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1.
Environ Res ; 252(Pt 3): 119033, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38685300

RESUMO

Aerobic composting is a common way for the disposal of feces produced in animal husbandry, and can reduce the release of antibiotic resistance genes (ARGs) from feces into the environment. In this study, we collected samples from two distinct treatments of swine manure compost with and without ceftiofur (CEF), and identified the ARGs, mobile genetic elements (MGEs), and bacterial community by metagenomic sequencing. The impacts of CEF on the bacterial community composition and fate of ARGs and MGEs were investigated. With increasing composting temperature and pH, the concentration of CEF in the manure decreased rapidly, with a degradation half-life of 1.12 d and a 100% removal rate after 10 d of aerobic composting. Metagenomics demonstrated that CEF in the manure might inhibit the growth of Firmicutes and Proteobacteria, thereby reducing some ARGs and MGEs hosted by these two bacteria, which was further confirmed by the variations of ARGs and MGEs. A further redundancy analysis suggested that pH and temperature are key environmental factors affecting ARG removal during composting, and intI1 and bacterial communities also have significant influence on ARG abundance. These results are of great significance for promoting the removal of some ARGs from animal manure by controlling some key environmental factors and the type of antibiotics used in animals.


Assuntos
Antibacterianos , Cefalosporinas , Compostagem , Esterco , Animais , Esterco/microbiologia , Esterco/análise , Suínos , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Bactérias/genética , Bactérias/efeitos dos fármacos
2.
Int J Cancer ; 148(4): 921-931, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33113150

RESUMO

Limited and inefficient treatment options exist for metastatic relapsed cervical cancer (MRCC), and there are currently no reliable indicators to guide therapeutic selection. We performed deep sequencing analyses targeting 322 cancer-related genes in plasma cell-free DNA and matched white blood cells in 173 serial blood samples from 82 locally advanced CC (LACC) or MRCC patients and when possible during treatment. We identified five notable nonsynonymous mutant genes (PIK3CA, BRAF, GNA11, FBXW7 and CDH1) in the MRCC samples as the metastatic relapse significantly mutated (MSG) genes and found that MRCC patients with any detectable MSG mutations had significantly shorter progression-free survival (PFS) (P = .005) and overall survival (OS) (P = .007) times than those without detectable MSG mutations. Additionally, analyses of matched prechemotherapy and postchemotherapy plasma revealed that a reduction in the number of MSG mutations after chemotherapy was significantly associated with partial remission (PR) and stable disease (SD) (P = .007). Among the patients included in the longitudinal tracking ctDNA analysis, an increase in MSG mutations was observed earlier in response to disease progression than radiological imaging. Our results outline the mutation profiles of MRCC. We show how longitudinal monitoring with ctDNA in liquid biopsy samples provides both predictive and prognostic information during treatment.


Assuntos
Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Mutação , Neoplasias do Colo do Útero/genética , Adulto , Idoso , DNA Tumoral Circulante/sangue , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Terapia de Salvação/métodos , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto Jovem
3.
Int J Cancer ; 145(9): 2547-2557, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30919951

RESUMO

The liquid biopsy is being integrated into cancer diagnostics and surveillance. However, critical questions still remain, such as how to precisely evaluate cancer mutation burden and interpret the corresponding clinical implications. Herein, we evaluated the role of peripheral blood cell-free DNA (cfDNA) in characterizing the dynamic mutation alterations of 48 cancer driver genes from cervical cancer patients. We performed targeted deep sequencing on 93 plasma cfDNA from 57 cervical cancer patients and from this developed an algorithm, allele fraction deviation (AFD), to monitor in an unbiased manner the dynamic changes of genomic aberrations. Differing treatments, including chemotherapy (n = 22), radiotherapy (n = 14) and surgery (n = 15), led to a significant decrease in AFD values (Wilcoxon, p = 0.029). The decrease of cfDNA AFD values was accompanied by shrinkage in the size of the tumor in most patients. However, in a subgroup of patients where cfDNA AFD values did not reflect a reduction in tumor size, there was a detection of progressive disease (metastasis). Furthermore, a low AFD value at diagnosis followed a later increase of AFD value also successfully predicted relapse. These results show that plasma cfDNA, together with targeted deep sequencing, may help predict treatment response and disease development in cervical cancer.


Assuntos
Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Alelos , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Quimiorradioterapia/métodos , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Feminino , Genoma/genética , Genômica/métodos , Humanos , Pessoa de Meia-Idade , Mutação/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia
4.
Front Endocrinol (Lausanne) ; 15: 1366297, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915896

RESUMO

Introduction: The aim of this meta-analysis was to evaluate the efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of knee osteoarthritis (OA). Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials, Scopus and Web of Science databases were searched from inception to May 6, 2024 to identify randomized controlled trials that compared MSCs and placebo or other nonsurgical approaches for treating OA. Two investigators independently searched the literature and extracted data, and conventional meta-analyses were conducted with Review Manager 5.3. The outcomes included pain relief, functional improvement, and risk of adverse events (AEs). Results: A total of 18 articles were included. Overall, MSCs were superior to placebo in terms of relieving pain and improving function at the 12-month follow-up. However, the differences in treatment-related AEs were not significant. Conclusion: MSCs may relieving pain and improving function of OA. The limitations of this study include the high heterogeneity of the included studies. Additionally, the follow-up time in the included studies was relatively short, so more clinical trials are needed to predict the long-term efficacy and safety of MSCs. Systematic review registration: https://doi.org/10.17605/OSF.IO/5BT6E, identifier CRD42022354824.


Assuntos
Transplante de Células-Tronco Mesenquimais , Osteoartrite do Joelho , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Osteoartrite do Joelho/terapia , Resultado do Tratamento , Osteoartrite/terapia , Células-Tronco Mesenquimais/citologia
5.
Pharmaceutics ; 16(2)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38399231

RESUMO

Bacterial resistance is a growing problem worldwide, and the number of deaths due to drug resistance is increasing every year. We must pay great attention to bacterial resistance. Otherwise, we may go back to the pre-antibiotic era and have no drugs on which to rely. Bacterial resistance is the result of several causes, with efflux mechanisms widely recognised as a significant factor in the development of resistance to a variety of chemotherapeutic and antimicrobial medications. Efflux pump inhibitors, small molecules capable of restoring the effectiveness of existing antibiotics, are considered potential solutions to antibiotic resistance and have been an active area of research in recent years. This article provides a review of the efflux mechanisms of common clinical pathogenic bacteria and their efflux pump inhibitors and describes the effects of efflux pump inhibitors on biofilm formation, bacterial virulence, the formation of bacterial persister cells, the transfer of drug resistance among bacteria, and mismatch repair. Numerous efforts have been made in the past 20 years to find novel efflux pump inhibitors which are known to increase the effectiveness of medicines against multidrug-resistant strains. Therefore, the application of efflux pump inhibitors has excellent potential to address and reduce bacterial resistance.

6.
Front Pharmacol ; 15: 1378034, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694922

RESUMO

Introduction: Streptococcus suis (S. suis) is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against S. suis. In this study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was used to determine the dosage regimens of ADP against S. suis and withdrawal intervals. Methods: The PBPK model of ADP injection can predict drug concentrations in plasma, liver, kidney, muscle, and fat. A semi-mechanistic pharmacodynamic (PD) model, including susceptible subpopulation and resistant subpopulation, is successfully developed by a nonlinear mixed-effect model to evaluate antibacterial effects. An integrated PBPK/PD model is conducted to predict the time-course of bacterial count change and resistance development under different ADP dosages. Results: ADP injection, administrated at 20 mg/kg with 12 intervals for 3 consecutive days, can exert an excellent antibacterial effect while avoiding resistance emergence. The withdrawal interval at the recommended dosage regimen is determined as 18 days to ensure food safety. Discussion: This study suggests that the PBPK/PD model can be applied as an effective tool for the antibacterial effect and safety evaluation of novel veterinary drugs.

7.
Sci Total Environ ; 912: 169598, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38157911

RESUMO

One Health closely integrates healthy farming, human medicine, and environmental ecology. Due to the ecotoxicity and risk of transmission of drug resistance, veterinary medicines (VMs) are regarded as emerging environmental pollutants. To reduce or mitigate the environmental risk of VMs, developing friendly, safe, and effective removal technologies is an important means of environmental remediation for VMs. Many previous studies have proved that biodegradation has significant advantages in removing VMs, and biodegradation based on enzyme catalysis presents higher operability and specificity. This review focused on biodegradation strategies of environmental pollutants and reviewed the enzymatic degradation of VMs including antimicrobial drugs, insecticides, and disinfectants. We reviewed the sources and catalytic mechanisms of peroxidase, laccase, and organophosphorus hydrolases, and summarized the latest research status of immobilization methods and bioengineering techniques in improving the performance of degrading enzymes. The mechanism of enzymatic degradation for VMs was elucidated in the current research. Suggestions and prospects for researching and developing enzymatic degradation of VMs were also put forward. This review will offer new ideas for the biodegradation of VMs and have a guide significance for the risk mitigation and detoxification of VMs in the environment.


Assuntos
Poluentes Ambientais , Inseticidas , Humanos , Biodegradação Ambiental , Poluentes Ambientais/metabolismo , Lacase/metabolismo , Agricultura
8.
Chin Med J (Engl) ; 136(17): 2058-2065, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37525354

RESUMO

BACKGROUND: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether baseline serum lipid parameters influence the benefits of intensive SBP control is unclear. METHODS: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to <130 mmHg) and standard (SBP target of 130 to <150 mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. A total of 8283 participants from the STEP study were included in this post hoc analysis to examine whether the effects of the SBP intervention differed by baseline low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) concentrations. RESULTS: Regardless of the randomized SBP intervention, baseline LDL-C and non-HDL-C concentrations had a J-shaped association with the hazard of the primary outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline LDL-C level ( P for interaction = 0.80) and non-HDL-C level ( P for interaction = 0.95). Adjusted subgroup analysis using tertiles in LDL-C1 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.52-1.13; P = 0.18), LDL-C2 (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29), and LDL-C3 (HR, 0.68; 95% CI, 0.47-0.98; P = 0.04) was provided, with an interaction P value of 0.49. Similar results were showed in non-HDL-C1 (HR, 0.87; 95% CI, 0.59-1.29; P = 0.49), non-HDL-C2 (HR, 0.70; 95% CI, 0.48-1.04; P = 0.08), and non-HDL-C3 (HR, 0.67; 95% CI, 0.47-0.95; P = 0.03), with an interaction P -value of 0.47. CONCLUSION: High baseline serum LDL-C and non-HDL-C concentrations were associated with increased risk of primary cardiovascular disease outcome, but there was no evidence that the benefit of the intensive SBP control differed by baseline LDL-C and non-HDL-C concentrations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03015311.


Assuntos
Doenças Cardiovasculares , Hipertensão , Idoso , Humanos , Pressão Sanguínea/fisiologia , LDL-Colesterol , Colesterol , Fatores de Risco
9.
Mol Med Rep ; 26(1)2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35656890

RESUMO

Myocardial ischemia­reperfusion (I/R) serves a crucial role in myocardial infarction. C1q/TNF­related protein 12 (CTRP12) is a secretory protein involved in metabolism. It has been reported that CTRP12 participates in the regulation of numerous cardiovascular diseases. However, its role in myocardial I/R injury remains unclear. In the present study, the left anterior descending coronary artery in mice was ligated to establish a mouse I/R model. A myocardial hypoxia­reoxygenation (H/R) cell model was also established. Cardiomyocyte injury was evaluated using hematoxylin and eosin staining, Cell Counting Kit­8 and a lactate dehydrogenase (LDH) kit. The expression levels of CTRP12 and Krueppel­like factor 15 (KLF15) in murine myocardial tissues and H9c2 cells were determined using reverse transcription­quantitative PCR and western blotting, as KLF15 was previously reported to protect against I/R­induced cardiomyocyte damage. Furthermore, inflammatory factors TNF­α, IL­1ß and IL­6 were analyzed using ELISA while apoptosis was assessed using TUNEL assays and western blotting. Moreover, the activity of the CTRP12 promoter was determined using a dual­luciferase reporter assay. The results demonstrated that I/R surgery markedly exacerbated myocardial tissue damage, whereas H/R treatment significantly reduced cell viability and significantly increased LDH activity as well as the release of inflammatory factors and apoptosis. I/R and H/R induction significantly reduced the expression levels of CTRP12 and KLF15. CTRP12 overexpression significantly alleviated H/R­induced cell injury and significantly inhibited inflammation and apoptosis. Further analysis demonstrated that KLF15 could significantly promote the activity of the CTRP12 promoter. However, following CTRP12 knockdown, KLF15 overexpression exacerbated cell injury, inflammation and apoptosis. In conclusion, the present study demonstrated that CTRP12 may mitigate inflammation and apoptosis in H/R­induced cardiomyocytes, possibly via the regulation of KLF15, which provided a theoretical basis for the potential treatment of I/R­induced myocardial infarction.


Assuntos
Adipocinas , Fatores de Transcrição Kruppel-Like , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Adipocinas/genética , Adipocinas/metabolismo , Animais , Apoptose , Modelos Animais de Doenças , Inflamação/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo
10.
Membranes (Basel) ; 12(2)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35207146

RESUMO

In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and extracellular vesicles (EVs) may play a major role in the efficacy of this treatment. Hypoxia can change the cargo and biological functions of MSC-derived EVs (MSC-EVs). The aim of the present study was to determine whether the effects of hypoxia-preconditioned MSC-EVs on OA cartilage repair are superior to normoxia-preconditioned MSC-EVs. By using in vitro and in vivo OA models, we verified that hypoxia-preconditioned MSC-EVs improved chondrocyte proliferation and migration and suppressed chondrocyte apoptosis to a greater extent than normoxia-preconditioned MSC-EVs. Furthermore, we found that hypoxia altered the microRNA expression in MSC-EVs and identified four differentially expressed microRNAs: hsa-miR-181c-5p, hsa-miR-18a-3p, hsa-miR-376a-5p, and hsa-miR-337-5p. Bioinformatics analysis revealed that hypoxic pretreatment may promote cartilage repair by stimulating chondrocyte proliferation and migration and suppressing chondrocyte apoptosis through the miRNA-18-3P/JAK/STAT or miRNA-181c-5p/MAPK signaling pathway. Therefore, hypoxia-preconditioned EVs may be a novel treatment for OA.

11.
Sci Total Environ ; 839: 156243, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35643147

RESUMO

Livestock manure is an important source of antibiotic resistance genes (ARGs) spreading to the environment, posing a potential threat to human health. Here, we investigated the dissipation of florfenicol (FF) and thiamphenicol (TAP), and their effects on the bacterial community, mobile genetic elements (MGEs), and ARGs during composting. The results indicated that FF and TAP dissipated rapidly in compost, with half-life values of 5.1 and 1.6 d, respectively. However, FF could not be completely removed during composting. The FF and TAP residues in manure could reduce the elimination of ARGs and MGEs during composting, and had a negative effect on the physicochemical factors of the compost. Significant correlations were found between floR and intI1, indicating that floR in manure may more easily diffuse to the soil environment. Meanwhile, the presence of FF in manure could increase the abundance of floR. Network analysis showed that Proteobacteria and Firmicutes were the dominant bacterial communities and important potential pathogen hosts carrying ARGs. The predicted environmental concentration of FF in the soil was over 100 µg kg-1, which indicates that FF poses a potential risk to the natural environment, and we verified this result through field experiments. The results showed that FF dissipated in the soil after it migrated from manure to soil. In contrast, TAP in manure posed lower environmental risk. This study highlights that changed in composting conditions may control the rate of removal of ARGs. Further studies are needed to investigate the best environmental conditions to achieve a faster degradation of FF and a more comprehensive elimination of ARGs during composting.


Assuntos
Compostagem , Tianfenicol , Animais , Antibacterianos/farmacologia , Bactérias/genética , Compostagem/métodos , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Esterco/microbiologia , Solo/química , Suínos , Tianfenicol/análogos & derivados
12.
Clin J Pain ; 37(12): 914-924, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34608021

RESUMO

OBJECTIVES: The aim of this meta-analysis was to evaluate the efficacy and safety of tanezumab for the treatment of patients with knee or hip osteoarthritis (OA). METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to July 2020. Randomized-controlled trials comparing tanezumab with placebo or nonsteroidal anti-inflammatory drugs in patients with OA. Two investigators identified studies and independently extracted data, and conventional meta-analyses were conducted with Review Manager 5.3. The outcomes were pain relief, functional improvement, and risk of adverse events (AEs). RESULTS: A total of 8 articles, comprising 9 randomized-controlled trials, were included. Overall, tanezumab was superior to placebo for relieving pain and improving function, as well as in the patient's global assessment. Tanezumab also had significant advantages over nonsteroidal anti-inflammatory drugs for relieving pain and improving function, as well as in the patient's global assessment. Significantly more patients discontinued treatment because of AEs after treatment with tanezumab. However, the differences in serious AEs and total joint replacement were not significant. Moreover, tanezumab-treated patients experienced significantly more rapid progression of osteoarthritis. DISCUSSION: Tanezumab can alleviate pain and improve function for patients with OA of the hip or knee. Although tanezumab does not cause serious AEs, rapid progression of OA occurred in a small number of participants, so more clinical trials are needed to explore its safety.


Assuntos
Osteoartrite do Joelho , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Nanomedicine (Lond) ; 16(15): 1297-1310, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34044578

RESUMO

Background: Some studies have reported results from the use of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) to treat osteoarthritis (OA). Objective: To evaluate the efficacy of MSC-EVs as a treatment for OA. Data sources: Databases were searched using the terms 'mesenchymal stem cells', 'osteoarthritis' and 'extracellular vesicles.' Study eligibility criteria: Studies performed in animal models utilizing MSC-EVs to treat OA that described the macroscopic evaluation or histological evaluation were included. Study appraisal: The quality of the studies was examined using the CAMARADES quality checklist. Results: MSC-EVs were superior to the placebo in the macroscopic evaluation and histological evaluation. MSC-EVs were more effective in the early stage of OA and once a week was better than multiple times a week. Limitations: The included studies were highly heterogeneous. Conclusion: MSC-EVs may improve the results of macroscopic and histological evaluations of OA.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Osteoartrite , Animais , Osteoartrite/terapia
14.
Cell Transplant ; 29: 963689720908500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32207341

RESUMO

Mesenchymal stem cells (MSCs) are multipotent stem cells that have attracted increasing interest in the field of regenerative medicine. Previously, the differentiation ability of MSCs was believed to be primarily responsible for tissue repair. Recent studies have shown that paracrine mechanisms play an important role in this process. MSCs can secrete soluble molecules and extracellular vesicles (EVs), which mediate paracrine communication. EVs contain large amounts of proteins and nucleic acids, such as mRNAs and microRNAs (miRNAs), and can transfer the cargo between cells. The cargoes are similar to those in MSCs and are not susceptible to degradation due to the protection of the EV bimolecular membrane structure. MSC-EVs can mimic the biological characteristics of MSCs, such as differentiation, maturation, and self-renewal. Due to their broad biological functions and their ability to transfer molecules between cells, EVs have been intensively studied by an increasing number of researchers with a focus on therapeutic applications, especially those of EVs secreted by MSCs. In this review, we discuss MSC-derived EVs and their therapeutic potential in tissue regeneration.


Assuntos
Diferenciação Celular/fisiologia , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/citologia , Medicina Regenerativa , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Comunicação Parácrina/fisiologia
15.
J Exp Clin Cancer Res ; 39(1): 243, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33187536

RESUMO

BACKGROUND: Radiotherapy is regarded as a milestone for the cure of cervical cancer. However, clinical outcome heavily be hindered by radioresistance. So, exploring the underlying mechanism of radioresistance, and find potential target, well deserve fully emphasis. METHODS: In this study, we developed two novel radiation resistance cervical cancer cell lines, which could mimic clinical radioresistance. In order to find new potential targets, RNA-Seq, database analysis, streptavidin-agarose and LC/MS were used. Pull-down, luciferase and rescue assays were conducted to explore the regulatory mechanisms. To further evaluate the correlation between therapeutic responses and HMGB3/hTERT expression, 172 cervical cancer patients were recruited. RESULTS: Knockdown of HMGB3 significantly inhibit the DNA damage repair and induced more γH2AX foci, leading to enhanced chemo- and radio-sensitivity in vitro and in vivo, whereas HMGB3 overexpression has the opposite effects. HMGB3 promotes cell growth and radioresistance by transcriptionally up-regulating hTERT via the specifical binding of HMGB3 at the hTERT promoter region from - 902 to - 321. HMGB3 knockdown-mediated radiosensitization could be reversed by the overexpressed hTERT in both cervical cancer cell lines and xenograft tumor mouse model. Furthermore, clinical data from 172 cervical cancer patients proved that there was a positive correlation between HMGB3 and hTERT expression, and high expression of HMGB3/hTERT predicted poor response to radiotherapy, worse TNM stages and shorter survival time. CONCLUSION: Here, we have identified HMGB3/hTERT signaling axis as a new target for cervical cancer radioresistance. Our results provide new insights into the mechanism of cervical cancer radioresistance and indicate that targeting the HMGB3/hTERT signaling axis may benefit cervical cancer patients.


Assuntos
Proteína HMGB3/efeitos da radiação , Tolerância a Radiação/genética , Neoplasias do Colo do Útero/radioterapia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais , Transfecção
16.
Clin Epidemiol ; 11: 911-921, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632152

RESUMO

BACKGROUND: There is no consensus at present regarding the differences in the risk of GI bleeding across various NOAC regimens. Therefore, we performed a network meta-analysis to compare the risk of gastrointestinal bleeding after different NOAC regimens. METHODS: PubMed, Cochrane, Web of Science, Clinicaltrial.gov and Clinicaltrialresults.org were searched for randomized controlled trials (RCTs) assessing gastrointestinal bleeding of all NOAC regimens from inception to January 2018. The primary endpoint was major gastrointestinal (MGI) bleeding. The meta-regression was performed to access the association between the MGI bleeding events and mortality. The network meta-analysis was carried out with the Bayesian random-effect model. RESULTS: A total of 25 RCTs, including 139,392 patients, were identified. Meta-regression analysis showed that MGI bleeding was correlated with fatal bleeding events (odds ratios [OR], 1.76; 95% confidence interval [CI], 1.13-2.77], P=0.015). The network meta-analysis results showed that compared to the conventional regimens, rivaroxaban was associated with increased risk of MGI bleeding (OR, 1.37; 95% credible interval [CrI], 1.00-1.85), but not the apixaban (OR, 0.77; 95% CrI, 0.53-1.07]), edoxaban (OR, 0.86; 95%CrI, 0.52-1.18) and dabigatran etexilate (OR, 1.22; 95% CrI, 0.82-1.69). Compared to rivaroxaban, apixaban (OR, 0.56; 95% CrI, 0.35-0.88) and edoxaban (OR, 0.62; 95% CrI, 0.35-0.96) showed a significantly lower risk of MGI bleeding. Apixaban had the highest probability of being the safest option with regard to the risk of MGI bleeding (89.1%), followed by edoxaban (77.4%), conventional therapy (51.4%), dabigatran etexilate (23.8%) and rivaroxaban (8.3%). CONCLUSION: The risk of GI bleeding significantly varies among different NOAC regimens, and evidence shows that apixaban and edoxaban had the most favorable MGI bleeding safety profile, while rivaroxaban and dabigatran etexilate were the least safe.

17.
Onco Targets Ther ; 12: 4203-4211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213838

RESUMO

Background: In cancers, tumor-associated macrophages (TAMs) play an important role in the progression, evasion of immunity and sensitivity to therapy. Unfortunately, radiation and hypoxia could induce the M2 macrophages infiltration and polarization. Materials and methods: In this study, we investigated the relevance of macrophage recruitment with radiation and hypoxia by transwell. We also evaluated the effect of ß-elemene on the infiltration of M2 macrophages and explored its underlying molecular mechanism by a series of in vitro and in vivo experiments. Results: Irradiated or hypoxia lung cancer cells recruit macrophages, and the recruitment is MCP-1 dependent. We also found that radiation and hypoxia-induced MCP-1 secretion follows upregulation of Prx-1, which leads to nuclear accumulation of NF-κB and HIF-1α expression. In addition, ß-elemene could effectively suppress this recruitment phenomenon through Prx-1/NF-κB/HIF-1α signaling. Conclusion: Our study showed that radiation and hypoxia significantly promoted the macrophages recruitment. ß-elemene could effectively suppress this recruitment phenomenon and MCP-1 expression via inhibiting Prx-1/NF-κB/HIF-1α pathways.

18.
Clin Exp Hypertens ; 30(7): 648-61, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18855268

RESUMO

Blood pressure (BP) is a complex trait regulated by the interaction among multiple physiologic regulatory systems, likely involving numerous genes that lead to inconsistent findings in genetic studies. One possibility of failure to replicate some single-locus results is that the underlying genetics of hypertension is based on multiple genes with minor effects. To learn the association between 17 single nucleotide polymorphisms (SNPs) in 13 cardiovascular disease-predisposing genes and blood pressure of Han males, the 17 SNPs genotypes of 375 Han males were detected and analyzed with BaiO gene chip. The relationship between the SNPs and blood pressure was analyzed with variance analysis and multiple linear regression analysis. Variance analysis and/or multiple linear regression showed that: systolic blood pressure (SBP) was increasing with the elevation of year; AGT(235)M, ApoE(112,158)E4, and SerpinA3(rs4934)A were relative to the increase of SBP; AGT(235)M, ET-2(985)G, ApoC3(3206)T, and ApoE(112,158)E4 may have had some relation with diastolic blood pressure (DBP) elevation; and ApoB(Xba) + was associated with the increase of pulse pressure (PP). These findings support the multigenic nature of the etiology of essential hypertension and propose a potential gene-gene interactive model for future studies.


Assuntos
Povo Asiático/genética , Pressão Sanguínea/genética , Doenças Cardiovasculares/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Análise de Variância , China , Predisposição Genética para Doença , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Herança Multifatorial , Análise de Sequência com Séries de Oligonucleotídeos , Adulto Jovem
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