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41.
Jin Wu Hao Wang Qing Li Qian-Ying Guo Si-Qi Tao Yu-Xian Shen Zheng-Sheng Wu 《Pathology, research and practice》2019,215(9):152523
Mammary carcinoma (MC) is one of most common malignancy in women, and ring finger protein 2 (RNF2) possesses various roles in vast human tumors. In MC tissues as well as in cell lines RNF2 exhibited high expression, had significant association with tumor size, lymph node status, TNM stage, patients’ poor survival, and promoted cell proliferation, colony formation, cell migration and invasion of MC cell lines which was mediated by downregulation of E-cadherin protein. These data reveal that RNF2 protein plays a vital role in the development of MC and may be a potential therapy target of MC. 相似文献
42.
Lukas Hechelhammer Gautier Müllhaupt Livio Mordasini Stefan Markart Sabine Güsewell Patrick Betschart Hans-Peter Schmid Daniel S. Engeler Dominik Abt 《Journal of vascular and interventional radiology : JVIR》2019,30(2):217-224
Purpose
To assess the frequency and potential predictors of prostatic central gland tissue detachment (CGD), an enucleation-like reaction that sporadically occurred in a randomized controlled trial assessing efficacy and safety of prostatic artery embolization (PAE).Materials and Methods
Trial data were analyzed to identify patients with CGD after PAE. Clinical parameters, MR imaging findings, technical details of PAE, and periinterventional data were compared between patients with and without CGD to identify parameters for prediction, induction, or early detection of CGD after PAE.Results
CGD occurred after PAE in 3 of 48 patients (6.3%); these cases had good functional outcomes, but CGD was associated with increased risk of ejaculatory dysfunction and occurrence of complications. Frequency of preoperative transurethral bladder catheterization (100% vs 13.3%; P = .005), central gland index (mean ± standard deviation, 0.86 ± 0.02 vs 0.69 ± 0.14; P < .001), amount of particles applied (1.93 mL ± 0.12 vs 0.96 mL ± 0.36; P < .001), maximum early postoperative pain score (7.33 ± 2.08 vs 1.89 ± 2.40; P = .009), and blood C-reactive protein (CRP) levels after 48 hours (69.0 vs 18.58 mg/dL; P = .045) and 1 week (113.50 vs 5.16 mg/dL; P = .004) were significantly higher in cases of CGD.Conclusions
CGD is a rare reaction that might be triggered by prostatic zonal anatomy, embolization technique, and mechanical or inflammatory processes. It should be considered in patients with severe postoperative pain and high CRP levels who experience voiding dysfunction after PAE to avoid complications. Investigation of larger cohorts might further elucidate this tissue response. 相似文献43.
Jae Eun Choi Tyler Werbel Zhenping Wang Chia Chi Wu Tony L. Yaksh Anna Di Nardo 《Journal of dermatological science》2019,93(1):58-64
Background
Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.Objectives
To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.Methods
Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.Results
Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.Conclusions
These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study. 相似文献44.
《Vaccine》2019,37(31):4382-4391
Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8+ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα+ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice. 相似文献
45.
《Vaccine》2019,37(24):3234-3240
Leucine aminopeptidase (FhLAP) and cathepsin L1 (FhCL1) of Fasciola hepatica play a critical role in parasite feeding, migration through host tissue, and immune evasion. These antigens have been tested for immune protection as single components with variable degrees of success. The chimeric-protein approach could improve protection levels against fasciolosis. Previously, we reported the design and construction of a chimeric protein composed of antigenic sequences of FhLAP and FhCL1 of F. hepatica. The goal of the present study was to express and evaluate the immune-protective capacity of this chimeric protein (rFhLAP-CL1) in sheep. Animals were randomly allocated into five groups with five animals in each group. Groups 1, 2 and 3 were immunized twice with 100 μg, 200 μg and 400 μg of rFhLAP-CL1 emulsified with Quil A adjuvant, whereas groups 4 and 5 were the adjuvant control and infection control groups, respectively. The animals were then challenged with 200 metacercariae two weeks after the rFhLAP-CL1 booster. The fluke burden was reduced by 25.5%, 30.7% (p < 0.05) and 46.5% (p < 0.01) in sheep immunized with 100 μg, 200 μg and 400 μg of chimeric protein, respectively, in comparison to the infection control group. There was a reduction of 22.7% (p < 0.05) and 24.4% (p < 0.01) in fecal egg count in groups 2 and 3, respectively, compared to the infection control group. Sheep immunized with chimeric protein produced F. hepatica excretion-secretion product-specific total IgG antibody, which were increased after challenge. Moreover, the levels of rFhLAP-CL1-specific IgG1 and IgG2 isotypes in immunized sheep increased rapidly two weeks after the first immunization and were significantly more elevated than those of the control groups, indicating a mixed Th1/Th2 response. This is a preliminary evaluation of the chimeric protein rFhLAP-CL1 as a possible immunogen against F. hepatica infection in sheep. 相似文献
46.
Shafqat R. Chaudhry Ilana S. Lendvai Sajjad Muhammad Philipp Westhofen Johannes Kruppenbacher Lukas Scheef Henning Boecker Dirk Scheele Rene Hurlemann Thomas M. Kinfe 《Brain stimulation》2019,12(3):643-651
Objective
To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.Methods
This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls.Results
No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1β was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p?<?0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-α (TNF-α), leptin, adiponectin, ghrelin remained unchanged [p?>?0.05]. No severe device-/stimulation-related adverse events occurred.Conclusion
2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1β plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-α, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics]. 相似文献47.
咳嗽临床常见,尤其是胸部影像学无明显异常的慢性咳嗽,病因复杂、易误诊误治,逐渐受到重视,国内外相继颁发相关指南,目前认为咳嗽高敏感性是其重要的病理生理机制。中医将慢性咳嗽归于"久咳""久嗽"范畴,在病因病机、治法方药上积累了丰富的临床经验,史利卿教授团队针对该病开展了专项临床及基础研究15年,根据传统中医理论及其突出临床症状提出"风邪伏肺"病机,应用祛风宣肺法治疗效果显著。文章结合西医学相关咳嗽机制研究进展及既往研究结果,初步探讨祛风宣肺法治疗该病的疗效机制,丰富慢性咳嗽风邪伏肺致咳相关学术理论的科学内涵,有利于提高中医药防治慢性咳嗽学术水平。 相似文献
48.
49.
Joshua Demb Esther K. Wei Monika Izano Stephen Kritchevsky Helen Swede Anne B. Newman Michael Shlipak Tomi Akinyemiju Steven Gregorich Dejana Braithwaite 《Journal of Geriatric Oncology》2019,10(2):265-271
Objectives
We examined the association between three inflammatory markers (Interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) and incident lung cancer using baseline, updated, and averaged inflammatory measures in older adults.Methods
We fitted multivariable Cox models to assess whether circulating levels of inflammation markers were associated with incident lung cancers in the Health Aging, Body and Composition (HealthABC) prospective cohort of 3075 older adults aged 70–79?years at baseline. IL-6 and CRP were measured biennially, whereas TNF-α was measured at baseline.Results
Baseline levels of IL-6 were significantly associated with incident lung cancer risk in a model that adjusted for age, gender, race, and site (Model 1) (Hazard RatioT3 vs. T1: 3.34, 95% Confidence Interval: 1.91, 5.85) and in a model adjusted for health factors linked to chronic inflammation (Model 2) (HR T3 vs. T1: 2.57, 95% CI: 1.41, 4.65). The associations observed in time-updated IL-6 (HR T3 vs. T1: 2.47, 95% CI: 1.43, 4.28), cumulatively averaged IL-6 (HR T3 vs. T1: 2.47, 95% CI: 1.43, 4.35), and baseline CRP levels (HR T3 vs. T1: 1.85, 95% CI: 1.11, 3.08) with incident lung cancer in Model 1 were not statistically significant in Model 2.Conclusions
Baseline CRP and IL-6 levels were associated with increased risk of lung cancer in Model 1 and both models, respectively. Chronic IL-6 inflammation, as quantified by repeated measures was associated with incident lung cancer in Model 1, but not Model 2. Further research is needed to understand the role of CRP and IL-6 in lung carcinogenesis. 相似文献50.
Hui Fan Xianzhen Jin Chunyan Liao Lina Qiao Wei Zhao 《Pathology, research and practice》2019,215(11):152667
MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment. 相似文献