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Type 2 diabetes mellitus (T2DM) is a risk factor for patients with impaired renal function. The onset of T2DM-induced diabetic kidney disease (DKD) is frequently sub-clinical, potentially culminating in end-stage renal disease. In the current study the factors influencing DKD in elderly patients diagnosed with T2DM were determined. A retrospective cohort study was conducted involving patients ≥60 years of age with T2DM from June 2019 to December 2022. The Cockcroft-Gault formula was used to estimate the glomerular filtration rate. The clinical information and biochemical indicators of patients with an estimated glomerular filtration rate (eGFR)â <â 90 mL/min/1.73m2 were collected. Patients were grouped based on a 3-year eGFR declineâ <â 15% andâ ≥â 15%. The differences between the two groups were compared and the factors influencing the 3-year eGFR declineâ ≥â 15% were analyzed. A total of 242 patients were included, including 154 in the group with a 3-year eGFR declineâ <â 15% and 88 in the group with a three-year eGFR declineâ ≥â 15%. Univariate logistic regression analysis showed that smoking cigarettes, and triglycerides (TG) and high-density lipoprotein levels were related to a 3-year eGFR declineâ ≥â 15% (Pâ =â .039, Pâ <â .001, and Pâ =â .011, respectively). Multivariate logistic regression analysis showed that the TG level was independently related to a 3-year eGFR declineâ ≥â 15% (Pâ =â .004; ORâ =â 2.316). There was a significant linear relationship between the eGFR decline and TG level (Pâ =â .002). Patients with a TG concentrationâ >â 1.7 mmol/L had a more apparent decrease in the eGFR (Pâ <â .05). For elderly patients with T2DM and an eGFRâ <â 90 mL/min/1.73m2, the TG level may be an important risk factor for deteriorating renal function that warrants actively intervention.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Taxa de Filtração Glomerular , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Pessoa de Meia-Idade , Fatores de Risco , Seguimentos , Idoso de 80 Anos ou maisRESUMO
Background: In China, Shen'ge formula (SGF), a Traditional Chinese Medicine blend crafted from ginseng and gecko, holds a revered place in the treatment of cardiovascular diseases. However, despite its prevalent use, the precise cardioprotective mechanisms of SGF remain largely uncharted. This study aims to fill this gap by delving deeper into SGF's therapeutic potential and underlying action mechanism, thus giving its traditional use a solid scientific grounding. Methods: In this study, rats were subjected to abdominal aortic constriction (AAC) to generate pressure overload. Following AAC, we administered SGF and bisoprolol intragastrically at specified doses for two distinct durations: 8 and 24 weeks. The cardiac function post-treatment was thoroughly analyzed using echocardiography and histological examinations, offering insights into SGF's influence on vital cardiovascular metrics, and signaling pathways central to cardiac health. Results: SGF exhibited promising results, significantly enhanced cardiac functions over both 8 and 24-week periods, evidenced by improved ejection fraction and fractional shortening while moderating left ventricular parameters. Noteworthy was SGF's role in the significant mitigation of myocardial hypertrophy and in fostering the expression of vital proteins essential for heart health by the 24-week mark. This intervention markedly altered the dynamics of the Akt/HIF-1α/p53 pathway, inhibiting detrimental processes while promoting protective mechanisms. Conclusion: Our research casts SGF in a promising light as a cardioprotective agent in heart failure conditions induced by pressure overload in rats. Central to this protective shield is the modulation of the Akt/HIF-1α/p53 pathway, pointing to a therapeutic trajectory that leverages HIF-1α promotion and p53 nuclear transport inhibition.
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Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Ratos Sprague-Dawley , Animais , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Masculino , Cardiotônicos/farmacologia , Cardiotônicos/administração & dosagem , Combinação de Medicamentos , Modelos Animais de Doenças , Medicina Tradicional ChinesaRESUMO
BACKGROUND: The rising number of women giving birth at advanced maternal age has posed significant challenges in obstetric care in recent years, resulting in increased incidence of neonatal transfer to the Neonatal Intensive Care Unit (NICU). Therefore, identifying fetuses requiring NICU transfer before delivery is essential for guiding targeted preventive measures. OBJECTIVE: This study aims to construct and validate a nomogram for predicting the prenatal risk of NICU admission in neonates born to mothers over 35 years of age. STUDY DESIGN: Clinical data of 4218 mothers aged ≥ 35 years who gave birth at the Department of Obstetrics of the Second Hospital of Shandong University between January 1, 2017 and December 31, 2021 were reviewed. Independent predictors were identified by multivariable logistic regression, and a predictive nomogram was subsequently constructed for the risk of neonatal NICU admission. RESULTS: Multivariate logistic regression demonstrated that the method of prenatal screening, number of implanted embryos, preterm premature rupture of the membranes, preeclampsia, HELLP syndrome, fetal distress, premature birth, and cause of preterm birth are independent predictors of neonatal NICU admission. Analysis of the nomogram decision curve based on these 8 independent predictors showed that the prediction model has good net benefit and clinical utility. CONCLUSION: The nomogram demonstrates favorable performance in predicting the risk of neonatal NICU transfer after delivery by mothers older than 35 years. The model serves as an accurate and effective tool for clinicians to predict NICU admission in a timely manner.
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Unidades de Terapia Intensiva Neonatal , Idade Materna , Nomogramas , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , China/epidemiologia , População do Leste Asiático , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Modelos Logísticos , Admissão do Paciente/estatística & dados numéricos , Nascimento Prematuro/epidemiologia , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de RiscoRESUMO
Acute myeloid leukemia (AML) is a hematologic malignancy with a high recurrence rate and poor long-term prognosis. DNA excision repair systems, such as base excision repair (BER) and nucleotide excision repair (NER), play a major role in maintaining genomic stability and integrity. Further intensive investigations are necessary to uncover additional AML prognosis loci. In this study, we analyzed 16 candidate SNPs within NER and BER pathways in AML patients. Our results showed the GT/GG genotype of the XPC rs2228001 polymorphism was significantly associated with WBC count in dominant models (OR = 0.41, 95 % CI = 0.18-0.96, p = 0.039). Additionally, the rs25487 and rs3213245 SNPs in the XRCC1 gene, in both co-dominant and dominant models, were significantly associated with PLT count in AML (p < 0.05). The GG genotype of rs1130409 in APEX1 was more prone to adverse cytogenetics in both the codominant and recessive models (p < 0.05). Furthermore, the GA genotypes of ERCC8 rs158572 in codominant model was significantly correlated with refractory group (p < 0.05). ERCC8 rs158572 and XRCC1 rs3213245 in both codominant and dominant models were significantly correlated with the MRD positivity (p < 0.05). Kaplan-Meier analysis revealed an link between overall survival (OS) and the co-dominant, dominant, and recessive models of rs2228001 in XPC. Additionally, patients with the GG and GT/GG genotype in the co-dominant, dominant model and recessive model in XPC rs2228001 exhibited significantly longer survival (p < 0.05). Multivariate Cox analyses indicated that rs2228001 in both co-dominant and dominant models were independent favorable factors impacting patient OS (OR < 1). Our findings suggest that genetic polymorphisms in DNA excision repair pathway genetic polymorphisms contribute to the chemosensitivity and prognosis of acute myeloid leukemia.
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Reparo por Excisão , Leucemia Mieloide Aguda , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , PrognósticoRESUMO
BACKGROUND: As the burden of mental disorders among patients with atrial fibrillation (AF) increases, researchers are beginning to pay close attention to the risk and prevalence of these comorbidities. Although studies have independently analyzed the risk of comorbidity with depression and anxiety in patients with AF, no study has systematically focused on the global epidemiology of these two mental disorders. AIM: To explore the prevalence of depression and anxiety in patients with AF. METHODS: Five databases were searched from their date of establishment until January 2023. Observational studies reporting the comorbidity of AF with depression and anxiety, were included in this study. Basic information, such as the first author/ publication year, study year, study type, and prevalence of depression and anxiety, were extracted. STATA SE 15.1 was used to analyze the data. Subgroup, meta-regression, and sensitivity analyses were performed to estimate study heterogeneity. RESULTS: After a thorough search, 26 studies were identified and included in this meta-analysis. The prevalence rates of depression and anxiety in adults with AF were 24.3% and 14.5%, respectively. Among adult males with AF, the prevalence was 11.7% and 8.7%, respectively, whereas in females it was 19.8% and 10.1%, respectively. In older adults with AF, the prevalence rates of depression and anxiety were 40.3% and 33.6%, respectively. The highest regional prevalence of depression and anxiety was observed in European (30.2%) and North American (19.8%) patients with AF. CONCLUSION: In this study, we found that the prevalence of depression and anxiety among patients with AF varies with sex, region, and evaluation scales, suggesting the need for psychological interventions for patients with AF in clinical practice.
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Most forms of chemotherapy for acute myeloid leukemia (AML) are often ineffective in eliminating leukemic stem cells (LSCs), as their underlying mechanisms remain unclear. Here, we have identified circFAM193B, which regulates the redox biology of LSCs and is associated with unfavorable outcomes in AML patients. In vitro and in vivo assays suggested that circFAM193B significantly inhibits LSCs chemotherapy resistance and AML progression. Knockdown circFAM193B enhances mitochondrial OXPHOS function and inhibits the accumulation of reactive oxygen species and lipid peroxidation mediated by chemotherapy, which protects AML cells from oxidative stress-induced cell death. Mechanistically, circFAM193B physically interacts with arginine methyltransferase PRMT6 catalytic domain and enhances the transcription efficiency of key lipid peroxidation factor ALOX15 by decreasing H3R2me2a modification. In summary, we have identified circFAM193B was downregulated in LSCs to promote the survival of LSC by modulating energy metabolism and the redox balance in the postchemotherapy persistence of LSC. Our studies provide a conceptual advance and biological insights regarding the drug resistance of LSCs via circRNA mediated PRMT6-deposited methylarginine signaling.
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Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda , Peroxidação de Lipídeos , Células-Tronco Neoplásicas , Proteínas Nucleares , Proteína-Arginina N-Metiltransferases , Humanos , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Camundongos , Animais , Estresse Oxidativo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismoRESUMO
Gene mutations are a pivotal component of the pathogenesis of MDS, and they hold profound prognostic significance for predicting treatment responses and survival outcomes. However, reports about mutation patterns in Chinese MDS patients are limited. In this study, we analyzed the genetic mutation of 23 genes in 231 patients with MDS using next-generation sequencing (NGS) technology, and explored the characteristics of gene mutations in MDS patients and their associations with clinical outcomes, survival, and transformation outcomes. Our results showed that 68.83% patients had at least one gene mutation, and the most common mutations were ASXL1 (21.65%), SF3B1 (17.32%), U2AF1 (16.02%), TET2 (14.72%) and TP53 (8.66%). We also showed that the genetic mutations of TP53, U2AF1 and DNMT3A are independent risk factors for death in patients with MDS, and the ETV6 gene mutation was an independent risk factor for the transformation of MDS patients to AML through the univariate and multivariate Cox regression analysis model. Additionally, the study developed a risk score based on gene mutation data that demonstrated robust predictive capability and stability for the overall survival of MDS patients. Our research provided a strong theoretical basis for the establishment of personalized treatment and prognostic risk assessment models for Chinese MDS patients.
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Síndromes Mielodisplásicas , Humanos , Fator de Processamento U2AF/genética , Mutação , Prognóstico , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Fatores de Transcrição/genéticaRESUMO
Short-chain fatty acids (SCFAs), particularly propionate and butyrate, have been reported in many cancers. However, the relationship between propionate and acute myeloid leukemia (AML) remains unclear. Additionally, Acyl-CoA synthetase long chain family member 4 (ACSL4) has been reported to regulate immunity in solid tumors, but there are still many gaps to be filled in AML. Here, we discovered the underlying mechanism of propionate and ACSL4-mediated ferroptosis for immunotherapy. Our results showed that the level of propionate in the AML patients' feces was decreased, which was correlated to gut microbiota dysbiosis. Moreover, we demonstrated that propionate suppressed AML progression both in vivo and in vitro. In mechanism, propionate induced AML cells apoptosis and ferroptosis. The imbalance of reactive oxygen species (ROS) and redox homeostasis induced by propionate caused mitochondrial fission and mitophagy, which enhanced ferroptosis and apoptosis. Furthermore, ACSL4-mediated ferroptosis caused by propionate increased the immunogenicity of AML cells, induced the release of damage-associated molecular patterns (DAMPs), and promoted the maturation of dendritic cells (DCs). The increased level of immunogenicity due to ferroptosis enable propionate-based whole-cell vaccines to activate immunity, thus further facilitating effective killing of AML cells. Collectively, our study uncovers a crucial role for propionate suppresses AML progression by inducing ferroptosis and the potential mechanisms of ACSL4-mediated ferroptosis in the regulation of AML immunity.
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Ferroptose , Leucemia Mieloide Aguda , Humanos , Propionatos/farmacologia , Mitofagia , Apoptose , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologiaRESUMO
Mitochondria are energy-generated organelles and take an important part in biological metabolism. Mitochondria could be transferred between cells, which serves as a new intercellular communication. Mitochondrial transfer improves mitochondrial defects, restores the biological functions of recipient cells, and maintains the high metabolic requirements of tumor cells as well as drug resistance. In recent years, it has been reported mitochondrial transfer between cells of bone marrow microenvironment and hematological malignant cells play a critical role in the disease progression and resistance during chemotherapy. In this review, we discuss the patterns and mechanisms on mitochondrial transfer and their engagement in different pathophysiological contexts and outline the latest knowledge on intercellular transport of mitochondria in hematological malignancies. Besides, we briefly outline the drug resistance mechanisms caused by mitochondrial transfer in cells during chemotherapy. Our review demonstrates a theoretical basis for mitochondrial transfer as a prospective therapeutic target to increase the treatment efficiency in hematological malignancies and improve the prognosis of patients.
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PURPOSE: Stem cells are known to play an important role in tumor treatment and many of them have shown tumor-suppressing ability in different cancers; however, whether hematopoietic stem cells (HSCs) have growth-inhibiting effects on leukemia cells has not been fully evaluated. Herein, we aimed to demonstrate the growth-restraining function of HSCs in acute leukemia treatment. METHODS: Cell fusion experiment was conducted by PEG-1500. The viability, proliferation, apoptosis and differentiation of leukemia cells were evaluated by cell counting, CCK-8 and flow cytometry analysis. The morphological changes were imaged using a fluorescence microscope. The expression of genes was detected by quantitative reverse transcription PCR (qRT-PCR). RESULTS: We observed that HSCs and their lytic extracts had the capability to suppress leukemia cells proliferation, promote apoptosis and especially induce acute myelogenous leukemia (AML) cells differentiation, which might have an effect on differentiation therapy to leukemia especially AML treatment. The expression levels of Bcl-2, Survivin decreased and Bax increased following HSCs extracts treatment. Furthermore, the expression of inflammatory cytokines also changed in AML cells which might have to do with the mechanism of HSCs/extracts suppressing effect. CONCLUSION: HSCs and their extracts can suppress the proliferation of leukemia cells and enhance the differentiation of AML cells and using the extracts of HSCs might be a probable therapeutic option for acute leukemia.
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Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/patologia , Diferenciação Celular , Proliferação de Células , Apoptose/genéticaRESUMO
BACKGROUND: Though immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear. METHODS: We investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune-related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA. RESULTS: By comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK-STAT, NF-κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter-OS genotypes. CONCLUSIONS: We used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune-related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.
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Linfoma , Humanos , Genótipo , Linfoma/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Modelos de Riscos Proporcionais , Predisposição Genética para Doença , Estudos de Casos e ControlesRESUMO
Aberrant expression of circRNAs has been proven to play a crucial role in the progression of acute myeloid leukemia (AML); however, its regulatory mechanism remains unclear. Herein, we identified a novel circRNA, Circ_0001187, which is downregulated in AML patients, and its low level contributes to a poor prognosis. We further validated their expression in large-scale samples and found that only the expression of Circ_0001187 was significantly decreased in newly diagnosed (ND) AML patients and increased in patients with hematological complete remission (HCR) compared with controls. Knockdown of Circ_0001187 significantly promoted proliferation and inhibited apoptosis of AML cells in vitro and in vivo, whereas overexpression of Circ _0001187 exerted the opposite effects. Interestingly, we found that Circ_0001187 decreases mRNA m6A modification in AML cells by enhancing METTL3 protein degradation. Mechanistically, Circ_0001187 sponges miR-499a-5p to enhance the expression of E3 ubiquitin ligase RNF113A, which mediates METTL3 ubiquitin/proteasome-dependent degradation via K48-linked polyubiquitin chains. Moreover, we found that the low expression of Circ _0001187 is regulated by promoter DNA methylation and histone acetylation. Collectively, our findings highlight the potential clinical implications of Circ _0001187 as a key tumor suppressor in AML via the miR-499a-5p/RNF113A/METTL3 pathway.
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BACKGROUND: Mutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but their clinical and prognostic relevance in acute myeloid leukemia (AML) have rarely been reported. METHODS: A total of 368 newly diagnosed non-M3 AML patients were included in this study. Next generation sequencing including four SF genes was performed on the genomicDNA. The clinical features and survival were analyzed using statistical analysis. RESULTS: We found that 64 of 368 patients harbored SF mutations. The SF mutations were much more frequently found in older or male patients. SRSF2 mutations were shown obviously co-existed with IDH2 mutation. The level of measurable residual disease after first chemotherapy was higher in SF-mutated patients compared to that in SF-wild patients, while the complete remission rate was significantly decreased. And the overall survival of SF-mutated patients was shorter than that of SF-wild patients. Moreover, our multivariable analysis suggests that the index of male, Kit mutation or ZRSR2 mutation was the independent risk factor for overall survival. SRSF2mut was associated with older age, higher proportion of peripheral blasts or abnormal cell proportion by flow cytometry. CONCLUSION: SF mutation is a distinct subgroup of AML frequently associated with clinic-biological features and poor outcome. SRSF2mut could be potential targets for novel treatment in AML.
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Leucemia Mieloide Aguda , Spliceossomos , Humanos , Masculino , Idoso , Spliceossomos/genética , Prognóstico , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de RNA/genética , Leucemia Mieloide Aguda/genética , Mutação/genéticaRESUMO
Background: HF and osteoporosis shared many common etiological risk factors. However, studies exploring whether patients with HF were associated with a higher risk of osteoporotic fracture resulted in inconsistent findings. This meta-analysis aimed to summarize the association between HF and the risk of incident fracture. Methods: Following the Meta-analysis of Observational Studies in Epidemiology group recommendations, we searched multiple electronic databases (PubMed, Cochran Library, and EMBASE) for related studies from inception to April 30, 2021. Studies evaluating the risk of incident fracture in patients with HF compared with those without HF were included for analysis. The random-effects models were used to combine the estimated hazard ratios (HRs) of incident fracture associated with HF. Results: We included 8 observational studies for meta-analysis. The sample size ranged from 5,613 to 87,748 participants, with a total of 260,410 participants included. The median follow-up duration was 5.0 years. Random-effects model analyses showed that compared with control groups, patients with HF were associated with a higher risk of all incident fractures (HR = 1.67, 95% CI = 1.30-2.16, P < 0.001) and hip fracture (HR = 2.20, 95% CI = 1.28-3.77, P < 0.001). The risk of all incident fractures was increased in all subgroup analyses according to age, sample size, sex, and follow-up duration. Conclusions: Patients with HF were associated with a higher risk of incident fracture, as well as hip fracture.
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PURPOSE: Bile acids are steroid synthesized in liver, which are essential for fat emulsification, cholesterol excretion and gut microbial homeostasis. However, the role of bile acids in leukemia progression remains unclear. We aim at exploring the effects and mechanisms of chenodeoxycholic acid (CDCA), a type of bile acids, on acute myeloid leukemia (AML) progression. RESULTS: Here, we found that CDCA was decreased in feces and plasma of AML patients, positively correlated with the diversity of gut microbiota, and negatively associated with AML prognosis. We further demonstrated that CDCA suppressed AML progression both in vivo and in vitro. Mechanistically, CDCA bound to mitochondria to cause mitochondrial morphology damage containing swelling and reduction of cristae, decreased mitochondrial membrane potential and elevated mitochondrial calcium level, which resulted in the production of excessive reactive oxygen species (ROS). Elevated ROS further activated p38 MAPK signaling pathway, which collaboratively promoted the accumulation of lipid droplets (LDs) through upregulating the expression of the diacylglycerol O-acyltransferase 1 (DGAT1). As the consequence of the abundance of ROS and LDs, lipid peroxidation was enhanced in AML cells. Moreover, we uncovered that CDCA inhibited M2 macrophage polarization and suppressed the proliferation-promoting effects of M2 macrophages on AML cells in co-cultured experiments. CONCLUSION: Our findings demonstrate that CDCA suppresses AML progression through synergistically promoting LDs accumulation and lipid peroxidation via ROS/p38 MAPK/DGAT1 pathway caused by mitochondrial dysfunction in leukemia cells and inhibiting M2 macrophage polarization.
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Leucemia Mieloide Aguda , Proteínas Quinases p38 Ativadas por Mitógeno , Ácidos e Sais Biliares/metabolismo , Cálcio/metabolismo , Ácido Quenodesoxicólico/metabolismo , Ácido Quenodesoxicólico/farmacologia , Colesterol/metabolismo , Diacilglicerol O-Aciltransferase/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Peroxidação de Lipídeos , Macrófagos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and can lead to heart failure (HF), stroke, pulmonary embolism (PE), and other complications, seriously affecting people's quality of life and health. Western medicine is limited in the treatment of AF, while Traditional Chinese Medicine (TCM) has unique advantages, such as less side effects, low toxicity, long effect duration, and high compliance. The prescription of HTDJ is a common prescription for the treatment of atrial fibrillation in Longhua Hospital, Shanghai University of Traditional Chinese Medicine. It has been used for many years and has a large number of clinically effective cases. It has a good clinical application prospect, but there is a lack of effective evaluation of its clinical efficacy. METHOD: This study adopts a randomized double-blind, single-simulated, placebo-controlled research method. Participants were randomly assigned in a 1:1 ratio through a centrally controlled, computer-generated, simple randomization schedule. Participants would take the medicine for 1 month, and the curative effect would be evaluated. Subsequently, the participants would not take TCM and only receive western medicine treatment. They would be followed up for another 8 weeks, and a clinical evaluation would be conducted. The secondary outcomes include echocardiography, Hamilton Anxiety Scale, Hamilton Depression Scale, rate of increase and decrease of anti-arrhythmia western medicine, the MOS 36-item short-form health survey, N-terminal-pro hormone B-type natriuretic peptide level, and integral TCM syndrome score. Adverse events will be monitored throughout the trial. Cases are from outpatient and inpatient with atrial fibrillation in the Cardiology Department of Longhua Hospital. Evaluations will be conducted at baseline and at weeks 4 and 12 after randomization. DISCUSSION: In this study, the efficacy and safety of HTDJ plus western medicine in the treatment of atrial fibrillation (qi deficiency and phlegm opacities) will be evaluated, so as to provide medical evidence of short-term and medium-term clinical efficacy for the treatment of atrial fibrillation with integrated traditional and western medicine and lay a foundation for further clinical development and application. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000030517 . Registered on March 5, 2020, with the Chinese Clinical Trial Registry.
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Fibrilação Atrial , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , China , Método Duplo-Cego , Humanos , Medicina Tradicional Chinesa , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Diastolic heart failure (DHF) is an important pathological type of heart failure, that involves multiple organ dysfunction and multiple complications. The prevalence of DHF is high, and effective treatments are lacking. Chinese herbs are an alternative therapy for DHF. Shen'ge formula (SGF) is a classical formula from which patients can benefit, but convincing evidence of its efficacy is lacking. Therefore, we designed this randomized controlled trial protocol. METHODS/DESIGN: This randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of SGF in the treatment of DHF. A total of 130 patients with DHF will be enrolled in the trial and treated with SGF granules or placebo for 12âweeks and followed up for 12âweeks. The primary outcome measurement will be to changes in plasma N-terminal brain natriuretic peptide precursor before versus after treatment, while the second primary outcome measurement will be changes in heart function before versus after treatment and the 12-week follow-up period. It will also include echocardiography, a cardiopulmonary exercise test, cardiac function grading, traditional Chinese medicine syndrome score, and the Minnesota Heart Failure Quality of Life Scale. Adverse events will be evaluated throughout the trial. DISCUSSION: The results of this trial will demonstrate whether SGF could alleviate symptoms, improve cardiac function, reduce readmission rates, and improve quality of life of patients with DHF. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000036533, registered on August 24, 2020.