Bone Morphogenetic Protein-7 Attenuates Inflammation And Apoptosis And Improves Cardiac Function In Diabetes

Bone Morphogenetic Protein-7 (BMP-7) belongs to the transforming growth factor-β (TGFβ) family of cytokines has is known to have potent anti-inflammatory properties. It has been used in patients to treat osteoporosis clinically and has been reported to treat diabetic nephropathy in murine models. Moreover, studies show that inflammation is up-regulated in patients with pre-diabetes (PD). We, therefore, hypothesize that the administration of BMP-7 will attenuate inflammation in the heart of Streptozotocin (STZ)-induced PD mice. In this study, we divided C57Bl/6 mice into three groups: CONTROL, PD, and PD+BMP-7. CONTROL mice received intraperitoneal (i.p.) injections of Sodium Citrate Buffer while PD and PD+BMP-7 groups received i.p. injections of Streptozotocin (STZ) for two days. In addition, PD+BMP-7 mice received intravenous injections (i.v.) of BMP-7 (200µg/kg) on the last day of STZ injection and for the following two days. Animals were sacrificed 21 days post last injection and examined for levels of oxidative stress, inflammatory immune response, apoptosis, fibrosis and cardiac function. Our results indicate significant glucose intolerance in PD mice (

Cellular Infiltration and Cytokine Expression Correlate with Fistulizing State in Crohn\u27s Disease

The purpose of this study was to determine the degree of infiltration of different cell subpopulations (tissue dendritic macrophages, T-helper cells, cytotoxic T lymphocytes, monocytes, neutrophils, and B cells) and the expression of the cytokines interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-alpha) in inflamed and noninflamed resected tissues from Crohn\u27s disease (CD) and non-CD patients. Twenty-one resected full-thickness intestinal tissue specimens representing 13 subjects (8 CD and 5 non-CD patients) were included in this study. Sections of 20 mu m in thickness were cut and then stained using immunohistochemistry. The sections were analyzed using confocal laser scanning microscopy (CLSM). Patterns of staining for inflamed CD and noninflamed CD tissues versus non-CD tissues demonstrated significant differences in the macrophage and T-helper subpopulations. Surprisingly, the T-helper subset was decreased significantly in the inflamed CD sections compared to the noninflamed CD and non-CD sections. The staining patterns also suggested differences in the expression of both IL-12 and TNF-alpha between the groups, with cytokine overexpression directly relating to the fistulizing state in CD patients. Cytokine expression is upregulated in chronic CD patients; therefore, the degree of inflammation and tissue damage in CD is dependent on the expression of specific cytokines within the tissue. Differentiation of cell subpopulations may be important for establishing a direct relationship with each state of CD (inflammatory, stricturing, and fistulizing states)

Bmp-7 Attenuates Adverse Cardiac Remodeling Mediated Through M2 Macrophages In Prediabetic Cardiomyopathy

The main objective of this study was to determine whether or not monocyte infiltration occurs in the prediabetic (PD) heart and its role in PD cardiomyopathy. We hypothesized that the PD heart is significantly populated with monocytes and that bone morphogenetic protein (BMP)-7, a novel mediator of monocyte polarization, activates infiltrated monocytes into anti-inflammatory M2 macrophages, thereby inhibiting apoptosis and fibrosis and improving cardiac function. C57Bl6 mice were assigned to control, PD, or PD + BMP-7 groups. PD and PD + BMP-7 groups were administered streptozotocin (50 mg/kg), whereas control animals received sodium citrate buffer. Afterward, the PD + BMP-7 group was administered BMP-7 (200 μg/kg) for 3 days. Our data showed significantly increased infiltrated monocytes and associated pro-inflammatory cytokines, adverse cardiac remodeling, and heart dysfunction in the PD group (P \u3c 0.05). Interestingly, M2 macrophage differentiation and associated anti-inflammatory cytokines were enhanced and there were reduced adverse cardiac remodeling and improved cardiac function in the PD + BMP-7 group (P \u3c 0.05). In conclusion, our data suggest that PD cardiomyopathy is associated with increased monocyte infiltration and released proinflammatory cytokines, which contributes to adverse cardiac remodeling and cardiac dysfunction. Moreover, we report that BMP-7 possesses novel therapeutic potential in its ability to differentiate monocytes into M2 macrophages and confer cardiac protection in the PD heart. © 2014 the American Physiological Society

BMP-7 attenuates adverse cardiac remodeling mediated through M2 macrophages in prediabetic cardiomyopathy

The main objective of this study was to determine whether or not monocyte infiltration occurs in the prediabetic (PD) heart and its role in PD cardiomyopathy. We hypothesized that the PD heart is significantly populated with monocytes and that bone morphogenetic protein (BMP)-7, a novel mediator of monocyte polarization, activates infiltrated monocytes into anti-inflammatory M2 macrophages, thereby inhibiting apoptosis and fibrosis and improving cardiac function. C57Bl6 mice were assigned to control, PD, or PD + BMP-7 groups. PD and PD + BMP-7 groups were administered streptozotocin (50 mg/kg), whereas control animals received sodium citrate buffer. Afterward, the PD + BMP-7 group was administered BMP-7 (200 μg/kg) for 3 days. Our data showed significantly increased infiltrated monocytes and associated pro-inflammatory cytokines, adverse cardiac remodeling, and heart dysfunction in the PD group (P < 0.05). Interestingly, M2 macrophage differentiation and associated anti-inflammatory cytokines were enhanced and there were reduced adverse cardiac remodeling and improved cardiac function in the PD + BMP-7 group (P < 0.05). In conclusion, our data suggest that PD cardiomyopathy is associated with increased monocyte infiltration and released proinflammatory cytokines, which contributes to adverse cardiac remodeling and cardiac dysfunction. Moreover, we report that BMP-7 possesses novel therapeutic potential in its ability to differentiate monocytes into M2 macrophages and confer cardiac protection in the PD heart

Trends and Perioperative Outcomes across Elective Benign Hysterectomy Procedures from the ACS-NSQIP 2007-2017

STUDY OBJECTIVE: In this study, we describe trends of all 3 routes of hysterectomy, patient demographics, and perioperative morbidity among women undergoing surgery for benign indications between 2007 and 2017. We also sought to compare the rates of extended length of stay (ELOS) and readmission rates among the laparoscopic, abdominal, and transvaginal routes. STUDY DESIGN: A retrospective cohort study. STUDY SETTING: National database study. PATIENTS: The American College of Surgeons National Surgical Quality Improvement Program database to identify patients who underwent an elective hysterectomy for benign indication between 2007 and 2017. INTERVENTIONS: Patients were identified using Current Procedural Terminology codes and excluded if their indication for surgery included cancer and pelvic organ prolapse diagnoses based on International Classification of Diseases codes. The collected variables of interest included age, body mass index, American Society of Anesthesiologists classification, uterine weight of \u3e250 grams, and operative time. Our outcomes of interest included ELOS and readmission within 30 days. ELOS was defined as a hospital admission of 2 days or more after laparoscopic and transvaginal hysterectomy and greater than 3 days for an abdominal hysterectomy. Summary statistics were used to evaluate shifts in patient characteristics and postoperative outcomes by hysterectomy route and year of surgery. Multivariable logistic regression analysis, stratified by year, comparing laparoscopic with transvaginal and abdominal hysterectomies was performed. MEASUREMENTS AND MAIN RESULTS: There were 224 357 patients who met the inclusion and exclusion criteria. Of those, 132 567 (59.1%) underwent a laparoscopic hysterectomy, 30 105 (13.4%) a vaginal hysterectomy, and 61 685 (27.5%) an abdominal hysterectomy. The rate of laparoscopic hysterectomy increased by \u3e200% between 2007 and 2017, whereas the rates of transvaginal and abdominal hysterectomies steadily decreased (-58% and -42%, respectively) The mean age, median obesity, and American Society of Anesthesiologists classification increased among women undergoing hysterectomy across all routes with the sharpest increase within the laparoscopic hysterectomy group (% increase in mean age [2.1%, 1.3%, 0.7%] and mean body mass index [9.1%, 4.3%, 3.7%] for laparoscopic, transvaginal, and abdominal routes, respectively). In 2017, the odds of ELOS were 29% lower for those who received laparoscopic than those who received abdominal hysterectomy (p \u3c.001). Comparing the rates of readmission between the laparoscopic and abdominal hysterectomy groups shows that the odds of readmission are significantly lower for patients who receive a laparoscopic hysterectomy across all 11 years (p \u3c.001). CONCLUSION: The rates of laparoscopic hysterectomy have been steadily increasing over the past 11 years. This large retrospective study confirms the lowest rates of readmission and ELOS within the laparoscopic hysterectomy group despite the rising medical complexity of the patients

Cellular Infiltration and Cytokine Expression Correlate with Fistulizing State in Crohn's Disease ▿

The purpose of this study was to determine the degree of infiltration of different cell subpopulations (tissue dendritic macrophages, T-helper cells, cytotoxic T lymphocytes, monocytes, neutrophils, and B cells) and the expression of the cytokines interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in inflamed and noninflamed resected tissues from Crohn's disease (CD) and non-CD patients. Twenty-one resected full-thickness intestinal tissue specimens representing 13 subjects (8 CD and 5 non-CD patients) were included in this study. Sections of 20 μm in thickness were cut and then stained using immunohistochemistry. The sections were analyzed using confocal laser scanning microscopy (CLSM). Patterns of staining for inflamed CD and noninflamed CD tissues versus non-CD tissues demonstrated significant differences in the macrophage and T-helper subpopulations. Surprisingly, the T-helper subset was decreased significantly in the inflamed CD sections compared to the noninflamed CD and non-CD sections. The staining patterns also suggested differences in the expression of both IL-12 and TNF-α between the groups, with cytokine overexpression directly relating to the fistulizing state in CD patients. Cytokine expression is upregulated in chronic CD patients; therefore, the degree of inflammation and tissue damage in CD is dependent on the expression of specific cytokines within the tissue. Differentiation of cell subpopulations may be important for establishing a direct relationship with each state of CD (inflammatory, stricturing, and fistulizing states)