The cardiac repair after myocardial infarction (MI) involves two phases, namely, inflammatory response and proliferative response. The former is an inflammatory reaction, evoked by different kinds of pro-inflammatory leukocytes and molecules stimulated by myocardial necrosis, while the latter is a repair process, predominated by a magnitude of anti-inflammatory cells and cytokines, as well as fibroblasts. Cardiac remodeling post-MI is dependent on the balance of individualized intensity of the post-MI inflammation and subsequent cardiac fibrosis. During the past 30 years, enormous studies have focused on investigating immune cells and mediators involved in cardiac inflammation and fibrosis, which are two interacting processes of post-MI cardiac repair. These results contribute to revealing the mechanism of adverse cardiac remodeling after MI and alleviating the impairment of cardiac function. In this study, we will broadly discuss the role of immune cell subpopulation and the involved cytokines and chemokines during cardiac repair post-MI, particular in cardiac inflammation and fibrosis. 相似文献
Oxytocin receptor (OXTR) is involved in social behaviors, thermoregulation, and milk ejection, yet little is known about its role in breast cancer. To investigate the role of OXTR in mammary gland development and tumorigenesis, a transgenic mouse model of OXTR overexpression (++Oxtr) was used. Overexpression of OXTR-induced progressive mammary hyperplasia, unexpected milk production, and tumorigenesis in females. OXTR-induced mammary tumors showed ERBB2 upregulation and mixed histological subtypes with predomination of papillary and medullary carcinomas. OXTR overexpression led to an activation of prolactin (PRL)/p-STAT5 pathway and created a microenvironment that promotes mammary-specific tumorigenesis. PRL inhibitor bromocriptine (Br) could mitigate OXTR-driven mammary tumor growth. The study demonstrates Oxtr is an oncogene and a potential drug target for HER2-type breast cancer.Subject terms: Breast cancer, Cancer models相似文献
Plant Growth Regulation - Shikonins (SK) and acetyl-shikonins (acetyl-SK) are known to possess great pharmaceutical potentials however, their ability to disrupt infectious bacterial communication... 相似文献
Metal block augmentations are common solutions in treating bone defects of total knee revision. However, the stress shielding and poor osteointegration resulted from metal block application could not be neglected in bone defects restoration. In this study, a novel porous metal block was designed with topology optimization to improve biomechanical performance. The biomechanical difference of the topologically optimized block, solid Ti6Al4V block, and porous Ti6Al4V block in treating bone defects of total knee revision was compared by finite element analysis. The inhomogeneous femoral model was created according to the computed tomography data. Combined with porous structures, minimum compliance topology optimization subjected to the volume fraction constraint was utilized for the redesign of the metal block. The region of interest was defined as a 10 mm area of the distal femur beneath the contacting surface. The biomechanical performance of daily motions was investigated. The von Mises stress, the strain energy density of the region of interest, and the von Mises stress of metal blocks were recorded. The results were analyzed in SPSS. In terms of the region of interest, the maximum von Mises stress of the topological optimized group increased obviously, and its average stress was significantly higher than that of the other groups (p < 0.05). Moreover, the topologically optimized block group had the highest maximum strain energy density of the three groups, and the lowest maximum stress of block was also found in this group. In this study, the stress shielding reduction and stress transfer capability were found obviously improved through topology optimization. Therefore, the topological optimized porous block is recommended in treating bone defects of total knee revision. Meanwhile, this study also provided a novel approach for mechanical optimization in block designing.
Ecosystems - Low nitrogen (N) availability in the Arctic and Subarctic constrains plant productivity, resulting in low litter inputs to soil. Increased N availability and litter inputs as a result... 相似文献
The chromobox (CBX) proteins mediate epigenetic gene silencing and have been implicated in the cancer development. By analyzing eight CBX family members in TCGA dataset, we found that chromobox 7 (CBX7) was the most strikingly downregulated CBX family member in urinary bladder cancer (UBC), as compared to normal tissues. Though dysregulation of CBX7 has been reported in multiple cancers, its specific role and clinical relevance in UBC remain unclear. Herein, we found that frequent downregulation of CBX7 in UBC specimens, which was due to its promoter hypermethylation, was correlated with poor prognosis. The ectopic expression of CBX7 suppressed UBC cell proliferation, migration, invasion, and cancer stemness, whereas CBX7 depletion promoted cancer cell aggressiveness. Importantly, CBX7 overexpression in UBC cells inhibited tumorigenicity, whereas CBX7 depletion promoted the tumor development, indicating its tumor-suppressive role in UBC. Using RNA-seq and chromosome immunoprecipitation (ChIP) assays, we identified aldo-keto reductase family 1 member 10 (AKR1B10) as a novel downstream target of CBX7, which was negatively modulated by CBX7 in a PRC1-dependent manner and involved in stimulating ERK signaling. Consistently, AKR1B10 overexpression induced cancer cell aggressiveness, whereas suppression of AKR1B10 by siRNA or its small molecular inhibitor, oleanolic acid, reversed the CBX7 deficiency-induced cellular effects. AKR1B10 overexpression was negatively associated with CBX7 downregulation and predicted poor clinical outcomes in UBC patients. Taken together, our results indicate that CBX7 functions as a tumor suppressor to downregulate AKR1B10 and further inactivates ERK signaling. This CBX7/AKR1B10/ERK signaling axis may provide a new therapeutic strategy against UBC.Subject terms: Tumour-suppressor proteins, Bladder cancer, Gene silencing, Bladder cancer相似文献
