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1.
Ann Vasc Surg ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39098723

RESUMO

BACKGROUND: Numerous studies have indicated that increased obesity in patients with established peripheral artery disease (PAD) is inversely associated with disease prognosis, a phenomenon coined as the "obesity paradox". A major cause of criticism in studies investigating the obesity paradox is the use of body mass index (BMI) as a surrogate marker in defining and quantifying the degree or severity of obesity. We conducted a retrospective review to verify whether the obesity paradox persists in patients with PAD when using body surface area (BSA) as an alternative anthropometric measure. METHODS: Patients undergoing surgery (open or endovascular) for PAD between January 2009 and March 2020 were identified from the Vascular Quality Initiative (VQI) national database. The association between BSA or BMI and risk of postoperative complications was evaluated using logistic regression and restricted cubic spline analysis, both of which were adjusted for demographic and comorbid risk predictors. When analyzing BSA and BMI as categorical variables, patients were grouped according to BSA quintiles and the World Health Organization (WHO) BMI categories. RESULTS: A total of 130,428 patients were included based on our eligibility criteria, of which 85,394 (65.5%) were men. Patients were typically hypertensive (87.8%), diabetic (50.4%), and overweight (63.0% over 25 kg/m2). Patients with a high BMI or BSA typically presented at a younger age and with greater preoperative administration of drugs (statin, angiotensin converting enzyme inhibitor, anticoagulant, and beta blocker). Our results indicate that BSA and BMI are inversely associated with postoperative risk of all-cause morbidity, mortality, and cardiac complications. This finding was displayed when analyzing BMI or BSA as a continuous variable or when indexing patients into BMI or BSA groups. CONCLUSIONS: Our data suggests that the obesity paradox persists in patients with PAD when using either BMI or BSA as anthropometric measures. Future studies with a prospective design and utilizing newer anthropometric indices should be conducted to fully verify the presence of this phenomenon.

2.
Curr Treat Options Oncol ; 24(10): 1472-1488, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37566213

RESUMO

OPINION STATEMENT: Cardio-oncology is going under rapid development in various areas across an increasing number of provinces in China. However there are still a myriad of challenges that need to be overcome in order to ensure its gradual and consistent expansion. The Cardio-Oncology Knowledge Transfer Model (KTM) forms the basis to allow exponential development of effective cardio-oncology services. This would ensure the implementation of precision-based practice while dynamically evolving cardio-oncology to integrate both Western and Chinese medical practices to become an official clinical sub-speciality in its own right in China, for the ultimate benefit of the patient.


Assuntos
Doenças Cardiovasculares , Neoplasias , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Neoplasias/epidemiologia , Neoplasias/terapia , Oncologia , China/epidemiologia
3.
Oncol Rep ; 49(2)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36633144

RESUMO

4­Methoxydalbergione (4­MD) can inhibit the progression of certain types of cancer; however, its effects on esophageal cancer (EC) remain unclear. The present study aimed to investigate the inhibitory effect of 4­MD on EC and its molecular mechanism. ECA­109 and KYSE­105 cells were treated with or without lipopolysaccharide (LPS) and 4­MD. Cell Counting Kit­8 and colony formation assays were used to analyze cell proliferation. Wound healing assay was performed to evaluate cell migration. ELISA and western blotting were performed to measure the expression levels of NF­κB and inflammatory cytokines. In cells treated with 4­MD, proliferation and migration were significantly inhibited, the levels of inflammatory cytokines were downregulated and the NF­κB signaling pathway was inactivated. Notably, proliferation, migration, inflammation and NF­κB were promoted by LPS, whereas 4­MD reversed the increases induced by LPS in EC cells. In conclusion, 4­MD may attenuate the proliferation and migration of EC cells by inactivating the NF­κB signaling pathway.


Assuntos
Benzoquinonas , Neoplasias Esofágicas , NF-kappa B , Humanos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Lipopolissacarídeos/farmacologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Benzoquinonas/farmacologia
4.
J Ovarian Res ; 16(1): 10, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36641458

RESUMO

BACKGROUND: Many epidemiological studies have shown that anovulatory polycystic ovary syndrome (PCOS) is accompanied by hyperandrogenism. However, the exact mechanism of hyperandrogen-induced anovulation remains to be elucidated. In this study, we aimed to investigate the potential mechanism of anovulation in PCOS. To investigate the role of klotho as a key factor in the androgen receptor (AR)-mediated development of PCOS, we investigated the effects of testosterone on ovarian klotho expression in vivo and in vitro. RESULTS: Testosterone propionate (TP)-induced rats showed cycle irregularity, hyperandrogenism, polycystic ovarian changes, dyslipidemia. However, inhibition of AR expression could relieve PCOS traits. We also found that AR and klotho showed relatively high expression in PCOS rat ovarian tissue and in TP-induced granulosa cells (GCs), which was inhibited by the addition of flutamide. TP-induced GCs apoptosis was suppressed by AR antagonist, as well as silencing klotho expression in human GCs. Chromatin immunoprecipitation assay demonstrated that AR indirectly binds to the klotho promoter. CONCLUSIONS: Our results demonstrated TP mediates the expression of klotho via androgen receptor and klotho alterations could be a reason for ovarian dysfunction in PCOS.


Assuntos
Androgênios , Anovulação , Hiperandrogenismo , Proteínas Klotho , Síndrome do Ovário Policístico , Animais , Feminino , Humanos , Ratos , Androgênios/farmacologia , Apoptose , Células da Granulosa/metabolismo , Síndrome do Ovário Policístico/metabolismo , Receptores Androgênicos/metabolismo , Proteínas Klotho/metabolismo
5.
Cytokine ; 135: 155242, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32799009

RESUMO

Midkine (MK) is a low molecular-weight protein that was first identified as the product of a retinoic acid-responsive gene involved in embryonic development. Recent studies have indicated that MK levels are related to various diseases, including cardiovascular disease (CVD), renal disease and autoimmune disease. MK is a growth factor involved in multiple pathophysiological processes, such as inflammation, the repair of damaged tissues and cancer. The pathophysiological roles of MK are diverse. MK enhances the recruitment and migration of inflammatory cells upon inflammation directly and also through induction of chemokines, and contributes to tissue damage. In lung endothelial cells, oxidative stress increased the expression of MK, which induced angiotensin-converting enzyme (ACE) expression and the consequent conversion from Ang I to Ang II, leading to further oxidative stress. MK inhibited cholesterol efflux from macrophages by reducing ATP-binding cassette transporter A1 (ABCA1) expression, which is involved in lipid metabolism, suggesting that MK is an important positive factor involved in inflammation, oxidative stress and lipid metabolism. Furthermore, MK can regulate the expansion, differentiation and activation of T cells as well as B-cell survival; mediate angiogenic and antibacterial activity; and possess anti-apoptotic activity. In this paper, we summarize the pathophysiological roles of MK in human disease.


Assuntos
Midkina/metabolismo , Animais , Apoptose/fisiologia , Doença , Humanos , Inflamação/metabolismo , Macrófagos/metabolismo
6.
DNA Cell Biol ; 39(8): 1401-1409, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32077751

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common female reproductive metabolisms. It is an endocrine disease that affects reproductive women and often exhibits with hyperandrogenemia, insulin resistance (IR), low inflammation, and an increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular events such as hypertension and dyslipidemia in patients. However, the molecular mechanism of PCOS is still unclear. Recently, an increasing number of studies have shown that the oxidative stress induced by mitochondrial dysfunction has negative effects on IR, lipid metabolism, and follicular development, suggesting that mitochondrial dysfunction plays an essential role in the development of PCOS. Abnormal mitochondrial DNA copy number in patients with PCOS, and mitochondrial gene mutations, has been the focus of research in recent years, and functional mitochondrial diseases have been gradually accepted as a related factor in PCOS. This review is intended to summarize and discuss previous and recent studies and findings on the connections between mitochondrial dysfunction and PCOS.


Assuntos
Variações do Número de Cópias de DNA/genética , Predisposição Genética para Doença , Mitocôndrias/genética , Síndrome do Ovário Policístico/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Dislipidemias/genética , Dislipidemias/patologia , Feminino , Humanos , Hiperandrogenismo/genética , Hiperandrogenismo/patologia , Hipertensão/genética , Hipertensão/patologia , Resistência à Insulina/genética , Mitocôndrias/patologia , Mutação/genética , Síndrome do Ovário Policístico/patologia
7.
Aging (Albany NY) ; 11(24): 12236-12245, 2019 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-31866580

RESUMO

Diabetic foot (DF) is a common complication of high severity for diabetes, a prevalent metabolic disorder that affects billions of people worldwide. Mesenchymal stem cells (MSCs) have a demonstrative therapeutic effect on DF, through their generation of pro-angiogenesis factors, like vascular endothelial growth factor (VEGF). Recently, genetically modified MSCs have been used in therapy and we have shown that depletion of micoRNA-205-5p (miR-205-5p) in human MSCs promotes VEGF-mediated therapeutic effects on DF. Here, we showed that a long non-coding RNA (lncRNA), MALAT1, is a competing endogenous RNA (ceRNA) for miR-205-5p, and is low expressed in human MSCs. Ectopic expression of MALAT1 in human MSCs significantly decreased miR-205-5p levels, resulting in upregulation of VEGF production and improved in vitro endothelial cell tube formation. In a DF model in immunodeficient NOD/SCID mice, transplantation of human miR-205-5p-depleted MSCs exhibited better therapeutic effects on DF recovery than control MSCs. Moreover, MALAT1-expressing MSCs showed even better therapeutic effects on DF recovery than miR-205-5p-depleted MSCs. This difference in DF recovery was shown to be associated with the levels of on-site vascularization. Together, our data suggest that MALAT1 functions as a sponge RNA for miR-205-5p to increase therapeutic effects of MSCs on DF.


Assuntos
Pé Diabético/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , RNA Longo não Codificante/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Exp Cell Res ; 359(2): 374-383, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28823833

RESUMO

Atherosclerosis is a common pathological basis of cardiovascular disease and remains the leading cause of mortality. Endothelial cell (EC) injury and autophagy dysfunction have been proved to contribute to the development of atherosclerosis. Recently, accumulating evidence confirms that microRNAs (miRNAs) have emerged as vital regulators and fine-tuners of various pathophysiological cellular impacts and molecular signaling pathways involved in atherosclerosis. Herein, the objective of the present study was to explore the biological function of miR-21 in oxidized low-density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs) injury and the underlying molecular mechanism. The results showed that ox-LDL treatment significantly decreased HAECs viability, increased caspase-3 activity, apoptosis ratio and Bax protein expression, and reduced Bcl-2 protein expression resulting in EC injuries. Simultaneously, ox-LDL treatment obviously reduced miR-21 level in a time-and dose-dependent manner. Notably, ox-LDL-induced EC injuries were abolished by miR-21 mimics transfection. In addition, miR-21 mimics alleviated ox-LDL-induced impaired autophagic flux as illustrated by the increases in LC3-II/LC3-I ratio and Beclin-1 protein expression, and the decrease in p62 protein expression in HAECs. Moreover, ox-LDL suppressed the expressions of lysosomal membrane protein (LAMP1) and cathepsin D proteins, and attenuated cathepsin D activity in HAECs, leading to lysosomal dysfunction, while these effects were also blocked by miR-21 mimics. These findings indicated that miR-21 restored impaired autophagic flux and lysosomal dysfunction, thereby attenuating ox-LDL-induced HAECs injuries.


Assuntos
Autofagia/genética , Células Endoteliais/efeitos dos fármacos , Lipoproteínas LDL/farmacologia , MicroRNAs/genética , Aorta/citologia , Aorta/efeitos dos fármacos , Aorta/metabolismo , Autofagia/efeitos dos fármacos , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Catepsina D/genética , Catepsina D/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Humanos , Proteínas de Membrana Lisossomal/genética , Proteínas de Membrana Lisossomal/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mimetismo Molecular , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais
9.
Exp Biol Med (Maywood) ; 242(3): 250-257, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27698252

RESUMO

Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor, which was most commonly examined in mucosal fluids such as saliva, is a versatile molecule and plays non-redundant roles. In addition to its anti-protease activity, SLPI has been shown to express anti-bacterial, anti-viral, anti-fungal, and anti-inflammatory properties as well as participating in innate and adaptive immune responses, most of which has been well documented. Recently, it is reported that SLPI is expressed in adipocytes and adipose tissue where it could play an important feedback role in the resolution of inflammation. Furthermore, circulating SLPI has been shown to correlate with progressive metabolic dysfunction. Moreover, adenoviral gene delivery of elafin and SLPI attenuates nuclear factor-κB-dependent inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli. This review contributes to unraveling the protective role of SLPI in obesity-related atherosclerosis development, and the potential role in preventing arterial plaque rupture.


Assuntos
Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Aterosclerose/patologia , Obesidade/patologia , Placa Aterosclerótica/patologia , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Aterosclerose/complicações , Elafina/genética , Elafina/metabolismo , Humanos , Inflamação/prevenção & controle , Obesidade/etiologia
10.
Chin Med J (Engl) ; 129(9): 1108-12, 2016 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-27098798

RESUMO

BACKGROUND: Adipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein-1 (MCP-1). Oxidized low-density lipoprotein (oxLDL) participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinflammatory function of oxLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L1 adipocytes induced by oxLDL and to elucidate the possible mechanisms. METHODS: Fully differentiated 3T3-L1 adipocytes were incubated in the medium containing various concentration of L-4F (0-50 µg/ml) with oxLDL (50 µg/ml) stimulated, with/without protein kinase A (PKA) inhibitor H-89 (10 µmol/L) preincubated. The concentrations of MCP-1 in the supernatant, the mRNA expression of MCP-1, the levels of CCAAT/enhancer binding protein α (C/EBPα), and CCAAT/enhancer binding protein ß (C/EBPß) were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber. RESULTS: OxLDL stimulation induced a significant increase of MCP-1 expression and secretion in 3T3-L1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F (50 µg/ml) (P > 0.05). OxLDL stimulation showed no significant effect on C/EBPα protein level but increased C/EBPß protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPß protein level in oxLDL-induced 3T3-L1 adipocytes. CONCLUSIONS: OxLDL induces C/EBPß protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPß signaling pathway may participate in it.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/fisiologia , Quimiocina CCL2/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , AMP Cíclico/fisiologia , Lipoproteínas LDL/antagonistas & inibidores , Peptídeos/farmacologia , Transdução de Sinais/fisiologia , Células 3T3-L1 , Animais , Proteína beta Intensificadora de Ligação a CCAAT/análise , Quimiocina CCL2/genética , Humanos , Lipoproteínas LDL/farmacologia , Camundongos
11.
Int J Clin Exp Med ; 8(8): 12498-508, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26550160

RESUMO

BACKGROUND: Therapeutic myocardial angiogenesis is an important compensatory mechanism in severely coronary stenosis. Previous studies demonstrated that interleukin-8 (IL-8) not only plays an important role in inflammation, but also a potent angiogenic factor through p38 mitogen-activated protein kinase (p38MAPK), nuclear factor-kappaB (NK-κB)-dependent pathway in carcinoma. Our study sought to investigate the effects of IL-8 on the angiogenesis and the underlying mechanism in the ischemic myocardium. METHODS: Acute myocardial infarction animal model was established with male rabbits by directly suturing the left anterior descending branch, then lentivirus-mediated IL-8 was quarterly injected into the borderline of infarction area immediately. We employed CoCl2 induced hypoxic HUVECs for in vitro ischemia study. Left ventricular end-diastolic diameter (LVEDd) and ejection fraction (EF) were measured by echocardiography in pre-operation and at 6(th) week after operation. CD34 was detected with immunohistochemisty to analyse angiogenesis. Western blot was performed with regard to IL-8, protein kinase B (PKB/Akt) and Glycogen synthase kinase-3ß(ser9) (GSK-3ß(ser9)). For the HUVECs' proliferation and apoptosis, multiscan spectrum reader at A570 nm and annexin V-FITC/PI staining method were used respectively. RESULTS: The levels of IL-8, phosphorylated Akt and GSK-3ß(ser9) in focal myocardium significantly increased, and the over expression of IL-8 led to an increasing in angiogenesis in rabbits. Hypoxia inhibited cell proliferation and promoted apoptosis. IL-8 induced cell proliferation, phosphorylation of Akt and GSK-3ß(ser9), inhibited apoptosis and Caspase3 expression in HUVECs, which were attenuated by anti-IL-8 or the Akt inhibitor LY294002. CONCLUSIONS: The present results indicate that IL-8 can increase angiogenesis in myocardial infarction, which maybe through enhancing Akt and GSK-3ß(ser9) expression, and inhibiting myocardial apoptosis.

12.
Int J Biol Sci ; 11(3): 256-65, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25678844

RESUMO

AIM: Previous studies have demonstrated that the dysregulated-secretion of adipokines by adipocytes may contribute to obesity-associated atherosclerosis (As) and high density lipoprotein (HDL) may protect against atherogenesis through multiple pathways. This study was to explore the effect of HDL on the oxLDL uptake in inflammatory adipocytes stimulated by endotoxin lipopolysaccharide (LPS) and the possible mechanism. METHODS AND RESULTS: 3T3-L1 adipocytes were cultured and induced to differentiation and maturation. Acute inflammation in adipocytes was induced by LPS (100 ng/ml) for 6 hours. The adipocytes were pretreated with HDL in various concentrations (10, 50, 100 µg/ml) for 16 hours or with specific PPARγ antagonist (GW9662, 10 µM) or agonist (Rosiglitazone, 10 µM) for 30 min before administration of LPS. The results showed that LPS significantly increased the release of inflammation-related adipokines, such as monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8 and IL-6, while decreasing the release of leptin and adiponectin. Meanwhile, LPS reduced the uptake and degradation of 125I-oxLDL, and down-regulated the expression of PPARγ and CD36. Pretreatment with HDL dose-dependently affected the release of IL-8 and IL-6 and the reduced uptake and degradation of oxLDL of adipocytes stimulated by LPS, accompanied with marked upregulation of PPARγ and CD36 expression. Pretreatment with GW9662 markedly inhibited the upregulation of CD36 expression mediated by HDL (100 µg/ml), while the effects of Rosiglitazone were opposite to GW9662. CONCLUSIONS: HDL may increase oxLDL uptake of inflammatory adipocytes stimulated by LPS via upregulation of PPARγ/CD36 pathway, which may be a new mechanism of anti-atherosclerosis mediated by HDL.


Assuntos
Adipócitos/metabolismo , Antígenos CD36/metabolismo , Lipoproteínas HDL/fisiologia , PPAR gama/metabolismo , Células 3T3 , Adipocinas/metabolismo , Animais , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Redes e Vias Metabólicas , Camundongos , Oxirredução
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