3 and 14a-7 showed significant antibacterial activity against the tested Gram-positive bacteria as compared to radezolid and linezolid. Further studies indicated that most of them exhibited improved water solubility and chemical stability. Compound 14a-7 had MIC values of 0.125-0.25 µg/mL against all tested Gram-positive bacteria, and showed excellent antibacterial activity against clinical isolates of antibiotic-susceptible and antibiotic-resistant bacteria. Moreover, it was stable in human liver microsome. From a safety viewpoint, it showed non-cytotoxic activity against hepatic cell and exhibited lower inhibitory activity against human MAO-A compared to linezolid. The potent antibacterial activity and all these improved drug-likeness properties and safety profile suggested that compound 14a-7 might be a promising drug candidate for further investigation.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Inibidores da Monoaminoxidase/farmacologia , Oxindóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/química , Oxindóis/síntese química , Oxindóis/química , Relação Estrutura-Atividade
20.
Eur J Med Chem ; 197: 112309, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32375077

RESUMO

Using a rational design strategy for isoform-selective inhibition of PI3Kα, two series of novel 2,3,4,5-tetra-substituted thiophene derivatives containing either diaryl urea or N-Acylarylhydrazone scaffold were designed and synthesized. The most promising compound 12k was demonstrated to bear nanomolar PI3Kα inhibitory potency with 12, 28, 30, 196-fold selectivity against isoforms ß, γ, δ and mTOR. Besides, it also showed good developability profiles in cell-based proliferation against a panel of human tumor cells as well as ADME assays. We herein report on their design, synthesis, SAR and potential developability properties.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Tiofenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Fosfatidilinositol 3-Quinases/química , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/síntese química , Inibidores de Fosfoinositídeo-3 Quinase/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacocinética , Ligação Proteica , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/antagonistas & inibidores , Tiofenos/síntese química , Tiofenos/metabolismo , Tiofenos/farmacocinética
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