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1.
World J Gastroenterol ; 30(11): 1497-1523, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38617454

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.


Assuntos
Carcinoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Humanos , MicroRNAs/genética , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/genética , Epigenômica
2.
Eur Spine J ; 33(2): 444-452, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38236278

RESUMO

PURPOSE: This study aimed to investigate the relationship between spinal-pelvic parameters and recurrence of lumbar disc herniation (rLDH) after percutaneous endoscopic lumbar discectomy (PELD) through a retrospective case-control study. METHODS: Patients who underwent PELD for single-segment LDH at our hospital were included in this study. The relationship between sagittal balance parameters of the spine and recurrence was analysed through correlation analysis, and ROC curves were plotted. The baseline characteristics, sagittal balance parameters of the spine and radiological parameters of the case and control groups were compared, and the relationship between sagittal balance parameters of the spine and recurrence of rLDH after PELD was determined through univariate and multivariate logistic regression analysis. RESULTS: Correlation analysis showed that PI and ∆PI-LL were negatively correlated with grouping (r = -0.090 and -0.120, respectively, P = 0.001 and 0.038). ROC curve analysis showed that the area under the curve (ROC-AUC) for predicting rLDH based on PI was 0.65 (CI95% = 0.598, 0.720), with a cut-off of 50.26°. The ROC-AUC for predicting rLDH based on ∆PI-LL was 0.56 (CI95% = 0.503, 0.634), with a cut-off of 28.21°. Multivariate logistic regression analysis showed that smoking status (OR = 2.667, P = 0.008), PI ≤ 50.26 (OR = 2.161, P = 0.009), ∆PI-LL ≤ 28.21 (OR = 3.185, P = 0.001) and presence of Modic changes (OR = 4.218, P = 0.001) were independent risk factors, while high DH (OR = 0.788, P = 0.001) was a protective factor. CONCLUSION: PI < 50.26 and ∆PI-LL < 28.21 were risk factors for recurrence of lumbar disc herniation after spinal endoscopic surgery and had some predictive value for post-operative recurrence.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Humanos , Estudos de Casos e Controles , Estudos Retrospectivos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia
3.
J Orthop Surg Res ; 18(1): 922, 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38042770

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA. MATERIALS AND METHODS: In the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial. CONCLUSION: The results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future. TRIAL REGISTRATION: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.


Assuntos
Moxibustão , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/complicações , Moxibustão/efeitos adversos , Moxibustão/métodos , Articulação do Joelho , Dor , Lasers , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Biosensors (Basel) ; 13(7)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37504145

RESUMO

MicroRNAs (miRNAs) are a class of small noncoding RNAs that are approximately 22 nt in length and regulate gene expression post-transcriptionally. miRNAs play a vital role in both physiological and pathological processes and are regarded as promising biomarkers for cancer, cardiovascular diseases, neurodegenerative diseases, and so on. Accurate detection of miRNA expression level in clinical samples is important for miRNA-guided diagnostics. However, the common miRNA detection approaches like RNA sequencing, qRT-PCR, and miRNA microarray are performed in a professional laboratory with complex intermediate steps and are time-consuming and costly, challenging the miRNA-guided diagnostics. Hence, sensitive, highly specific, rapid, and easy-to-use detection of miRNAs is crucial for clinical diagnosis based on miRNAs. With the advantages of being specific, sensitive, efficient, cost-saving, and easy to operate, point-of-care testing (POCT) has been widely used in the detection of miRNAs. For the first time, we mainly focus on summarizing the research progress in POCT of miRNAs based on portable instruments and visual readout methods. As widely available pocket-size portable instruments and visual detection play important roles in POCT, we provide an all-sided discussion of the principles of these methods and their main limitations and challenges, in order to provide a guide for the development of more accurate, specific, and sensitive POCT methods for miRNA detection.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/análise , Testes Imediatos , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase
5.
Am J Transl Res ; 15(5): 3172-3187, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37303621

RESUMO

OBJECTIVE: To observe the anti-aging effects of moxibustion on age-related alterations in middle-aged mice. METHODS: Thirty, 9-month-old, male ICR mice were randomly divided into the moxibustion and control groups (N = 15). Mice in the moxibustion group were given mild moxibustion at the Guanyuan acupoint for 20 minutes every other day. After 30 treatments, neurobehavior tests, lifespan, gut microbiota composition and splenic gene expression were observed in the mice. RESULTS: Moxibustion improved the locomotor activity as well as motor function, activated the SIRT1-PPARα signaling pathway, ameliorated age-related alterations in gut microbiota, and affected the expression of genes related to energy metabolism in spleen. CONCLUSION: Moxibustion ameliorated age-related alterations in neurobehavior and gut microbiota in middle-aged mice.

6.
Front Mol Neurosci ; 15: 1004221, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438184

RESUMO

Central nervous system (CNS) disease is a general term for a series of complex and diverse diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), CNS tumors, stroke, epilepsy, and amyotrophic lateral sclerosis (ALS). Interneuron and neuron-glia cells communicate with each other through their homeostatic microenvironment. Exosomes in the microenvironment have crucial impacts on interneuron and neuron-glia cells by transferring their contents, such as proteins, lipids, and ncRNAs, constituting a novel form of cell-to-cell interaction and communication. Exosomal noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs), regulate physiological functions and maintain CNS homeostasis. Exosomes are regarded as extracellular messengers that transfer ncRNAs between neurons and body fluids due to their ability to cross the blood-brain barrier. This review aims to summarize the current understanding of exosomal ncRNAs in CNS diseases, including prospective diagnostic biomarkers, pathological regulators, therapeutic strategies and clinical applications. We also provide an all-sided discussion of the comparison with some similar CNS diseases and the main limitations and challenges for exosomal ncRNAs in clinical applications.

7.
Expert Rev Med Devices ; 19(8): 649-656, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36200143

RESUMO

BACKGROUND: This multicenter prospective, randomized controlled clinical trial compared the clinical performance of supraglottic airway device (SAD) BlockBusterTM and laryngeal mask airway (LMA) Supreme for airway maintenance in anesthetized, paralyzed adult patients. METHODS: A total of 651 adult patients scheduled for elective surgery in 13 hospitals were randomly allocated into BlockBuster group (n = 351) or Supreme group (n = 300). The primary outcome was oropharyngeal leak pressure (OLP). Duration and ease of insertion, fiberscopic view of positioning, airway manipulations, and complications were also assessed. RESULTS: The OLP was significantly higher in BlockBuster group compared with Supreme group (29.9 ± 4.2 cmH2O vs 27.4 ± 4.3 cmH2O, p < 0.001). Success rate of insertion at the first attempt (90.2% vs 85.1%, p = 0.027), rate of optimal fiberscopic view (p = 0.002) and satisfactory positioning of SAD (p < 0.001) were significantly increased in BlockBuster group. CONCLUSIONS: Both SAD BlockBusterTM and LMA Supreme are safe, effective, and easy-to-use devices for airway maintenance in anesthetized, paralyzed adult patients, but the SAD BlockBusterTM is superior to LMA Supreme in terms of OLP, success rate at the first attempt, and fiber-optic view of positioning. TRIAL REGISTRATION: The trial is registered at www.chictr.org.cn (ChiCTR-ONC-16009105).


Assuntos
Máscaras Laríngeas , Adulto , Humanos , Estudos Prospectivos , Tecnologia de Fibra Óptica , Orofaringe
8.
J Clin Med ; 11(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36143035

RESUMO

INTRODUCTION: Predicting survival time for patients with spinal metastases is important in treatment choice. Generally speaking, six months is a landmark cutoff point. Revised Tokuhashi score (RTS), the most widely used scoring system, lost its accuracy in predicting 6-month survival, gradually. Therefore, a more precise scoring system is urgently needed. OBJECTIVE: The aim of this study is to create a new scoring system with a higher accuracy in predicting 6-month survival based on the previously used RTS. METHODS: Data of 171 patients were examined to determine factors that affect prognosis (reference group), and the remaining (validation group) were examined to validate the reliability of a new score, adjusted Tokuhashi score (ATS). We compared their discriminatory abilities of the prediction models using area under receiver operating characteristic curve (AUC). RESULTS: Target therapy and the Z score of BMI (Z-BMI), which adjusted to the patients' sex and age, were additional independent prognostic factors. Patients with target therapy use are awarded 4 points. The Z score of BMI could be added directly to yield ATS. The AUCs were 0.760 for ATS and 0.636 for RTS in the validation group. CONCLUSION: Appropriate target therapy use can prolong patients' survival. Z-BMI which might reflect nutritional status is another important influencing factor. With the optimization, surgeons could choose a more individualized treatment for patients.

9.
Sci Total Environ ; 847: 157443, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35868369

RESUMO

Currently, cardiovascular disease (CVD) is a health hazard that is associated with progressive deterioration upon exposure to environmental pollutants. Di(2-ethylhexyl) phthalate (DEHP) has been one of the focuses of emerging concern due to its ubiquitous nature and its toxicity to the cardiovascular (CV) system. DEHP has been noted as a causative risk factor or a risk indicator for the initiation and augment of CVDs. DEHP represents a precursor that contributes to the pathogenesis of CVDs through its active metabolites, which mainly include mono (2-ethylhexyl) phthalate (MEHP). Herein, we systematically presented the association between DEHP and its metabolites and adverse CV outcomes and discussed the corresponding effects, underlying mechanisms and possibly interventions. Epidemiological and experimental evidence has suggested that DEHP and its metabolites have significant impacts on processes and factors involved in CVD, such as cardiac developmental toxicity, cardiac injury and apoptosis, cardiac arrhythmogenesis, cardiac metabolic disorders, vascular structural damage, atherogenesis, coronary heart disease and hypertension. DNA methylation, PPAR-related pathways, oxidative stress and inflammation, Ca2+ homeostasis disturbance may pinpoint the relevant mechanisms. The preventive and therapeutic measures are potentially related with P-glycoprotein, heat-shock proteins, some antioxidants, curcumin, apigenin, ß-thujaplicin, glucagon-like peptide-1 receptor agonists and Ang-converting enzyme inhibitors and so on. Promisingly, future investigations should aid in thoroughly assessing the causal relationship and molecular interactions between CVD and DEHP and its metabolites and explore feasible prevention and treatment measures accordingly.


Assuntos
Doenças Cardiovasculares , Curcumina , Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Subfamília B de Transportador de Cassetes de Ligação de ATP , Apigenina , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Dietilexilftalato/análogos & derivados , Dietilexilftalato/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Ácidos Ftálicos/metabolismo
10.
Front Cell Neurosci ; 16: 884296, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35634463

RESUMO

N6-methyladenosine (m6A) is the most abundant methylation modification on mRNA in mammals. Fat mass and obesity-related protein (FTO) is the main RNA m6A demethylase. FTO is involved in the occurrence and maintenance of neuropathic pain (NP). NP often induces mental disorders. We found that NP downregulated the expression of FTO in the anterior cingulate cortex (ACC), inhibited the expression of matrix metalloproteinase-9 (MMP-9) in the ACC, maladjusted the brain-derived neurotrophic factor precursor (proBDNF) and mature brain-derived neurotrophic factor (mBDNF) levels in the ACC, and induced anxiety- and depression-like behaviors in mice. Blocking the downregulation of FTO in the ACC induced by peripheral nerve injury could reverse the anxiety- and depression-like behaviors of mice. Contrarily, downregulation of simulated FTO induced anxiety- and depression-like behaviors in mice. After peripheral nerve injury, the binding of FTO to MMP-9 mRNA decreased and the enrichment of m6A on MMP-9 mRNA increased. In conclusion, downregulation of FTO in ACC by regulating MMP-9 mRNA methylation level contributes to the occurrence of anxiety- and depression-like behaviors in NP mice.

11.
Rare Metals ; 41(7): 2129-2152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35291268

RESUMO

CO2-assisted oxidative dehydrogenation of propane (CO2-ODHP) is an attractive strategy to offset the demand gap of propylene due to its potentiality of reducing CO2 emissions, especially under the demands of peaking CO2 emissions and carbon neutrality. The introduction of CO2 as a soft oxidant into the reaction not only averts the over-oxidation of products, but also maintains the high oxidation state of the redox-active sites. Furthermore, the presence of CO2 increases the conversion of propane by coupling the dehydrogenation of propane (DHP) with the reverse water gas reaction (RWGS) and inhibits the coking formation to prolong the lifetime of catalysts via the reverse Boudouard reaction. An effective catalyst should selectively activate the C-H bond but suppress the C-C cleavage. However, to prepare such a catalyst remains challenging. Chromium-based catalysts are always applied in industrial application of DHP; however, their toxic properties are harmful to the environment. In this aspect, exploring environment-friendly and sustainable catalytic systems with Cr-free is an important issue. In this review, we outline the development of the CO2-ODHP especially in the last ten years, including the structural information, catalytic performances, and mechanisms of chromium-free metal-based catalyst systems, and the role of CO2 in the reaction. We also present perspectives for future progress in the CO2-ODHP.

12.
Acta Haematol ; 145(4): 419-429, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35231903

RESUMO

INTRODUCTION: The overall outcome of patients with refractory AML (rAML) remains poor. Though allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as the only curative therapy, it is routinely recommended only for patients after remission with salvage chemotherapy. OBJECTIVE: In this study, we evaluated the impact of salvage chemotherapy or allo-HSCT on the overall outcome in rAML. METHODS: We collected the clinical data of 220 patients from 4 medical centers and performed retrospective analysis of prognosis factors, including salvage chemotherapy, intensity of chemotherapy, and allo-HSCT. RESULTS: A total of 29 patients received allo-HSCT directly without salvage chemotherapy, 26 patients achieved complete remission (CR) or complete remission with incomplete hematological recovery (CRi) after transplantation and 4-year leukemia-free survival (LFS) and overall survival (OS) were 45.0 ± 10.7 and 51.0 ± 10.6%, respectively. Another 191 patients received salvage chemotherapy and 81 (42.2%) achieved CR or CRi. Thirty-four patients among them underwent subsequent allo-HSCT with 4-year LFS and OS of 46.0 ± 8.8 and 46.2 ± 9.0%. The 4-year LFS and OS in 26 patients who failed to obtain CR or CRi but received allo-HSCT with active disease were 32.9 ± 10.0 and 36.9 ± 10.8%, respectively. For patients who received salvage chemotherapy but not allo-HSCT, few of them became long-term survivors. In multivariate analysis, salvage chemotherapy and the intensity of chemotherapy failed to have significant impact on both OS and LFS. Allo-HSCT was the only prognostic factor for improved OS and LFS in multivariate analysis. CONCLUSIONS: These results indicate the benefit of allo-HSCT in patients with rAML and direct allo-HSCT without salvage chemotherapy could be treatment option.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mieloide Aguda/terapia , Indução de Remissão , Estudos Retrospectivos , Terapia de Salvação/métodos
13.
Clin Nutr ; 41(3): 620-629, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35124469

RESUMO

BACKGROUND AND AIMS: Survival estimation for patients with spinal metastasis is crucial to treatment decisions. Psoas muscle area (PMA), a surrogate for total muscle mass, has been proposed as a useful survival prognosticator. However, few studies have validated the predictive value of decreased PMA in an Asian cohort or its predictive value after controlling for existing preoperative scoring systems (PSSs). In this study, we aim to answer: (1) Is PMA associated with survival in Han Chinese patients with spinal metastasis? (2) Is PMA a good prognosticator according to concordance index (c-index) and decision curve analysis (DCA) after controlling for six existing and commonly used PSSs? METHODS: This study included 180 adult (≥18 years old) Taiwanese patients with a mean age of 58.3 years (range: 22-85) undergoing surgical treatment for spinal metastasis. A patient's PMA was classified into decreased, medium, and large if it fell into the lower (0-33%), middle (33-67%), and upper (67-100%) 1/3 in the study cohort, respectively. We used logistic and cox proportional-hazard regressions to assess whether PMA was associated with 90-day, 1-year, and overall survival. The model performance before and after addition of PMA to six commonly used PSSs, including Tomita score, original Tokuhashi score, revised Tokuhashi score, modified Bauer score, New England Spinal Metastasis Score, and Skeletal Oncology Research Group machine learning algorithms (SORG-MLAs), was compared by c-index and DCA to determine if PMA was a useful survival prognosticator. RESULTS: Patients with a larger PMA is associated with better 90-day, but not 1-year, survival. The model performance of 90-day survival prediction improved after PMA was incorporated into all PSSs except SORG-MLAs. PMA barely improved the discriminatory ability (c-index, 0.74; 95% confidence interval [CI], 0.67-0.82 vs. c-index, 0.74; 95% CI, 0.66-0.81) and provided little gain of clinical net benefit on DCA for SORG-MLAs' 90-day survival prediction. CONCLUSIONS: PMA is a prognosticator for 90-day survival and improves the discriminatory ability of earlier-proposed PSSs in our Asian cohort. However, incorporating PMA into more modern PSSs such as SORG-MLAs did not significantly improve its prediction performance.


Assuntos
Músculos Psoas , Neoplasias da Coluna Vertebral , Adolescente , Adulto , Estudos de Coortes , Humanos , Aprendizado de Máquina , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/cirurgia
14.
Huan Jing Ke Xue ; 42(9): 4566-4574, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414757

RESUMO

Perfluorooctane sulfonates (PFOS) are regarded as a category of chemicals with persistence, bioaccumulation, and toxicity. Understanding dynamic flows, stocks, and emissions of PFOS on a macro spatial and temporal scale can help provide a scientific basis for their sound management. In this work, a dynamic material flow analysis (d-MFA) model was built to characterize and analyze the cycles of PFOS in mainland China over the period 1985-2019. Flows, stocks, and environmental emissions were calculated and the sensitivity and uncertainty of the results were then analyzed. Results show that domestic production was the primary source of PFOS in China, most of which was flowed to the domestic market in the form of final products, with the remainder exported to international markets; soil and water were the main sinks of PFOS in China, with emissions from the usage stage contributing the largest portion (103 tons in 2019). The number of inflows and outflows were relatively low before 2000, but gradually increased until 2009 when the relevant convention was issued. Since 2005, in-use stocks and emissions of PFOS have grown yearly. In addition, stocks in landfill have been climbing since 1985. End-of-life management was still dominated by traditional methods, such as landfill and incineration, while there was a trend towards green treatments. This study can provide basic data and theoretical support for the sound management of PFOS in China.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Ácidos Alcanossulfônicos/análise , China , Monitoramento Ambiental , Fluorocarbonos/análise
15.
Blood ; 135(17): 1472-1483, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32315388

RESUMO

Internal tandem duplication (ITD) mutations within the FMS-like receptor tyrosine kinase-3 (FLT3) can be found in up to 25% to 30% of acute myeloid leukemia (AML) patients and confer a poor prognosis. Although FLT3 tyrosine kinase inhibitors (TKIs) have shown clinical responses, they cannot eliminate primitive FLT3-ITD+ AML cells, which are potential sources of relapse. Therefore, elucidating the mechanisms underlying FLT3-ITD+ AML maintenance and drug resistance is essential to develop novel effective treatment strategies. Here, we demonstrate that FLT3 inhibition induces histone deacetylase 8 (HDAC8) upregulation through FOXO1- and FOXO3-mediated transactivation in FLT3-ITD+ AML cells. Upregulated HDAC8 deacetylates and inactivates p53, leading to leukemia maintenance and drug resistance upon TKI treatment. Genetic or pharmacological inhibition of HDAC8 reactivates p53, abrogates leukemia maintenance, and significantly enhances TKI-mediated elimination of FLT3-ITD+ AML cells. Importantly, in FLT3-ITD+ AML patient-derived xenograft models, the combination of FLT3 TKI (AC220) and an HDAC8 inhibitor (22d) significantly inhibits leukemia progression and effectively reduces primitive FLT3-ITD+ AML cells. Moreover, we extend these findings to an AML subtype harboring another tyrosine kinase-activating mutation. In conclusion, our study demonstrates that HDAC8 upregulation is an important mechanism to resist TKIs and promote leukemia maintenance and suggests that combining HDAC8 inhibition with TKI treatment could be a promising strategy to treat FLT3-ITD+ AML and other tyrosine kinase mutation-harboring leukemias.


Assuntos
Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proteína Forkhead Box O1/metabolismo , Histona Desacetilases/metabolismo , Leucemia Mieloide Aguda/patologia , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor p53/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Proteína Forkhead Box O1/genética , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/genética , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mutação , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Repressoras/genética , Sequências de Repetição em Tandem , Células Tumorais Cultivadas , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Pak J Med Sci ; 36(2): 121-125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32063944

RESUMO

OBJECTIVE: To discuss the clinical effect and safety evaluation of laparoscopic nephron sparing surgery (LNSS) under selective segmental renal artery clamping (SSRAC) and main renal artery clamping (MRAC). METHODS: Eighty-four patients with T1 localized renal tumors who were admitted and treated from October 2017 to October 2018 were retrospectively analyzed, and they were classified into the S group (42 patients) and M group (42 patients). The patients in the S group received LNSS under SSRAC, while the patients in the M group received LNSS under MRAC. The duration of the operation, amount of intraoperative blood loss, intraoperative warm ischemia time, duration of postoperative hospital stay and positive rate of incisal edge; the serum creatinine and blood urea nitrogen values before and after the operation; and the occurrence rates of intraoperative and postoperative complications were compared. RESULTS: All operations were completed smoothly. No patients had a positive incisal edge, and no patients were converted to MRAC during the operation. The duration of the operation and the amount of intraoperative blood loss increased in the S group compared with the M group. The differences were statistically significant (P <0.05). The differences in the intraoperative warm ischemia time, postoperative drainage and duration of postoperative hospital stay in both groups had no statistical significance (P >0.05). The differences in serum creatinine (SCr) and blood urea nitrogen (BUN) in both groups before the operation had no statistical significance (P >0.05). The SCr and BUN levels significantly increased 1 d and 1 m after the operation. The SCr and BUN levels 1 d and 1 m after the operation were significantly lower in the S group than in the M group, and the differences were statistically significant (P <0.05). The differences in the occurrence rates of intraoperative and postoperative complications in both groups had no statistical significance (P >0.05). CONCLUSION: SSRAC is a new renal artery clamping technology, and its curative effect on LNSS patients is significant. In addition, SSRAC has high safety and little influence on renal functions.

17.
Sci Total Environ ; 705: 134651, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31838429

RESUMO

The Loess Plateau of China is one of the most eroded areas in the world. In the past 20 years, effective vegetation restoration measures have significantly changed the near-surface characteristics of soil. In natural conditions, plant litter is widespread in the topsoil. The effects of litter incorporated into soil on the process of soil detachment, which is closely related to plant litter morphology, are still not well known. This study aimed to detect the variation of litter morphological characteristics and quantify their effects on soil detachment capacity and rill erodibility when litter is incorporated into the soil. Four plant litters (Bothriochloa ischaemum (L.) Keng., Artemisia sacrorum Ledeb., Setaria viridis (L.) Beauv., and Artemisia capillaris Thunb.) with five length levels (<0.5, 0.5-2, 2-4, 4-6, and 6-8 cm) were incorporated into soil (idle for 50 days) at the same litter biomass rate (0.7 kg m-2). Then the soil was sampled and cores were subjected to overland flow under six flow shear stress levels (5.66, 8.31, 12.21, 15.55, 19.15 and, 22.11 Pa) using a hydraulic flume (4.0 m × 0.35 m). The results showed that the litter morphological characteristics of litter length density (LLD), litter surface area density (LSAD) and litter volume ratio (LVR) differed in plant species at the same litter biomass rate. Correspondingly, soil detachment capacity (ranging from 0.414 to 2.179 kg m-2 s-1) and rill erodibility (ranging from 0.037 to 0.177 s m-1) varied significantly and mean values from the Bothriochloa ischaemum (L.) Keng. treatments were the minimums, which were 28% to 37% and 23% to 35% less than that of the other treatments, respectively. The soil detachment capacity and rill erodibility were significantly correlated with the litter morphological characteristics of LLD, LSAD and LVR (p < 0.01). The contact area between litter and soil was the most critical factor affecting soil detachment. Incorporated plant litter residue litter effect on rill erodibility could be well estimated by LSAD.


Assuntos
Pradaria , Solo , Biomassa , China , Poaceae
18.
J Nat Med ; 73(2): 388-396, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30617707

RESUMO

To investigate if andrographolide impairs cholestatic liver injury. All rats were randomly divided into six groups-(1) control (n = 6), (2) control + 200 mg/kg andrographolide (n = 6), (3) alpha-naphthylisothiocyanate (ANIT)-control (n = 6), (4) ANIT + 50 mg/kg andrographolide (n = 6), (5) ANIT + 100 mg/kg andrographolide (n = 6), and (6) ANIT + 200 mg/kg andrographolide (n = 6). We gavaged 50 mg/kg ANIT to mimic cholestatic liver injury in rats. Seven days after treatment, all the rats were killed. Serum biochemistry and hepatic histopathological assays were performed to evaluate liver injury. We observed that 200 mg/kg andrographolide significantly decreased the level of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, total bilirubin, and total bile acid in the blood. It also markedly decreased hepatic interleukin-6 and tumor necrosis factor α. Furthermore, 200 mg/kg andrographolide significantly decreased malondialdehyde but increased superoxide dismutase, glutathione, and erythrocyte glutathione peroxidase. Moreover, 200 mg/kg andrographolide effectively increased the accumulation of sirtuin 1 and nuclear erythroid 2-related factor-2. It also attenuated the level of nuclear factor kappa-light-chain-enhancer of activated B and cyclooxygenase-2. These data suggest that andrographolide may impair cholestatic liver injury via anti-inflammatory and anti-oxidative stress.


Assuntos
Colestase/tratamento farmacológico , Diterpenos/uso terapêutico , Fígado/efeitos dos fármacos , 1-Naftilisotiocianato , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Colestase/sangue , Colestase/induzido quimicamente , Diterpenos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas , Inflamação/prevenção & controle , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sirtuína 1/metabolismo
19.
Int J Mol Med ; 42(1): 461-470, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29693173

RESUMO

Epithelial-to-mesenchymal transition (EMT) is essential for the progression of non-invasive tumor cells into malignancy and metastasis. We found that miR-214 was increased in lung adenocarcinoma (LAD) and positively associated with metastasis, which was mediated by EMT. However, the mechanism whereby the overexpression of microRNAs (miRNAs), such as miR-214, promote EMT in LAD remains unclear. In this study, we found that TWIST1, an independent prognostic factor for overall survival, was increased in LAD and correlated positively with LAD recurrence and progression. We also found that TWIST1 contributes to the EMT process and metastasis of LAD cells. Most importantly, a positive correlation was found between the expression of miR-214 and TWIST1 in clinical LAD tissue. Additionally, miR-214 expression was decreased and its target gene suppressor of fused homolog (SUFU) was increased in LAD cells in response to the impairment of TWIST1 expression by shRNA. Overall, this study provides the first evidence to show that the high expression of TWIST1 increases the expression of miR-214 to promote the EMT process and metastasis in LAD. These findings contribute to clarify the mechanisms whereby miRNAs regulate the EMT process and implicate a new TWIST1-miR-214 pathway in the control of migration and invasion of LAD.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Transição Epitelial-Mesenquimal/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Regulação para Cima/genética , Adenocarcinoma de Pulmão , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Metástase Neoplásica , Proteínas Nucleares/genética , Prognóstico , RNA Interferente Pequeno/metabolismo , Proteína 1 Relacionada a Twist/genética
20.
Life Sci ; 194: 88-97, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29241711

RESUMO

Cardiovascular disease (CVD) is a key cause of deaths worldwide, comprising 15-17% of healthcare expenditure in developed countries. Current records estimate an annual global average of 30 million cardiac dysfunction cases, with a predicted escalation by two-three folds for the next 20-30years. Although ß-blockers and angiotensin-converting-enzymes are commonly prescribed to control CVD risk, hepatotoxicity and hematological changes are frequent adverse events associated with these drugs. Search for alternatives identified endogenous cofactor l-carnitine, which is capable of promoting mitochondrial ß-oxidation towards a balanced cardiac energy metabolism. l-Carnitine facilitates transport of long-chain fatty acids into the mitochondrial matrix, triggering cardioprotective effects through reduced oxidative stress, inflammation and necrosis of cardiac myocytes. Additionally, l-carnitine regulates calcium influx, endothelial integrity, intracellular enzyme release and membrane phospholipid content for sustained cellular homeostasis. Carnitine depletion, characterized by reduced expression of "organic cation transporter-2" gene, is a metabolic and autosomal recessive disorder that also frequently associates with CVD. Hence, exogenous carnitine administration through dietary and intravenous routes serves as a suitable protective strategy against ventricular dysfunction, ischemia-reperfusion injury, cardiac arrhythmia and toxic myocardial injury that prominently mark CVD. Additionally, carnitine reduces hypertension, hyperlipidemia, diabetic ketoacidosis, hyperglycemia, insulin-dependent diabetes mellitus, insulin resistance, obesity, etc. that enhance cardiovascular pathology. These favorable effects of l-carnitine have been evident in infants, juvenile, young, adult and aged patients of sudden and chronic heart failure as well. This review describes the mechanism of action, metabolism and pharmacokinetics of l-carnitine. It specifically emphasizes upon the beneficial role of l-carnitine in cardiomyopathy.


Assuntos
Cardiotônicos/uso terapêutico , Carnitina/uso terapêutico , Cardiopatias/tratamento farmacológico , Coração/efeitos dos fármacos , Animais , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patologia , Cardiotônicos/metabolismo , Carnitina/metabolismo , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Disfunção Ventricular/tratamento farmacológico , Disfunção Ventricular/metabolismo , Disfunção Ventricular/patologia
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