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  • 机译 FBXW7在EGFR突变型非小细胞肺癌中对吉非替尼耐药的肺癌干细胞的静止中的作用
    摘要:Several recent studies suggest that cancer stem cells (CSCs) are involved in intrinsic resistance to cancer treatment. Maintenance of quiescence is crucial for establishing resistance of CSCs to cancer therapeutics. F-box/WD repeat-containing protein 7 (FBXW7) is a ubiquitin ligase that regulates quiescence by targeting the c-MYC protein for ubiquitination. We previously reported that gefitinib-resistant persisters (GRPs) in -mutant non-small cell lung cancer (NSCLC) cells highly expressed octamer-binding transcription factor 4 (Oct-4) as well as the lung CSC marker CD133, and they exhibited distinctive features of the CSC phenotype. However, the role of FBXW7 in lung CSCs and their resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in NSCLC is not fully understood. In this study, we developed GRPs from the two NSCLC cell lines PC9 and HCC827, which express an exon 19 deletion mutation, by treatment with a high concentration of gefitinib. The GRPs from both PC9 and HCC827 cells expressed high levels of CD133 and FBXW7, but low levels of c-MYC. Cell cycle analysis demonstrated that the majority of GRPs existed in the G0/G1 phase. Knockdown of the gene significantly reduced the cell number of CD133-positive GRPs and reversed the cell population in the G0/G1-phase. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in gefitinib-resistant tumors of PC9 cells in mice and in 9 out of 14 tumor specimens from EGFR-mutant NSCLC patients with acquired resistance to gefitinib. These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in mutation-positive NSCLC.
  • 机译 TCF7L2 rs7903146变体对2型糖尿病患者二甲双胍反应的影响
    摘要:The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7-like 2 gene ( ) is the strongest genetic risk factor associated with T2D to date. In this study, we explored the effects of the rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA , total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of the rs7903146 was performed by the Sequenom MassARRAY iPLEX platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels ( = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9–38.3%, = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1–44.1%, = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1–12.0%, = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in the TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0–25.6%, = 0.002) compared to the patients with CC genotype. Our results suggest that the rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.
  • 机译 年龄分层高级别颅内神经胶质瘤患者的特征和预后因素:基于人群的分析
    摘要:We evaluated characteristics and different prognostic factors for survival in age-stratified high-grade glioma in a U.S. cohort. Eligible patients were identified in the Surveillance, Epidemiology, and End Results (SEER) registries and stratified into 3 age groups: 20–39 years old (1,043 patients), 40–59 years old (4,503 patients), and >60 years old (5,045 patients). Overall and cancer-related survival data were obtained. Cox models were built to analyze the outcomes and risk factors. It showed that race was a prognostic factor for survival in patients 40 to 59 years old and in patients ≥60 years old. Partial resection was associated with lower overall survival and cause-specific survival in all age groups (overall survival: 20–39 yr: HR = 6.41; 40–59 yr: HR = 4.84; >60 yr: HR = 5.06; cause-specific survival: 20–39 yr: HR = 5.87; 40–59 yr: HR = 4.01; >60 yr: HR = 3.36). The study highlights that, while some prognostic factors are universal, others are age-dependent. The effectiveness of treatment approaches differs for patients in different age groups. Results of this study may help to develop personalized treatment protocols for glioma patients of different ages.
  • 机译 1型糖尿病患者早期心脏变化的预测指标:基于超声心动图的研究
    摘要:In patients with type 1 diabetes mellitus (T1DM) imaging studies have demonstrated an increased prevalence of left ventricular diastolic dysfunction and increased left ventricular mass (LVM) unrelated to arterial hypertension and ischemic heart disease. The aim of our study was to identify potential predictors of early subclinical changes in cardiac chamber size and function in such patients. Sixty-one middle-aged asymptomatic normotensive patients with T1DM were included in the study. Conventional and tissue Doppler echocardiography was performed and fasting serum levels of glucose, glycated hemoglobin (HbA1c), lipids, and creatinine were measured. We found moderate bivariate correlations of body mass index (BMI) with left atrial volume (r = 0.47, < 0.01), LVM (r = 0.42, < 0.01), left ventricular relative wall thickness (r = 0.32, p = 0.01), and all observed parameters of diastolic function of both ventricles. The five-year average value of HbA1c weakly correlated with the Doppler index of left ventricular filling pressure E/e´sept (r = 0.27, p = 0.04). We found no significant association of diabetes duration, five-year trend of HbA1c, serum lipids, and glomerular filtration rate with cardiac structure and function. After adjusting for other parameters, BMI remained significantly associated with left atrial volume, LVM as well as with the transmitral Doppler ratio E/A. In our study, BMI was the only observed parameter significantly associated with subclinical structural and functional cardiac changes in the asymptomatic middle-aged patients with T1DM.
  • 机译 肺动脉高压患者当代队列的术后肺部并发症
    摘要:Patients with pulmonary hypertension are at increased risk for postoperative pulmonary complications (PPCs). Herein, we review PPCs in pulmonary hypertension patients undergoing non-cardiac procedures under general anesthesia. The medical records of pulmonary hypertension patients who underwent surgery with general anesthesia between 2010 and 2017 were reviewed for PPCs. In addition we reviewed nursing-documented respiratory depressive episodes in the post-anesthesia care unit to assess the associations between these episodes and later PPCs. There were 20 PPCs among 128 patients who underwent 197 procedures (10.2 per 100 surgeries) [95% CI 6.7–15.2]. Of these, 5 occurred during anesthesia recovery and 15 following anesthesia recovery. Three-quarters of the PPCs occurred within 24 postoperative hours. All the PPCs were severe. The frequency of PPCs was significantly higher in those who experienced respiratory depression during anesthesia recovery vs. in those who did not (5/17, 29% vs. 10/175, 6%; odds ratio 5.15, 95% CI 1.58–16.81, p = 0.007). Increased PPC rates were observed among patients who were current/previous smokers and who routinely use benzodiazepines, and among those undergoing emergent surgery. With treatment, all PPCs resolved. The rate of PPCs in the population of contemporary surgical pulmonary hypertension patients was 10.2%, and three-quarters occurred during first 24 postoperative hours. Patients who had respiratory depression during anesthesia recovery were 5-fold more likely to experience later PPCs.
  • 机译 膀胱透明细胞尿路上皮癌-一种罕见的病理学实体。病例报告和文献综述
    摘要:The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). In contrast, the clear cell variant of urothelial carcinoma (CCUC) is quite a rare neoplasm. In this study, we report a case of an 81-year-old male, presenting with gross hematuria and acute urinary retention, which was subsequently diagnosed with CCUC at our pathology department. Furthermore, we provide a short systematic review of the literature (PubMed, Scopus, and Science Citation Index) for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.
  • 机译 胰腺癌中天冬氨酸β-羟化酶(ASPH)研究的最新进展:简要更新
    摘要:Pancreatic cancer (PC) is a highly aggressive tumor, often difficult to diagnose and treat. Aspartate β-hydroxylase (ASPH) is a type II transmembrane protein and the member of α-ketoglutarate-dependent dioxygenase family, found to be overexpressed in different cancer types, including PC. ASPH appears to be involved in the regulation of proliferation, invasion and metastasis of PC cells through multiple signaling pathways, suggesting its role as a tumor biomarker and therapeutic target. In this review, we briefly summarize the possible mechanisms of action of ASPH in PC and recent progress in the therapeutic approaches targeting ASPH.
  • 机译 131I甲状腺功能减退症对一氧化氮(NO),白介素6(IL-6),肿瘤坏死因子α(TNF-α),总一氧化氮合酶(NOS)活性以及NOS亚型表达的影响老鼠
    摘要:Accumulating evidence has shown that hypothyroidism affects the cardiovascular system, significantly increasing the incidence of cardiovascular diseases. In the present study we investigated the effect of radioactive iodine (I-131)-induced hypothyroidism on several parameters of vascular function, such as nitric oxide (NO), total nitric oxide synthase (NOS) activity and expression of NOS isoforms, as well as on interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) as indicators of inflammation, in rats. A dose of 150 µCi of 131-I was determined as optimal for establishing the model of hypothyroidism in rats. After administration of 131-I, at the end of month 1, 2, and 4 (n = 3 for each time point), NO, IL-6, and TNF-α in the serum and total NOS activity in the aorta were determined in 150 µCi group, compared to controls. The mRNA and protein expression of endothelial, neuronal, and inducible NOS (eNOS, nNOS, and iNOS) in the rat aorta was also estimated, using quantitative reverse transcription polymerase chain reaction and Western blot, respectively. The levels of IL-6 and TNF-α increased in 150 µCi group; the results were significant at the end of month 2 and 4 for IL-6, and at all time points for TNF-α. The levels of NO decreased significantly at the end of month 2 and 4 in 150 µCi group. The total NOS activity increased significantly in 150 µCi group, at all three time points. Significant changes in the mRNA and protein expression of all three NOS isoforms were observed in 150 µCi group compared to controls. NO, IL-6, TNF-α levels and NOS activity and expression are altered in hypothyroid state, and the underlying mechanism should be further investigated.
  • 机译 醛脱氢酶1(ALDH1)在浸润性乳腺癌中的预后价值
    摘要:Aldehyde dehydrogenase 1 (ALDH1) has been identified as a marker of cancer stem cells in breast cancer (BC). Recent studies showed that ALDH1 expression is correlated with poor prognostic parameters and worse clinical outcome in BC. We evaluated ALDH1 expression by immunohistochemistry in a series of 217 invasive BCs and investigated the correlation between ALDH1 expression and clinicopathological parameters, molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2] type, and triple-negative BC [TNBC]), and patient survival. There was a significant association between ALDH1 expression and tumor grade (p < 0.001), i.e., the expression of ALDH1 was higher in high-grade tumors. ALDH1 expression was significantly associated with estrogen and progesterone receptor (ER and PR) negativity (p < 0.001) and HER2 positivity (p = 0.001). ALDH1 expression ratios were higher in HER2 type and TNBC. There was a statistically significant correlation between ALDH1 negativity and luminal A subtype (p < 0.001). The overall and disease free survival were shorter in ALDH1+ tumors, although without statistical significance. We confirm that ALDH1 is a potentially important, poor prognostic factor in BC, associated with high histological grade, ER/PR negativity and HER2 positivity. For more accurate results, ALDH1 expression should be evaluated in larger case series including various types/subtypes of BC.
  • 机译 姜黄素对氯胺酮诱导的大鼠胸腺细胞毒性的调节作用:活性氧(ROS)和磷酸肌醇3-激酶(PI3K)/蛋白激酶B(Akt)途径的参与
    摘要:Ketamine is a widely used anesthetic in pediatric clinical practice. Previous studies have demonstrated that ketamine induces neurotoxicity and has a modulatory effect on the cells of the immune system. Here, we evaluated the potential protective effect and underlying mechanisms of natural phenolic compound curcumin against ketamine-induced toxicity in rat thymocytes. Rat thymocytes were exposed to 100 µM ketamine alone or combined with increasing concentrations of curcumin (0.3, 1, and 3 µM) for 24 hours. Cell viability was analyzed with CCK-8 assay kit. Apoptosis was analyzed using flow cytometry and propidium iodide as well as Z-VAD-FMK and Z-LEHD-FMK inhibitors. Reactive oxygen species (ROS) production and mitochondrial membrane potential [MMP] were measured by flow cytometry. Colorimetric assay with DEVD-pNA substrate was used for assessing caspase-3 activity. Involvement of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was tested with Wortmannin inhibitor. Ketamine induced toxicity in cells, increased the number of hypodiploid cells, caspase-3 activity and ROS production, and inhibited the MMP. Co-incubation of higher concentrations of curcumin (1 and 3 µM) with ketamine markedly decreased cytotoxicity, apoptosis rate, caspase-3 activity, and ROS production in rat thymocytes, and increased the MMP. Application of Z-VAD-FMK (a pan caspase inhibitor) or Z-LEHD-FMK (caspase-9 inhibitor) with ketamine effectively attenuated the ketamine-induced apoptosis in rat thymocytes. Administration of Wortmannin (a PI3K inhibitor) with curcumin and ketamine significantly decreased the protective effect of curcumin on rat thymocytes. Our results indicate that ketamine-induced toxicity in rat thymocytes mainly occurs through the mitochondria-mediated apoptotic pathway and that the PI3K/Akt signaling pathway is involved in the anti-apoptotic effect of curcumin.
  • 机译 miR-210的上调促进间充质干细胞(MSCs)分化为成骨细胞
    摘要:Numerous studies indicated that microRNAs are critical in the regulation of cellular differentiation, by controlling the expression of underlying genes. The aim of this study was to investigate the effect of miR-210 upregulation on differentiation of human umbilical cord blood (HUCB)-derived mesenchymal stem cells (MSCs) into osteoblasts. MSCs were isolated from HUCB and confirmed by their adipogenic/osteogenic differentiation and flow cytometric analysis of surface markers. Pre-miR-210 was amplified from human DNA, digested and ligated with plenti-III-mir-green fluorescent protein (GFP) vector, and cloned in STBL4 bacteria. After confirmation with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), the plenti-III-GFP segment bearing pre-miR-210 was transfected into MSCs by electroporation. Two control vectors, pmaxGFP and Scramble, were transfected separately into MSCs. The expression of miR-210 and genes related to osteoblast differentiation, i.e. runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin gene, in the three groups of transfected MSCs was analyzed 0, 7, 14, and 21 days of transfection by quantitative reverse transcription PCR (qRT-PCR). Overexpression of miR-210 was observed in MSCs transfected with miR-210-bearing plasmid, and this was significantly different compared to Scramble group (p < 0.05). Significantly increased expression of Runx2 (at day 7 and 14), ALP and osteocalcin genes (at all time points for both genes) was observed in MSCs with miR-210-bearing plasmid compared to controls. Overall, the overexpression of miR-210 in MSCs led to MSC differentiation into osteoblasts, most probably by upregulating the Runx2, ALP, and osteocalcin genes at different stages of cell differentiation. Our study confirms the potential of miRNAs in developing novel therapeutic strategies that could target regulatory mechanisms of cellular differentiation in various disease states.
  • 机译 头颈部鳞状细胞癌(HNSCC)球形培养物中上皮-间质转化(EMT)和Gli1表达的诱导
    摘要:Tumor microenvironment provides a specialized niche in which a population of stem-like cells is enriched and contributes to cancer progression. Moreover, cancer stem cell (CSC) phenotype has been associated with epithelial-mesenchymal transition (EMT). Here we investigated the effect of tumor microenvironment on the phenotypic characteristics of head and neck cancer cells and expression of CSC markers using a three-dimensional (3D), spheroid, culture system of CAL33 cell line from human tongue squamous cell carcinoma. CAL33 cells derived from 2D monolayer cultures were grown in spheroid cultures containing serum-free medium (epidermal growth factor [EGF], fibroblast growth factor [FGF], and insulin). Adherent CAL33 cells from spheroids or standard control cultures were grown in the presence/absence of serum in combination with hypoxia/normoxia. Markers of EMT, CSC, and hypoxia were analyzed either by Western blotting, immunofluorescence, or reverse transcription quantitative PCR. Spheroid cultures showed hypoxic microenvironment (high carbonic anhydrase IX [CAIX] expression), mesenchymal-like characteristics (reduced E-cadherin and increased vimentin and N-cadherin expression, presence of larger colonies comprised of larger, spread cells with lower density), and increased expression of the CSC marker glioma-associated oncogene homolog 1 (Gli1). These effects were recapitulated in serum-free adherent CAL33 cells maintained for prolonged periods in hypoxia (1% O2) but, in contrast, were completely abolished by the presence of serum. Overall, we found that a combination of hypoxia, EGF and FGF was essential to induce the EMT in adherent CAL33 cell cultures. The addition of serum rapidly reverts the EMT of cells, affects CSC phenotype and, thus, prevents the detection of such cells in tumor cell lines.
  • 机译 白细胞介素4(IL4)-590C / T(rs2243250)基因多态性与2型糖尿病(T2DM)高加索人的糖尿病肾病(DN)不相关
    摘要:Diabetic nephropathy (DN) is a microvascular complication that affects up to 40% of diabetic patients and can lead to end-stage kidney disease. Inflammatory cytokines such as interleukin 1 (IL-1), IL-6, IL-18 and tumor necrosis factor-α (TNFα) have been linked to the development and progression of DN. The aim of our study was to examine the relationship between interleukin-4 (IL4) -590C/T (rs2243250) gene polymorphism and DN in patients with type 2 diabetes mellitus (T2DM). This study is a continuation of our previous research on the association between angiotensinogen (AGT) gene polymorphisms and DN in patients with T2DM. We included 651 unrelated Slovenian (Caucasian) patients who had had T2DM for at least 10 years. The participants were classified into a group of T2DM patients with DN (276 cases) and a group without DN (375 controls). IL4 rs2243250 polymorphism was analyzed using a TaqMan SNP genotyping assay and StepOne Real-Time PCR System. The frequencies of rs2243250 TT, CT and CC (wild type) genotypes were 3.2%, 29.4% and 67.4%, respectively in patients with DN, and 2.7%, 34.4% and 62.9%, respectively in controls. Our logistic regression analysis adjusted for gender, age, diabetes duration, and glycated hemoglobin showed no association between rs2243250 and the risk for DN (OR 1.06; CI 0.37-3.05; p = 0.9). IL4 rs2243250 is not associated with DN in our subset of Slovenian patients with T2DM.
  • 机译 表皮生长因子(EGF)促进外科手术引起的股骨头骨坏死(ONFH)的骨愈合
    摘要:Angiogenic effects of epidermal growth factor (EGF), a potent mitogen, have been demonstrated previously. Moreover, different in vitro studies showed that EGF affects processes associated with bone healing, such as osteoblast differentiation and bone resorption. The aim of this study was to investigate the effect of combined core decompression (CD) and recombinant human EGF (rhEGF) treatment on early-stage osteonecrosis of the femoral head (ONFH) surgically induced in rats. ONFH was induced by dissecting the cervical periosteum and placing a ligature tightly around the femoral neck. Thirty rats were assigned to one of the following groups (n = 10 each group): sham-operated control, CD, and CD+rhEGF group. rhEGF was injected intraosseously into infarcted areas 2 weeks after the surgery. Preservation of femoral head architecture was assessed at 8 weeks post treatment by radiographic and histomorphological analyses. Osteopontin (OPN) and cluster of differentiation 31 (CD31) were detected by immunochemistry, as indicators of bone remodeling and vascular density, respectively. Inter- and intra-group (non-operated left and operated right femur) differences in radiographic and histomorphological results were analyzed. The femoral head area and sphericity were more preserved in CD+rhEGF compared to CD and sham-control group. CD31 levels were significantly different between the three groups, and were higher in CD+rhEGF compared to CD group. OPN levels were increased in CD and CD+rhEGF groups compared to sham control, but with no significant difference between CD and CD+rhEGF groups. Overall, our results indicate that EGF promotes bone formation and microvascularization in ONFH and thus positively affects the preservation of femoral head during healing.
  • 机译 头孢曲松治疗复杂的尿路感染是肠球菌再感染和长期住院的危险因素:一项为期6年的回顾性研究
    摘要:A frequent complication during hospital stay of patients with urinary tract infections (UTIs) is a re-infection of the urinary tract after the initial improvement. In this study, we investigated the impact of two empirical antibiotic therapies on the outcomes of complicated bacterial UTIs. We retrospectively evaluated 325 adult patients hospitalized during 6 years period with a diagnosis of complicated bacterial UTIs. The patients were classified into two groups according to the antibiotic therapy: ceftriaxone- and co-amoxiclav+gentamicin-treated group. Clinical data were collected from the patient records into a designed form. Output data included information on the treatment outcome, length of stay (LOS), development of complications, and cause of re-infections. The patients treated with ceftriaxone had significantly longer LOS (p = 0.012), as well as higher occurrence of complications (p = 0.023) and urinary tract re-infections (p < 0.001), compared to co-amoxiclav+gentamicin-treated group. No significant difference was observed in the treatment outcome between the two groups (p = 0.137). The most common complication in both investigated groups were re-infections of the urinary tract, and Enterococcus spp. was detected as the cause of re-infections only in patients from ceftriaxone-treated group (40/69 patients). Out of the 40 ceftriaxone-treated patients with enterococcal urinary tract re-infections, 35 patients had one or more chronic diseases and 29 patients had urinary catheter inserted. Ceftriaxone therapy should be considered carefully in patients with complicated UTIs due to the possibility of enterococcal re-infection and consequent prolonged hospital stay.
  • 机译 一种简单,可靠且省时的比色法,用于评估线粒体功能和毒性
    摘要:Mitochondria are organelles involved in the production of cellular energy, regulation of Ca2+ and redox signaling, and are critical for normal functioning of eukaryotic cells. The dysfunction of mitochondria has been implicated in a wide range of diseases, including metabolic and neurodegenerative disorders and different types of cancers. To better understand the role of mitochondria in healthy and disease states, the development of efficient and reliable tools for the assessment of mitochondrial function is particularly important. Janus green B (JG-B) is a supravital lipophilic cationic dye which, in its oxidized form, has a green-blue color. As JG-B is taken up and reduced by metabolically active mitochondria, the dye has been used for assessing the purity, integrity and metabolic activity of mitochondria with microscopy-based methods. Here we present a simple, time- and cost-efficient JG-B-based colorimetric assay for assessing mitochondrial function, activity and toxicity. The method is based upon reduction of JG-B by mitochondrial dehydrogenases to diethylsafranine, which is pink colored and has a maximum absorption at 550 nm. In this proof of principle study, using in vitro mitochondrial preparations isolated from rat brain, we provide evidence that monitoring JG-B conversion to diethylsafranine can be used as a reliable and robust indicator of mitochondrial activity and toxicity. Because of its simplicity and efficiency in terms of costs and time, this assay has a wide potential in analytical as well as therapeutic areas of biomedical research.
  • 机译 非内镜下脑血肿微创排空术1例
    • 作者:Tomaz Velnar
    • 刊名:Bosnian Journal of Basic Medical Sciences
    • 2018年第4期
    摘要:Spontaneous intracerebral hemorrhage (ICH) is one of the most serious causes of stroke, leading to high rates of disability and mortality. In addition to intensive medical treatment, surgery may help to improve the prognosis in patients with ICH. A rapid reversal of coagulopathy is essential in these patients, although it may be difficult to achieve in various bleeding disorders. In such cases, when surgery is needed, a minimally invasive approach is recommended. In this case report, we described and shortly discussed the evacuation of ICH with a minimally invasive non-endoscopic surgical technique.
  • 机译 甲氨蝶呤在小儿克罗恩病中的治疗作用
    摘要:The main role of therapy in Crohn’s disease (CD) is to achieve long-term clinical remission, and to allow for normal growth and development of children. The immunomodulatory drugs used for the maintenance of remission in CD include thiopurines (azathioprine and 6-mercaptopurine) and methotrexate (MTX). Development of hepatosplenic T-cell lymphoma in some patients with inflammatory bowel disease, treated with thiopurines only or in combination with anti-tumor necrosis factor agents, resulted in a growing interest in the therapeutic application of MTX in children suffering from CD. This review summarizes the literature on the therapeutic role of MTX in children with CD. MTX is often administered as a second-line immunomodulator, and 1-year clinical remission was reported in 25–69% of children with CD after excluding for the use of thiopurines. Initial data on MTX effectiveness in mucosal healing, and as a first-line immunomodulator in pediatric patients with CD, are promising. A definite conclusion, however, may only be made on the basis of additional research with a larger number of subjects.
  • 机译 口腔扁平苔藓(OLP)的临床特征和管理,重点是丙型肝炎病毒(HCV)相关OLP的管理
    摘要:Oral lichen planus (OLP) is a chronic inflammatory disease characterized by the occurrence of multiple, symmetrical lesions in the oral cavity. Hepatitis C virus (HCV) infection has been suggested as an etiological factor in OLP. The purpose of this review was to summarize the current literature regarding the treatment of OLP in patients with HCV infection. An electronic search of the PubMed database was conducted until January 2018, using the following keywords: OLP, HCV, corticosteroids, retinoids, immunomodulatory agents, surgical interventions, photochemotherapy, laser therapy, interferon, ribavirin, and direct-acting antivirals. We selected the articles focusing on the clinical features and treatment management of OLP in patients with/without HCV infection. Topical corticosteroids are considered the first-line treatment in OLP. Calcineurin inhibitors or retinoids can be beneficial for recalcitrant OLP lesions. Systemic therapy should be used in the case of extensive and refractory lesions that involve extraoral sites. Surgical intervention is recommended for isolated lesions. In patients with HCV, monotherapy with interferon (IFN)-α may either improve, aggravate or trigger OLP lesions, while combined IFN-α and ribavirin therapy does not significantly influence the progression of lesions. Direct-acting antiviral (DAA) therapy appears to be a promising approach in patients with HCV-related OLP, as it can improve symptoms of both liver disease and OLP, with fewer side effects. Nevertheless, for clinical utility of DAAs in OLP patients, further studies with larger sample sizes, adequate treatment duration, and long term follow-up are required.
  • 机译 汉方药Yokukansan(YKS)增强神经生长因子(NGF)诱导的PC12细胞神经突生长
    摘要:Accumulating evidence indicates that neurotrophic factor-like substances involved in the induction of neurotrophic factor synthesis may aid in the treatment of neurological disorders, such as Alzheimer’s disease. Yokukansan (YKS), a traditional Kampo medicine, has been used for the treatment of anxiety and mood disorders. In the present study, we aimed to identify the signaling pathways associated with YKS-mediated enhancement of nerve growth factor (NGF)-induced neurite extension in rat pheochromocytoma (PC12) cells. Akt and extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation levels were assessed by western blot analysis, in the presence of YKS and following the treatment with TrkA inhibitor, K252a. YKS treatment (NGF+YKS 0.5 group) enhanced NGF-induced neurite outgrowth and phosphorylation/activation of Akt and ERK1/2 in PC12 cells. Moreover, YKS-induced effects were inhibited by the treatment with the TrkA receptor antagonist K252a (NGF+YKS 0.5+K252a group); no significant difference in neurite outgrowth was observed between K252a-treated (NGF+YKS 0.5+K252a group) and NGF-K252a-treated cells (NGF+K252a group). However, neurite outgrowth in K252a-treated cells (NGF+K252a and NGF+YKS 0.5+K252a group) reached only one-third of the level in NGF-treated cells (NGF group). NGF-mediated Akt phosphorylation increased by YKS was also inhibited by K252a treatment (NGF+YKS 0.5+K252a group), but no significant difference in ERK1/2 phosphorylation was observed between NGF-YKS-K252a- and NGF-treated cells (NGF group). Our results indicate that YKS treatment enhanced NGF-induced neurite outgrowth via induction of Akt and ERK1/2 phosphorylation, following the binding of NGF to the TrkA receptor. These findings may be useful in the development of novel therapeutic strategies for the treatment of Alzheimer’s disease.

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