RESUMO
BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death around the world. Most CVDs-related death can be prevented by the optimal management of risk factors such as unhealthy diet and physical inactivity. Clinical practice guidelines (CPGs) for CVDs, provide some evidence-based recommendations which help healthcare professionals to achieve the best care for patients with CVDs. This systematic review aims to appraise the methodological quality of CPGs systematically and summarize the recommendations of self-managed non-pharmacological interventions for the prevention and management of CVDs provided by the selected guidelines. METHODS: A comprehensive electronic literature search was conducted via six databases (PubMed, Medline, The Cochrane Library, Embase, CINAHL, and Web of Science), seven professional heart association websites, and nine guideline repositories. The Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument was adopted to critically appraise the methodological quality of the selected guidelines. Content analysis was used to summarise recommended self-managed non-pharmacological interventions for CVDs. RESULTS: Twenty-three CPGs regarding different CVDs were included, in which four guidelines of CVDs, three for coronary heart diseases, seven for heart failure, two for atrial fibrillation, three for stroke, three for peripheral arterial disease, and one for hypertrophic cardiomyopathy. Twenty CPGs were appraised as high quality, and three CPGs as moderate quality. All twenty-three CPGs were recommended for use with or without modification. The domain of "Editorial Independence" had the highest standardized percentage (93.47%), whereas the domain of "Applicability" had the lowest mean domain score of 75.41%. The content analysis findings summarised some common self-managed non-pharmacological interventions, which include healthy diet, physical activity, smoking cessation, alcohol control, and weight management. Healthy diet and physical acidity are the most common and agreed on self-managed interventions for patients with CVDs. There are some inconsistencies identified in the details of recommended interventions, the intervention itself, the grade of recommendation, and the supported level of evidence. CONCLUSION: The majority of the summarized non-pharmacological interventions were strongly recommended with moderate to high-quality levels of evidence. Healthcare professionals and researchers can adopt the results of this review to design self-managed non-pharmacological interventions for patients with CVDs.
Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Doença Arterial Periférica , Autogestão , Humanos , Doenças Cardiovasculares/terapia , Guias de Prática Clínica como AssuntoRESUMO
The first amidation of carbazoles at the N9 position via palladium-catalyzed hydroamination of isocyanates is demonstrated. This simple, general and efficient method could deliver a wide range of carbazole-N-carboxamides in up to 99% yield. The salient features of this transformation include simple conditions with no need for a strong base, high chemo- and regio-selectivities and good functional group tolerance. In particular, this work-up-free and chromatography-free protocol is time-saving, cost-effective and user-friendly.
RESUMO
PURPOSE: To explore care requirements of older adults with urinary incontinence (UI) and contributing factors. METHOD: This cross-sectional study used the Older Adults Urinary Incontinence Care Needs Inventory to survey participants with UI in three large-scale tertiary hospitals located in Guangzhou City, China, from January 2023 to November 2023. Statistical analyses, including analysis of variance, t tests, correlation analyses, and linear regression models, were conducted to assess factors influencing participants' care needs. RESULTS: A total of 530 older adults with UI participated in the survey and mean standardized score for overall care needs was 78.65 (SD = 5.01), with mean scores for each dimension ranging from 70.88 (SD = 10.55) for social participation needs to 82.45 (SD = 7.11) for health education needs. Factors that were found to influence incontinence care needs in older adults included age, literacy level, number of leaks, and type of disease (F = 37.07, adjusted R2 = 0.290, p < 0.001). CONCLUSION: Comprehensive care for older adults with UI, encompassing physiological, psychological, and social aspects, is crucial. It is essential to tailor care to individual needs and characteristics, taking into account factors, such as age and education, to ensure effective care. [Journal of Gerontological Nursing, 50(5), 43-49.].
Assuntos
Incontinência Urinária , Humanos , Incontinência Urinária/enfermagem , Estudos Transversais , Idoso , Feminino , Masculino , Idoso de 80 Anos ou mais , China , Pessoa de Meia-Idade , Inquéritos e Questionários , Avaliação das Necessidades , Necessidades e Demandas de Serviços de SaúdeRESUMO
IgA nephropathy (IgAN) is the most common primary glomerulonephritis and a leading cause of chronic kidney disease. The pathogenic mechanism of IgAN remains largely unknown and thus a specific therapeutic target is lacking. Here, we reported that the cytochrome P450 (CYP) epoxygenase/epoxide hydrolase (EH) axis was activated in the patients and is likely a therapeutic target for IgAN. Specifically, quantitative profiling of the plasma from IgAN patients and healthy controls revealed significant changes in plasma levels of CYP/EH-mediated lipid epoxides and diols. Subsequently, CYP2C8, CYP2C18, CYP2J2, EPHX1, and EPHX2 were found to be significantly increased in whole blood cells at mRNA levels from the IgAN patients when compared with those of healthy controls. Immunohistochemical analysis showed that all five CYPs and two EHs were upregulated in the kidney tissue from IgAN patients when compared with normative renal tissue, but the expression locations of the proteins were different with most of them. Treatment of HK-2 cells with IgA1 increased cell viability, compressed cell apoptosis, and increased the protein levels of CYP2C9, EPHX1, and EPHX2. All the results agreed that CYPs/EHs axis is likely the prophylactic and therapeutic target for IgAN, providing IgAN patients with a new intervention strategy.
Assuntos
Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/metabolismo , Epóxido Hidrolases/genética , Epóxido Hidrolases/metabolismo , Citocromo P-450 CYP2J2 , Imunoglobulina A , Sistema Enzimático do Citocromo P-450/genética , MetabolômicaRESUMO
Two new trimethoxyl A2B triaryl corroles 10-(2,4,6-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)- corrole (1) and 10-(3,4,5-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)-corrole (2) and their gallium(III) and phosphorus(V) (1-Ga, 1-P, 2-Ga and 2-P) complexes had been prepared and well characterized by UV-vis, NMR and HR-MS. Among all compounds, 2-Ga, 1-P and 2-P showed excellent in vivo photodynamic activity against the MDA-MB-231, A549, Hela and HepG2 cell lines upon light irradiation at 625 nm. And 2-P even exhibited higher phototoxicity than the clinical photosensitizer temoporfin. Also, 2-P exhibited the highest singlet oxygen quantum yield and photostability. The preliminary investigation revealed that 2-P could be rapidly absorbed by tumor cells and mainly located in the cytoplasm. After photodynamic therapy (PDT) treatment with 2-P, mitochondrial membrane potential destruction, intracellular ROS level increasing and nuclear fragmentation of cancer cells could be observed. Cell cycle analysis demonstrated that the 2-P PDT may cause tumor cell arrest at sub-G1 stage and induce early and late apoptosis of cells. These results suggest that 2-P is a promising candidate as a photosensitizer for photodynamic therapy.
Assuntos
Gálio , Fotoquimioterapia , Humanos , Gálio/farmacologia , Gálio/química , Fármacos Fotossensibilizantes/farmacologia , Fósforo/farmacologia , Linhagem Celular TumoralRESUMO
A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury. Here we report that HFD-caused renal injury involved the inactivation of Pax2 and Ampk, and the activation of soluble epoxide hydrolase (sEH), in a murine model. Specifically, mice fed on an HFD for 2, 4, and 8 wk showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, and a significant increase in renal sEH at mRNA, protein, and molecular levels. Also, administration of an sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea, significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused significant increase in Mcp-1, and decrease in both Pax2 and Ampk in murine renal mesangial cells (mRMCs) time- and dose-dependently. Also, 14(15)-EET (a major substrate of sEH), but not its sEH-mediated metabolite 14,15-DHET, significantly reversed PA-induced increase in Mcp-1, and PA-induced decrease in Pax2 and Ampk. In addition, plasmid construction revealed that Pax2 may positively regulate Ampk transcriptionally in mRMCs. This study provides insights into and therapeutic target for the HFD-mediated renal injury.
Assuntos
Adenilato Quinase/metabolismo , Dieta Hiperlipídica , Epóxido Hidrolases/antagonistas & inibidores , Rim/lesões , Fator de Transcrição PAX2/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Modelos Animais de Doenças , Eicosanoides/metabolismo , Inibidores Enzimáticos/farmacologia , Epóxido Hidrolases/metabolismo , Hipertrofia , Rim/patologia , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Camundongos , Ácido Palmítico , Compostos de Fenilureia/farmacologia , Piperidinas/farmacologia , Solubilidade , Fatores de Tempo , Aumento de PesoRESUMO
INTRODUCTION: The aim of the study was to explore the effects of low-frequency electrical stimulation (LFES) in preventing urinary retention after radical hysterectomy (RH) in women with cervical cancer. METHODS: Seven electronic bibliographic databases were searched from inception to December 25, 2021. The mean difference (MD) or risk ratio (RR) with its corresponding 95% CI was selected as effect size. The meta-analysis of all data was conducted using RevMan 5.4 and the evidence was summarized according to GRADE (the grading of recommendation, assessment, development, and evaluation). RESULTS: Twelve randomized control trials consisting of 1,033 women with cervical cancer who had undergone RH were included. Compared with women in the control group, women receiving LFES had improved therapeutic effect (RR = 0.22, 95% CI: 0.16-0.29) and reduced residual urine volume (MD = -32.27, 95% CI: -34.10 to -30.43) and catheter retention time (MD = -4.46, 95% CI: -5.17 to -3.76) following treatment. Muscle strength scores of pelvic floor type I and type II muscle fibers in the LFES group were also higher than in the control group (MD = 1.07, 95% CI: 0.91-1.24). CONCLUSION: LFES may be an effective auxiliary treatment for women with cervical cancer after hysterectomy, which can help reduce the duration of indwelling urethral catheter and residual urine volume.
Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/cirurgia , Histerectomia , Diafragma da Pelve , Bexiga Urinária , Estimulação ElétricaRESUMO
Endometrial decidualization plays a pivotal role during early pregnancy. Compromised decidualization has been tightly associated with recurrent implantation failure (RIF). Primary cilium is an antenna-like sensory organelle and acts as a signaling nexus to mediate Hh, Wnt, TGFß, BMP, FGF, and Notch signaling. However, whether primary cilium is involved in human decidualization is still unknown. In this study, we found that primary cilia are present in human endometrial stromal cells. The ciliogenesis and cilia length are increased by progesterone during in vitro and in vivo decidualization. Primary cilia are abnormal in the endometrium of RIF patients. Based on data from both assembly and disassembly of primary cilia, it has been determined that primary cilium is essential to human decidualization. Trichoplein (TCHP)-Aurora A signaling mediates cilia disassembly during human in vitro decidualization. Mechanistically, primary cilium modulates human decidualization through PTEN-PI3K-AKT-FOXO1 signaling. Our study highlights primary cilium as a novel decidualization-related signaling pathway.
Assuntos
Cílios , Proteínas Proto-Oncogênicas c-akt , Gravidez , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cílios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Endométrio/metabolismo , Transdução de Sinais , Células Estromais/metabolismo , Decídua/metabolismoRESUMO
Nardosinone, a sesquiterpene peroxide, is one of the main active constituents of the ethnomedicine Nardostachyos Radix et Rhizoma, and it has many bioactivities, such as antiarrhythmia and cardioprotection. To elucidate its in vivo existence forms, its metabolism is first studied using mice. All urine and feces are collected during the six days of oral dosing of nardosinone, and blood is collected at one hour after the last dose. Besides, to validate some metabolites, a fast experiment is performed, in which nardosinone was orally administered and the subsequent one-hour urine is collected and immediately analyzed by UHPLC-Q-TOF-MS. In total, 76 new metabolites are identified in this study, including 39, 51, and 12 metabolites in urine, plasma, and feces, respectively. Nardosinone can be converted into nardosinone acid or its isomers. The metabolic reactions of nardosinone included hydroxylation, hydrogenation, dehydration, glucuronidation, sulfation, demethylation, and carboxylation. There are 56 and 20 metabolites with the structural skeleton of nardosinone and nardosinone acid, respectively. In total, 77 in vivo existence forms of nardosinone are found in mice. Nardosinone is mainly excreted in urine and is not detected in the feces. These findings will lay the foundation for further research of the in vivo effective forms of nardosinone and Nardostachyos Radix et Rhizoma.
Assuntos
Medicamentos de Ervas Chinesas , Ratos , Camundongos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Ratos Sprague-Dawley , Sesquiterpenos Policíclicos , Medicamentos de Ervas Chinesas/química , Fezes/química , Administração OralRESUMO
There are around 300 million adolescent pregnancies worldwide, accounting for 11% of all births worldwide. Accumulating evidence demonstrates that many adverse perinatal outcomes are associated with adolescent pregnancies. However, how and why these abnormalities occur remain to be defined. In this study, pregnancy at different stages was compared between 25- and 30- day-old and mature female mice. We found that the litter size of adolescent pregnancy is significantly decreased from F1 to F3 generations compared to mature pregnancy. On days 8 and 12 of pregnancy, multiple abnormalities in decidual and placental development appear in F3 adolescent pregnancy. On days 5 and 8, uterine endoplasmic reticulum stress is dysregulated in F3 adolescent pregnancy. Embryo implantation and decidualization are also compromised in adolescent pregnancy. Many genes are abnormally expressed in adolescent estrous uteri. The abnormal endocrine environment and abnormal implantation from uterine immaturity may result in multiple pregnancy failures in adolescent pregnancy. The aim of this study is to shed light on human adolescent pregnancy.
Assuntos
Gravidez na Adolescência , Adolescente , Animais , Decídua , Implantação do Embrião , Feminino , Humanos , Camundongos , Placenta , Gravidez , Reprodução , ÚteroRESUMO
Glucocorticoids (GCs), stress-induced steroid hormones, are released by adrenal cortex and essential for stress adaptation. Recently, there has been renewed interest in the relationship between GCs and pregnancy following the discovery that glucocorticoid receptor is necessary for implantation. It has been widely recognized that stress is detrimental to pregnancy. However, effects of stress-induced GC exposure on uterine receptivity and decidualization are still poorly understood. This study aims to explore the effects of GCs exposure on uterine receptivity, decidualization, and their underlying mechanisms in mice. Single prolonged stress (SPS) and corticosterone (Cort) injection models were used to analyze effects of GC exposure on early pregnancy, respectively. SPS or Cort injection inhibits embryo implantation by interfering Lif signaling and stimulating the uterine deposition of collagen types I, III, and IV on day 4 of pregnancy. Uterine decidualization is also attenuated by SPS or Cort injection through suppressing Cox-2 expression. Cort-induced collagen disorder also suppresses decidualization through regulating mesenchymal-epithelial transition. Our data should shed lights for a better understanding for the effects of GCs on embryo implantation for clinical research.
Assuntos
Anti-Inflamatórios/toxicidade , Corticosterona/toxicidade , Decídua/patologia , Implantação do Embrião/efeitos dos fármacos , Estresse Fisiológico , Útero/patologia , Animais , Decídua/efeitos dos fármacos , Feminino , Masculino , Camundongos , Gravidez , Útero/efeitos dos fármacosRESUMO
A facile spray pyrolysis method is introduced to construct the hollow CeO2-Al2O3 spheres with atomically dispersed Fe. Only nitrates and ethanol were involved during the one-step preparation process using the ultrasound spray pyrolysis approach. Detailed explorations demonstrated that differences in the pyrolysis temperature of the precursors and heat transfer are crucial to the formation of the hollow nanostructure. In addition, iron species were in situ atomically dispersed on the as-formed CeO2-Al2O3 hollow spheres via this strategy, which demonstrated promising potential in transferring syn-gas to valuable gasoline products.
RESUMO
BACKGROUND: Strength recovery of injured knee is an important parameter for patients who want to return to sport after anterior cruciate ligament reconstruction (ACLR). Comparison of muscle strength between anatomical and non-anatomical ACLR has not been reported. PURPOSE: To evaluate the difference between anatomical and non-anatomical single-bundle ACLR in hamstring and quadriceps strength and clinical outcomes. METHODS: Patients received unilateral primary single-bundle hamstring ACLR between January 2017 to January 2018 were recruited in this study. Patients were divided into anatomical reconstruction group (AR group) and non-anatomical reconstruction group (NAR group) according to femoral tunnel aperture position. The hamstring and quadriceps isokinetic strength including peak extension torque, peak flexion torque and H/Q ratio were measured at an angular velocity of 180°/s and 60°/s using an isokinetic dynamometer. The isometric extension and flexion torques were also measured. Hamstring and quadriceps strength were measured preoperatively and at 3, 6, and 12 months after surgery. Knee stability including Lachman test, pivot-shift test, and KT-1000 measurement and subjective knee function including International Knee Documentation Committee (IKDC) and Lysholm scores were evaluated during the follow-up. RESULTS: Seventy-two patients with an average follow-up of 30.4 months (range, 24-35 months) were included in this study. Thirty-three were in AR group and 39 in NAR group. The peak knee flexion torque was significant higher in AR group at 180°/s and 60°/s (P < 0.05 for both velocity) at 6 months postoperatively and showed no difference between the two groups at 12 months postoperatively. The isometric knee extension torque was significant higher in AR group at 6 months postoperatively (P < 0.05) and showed no difference between the two groups at 12 months postoperatively. No significant differences between AR group and NAR group were found regarding knee stability and subjective knee function evaluations at follow-up. CONCLUSIONS: Compared with non-anatomical ACLR, anatomical ACLR showed a better recovery of hamstring and quadriceps strength at 6 months postoperatively. However, the discrepancy on hamstring and quadriceps strength between the two groups vanished at 1 year postoperatively.
Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Músculos Isquiossurais , Lesões do Ligamento Cruzado Anterior/diagnóstico , Lesões do Ligamento Cruzado Anterior/cirurgia , Humanos , Articulação do Joelho/cirurgia , Força Muscular , Músculo Quadríceps , Estudos RetrospectivosRESUMO
Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by Laminin α5) is a member of the laminin family, which is mainly expressed in the basement membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of Prl8a2, a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPß pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPß pathway.
Assuntos
Decídua/metabolismo , Laminina/metabolismo , Adulto , Animais , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Decídua/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Laminina/genética , Masculino , Camundongos Endogâmicos ICR , Modelos Biológicos , Gravidez , Progesterona/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismoRESUMO
Watershed models are important tools for predicting the possible change of watershed responses. Environmental models comprise the deterministic model and the probabilistic model. This study discusses the Hydrological Simulation Program Fortran (HSPF) and the Back-Propagation Neural Network (BPNN); these two models represent the deterministic model and the probabilistic model, respectively. As the properties of the two models are distinct, they have differing abilities to predict surface-runoff pollution. For the two models, the runoff simulation results are satisfactory. However, due to the limitation of the water quality monitoring records, pollution simulation is more difficult than runoff simulation. The results indicate that the prediction accuracy in the pollution simulation can be improved by adjusting the BPNN neurons. On the contrary, improving the prediction accuracy is limited by HSPF. Although the flexibility of BPNN is higher than HSPF, sufficient historical monitoring records are important for both of these models.
Assuntos
Poluição Ambiental , Modelos Teóricos , Redes Neurais de Computação , Mudança Climática , Simulação por ComputadorRESUMO
AIM: Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2-((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. METHODS: In vitro tyrosine kinase activity was measured using ELISA, and intracellular signaling pathway proteins were detected by Western blot analysis. Endothelial cell proliferation was examined with CCK-8 assays, and tumor cell proliferation was determined with SRB assays. Cell migration, tube formation and rat aortic ring assays were used to detect antiangiogenic activity. Antitumor efficacy was further evaluated in U87-MG human glioblastoma xenograft tumors in nude mice receiving DW10075 (500 mg · kg(-1) · d(-1), po) for two weeks. RESULTS: Among a panel of 21 kinases tested, DW10075 selectively inhibited VEGFR-1, VEGFR-2 and VEGFR-3 (the IC50 values were 6.4, 0.69 and 5.5 nmol/L, respectively), but did not affect 18 other kinases including FGFR and PDGFR at 10 µmol/L. DW10075 significantly blocked VEGF-induced activation of VEGFR and its downstream signaling transduction in primary human umbilical vein endothelial cells (HUVECs), thus inhibited VEGF-induced HUVEC proliferation. DW10075 (1-100 nmol/L) dose-dependently inhibited VEGF-induced HUVEC migration and tube formation and suppressed angiogenesis in both the rat aortic ring model and the chicken chorioallantoic membrane model. Furthermore, DW10075 exhibited anti-proliferative activity against 22 different human cancer cell lines with IC50 values ranging from 2.2 µmol/L (for U87-MG human glioblastoma cells) to 22.2 µmol/L (for A375 melanoma cells). In U87-MG xenograft tumors in nude mice, oral administration of DW10075 significantly suppressed tumor growth, and reduced the expression of CD31 and Ki67 in the tumor tissues. CONCLUSION: DW10075 is a potent and highly selective inhibitor of VEGFR that deserves further development.
Assuntos
Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Glioblastoma/tratamento farmacológico , Pirimidinas/química , Pirimidinas/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Galinhas , Glioblastoma/irrigação sanguínea , Glioblastoma/metabolismo , Glioblastoma/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Ratos Sprague-Dawley , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
AIM: 7,8-Dihydroxy-4-(3-hydroxy-4-methoxyphenyl)-2H-chromen-2-one (DW532) is one of simplified analogues of hematoxylin that has shown broad-spectrum inhibition on tyrosine kinases and in vitro anti-cancer activities. The aim of this study was to identify DW532 as a agent targeting both kinases and tubulin, and to investigate its anti-cancer and anti-angiogenesis activities. METHODS: In vitro tyrosine kinases activity was examined with ELISA, and tyrosine kinases activity in cells was evaluated with Western blot analysis. Tubulin turbidity assay, surface plasmon resonance and immunofluorescence technique were used to characterize the tubulin inhibitory activity. Cell proliferation was examined with SRB assay, and cell apoptosis and cell cycle distribution were analyzed with Annexin-V/PI staining and flow cytometry. Tube formation, aortic ring and chick chorioallantoic membrane assays were used to evaluate the anti-angiogenesis efficacy. RESULTS: DW532 inhibited EGFR and VEGFR2 in vitro kinase activity (the IC50 values were 4.9 and 5.5 µmol/L, respectively), and suppressed their downstream signaling. DW532 dose-dependently inhibited tubulin polymerization via direct binding to tubulin, thus disrupting the mitotic spindle assembly and leading to abnormal cell division. In a panel of human cancer cells, DW532 (1 and 10 µmol/L) induced G2/M phase arrest and cell apoptosis, which subsequently resulted in cytotoxicity. Knockdown of BubR1 or Mps1, the two core proteins of the spindle assembly checkpoint dramatically decreased DW532-induced cell cycle arrest in MDA-MB-468 cells. Moreover, treatment with DW532 potently and dose-dependently suppressed angiogenesis in vitro and in vivo. CONCLUSION: DW532 is a dual inhibitor against tubulin and tyrosine kinases, and deserves further development as a novel anti-cancer agent.
Assuntos
Antineoplásicos/química , Cromonas/química , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/química , Moduladores de Tubulina/química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromonas/farmacologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Background: Cervical cancer is the fourth most common cancer among females globally, with a high incidence and high mortality among females in developing countries. This retrospective case-control study aimed to investigate the association between oral contraceptives and cervical cancer, on which insufficient evidence still exists. Material and Methods: To examine the association between oral contraceptives and cervical cancer based on 7,496 females aged over 20 years from the National Health and Nutrition Examination Survey, multivariable logistic regression conducted from 1999 to 2016 was used. Results: Contraceptive use was positively associated with cervical cancer risk. In model 1 (unadjusted), a 195% increased risk of cervical cancer was observed among those who used oral contraceptives (odds ratio [OR] = 2.27, 95% confidence interval [CI] = 1.39-3.98, p = 0.002) compared to those who did not. In addition, the ORs for the exposed population were 1.74 (95% CI = 1.05-3.08, p = 0.041) and 1.93 (95% CI = 1.16-3.44, p = 0.017) in model 2 (adjusted for age, race, and body mass index [BMI]) and model 3 (adjusted for education level, ratio of family income to poverty, drinking status, smoking status, number of pregnancies, age at first sex, number of sexual partners, and whether to receive the human papillomavirus (HPV) vaccine in addition to model 2), respectively. Furthermore, subgroup analyses stratified by age, smoking status, BMI, age at first sex, number of sexual partners, and whether to receive the HPV vaccine also revealed that oral contraceptives were significantly associated with cervical cancer. Conclusion: This study demonstrated that oral contraceptive use increased the risk of cervical cancer. In addition, the higher risk, including individuals older than 45 years, having a high BMI (≥30 kg/m2), being current smokers, and having more than five sexual partners, may contribute to the development of cervical cancer.
RESUMO
Objective: To summarize nonpharmacological interventions and assess their effects on symptom clusters and quality of life (QoL) in breast cancer (BC) survivors. Methods: Seven English and three Chinese electronic databases and three clinical trial registries were searched from January 2001 to August 2023. A narrative approach was applied to summarize the data. The primary outcome was symptom clusters measured by any patient-reported questionnaires, and the secondary outcomes were QoL and intervention-related adverse events. Results: Six published articles, one thesis, and one ongoing trial involving 625 BC survivors were included. The fatigue-sleep disturbance-depression symptom cluster was the most frequently reported symptom cluster among BC survivors. The nonpharmacological interventions were potentially positive on symptom clusters and QoL among the BC survivors. However, some of the included studies exhibited methodological concerns (e.g., inadequate blinding and allocation concealment). The intervention protocols in only two studies were developed following a solid evidence-based approach. Adverse events related to the targeted interventions were reported in six included studies, with none performing a causality analysis. Conclusions: The nonpharmacological interventions could be promising strategies for alleviating symptom clusters in BC survivors. Future studies should adopt rigorously designed, randomized controlled trials to generate robust evidence. Systematic review registration: INPLASY202380028.
RESUMO
(1) Background: Inflammatory responses are implicated in embryo implantation, decidualization, pregnancy maintenance and labor. Both embryo implantation and decidualization are essential to successful pregnancy in rodents and primates. S100A6 is involved in inflammation, tumor development, apoptosis and calcium homeostasis. S100A6 is strongly expressed in mouse decidua, but the underlying mechanisms of how S100A6 regulates implantation and decidualization are poorly defined. (2) Methods: Mouse endometrial stromal and epithelial cells are isolated from day 4 pseudopregnant mouse uteri. Both immunofluorescence and Western blotting are used to analyze the expression and localization of proteins. The molecular mechanism is verified in vitro by Western blotting and the quantitative polymerase chain reaction. (3) Results: From days 4 to 8 of pregnancy, S100A6 is specifically expressed in mouse subluminal stromal cells. Blastocyst-derived lactic acid induces AA secretion by activating the luminal epithelial p-cPLA2. The epithelial AA induces stromal S100A6 expression through the COX2/PGI2/PPAR δ pathway. Progesterone regulates S100A6 expression through the progesterone receptor (PR). S100A6/RAGE signaling can regulate decidualization via EGFR/ERK1/2 in vitro. (4) Conclusions: S100A6, as an inflammatory mediator, is important for mouse implantation and decidualization.