Metformin inhibits inflammatory signals in the gut by controlling AMPK and p38 MAP kinase activation
Metformin, a hypoglycemic drug used for treatment of type 2 diabetes, regulates also inflammatory pathways. By using several models of intestinal inflammation, we examined whether metformin exerts anti-inflammatory effects and investigated the basic mechanism by which metformin blocks pathologic signals. Colitic mice given metformin exhibited less colonic inflammation and increased expression of active AMP-activated protein kinase, a mediator of the metabolic effects of metformin, in both epithelial and lamina propria compartments. Pharmacological inhibition of AMP-activated protein kinase reduced but did not prevent metfo...
Source: Clinical Science - March 14, 2018 Category: Biomedical Science Authors: Di Fusco, D., Dinallo, V., Monteleone, I., Laudisi, F., Marafini, I., Franze, E., Di Grazia, A., Dwairi, R., Colantoni, A., Ortenzi, A., Stolfi, C., Monteleone, G. Tags: PublishAheadOfPrint Source Type: research
A77 1726 (Leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice
In conclusion, A77 1726 attenuated cardiac hypertrophy and cardiac fibrosis via inhibiting FYN/AKT signaling pathway. (Source: Clinical Science)
Source: Clinical Science - March 14, 2018 Category: Biomedical Science Authors: Ma, Z.-G., Zhang, X., Yuan, Y.-P., Jin, Y.-G., Li, N., Kong, C.-Y., Song, P., Tang, Q.-Z. Tags: PublishAheadOfPrint Source Type: research
High level of C-type natriuretic peptide induced by hyperandrogen-mediated anovulation in polycystic ovary syndrome mice
Polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, is a complex endocrinopathy that affects the fertility of 9%-18% of reproductive-age women. However, the exact mechanism of PCOS, especially hyperandrogen-induced anovulation, is largely unknown to date. Physiologically, the natriuretic peptide type C/natriuretic peptide receptor 2 (CNP/NPR2) system is essential for sustaining oocyte meiotic arrest until the preovulatory luteinizing hormone (LH) surge. We therefore hypothesized that the CNP/NPR2 system is also involved in PCOS and contributes to arresting oocyte meiosis and ovulation. Here, based...
Source: Clinical Science - March 13, 2018 Category: Biomedical Science Authors: Wang, X., Wang, H., Liu, W., Zhang, Z., Zhang, Y., Zhang, W., Chen, Z., Xia, G., Wang, C. Tags: PublishAheadOfPrint Source Type: research
Prader-Willi region non-protein coding RNA 1 suppressed gastric cancer growth as a competing endogenous RNA of microRNA-425-5p
Gastric cancer (GC) is one of a major global health problem especially in Asia. Nowadays, long non-coding RNA has gained significantly attention in the current research climate such as carcinogenesis. This research desired to explore the mechanism of Prader-Willi region non-protein coding RNA 1 (PWRN1) on regulating GC process. Differentially expressed lncRNAs in GC tissues were screened out through microarray analysis. The RNA and protein expression level was detected by qRT-PCR and western blot. Cell proliferation, apoptosis rate, metastasis abilities were respectively determined by CCK8, flow cytometry, wound healing an...
Source: Clinical Science - March 13, 2018 Category: Biomedical Science Authors: Chen, Z., Ju, H., Yu, S., Zhao, T., Jing, X., Li, P., Jia, J., Li, N., Tan, B., Li, Y. Tags: PublishAheadOfPrint Source Type: research
Interleukin-3 stimulates matrix metalloproteinase 12 production from macrophages promoting thoracic aortic aneurysm/dissection
In this study, 3-aminopropionitrile (BAPN) treatment was used to induce TAAD mouse model. Through transcriptome analysis, we found the expression levels of genes associated with interleukin-3 (IL-3) signaling pathway were upregulated during TAAD development in mouse, which were validated by real-time PCR. IL-3 positive cells were increased in TAAD mouse aortas, especially for smooth muscle cells (SMCs). IL-3 deficiency reduced BAPN-induced TAAD formation. We then examined the matrix metalloproteinases (MMPs) expression during TAAD formation in both wild-type and IL-3 deficient mice, showing that MMP12 were significantly do...
Source: Clinical Science - March 9, 2018 Category: Biomedical Science Authors: Liu, C., Zhang, C., Jia, L., Chen, B., Liu, L., Sun, J., Zhang, W., You, B., Li, Y., Li, P., Du, J. Tags: PublishAheadOfPrint Source Type: research
Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure
Recent evidence indicates a link between gut pathology and microbiome with hypertension in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in this study were to test the hypotheses that high blood pressure patients have distinct gut microbiomes and that gut epithelial barrier function markers and microbiome composition could predict systolic blood pressure. Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high blood pressure and reference subjects. Significant increases ...
Source: Clinical Science - March 5, 2018 Category: Biomedical Science Authors: Kim, S., Goel, R., Kumar, A., Qi, Y., Lobaton, G., Hosaka, K., Mohammed, M., Handberg, E. M., Richards, E. M., Pepine, C. J., Raizada, M. K. Tags: PublishAheadOfPrint Source Type: research
TLR2 and TLR4 Play Opposite Role in Autophagy associated with Cisplatin-Induced Acute Kidney Injury
Acute kidney injury (AKI) is considered an inflammatory disease in which Toll-like receptors (TLRs) signaling pathways play an important role. The activation of TLRs results in production of several inflammatory cytokines leading to further renal damage. In contrast, TLRs are key players on autophagy induction, which is associated with a protective function on cisplatin-induced AKI. Hence, this study aimed evaluate the specific participation of TLR2 and TLR4 molecules on development of cisplatin-induced AKI. Complementarily, we also investigated the link between TLRs and HO-1, a promisor cytoprotective molecule. Firstly, w...
Source: Clinical Science - March 2, 2018 Category: Biomedical Science Authors: Andrade-Silva, M., Cenedeze, M. A., Perandini, L. A., Felizardo, R. J. F., Watanabe, I. M., Agudelo, J. S. H., Castoldi, A., Goncalves, G. M., Origassa, C. S. T., Semedo, P., Hiyane, M. I., Neto, O. F., Malheiros, D. M. A. C., Reis, M. A., Fujihara, C. K. Tags: PublishAheadOfPrint Source Type: research
Protective Effects of the Angiotensin II AT2 Receptor Agonist Compound 21 in Ischemic Stroke: A Nose-to-Brain Delivery Approach
Significant neuroprotective effects of angiotensin II type 2 (AT2) receptor agonists in ischemic stroke have been previously demonstrated in multiple studies. However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular and systemic administration, are unsuitable for translation to humans; in the latter case because AT2 receptor agonists are blood brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the blood brain barrier and deliver the selective AT2 receptor agonist Co...
Source: Clinical Science - March 2, 2018 Category: Biomedical Science Authors: Bennion, D. M., Jones, C. H., Dang, A. N., Isenberg, J. D., Graham, J. T., Lindblad, L., Domenig, O., Waters, M. F., Poglitsch, M., Sumners, C., Steckelings, U. M. Tags: PublishAheadOfPrint Source Type: research
Cardiac-specific inducible over-expression of human Plasma Membrane Ca2+ ATPase 4b is cardioprotective and improves survival in mice following ischemic injury.
Conclusions: Cardiac PMCA4b regulates nNOS activity, cardiac mass and contractility, such that PMCA4b overexpression preserves cardiac function following IRI, heightens cardiac performance and limits infarct progression, cardiac hypertrophy and HF, even when induced late post-MI. These data identify PMCA4b as a novel therapeutic target for IRI and HF. (Source: Clinical Science)
Source: Clinical Science - February 27, 2018 Category: Biomedical Science Authors: Sadi, A. M., Afroze, T., Siraj, M. A., Momen, A., White-Dzuro, C., Zarrin-Khat, D., Handa, S., Ban, K., Kabir, M. G., Trivieri, M. G., Gros, R., Backx, P., Husain, M. Tags: PublishAheadOfPrint Source Type: research
Alterations in Placental Long Chain Polyunsaturated Fatty Acid Metabolism in Human Intrauterine Growth Restriction
Fatty acids (FA) are critical for fetal brain development and are transferred across the placenta by membrane-bound FA transport proteins (FATP), translocases (FAT/CD36) and cytosolic binding proteins (FABP). The cytosolic protein perilipin-2 aids in neutral lipid storage within lipid droplets. Decreased placental nutrient transport is believed to contribute to intrauterine growth restriction (IUGR); however, IUGR placental lipid transport and metabolism are poorly understood. We hypothesized protein expression of FATPs, FABPs, and perilipin-2 in human placenta is decreased and placental lipid content and incorporation int...
Source: Clinical Science - February 20, 2018 Category: Biomedical Science Authors: Chassen, S. S., Ferchaud-Roucher, V., Gupta, M. B., Jansson, T., Powell, T. L. Tags: PublishAheadOfPrint Source Type: research
Extrahepatic angiogenesis hinders recovery of portal hypertension and collaterals in rats with cirrhosis resolution
In conclusion, cirrhosis resolution attenuates but not completely normalizes portal hypertension because of persistently high splanchnic inflow and angiogenesis. In clinical setting, vascular complications such as varices could persist after cirrhosis resolution and further investigation to define the follow-up and treatment strategies is anticipated. (Source: Clinical Science)
Source: Clinical Science - February 15, 2018 Category: Biomedical Science Authors: Hsu, S.-J., Tsai, M.-H., Chang, C.-C., Hsieh, Y.-H., Huang, H.-C., Lee, F.-Y., Chuang, C.-L., Hou, M.-C., Lee, S.-D. Tags: PublishAheadOfPrint Source Type: research
Quantification of hepatic perfusion and hepatocyte function with dynamic gadoxetic acid-enhanced MR imaging in patients with chronic liver disease
The purpose of this study was to develop and perform initial validation of dynamic MR imaging enhanced with gadoxetic acid as hepatobiliary contrast agent to quantify hepatic perfusion and hepatocyte function in patients with chronic liver disease. Free-breathing, dynamic gadoxetic acid-enhanced MR imaging was performed at 3.0 T using a three-dimensional time-resolved angiography sequence with stochastic trajectories during 38 minutes. A dual-input three-compartment model was developed to derive hepatic perfusion and hepatocyte function parameters. Method feasibility was assessed in 23 patients with biopsy-proven chronic l...
Source: Clinical Science - February 12, 2018 Category: Biomedical Science Authors: Leporq, B., Daire, J.-L., Pastor, C. M., Deltenre, P., Sempoux, C., Schmidt, S., Van Beers, B. E. Tags: PublishAheadOfPrint Source Type: research
Urinary levels of sirtuin-1 associated with disease activity in lupus nephritis
Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of this study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in...
Source: Clinical Science - February 12, 2018 Category: Biomedical Science Authors: Olivares, D., Perez-Hernandez, J., Forner, M. J., Perez-Soriano, C., Tormos, M. C., Saez, G. T., Chaves, F. J., Redon, J., Cortes, R. Tags: PublishAheadOfPrint Source Type: research
Short-term early exposure to thirdhand cigarette smoke increases lung cancer incidence in mice
Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to-7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and multiplicity, compared to controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell prol...
Source: Clinical Science - February 12, 2018 Category: Biomedical Science Authors: Hang, B., Wang, Y., Huang, Y., Wang, P., Langley, S. A., Bi, L., Sarker, A. H., Schick, S. F., Havel, C., Jacob, P., Benowitz, N., Destaillats, H., Tang, X., Xia, Y., Jen, K.-Y., Gundel, L. A., Mao, J.-H., Snijders, A. Tags: PublishAheadOfPrint Source Type: research
Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels
Conclusions: Reduced expression and function of SKCa, IKCa and Kir2.1 channels is associated with elevated blood pressure in rats fed a long-term high fat/high fructose diet. Rats fed a 28-week high fat/high fructose diet provide a relevant model of diet-induced hypertension. (Source: Clinical Science)
Source: Clinical Science - February 7, 2018 Category: Biomedical Science Authors: Gradel, A. K. J., Salomonsson, M., Sorensen, C. M., Holstein-Rathlou, N.-H., Jensen, L. J. Tags: PublishAheadOfPrint Source Type: research
