Identification of Amino Acid Residues in Angiotensin II Type 1 Receptor Sensing Mechanical Stretch and Function in Cardiomyocyte Hypertrophy.

BACKGROUND/AIMS: Angiotensin II (AngII) type 1 receptor (AT1R) could be activated by mechanical stress without the involvement of AngII during the development of cardiac hypertrophy. We aimed to identify sensing sites of AT1R for activation by mechanical stretch. METHODS: We constructed several site-directed mutations of AT1R (AT1R(K199Q), AT1R(L212F), AT1R(Q257A) and AT1R(C289A)), transfected them respectively into COS7 cells or angiotensinogen knockout cardiomyocytes (ATG(−/−)-CMs), and observed cellular events after mechanical stretch. RESULTS: AngII-induced phosphorylation of ERKs and Jak2, and redistribution of Gαq11 in AT1R(WT)- COS7 or -ATG(−/−)-CMs were dramatically decreased in AT1R(K199Q)- or AT1R(Q257A)- COS7 cells or -ATG(−/−)- CMs, while those effects induced by mechanical stretch were greatly suppressed in COS7 cells or ATG(−/−)-CMs expressing AT1R(L212F), AT1R(Q257A) or AT1R(C289A) compared with these cells expressing AT1R(WT). AngII-induced hypertrophic responses (the increase in hypertrophic genes expression and cross-sectional area) in AT1R(WT)- ATG(−/−)-CMs were partly abolished in AT1R(K199Q)-ATG(−/−)- CMs or AT1R(Q257A) -ATG(−/−)-CMs, while these responses induced by mechanical stretch were greatly inhibited in ATG(−/−)-CMs overexpressing AT1R(L212F), AT1R(Q257A )or AT1R(C289A). CONCLUSION: These results indicated that Leu212, Gln257 and Cys289 in AT1R are not only sensing sites for mechanical stretch but also functional amino residues for activation of the receptor and cardiomyocytes hypertrophy induced by mechanical stretch.

Characteristics, scope of activity, and negative emotions in elderly women with urinary incontinence: Based on a longitudinal follow-up in Shanghai, China.

We conducted a study to assess the characteristics, scope of activity, and negative emotions in elderly women with urinary incontinence (UI) based on a longitudinal follow-up conducted in Shanghai, China from 2013 to 2019. A total of 3,531 elderly women were included in the final analysis, and 697 women who experienced UI during follow-up were included in the UI group. Subjects with UI were subdivided into those with partial UI (UI once a day or less) and UI (frequent UI). Two thousand eight hundred and thirty-four women who did not have UI during the same period served as the control group. The prevalence of UI was 19.74% in this study. Logistic regression analysis revealed that being older (> 80 years of age), having a high level of education (> 12 years; elderly people with a high level of education may pay more attention to their health and notice UI more readily), a low personal monthly income (≤ 3,000 RMB), more gravidity/parity, and having a chronic disease (chronic obstructive pulmonary disease (COPD), dementia, or Parkinson's disease) were risk factors for UI (p < 0.05). About 60% of women in the partial UI group engaged in daily activities outdoors, while this number decreased sharply to 3.6% in the UI group. Women in the UI group were more likely to have negative emotions, such as depression, anxiety, irritability, or feeling worthless (p < 0.001). Among elderly women with dementia, those with UI had defects in terms of judgment in everyday life, the ability of convey information, and the ability to understand information (p < 0.05). More attention needs to be paid to the adverse effects of UI on activities of daily living (ADL) and mental health in the future.

AngiotensinII preconditioning promotes angiogenesis in vitro via ERKs phosphorylation.

AngiotensinII (AngII) is involved in not only the formation of cardiac hypertrophy but also the development of cardiac remodeling both of which are associated with myocardial angiogenesis. This study was therefore performed to clarify the effects of AngII on the formation of vasculatures by cultured cardiac microvascular endothelial cells (CMVECs) after a long-period stimulation with or without the AngII preconditioning. Incubation with AngII for 18 hrs significantly impaired the formation of capillary-like tubes comparing to that without AngII. CMVECs with AngII pretreatment for 5 and 10 min formed more capillary-like tubes than those without AngII pretreatment, suggesting that preconditioning with AngII at a lower dose for a short period could prevent the further damage of CMVECs by a higher concentration of AngII. Moreover, AngII (10(-7) M) stimulation for 5 and 10 min significantly induced the increase in extracellular signal-regulated protein kinases (ERKs) phosphorylation, and an ERKs inhibitor, PD98059, abrogated the increase in the formation of capillary-like tubes induced by the AngII-pretreatment. In conclusion, preconditioning with a lower concentration of AngII for a short period prevents the subsequent impairment of CMVECs by a higher dose of AngII, at least in part, through the increase in ERKs phosphorylation.

The management of dementia worldwide: A review on policy practices, clinical guidelines, end-of-life care, and challenge along with aging population.

Dementia, with a high incidence rate, fast-developing syndrome and large disease burden, raises challenges to global health and social systems. In this review, in order to elaborate current management and diagnosis statements of dementia, and provide further reference to improve dementia service system, we stated policies, clinical guidelines and management experiences concerning dementia across the world. According to the existing dementia management policies and plans, most countries focus on the following aspects: timely detection of dementia, improvement of service quality, person-centered and integrated dementia services at all stages, dementia awareness and friendliness, and scientific research of dementia. Detection of dementia requires knowledge of medical history and cognitive examination, while dementia diagnosis requires more professional medical examination results. Regarding different types of dementia, multiple international standards are used in practice. The overall goals of dementia treatments include postponing the process of cognitive decline and reducing pain caused by cognitive decline, behavioral and psychological symptoms of dementia (BPSD). Treatments include pharmacotherapy interventions and non-pharmacotherapy interventions. In the end-of-life, palliative care is required to improve the quality of life of people with dementia, and maintain their functions. Challenges exist in reducing the disease burden of dementia in the situation of aging population. There are policy bottlenecks and shortcomings to overcome providing medical care services for people with dementia. We would like to suggest strengthening continuous integrated dementia services, improving community services and management support, encouraging policy and financial support for nursing workers, and better support in the end-of-life.

Heat shock transcription factor 1 protects heart after pressure overload through promoting myocardial angiogenesis in male mice.

Heat shock transcription factor 1 (HSF1) plays an important role not only in excise-induced cardiac hypertrophy but also in protection against pressure overload-induced cardiac dysfunction. However, the mechanism is not completely understood. We here elucidate the potential mechanisms by which HSF1 protects against pressure overload-induced cardiac remodeling and dysfunction. A sustained constriction of transverse aorta (TAC) was imposed to HSF1 transgenic (TG), knockout (KO) and their littermate wild type (WT) male mice. Four weeks later, adaptive responses to TAC, such as cardiac hypertrophy, contractility and angiogenesis evaluated by echocardiography, catheterization, coronary perfusion pressure and immunohistochemistry were well preserved in TG but not in KO compared with WT mice. An angiogenesis inhibitor TNP-470 abrogated all these adaptive responses in TG mice, while cardiac transfection of VEGF with angiopoietin-1 rescued the broken heart in KO mice. In response to TAC, p53 was downregulated and hypoxia-inducing transcription factor-1 (HIF-1) was upregulated not only in the heart but also in the cultured cardiac endothelial cells (EC) of TG mice as compared to WT mice whereas these changes became opposite in KO mice. A small interfering RNA (siRNA) of HIF-1 but not a p53 gene impaired the adaptive responses of the heart and EC in TG mice, and a siRNA of p53 but not a HIF-1 gene significantly reversed the heart and EC disorders in KO mice after TAC. We conclude that HSF1 promotes cardiac angiogenesis through suppression of p53 and subsequent upregulation of HIF-1 in endothelial cells during chronic pressure overload, leading to the maintenance of cardiac adaptation.

Mechanical stress-evoked but angiotensin II-independent activation of angiotensin II type 1 receptor induces cardiac hypertrophy through calcineurin pathway.

Mechanical stress can induce cardiac hypertrophy through angiotensin II (AngII) type 1 (AT(1)) receptor independently of AngII, however, the intracellular mechanisms remain largely indeterminate. Since calcineurin, a Ca(2+)-dependent phosphatase, plays a critical role in pressure overload-induced cardiac hypertrophy, we therefore, asked whether calcineurin is involved in the AT(1) receptor-mediated but AngII-independent cardiac hypertrophy. Mechanical stretch failed to elicit hypertrophic responses in COS7 cells co-transfected with plasmid of AT(1) receptor and siRNA of calcineurin. Mechanical stresses for 2weeks in vivo and for 24h in vitro significantly induced upregulation of calcineurin expression and hypertrophic responses, such as the increases in cardiomyocytes size and specific gene expressions, in cardiomyocytes of angiotensinogen gene knockout (ATG(-/-)) mice, both of which were significantly suppressed by a specific calcineurin inhibitor FK506, suggesting a critical role of calcineurin in mechanical stress-induced cardiac hypertrophy in the ATG(-/-) mice. Furthermore, an AT(1) receptor blocker Losartan not only attenuated cardiac hypertrophy but also abrogated upregulation of cardiac calcineurin expression induced by mechanical stresses in the AngII-lacking mice, indicating that calcineurin expression is regulated by AT(1) receptor without the involvement of AngII after mechanical stress. These findings collectively suggest that mechanical stress-evoked but AngII-independent activation of AT(1) receptor induces cardiac hypertrophy through calcineurin pathway.

Effects of heart rate and anesthetic timing on high-resolution echocardiographic assessment under isoflurane anesthesia in mice.

OBJECTIVE: Anesthesia provides sedation and immobility, facilitating echocardiography in mice, but it influences cardiovascular function and therefore outcomes of measurement. This study aimed to determine the effect of the optimal heart rate (HR) and anesthetic timing on echocardiographic reproducibility under isoflurane anesthesia. METHODS: Male C57BL/6J mice underwent high-resolution echocardiography with relative fixed HRs and anesthetic timing. The same experiment was repeated once again after 1 week. RESULTS: Echocardiography was highly reproducible in repeated measurements under low-HR (350-400 beats per minute [bpm]) and high-HR (475-525 bpm) conditions except some M-mode parameters under low-HR conditions. With similar anesthetic timing, mice with a high HR had decreased preload indices and increased ejection phase and Doppler indices. Inversely, when the HR was similar, the echocardiographic results of mice under short anesthetic timing showed little difference from the ones under long anesthetic timing. CONCLUSIONS: This study shows that echocardiographic assessment is greatly reproducible under a high HR. The HR is more important than anesthetic timing for echocardiographic evaluation in mice.

Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction.

AIMS: We sought to determine whether repeat administration of bone marrow mononuclear cells (BMC) can improve left ventricular function compared with a single infusion in patients with large acute myocardial infarction (AMI). METHODS AND RESULTS: Thirty-nine patients with a ST-elevation AMI of the anterior wall and a significantly decreased left ventricular ejection fraction (LVEF 20-39%) were randomly assigned to three groups following primary percutaneous coronary intervention: Group A (n = 12) received a single intracoronary infusion of BMC (1.9 +/- 1.2 x 10(8)) at 3-7 days after AMI; Group B (n = 15) received BMC administration both at 3-7 days (2.0 +/- 1.4 x 10(8)) and at 3 months (2.1 +/- 1.7 x 10(8)); and the control group (CON, n = 12) received one placebo injection at 3-7 days. We noted no severe complications associated with the BMC transfer. The increase in LVEF evaluated by magnetic resonance imaging (MRI) after 12 months in Group B (11.7 +/- 2.6%) was significantly greater than that in Group A (7.2 +/- 1.6%, P < 0.001) or in CON (2.9 +/- 2.0%, P < 0.001). Magnetic resonance imaging-derived myocardial infarct size decreased significantly in Group B compared with Group A (11.3 +/- 2.7% vs. 6.3 +/- 1.6%, P < 0.001). CONCLUSION: Data from this preliminary study suggest that repeated BMC administration might be a safe and feasible therapeutic strategy for patients with large AMI.

[Effect of glutathione and sodium selenite on the metabolism of arsenic in mice exposed to arsenic through drinking water].

OBJECTIVE: To explore the effect of glutathione (GSH) and sodium selenite on the metabolism of arsenic in the liver, kidney and blood of mice exposed to iAsIII through drinking water. METHODS: The mice were randomly divided into control, arsenic, GSH and sodium selenite group, respectively. And each group had eight mice and the mice were exposed to 50 mg/L arsenite by drinking water for 4 weeks. Mice were intraperitoneally injected with GSH (600 mg/kg) and sodium selenite (1 mg/kg) for seven days from the beginning of the fourth week. At the end of the fourth week, liver, kidney and blood were sampled to assess the concentrations of inorganic arsenic (iAs), monomethylarsenic acid (MMA), dimethylarsenic acid (DMA) by hydride generation trapping by ultra-hypothermia coupled with atomic absorption spectrometry. RESULTS: The liver DMA (233.76 +/- 60.63 ng/g) concentration in GSH group was significantly higher than the arsenic group (218.36 +/- 42.71 ng/g). The concentration of DMA (88.52 +/- 30.86 ng/g) and total arsenic (TAs) (162.32 +/- 49.45 ng/g) in blood of GSH group was significantly higher than those [(45.32 +/- 12.19 ng/g), (108.51 +/- 18.00 ng/g), respectively] of arsenic groups(q values were 3.06, 6.40, 10.72 respectively, P < 0.05). The primary methylated index (PMI) (0.65 +/- 0.050) and secondary methylated index (SMI) (0.55 +/- 0.050) in liver sample of GSH group were significantly higher than those (0.58 +/- 0.056, 0.44 +/- 0. 093) in arsenic group. In blood samples, the PMI (0.85 +/- 0.066) in GSH group was significantly higher than that (0.54 +/- 0.113) in arsenic group (q values were 3.75, 5.26, 4.21 respectively, P < 0.05). However, no significant difference was identified between sodium selenite and arsenic groups in liver, kidney or blood samples. And no significant difference was detected in kidney samples among all arsenic exposing groups. CONCLUSION: Exogenous GSH could promote the methylated metabolism of iAsIII, but sodium selenite showed no significant effects.

[Effect of glutathione and methionine on the distribution and methylic metabolism of arsenic speciation in mice exposed to arsenic through drinking water].

OBJECTIVE: To explore the effect of glutathione and L-methionine on the distribution and methylic metabolism of arsenic speciation in the liver, blood and kidney of mice exposed to inorganic As through drinking water. METHODS: Mice were randomly divided into control groups (Con), the only groups with arsenic (As group), GSH intervention groups (GSH) and L-Met intervention groups (L-Met). The mice of experimental groups were exposed to arsenite by drinking water at the concentration of 50 mg/L arsenite for 4 weeks. The GSH groups and the L-methionine groups were injected with glutathinone and L-methionine respectively on the fifth week. Livers, bloods and kidneys were taken to determinate the concentrations of inorganic (iAs), monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) using hydride generation trapping by ultra-hypothermia coupled with atomic absorption spectrometry. RESULTS: In liver, contents of DMA in L-methionine groups were moer higher than those of the As group. The primary methylic indexes (PMI) of arsenic speciation in the GSH groups and the secondary methylic indexes (SMI) of arsenic speciation in the GSH groups and L-methionine groups were more higher than those of the As group. In blood, contents of DMA and the total arsenic speciation (TAs) in both GSH groups and L-methionine groups were more higher than those of the As group. The PMI of arsenic speciation in both GSH groups and L-methionine groups were more higher than those of the As group. CONCLUSION: GSH and L-methionine could promote the methyee metabolism of iAs. As a result, the content of DMA, the end product of methylated metabolism of arsenic, rises, which facilitates the methylic metabolism and excretion of iAs.

[Evaluation of myocardial viability with 201Tl/18F-FDG DISA-SPECT technique in patients with acute myocardial infarction after emergent intracoronary autologous bone marrow mononuclear cells transplantation].

OBJECTIVE: To evaluate the myocardial viability with (201)Tl/(18)F-FDG DISA-SPECT technique in patients with acute myocardial infarction underwent emergent intracoronary autologous bone marrow mononuclear cells (BM-MNC) transplantation. METHODS: Patients with first acute myocardial infarction underwent emergent percutaneous coronary intervention (PCI) were randomized in a 1:1 ratio to either intracoronary transplantation of autologous BM-MNC (n = 20) or to sodium chloride concluding heparin (control, n = 20) via a micro infusion catheter group immediately after PCI. Change in global left ventricular function (LVEF measured by echocardiography) and the myocardial viability detected by (201)Tl/(18)F-FDG DISA-SPECT from baseline and 6-months post transplantation were analyzed. RESULTS: Left ventricular ejection fraction (LVEF) was improved in both groups and the absolute increase (DeltaLVEF) in BM-MNC group was significantly higher than that in control group (7.6% +/- 2.8% vs. 3.0% +/- 2.8%, P < 0.001). In addition, the absolute decrease of myocardial infusion defect detected by (201)Tl SPECT was more significant in BM-MNC group than that in control group (6.7% +/- 3.0% vs. 2.6% +/- 2.6%, P < 0.001) and the number of mismatched segments (indicating viable myocardium) detected by (18)F-FDG SPECT in border zone was also significantly higher in BM-MNC group than that in control group. CONCLUSION: Improved myocardial viability and reduced myocardial infusion defect post emergent intracoronary transplantation of autologous BM-MNC in patients with acute myocardial infarction could be detected by (201)Tl/(18)F-FDG DISA-SPECT technique.

Activity outside the home, environmental barriers, and healthy aging for community-dwelling elderly individuals in China.

Elderly individuals benefit from frequently engaging in activities outside the home because such activities sustain the overall health and functioning of an aging body. However, environmental barriers can limit participation in activities outside the home by elderly individuals. The current study examined the factors that influence the frequency with which elderly individuals living in China engage in activity outside the home. Data were collected from 2,402 elderly individuals residing in the Jiangning district of Shanghai, China in 2015. Face-to-face interviews were conducted based on a questionnaire, and multiple regression analysis was used to measure influencing factors. Results revealed that elderly respondents with a better self-reported health status (p = 0.2499) engaged in activities outside the home more frequently. In addition, elderly respondents residing on higher floors of multi-floor residential buildings (p < 0.001) were less likely to participate in activities outside of the home. This effect was virtually eliminated, however, when the residence in question was equipped with an elevator (p < 0.001).

[Long term follow-up on emergent intracoronary autologous bone marrow mononuclear cell transplantation for acute inferior-wall myocardial infarction].

OBJECTIVE: To investigate the effects of emergent intracoronary autologous bone marrow mononuclear cell (BM-MNC) transplantation on left ventricular function and myocardium lesion area in patients with first acute inferior-wall myocardial infarction. METHODS: Forty patients with first onset of acute inferior-wall myocardial infarction, 28 males and 12 females, aged < or = 75, treated with emergent percutaneous coronary intervention (PCI) were randomly divided into 2 equal groups: group undergoing intracoronary transplantation of autologous BM-MNC via a micro-catheter right after PCI (BM-MNC group), and control group receiving normal saline and heparin. Blood routine examination, myocardium zymogram, and serum high sensitive C reactive protein (hsCRP) were detected, and 24-hour dynamic electrocardiography, delayed-enhancement myocardial magnetic resonance imaging (CMR), and angiography of the coronary artery and left ventricle were conducted before the transplantation and immediately, 1 week, and 6 months after transplantation. RESULTS: CMR showed that 6 months later the left ventricular ejection fraction (LVEF) of the control group was 47.9% +/- 6.7%, significantly higher than that 1 week later (43.4% +/- 6.7%, P = 0.001), and the LVEF of the BM-MNC group 6 months later was 51.5% +/- 5.2%, significantly higher than that 1 week later (44.5% +/- 7.1%, P = 0.001; however, the absolute change of LVEF (DeltaLVEF) of the BM-MNC group was 6.95% +/- 3.33%, significantly higher than that of the control group (4.05% +/- 1.68%, P = 0.047). Six months later the myocardial lesion area of the BM-MNC group decreased more significantly in comparison with the control group. Nevertheless, there was no difference in change of left ventricular end diastolic volume (LVEDV) between these two groups. The serum hsCRP 48 h after transplantation of the BM-MNC group was 2.8 g/L +/- 0.8 g/L, significantly lower than that before transplantation (13.4 g/L +/- 3.6 g/L, P < 0.001). No severe clinical events, such death, recurrent cardiac infarction, malignant arrhythmia, occur in these 2 groups. CONCLUSION: Emergent intracoronary transplantation of autologous BM-MNC in patients with acute inferior-wall myocardial infarction improves the left ventricular function and myocardial infusion, minimizes the myocardial lesion area significantly.

[Observation on the safety: clinical trail on intracoronary autologous bone marrow mononuclear cells transplantation for acute myocardial infarction].

OBJECTIVE: To investigate the safety of autologous bone marrow mononuclear cell (BM-MNCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). METHODS: One hundred and eighty-four patients with AMI treated with percutaneous coronary intervention (PCI) were randomized in a 1:1 way to either intracoronary transplantation of autologous BM-MNCs (n = 92) right after PCI or to sodium chloride concluding heparin (controlled, n = 92) via a micro infusion catheter. In the process of the intracoronary infusion of BM-MNCs, the complications should be recorded, which were aberration reflect (including of pale, syncope, nausea, hypotension and shock), deterioration of angina or heart failure, arrhythmias (including of bradycardia, sinus arrest or atrial ventricular block or ventricular fibrillation), embolism etc. Body temperature, blood pressure and heart rates should be monitored during the first week after transplantation. Holter, coronary angiography and ultrasonic cardiography were performed at the designed time points. Main heart accidents, restenosis and tumor were recorded during 2-years follow up. RESULTS: During the period of bone marrow puncture and intracoronary infusion of BM-MNCs, few patients occurred pale, dizziness, bradycardia and hypotension, which were transient and due to vagus reflect. No stem cell-related arrhythmias, deterioration of angina were noted. In BM-MNCs group one patient developed in-stent reocclusion in one week after transplantation, five developed in-stent restenosis during further follow-up 30 months, which were similar with control group. There were no deaths, major adverse cardiac events, tumor and other late adverse events during follow-up period in both groups. CONCLUSION: Intracoronary transplantation of autologous BM-MNCs in the acute phase after AMI is feasible and seems safe in the 30 months of follow-up.

[Transplantation of autologous bone marrow mononuclear cells on patients with idiopathic dilated cardiomyopathy: early results on effect and security].

OBJECTIVE: The aim of this study is to identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy (IDC) patients who were treated by intracoronary transplantation of autologous mononuclear bone marrow cells (BMCs) in addition to standard therapy. METHODS: Based on given standard therapy, eighteen patients with idiopathic dilated cardiomyopathy were enrolled and divided into transplantation group and control group. The clinical characteristics of two groups were comparable. Among these patients, 10 patients were performed percutaneous coronary autologous BMCs transplantation. Blood routine test, hepatic function, renal function, glucose, triglyceride (TG), cholesterol, low density cholesterol (LDL), high density cholesterol (HDL), uric acid (UA) and high sensitive C-reactive protein (hsCRP) were measured at the time point of pre-operation and some time after transplantation. All patients were monitored under ultrasonic cardiography, Holter, six-minute-walk test and magnetic resonance imaging over a period of at least 6 months. Annual hospital days were recorded during two-year follow-up. RESULTS: Blood routine test, hepatic function, renal function, glucose, TG, cholesterol, LDL, HDL, UA and hsCRP had no significant differences among 48 hours, 3 months and 6 months after transplantation compared with control and pre-transplantation (P > 0.05). Six-minute-walk distance elevated significantly six months after BMCs transplantation compared with control and pre-transplantation [(494.3 +/- 62.8) m vs (307.2 +/- 75.0) m, (321.5 +/- 63.7) m, P < 0.05]. Left ventricular ejection fraction (LVEF) and the sizes of LVEDd had no significant changes compared with that of control and pre-transplantation (P > 0.05). Myocardium lesion area measured by (MRI) seemed decrease in transplantation group compared with that of control and pre-operation [(4.96 +/- 0.47) cm(2) vs (5.12 +/- 0.54) cm(2), (5.02 +/- 0.39) cm(2), P > 0.05], but there was no significance. None of proarrhythmias and side effects had been observed around transplantation and 2 years follow-up. There was no significant difference in survival between two groups in 2 years follow-up. Interestingly, annual hospital day in BMCs transplantation patients was significantly shorter than that in control group [(30.2 +/- 11.2) d vs (43.6 +/- 9.8) d, P < 0.05]. CONCLUSIONS: Autologous bone marrow mononuclear cells transplantation can prolong six-minute-walk, decrease re-hospitalization rate, elevate exercise ability and help to improve cardiac function in patients with IDC. In addition, it was demonstrated that cell transplantation is safe.

Effects of Diets Supplemented with Ensiled Mulberry Leaves and Sun-Dried Mulberry Fruit Pomace on the Ruminal Bacterial and Archaeal Community Composition of Finishing Steers.

This study investigated the effects of ensiled mulberry leaves (EML) and sun-dried mulberry fruit pomace (SMFP) on the ruminal bacterial and archaeal community composition of finishing steers. Corn grain- and cotton meal-based concentrate was partially replaced with EML or SMFP. The diets had similar crude protein (CP), neutral detergent fiber (NDF), and metabolizable energy. Following the feeding trial, the steers were slaughtered and ruminal liquid samples were collected to study the ruminal microbiome. Extraction of DNA, amplification of the V4 region of the 16S rRNA gene, and Illumina MiSeq pyrosequencing were performed for each sample. Following sequence de-noising, chimera checking, and quality trimming, an average of 209,610 sequences were generated per sample. Quantitative real-time PCR was performed to examine the selected bacterial species in the rumen. Our results showed that the predominant phyla were Bacteroidetes (43.90%), Firmicutes (39.06%), Proteobacteria (4.31%), and Tenericutes (2.04%), and the predominant genera included Prevotella (13.82%), Ruminococcus (2.51%), Butyrivibrio (2.38%), and Succiniclasticum (2.26%). Compared to the control group, EML and SMFP groups had a higher abundance of total bacteria (p < 0.001); however, the bacterial community composition was similar among the three groups. At the phylum level, there were no significant differences in Firmicutes (p = 0.7932), Bacteroidetes (p = 0.2330), Tenericutes (p = 0.2811), or Proteobacteria (p = 0.0680) levels among the three groups; however, Fibrobacteres decreased in EML (p = 0.0431). At the genus level, there were no differences in Prevotella (p = 0.4280), Ruminococcus (p = 0.2639), Butyrivibrio (p = 0.4433), or Succiniclasticum (p = 0.0431) levels among the groups. Additionally, the dietary treatments had no significant effects on the archaeal community composition in the rumen. Therefore, EML and SMFP supplementation had no significant effects on the ruminal bacterial or archaeal community composition of finishing steers.

Impact of pathogen burden on in-stent restenosis in patients after coronary stent implantation.

BACKGROUND: Although some certain infectious pathogens could be detected in the patients with coronary artery disease, the roles of these infectious factors in the development of coronary artery diseases remain largely unknown. Since the number of infectious pathogens has been argued to be relative to the coronary artery diseases, we therefore examined whether there is a link between the number of infections and the incidence of in-stent restenosis after stent implantation. METHODS: One hundred and eighty-one patients were enrolled in this study. Infectious pathogens including serum anti-Chlymydia pneumoniae, cytomegalovirus, Helico pylori, human herpes simplex virus-1, human herpes simplex virus-2 antibodies and hepatitis B virus antigen were measured in all patients before coronary stent implantation. Coronary angiography was performed before, immediately after and 6 months after stent implantation. RESULTS: Restenosis rate 6 months post stent implantation was similar in patients with low pathogen burden (< 3 pathogens, 33.3%) to those with high pathogen burden (> or = 3 pathogens, 29.1%). CONCLUSIONS: Previous infections with Chlymydia pneumoniae, cytomegalovirus, Helico pylori, human herpes simplex virus-1, human herpes simplex virus-2 and hepatitis B virus do not contribute to the incidence of restenosis after stent implantation.

[Relationship between infection burden and atherosclerosis and plaque feature].

OBJECTIVE: To evaluate the relationship between infection burden and coronary atherosclerosis and the plaque feature. METHODS: One hundred and eighty two patients underwent coronary angiography in Zhongshan Hospital from 2002 - 2003. Atherosclerosis and vulnerable plaque were determined by intravascular ultrasound (IVUS). Seropositivity of cytomegalovirus, helicobacter pylori, chlamydia pneumonia, hepatitis B virus, EB virus, CoxB virus, influenza A virus, influenza B virus and mycobacterium tuberculosis were determined by ELISA. The serum hs-CRP was detected by Dade Behring prospect (Immuno-nehelomitery). Patients were divided into three groups according to the pathogen burden: group A, n or= 6. RESULTS: The pathogen burden was independent of the C-reactive protein level. Increasing pathogen burden was significantly associated with increasing atherosclerosis risk, the prevalence of atherosclerosis was 44.4%, 70.6% and 76.7% in group A, B and C. The risk associated with elevated pathogen burden was much higher when CRP was also elevated (> 5.0 mg/L) (43.8%, 70.0%, 70.8%) vs (45.5%, 63.7%, 96.8%). The positively of vulnerable plaque increased significantly when the pathogen burden was high (n > 5) (33.3%, 32.4% and 51.7% P < 0.05). CONCLUSION: Our data suggested that infection burden was associated with prevalence of coronary atherosclerosis, and it was particularly important when C-reactive protein was elevated. The high level infection burden could predict vulnerable plaque.

Timing for intracoronary administration of bone marrow mononuclear cells after acute ST-elevation myocardial infarction: a pilot study.

INTRODUCTION: Most studies on intracoronary bone marrow mononuclear cell transplantation for acute myocardial infarction involve treatment 3-7 days after primary percutaneous coronary intervention (PCI); however, the optimal timing is unknown. The present study assessed the therapeutic effect at different times after ST-elevation myocardial infarction. METHODS: The present trial was not blinded. A total of 104 patients with a first ST-elevation myocardial infarction and a left ventricular ejection fraction below 50 %, who had PCI of the infarct-related artery, were randomly assigned to receive intracoronary infusion of bone marrow mononuclear cells within 24 hours (group A, n = 27), 3 to 7 days after PCI (group B, n = 26), or 7 to 30 days after PCI (group C, n = 26), or to the control group (n = 25), which received saline infusion performed immediately after emergency PCI. All patients in groups A, B and C received an injection of 15 ml cell suspension containing approximately 4.9 × 10(8) bone marrow mononuclear cells into the infarct-related artery after successful PCI. RESULTS: Compared to control and group C patients, group A and B patients had a significantly higher absolute increase in left ventricular ejection fraction from baseline to 12 months (change: 3.4 ± 5.7 % in control, 7.9 ± 4.9 % in group A, 6.9 ± 3.9 % in group B, 4.7 ± 3.7 % in group C), a greater decrease in left ventricular end-systolic volumes (change: -6.4 ± 15.9 ml in control, -20.5 ± 13.3 ml in group A, -19.6 ± 11.1 ml in group B, -9.4 ± 16.3 ml in group C), and significantly greater myocardial perfusion (change from baseline: -4.7 ± 5.7 % in control, -7.8 ± 4.5 % in group A, -7.5 ± 2.9 % in group B, -5.0 ± 4.0 % in group C). Group A and B patients had similar beneficial effects on cardiac function (p = 0.163) and left ventricular geometry (left ventricular end-distolic volume: p = 0.685; left ventricular end-systolic volume: p = 0.622) assessed by echocardiography, whereas group C showed similar results to those of the control group. Group B showed more expensive care (p < 0.001) and longer hospital stays during the first month after emergency PCI (p < 0.001) than group A, with a similar improvement after repeat cardiac catheterization following emergency PCI. CONCLUSION: Cell therapy in acute myocardial infarction patients that is given within 24 hours is similar to 3-7 days after the primary PCI. TRIAL REGISTRATION: NCT02425358 , registered 30 April 2015.

[Inhibition of activation of nuclear factor-KappaBeta enhances apoptosis induced by chemotherapeutic drugs in P388 cell line].

OBJECTIVE: To explore the effects of glucocorticoid on apoptosis of mouse acute lymphocytic leukemia P388 cells and activation of nuclear factor-Kappa-gene binding (NF-KappaBeta) in P388 cells induced by chemotherapeutic drugs. METHODS: Mouse acute lymphcytic leukemia P388 cells were cultured. with 1.0 micro mol/L thasone (DXM) hours. Then Cytosine arabinoside Ara-C), cyclophosphamide Cy , and etoposide VP16 , of different concentrations were added into the cultures. Twelve hours later, the apoptosis induced by these drugs in P388 cells was analysed by TdT-mediated kappa-dUTP nick and end labeling (Tunel) and DNA electrophoresis. P388 cells in the exponential growth stage (1 x 10(6)/ml) were cultured with DXM (1.0 micro mol/L) for 2 hours. Then Ara-C, Cy, DXM, and VP16 were added into the culture. Three hours later electrophoretic mobility shift assay (EMSA) was conducted to determine the DNA binding activation of NF-KappaBeta. RESULTS: The highest apoptosis rates of P388 cells induced by Ara-C, Cy, and VP-16, were 48.3% +/- 2.6%, 21.4% +/- 6.8%, and 38.1% +/- 3.8%, respectively. The apoptosis rate of P388 cells induced by Ara-C + DXM was 69.6% +/- 7.7%, 44% higher than that induced by only Ara-C (48.3% +/- 2.6%); the apoptosis rate of P388 cells induced by Cy + DXM was 35.6% +/- 6.8%, 89% higher than that induced by only Cy (21.4% +/- 6.8%); and the apoptosis rate of P388 cells induced by VP-16 + DXM was 71.9% +/- 9.9%, 66% higher than that induced by only VP-16 (38.1% +/- 3.8%) (all P < 0.01). Ara-C, Cy, and VP-16 significantly increased the activation of NF-KappaBeta in P388 cells. Pre-processing of 1.0 micro mol/L DXM suppressed the activation of NF-KappaBeta in P388 cells induced by Ara-C, Cy and VP16 by 90 , 71 and 68 respectively. CONCLUSION: Chemotherapeutic drugs (Ara-C, Cy, and VP-16) induce apoptosis and meanwhile induce the activation of NF-KappaBeta in P388 cells. Glucocorticoids, such as DXM, suppress the activation of NF-KappaBeta in leukemic cells, thus increasing the apoptosis induced by chemotherapeutic drugs.