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CONTEXT: Qi-dan-dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood. OBJECTIVE: This study reveals the mechanism by which QDD ameliorates DKD. MATERIALS AND METHODS: The compounds in QDD were identified by high-performance liquid chromatography and quadrupole-time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD-low (QDD-L), and 2% QDD-high (QDD-H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose-treated HK-2 and NRK-52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated. RESULTS: A total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial-mesenchymal transition (EMT) via the p38MAPK and AKT-mammalian target of rapamycin (mTOR) pathways. DISCUSSION AND CONCLUSION: QDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD.
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Diabetes Mellitus Experimental , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Ratos , Linhagem Celular , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Medicamentos de Ervas Chinesas/farmacologia , Fibrose , Rim/efeitos dos fármacos , Rim/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: The present study aimed to investigate oral cancer awareness and its related knowledge among residents in Beijing. METHODS: A questionnaire survey was conducted among Beijing residents concerning their knowledge of oral cancer, and its prevention and treatment. RESULTS: A total of 3055 questionnaires were completed, 45.8% by males and 54.2% by females. The ages of the respondents ranged from 15 to 93 years; 12.4% were smokers, 1.1% chewed betel nuts, and 82.5% brushed their teeth at least twice a day. Lung cancer was heard of by the most respondents, followed by gastric cancer and liver cancer; oral cancer was the least heard of. More than 60% of respondents were unaware of the risk factors and early signs of oral cancer. CONCLUSIONS: This survey demonstrated a general lack of public awareness and knowledge about oral cancer. Specific measures should be taken to improve public awareness of oral cancer and its prevention and treatment.
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Neoplasias Bucais , Fumar , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Conscientização , Pequim , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: Ilex pubescens Hook et Arn mainly contains triterpenoids that possess antithrombotic, anti-inflammatory and analgesic effects. Quantitative and qualitative analyses of the triterpenoids in I. pubescens can be useful for determining the authenticity and quality of raw materials and guiding its clinical preparation. OBJECTIVES: To establish a method for rapid and comprehensive analysis of triterpenoids in I. pubescens using ultra-high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS), which will also be applied to evaluate the contents of nine triterpenoids among root, root heartwood and root bark of I. pubescens to judge the value of the root bark to avoid wastage. METHODS: UPLC-ESI-QTOF-MS data from the extracts of I. pubescens in negative mode were analysed using Peakview and Masterview software that provided molecular weight, mass errors, isotope pattern fit and MS/MS fragments for the identification of triterpenoids. The quantification of nine investigated compounds of I. pubescens was accomplished using MultiQuant software. RESULTS: A total of 33 triterpenoids, five phenolic acids, two lignans and a flavonol were characterised in only 14 min. The total content of the nine compounds in the root bark was generally slightly higher than that of the root and root heartwood, which has not been reported before. CONCLUSION: The developed UPLC-ESI-QTOF-MS method was proven to be rapid and comprehensive for simultaneous qualitative and quantitative analyses of the characteristic triterpenoids in I. pubescens. The results may provide a basis for holistic quality control and metabolic studies of I. pubescens, as well as serve as a reference for the analysis of other Ilex plants. Copyright © 2017 John Wiley & Sons, Ltd.
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Cromatografia Líquida de Alta Pressão/métodos , Ilex/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Triterpenos/análise , Flavonóis/análise , Hidroxibenzoatos/análise , Lignanas/análise , Limite de Detecção , Estruturas Vegetais/química , Padrões de Referência , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown. RESULTS: A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3-/-) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated. CONCLUSION: Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract.
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Disbiose , Microbioma Gastrointestinal , Hiperuricemia , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Disbiose/microbiologia , Inflamassomos/metabolismo , Camundongos , Ratos , Masculino , Modelos Animais de Doenças , Rim , Camundongos Knockout , RNA Ribossômico 16S/genética , Transplante de Microbiota Fecal , Urato Oxidase/metabolismo , Camundongos Endogâmicos C57BLRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Simiao Pills, a classical traditional Chinese medicine prescription recorded in Cheng Fang Bian Du, has been traditionally used to treat hyperuricemia due to its heat-clearing and diuretic properties. Studies have shown that Simiao Pills effectively reduce uric acid levels. However, further research is needed to elucidate the precise composition of Simiao Pills for treating hyperuricemia and their potential pharmacological mechanism. AIM OF THE STUDY: This study aimed to investigate the therapeutic effects of Simiao Pills on hyperuricemia, with a particular focus on evaluating their protective role against hyperuricemia-induced renal injury and elucidating the underlying mechanism of action. MATERIALS AND METHODS: UPLC-MS/MS was used to identify the components of Simiao Pills. The hyperuricemia model mice were established by intraperitoneal injecting potassium oxonate (PO) and oral administrating hypoxanthine (HX). Network pharmacology, transcriptome, and metabolomics analyses were integrated to explore the mechanism of Simiao Pills in reducing uric acid and protecting the kidney. Mechanistic and functional studies were conducted to validate the potential mechanisms. RESULTS: Simiao Pills were found to contain 12 characteristic components. Treatment with Simiao Pills significantly reduced serum uric acid levels and ameliorated hyperuricemia-induced renal injury. Simiao Pills inhibited the enzymatic activities of XOD and XDH, and regulated the uric acid transporters in the kidney and ileum. Transcriptome and network pharmacology analyses highlighted quercetin, berberine, kaempferol, and baicalein as the principal active components of Simiao Pills acting on the kidney during hyperuricemia treatment, primarily impacting fibrosis, apoptosis, and inflammation-related signaling pathways. Metabolomic analysis unveiled 21 differential metabolites and 5 metabolic pathways associated with Simiao Pills against renal injury associated with hyperuricemia. Further experimental results validated that Simiao Pills reduced renal fibrosis, apoptotic renal cells, serum inflammation levels, and inhibited the NF-κB/NLRP3/IL-1ß signaling pathway. CONCLUSION: This study demonstrated that Simiao Pills significantly reduced serum uric acid levels and improved renal injury by regulating inflammation, apoptosis, and renal fibrosis. These findings have provided a robust scientific pharmacological basis for the use of Simiao Pills in treating hyperuricemia patients.
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Medicamentos de Ervas Chinesas , Hiperuricemia , Metabolômica , Ácido Úrico , Animais , Hiperuricemia/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Camundongos , Ácido Úrico/sangue , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Espectrometria de Massas em Tandem , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Farmacologia em Rede , Nefropatias/tratamento farmacológico , MultiômicaRESUMO
BACKGROUND: The gut microbiota is crucial in human health and diseases. Traditional Chinese Medicine Constitution (TCMC) divides people into those with a balanced constitution (Ping-he [PH]) and those with an unbalanced constitution. Dampness-heat constitution (Shi-re [SR]) is a common unbalanced constitution in the Chinese population and is susceptible to diseases. However, unbalanced constitutions can be regulated by Chinese medicine and lifestyle interventions in clinical practice. Ermiao Pill (EMP) is a Chinese medicine known for clearing heat and draining dampness and improving SR. However, the efficacy and mechanism of EMP are unclear. HYPOTHESIS/PURPOSE: To determine alterations in the gut microbiota and metabolome in SR and any changes after EMP treatment combined with lifestyle intervention. STUDY DESIGN: Randomized clinical trial. METHODS: We enrolled 112 healthy SR individuals and evaluated the efficacy of EMP along with lifestyle interventions. We further assessed serum cytokine levels, serum and urinary metabolomes, and the gut microbiota by 16S rRNA gene sequencing analysis before and after the EMP and lifestyle interventions. RESULTS: 107 SR individuals (55 in the intervention group and 52 in the control group) completed the 1-month-intervention and 1-year-follow-up. The intervention group significantly improved their health status within 1 month, with a reduced SR symptom score, and the efficacy lasted to the 1-year follow-up. The control group needed a further 6 months to reduce the SR symptom score. The gut microbiota of PH individuals was more diverse and had significantly higher proportions of many bacterial species than the SR. Microbiota co-occurrence network analysis showed that SR enriches metabolites correlating with microbial community structure, consistent with traits of healthy SR-enriched microbiota. CONCLUSION: EMP combined with lifestyle intervention produced health benefits in SR individuals. Our study indicates a pivotal role of gut microbiota and metabolome alterations in distinguishing between healthy SR and PH. Furthermore, the study reveals structural changes of gut microbiota and metabolites induced by EMP and lifestyle intervention. The treatment enriched the number of beneficial bacteria, such as Akkermansia muciniphila and Lactobacillus in the gut. Our findings provide a strong indication that several metabolite factors are associated with the gut microbiota. Moreover, the gut microbiome and metabolome might be powerful tools for TCMC diagnosis and personalized therapy.
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Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Estilo de Vida , Medicina Tradicional Chinesa , Metaboloma , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Feminino , Adulto , Metaboloma/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Pessoa de Meia-Idade , Citocinas/sangue , Citocinas/metabolismo , Adulto Jovem , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: Alzheimer's disease (AD) is a common progressive neurodegenerative disease characterized by memory impairments, and there is no effective therapy. Neural stem/progenitor cell (NSPC) has emerged as potential novel therapy for AD, and we aim to explore whether neural stem/progenitor cell therapy was effective for rodent models of AD. METHODS: We searched PubMed, Embase, Cochrane Library and Web of Science up to December 6, 2022. The outcomes included cognitive function, pathological features and BDNF. The GetData Graph Digitizer software (version 2.26) was applied to extract numerical values, and RevMan 5.3 and Stata 16 were used to analyze data. The SYRCLE risk of bias tool was used to assess study quality. RESULTS: We evaluated 22 mice studies and 8 rat studies. Compared to control groups, cognitive function of NSPC groups of both mice studies (SMD = - 1.96, 95% CI - 2.47 to - 1.45, I2 = 75%, P < 0.00001) and rat studies (SMD = - 1.35, 95% CI - 2.11 to - 0.59, I2 = 77%, P = 0.0005) was apparently improved. In mice studies, NSPC group has lower Aß deposition (SMD = - 0.96, 95% CI - 1.40 to - 0.52, P < 0.0001) and p-tau level (SMD = - 4.94, 95% CI - 7.29 to - 2.95, P < 0.0001), higher synaptic density (SMD = 2.02, 95% CI 0.50-3.55, P = 0.009) and BDNF (SMD = 1.69, 95% CI 0.61-2.77, P = 0.002). Combined with nanoformulation (SMD = - 1.29, 95% CI - 2.26 to - 0.32, I2 = 65%, P = 0.009) and genetically modified (SMD = - 1.29, 95% CI - 1.92 to - 0.66, I2 = 60%, P < 0.0001) could improve the effect of NSPC. In addition, both xenogeneic and allogeneic transplant of NSPC could reverse the cognitive impairment of AD animal models. CONCLUSIONS: Our results suggested that NSPC therapy could improve the cognitive function and slow down the progression of AD. Due to the limitations of models, more animal trials and clinical trials are needed.
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Doença de Alzheimer , Doenças Neurodegenerativas , Camundongos , Ratos , Animais , Doença de Alzheimer/terapia , Roedores , Fator Neurotrófico Derivado do Encéfalo/genética , Células-TroncoRESUMO
BACKGROUND: Pulmonary fibrosis (PF) is a fatal disease distinguished by structural destruction and dysfunction, accompanied by continuous accumulation of fibroblasts, which eventually leads to lung failure. Preclinical studies have shown that the administration of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may be a safe and effective treatment for PF. The purpose of our meta-analysis is to evaluate the efficacy of MSC-EVs therapy and identify therapeutic aspects related to PF. METHODS: Our study (up to April 6, 2022) identified English and Chinese, preclinical, controlled, and in vivo studies to examine the application of MSC-EVs in the treatment of PF. The risk of bias (ROB) is assessed using the SYRCLE bias risk tool. The primary outcomes include collagen content, α-smooth muscle actin (α-SMA), hydroxyproline (HYP) content, and transforming growth factor-ß1 (TGF-ß1). RESULTS: Thirteen studies were included in this meta-analysis. Ten studies evaluated the collagen content, five studies evaluated the α-SMA, five studies evaluated the HYP content, and six studies evaluated the TGF-ß1. Compared to the control group, MSC-EVs therapy was associated with a significant reduction of collagen accumulation, α-SMA, HYP content, and TGF-ß1. CONCLUSION: The administration of MSC-EVs is beneficial for the treatment of rodent PF models. However, the safety and effectiveness of the application in human PF diseases have yet to be confirmed. The application of MSC-EVs in the treatment of PF needs to be further standardized in terms of source, route of administration, and culture method.
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ETHNOPHARMACOLOGICAL RELEVANCE: Zhenwu Decoction (ZWD) is a traditional Chinese medicine (TCM) formula which has wide scope of indications related to Yang deficiency and dampness retention in TCM syndrome. Cardiac hypertrophy can induce similar symptoms and signs to the clinical features of Yang deficiency and dampness retention syndrome. ZWD can increase the left ventricular ejection fraction, reduce cardiac hypertrophy of patients with chronic heart failure. However, its underlying pharmacological mechanism remains unclear. AIM OF THE STUDY: The study aimed to confirm the protective effects of ZWD on cardiac hypertrophy and explore the underlying mechanisms. MATERIALS AND METHODS: The potential targets and pathways of ZWD in cardiac hypertrophy were highlighted by network pharmacology and validated by mechanistic and functional studies. RESULTS: Our network pharmacology analysis suggests that the protective effects of ZWD on cardiac hypertrophy are related to cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway. Subsequent animal studies showed that ZWD significantly ameliorated cardiac function decline, cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. To explore the underlying mechanisms of action, we performed Western blotting, immunohistochemical analysis, and detection of inflammatory response and oxidative stress. Our results showed that ZWD activated the soluble guanylate cyclase (sGC) - cGMP - PKG signaling pathway. The sGC inhibitor ODQ that blocks the sGC-cGMP-PKG signaling pathway in zebrafish abolished the protective effects of ZWD, suggesting sGC-cGMP-PKG is the main signaling pathway mediates the protective effect of ZWD in cardiac hypertrophy. In addition, three major ingredients from ZWD, poricoic acid C, hederagenin and dehydrotumulosic acid, showed a high binding energy with prototype sGC. CONCLUSION: ZWD reduces oxidative stress and inflammation and exerts cardioprotective effects by activating the sGC-cGMP-PKG signaling pathway.
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Proteínas Quinases Dependentes de GMP Cíclico , Guanosina Monofosfato , Animais , Cardiomegalia/tratamento farmacológico , GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas , Guanilato Ciclase/metabolismo , Óxido Nítrico/metabolismo , Guanilil Ciclase Solúvel/metabolismo , Volume Sistólico , Função Ventricular Esquerda , Deficiência da Energia Yang , Peixe-ZebraRESUMO
Introduction: Brain metastasis is the terminal event of breast cancer with poor prognoses. Therefore, this article aimed to provide an updated summary on the development, hotspots, and research trends of brain metastasis from breast cancer based on bibliometric analysis. Method: Publications on breast cancer with brain metastasis retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, and other online bibliometric analysis platforms were used to analyze and visualize the result. Result: In totality, 693 researchers from 3,623 institutions across 74 counties and regions published a total of 2,790 papers in 607 journals. There was a noticeable increase in publications in 2006. The United States was the dominant country with the most publications followed by China. University Texas MD Anderson Cancer Center was the most productive institution, while Dana Farber Cancer Institution was the most cited. Journal of Neuro-Oncology published the most papers, while Journal of Clinical Oncology ranked first based on cocited analysis. Nancy U. Lin was the most productive and cited author with high influence. There was a focus on basic research, clinical trials, local therapy, treatment optimization, and epidemiological studies regarding brain metastases from breast cancer. References focused on pathogenesis, prevention, treatment, and prognosis were cited most frequently, among which the clinical trial of novel treatment attracted most attention from researchers. Reference citation burst detection suggested that new therapies such as the novel tyrosine kinase inhibitor and antibody-drug conjugate may lead the research trends in the future. Conclusion: High-income countries contributed more to the field of breast cancer with brain metastasis, while developing countries like China developed quickly. Furthermore, the success of novel therapies in recent years may lead to the new era of treatment of breast cancer with brain metastasis in the future.
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Purpose: Variability in volume delineation is a possible error source in brachytherapy. This study assessed the interobserver variations in clinical target volume (CTV) delineation in postoperative adjuvant 125I seed implant brachytherapy after parotid gland cancer surgical resection and evaluated the image fusion technique for target volume delineation. Material and Methods: Five radiation oncologists delineated gross tumor volume (GTV) and CTV in 20 patients using conventional delineation and image fusion methods. The consistency in target volume delineation was determined on the basis of differences between the oncologists. Variability was determined using Kendall's W-test, the mean conformity index (CI), the mean distance to conformity (MDC), and the center of gravity distance (CGD). Results: There were significant variations in the delineated target volumes among radiation oncologists, but the CTV consistency was significantly enhanced using the image fusion technique, based on Kendall's W, mean CI, average MDC, and average CGD, which were 0.752, 0.41, 2.75, and 4.997, respectively, using the conventional method, and 0.987, 0.86, 0.55, and 1.27, respectively, using the image fusion method. Conclusions: The interobserver variation in the delineation of the postoperative parotid target volume is large, but it can be considerably decreased using image fusion technology, which resulted in a noticeable improvement in the delineation precision of the target volume for parotid gland cancer. Thus, this technology can enhance the efficacy of 125I seed implant brachytherapy and decrease any adverse effects induced by errors in target delineation.
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Braquiterapia , Neoplasias , Braquiterapia/métodos , Humanos , Radioisótopos do Iodo , Glândula Parótida/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
PURPOSE: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. METHODS: PCCL was orally administered at a dose of 20 mg·kg-1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg-1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1ß levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. RESULTS: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. CONCLUSIONS: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.
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Cuscuta , Mucosite , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Peso Corporal , Caspase 3/metabolismo , Cuscuta/metabolismo , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/patologia , Fluoruracila/efeitos adversos , Mucosa Intestinal/patologia , Camundongos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Sementes , Proteína X Associada a bcl-2/metabolismoRESUMO
Background: Lung cancer is the leading cause of cancer-associated mortality worldwide, and most lung cancers are classified as non-small cell lung cancer (NSCLC). MiR-328 influence the progression of multiple tumors, but the role of miR-328-5p in NSCLC has not been elucidated. The aim of this study was to illuminate the oncogenic role and potential molecular mechanisms of the miR-328-5p and lysyl oxidase like 4 (LOXL4) in NSCLC. Methods: Expression of miR-328-5p was detected by real-time quantitative polymerase chain reaction (qRT-PCR) in tumor and non-tumor adjacent tissues. After Lentivirus-miR-328-5p was employed to intervene this miRNA in NSCLC cell lines, RT-qPCR was used to detect the expression levels of miR-328-5p. Cell Counting Kit-8 (CCK-8), cell colony formation, flow cytometry, wound healing, Transwell assays were used to determine the malignant phenotypes of NSCLC cells. Nude mice models of subcutaneous tumors were established to observe the effect of miR-328-5p on tumorigenesis. Targeting the 3'UTR of LOXL4 by miR-328-5p was verified by integrated analysis including transcriptome sequencing, dual-luciferase and western-blot assays. Results: High miR-328-5p level was observed in NSCLC cells from The Cancer Genome Atlas (TCGA) database and tumor tissues collected from NSCLC patients. Overexpressed miR-328-5p promoted NSCLC cell proliferation, survival, and migration, and promoted tumor growth in vivo. Knockdown of miR-328-5p suppressed tumorigenic activities. Transcriptome sequencing analysis revealed that LOXL4 was downregulated by miR-328-5p, which was confirmed by dual-luciferase reporter and western-blot assays. Conclusions: miR-328-5p showed targeted regulation of LOXL4 to promote cell proliferation and migration in NSCLC.
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Background: High serum uric acid (SUA) levels increase the risk of overall cancer morbidity and mortality, particularly for digestive malignancies. Nevertheless, the correlation between SUA level and clinical outcomes of the postoperative patients with colorectal cancer (CRC) treated by chemotherapy is unclear. This study aimed at exploring the relationship between baseline SUA level and progression-free survival (PFS), disease control rate (DCR), and safety in postoperative CRC patients receiving chemotherapy. Patients and Methods: We conducted a retrospective study to evaluate the relationship between baseline SUA level and PFS, DCR, and incidence of serious adverse events of 736 postoperative CRC patients treated with FOLFOX, FOLFIRI or XELOX at our center. Results: Data from our center suggested that high baseline SUA level is linked to poor PFS in non-metastatic CRC patients using FOLFOX (HR=2.59, 95%CI: 1.29-11.31, p=0.018) and in male patients using FOLFIRI (HR=3.77, 95%CI: 1.57-39.49, p=0.012). In patients treated by FOLFIRI, a high SUA is also linked to a low DCR (p=0.035). In patients using FOLFOX, high baseline SUA level is also linked to a high incidence of neutropenia (p=0.0037). For patients using XELOX, there is no significant correlation between SUA level and PFS, effectiveness, or safety. Conclusions: These findings imply that a high SUA level is a promising biomarker associated with poor PFS, DCR and safety of postoperative CRC patients when treated with FOLFOX or FOLFIRI.
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Inflammation and apoptosis of vascular endothelial cells play a key role in the occurrence and development of atherosclerosis (AS), and the AMPK/mTOR/Nrf2 signaling pathway plays an important role in alleviating the symptoms of AS. Geniposide combined with notoginsenoside R1 (GN combination) is a patented supplement for the prevention and treatment of AS. It has been proven to improve blood lipid levels and inhibit the formation of AS plaques; however, it is still unclear whether GN combination can inhibit inflammation and apoptosis in AS by regulating the AMPK/mTOR/Nrf2 signaling pathway and its downstream signals. Our results confirmed that the GN combination could improve blood lipid levels and plaque formation in ApoE -/- mice fed with a high-fat diet (HFD), inhibit the secretion of serum inflammatory factors and oxidative stress factors. It also decreased the expression of pyrin domain containing protein 3 (NLRP3) inflammasome-related protein and Bax/Bcl2/caspase-3 pathway-related proteins. At the same time, the GN combination could also inhibit the H2O2-induced inflammatory response and apoptosis of human umbilical vein endothelial cells (HUVECs), which is mainly related to the activation of the AMPK/mTOR pathway by GN combination, which in turn induces the activation of Nrf2/HO-1 signal. In addition, the above phenomenon could be significantly reversed by dorsomorphin. Therefore, our experiments proved for the first time that the GN combination can effectively inhibit AS inflammation and apoptosis by activating the AMPK/mTOR/Nrf2 signaling pathway to inhibit the NLRP3 inflammasome and Bax/Bcl2/caspase-3 pathway.
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Background: Studies have shown that gut microbe disorder in mice due to early-life antibiotic exposure promotes glycolipid metabolism disorder in adulthood. However, the underlying mechanism remains unclear and there is not yet an effective intervention or treatment for this process. Purpose: The study investigated whether early-life azithromycin (AZT) exposure in mice could promote high-fat diet (HFD)-induced glycolipid metabolism disorder in adulthood. Moreover, the effect of citrus reticulata pericarpium (CRP) extract on glycolipid metabolism disorder via regulation of gut microbiome in mice exposed to antibodies early in life were investigated. Methods and Results: Three-week-old mice were treated with AZT (50 mg/kg/day) via drinking water for two weeks and then were fed a CRP diet (1% CRP extract) for four weeks and an HFD for five weeks. The results showed that early-life AZT exposure promoted HFD-induced glycolipid metabolism disorder, increased the levels of inflammatory factors, promoted the flora metabolism product trimethylamine N-oxide (TMAO), and induced microbial disorder in adult mice. Importantly, CRP extract mitigated these effects. Conclusion: Taken together, these findings suggest that early-life AZT exposure increases the susceptibility to HFD-induced glycolipid metabolism disorder in adult mice, and CRP extract can decrease this susceptibility by regulating gut microbiome.
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Citrus/química , Glicolipídeos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Extratos Vegetais/farmacologia , Animais , Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , Biomarcadores , Cromatografia Líquida de Alta Pressão , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Suscetibilidade a Doenças , Teste de Tolerância a Glucose , Mediadores da Inflamação/sangue , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/prevenção & controle , Camundongos , Extratos Vegetais/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Background: Intestinal microbial colonization in early life plays a crucial role in immune development and mucosal homeostasis in later years. Antibiotic exposure in early life increases the risk of inflammatory bowel disease (IBD). Ginger acts like a prebiotic and has been used in traditional Chinese medicine for colitis. We investigated the protective effect of ginger against dextran sulfate sodium (DSS)-induced colitis in mice exposed to antibiotic in their early years. Methods: A weaned mouse model exposed to azithromycin (AZT) for 2 weeks was used to mimic antibiotic exposure in childhood among humans. A diet containing ginger extract was administered to mice for 4 weeks after antibiotic exposure. The susceptibility to DSS-induced colitis was evaluated in terms of weight loss, disease activity index (DAI) score, colon length, colitis biomarkers, and intestinal barrier function. The gut microbiota was analyzed in terms of 16S rRNA levels. Results: Ginger extract prevented weight loss, colon shortening, inflammation, and intestinal barrier dysfunction in mice exposed to antibiotics in early life. Ginger increased the bacterial diversity and changed the abundance of bacterial belonging to family Peptococcaceae and Helicobacter species to modulate microbiota structure and composition adversely affected by early antibiotic exposure. Conclusion: Ginger has a protective effect in potentially decreasing the susceptibility to colitis in mice exposed to antibiotics early in life.
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The association between schizophrenia (SZ) and uric acid (UA) levels has been suggested for many years, but without solid evidence. Therefore, we conducted a systematic review and meta-analysis of all case-control studies examining the serum and plasma UA levels in SZ subjects in comparison to those in healthy controls. Relevant studies published before October 29, 2018, were searched in the main electronic databases, and 17 studies were finally included into the meta-analysis after screening with the criteria. Our results revealed that there were no statistically significant differences of the UA levels between SZ subjects and healthy controls. Further subgroup analyses of the antipsychotic status reported the same finding. Subgroup analyses of clinical status showed that UA levels were decreased in subjects with first episode psychosis (FEP). The subgroup analyses of gender and ethnicity demonstrated that UA levels were decreased in male subjects and in Americans with SZ. Overall, these findings strengthen the clinical evidence that FEP is accompanied by increased oxidative stress response. Reduced UA levels may be a potential risk factor for SZ in male and in the Americans. However, whether there is a causal relationship between the reduced UA levels and the development of SZ deserves further investigation.
Assuntos
Estresse Oxidativo/fisiologia , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Ácido Úrico/sangue , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fatores de Risco , Esquizofrenia/tratamento farmacológicoRESUMO
Heart, liver, and kidney, which are known as the essential organs for metabolism, possess the unique ability to regulate the proliferation function of the body against injury. Silibinin (SB), a natural polyphenolic flavonoid extracted from traditional herb Silybum marianum L., has been used to protect hepatocytes. Whether SB can regulate mitochondrial fission in normal cells and the underlying mechanisms remain unclear. Here, we showed that SB markedly promoted cell proliferation by facilitating G1/S transition via activating dynamin-related protein 1 (Drp1), which in turn mediated mitochondrial fission in these normal cells. SB dose-dependently increased the mitochondrial mass, mtDNA copy number, cellular adenosine triphosphate production, mitochondrial membrane potential, and reactive oxygen species in normal cells. Furthermore, SB dose-dependently increased the expression of Drp1. Blocking Drp1 abolished SB-induced mitochondrial fission. In conclusion, we demonstrate that SB promotes cell proliferation through facilitating G1/S transition by activating Drp1-mediated mitochondrial fission. This study suggests that SB is a potentially useful herbal derivative for the daily prevention of various diseases caused by impaired mitochondrial fission.
Assuntos
Dinaminas/metabolismo , Fase G1/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Fase S/efeitos dos fármacos , Silibina/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Túbulos Renais/citologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismoRESUMO
Background. Chinese herbal medicines are widely used to lower serum uric acid levels. However, no systemic review summarizes and evaluates their efficacies and the underlying mechanisms of action. Objectives. To evaluate the clinical and experimental evidences for the effectiveness and the potential mechanism of Chinese herbal medicines in lowering serum uric acid levels. Methods. Four electronic databases PubMed, Wed of Science, the Cochrane Library and Embase were used to search for Chinese herbal medicines for their effects in lowering serum uric acid levels, dated from 1 January 2009 to 19 August 2020. For clinical trials, randomized controlled trials (RCTs) were included; and for experimental studies, original articles were included. The methodological quality of RCTs was assessed according to the Cochrane criteria. For clinical trials, a meta-analysis of continuous variables was used to obtain pooled effects. For experimental studies, lists were used to summarize and integrate the mechanisms involved. Results. A total of 10 clinical trials and 184 experimental studies were included. Current data showed that Chinese herbal medicines have promising clinical efficacies in patients with elevated serum uric acid levels (SMD: -1.65, 95% CI: -3.09 to -0.22; p = 0.024). There was no significant difference in serum uric acid levels between Chinese herbal medicine treatments and Western medicine treatments (SMD: -0.13, 95% CI: -0.99 to 0.74; p = 0.772). Experimental studies revealed that the mechanistic signaling pathways involved in the serum uric acid lowering effects include uric acid synthesis, uric acid transport, inflammation, renal fibrosis and oxidative stress. Conclusions. The clinical studies indicate that Chinese herbal medicines lower serum uric acid levels. Further studies with sophisticated research design can further demonstrate the efficacy and safety of these Chinese herbal medicines in lowering serum uric acid levels and reveal a comprehensive picture of the underlying mechanisms of action.