Background: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide, triggering irreversible myocardial cell damage and heart failure. The role of low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) as coreceptors of the Wnt/β-catenin pathway in the adult heart remain unknown. Insulin-like growth factor binding protein 4 and dickkopf-related protein 1 (Dkk1) are 2 secreted LRP5/6 binding proteins that play a crucial role in heart development through preventing Wnt/β-catenin pathway activation. However, their roles in the adult heart remain unexplored. Methods: To understand the role of LRP5/6 and β-catenin in the adult heart, we constructed conditional cardiomyocyte-specific LRP5/6 and β-catenin knockout mice and induced surgical myocardial infarction. We also directly injected recombinant proteins of insulin-like growth factor binding protein 4 and Dkk1 into the heart immediately following myocardial infarction to further examine the mechanisms through which these proteins regulate LRP5/6 and β-catenin. Results: Deletion of LRP5/6 promoted cardiac ischemic insults. Conversely, deficiency of β-catenin, a downstream target of LRP5/6, was beneficial in ischemic injury. It is interesting to note that although both insulin-like growth factor binding protein 4 and Dkk1 are secreted Wnt/β-catenin pathway inhibitors, insulin-like growth factor binding protein 4 protected the ischemic heart by inhibiting β-catenin, whereas Dkk1 enhanced the injury response mainly through inducing LRP5/6 endocytosis and degradation. Conclusions: Our findings reveal previously unidentified dual roles of LRP5/6 involved in the cardiomyocyte response to ischemic injury. These findings suggest new therapeutic strategies in ischemic heart disease by fine-tuning LRP5/6 and β-catenin signaling within the Wnt/β-catenin pathway.

How to find early gastric cancer cellsin vivois a great challenge for the diagnosis and therapy of gastric cancer. This study is aimed at investigating the feasibility of using fluorescent magnetic nanoparticle (FMNP)-labeled mesenchymal stem cells (MSCs) to realize targeted imaging and hyperthermia therapy ofin vivogastric cancer. The primary cultured mouse marrow MSCs were labeled with amino-modified FMNPs then intravenously injected into mouse model with subcutaneous gastric tumor, and then, thein vivodistribution of FMNP-labeled MSCs was observed by using fluorescence imaging system and magnetic resonance imaging system. After FMNP-labeled MSCs arrived in local tumor tissues, subcutaneous tumor tissues in nude mice were treated under external alternating magnetic field. The possible mechanism of MSCs targeting gastric cancer was investigated by using a micro-multiwell chemotaxis chamber assay. Results show that MSCs were labeled with FMNPs efficiently and kept stable fluorescent signal and magnetic properties within 14 days, FMNP-labeled MSCs could target and imagein vivogastric cancer cells after being intravenously injected for 14 days, FMNP-labeled MSCs could significantly inhibit the growth ofin vivogastric cancer because of hyperthermia effects, and CCL19/CCR7 and CXCL12/CXCR4 axis loops may play key roles in the targeting of MSCs toin vivogastric cancer. In conclusion, FMNP-labeled MSCs could targetin vivogastric cancer cells and have great potential in applications such as imaging, diagnosis, and hyperthermia therapy of early gastric cancer in the near future.

Background: Gastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. How to recognize early gastric cancer cells is still a great challenge for early diagnosis and therapy of patients with gastric cancer. This study is aimed to develop one kind of multifunctional nanoprobes forin vivotargeted magnetofluorescent imaging of gastric cancer.Methods: BRCAA1 monoclonal antibody was prepared, was used as first antibody to stain 50 pairs of specimens of gastric cancer and control normal gastric mucous tissues, and conjugated with fluorescent magnetic nanoparticles with 50 nm in diameter, the resultant BRCAA1-conjugated fluorescent magnetic nanoprobes were characterized by transmission electron microscopy and photoluminescence spectrometry, as-prepared nanoprobes were incubated with gastric cancer MGC803 cells, and were injected into mice model loaded with gastric cancer of 5 mm in diameter via tail vein, and then were imaged by fluorescence optical imaging and magnetic resonance imaging, their biodistribution was investigated. The tissue slices were observed by fluorescent microscopy, and the important organs such as heart, lung, kidney, brain and liver were analyzed by hematoxylin and eosin (HE) stain method.Results: BRCAA1 monoclonal antibody was successfully prepared, BRCAA1 protein exhibited over-expression in 64% gastric cancer tissues, no expression in control normal gastric mucous tissues, there exists statistical difference between two groups (P< 0.01). The BRCAA1-conjugated fluorescent magnetic nanoprobes exhibit very low-toxicity, lower magnetic intensity and lower fluorescent intensity with peak-blue-shift than pure FMNPs, could be endocytosed by gastric cancer MGC803 cells, could targetin vivogastric cancer tissues loaded by mice, and could be used to image gastric cancer tissues by fluorescent imaging and magnetic resonance imaging, and mainly distributed in local gastric cancer tissues within 12 h post-injection. HE stain analysis showed that no obvious damages were observed in important organs.Conclusions: The high-performance BRCAA1 monoclonal antibody-conjugated fluorescent magnetic nanoparticles can targetin vivogastric cancer cells, can be used for simultaneous magnetofluorescent imaging, and may have great potential in applications such as dual-model imaging and local thermal therapy of early gastric cancer in near future.

The Forgotten Joint Score (FJS) is a newly developed health-related quality of life (HRQoL) questionnaire designed to evaluate the awareness after total knee arthroplasty (TKA). This study cross-culturally adapted and psychometrically validated a simplified Chinese version of the FJS (SC-FJS). Cross-cultural adaptation was performed according to the internationally recognized guidelines. One-hundred and fifty participants who underwent primary TKA were recruited in this study. Cronbach’s α and intra-class correlations were used to determine reliability. Construct validity was analyzed by evaluating the correlations between SC-FJS and the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the short form (36) health survey (SF-36). Each of the 12 items was properly responded and correlated with the total items. SC-FJS had excellent reliability [Cronbach’s α = 0.907, intra-class correlation coefficient (ICC) = 0.970, 95% CI 0.959–0.978). Elimination of any one item in all did not result in a value of Cronbach’s α of <0.80. SC-FJS had a high correlation with symptoms (0.67, p < 0.001) and pain (0.60, p < 0.001) domains of KOOS and social functioning (0.66, p < 0.001) domain of SF-36, and it also moderately correlated with function in daily living (0.53, p < 0.001) and function in sport and recreation (0.40, p < 0.001) domains of KOOS, and physical subscale of SF-36 (0.49–0.53, p < 0.001) but had a low (r = 0.20) or not significant (p > 0.05) correlation with mental subscale of SF-36. SC-FJS demonstrated excellent acceptability, internal consistency, reliability, and construct validity, which can be recommended for patients who underwent joint arthroplasty in Mainland China.