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1.
Cell Prolif ; : e12772, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32003505

RESUMO

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high worldwide prevalence and poor prognosis. Researches are urgently needed on its molecular pathogenesis and biological characteristics. Metabolic reprogramming for adaptation to the tumour microenvironment (TME) has been recognized as a hallmark of cancer. Dysregulation of lipid metabolism especially fatty acid (FA) metabolism, which involved in the alternations of the expression and activity of lipid-metabolizing enzymes, is a hotspot in recent study, and it may be involved in HCC development and progression. Meanwhile, immune cells are also known as key players in the HCC microenvironment and show complicated crosstalk with cancer cells. Emerging evidence has shown that the functions of immune cells in TME are closely related to abnormal lipid metabolism. In this review, we summarize the recent findings of lipid metabolic reprogramming in TME and relate these findings to HCC progression. Our understanding of dysregulated lipid metabolism and associated signalling pathways may suggest a novel strategy to treat HCC by reprogramming cell lipid metabolism or modulating TME.

2.
Int Immunopharmacol ; 77: 105973, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677992

RESUMO

Sepsis is a syndrome of life-threatening organ dysfunction caused by dysregulated host responses to infection. Macrophage polarization is a key process involved in the pathogenesis of sepsis. Recent evidence has demonstrated that autophagy participates in the regulation of macrophage polarization in different phases of inflammation. Here, we investigated whether trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes the macrophage M2 phenotype by enhancing autophagy to counteract excessive inflammation in a cecal ligation and puncture (CLP) mouse model. TSA stimulation increased the proportions of M2 marker (CD206, CD124 and CD23)-labeled RAW264.7 macrophages. Furthermore, with increasing TSA doses, autophagy was enhanced gradually. Interestingly, the autophagy activator rapamycin (Rap), also known as an mTOR inhibitor, unexpectedly decreased the proportions of M2 marker-labeled macrophages. However, TSA treatment reversed the Rap-induced decreases in CD206-labeled macrophages. Next, we stimulated different groups of RAW264.7 cells with the autophagy inhibitors MHY1485 or 3-methyladenine (3-MA). Inhibition of autophagy at any stage in the process suppressed TSA-induced macrophage M2 polarization, but the effect was not associated with mTOR activity. In vivo, TSA administration promoted peritoneal macrophage M2 polarization, increased LC3 II expression, attenuated sepsis-induced organ (lung, liver and kidney) injury, and altered systemic inflammatory cytokine secretion. However, 3-MA abolished the protective effects of TSA in CLP mice and decreased the number of M2 peritoneal macrophages. Therefore, TSA promotes the macrophage M2 phenotype by enhancing autophagy to reduce systemic inflammation and ultimately improves the survival of mice with polymicrobial sepsis.

3.
Front Oncol ; 9: 1081, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681610

RESUMO

Solasonine (SS), a natural glycoalkaloid component, has been shown to have potent inhibitory activity and cytotoxicity against many cancer types. However, the precise mechanisms underlying this, particularly in hepatocellular carcinoma (HCC) are poorly understood. In this study, we showed that SS inhibited growth of HCC cells. Mechanistically, we observed that SS increased the expression of miR-375-3p, whereas reducing levels of long non-coding RNAs (lncRNAs) CCAT1 was noticed in HepG2 HCC and other cells. In addition, we found that SS repressed transcription factors, SP1 and interferon regulatory factor 5 (IRF5), protein expressions. There was a reciprocal interaction among miR-375-3p, CCAT1, and SP1. Moreover, SS inhibited IRF5 promoter activity, which was not observed in cells transfected with excessive expressed SP1 vectors. Interestingly, exogenously expressed IRF5 was shown to reverse expressions of SS-inhibited CCAT1 and induced-miR-375-3p; and neutralized SS-inhibited growth of HCC cells. Similar results were also found in vivo mouse model. Collectively, our results show that SS inhibits HepG2 HCC growth through the reciprocal regulation between the miR-375-3p and lncRNA CCAT1, and this results in transcription factor SP1-mediated reduction of IRF5 expression. The regulations and interactions among miR-375-3p, CCAT1, SP1, and IRF5 axis unveil a novel molecular mechanism underlying the anti-HCC growth by SS. IRF5 may be a potential target for treatment of HCC.

4.
Int J Mol Med ; 44(6): 2015-2026, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638181

RESUMO

Bruceine D is one of the active components of Brucea javanica (L.) Merr., which is widely used to treat cancer in China. The aim of the present study was to evaluate the potential effect of bruceine D against non­small­cell lung cancer (NSCLC) cells and delineate its underlying mechanisms. The results indicated that treatment with bruceine D markedly inhibited the proliferation of wild­type NSCLC cells and epidermal growth factor receptor­mutant cells in a dose­ and time­dependent manner, and significantly decreased the colony­forming ability and migration of A549 cells. Hoechst 33342 staining and flow cytometric analysis demonstrated that treatment with bruceine D effectively induced apoptosis of A549 cells. In addition, the proapoptotic effect of bruceine D was found to be associated with G0­G1 cell cycle arrest, accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde, depletion of glutathione levels and disruption of mitochondrial membrane potential. Additionally, pretreatment with N­acetylcysteine, a ROS scavenger, significantly attenuated the bruceine D­induced inhibition in A549 cells. Western blotting demonstrated that treatment with bruceine D significantly suppressed the expression of the anti­apoptotic proteins Bcl­2, Bcl­xL and X­linked inhibitor of apoptosis, enhanced the expression levels of apoptotic proteins Bax and Bak, and inhibited the expression of pro­caspase­3 and pro­caspase­8. Based on these results, it may be suggested that inhibition of A549 NSCLC cell proliferation by bruceine D is associated with the modulation of ROS­mitochondrial­mediated death signaling. This novel insight may provide further evidence to verify the anticancer efficacy of B. javanica, and support a role for bruceine D in the anti­NSCLC treatment.

5.
Zhen Ci Yan Jiu ; 44(10): 709-14, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31657159

RESUMO

OBJECTIVE: To investigate the mechanism of Warming-promotion needling underlying improvement of vascular dementia (VD) by observing its effect on learning-memory ability and expression of hippocampal nicotinic acetylcholine receptor(nAChR)subunit proteins and mRNAs in rats with VD. METHODS: Sixty male SD rats were randomized into normal control, model, medication, warming-promotion needling(WPN), uniform reinforcing-reducing needling (URRN), and needle-twirling groups (n=10 in each group). The VD model was established via repeated occlusion and reperfusion of the bilateral common carotid arteries. Rats of the medication group were fed with Nimodipine twice a day for 14 days. For rats of the 3 acupuncture groups, WPN, or URRN or needle-twirling was applied to"Dazhui"(GV14),"Baihui"(GV20) and"Shuigou"(GV26) for 30 min, once a day for 14 days. The learning-memory ability was detected by Morris water maze tests, and the expression levels of nAChR α4, α7 and ß2 subunit proteins and mRNAs in the hippocampus were detected by Western blot and real-time PCR, separately. RESULTS: Compared with the normal group, the escape latency of Morris water maze tests was significantly prolonged (P<0.05), and the number of the original safe-platform quadrant crossing was significantly reduced in the model group (P<0.05). The expression levels of nAChR α4, α7, ß2 subunit proteins and mRNAs (except ß2 mRNA) in the hippocampus were significantly decreased in the model group relevant to the normal group (P<0.05). Following the interventions, the increased escape latency, and the reduced safe-platform quadrant crossing times, and the down-regulated expression levels of hippocampal nAChR α4, α7, ß2 subunit proteins and mRNAs in the medication, WPN, URRN and needle-twirling groups were all reversed (P<0.05). The effects of WPN were significantly superior to those of URRN and needle-twirling in up-regulating nAChR α4, α7, ß2 subunit proteins and mRNAs (P<0.05). CONCLUSION: The warming-promotion needling can improve the learning and memory ability in VD rats, which may be related to its effects in up-regulating the expression of nAChR su-bunits in the hippocampus.


Assuntos
Demência Vascular , Receptores Nicotínicos , Animais , Hipocampo , Masculino , Memória , Agulhas , Ratos , Ratos Sprague-Dawley
6.
Med Oncol ; 36(11): 94, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605245

RESUMO

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a variety of solid tumors; nonetheless, they have not been well investigated and are still recognized as a relative contraindication for patients with a liver transplantation (LT) history, since ICIs treatment might potentially lead to graft rejection. The program death-1 (PD-1) and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways are implicated in the tolerance of transplanted organ, as well as blockade of the pathways, which contribute to eliminating tumors and may inadvertently lead to peripheral transplant rejection. Currently, no guidelines are available regarding the treatment for ICIs patients with a prior LT history. Therefore, this study was carried out to review the recent studies, attempting to introduce the ICIs-related graft rejection after LT from various aspects. We believed that ICIs could be given for the well-informed patients receiving LT and developed recurrence in a controlled setting. Typically, these patients should be treated according to a clinical care path or a prospective clinical trial, so as obtain a persistent anti-tumor immune response in the meantime of avoiding graft rejection, adjust the immunosuppression, reduce the possibility of graft loss following rejection, and have the opportunity to develop biomarkers for tumor response and transplant rejection.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Rejeição de Enxerto/induzido quimicamente , Transplante de Fígado , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Rejeição de Enxerto/imunologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
7.
World J Clin Cases ; 7(11): 1330-1336, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31236397

RESUMO

BACKGROUND: Sarcomatoid hepatocellular carcinoma (SHC) combined with paraneoplastic leukemoid reaction (PLR), which is associated with a poor prognosis, is rarely seen in the clinic. Here, we report the case of a patient in the above situation. CASE SUMMARY: A 75-year-old female patient with a past medical history of hypertension and cerebral infarction paid a hospital visit as a result of right upper quadrant abdominal pain and anorexia for two months. Laboratory examination revealed a white blood cell (WBC) count of 43790/µL, which was then increased up to 77050/µL. In addition, the results of bone marrow examination suggested a leukemoid reaction. Computed tomography (CT) revealed a focal hepatic mass, which was confirmed through pathological examination to be an SHC postoperatively. In addition, the WBC count had fallen to a normal level before she left the hospital. However, the patient died two and a half months after the second hospital admission. CONCLUSION: This is a rare case of SHC combined with PLR, both of which have an extremely poor prognosis.

8.
Phytomedicine ; 52: 272-283, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30599908

RESUMO

BACKGROUND: Berberine (BBR) is the most abundant and major active constituent of Rhizoma Coptidis (RC), which has been widely used to treat inflammatory diseases in traditional oriental medicine. Despite BBR has been found to exhibit pronounced anti-inflammatory effect, the anti-inflammatory activities of its natural derivatives were sparsely dissected out. PURPOSE: To comparatively investigate the anti-inflammatory potential of BBR, and its natural oxoderivative (oxyberberine, OBB) and reduced derivative (dihydroberberine, DHBB) in vitro and in vivo, and delineate the possible underlying mechanism. METHODS: LC-MS/MS was used to identify the natural derivatives of BBR in RC. The potential anti-inflammatory properties of BBR and its natural derivatives were comparatively evaluated in vitro by lipopolysaccharide (LPS)-induced RAW264.7 macrophages cells, and in vivo via three typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by ELISA, qRT-PCR and Western blotting. RESULTS: LC-MS/MS led to the identification of BBR, OBB and DHBB in RC ethyl acetate extract. The in vitro assay indicated that BBR, OBB and DHBB (1.25, 2.5 and 5 µM) pretreatment significantly decreased the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and nitricoxide (NO), and inhibited the mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitricoxide synthase (iNOS) in a dose-dependent manner, with relative efficiency of OBB > BBR > DHBB. Furthermore, OBB, BBR and DHBB remarkably inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 and inhibitory kappa Bα (IκBα). In vivo, BBR (20 mg/kg) and OBB (5, 10, and 20 mg/kg) pretreatment significantly ameliorated the xylene-induced ear edema, carrageenan-stimulated paw edema, and acetic acid-elicited vascular permeability in mice in a dose-dependent manner, with OBB exhibiting superior anti-inflammatory effect at the same dose (20 mg/kg). Histopathological analysis indicated that OBB and BBR could markedly attenuate the inflammatory deterioration and decrease the cellular infiltration in paw tissues. Additionally, the carrageenan-induced increases in TNF-α, IL-6, IL-1ß, PGE2 and NO productions, and COX-2 and iNOS mRNA expressions were effectually and concentration-dependently suppressed by OBB and BBR pretreatment. CONCLUSION: The anti-inflammatory activity of BBR and its natural derivatives was in the order of OBB > BBR > DHBB. OBB was for the first time found to be endowed with pronounced anti-inflammatory property, which was probably associated with suppressing the activation of NF-κB signaling pathway, and the subsequent gene expressions and productions of pro-inflammatory mediators. The results might contribute to illuminating the pharmacodynamic underpinnings of RC and provide evidence for developing OBB as a safe and promising natural lead compound in inflammation treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Animais , Berberina/análogos & derivados , Carragenina/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
Opt Express ; 26(21): 27528-27544, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30469818

RESUMO

An anamorphic fractional Fourier transform (AFrFT) lens based on graded index (GRIN) materials and designed with the help of transformation optics is proposed. Cross sections of the new lens are mapped from those of a standard quadratic GRIN lens via gradually varied conformal transformations. This lens can afford complicated anamorphic patterns in the fractional Fourier domain for any fractional order, possibly leading to many new applications. Three samples are shown, which offer higher distinguishability in the fractional Fourier domain, a more precisely recognized matched filter, and stronger security of the AFrFT-based optical encryption. With metamaterials development, including three-dimensional printing technologies, GRIN media fabrication has become more convenient; thus, the proposed lens may have vast application prospects in signal processing. The design also demonstrates the ability and flexibility of the transformation optics in exploring new Fourier optics devices.

10.
Cell Physiol Biochem ; 49(4): 1615-1632, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30223276

RESUMO

BACKGROUND/AIMS: We previously showed that the major bioactive compound of Atractylodes macrocephula Koidz atractylenolide 1 (ATL-1) inhibited human lung cancer cell growth by suppressing the gene expression of 3-Phosphoinositide dependent protein kinase-1 (PDK1 or PDPK1). However, the potentially associated molecules and downstream effectors of PDK1 underlying this inhibition, particularly the mechanism for enhancing the anti-tumor effects of epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs), remain unknown. METHODS: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Western blot analyses were performed to examine the protein expressions of PDK1 and of zeste homolog 2 (EZH2). The levels of long non-coding RNA (lncRNA) and HOX transcript antisense RNA (HOTAIR) were examined via qRT-PCR. RNA-binding protein immunoprecipitation assays were used to analyze HOTAIR interaction with EZH2. The promoter activity of the EZH2 gene was determined using Secrete-Pair Dual Luminescence Assay Kit. Exogenous expressions of PDK1, HOTAIR, and EZH2 were conducted via transient transfection assays. A xenografted tumor model was used to further evaluate the effect of ATL-1 in the presence or absence of erlotinib in vivo. RESULTS: We showed that the combination of ATL-1 and EGFR-TKI erlotinib further inhibited growth and induced cell arrest of the human lung cancer cells, determined by both MTT and flow cytometry assays. ATL-1 inhibited the protein expression and the promoter activity of EZH2, which was reversed in cells with PDK1 overexpression. Interestingly, ATL-1 inhibited the expression levels of HOTAIR. While silencing HOTAIR inhibited the expressions of PDK1 and EZH2, overexpression of HOTAIR reduced the ATL-1-reduced PDK1 and EZH2 protein expressions and EZH2 promoter activity. In addition, ATL-1 reduced the HOTAIR binding to the EZH2 protein. Moreover, we found that exogenously expressed EZH2 antagonized the effect of ATL-1 on cell growth inhibition. Consistent with the in vitro results, ATL-1 inhibited tumor growth and the expression levels of HOTAIR, protein expressions of EZH2 and PDK1 in vivo. Importantly, there was synergy of the combination of ATL-1 and erlotinib in this process. CONCLUSION: Here, we provide the first evidence that ATL-1 inhibits lung cancer cell growth through inhibiting not only the PDK1 but also the lncRNA HOTAIR, which results in the reduction of one downstream effector EZH2 expression. The novel interplay between the HOTAIR and EZH2, as well as repressions of the PDK1 and HOTAIR coordinate the overall effects of ATL-1. Importantly, the combination of ATL-1 and EGFR-TKI erlotinib exhibits synergy. Thus, targeting the PDK1- and HOTAIR-mediated downstream molecule EZH2 by the combination of ATL-1 and erlotinib potentially facilitates the development of an additional novel strategy to combat lung cancer.


Assuntos
Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Cloridrato de Erlotinib/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lactonas/farmacologia , RNA Longo não Codificante/metabolismo , Sesquiterpenos/farmacologia , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/antagonistas & inibidores , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/genética , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Cloridrato de Erlotinib/uso terapêutico , Feminino , Humanos , Lactonas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Sesquiterpenos/uso terapêutico
11.
World J Gastroenterol ; 24(29): 3281-3292, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30090008

RESUMO

AIM: To investigate the prognostic role of fibrinogen-to-albumin ratio (FAR) on patients with gallbladder cancer (GBC) in this study. METHODS: One hundred and fifty-four GBC patients were retrospectively analyzed, who received potentially curative cholecystectomy in our institute from March 2005 to December 2017. Receiver operating characteristic curve (ROC curve) was used to determine the optimal cut-offs for these biomarkers. In addition, Kaplan-Meier survival analysis as well as multivariate analysis were applied for prognostic analyses. RESULTS: ROC curve revealed that the optimal cut-off value for FAR was 0.08. FAR was significantly correlated with age (P = 0.045), jaundice (P < 0.001), differentiation (P = 0.002), resection margin status (P < 0.001), T stage (P < 0.001), TNM stage (P < 0.001), and CA199 (P < 0.001) as well as albumin levels (P < 0.001). Multivariate analysis indicated that the resection margin status [hazard ratio (HR): 2.343, 95% confidence interval (CI): 1.532-3.581, P < 0.001], TNM stage (P = 0.035), albumin level (HR = 0.595, 95%CI: 0.385-0.921, P = 0.020) and FAR (HR: 2.813, 95%CI: 1.765-4.484, P < 0.001) were independent prognostic factors in GBC patients. CONCLUSION: An elevated preoperative FAR was significantly correlated with unfavorable overall survival in GBC patients, while an elevated preoperative albumin level was a protective prognostic factor for patients with GBC. The preoperative FAR could be used to predict the prognosis of GBC patients, which was easily accessible, cost-effective and noninvasive.


Assuntos
Biomarcadores Tumorais/sangue , Fibrinogênio/análise , Neoplasias da Vesícula Biliar/sangue , Albumina Sérica/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Colecistectomia , Estudos de Viabilidade , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
12.
Trials ; 19(1): 367, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29996882

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic, recurring condition, prevalent in the general population. Current medication treatments usually leave patients undertreated. Nowadays, Chinese medicine (CM) is being considered as a promising treatment approach for IBS. However, due to methodological limitations, there is no strong evidence to support CM. Although IBS relapses are common, the relapse assessment has always been neglected in CM study designs. Meanwhile, in clinical practice and studies, it has been found that certain CM formulas can only benefit certain kinds of patients. Discovering what population and illness characteristics likely respond to outcomes may help improve the effectiveness of CM. The aims of this study are to evaluate the efficacy and safety of Tiao-Chang Ke-Min (TCKM) granules for IBS, especially in reducing IBS symptoms' relapse, by a high-quality randomized controlled trial and then to optimize the indication of the TCKM granules. METHODS/DESIGN: This is a parallel-group, randomized, double-blind, placebo-controlled trial embedded with outcome predictive factors. Eligible patients with diarrhea-predominant IBS will be randomized into either a TCKM granule group or a placebo group. Patients from both groups will receive health education. The treatment duration is 4 weeks and the follow-up is 12 weeks. The primary outcome is global improvement measured with adequate relief (AR). The second outcome measures include time until relief, time until first relapse, total relapse times, long-term effectiveness, individual symptoms, IBS-Symptom Severity Score (IBS-SSS), IBS-Quality of Life Questionnaire (IBS-QOL), and Hospital Anxiety and Depression Scale (HADS). Predictive factors associated with patient and illness characteristics have been widely collected. These factors will be embedded in this trial for further identification. DISCUSSION: This trial may provide high-quality evidence on the efficacy and safety of TCKM granules for IBS and a more accurate indication. Importantly, this trial will provide a new research method for improving the therapeutic effects of CM for clinicians and researchers. To address IBS relapse assessment, a series of special definitions of relapse incidents has been made for this trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17010600 . Registered on 9 February 2017.


Assuntos
Diarreia/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Síndrome do Intestino Irritável/psicologia , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Garantia da Qualidade dos Cuidados de Saúde , Qualidade de Vida , Projetos de Pesquisa , Índice de Gravidade de Doença
13.
World J Gastroenterol ; 24(19): 2120-2129, 2018 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-29785080

RESUMO

AIM: To clarify the previous discrepant conclusions, we performed a meta-analysis to evaluate the prognostic value of red cell distribution width (RDW) in esophageal cancer (EC). METHODS: We searched the PubMed, EMBASE, Web of Science and Cochrane Library databases to identify clinical studies, followed by using STATA version 12.0 for statistical analysis. Studies that met the following criteria were considered eligible: (1) Studies including EC patients who underwent radical esophagectomy; (2) studies including patients with localized disease without distant metastasis; (3) studies including patients without preoperative neoadjuvant therapy; (4) studies including patients without previous antiinflammatory therapies and with available preoperative laboratory outcomes; (5) studies reporting association between the preoperative RDW and overall survival (OS)/disease-free survival (DFS)/cancer-specific survival (CSS); and (6) studies published in English. RESULTS: A total of six articles, published between 2015 and 2017, fulfilled the selection criteria in the end. Statistical analysis showed that RDW was not associated with the prognosis of EC patients, irrespective of OS/CSS [hazard ratio (HR) = 1.27, 95% confidence interval (CI): 0.97-1.57, P = 0.000] or DFS (HR = 1.42, 95%CI: 0.96-1.88, P = 0.000). Subgroup analysis indicated that elevated RDW was significantly associated with worse OS/CSS of EC patients when RDW > 13% (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000), when the patient number ≤ 400 (HR = 1.45, 95%CI: 1.13-1.76, P = 0.000) and when the study type was retrospective (HR = 1.42, 95%CI : 1.16-1.69, P = 0.000). CONCLUSION: Contrary to our general understanding, this meta-analysis revealed that RDW cannot serve as an indicator of poor prognosis in patients with EC. However, it may still be a useful predictor of unfavorable prognosis using an appropriate cut-off value.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Índices de Eritrócitos , Neoplasias Esofágicas/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Esôfago/patologia , Esôfago/cirurgia , Humanos , Terapia Neoadjuvante/métodos , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida
14.
World J Gastroenterol ; 24(13): 1451-1463, 2018 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-29632426

RESUMO

AIM: To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma (GBC). METHODS: The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. Based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0. RESULTS: ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival (OS) (HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735 (for preoperative plasma fibrinogen only) and 0.729 (for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199 (P < 0.001), resection margin (P < 0.001) and TNM stage (P = 0.010) were independent prognostic factors for GBC. CONCLUSION: The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Carcinoma/sangue , Fibrinogênio/análise , Neoplasias da Vesícula Biliar/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/cirurgia , China/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
15.
Artigo em Inglês | MEDLINE | ID: mdl-29366783

RESUMO

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

16.
Appl Opt ; 56(32): 9119-9125, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29131202

RESUMO

Estimating the chirpiness of a spatial chirp signal is important in many optical engineering applications. With the help of transformation optics, a new kind of fractional Fourier transform lens is designed by deforming the conventional graded index lens through conformal mapping, which can manipulate the chirpiness of the input chirp signal. The low-input chirpiness is magnified by the transformation material, and the error of the detection is kept approximately the same; thus, the designed lens has enhanced chirpiness detection precision and distinguishability for low chirpiness. The design is validated by numerical simulations.

17.
World J Surg Oncol ; 15(1): 147, 2017 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-28774300

RESUMO

BACKGROUND: Previous studies have revealed the importance of microRNAs' (miRNAs) function as biomarkers in diagnosing human bladder cancer (BC). However, the results are discordant. Consequently, the possibility of miRNAs to be BC biomarkers was summarized in this meta-analysis. METHODS: In this study, the relevant articles were systematically searched from CBM, PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI). The bivariate model was used to calculate the pooled diagnostic parameters and summary receiver operator characteristic (SROC) curve in this meta-analysis, thereby estimating the whole predictive performance. STATA software was used during the whole analysis. RESULTS: Thirty-one studies from 10 articles, including 1556 cases and 1347 controls, were explored in this meta-analysis. In short, the pooled sensitivity, area under the SROC curve, specificity, positive likelihood ratio, diagnostic odds ratio, and negative likelihood ratio were 0.72 (95%CI 0.66-0.76), 0.80 (0.77-0.84), 0.76 (0.71-0.81), 3.0 (2.4-3.8), 8 (5.0-12.0), and 0.37 (0.30-0.46) respectively. Additionally, sub-group and meta-regression analyses revealed that there were significant differences between ethnicity, miRNA profiling, and specimen sub-groups. These results suggested that Asian population-based studies, multiple-miRNA profiling, and blood-based assays might yield a higher diagnostic accuracy than their counterparts. CONCLUSIONS: This meta-analysis demonstrated that miRNAs, particularly multiple miRNAs in the blood, might be novel, useful biomarkers with relatively high sensitivity and specificity and can be used for the diagnosis of BC. However, further prospective studies with more samples should be performed for further validation.


Assuntos
Biomarcadores Tumorais/sangue , MicroRNAs/sangue , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/genética , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/urina , Cistoscopia/efeitos adversos , Humanos , Estadiamento de Neoplasias , Proteínas Nucleares/urina , Razão de Chances , Curva ROC , Análise de Regressão , Sensibilidade e Especificidade , Urinálise/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina
18.
PLoS One ; 12(5): e0178781, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28562696

RESUMO

Steroid-associated osteonecrosis (SAON) might induce bone collapse and subsequently lead to joint arthroplasty. Core decompression (CD) is regarded as an effective therapy for early-stage SAON, but the prognosis is unsatisfactory due to incomplete bone repair. Parathyroid hormone[1-34] (PTH[1-34]) has demonstrated positive efficacy in promoting bone formation. We therefore evaluated the effects of PTH on improving the effects of CD in Early-Stage SAON. Distal femoral CD was performed two weeks after osteonecrosis induction or vehicle injection, with ten of the ON-induced rabbits being subjected to six-week PTH[1-34] treatment and the others, including ON-induced and non-induced rabbits, being treated with vehicle. MRI confirmed that intermittent PTH administration improved SAON after CD therapy. Micro-CT showed increased bone formation within the tunnel. Bone repair was enhanced with decreased empty osteocyte lacunae and necrosis foci area, resulting in enhanced peak load and stiffness of the tunnel. Additionally, PTH enlarged the mean diameter of vessels in the marrow and increased the number of vessels within the tunnels, as well as elevated the expression of BMP-2, RUNX2, IGF-1, bFGF and VEGF, together with serum OCN and VEGF levels. Therefore, PTH[1-34] enhances the efficacy of CD on osteogenesis and neovascularization, thus promoting bone and blood vessels repair in the SAON model.


Assuntos
Corticosteroides/efeitos adversos , Descompressão Cirúrgica , Modelos Animais de Doenças , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese , Osteonecrose/tratamento farmacológico , Hormônio Paratireóideo/farmacologia , Animais , Masculino , Osteonecrose/induzido quimicamente , Osteonecrose/fisiopatologia , Coelhos
19.
Eur J Pharmacol ; 811: 222-231, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28648405

RESUMO

Coptisine is one of the main constituents of Coptis chinensis which has been widely used for the remedy of inflammatory disorders. Although the biological activities of coptisine have been well known, the pharmacological properties of its free base have seldomly been elucidated thus far. The aim of this study was to investigate the potential anti-inflammatory properties of coptisine free base (CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema. The results exhibited that CFB exerted a dose-dependent suppression on ear edema induced by xylene, significantly mitigated the aggravation of vascular permeability caused by acetic acid and paw edema induced by carrageenan. Additionally, CFB significantly suppressed the productions of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and tumor necrosis factor (TNF-α) in the drug-treated groups as compared with the vehicle group after treatment with carrageenan. Signaling events of nuclear factor-κB (NF-κB) translocation, such as p-IKKα, p-IKKß, p-IκBα and p65 (nucleus) were significantly inactivated, while inhibitor of nuclear factor κBα (IκBα) and p65 (cytosolic) were markedly up-regulated by CFB. Furthermore, CFB also significantly suppressed the mitogen-activated protein kinase (MAPK) pathway by blocking the phosphorylation of p-p38 (phospho-p38 mitogen-activated protein kinases) and p-JNK (phospho-c-jun N-terminal kinase) but not p-ERK (phospho-extracellular signal-regulated kinase). Hence, CFB efficiently prevented inflammation, at least partially, via inhibition of NF-κB and MAPK pathways. These findings provided a pioneering pharmacological basis for the anti-inflammatory effect of CFB and suggested CFB might be a potential candidate for the therapy of inflammatory disorders.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/análogos & derivados , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Ácido Acético/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Berberina/farmacologia , Berberina/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/metabolismo , Edema/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
20.
Front Neurol ; 8: 150, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28469595

RESUMO

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating and complicated disease with significant morbidity and mortality. Previous studies have shown that genetic susceptibility may play an important role in the outcome of a given individual with aSAH. This study evaluates the potential association in effects of the APOE allele on the early brain injury (EBI) in light of elevated intracranial pressure (ICP) and cerebral perfusion disorders in a consecutive series of non-comatose Chinese patients with aSAH. A total of 122 patients with aSAH (54 males and 68 females) were enrolled in this study. Demographic and clinical data were collected. We measured ICP before microsurgical clipping or endovascular coiling during the first 72 h after aneurysm rupture. Computed tomography perfusion (CTP) examination in patients was performed before treatment. The distributions of APOE genotypes and alleles matched Hardy-Weinberg law (p > 0.05). In this study, 68 patients (55.7%) had a normal ICP, whereas 54 (44.3%) had an elevated ICP. Fourteen of 21 patients with APOE ε4 had an elevated ICP, which was significantly different from those without APOE ε4 (p = 0.03). The patients with the ε4 allele had a higher incidence of elevated ICP [p = 0.009, 95% confidence interval (CI) = 1.481-15.432, odds ratio = 4.780] than those without this allele. For CTP measurements, a lower mean cerebral blood flow (difference, -4.74; 95% CI, 0.53-8.94 s, p = 0.03), longer mean transit time (difference, 0.47; 95% CI, -0.87 to -0.78, p = 0.02), and time-to-peak (difference, 2.29; 95% CI, -3.64 to -0.93 s, p = 0.02) were observed in patients with ε4 allele than in those without in the internal capsule regions. In conclusion, the APOE ε4 allele predisposes patients to elevated ICP and perfusion disorders in white matter regions during the first 72 h after aSAH. The presence of an APOE ε4 allele plays an important role in the EBI response to aSAH.

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