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1.
J Cachexia Sarcopenia Muscle ; 15(4): 1483-1490, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38845599

RESUMO

BACKGROUND: Cardiorespiratory fitness (CRF) could reduce the risk of metabolic syndrome (MetS) while the association between muscular endurance capacity (MEC) and incident MetS has rarely been investigated in young adults. METHODS: A total of 2890 military men and women, aged 18-39 years, free of baseline MetS in Taiwan, were followed for incident MetS from baseline (2014) until the end of 2020. All subjects received annual health examinations for assessment of MetS. Physical fitness was assessed by CRF (estimated maximal oxygen uptake, VO2 max [mL/kg/min], in a 3000-m run) and MEC (numbers of 2-min push-ups). MetS was defined according to the International Diabetes Federation (IDF) criteria. Multiple Cox regression analysis was conducted with adjustments for baseline age, sex, substance use status and physical activity to determine the associations of CRF and MEC with incidences of new-onset MetS and related features, for example, central obesity, hypertension, dyslipidaemia and prediabetes or diabetes. To examine the combined effects of CRF and MEC status on incidence of MetS, high and low levels of CRF and MEC were separately defined by over and under the sex-specific median in each exercise test. RESULTS: During a median follow-up of 5.8 years, there were 673 (23.3%) new-onset MetS. Higher CRF was associated with a lower incidence of MetS (hazard ratio [HR] and 95% confidence interval: 0.905 [0.877-0.933]), and its components separately, except hypertension. No association was observed between MEC and incident MetS, and its components separately, except hypertension. When evaluating the combined effects of MEC and CRF status on the incidence of MetS, it was observed that compared with the low CRF/low MEC, the high CRF/high MEC (HR: 0.553 [0.439-0.697]) and the high CRF/low MEC (HR: 0.730 [0.580-0.918]) had a lower incidence of new-onset MetS (P value for the intergroup difference = 0.04). There was no significant result for the low CRF/high MEC. CONCLUSIONS: This study highlights that although the protective effects of MEC to reduce the incidence of MetS and most of its related features were mainly driven by CRF in young adults, there was an addictive effect of greater MEC on CRF to prevent the development of new-onset MetS before midlife.


Assuntos
Aptidão Cardiorrespiratória , Síndrome Metabólica , Humanos , Síndrome Metabólica/epidemiologia , Masculino , Feminino , Adulto , Incidência , Aptidão Cardiorrespiratória/fisiologia , Adulto Jovem , Taiwan/epidemiologia , Adolescente , Aptidão Física/fisiologia
2.
Environ Toxicol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884142

RESUMO

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

3.
J Dent Sci ; 19(2): 998-1003, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38618117

RESUMO

Background/purpose: It is unclear about whether the oral health has impact on physical performance. Therefore, this study aimed to examine the association between oral health and physical performance in 300 military adults in Taiwan. Materials and methods: Oral health was assessed by the presence of periodontitis and dental caries. The status of cardiorespiratory and muscular endurance capacity was respectively assessed by tertiles of time for a 3000-m run and 2-min push-up numbers. Multivariable logistic and linear regression analyses with adjustments for age, smoking, alcohol drinking, blood pressure, anthropometric variables, lipid profile, fasting glucose and physical activity were used to determine the association. Results: Participants with periodontitis were more likely to have worse 3000-m running performance classified in the lowest tertile [odds ratio (OR) and 95% confidence interval: 1.94 (1.03, 3.66)]. Participants with any dental caries were more likely to have worse push-ups performance classified in the lowest tertile [OR: 2.50 (1.27, 4.92)]. In linear regression analyses, dental caries numbers were inversely correlated with 2-min push-ups numbers [ß = -1.04 (-2.07, -0.01)]. Conclusion: This study suggests that oral health is crucial to maintain physical fitness, and dental caries and periodontitis may affect differently on aerobic and muscular endurance capacities.

4.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473983

RESUMO

Asians have a higher carrier rate of pulmonary arterial hypertension (PAH)-related genetic variants than Caucasians do. This study aimed to identify PAH-related genetic variants using whole exome sequencing (WES) in Asian idiopathic and heritable PAH cohorts. A WES library was constructed, and candidate variants were further validated by polymerase chain reaction and Sanger sequencing in the PAH cohort. In a total of 69 patients, the highest incidence of variants was found in the BMPR2, ATP13A3, and GDF2 genes. Regarding the BMPR2 gene variants, there were two nonsense variants (c.994C>T, p. Arg332*; c.1750C>T, p. Arg584*), one missense variant (c.1478C>T, p. Thr493Ile), and one novel in-frame deletion variant (c.877_888del, p. Leu293_Ser296del). Regarding the GDF2 variants, there was one likely pathogenic nonsense variant (c.259C>T, p. Gln87*) and two missense variants (c.1207G>A, p. Val403Ile; c.38T>C, p. Leu13Pro). The BMPR2 and GDF2 variant subgroups had worse hemodynamics. Moreover, the GDF2 variant patients were younger and had a significantly lower GDF2 value (135.6 ± 36.2 pg/mL, p = 0.002) in comparison to the value in the non-BMPR2/non-GDF2 mutant group (267.8 ± 185.8 pg/mL). The BMPR2 variant carriers had worse hemodynamics compared to the patients with the non-BMPR2/non-GDF2 mutant group. Moreover, there was a significantly lower GDF2 value in the GDF2 variant carriers compared to the control group. GDF2 may be a protective or corrected modifier in certain genetic backgrounds.


Assuntos
Hipertensão Arterial Pulmonar , Humanos , Hipertensão Arterial Pulmonar/genética , Hipertensão Pulmonar Primária Familiar/genética , Mutação de Sentido Incorreto , Hemodinâmica , Deleção de Sequência , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Mutação , Adenosina Trifosfatases/genética , Proteínas de Membrana Transportadoras/genética , Fator 2 de Diferenciação de Crescimento/genética
5.
Cardiovasc Res ; 120(2): 203-214, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38252891

RESUMO

AIMS: Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared with the induced pluripotent stem cells (iPSCs). Moreover, the exact mechanism is not known. METHODS AND RESULTS: In this study, we used murine iPSCs generated from mouse embryonic fibroblasts with triple factor (Oct4, Klf4, and Sox2) transduction to determine the efficacy and action mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension. Both early and late iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats. Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and P21-activated kinase 1/AKT/Runx2 pathways. CONCLUSION: IPSC-Exo are effective at reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.


Assuntos
Exossomos , Hipertensão Pulmonar , Células-Tronco Pluripotentes Induzidas , Hipertensão Arterial Pulmonar , Ratos , Animais , Camundongos , Hipertensão Arterial Pulmonar/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Remodelação Vascular , Exossomos/metabolismo , Fibroblastos/metabolismo , Hipertensão Pulmonar Primária Familiar/metabolismo , Artéria Pulmonar , Monocrotalina/efeitos adversos , Monocrotalina/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo
6.
Front Psychiatry ; 14: 1255516, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034917

RESUMO

Backgrounds: This study aimed to clarify the association of American guideline-based leisure time physical activity (PA) level with mental health in 4,080 military personnel in Taiwan. Methods: The moderate intensity PA level was assessed according to the total running time per week (wk) reported in a self-administered questionnaire over the previous 6 months and was categorized into PA level <150, 150-299, and ≥300 min/wk. Mental stress was assessed by the Brief Symptom Rating Scale (BSRS)-5 for which ≥15 points were classified as great mental stress. Suicide ideation (SI) was graded as 1 for mild, 2 for moderate, and 3 or 4 for severe. Multivariable logistic regression analysis was employed to determine the association between PA and mental health while adjusting for demographics, smoking, alcohol intake, betel nut chewing, and obesity. Results: As compared to participants with a PA level of <150 min/wk., those with PA levels 150-299 min/wk. and ≥ 300 min/wk. had a lower possibility of SI ≥1 [odds ratios (ORs) and 95% confidence intervals (CIs): 0.58 (0.40-0.83) and 0.23 (0.14-0.36), respectively] and SI ≥1 and/or BSRS-5 ≥ 15 [ORs: 0.55 (0.39-0.79) and 0.21 (0.13-0.34), respectively]. The possibilities were more significantly lower for SI ≥2 [ORs: 0.37 (0.20-0.68) and 0.10 (0.04-0.26), respectively] and SI ≥2 and/or BSRS-5 ≥ 15 [ORs: 0.35 (0.20-0.62) and 0.10 (0.04-0.25), respectively]. Conclusion: Our findings indicate that participating in moderate-intensity leisure time PA level for ≥150 min/wk. may have a positive effect on mental health among military personnel. The impact appears to be even more significant when engaging in a higher PA level of ≥300 min/wk.

7.
J Chin Med Assoc ; 86(11): 950-959, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37801590

RESUMO

With the discovery of new biomarkers for the early detection of acute myocardial infarction (AMI), advancements in valid medication, and percutaneous coronary intervention (PCI), the overall prognosis of AMI has improved remarkably. Nevertheless, challenges remain which require more difficult work to overcome. Novel diagnostic and therapeutic techniques include new AMI biomarkers, hypothermia therapy, supersaturated oxygen (SSO 2 ) therapy, targeted anti-inflammatory therapy, targeted angiogenesis therapy, and stem cell therapy. With these novel methods, we believe that the infarction size after AMI will decrease, and myocardial injury-associated ventricular remodeling may be avoided. This review focuses on novel advances in the diagnosis and management of AMI.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Prognóstico , Biomarcadores , Resultado do Tratamento
8.
Medicine (Baltimore) ; 102(38): e35170, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37746984

RESUMO

Varicocele is a major cause of male infertility. However, few studies have discussed the potential associations between the pain caused by varicocele and preoperative and intraoperative factors. The aim of this study was to evaluate factors potentially associated with changes in pain score after microsurgical varicocelectomy. This retrospective study was conducted between August 2020 and August 2022 at China Medical University Hospital in Taichung, Taiwan. Patient characteristics including age, body mass index, semen analysis, testicular volume, and the number of veins ligated were collected. Preoperative and intraoperative factors were analyzed to determine if they were correlated with changes in numeric rating scale (NRS) after microsurgical varicocelectomy. A total of 44 patients with clinical varicocele underwent subinguinal microsurgical varicocelectomy and were analyzed. The overall pain resolution rate was 91%, and the average satisfaction score after surgery was 9.2 according to their subjective feelings. Multivariate analysis revealed that severe varicocele grade (odds ratio [OR] 16.5, 95% confidence interval [CI] 3.01-90.47; P = .018) and the number of veins ligated (OR 6, 95% CI 1.6-22.48; P = .013), were significantly associated with changes in NRS after surgery. In addition, the area under the receiver operating characteristic curve for changes in NRS and the total number of veins ligated was 0.869. Microsurgical varicocelectomy had a high success rate for scrotal pain and satisfaction. Severe varicocele grade and the number of veins ligated in microsurgical varicocelectomy were associated with postoperative pain improvement.


Assuntos
Varicocele , Humanos , Masculino , Varicocele/complicações , Varicocele/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Vasculares , Veias , Dor Pélvica
9.
J Int Med Res ; 51(4): 3000605231168033, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37077173

RESUMO

OBJECTIVE: To investigate the impact of metformin on survival of diabetic patients following surgery for colorectal cancer (CRC). METHODS: This was a retrospective cohort study. From Taiwan's population-based National Health Insurance Research Database (NHIRD) we identified 12,512 patients with CRC and type II diabetes who underwent curative surgery between 2000 and 2012. Of these, 6222 patients were included in a matched cohort. Using Cox regression models with time-dependent covariates we examined the impact of metformin on survival. RESULTS: Average duration of follow-up was 49 and 54 months for metformin users and non-users, respectively. Cox proportional hazard model showed that metformin was associated with 5-year overall survival benefit (Hazard ratio, 0.23 [95% CI, 0.20-0.26]) and inverse association with risk of liver metastasis (Hazard ratio, 0.79 [95% CI, 0.68-0.93]). CONCLUSIONS: Metformin was associated with a survival benefit in diabetic patients with CRC following surgery, and an inverse association with risk of liver metastases suggesting a potential anti-tumorigenic effect.


Assuntos
Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Metformina , Humanos , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Estudos Retrospectivos , Modelos de Riscos Proporcionais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia
10.
Ann Noninvasive Electrocardiol ; 28(2): e13045, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36652287

RESUMO

OBJECTIVE: Both electrocardiographic and echocardiographic left ventricular hypertrophy (LVH) have been reported with an association with greater carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis in patients with hypertension, while the associations are unclear in physically fit young adults. METHODS: A total of 1822 Taiwanese military personnel, aged 18-40 years, received an annual health examination including electrocardiography (ECG) and echocardiography in 2018-2020. Left carotid bulb cIMT was measured by high-resolution ultrasonography. Multiple logistic regression analysis with adjustments for age, sex, smoking, alcohol consumption, body mass index, mean blood pressure, and physical fitness was used to determine the associations between echocardiographic and ECG parameters and the highest quintile of cIMT (≥0.8 mm). RESULTS: Cornell-based LVH, Myers et al.-based RVH and heart rate ≥75/min were associated with cIMT ≥0.8 mm [odds ratios (ORs) and 95% confidence intervals: 1.54 (1.01, 2.35), 1.66 (1.18, 2.33), and 1.39 (1.06, 1.83), respectively], while echocardiographic LVH defined as ≥46.0 g/m2.7 for men and ≥38.0 g/m2.7 for women was inversely associated with cIMT ≥0.8 mm [OR: 0.45 (0.24, 0.86)]. CONCLUSION: In tactical athletes of military, the associations of ECG and echocardiographic LVH with cIMT were in opposite directions. Higher physical fitness may cause cardiac muscle hypertrophy and reduce the atherosclerosis severity, possibly leading to the paradoxical echocardiographic finding. This study suggests that ECG-based LVH remains a good marker of subclinical atherosclerosis in our military population.


Assuntos
Aterosclerose , Eletrocardiografia , Masculino , Adulto Jovem , Humanos , Feminino , Espessura Intima-Media Carotídea , Ecocardiografia , Hipertrofia Ventricular Esquerda , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Fatores de Risco
11.
J Clin Med ; 11(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36143108

RESUMO

Background: Greater muscular strength (MusS) has been found to have an inverse association with subclinical atherosclerosis in children, as well as with mortality from cardiovascular diseases (CVDs) in middle-aged and elderly individuals. However, the association of the degree of MusS with atherosclerosis may differ by sex and has not been clarified in young adults. Methods and Results: A total of 1021 Taiwanese military personnel, aged 18−40 years, participated in annual health examinations in 2018−2020. MusS was separately assessed by 2-min push-up and 2-min sit-up numbers. Subclinical atherosclerosis was measured by the left carotid bulb intima−media thickness (cIMT) using high-resolution ultrasonography. Multiple linear regression with adjustments for age, sex, alcohol intake, cigarette smoking, anthropometric indices, blood pressure, and lipid profiles was utilized to determine the correlation between MusS and cIMT. Both 2-min push-up and 2-min sit-up numbers were inversely correlated with cIMT (standardized ß: −0.089 and −0.072, respectively; both p-values < 0.05). In men, both 2-min push-up and 2-min sit-up numbers were inversely correlated with cIMT (standardized ß: −0.076 and −0.086, respectively; both p-values < 0.05), while in women, 2-min push-up numbers but not 2-min sit-up numbers were inversely correlated with cIMT (standardized ß: −0.204 and −0.01; p = 0.03 and 0.99, respectively). Conclusions: Among young adults, there was an inverse association between MusS and cIMT, emphasizing the beneficial impact of MusS on the regression of atherosclerosis. The study also revealed a sex difference and suggested that training of the upper arm muscles may be an effective preventive measure for young women to reduce the risk of early cardiovascular diseases.

12.
Crit Care ; 26(1): 253, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35996117

RESUMO

BACKGROUND: Although lung protective strategy and adjunctive intervention are associated with improved survival in patients with acute respiratory distress syndrome (ARDS), the implementation of effective therapies remains low. This study aimed to evaluate whether the use of business intelligence (BI) for real-time data visualization is associated with an improvement in lung protective strategy and adjunctive therapy. METHODS: A retrospective observational cohort study was conducted on patients with ARDS admitted between September 2020 and June 2021 at two intensive care units (ICUs) of a tertiary referral hospital in Taiwan. BI was imported for data visualization and integration to assist in clinical decision in one of the ICUs. The primary outcomes were the implementation of low tidal volume ventilation (defined as tidal volume/predicted body weight ≤ 8 mL/kg) within 24 h from ARDS onset. The secondary outcomes included ICU and hospital mortality rates. RESULTS: Among the 1201 patients admitted to the ICUs during the study period, 148 (12.3%) fulfilled the ARDS criteria, with 86 patients in the BI-assisted group and 62 patients in the standard-of-care (SOC) group. Disease severity was similar between the two groups. The application of low tidal volume ventilation strategy was significantly improved in the BI-assisted group compared with that in the SOC group (79.1% vs. 61.3%, p = 0.018). Despite their ARDS and disease severity, the BI-assisted group tended to achieve low tidal volume ventilation. The ICU and hospital mortality were lower in the BI-assisted group. CONCLUSIONS: The use of real-time visualization system for data-driven decision support was associated with significantly improved compliance to low tidal volume ventilation strategy, which enhanced the outcomes of patients with ARDS in the ICU.


Assuntos
Síndrome do Desconforto Respiratório , Humanos , Unidades de Terapia Intensiva , Pulmão , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Volume de Ventilação Pulmonar
13.
J Clin Med ; 11(13)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35806938

RESUMO

Background: The relationship of cardiorespiratory fitness (CRF) with subclinical atherosclerosis affected by the body adiposity has been observed in children, whereas this relationship remains unclear in young adults. Methods and Results: A total of 1520 military recruits, aged 18−40 years, were included in Taiwan in 2018−2020. All subjects underwent detailed physical and blood laboratory examinations. CRF was evaluated by time for a 3000 m run, and subclinical atherosclerosis was evaluated by intima−media thickness of the bulb of the left common carotid artery (cIMT) utilizing high-resolution ultrasonography. Multivariable linear regression analysis with adjustments for age, sex, cigarette smoking, alcohol intake, systolic and diastolic blood pressure, high- and low-density lipoprotein cholesterols, fasting glucose, waist circumference, serum uric acid and serum triglycerides were utilized to determine the correlation between CRF and cIMT. CRF was independently correlated with cIMT (standardized ß: 0.11, p < 0.001). Of the cardiometabolic risk markers, serum triglycerides were the only independent risk marker of cIMT (standardized ß: 0.063, p = 0.03). In addition, the association of CRF with cIMT did not differ between those with a body mass index (BMI) ≥ 25 kg/m2 and those with BMI < 25 kg/m2 (standardized ß: 0.103 and 0.117; p = 0.01 and 0.005, respectively). Conclusions: In physically active young men and women, there was an inverse association of cIMT with CRF, which was observed in both overweight/mild obesity and normal-weight individuals, highlighting the importance of endurance capacity on reducing risk of early atherosclerosis and implying that the moderation effect of body adiposity might not be present in this population.

14.
Int J Biol Sci ; 18(1): 331-348, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975336

RESUMO

Pulmonary arterial hypertension (PAH) is characterized by muscularized pulmonary blood vessels, leading to right heart hypertrophy and cardiac failure. However, state-of-the-art therapeutics fail to target the ongoing remodeling process. Here, this study shows that matrix metalloproteinases (MMP)-1 and MMP-10 levels are increased in the medial layer of vessel wall, serum, and M1-polarized macrophages from patients with PAH and the lungs of monocrotaline- and hypoxia-induced PAH rodent models. MMP-10 regulates the malignant phenotype of pulmonary artery smooth muscle cells (PASMCs). The overexpression of active MMP-10 promotes PASMC proliferation and migration via upregulation of cyclin D1 and proliferating cell nuclear antigen, suggesting that MMP-10 produced by infiltrating macrophages contributes to vascular remodeling. Furthermore, inhibition of STAT1 inhibits hypoxia-induced MMP-10 but not MMP-1 expression in M1-polarized macrophages from patients with PAH. In conclusion, circulating MMP-10 could be used as a potential targeted therapy for PAH.


Assuntos
Macrófagos/metabolismo , Metaloproteinase 10 da Matriz/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Remodelação Vascular , Adulto , Idoso , Animais , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Ratos , Regulação para Cima
15.
J Cell Physiol ; 237(2): 1299-1314, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34612516

RESUMO

The lung is the first and most frequent organ to fail among sepsis patients. The mortality rate of sepsis-related acute lung injury (ALI) is high. Despite appropriate antimicrobial therapy, no treatment strategies are available for sepsis-induced ALI. Stem cell-mediated paracrine signaling is a potential treatment method for various diseases. This study aimed to examine the effects of induced pluripotent stem cell-derived conditioned medium (iPSC-CM) combined with antibiotics on ALI in a rat model of Escherichia coli-induced sepsis. Rats were administered either iPSC-CM or the vehicle (saline) with antibiotics (ceftriaxone). After 72 h, liquid biopsy, bronchoalveolar lavage fluid (BALF), and tissues were harvested for analysis. Survival rates were observed for up to 3 days. Furthermore, we examined the effects of iPSC-CM on cytokine production, metalloproteinase 9 (MMP-9) expression, and NLRP3-ASC interaction in RAW264.7 cells stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ). Combined treatment of iPSC-CM with antibiotics significantly improved survival in E. coli-infected rats (p = 0.0006). iPSC-CM ameliorated E. coli-induced infiltration of macrophages, reducing the number of cells in BALF, and suppressing interleukin (IL)-1ß, MIP-2, IL-6, and MMP-9 messenger RNA in lung sections. iPSC-CM treatment attenuated NLRP3 expression and inhibited NLRP3 inflammasome activation by disrupting NLRP3-mediated ASC complex formation in LPS/IFN-γ-primed RAW264.7 cells. This study reveals the mechanisms underlying iPSC-CM-conferred anti-inflammatory activity in ALI through the attenuation of macrophage recruitment to the lung, thus inactivating NLRP3 inflammasomes in macrophages. iPSC-CM therapy may be a useful adjuvant treatment to reduce sepsis-related mortality by ameliorating ALI.


Assuntos
Lesão Pulmonar Aguda , Células-Tronco Pluripotentes Induzidas , Sepse , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Antibacterianos/efeitos adversos , Ceftriaxona/efeitos adversos , Meios de Cultivo Condicionados/farmacologia , Escherichia coli/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Inflamassomos/metabolismo , Lipopolissacarídeos/farmacologia , Metaloproteinase 9 da Matriz , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Sepse/tratamento farmacológico
16.
J Formos Med Assoc ; 121(1 Pt 2): 294-303, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33934947

RESUMO

BACKGROUND: Target temperature management (TTM) is a recommended therapy for patients after cardiac arrest (PCA). The TaIwan Network of Targeted Temperature ManagEment for CARDiac Arrest (TIMECARD) registry was established for PCA who receive TTM therapy in Taiwan. We aim to determine the variables that may affect neurologic outcomes in PCA who undergo TTM. METHODS: We retrieved demographic variables, resuscitation variables, and cerebral performance category (CPC) scale score at hospital discharge from the TIMECARD registry. The primary outcome was a favorable neurologic outcome, defined as a CPC scale of 1 or 2 at discharge. A total of 540 PCA treated between January 2014 and September 2019 were identified from the registry. Univariate and multivariate analyses were performed to identify significant variables. RESULTS: The mortality rate was 58.1% (314/540). Favorable neurologic outcomes were noted in 117 patients (21.7%). The factors significantly influencing the neurologic outcome (p < 0.05) were the presence of an initial shockable rhythm or pulseless electric activity, a witnessed cardiac-arrest event, bystander cardiopulmonary resuscitation, a smaller total dose of epinephrine, the diastolic blood pressure value at return of spontaneous circulation, a pre-arrest CPC score of 1, coronary angiography, new-onset seizure, and new-onset serious infection. Older patients and those with premorbid diabetes mellitus, chronic kidney disease, malignancy, obstructive lung disease, or cerebrovascular accident were more likely to have an unfavorable neurologic outcome. CONCLUSION: In the TIMECARD registry, some PCA baseline characteristics, cardiac arrest events, cardiopulmonary resuscitation characteristics, and post-arrest management characteristics were significantly associated with neurologic outcomes.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Hipotermia Induzida , Parada Cardíaca/terapia , Humanos , Sistema de Registros , Temperatura
17.
J Cardiovasc Dev Dis ; 8(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34436241

RESUMO

BACKGROUNDS: Reducing radiation exposure is the basic principle for performing percutaneous coronary intervention (PCI). Many studies have confirmed the effect of radiation protection for medical staff, but studies about the effectiveness of protection for patients and real measurement of radiation dose in patients' specific organs are lacking. AIM: To measure the radiation doses absorbed by patients' radiosensitive organs during PCI and the effectiveness of radiation protection. METHODS: A total of 120 patients were included and allocated into three groups as the ratio of 1:1:2. A total of 30 patients received PCI at 15 frames rate per second (fps), 30 patients at 7.5 fps, and 60 patients wore radiation protective hat and glasses during PCI at 7.5 fps. The radiation doses were measured at right eyebrow (lens), neck (thyroid), back (skin), and inguinal area (genital organs) by using thermoluminescent dosimeters (TLDs). RESULTS: Dose-area product (DAP) reduced by 58.8% (from 534,454 ± 344,660 to 220,352 ± 164,101 mGy·cm2, p < 0.001) after reducing the frame rate, without affecting successful rate of PCI. Radiation doses measured on skin, lens, genital organs, and thyroid decreased by 73.3%, 40.0%, 40.0%, and 35.3%, respectively (from 192.58 ± 349.45 to 51.10 ± 59.21; 5.29 ± 4.27 to 3.16 ± 2.73; 0.25 ± 0.15 to 0.15 ± 0.15; and 17.42 ± 12.11 to 11.27 ± 8.52 µSv, p < 0.05). By providing radiation protective equipment, radiation doses at lens and thyroid decreased further by 71.8% and 65.9% (from 3.16 ± 2.73 to 0.89 ± 0.79; 11.27 ± 8.52 to 3.84 ± 3.49 µSv, p < 0.05). CONCLUSIONS: By lowering the frame rate and providing protective equipment, radiation exposure in radiosensitive organs can be effectively reduced in patients.

18.
PLoS One ; 16(5): e0251109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33979377

RESUMO

Recent clinical trials showed that short aspirin duration (1 or 3 months) in dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy reduced the risk of bleeding and did not increase the ischemic risk compared to 12-month DAPT in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, it is unclear about the optimal duration of aspirin in P2Y12 inhibitor monotherapy. The purpose of this study was to evaluate the influence of aspirin treatment duration on clinical outcomes in a cohort of ACS patients with early aspirin interruption and received P2Y12 inhibitor monotherapy. From January 1, 2014 to December 31, 2018, we included 498 ACS patients (age 70.18 ± 12.84 years, 71.3% men) with aspirin stopped for various reasons before 6 months after PCI and received P2Y12 inhibitor monotherapy. The clinical outcomes between those with aspirin treatment ≤ 1 month and > 1 month were compared in 12-month follow up after PCI. Inverse probability of treatment weighting was used to balance the covariates between groups. The mean duration of aspirin treatment was 7.52 ± 8.10 days vs. 98.05 ± 56.70 days in the 2 groups (p<0.001). The primary composite endpoint of all-cause mortality, recurrent ACS or unplanned revascularization and stroke occurred in 12.6% and 14.4% in the 2 groups (adjusted HR 1.19, 95% CI 0.85-1.68). The safety outcome of BARC 3 or 5 bleeding was also similar (adjusted HR 0.69, 95% CI 0.34-1.40) between the 2 groups. In conclusion, patients with ≤ 1 month aspirin treatment had similar clinical outcomes to those with treatment > 1 month. Our results indicated that ≤ 1-month aspirin may be enough in P2Y12 inhibitor monotherapy strategy for ACS patients undergoing PCI.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada/métodos , Terapia Antiplaquetária Dupla/métodos , Duração da Terapia , Feminino , Humanos , Masculino , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Receptores Purinérgicos P2Y12/metabolismo , Taiwan
19.
J Formos Med Assoc ; 120(9): 1740-1748, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33846021

RESUMO

BACKGROUND: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is complex, and the modality of treatment is surgery and targeted medication. Patients with CTEPH could have a poor prognosis if their diagnosis or treatment is delayed. The incidence of CTEPH and its clinical features are largely unknown in Taiwan, even among other Asian populations. In this study, we aimed to investigate the geodemographics of CTEPH in Taiwan and describe the practical management and treatment outcomes in patients with CTEPH. METHODS: This study retrospectively enrolled patients in the Taiwan cohort - Registry of CTEPH. The study was conducted over 2 years inclusive of follow-up. The enrolment criteria depended on the current global guideline. RESULTS: From January 2018 to March 2020, 107 CTEPH patients enrolled in the Taiwan registry. All patients received right heart catheterisation examinations. The overall median age was 61.4 ± 16.5 years, and the cohort was dominated by female patients (75/107). Risk factors included pulmonary embolism (81.3%), deep vein thrombosis (22.4%), and previous major surgery (20.6%). Twenty-one (19.6%) patients underwent pulmonary endarterectomy operation alone, and 38 (35.5%) patients underwent balloon pulmonary angioplasty alone. CONCLUSION: To our knowledge, this is the first national cohort study that demonstrated the raw CTEPH incidence in Taiwan. It also showed the CTEPH incidence between male and female patients in the Asian population was different from the Caucasian population.


Assuntos
Hipertensão Pulmonar , Embolia Pulmonar , Adulto , Idoso , Doença Crônica , Estudos de Coortes , Endarterectomia , Feminino , Humanos , Hipertensão Pulmonar/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos , Taiwan/epidemiologia
20.
Eur J Anaesthesiol ; 38(7): 684-691, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399371

RESUMO

BACKGROUND: Early identification of patients at high risk of prolonged mechanical ventilation is important in critical care. Sarcopenia, the loss of muscle mass and function, has been reported to be associated with extended mechanical ventilation and prolonged ICU stay. Although ultrasound is noninvasive and widely used in critical care, there is no standard method of using it to assess sarcopenia. OBJECTIVES: The study aims to investigate the relationship between outcomes of critically ill patients and the ratio of BMI to the thickness of rectus abdominis measured by a standardised ultrasound examination. DESIGN: A retrospective cohort study. SETTING: Surgical ICU of a tertiary referral hospital, from October 2017 to June 2018. The thickness of rectus abdominis (RA) was measured while performing extended focused assessment sonography for trauma. BMI was divided by the thickness of rectus abdominis over the upper abdomen to derive the BMI-RA thickness ratio. PATIENTS: Sixteen male and 11 female patients admitted to ICU after major abdominal surgery. MAIN OUTCOME MEASURES: The primary outcome was in-hospital mortality, and the secondary outcomes were durations of mechanical ventilation, ICU stay and hospital stay. The disease severity, serum albumin level and BMI-RA thickness ratio were also analysed. RESULTS: Ultrasound measurement was easy to perform without adverse effects. The BMI-RA thickness ratio was significantly higher in nonsurvivors and was associated with ICU stay, hospital stay and duration of mechanical ventilation. Multivariable logistic regression showed that the BMI-RA thickness ratio was a predictor of in-hospital mortality. CONCLUSION: The BMI-RA thickness ratio is related to the outcomes of patients transferred to ICU after major abdominal surgery. Measuring the thickness of rectus abdominis by ultrasound is well tolerated and easy to perform in surgical ICU. Larger prospective studies are required to confirm current findings.


Assuntos
Estado Terminal , Reto do Abdome , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Estudos Prospectivos , Reto do Abdome/diagnóstico por imagem , Respiração Artificial , Estudos Retrospectivos
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