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Aim: Myofibroblasts play important roles in the pathogenesis of lung fibrosis. Transforming growth factor (TGF)‐β1 has been widely recognized as a key fibrogenic cytokine. The major signaling pathway of TGF‐β1 is through cytoplasmic Smad proteins. Our study investigated the role of individual TGF‐β1/Smad signal proteins in mediating α‐smooth muscle actin (α‐SMA) gene expression, which is a well‐known key marker of myofibroblast differentiation. Methods: We transiently cotransfected α‐SMA promoter‐luciferase fusion plasmid (p895‐Luc) and Smad expression plasmids and measured Luc activity in TGF‐β1‐treated human fetal lung fibroblasts. We induced Smad3 knockout mice lung fibrosis by bleomycin. α‐SMA protein expression was assessed by Western blotting. Collagen protein was analyzed by measuring hydroxyprolin. Myofibroblast morphology was assessed by immunohistochemistry. Results: We found that the overexpression of Smad3, not Smad2 markedly increased TGF‐β1‐induced α‐SMA promoter activity and α‐SMA protein expression in vitro, whereas the over‐expression of dominant negative mutant Smad3 and Smad7 repressed TGF‐β1 induced α‐SMA gene expression. Compared to wild‐type mice, Smad3 knockout mice showed attenuated lung fibrosis after bleomycin treatment, manifested by lower collagen production and myofibroblast differentiation. Conclusion: Our study suggested TGF‐β1/Smad3 is a major pathway which regulated the myofibroblast differentiation. This result indicates a potential significance for future attempts of attenuating the progression of human lung fibrosis by the inhibition of the Smad3 cascade.

These results revealed that circRNAs may play a role in breast cancer chemoresistance and that hsa_circ_0006528 might be a promising candidate for further functional analysis.

Background Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing‐related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. Methods A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non‐sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty‐two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre‐intensive and post‐intensive lifestyle interventions, were measured. Results The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non‐sarcopenic subjects, serum interleukin (IL)‐6, IL‐18, tumour necrosis factor‐α (TNF‐α), TNF‐like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF‐α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6‐fold and 14.3‐fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4‐fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF‐α, IL‐18, insulin, and adiponectin (all P < 0.05). Conclusions High levels of the inflammatory cytokines TWEAK and TNF‐α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could signif...

Results of the present study suggest potential clinical utilities of CTC enumeration on lung cancer patients in terms of rapid evaluation of chemotherapy effect in real time and monitoring lung cancer recurrence. A large scale of study which is necessary for further validation of the significance of lung cancer CTC is being performed.

Emerging research has indicated that circular RNAs (circRNAs), a novel class of noncoding RNAs, play a vital role in human tumorigenesis and progression. Our previous results suggested that hsa_circ_0006528 (circ_0006528), a circRNA with an unknown function, mediates adriamycin resistance in human breast cancer cells. However, the role of circ_0006528 in breast cancer progression remains unknown. Here, we investigated the probable involvement of circ_0006528 in breast cancer. We analyzed a cohort of 97 patients and found that circ_0006528 expression was significantly upregulated in human breast cancer tissues compared with that in adjacent nontumorous tissues and was significantly associated with advanced tumor-nodemetastasis (TNM) stage and poor prognosis. In addition, we found that in breast cancer cells, circ_0006528 could promote DNA synthesis and cell proliferation, invasion, and migration. Downregulating circ_0006528 induced G2 phase arrest and cell apoptosis. Further mechanistic studies revealed that circ_0006528 could sponge endogenous miR-7-5p and inhibit its activity. We also identified Raf1, which activates the MAPK/ERK signaling pathway, as a target of miR-7-5p and determined that circ_0006528 promotes breast cancer growth, invasion, and migration by promoting the expression of Raf1 and activates the MAPK/ERK pathway. Thus, this study provides the first evidence of the circ_0006528/miR-7-5p/Raf1/MEK/ERK regulatory network in the development of breast cancer and suggests that circ_0006528 is a potential therapeutic target and prognostic predictor for breast cancer.breast cancer, hsa_circ_0006528, invasion, migration, miR-7-5p, proliferation | INTRODUCTIONBreast cancer is the most prevalent cancer in women worldwide and represents a serious public health problem. One complication in the clinical management of breast cancer is the tendency of malignant cells to shed into the circulation during the early stages of tumor development, 1,2 causing the formation of metastatic foci, a phenomenon that directly contributes to approximately 90% of breast cancerrelated mortality. 3,4 The precise genetic and epigenetic mechanisms that regulate the formation and malignant progression of tumors remain unclear and require further study. Therefore, it is essential to Danfeng Gao, Xiaowei Qi, and Xiufen Zhang contributed equally to this work. |

BackgroundMetabolites of arachidonic acid such as prostacyclin (PGI2) have been shown to participate in the pathogenesis of pulmonary fibrosis by inhibiting the expression of pro-inflammatory and pro-fibrotic mediators. In this investigation, we examined whether iloprost, a stable PGI2 analogue, could prevent bleomycin-induced pulmonary inflammation and fibrosis in a mouse model.MethodsMice received a single intratracheal injection of bleomycin with or without intraperitoneal iloprost. Pulmonary inflammation and fibrosis were analysed by histological evaluation, cellular composition of bronchoalveolar lavage (BAL) fluid, and hydroxyproline content. Lung mechanics were measured. We also analysed the expression of inflammatory mediators in BAL fluid and lung tissue.ResultsAdministration of iloprost significantly improved survival rate and reduced weight loss in the mice induced by bleomycin. The severe inflammatory response and fibrotic changes were significantly attenuated in the mice treated with iloprost as shown by reduction in infiltration of inflammatory cells into the airways and pulmonary parenchyma, diminution in interstitial collagen deposition, and lung hydroxyproline content. Iloprost significantly improved lung static compliance and tissue elastance. It increased the expression of IFNγ and CXCL10 in lung tissue measured by RT-PCR and their levels in BAL fluid as measured by ELISA. Levels of TNFα, IL-6 and TGFβ1 were lowered by iloprost.ConclusionsIloprost prevents bleomycin-induced pulmonary fibrosis, possibly by upregulating antifibrotic mediators (IFNγ and CXCL10) and downregulating pro-inflammatory and pro-fibrotic cytokines (TNFα, IL-6, and TGFβ1). Prostacyclin may represent a novel pharmacological agent for treating pulmonary fibrotic diseases.