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With the surge in the human coastal population and the increasing frequency of human activities along the coast, cases of marine envenomation, particularly jellyfish envenomation, have notably risen. Jellyfish stings can induce a spectrum of symptoms that vary in severity, encompassing skin injuries, acute systemic venom effects, delayed indirect sequelae, and even fatality, causing significant distress to patients. Among these manifestations, the occurrence of skin lesions following jellyfish stings is prevalent and substantial. These lesions are characterized by evident blister formation, development of bullae, subcutaneous hemorrhage, erythema, papules, wheal, ecchymosis, and ulceration or skin necrosis. Local cutaneous manifestations may persist for several weeks or even months after the initial sting. Despite aggressive treatment, many skin injuries still result in significant pigmentation or scarring after recovery. To address this issue effectively, it is imperative to conduct comprehensive evidence-based medical research, elucidate various components within jellyfish venom, and elucidate its pathogenic mechanism to develop targeted treatment programs. This article aims to review the skin symptoms, pathophysiology, and management of jellyfish stings. Such considerations can provide comprehensive guidance to medical professionals and the public and minimize the harm caused by jellyfish stings.
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Mordeduras e Picadas , Venenos de Cnidários , Pele , Humanos , Mordeduras e Picadas/terapia , Mordeduras e Picadas/fisiopatologia , Mordeduras e Picadas/complicações , Animais , Pele/patologia , Pele/fisiopatologia , Cnidários , Dermatopatias/terapia , Dermatopatias/fisiopatologia , Dermatopatias/etiologia , CifozoáriosRESUMO
BACKGROUND: Inflammation-related parameters have been revealed to have prognostic value in multiple caners. However, the significance of some inflammation-related parameters, including the peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and prognostic nutritional index (PNI), remains controversial in T1-2 rectal cancer (RC). METHODS: Clinical data of 154 T1-2 RC patients were retrospectively reviewed. The cut-off values for NLR, PLR, LMR, and PNI were determined by receiver operating characteristic curves. The relationships of these parameters with postoperative morbidities and prognosis were statistically analysed. RESULTS: The optimal cut-off values for preoperative NLR, PLR, LMR and PNI were 2.8, 140.0, 3.9, and 47.1, respectively. Significant but heterogeneous associations were found between NLR, PLR, LMR and PNI and clinicopathological factors. In addition, high NLR, high PLR, and low PNI were correlated with an increased postoperative morbidity rate. Patients with high NLR/PLR or low LMR/PNI had lower OS and DFS rates. On multivariate analysis, only high NLR was identified as an independent risk factor for poor DFS. CONCLUSIONS: NLR, PLR, and PNI are valuable factors for predicting postoperative complications in T1-2 RC patients. A preoperative NLR of more than 2.8 is an independent prognostic factor for poor DFS in T1-2 RC patients.
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Monócitos/metabolismo , Neutrófilos/metabolismo , Neoplasias Retais/sangue , Neoplasias Retais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Contagem de Plaquetas , Prognóstico , Curva ROC , Neoplasias Retais/mortalidade , Estudos RetrospectivosRESUMO
BACKGROUND: As a serious clinical disease, ischemic stroke is usually detected through magnetic resonance imaging and computed tomography. In this study, a noninvasive, non-contact, real-time continuous monitoring system was constructed on the basis of magnetic induction phase shift (MIPS) technology. The "thrombin induction method", which conformed to the clinical pathological development process of ischemic stroke, was used to construct an acute focal cerebral ischemia model of rabbits. In the MIPS measurement, a "symmetric cancellation-type" magnetic induction sensor was used to improve the sensitivity and antijamming capability of phase detection. METHODS: A 24-h MIPS monitoring experiment was carried out on 15 rabbits (10 in the experimental group and five in the control group). Brain tissues were taken from seven rabbits for the 2% triphenyl tetrazolium chloride staining and verification of the animal model. RESULTS: The nonparametric independent-sample Wilcoxon rank sum test showed significant differences (p < 0.05) between the experimental group and the control group in MIPS. Results showed that the rabbit MIPS presented a declining trend at first and then an increasing trend in the experimental group, which may reflect the pathological development process of cerebral ischemic stroke. Moreover, TTC staining results showed that the focal cerebral infarction area increased with the development of time CONCLUSIONS: Our experimental study indicated that the MIPS technology has a potential ability of differentiating the development process of cytotoxic edema from that of vasogenic edema, both of which are caused by cerebral ischemia.
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Hemorragia Cerebral/fisiopatologia , Condutividade Elétrica , Fenômenos Magnéticos , Monitorização Fisiológica/métodos , Doença Aguda , Animais , Coelhos , Fatores de TempoRESUMO
Sixty novel allogibberic acid derivatives containing 1,2,3-triazole pharmacophore were designed and synthesized. The key chemical processes include aromatization of the A ring in gibberellins, formation of allogibberic azides and its copper mediated Huisgen 1,3-dipolar cycloaddition with alkynes. A number of hybrids containing α,ß-unsaturated ketone moiety exhibited excellent in vitro cytotoxic activities. Some of the hybrids were more selective to MCF-7 and SW480 cell lines with IC50 values at least 8-fold more cytotoxic than cisplatin (DDP). The most potent compounds C43 and C45 are more cytotoxic than cisplatin (DDP) against all tested five tumor cell lines, with IC50 values of 0.25-1.72⯵M. Mechanism of action studies indicated that allogibberic-triazole derivative C45 could induce the S phase cell cycle arrest and apoptosis in SMMC-7721 cell lines.
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Antineoplásicos/farmacologia , Giberelinas/farmacologia , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Giberelinas/síntese química , Giberelinas/química , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
Grasslands, the largest carbon pool in China, possess enormous potential for carbon sequestration. Increasing the stomatal aperture to increase the CO2 absorption capacity is a potential method to improve plant photosynthetic efficiency and ultimately enhance the carbon sequestration capacity of grass plants. Research on stomatal aperture regulation has focused mostly on Arabidopsis or crops, while research on grass plants in these areas is scarce, which seriously restricts the implementation of this grassland carbon sequestration strategy. Here, a widely used ecological grass, centipedegrass, was used as the experimental material. First, a convenient method for observing the stomatal aperture was developed. The leaves were floated in a potassium ion-containing open solution (67 mM KCl, pH 6.0) with the adaxial surface rather than the abaxial surface in contact with the solution and were cultivated under light for 1.5 h. Then, nail polish was applied on the adaxial surface, and a large number of open stomata were imprinted. Second, with the help of this improved method, the concentrationâresponse characteristics of the stomatal aperture to eleven environmental stimuli were tested. The stomatal aperture is dependent on these environmental stimuli in a concentration-dependent manner. The addition of 100 µM brassinolide led to the maximal stomatal aperture. This study provided a technical basis for manipulating stomatal opening to increase the carbon sequestration capacity of centipedegrass.
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Estômatos de Plantas , Poaceae , Estômatos de Plantas/fisiologia , Poaceae/fisiologia , Poaceae/metabolismo , Folhas de Planta/fisiologia , Folhas de Planta/metabolismo , Brassinosteroides/metabolismoRESUMO
Gene therapy and nerve stem cells isolated from the developing human enteric nervous system (ENS) are significant. They may open the route for the cell therapy of Hirschsprung's disease (HD). We have constructed the recombinant adenovirus-carrying glial cell line-derived neurotrophic factor (GDNF) and endothelin receptor B (EDNRB) gene, and investigated the exosomatic coexpression in neural stem cells. The recombinant adenovirus Ad-GE coexpressing GDNF and EDNRB gene was constructed by the AdEasy system and confirmed by the reverse transcription polymerase chain reaction (RT-PCR) method. Expression of exogenous genes in neural stem cells after transfection was confirmed by the flow cytometry and real-time fluorescence quantitative PCR. Fragments of pAd Track-CMV-GE were consistent with GDNF and EDNRB. The green fluorescence of the positive cells was followed by fluorescence microscopy at 24 h after NSCs had been transfected, reaching a peak at 72 h after transfection. Flow cytometry showed that the efficiency of transfection was 15.0, 23.6, and 25.4% at 24, 48 and 72 h respectively. Real-time fluorescence quantitative PCR showed the expression levels of mRNA of GDNF and EDNRB in 48 and 72 h groups were obviously higher than that in 24 and 96 h groups. Recombinant adenovirus carrying GDNF and EDNRB genes are coexpressed in neural stem cells, which may offer the possibility of a novel approach to local combination gene therapy for Hirschsprung's disease.
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Adenoviridae/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Receptor de Endotelina B/metabolismo , Animais , Células Cultivadas , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Microscopia de Fluorescência , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor de Endotelina B/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genéticaRESUMO
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Figs. 2, 4 and 8 were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Chen W, Wang J, Liu S, Wang S, Cheng Y, Zhou W, Duan C and Zhang C: MicroRNA3613p suppresses tumor cell proliferation and metastasis by directly targeting SH2B1 in NSCLC. J Exp Clin Cancer Res 35: 76, 732516, 2016]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 16881694, 2017; DOI: 10.3892/or.2017.5794].
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Reasonable nitrogen fertilizer application is an important strategy to maintain optimal growth of grasslands, thereby enabling them to better fulfil their ecological functions while reducing environmental pollution caused by high nitrogen fertilizer production and application. Optimizing the ammonium (NH4 +):nitrate (NO3 -) ratio is a common approach for growth promotion in crops and vegetables, but research on this topic in grass plants has not received sufficient attention. Centipedegrass, which is widely used in landscaping and ecological protection, was used as the experimental material. Different NH4 +:NO3 - ratios (0: 100, 25:75, 50:50, 75:25, 100:0) were used as the experimental treatments under hydroponic conditions. By monitoring the physiological and morphological changes under each treatment, the appropriate NH4 +:NO3 - ratio for growth and its underlying mechanism were determined. As the proportion of ammonium increased, the growth showed a "bell-shaped" response, with the maximum biomass and total carbon and nitrogen accumulation achieved with the NH4 +:NO3 - ratio of 50:50 treatment. Compared with the situation where nitrate was supplied alone, increasing the ammonium proportion increased the whole plant biomass by 93.2%, 139.7%, 59.0%, and 30.5%, the whole plant nitrogen accumulation by 44.9%, 94.6%, 32.8%, and 54.8%, and the whole plant carbon accumulation by 90.4%, 139.9%, 58.7%, and 26.6% in order. As a gateway for nitrogen input, the roots treated with an NH4 +:NO3 - ratio of 50:50 exhibited the highest ammonium and nitrate uptake rate, which may be related to the maximum total root length, root surface area, average root diameter, root volume, and largest root xylem vessel. As a gateway for carbon input, leaves treated with an NH4 +:NO3 - ratio of 50:50 exhibited the highest stomatal aperture, stomatal conductance, photosynthetic rate, transpiration rate, and photosynthetic products. The NH4 +:NO3 - ratio of 50:50 treatment had the largest stem xylem vessel area. This structure and force caused by transpiration may synergistically facilitate root-to-shoot nutrient translocation. Notably, the change in stomatal opening occurred in the early stage (4 hours) of the NH4 +:NO3 - ratio treatments, indicating that stomates are structures that are involved in the response to changes in the root NH4 +:NO3 - ratio. In summary, we recommend 50:50 as the appropriate NH4 +:NO3 - ratio for the growth of centipedegrass, which not only improves the nitrogen use efficiency but also enhances the carbon sequestration capacity.
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OBJECTIVE: To investigate the protective effect of quercetin on diabetic nephropathy and to explore its possible mechanism. METHODS: Type 2 diabetes mellitus rat model was established by feeding high-carbohydrate-fat diet and injecting with streptozotocin. At 72 hour after injection, blood samples were collected from the tail veins of all rats. Those rats with blood glucose level ≥ 16.7 mmol/L were considered as the diabetes model been successfully established. The model rats were randomly divided into type 2 diabetic group (group DM, n = 9) and quercetin group (group QUE, n = 9). Other rats were used as normal controls (group NC, n = 8). All rats were performed by intragastric administration for 8 weeks. At the end of experiment, the rats were sacrificed and fasting plasma glucose (FPG), fasting insulin(FIns), serum creatinine (SCr), blood urea nitrogen (BUN), TG, TC, LDL-C, 24 h urine protein (24 h UP), and kidney index (KI) were evaluated. Pathological changes of kidney were observed by periodic acid-silver methenamine (PASM). The expressions of ubiquitin and NF-κB p65 on glomeruli were examined by immunohistochemical method, and its association with the incidence of proteinuria was analyzed. RESULTS: In groups DM and QUE, the level of FPG [(25.45 ± 1.23) mmol/L and (19.99 ± 1.20) mmol/L], FIns [(25.67 ± 2.58) mU/L and (19.29 ± 1.80) mU/L], SCr [(44.00 ± 2.53) µmol/L and (34.43 ± 2.23) µmol/L], BUN[(11.60 ± 0.39) mmol/L and (8.20 ± 0.37) mmol/L], TG[(3.32 ± 0.22)mmol/L and (2.43 ± 0.25) mmol/L], TC [(2.95 ± 0.21) mmol/L and (2.24 ± 0.17) mmol/L], LDL-C [(2.03 ± 0.22) mmol/L and (1.49 ± 0.13) mmol/L], 24 h UP[(46.67 ± 2.50) mg/24 h and (25.57 ± 2.82) mg/24 h] and KI [(9.76 ± 0.30)×10³ and (8.44 ± 0.26)×10³] were significantly increased than the indexes of group NC [(6.56 ± 0.41) mmol/L, (12.63 ± 1.41) mU/L, (22.88 ± 2.36) µmol/L, (5.45 ± 0.51) mmol/L, (1.64 ± 0.11) mmol/L, (1.33 ± 0.17) mmol/L, (0.46 ± 0.05) mmol/L, (12.38 ± 1.19)/24 h and (6.78 ± 0.12)×10³]. Moreover, the above indexes in group QUE were obviously lower than group DM. There was evidence of pathological changes associated with diabetes, such as focal and segmental sclerosis and thickened basement and mesangial expansion. The expressions of ubiquitin and NF-κB p65 in renal tissues of group DM increased significantly (P < 0.01). The expression of ubiquitin and NF-κB p65 were positively related with the level of 24 h UP (r = 0.893, 0.879, P < 0.01). Compared with group DM, all above indexes in group QUE were markedly alleviated (P < 0.01). The expression of ubiquitin and NF-κB p65 was reduced but didn't reach level in group NC (P < 0.01). CONCLUSION: The increased expression of NF-κB induced by ubiquitin-proteasome system may participate in the pathogenesis of proteinuria in diabetic nephropathy. Quercetin has renal protective effects partly through reducing NF-κB p65 expression.
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Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Rim/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Quercetina/farmacologia , Fator de Transcrição RelA/metabolismo , Ubiquitina/metabolismo , Animais , Nefropatias Diabéticas/metabolismo , Rim/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Ca(2+) signaling pathways are well studied in cardiac myocytes, but not in cardiac fibroblasts. The aim of the present study is to characterize Ca(2+) signaling pathways in cultured human cardiac fibroblasts using confocal scanning microscope and RT-PCR techniques. It was found that spontaneous intracellular Ca(2+) (Ca(i) (2+)) oscillations were present in about 29% of human cardiac fibroblasts, and the number of cells with Ca(i) (2+) oscillations was increased to 57.3% by application of 3% fetal bovine serum. Ca(i) (2+) oscillations were dependent on Ca(2+) entry. Ca(i) (2+) oscillations were abolished by the store-operated Ca(2+) (SOC) entry channel blocker La(3+), the phospholipase C inhibitor U-73122, and the inositol trisphosphate receptors (IP3Rs) inhibitor 2-aminoethoxydiphenyl borate, but not by ryanodine. The IP3R agonist thimerosal enhanced Ca(i) (2+) oscillations. Inhibition of plasma membrane Ca(2+) pump (PMCA) and Na(+)-Ca(2+) exchanger (NCX) also suppressed Ca(i) (2+) oscillations. In addition, the frequency of Ca(i) (2+) oscillations was reduced by nifedipine, and increased by Bay K8644 in cells with spontaneous Ca(2+) oscillations. RT-PCR revealed that mRNAs for IP3R1-3, SERCA1-3, Ca(V)1.2, NCX3, PMCA1,3,4, TRPC1,3,4,6, STIM1, and Orai1-3, were readily detectable, but not RyRs. Our results demonstrate for the first time that spontaneous Ca(i) (2+) oscillations are present in cultured human cardiac fibroblasts and are regulated by multiple Ca(2+) pathways, which are not identical to those of the well-studied contractile cardiomyocytes. This study provides a base for future investigations into how Ca(2+) signals regulate biological activity in human cardiac fibroblasts and cardiac remodeling under pathological conditions.
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Sinalização do Cálcio , Cálcio/metabolismo , Fibroblastos/metabolismo , Ventrículos do Coração/metabolismo , Adulto , Agonistas dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Fibroblastos/efeitos dos fármacos , Ventrículos do Coração/citologia , Ventrículos do Coração/efeitos dos fármacos , Humanos , Receptores de Inositol 1,4,5-Trifosfato/efeitos dos fármacos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Microscopia Confocal , ATPases Transportadoras de Cálcio da Membrana Plasmática/antagonistas & inibidores , ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trocador de Sódio e Cálcio/antagonistas & inibidores , Trocador de Sódio e Cálcio/metabolismo , Fatores de Tempo , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/metabolismoRESUMO
BACKGROUND: The development of atrium-selective antiarrhythmic agents is a current strategy for inhibiting atrial fibrillation (AF). The present study investigated whether the natural flavone acacetin from the traditional Chinese medicine Xuelianhua would be an atrium-selective anti-AF agent. METHODS AND RESULTS: The effects of acacetin on human atrial ultrarapid delayed rectifier K(+) current (I(Kur)) and other cardiac ionic currents were studied with a whole-cell patch technique. Acacetin suppressed I(Kur) and the transient outward K(+) current (IC(50) 3.2 and 9.2 mumol/L, respectively) and prolonged action potential duration in human atrial myocytes. The compound blocked the acetylcholine-activated K(+) current; however, it had no effect on the Na(+) current, L-type Ca(2+) current, or inward-rectifier K(+) current in guinea pig cardiac myocytes. Although acacetin caused a weak reduction in the hERG and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells, it did not prolong the corrected QT interval in rabbit hearts. In anesthetized dogs, acacetin (5 mg/kg) prolonged the atrial effective refractory period in both the right and left atria 1 to 4 hours after intraduodenal administration without prolongation of the corrected QT interval, whereas sotalol at 5 mg/kg prolonged both the atrial effective refractory period and the corrected QT interval. Acacetin prevented AF induction at doses of 2.5 mg/kg (50%), 5 mg/kg (85.7%), and 10 mg/kg (85.7%). Sotalol 5 mg/kg also prevented AF induction (60%). CONCLUSIONS: The present study demonstrates that the natural compound acacetin is an atrium-selective agent that prolongs the atrial effective refractory period without prolonging the corrected QT interval and effectively prevents AF in anesthetized dogs after intraduodenal administration. These results indicate that oral acacetin is a promising atrium-selective agent for the treatment of AF.
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Fibrilação Atrial/prevenção & controle , Flavonas/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Antiarrítmicos/farmacologia , Fibrilação Atrial/tratamento farmacológico , Função Atrial/efeitos dos fármacos , Células Cultivadas , Flavonas/uso terapêutico , Cobaias , Humanos , Medicina Tradicional Chinesa , Miócitos Cardíacos , Técnicas de Patch-Clamp , Potássio/metabolismoRESUMO
Gastric cancer (GC) is one of the most common types of cancer in humans and the second leading cause of cancer-associated mortality worldwide. Identifying novel risk factors will facilitate the development of therapeutic strategies to prevent and treat GC. Increased expression of the Src homology 2 B adaptor protein 1 (SH2B1) may stimulate the malignant progression of lung cancer, esophageal cancer and neuroblastoma. However, its function in GC has not yet been investigated. To identify whether increased serum SH2B1 is a risk factor for GC, the present study performed a nested case-control study of patients within the Chinese cohort study. Levels of serum SH2B1 were measured in 563 patients diagnosed with GC during the follow-up period and in 1,126 matched healthy controls. The results demonstrated that high levels of serum SH2B1 were associated with an increased GC risk (odds ratio, 3.23; 95% confidence interval, 2.45-5.65). When analyses were stratified further by sex, age and smoking, an association between increased levels of SH2B1 and GC was identified in males but not in females. Furthermore, the association between SH2B1 levels and GC was more evident in younger than in older participants, and statistically significant in current smokers but not in nonsmokers. These results were not altered following the exclusion of outliers. Furthermore, it was demonstrated that overexpression of SH2B1 contributes to the malignant transformation of normal gastric epithelial cells. Thus, the present study demonstrated that elevated serum SH2B1 levels may increase the risk of GC.
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Gastric cancer (GC) is one of the most common human cancers and the second leading cause of cancer-related mortality worldwide. The major cause of death is metastasis. Elucidating molecular mechanism of metastasis in gastric cancer will help us to further understand the pathogenesis and progression of the disease, and offer new targets for effective therapies. In this study, we found that SH2B1 overexpression promoted invasion, migration and anoilds resistance and silencing it inhibited invasion, migration and anoilds resistance in gastric cancer SGC-7901 cells. However, over-expressing or silencing it did not affect proliferation in the cells. miR-874 could degrade SH2B1 by targeting its 3'UTR and was negatively associated with metastasis traits in SGC-7901 cells. Its overexpression inhibited proliferation in the cells. Thus, we concluded that miR-874 inhibits metastasis-relevant traits via targeting SH2B1 in gastric cancer SGC-7901 cells.
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Cancer initiating cells (CIC) are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. In this study, we found that EHF overexpression promoted formation of CIC traits and silencing it inhibited the traits in gastric cancer NCIN87 cells. Overexpressing EHF downregulated the antitumor effect of 5-fluorouracil (5-FU) in NCIN87 cells. We found that miR206 downregulated EHF protein expression by targeting its 3'UTR in NCIN87 cells and GES-1 cells. Overexpressing miR206 inhibited formation of CIC in NCIN87 cells. In gastric cancer tissues, EHF protein expression was upregulated and miR206 was downregulated. We identified a negative correlation between EHF protein and miR206 expression in gastric cancer tissues. Thus, we concluded that miR206 inhibits formation of CICs by targeting EHF in gastric cancer.
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MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Regiões 3' não Traduzidas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Regulação para Cima/genéticaRESUMO
PURPOSE: GA-13315 is a gibberellin derivative that reveals antitumor and antineoplastic effects both in vitro and in vivo. In the present study, the chemosensitizing effects of GA-13315 in multidrug-resistant cell lines were examined and the underlying mechanisms were investigated. METHODS: Cytotoxicity and chemosensitizing effects of GA-13315 were determined by MTT assay. Function of ABC transporter was analyzed by measuring intracellular drug accumulation of doxorubicin and rhodamine 123 and by determining the ATPase activity of ABC transporter. Expression levels of apoptosis regulators were analyzed using real-time quantitative PCR and Western blot. RESULTS: GA-13315 selectively killed MCF-7/adr cells that overexpress P-glycoprotein (ABCB1) over the parent MCF-7 cells. In combination with conventional chemotherapeutic agents, GA-13315 at sub-toxic concentrations reversed the multidrug resistance mediated by ABCB1 but exacerbated the resistance conferred by multidrug resistance-associated protein 1 (ABCC1). GA-13315 increased intracellular accumulation of doxorubicin and rhodamine 123 in MCF-7/adr cells and in ABCB1-transfected HEK293 cells but facilitated drug flush-out from cells that overexpress ABCC1. GA-13315 inhibited the ATPase activity of ABCB1 while stimulated that of ABCC1. Moreover, the downregulated expression of Bax in MCF-7/adr cells was restored by GA-13315 markedly. CONCLUSION: These data suggest that GA-13315 sensitizes multidrug-resistant cells at least partially by impeding the efflux function of ABCB1. The upregulation of Bax by GA-13315 may also contribute to the sensitizing action. The opposite effects of GA-13315 on different ATP-binding cassette transporters and their implications in overcoming drug resistance require further investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Giberelinas/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/agonistas , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Western Blotting , Regulação para Baixo/efeitos dos fármacos , Doxorrubicina/farmacocinética , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Giberelinas/administração & dosagem , Células HEK293 , Humanos , Células MCF-7 , Reação em Cadeia da Polimerase em Tempo Real , Rodamina 123/farmacocinética , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/genéticaRESUMO
Background and Goal. The application of digital image processing techniques and machine learning methods in tongue image classification in Traditional Chinese Medicine (TCM) has been widely studied nowadays. However, it is difficult for the outcomes to generalize because of lack of color reproducibility and image standardization. Our study aims at the exploration of tongue colors classification with a standardized tongue image acquisition process and color correction. Methods. Three traditional Chinese medical experts are chosen to identify the selected tongue pictures taken by the TDA-1 tongue imaging device in TIFF format through ICC profile correction. Then we compare the mean value of L*a*b* of different tongue colors and evaluate the effect of the tongue color classification by machine learning methods. Results. The L*a*b* values of the five tongue colors are statistically different. Random forest method has a better performance than SVM in classification. SMOTE algorithm can increase classification accuracy by solving the imbalance of the varied color samples. Conclusions. At the premise of standardized tongue acquisition and color reproduction, preliminary objectification of tongue color classification in Traditional Chinese Medicine (TCM) is feasible.
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Medicina Tradicional Chinesa/métodos , Língua/fisiologia , Área Sob a Curva , Cor , Mineração de Dados , Humanos , Aprendizado de Máquina , Máquina de Vetores de SuporteRESUMO
MicroRNA-17 (miRNA-17/miR17) expression has been confirmed to be significantly higher in colorectal cancer tissues than in normal tissues. However, its exact role in colorectal cancer has not yet been fully elucidated. In this study, we found that miR-17 not only promoted epithelial-mesenchymal transition (EMT), but also promoted the formation of a stem cell-like population in colon cancer DLD1 cells. We also wished to determine the role of cytochrome P450, family 7, subfamily B, polypeptide 1 (CYP7B1) in CRC. miR-17 was overexpressed using a recombinant plasmid and CYP7B1 was silenced by transfection with shRNA. Western blot analysis was used to determine protein expression in the DLD1 cells and in tumor tissues obtained from patients with colon cancer. Our results revealed that miR17 overexpression led to the degradation of CYP7B1 mRNA expression in DLD1 cells. In addition, we found that the silencing of CYB7B1 promoted EMT and the formation of a stem cell-like population in the cells. Thus, our findings demonstrate that miR17 induces EMT consistent with the cancer stem cell phenotype by regulating CYP7B1 expression in colon cancer.
Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Família 7 do Citocromo P450/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Esteroide Hidroxilases/genética , Sequência de Bases , Linhagem Celular Tumoral , Família 7 do Citocromo P450/metabolismo , Inativação Gênica , Humanos , MicroRNAs/genética , Fenótipo , Proteólise , Esteroide Hidroxilases/metabolismoRESUMO
OBJECTIVE: To analyse CT and high resolution computerized tomography (HRCT) diagnostic value and morphologic manifestation in coal miner's pneumoconiosis with pleural pathological changes. METHODS: One hundred and thirty-one cases of coal miner patients with pneumoconiosis (0(+) type: 14 cases, type I: 46 cases, type II: 58 cases, type III: 13 cases) and 20 normal people as control group were first examined by routine CT scan at 4 fixed slices, followed by HRCT examination at the region of interest (ROI). Meanwhile, all of them had high-kV chest radiography. RESULTS: According to the national standard of the People's Republic of China in the diagnosis of coal miner's pneumoconiosis with pleural plaque, 68 cases of pleural disease making up 51.91% (68/131) were found (type I accounted for 17.65%, type II 63.24%, type III 19.12%). The morphologic manifestation of pleural pathology by HRCT could be classified into four types: (1) nodular type: 73.38%, (2) flat type: 18.71%, (3) irregular type: 7.91%, (4) mixed type. The pleural pathological changes were found in thoracic wall pleura (65.02%), surface of mediastinum (22.16%), and pericardium (12.80%), but not found in the top of lung and costo-phrenic angles. The thickness of pleura was often about 5 approximately 10 mm (88.17%). CONCLUSION: Pleural pathological changes were not seldom seen in coal miner's pneumoconiosis. HRCT is a reliable examination method aiding routine CT to show pleural pathological changes, thus it has a great diagnostic and practical value. It is necessary to make a further comparison study between pathology and imagology.
Assuntos
Minas de Carvão , Pleura/patologia , Pneumoconiose/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pleura/diagnóstico por imagem , Doenças Pleurais/diagnósticoRESUMO
The inclusion complex of GA-13316 with ß-cyclodextrin (ß-CD) is one of a unique series of gibberellin derivatives possessed of potential anticancer activities. The complex with ß-CD was characterized by means of UV, XRD, DSC, TG, (1)H, and 2D NMR spectroscopy. In addition, we investigated the main aspects of the interaction between GA-13316 and ß-CD using both experimental and molecular modeling approaches. The complex still maintained its anticancer activity, as shown by in vitro cell survival assay on the human colon carcinoma cell line (HCT116) and the human lung cancer cell line (H460). The results showed that the use of ß-CD could be obviously improved the water solubility and stability of GA-13316, implying that the inclusion complex could be a promising future therapeutic agent.