Impact of moderate to vigorous intensity physical activity on change in renal function in patients after acute myocardial infarction.

Acute myocardial infarction (AMI) is associated with a decline in renal function. This study aimed to investigate the impact of engaging in moderate to vigorous intensity physical activity (MVPA) for more than 30 min per day on changes in renal function during the first 3 months after AMI onset. A prospective, observational study was conducted, enrolling 87 patients (75 men; average age, 65.2 ± 12.5 years) who had experienced AMI. The cystatin C-based estimated glomerular filtration rate (eGFRcys) was collected at and 3 months after discharge. Daily MVPA was measured using triaxial accelerometers at a threshold of 3.0 Metabolic equivalent of the task for 3 months. Generalized estimating equations (GEE) were applied to evaluate the longitudinal association between the number of days per week of MVPA for 30 min or more and within-patient changes in eGFRcys. The patients were categorized into three groups based on their MVPA engagement days: 0 days (n = 20), 1-2 days (n = 14), and 3-7 days (n = 53) groups. After adjusting for potential confounding variables, GEE analysis revealed that the eGFRcys slope over 3 months was significantly higher in the 3-7 days group than in 0 days group (B = 2.9, (95% confidence interval: 1.5-4.2), p < 0.001). Similar results were obtained when MVPA time thresholds were set to 40 and 60 min. These findings suggest a significant positive effect of engaging in MVPA for 30 min or more for 3-7 days per week in the improvement of renal function after AMI onset.

EMID1, a multifunctional molecule identified in a murine model for the invasion independent metastasis pathway.

EMI Domain Containing 1 (EMID1) was identified as a potential candidate metastasis-promoting gene. We sought to clarify the molecular function of EMID1 and the protein expression. Overexpression and knockdown studies using mouse tumor cell lines identified two novel functions of EMID1: intracellular signaling involving enhancement of cell growth via cell cycle promotion and suppression of cell motility, and inhibition of cell-matrix adhesion by extracellularly secreted EMID1. EMID1 deposited on the culture dish induced self-detachment of cells that overexpressed the protein and inhibited adhesion of additionally seeded cells. This multifunctional property involving both intracellular signaling and the extracellular matrix suggests that EMID1 may be a matricellular proteins. Expression analysis using immunohistochemical staining revealed expression of EMID1 that was limited to chief cells of the gastric fundic gland and ß cells of the pancreatic islets in normal adult human tissues, implying cell-specific functions of this molecule. In addition, increased expression of EMID1 protein detected in some cases of human cancers implies that EMID1 might be a new therapeutic target for cancer treatment.

Association between physical activity and changes in renal function in patients after acute myocardial infarction: A dual-center prospective study.

BACKGROUND: Acute myocardial infarction (AMI) causes a decline in renal function. This study aimed to elucidate the longitudinal association between physical activity levels and changes in renal function up to 6 months after the onset of AMI. METHODS: In this dual-center prospective observational study, 73 AMI patients (67 men; average age, 65.0±11.7 years) were enrolled from 2017 to 2019. Blood biochemistry, urinalysis, and physical function tests were conducted at discharge and 3 and 6 months post-discharge. The renal function was evaluated based on cystatin C-based estimated glomerular filtration rate (eGFRcys). The number of steps was recorded for 6 months post-discharge. Generalized estimating equation (GEE) models were used to test the longitudinal association between physical activity levels and within-patient changes in eGFRcys. Both GEE models with a follow-up period of 3 and 6 months were constructed to assess the effects of the passage of time. RESULTS: Patients were stratified into the low (n=36; 2903±1187 steps/day) and high groups (n=37; 7988±3192 steps/day) based on the median number of steps. Both GEE models at the 3- (p=0.027) and 6-month follow-up (p=0.034) showed a significant positive association between the physical activity levels and within-patient changes in eGFRcys. The changes in eGFRcys at 6 months were -0.3 mL/min/1.73 m2 and +4.4 mL/min/1.73 m2 among the low and high group participants, respectively. CONCLUSIONS: There was a significant positive association between physical activity and renal function changes after the onset of AMI, which persisted when the follow-up period was extended from 3 to 6 months. Our findings support the importance of interventions that enable maintaining high physical activity levels as a strategy for preserving renal function in AMI patients.

Identification of S100A14 as a metastasis-promoting molecule in a murine organotropic metastasis model.

Cancer metastasis shows great diversity in target organs, routes and molecular mechanisms depending on the type of cancer and even on the individual patients. To identify key molecules involved in metastasis, we constructed a murine model system including multiple sublines with different organotropism and pathways of metastasis. We selected metastatic sublines from a murine mammary tumor cell line MCH66. Using this model, we extracted metastasis-related molecules by gene expression screening methods and verified their metastasis-promoting effects by gene knockdown or overexpression experiments. For the candidates promoting metastasis, we analyzed molecular functions involved in metastasis: cell growth, motility and invasive activity. We established a metastasis model including low metastatic sublines (66C8, 66LM, 66-4) and highly metastatic counterparts with various organotropism, such as to the lung (66Lu10), liver (HM-KAN5) and general organs (66HM and its clones: HM1-6 and HM1-7). The sublines basically exhibited the invasion-independent metastasis pathway characterized by endothelial cell-covered tumor emboli, whereas 66HM and HM-KAN5 showed an alternative metastasis pathway based on invasion in part and in whole, respectively. Comprehensive gene analysis extracted several molecular candidates responsible for metastasis. S100A14 was identified as one of the promissing candidates promoting lung-metastasis, which was verified by gene knockdown experiments in vivo. In addition, in vivo and in vitro functional analyses demonstrated that S100A14 enhanced scattering, motility and invasiveness of mouse tumor cells. Our model system may be adaptable to the diversity of metastasis in human cancers and useful for exploring the molecular mechanism responsible for metastasis.

Association between physical activity and change in renal function in patients after acute myocardial infarction.

BACKGROUND: Combined renal dysfunction worsens the subsequent prognosis in patients after acute myocardial infarction (AMI). Therefore, establishing a therapeutic modality to maintain or improve renal function in AMI patients is necessary. This study aimed to elucidate the association between physical activity level and change in renal function in such patients. DESIGN: Prospective and observational study. METHODS: We enrolled 41 patients (35 men; average age, 67.5 ± 12.6 years) after AMI onset. Blood biochemistry, urinalysis, and physical function tests were conducted at discharge and 3 months after discharge. Renal function was evaluated based on cystatin C based-estimated glomerular filtration rate (eGFRcys). The number of steps was recorded for 3 months post-discharge. Generalized estimating equations (GEE) was used to test the association between physical activity level and within-patient changes in eGFRcys. RESULTS: Patients were stratified into low (n = 21; number of steps, 2335 ± 1219 steps/day) and high groups (n = 20; number of steps, 7102 ± 2365 steps/day). eGFRcys significantly increased from baseline to after 3 months in the high group (76.5 ± 13.8 to 83.2 ± 16.0 mL/min/1.73 m2, q = 0.004), whereas no significant change was observed in the low group (65.1 ± 15.9 to 62.2 ± 20.2 mL/min/1.73 m2, q = 0.125). Result of GEE adjusted for potential confounding variables showed a significant positive association between physical activity level and within-patient changes in eGFRcys (p = 0.003). Changes in eGFRcys was -2.9 mL/min/1.73 m2 among low group versus +6.7 mL/min/1.73 m2 among high group. CONCLUSIONS: Physical activity level was positively associated with changes in renal function, demonstrating that high physical activity may suppress renal function decline in patients after AMI.

A combined human case of Dirofilaria ursi infection in dorsal subcutaneous tissue and Anisakis simplex sensu stricto (s.s.) infection in ventral subcutaneous tissue.

BACKGROUND: Dirofilaria ursi is a filarial nematode that parasitizes the subcutaneous tissues of the American black bear (Ursus americanus) and Japanese black bear (Ursus thiabetanus japonicus). D. ursi that has parasitized black bears has the potential to subsequently infect humans. In addition, extra-gastrointestinal anisakiasis is less common in Japan. CASE PRESENTATION: We report a case of ventral subcutaneous anisakiasis and dorsal subcutaneous dirofilariasis that was acquired in Fukushima, in the northern part of Japan. The patient was an 83-year-old Japanese female, and subcutaneous parasitic granulomas were present on her left abdomen (near the navel) and left scapula. A pathological examination of the surgically dissected tissue sections from each region demonstrated eosinophilic granulomas containing different species of parasites. To enable the morphological and molecular identification of these parasites, DNA was extracted from paraffin-embedded sections using DEXPAT reagent, and the cytochrome oxidase 2 (COX2), internal transcribed spacer 1 (ITS1), 5.8S and ITS2 regions of the Anisakis larvae, and the 5S rRNA region of the male Dirofilaria were sequenced. The PCR products were examined and compared with DNA databases. Molecular analysis of the COX2 and 5S rRNA sequences of each worm revealed that the nematode found in the ventral region belonged to Anisakis simplex sensu stricto (s.s.) and the male Dirofilaria found in the dorsal region was classified as D. ursi. CONCLUSION: The present case showed a combined human case of D. ursi and A. simplex s.s. infections in subcutaneous tissues. The results of this study will contribute to the identification of unknown parasites in histological sections.

Co-expression of S100A14 and S100A16 correlates with a poor prognosis in human breast cancer and promotes cancer cell invasion.

BACKGROUND: S100 family proteins have recently been identified as biomarkers in various cancers. Of this protein family, S100A14 and S100A16 are also believed to play an important role in tumor progression. The aim of the present study was to clarify the clinical significance and functional role of these molecules in breast cancer. METHODS: In a clinical study, an immunohistochemical analysis of S100A14 and S100A16 expression in archival specimens of primary tumors of 167 breast cancer patients was performed. The relationship of S100A14 and S100A16 expression to patient survival and clinicopathological variables was statistically analyzed. In an experimental study, the subcellular localization and function of these molecules was examined by using the human breast cancer cell lines MCF7 and SK-BR-3, both of which highly express S100A14 and S100A16 proteins. Cells transfected with expression vectors and siRNA for these genes were characterized using in vitro assays for cancer invasion and metastasis. RESULTS: Immunohistochemical analysis of 167 breast cancer cases showed strong cell membrane staining of S100A14 (53% of cases) and S100A16 (31% of cases) with a significant number of cases with co-expression (p < 0.001). Higher expression levels of these proteins were significantly associated with a younger age (<60 years), ER-negative status, HER2-positive status and a poorer prognosis. Co-expression of the two proteins showed more aggressive features with poorer prognosis. In the human breast cancer cell lines MCF7 and SK-BR-3, both proteins were colocalized on the cell membrane mainly at cell-cell attachment sites. Immunoprecipitation and immunofluorescence analyses demonstrated that the 100A14 protein can bind to actin localized on the cell membrane in a calcium-independent manner. A Boyden chamber assay showed that S100A14 and S100A16 knockdown substantially suppressed the invasive activity of both cell lines. Cell motility was also inhibited by S100A14 knockdown in a modified dual color wound-healing assay. CONCLUSIONS: To our knowledge, this is the first report showing the correlation of expression of S100A14, S100A16, and co-expression of these proteins with poor prognosis of breast cancer patients. In addition, our findings indicate that S100A14 and S100A16 can promote invasive activity of breast cancer cells via an interaction with cytoskeletal dynamics. S100A14 and S100A16 might be prognostic biomarkers and potential therapeutic targets for breast cancer.