Sex-dependent differences in inflammatory responses during liver regeneration in a murine model of acute liver injury
A sexual dimorphism in liver inflammation and repair was previously demonstrated. Its cellular dissection in the course of acute liver injury (ALI) was explored. BALB/c mice were treated with carbon tetrachloride (CCl4) by intraperitoneal injection and sacrificed after 3, 5 and 8 days. Histological and hepatic cell population analyses were performed. The correlation between androgen receptor (AR) expression and liver recruited inflammatory cells was investigated by treatment with the AR antagonist flutamide. Additionally, patients with a diagnosis of Drug Induced Liver Injury (DILI) were included in the study, with a parti...
Source: Clinical Science - December 11, 2017 Category: Biomedical Science Authors: Bizzaro, D., Crescenzi, M., Di Liddo, R., Arcidiacono, D., Cappon, A., Bertalot, T., Amodio, V., Tasso, A., Stefani, A., Bertazzo, V., Germani, G., Frasson, C., Basso, G., Parnigotto, P., Alison, M. R., Burra, P., Conconi, M. T., Russo, F. P. Tags: PublishAheadOfPrint Source Type: research

Targeted disruption of the KCNJ5 gene in the female mouse lowers aldosterone levels
Aldosterone is released from adrenal zona glomerulosa cells and plays an important role in Na and K homeostasis. Mutations in the human KCNJ5 gene encoding the GIRK4 potassium channel cause abnormal aldosterone secretion and hypertension. To better understand the role of wild-type (WT) GIRK4 in regulating aldosterone release we have looked at aldosterone secretion in a Kcnj5 knock-out (KO) mouse.  We found that female, but not male, KO mice have reduced aldosterone levels compared to WT female controls, but higher levels of aldosterone after Ang-II stimulation. These differences could not be explained by sex-diffe...
Source: Clinical Science - December 8, 2017 Category: Biomedical Science Authors: Hardege, I., Long, L., Al Maskari, R., Figg, N., O'Shaughnessy, K. M. Tags: PublishAheadOfPrint Source Type: research

Endoplasmic reticulum stress/autophagy pathway is involved in diabetes-induced neuronal apoptosis and cognitive decline in mice
Diabetes mellitus is a significant global public health problem depicting a rising prevalence worldwide. As a serious complication of diabetes, diabetes-associated cognitive decline is attracting increasing attention. However, the underlying mechanisms are yet to be fully determined. Both endoplasmic reticulum (ER) stress and autophagy have been reported to modulate neuronal su...
Source: Clinical Science - December 6, 2017 Category: Biomedical Science Authors: Kong, F.-J., Ma, L.-L., Guo, J.-J., Xu, L.-H., Li, Y., Qu, S. Tags: PublishAheadOfPrint Source Type: research

A critical evaluation of the anabolic response after bolus or continuous feeding in COPD and healthy older adults
In conclusion, several factors complicate a comparison of the anabolic capacity of bolus and continuous feeding in acute studies, including the critical role of SPE calculation and assumptions, and the duration of postprandial assessments after bolus feeding. (Source: Clinical Science)
Source: Clinical Science - November 29, 2017 Category: Biomedical Science Authors: Jonker, R., Deutz, N. E., Harrykissoon, R., Zachria, A. J., Veley, E. A., Engelen, M. P. Tags: PublishAheadOfPrint Source Type: research

Therapeutic Effect of a Novel Wnt Pathway Inhibitor on Cardiac Regeneration after Myocardial Infarction
In conclusion, porcupine inhibitor CGX1321 reduces MI injury by limiting fibrosis and promoting regeneration. It promotes cardiomyocyte proliferation by stimulating cell cycle regulating genes with a Hippo/YAP independent pathway. (Source: Clinical Science)
Source: Clinical Science - November 26, 2017 Category: Biomedical Science Authors: Yang, D., Fu, W., Li, L., Xia, X., Liao, Q., Yue, R., Chen, H., Chen, X., An, S., Zeng, C., Wang, W. E. Tags: PublishAheadOfPrint Source Type: research

Hypertrophied myocardium is vulnerable to ischemia reperfusion injury and refractory to rapamycin-induced protection due to increased oxidative/nitrative stress
Left ventricular hypertrophy (LVH) is causally related to increased morbidity and mortality following acute myocardial infarction (AMI) via still unknown mechanisms. Although rapamycin exerts cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury in normal animals, whether rapamycin-elicited cardioprotection are altered in the presence of LVH has yet to be determined. Pressure overload-induced cardiac hypertrophied mice and sham-operated controls were exposed to AMI by coronary artery ligation, and treated with vehicle or rapamycin  10 min before reperfusion. Rapamycin produced marked cardiop...
Source: Clinical Science - November 24, 2017 Category: Biomedical Science Authors: Ma, L.-L., Yin, P.-P., Li, Y., Kong, F.-J., Guo, J.-J., Shi, H.-T., Zhu, J.-B., Zou, Y.-Z., Ge, J.-B. Tags: PublishAheadOfPrint Source Type: research

TRAIL reduces impaired glucose tolerance and NAFLD in the high-fat diet-fed mouse
Conclusion/interpretation: This study shows for the first time that TRAIL is effective when administered after disease onset. In addition, our data sheds light on TRAIL therapeutic potential not only against impaired glucose tolerance, but also against NAFLD. (Source: Clinical Science)
Source: Clinical Science - November 22, 2017 Category: Biomedical Science Authors: Bernardi, S., Toffoli, B., Tisato, V., Bossi, F., Biffi, S., Lorenzon, A., Zauli, G., Secchiero, P., Fabris, B. Tags: PublishAheadOfPrint Source Type: research

Rodent Vertical Sleeve Gastrectomy Alters Maternal Immune Health and Feto-placental Development
Bariatric surgery is increasingly employed to improve fertility and reduce obesity related co-morbidities in obese women. Surgical weight loss not only improves the chance of conception but reduces the risk of pregnancy complications including pre-eclampsia, gestational diabetes, and macrosomia. However, bariatric procedures increase the incidence of intrauterine growth restriction (IUGR), fetal demise, thromboembolism and other gestational disorders. Using our rodent model of vertical sleeve gastrectomy (VSG), we tested the hypothesis that VSG in diet-induced, obese dams would cause immune and placental structural abnorma...
Source: Clinical Science - November 22, 2017 Category: Biomedical Science Authors: Spann, R. A., Lawson, W. J., Bidwell, G. L., Zamarripa, C. A., Maranon, R. O., Bandyopadhyay, S., Taylor, E. R., Reckelhoff, J. F., Garrett, M. R., Grayson, B. E. Tags: PublishAheadOfPrint Source Type: research

Does sympathetic dysfunction occur before denervation in pure autonomic failure?
Conclusions: The finding of normal NET abundance in PAF suggests intact sympathetic nerves but with reduced NE synthesis. The finding of elevated plasma ratio of 3,4-DHPG: NE and reduced VMAT2 in PAF indicates a shift towards intraneuronal NE metabolism over sequestration in sympathetic nerves and suggests that sympathetic dysfunction may occur ahead of denervation. (Source: Clinical Science)
Source: Clinical Science - November 21, 2017 Category: Biomedical Science Authors: Guo, L., Esler, M. D., Sari, C., Phillips, S., Lambert, E. A., Straznicky, N. E., Lambert, G. W., Corcoran, S. J. Tags: PublishAheadOfPrint Source Type: research

Vascular Dysfunction in the Stroke Prone Spontaneously Hypertensive Rat Is Dependent on Constrictor Prostanoid Activity and Y Chromosome Lineage
Vascular dysfunction is a hallmark of hypertension and the strongest risk factor to-date for coronary artery disease. As Y chromosome lineage has emerged as one of the strongest genetic predictors of cardiovascular disease risk to-date, we investigated if Y chromosome lineage modulated this important facet in the stroke-prone spontaneously hypertensive rat (SHRSP) using consomic strains. Here we show that vascular dysfunction in the SHRSP is attributable to differential cyclo-oxygenase (COX) activity with NO levels playing a less significant role. Measurement of prostacyclin, the most abundant product of COX in the vascula...
Source: Clinical Science - November 21, 2017 Category: Biomedical Science Authors: Khan, S. I., Andrews, K. L., Jefferis, A.-M., Jennings, G. L., Sampson, A. K., Chin-Dusting, J. P. F. Tags: PublishAheadOfPrint Source Type: research

Therapeutic Effect of a Novel Wnt Pathway Inhibitor on Cardiac Regeneration after Myocardial Infarction
In conclusion, porcupine inhibitor CGX1321 reduces MI injury by limiting fibrosis and promoting regeneration. It promotes cardiomyocyte proliferation by stimulating cell cycle regulating genes with a Hippo/YAP independent pathway. (Source: Clinical Science)
Source: Clinical Science - November 21, 2017 Category: Biomedical Science Authors: Zeng, C., Yang, D., Fu, W., Li, L., Xia, X., Liao, Q., Yue, R., Chen, H., Chen, X., An, S., Wang, W. E. Tags: PublishAheadOfPrint Source Type: research

Hepatic accumulation of S-Adenosylmethionine in hamsters with non-alcoholic-fatty liver disease associated to metabolic syndrome under selenium and vitamin E deficiency.
In conclusion, our results suggest that progression of NAFLD in the context of MetS can take place even in a situation of hepatic SAM excess and that selenium and vitamin E status might be considered in current therapies against NASH based on SAM supplementation. (Source: Clinical Science)
Source: Clinical Science - November 9, 2017 Category: Biomedical Science Authors: del Bas, J. M., Rodriguez, B., Puiggros, F., Marine, S., Rodriguez, M. A., Morina, D., Armengol, L., Caimari, A., Arola, L. Tags: PublishAheadOfPrint Source Type: research

The shifted balance between circulating follicular regulatory T cells and follicular helper T cells in patients with ulcerative colitis
B cell immunity participates in the pathogenesis of ulcerative colitis (UC). The immune balance between follicular regulatory T (TFR) cells and follicular helper T (TFH) cells is important in regulating B cell responses. However, the alteration of TFR/TFH balance in UC remains unclear. Peripheral blood from 25 UC patients and 15 healthy controls was examined for the frequencies of circulating TFR, TFH, and regulatory T (Treg) cells by flow cytometry. Levels of serum cytokines were measured using cytometric bead array (CBA). Disease activity was evaluated by the Mayo clinic score. Compared to controls, UC patients exhibited...
Source: Clinical Science - November 6, 2017 Category: Biomedical Science Authors: Wang, X., Zhu, Y., Zhang, M., Hou, J., Wang, H., Jiang, Y., Wang, H., Gao, P. Tags: PublishAheadOfPrint Source Type: research

Mesenchymal stromal cells improve human islet function through released products and extracellular matrix
Conclusions: Our results suggest that hASCs have the potential to improve the quality of human islets isolated for transplantation therapy of Type 1 diabetes. Furthermore, it may be possible to achieve improvements in human islet quality in a cell-free culture system by using the MSC-derived products ANXA1 and ECM. (Source: Clinical Science)
Source: Clinical Science - November 3, 2017 Category: Biomedical Science Authors: Arzouni, A. A., Vargas-Seymour, A., Rackham, C. L., Dhadda, P., Huang, G.-C., Choudhary, P., Nardi, N., King, A. J. F., Jones, P. M. Tags: PublishAheadOfPrint Source Type: research

Relaxin contributes to the regulation of arterial pressure in adult female mice
Relaxin is increasingly being recognized as a potent vasodilatory and anti-fibrotic hormone. Given that relaxin is present in the circulation during luteal phase of the menstrual cycle and during pregnancy, when arterial pressure is lowest in women, relaxin may contribute to the relative cardiovascular protection observed in premenopausal women as compared to age-matched men and post-menopausal women. In the present study, we investigated the contribution of relaxin to the normal regulation of arterial pressure in adult female and male mice and during pregnancy. Mean arterial pressure (MAP) was measured via radiotelemetry ...
Source: Clinical Science - November 3, 2017 Category: Biomedical Science Authors: Mirabito Colafella, K. M., Samuel, C. S., Denton, K. M. Tags: PublishAheadOfPrint Source Type: research