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101.
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Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.

Methods

Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.

Results

Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.

Conclusion

We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment.  相似文献   
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Introduction: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a microtubule inhibitor, has demonstrated clinical efficacy in the treatment of advanced non-small cell lung cancer (NSCLC) either as monotherapy or in combination. Nab-paclitaxel was developed to reduce the toxicities associated with solvent-bound paclitaxel (sb-paclitaxel).

Areas covered: This review first focuses on the clinical trials evaluating the efficacy and tolerability of nab-paclitaxel in NSCLC at different settings. The approval of nab-paclitaxel in combination with carboplatin at the front-line setting for advanced NSCLC was based on the key phase III study, which showed that nab-paclitaxel/carboplatin was associated with superior overall response rate and favorable toxicity profile compared to sb-paclitaxel/carboplatin. The review also addresses the nab-paclitaxel pharmacology, other combinations (e.g. immunotherapy with PD-1/PD-L1 inhibitors), potential biomarkers (e.g. caveolin-1), and special subgroups (e.g. the elderly, squamous histology).

Expert opinion: Existing data has established the role of nab-paclitaxel in the management of advanced NSCLC. Emerging evidence, such as preliminary results from Keynote-407 and IMpower 131 studies, indicates that novel combinations of nab-paclitaxel/carboplatin and PD-1/PD-L1 inhibitors could further improve clinical benefits with manageable toxicity. Nevertheless, in order to better position nab-paclitaxel and to improve patient selection, future studies are warranted to further understand its mechanism of action, predictive biomarkers, and potential synergism with other agents.  相似文献   

105.

Background

Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.

Methods

In eighteen consecutive AMI patients (mean age 56.78?±?12.4 years, mean left ventricle ejection fraction – LVEF: 41.9?±?9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice – on admission and after 19.2?±?5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.

Results

AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p?=?0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p?=?0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p?=?0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p?=?0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p?=?0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p?=?0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines ? IL-6 and TNF-α.

Conclusions

These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium.  相似文献   
106.
Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has a high death rate in patients with comorbidities or in an immunocompromised state. We report a mild and attenuated SARS CoV-2 infection in a patient who is 17 months post stem cell transplantation and maintained on the JAK/STAT inhibitor ruxolitinib, a proposed novel therapy for SARS CoV-2 pneumonia.  相似文献   
107.
INTRODUCTIONThis study aimed to investigate the therapeutic response to injected human umbilical cord blood mesenchymal stem cells (UCBMSCs) among albino rats with streptozotocin (STZ)-induced diabetes mellitus.METHODSControl group (GI; n = 25) rats were fed with standard rat diet. Rats with STZ-induced diabetes mellitus without (GII; n = 25) and with (GIII; n = 25) differentiated human UCBMSCs implantation were the test groups. Rats were sacrificed in Week 11 following implantation. Liver biopsies were sectioned and stained in order to highlight both the presence and function of impregnated cells in the liver tissue.RESULTSHaematoxylin and eosin-stained sections in GI and GII rats showed normal liver architecture while GIII rats showed presence of cell clusters inside the liver tissue and around the central veins. Cell clusters with blue cytoplasm were present in sections in GIII rats but absent in GI and GII rats, indicating the presence of injected differentiated human UCBMSCs. The anti-human insulin immunostaining of GIII rats showed clusters of cells within the liver parenchyma and around central veins, indicating that these cells were active and secreting insulin.CONCLUSIONUCBMSCs are proficient in differentiating into insulin-producing cells in vivo under specific conditions and, when transplanted into the liver of albino rats with STZ-induced diabetes mellitus, were able to secrete insulin and partially control the status of diabetes mellitus in rats.  相似文献   
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目的探讨负载 IL-4 和 BMP-2 的氧化石墨烯(graphene oxide,GO)-羧甲基壳聚糖(carboxymethyl chitosan,CMC)凝胶诱导巨噬细胞 M2 型分化及对 BMSCs 成骨分化的影响。方法取 CMC、GO 制备混合溶液后,分别添加 PBS、IL-4、BMP-2 或 IL-4+BMP-2,在交联剂作用下制备单纯或负载不同因子的 GO-CMC 凝胶支架;取单纯 GO-CMC 凝胶表征观测,包括大体、扫描电镜及傅里叶变换红外吸收光谱仪(Fourier transform infrared spectroscopy,FTIR)检测,以单纯 CMC 凝胶作为对照;取负载不同因子的 GO-CMC 凝胶行体外缓释实验。取 4~5 周龄 SPF 级 SD 雌性大鼠分离培养巨噬细胞,分别与单纯以及负载不同因子的 GO-CMC 凝胶培养,24 h 后行 CD206 免疫荧光检测巨噬细胞分化情况;取第 3 代大鼠 BMSCs 分别与单纯以及负载不同因子的 GO-CMC 凝胶成骨诱导培养,10 d 后行 ALP 染色观测早期成骨,21 d 行茜素红染色观测晚期成骨。结果大体观察 GO-CMC 凝胶呈棕色、半透明状;扫描电镜观察示,GO-CMC 凝胶孔径及孔壁厚度与单纯 CMC 凝胶相似,但内壁粗糙度增加;FTIR 检测显示 CMC 发生聚合形成凝胶。体外缓释实验示 3 种负载不同因子的 GO-CMC 凝胶缓释性能相似,均呈线性缓慢释放因子。CD206 免疫荧光检测示 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化,ALP 及茜素红染色示 GO-CMC 凝胶可诱导 BMSCs 成骨分化;其中负载 IL-4+BMP-2 的 GO-CMC 凝胶作用最显著(P<0.05)。 结论负载 IL-4 和 BMP-2 的 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化,增强 BMSCs 成骨分化能力,为后期骨缺损修复及骨免疫调节研究提供了新的策略。  相似文献   
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