Mitochondrial dysfunction is associated with long-term cognitive impairment in an animal sepsis model
Conclusion:Long-term impairment of brain function is temporally related to mitochondrial dysfunction. Activators of autophagy and mitochondrial biogenesis could rescue animals from cognitive impairment. (Source: Clinical Science)
Source: Clinical Science - September 15, 2019 Category: Biomedical Science Authors: Manfredini, A., Constantino, L., Pinto, M. C., Michels, M., Burger, H., Kist, L. W., Silva, M. C., Gomes, L. M., Dominguini, D., Steckert, A., Simioni, C., Bogo, M., Streck, E., Barichello, T., de Quevedo, J., Singer, M., Ritter, C., Dal-Pizzol, F. Tags: PublishAheadOfPrint Source Type: research

Angiotensin 1-7 alleviates aging-associated muscle weakness and bone loss, but is not associated with accelerated aging in ACE2-knockout mice
In this study, we investigated the role of the A1-7-Mas pathway in the effect of ACE2 on physiological aging. Male wild-type, ACE2KO, and Mas knockout (MasKO) mice were subjected to periodical grip strength measurement, followed by administration of A1-7 or vehicle for 4 weeks at 24 months of age. ACE2KO mice exhibited decreased grip strength after 6 months of age, while grip strength of MasKO mice was similar to that of wild-type mice. A1-7 improved grip strength in ACE2KO and wild-type mice, but not in MasKO mice. Muscle fibre size was smaller in ACE2KO mice than that in wild-type and MasKO mice, and increased with A1-7 ...
Source: Clinical Science - September 12, 2019 Category: Biomedical Science Authors: Nozato, S., Yamamoto, K., Takeshita, H., Nozato, Y., Imaizumi, Y., Fujimoto, T., Yokoyama, S., Nagasawa, M., Takeda, M., Hongyo, K., Akasaka, H., Takami, Y., Takeya, Y., Sugimoto, K., Mogi, M., Horiuchi, M., Rakugi, H. Tags: PublishAheadOfPrint Source Type: research

Oxytocin system alleviates intestinal inflammation by regulating macrophages polarization in experimental colitis
In this study, we investigated the effect of oxytocin, a neuroendocrinal and pro-health peptide, on the modulation of macrophages polarization and the progression of experimental colitis. Our data demonstrated that oxytocin decreased the sensitivity of macrophages to LPS stimulation with lower expression of inflammatory cytokines, like IL-1β, IL-6, and TNF-α, but increased the sensitivity to IL-4 stimulation with enhanced expression of M2-type genes, arginase (ARG1), CD206, and chitinase-like 3 (Chil3). This bidirectional modulation was partly due to the upregulation of β-arrestin2 and resulted in the inhib...
Source: Clinical Science - September 12, 2019 Category: Biomedical Science Authors: Tang, Y., Shi, Y., Gao, Y., Xu, X., Han, T., Li, J., Liu, C. Tags: PublishAheadOfPrint Source Type: research

Circ-0000284 arouses malignant phenotype of cholangiocarcinoma cells and regulates the biological functions of peripheral cells through cellular communication
Circular RNAs (circRNAs) play a vital role in cancers. Accumulated evidences showed that the physiological condition of cells can be reflected by the circRNAs in the exosomes they secrete, and these exosomal circRNAs can be captured by the receptor cells, thereby inducing a series of cellular responses. We performed qRT-PCR to detect the expression level of circ-0000284 in cholangiocarcinoma cell lines, tissues and plasma exosomes. Then the direct interaction between circ-0000284 and miR-637 was investigated through dual-luciferase reporter assay, RIP assay and FISH assay. Subsequently, EdU, migration, invasion assay, flow...
Source: Clinical Science - September 8, 2019 Category: Biomedical Science Authors: Wang, S., Hu, Y., Lv, X., Li, B., Gu, D., Li, Y., Sun, Y., Su, Y. Tags: PublishAheadOfPrint Source Type: research

CD8+CD28-T-cells: Key cytotoxic players impacting disease pathogenesis in chronic HBV infection
During chronic hepatitis B (CHB), CD8+T-cells downregulate CD28, the primary costimulation molecule for T-cell activation. Diverse functional attributes of CD8+CD28-T-cells are suggested in various disease contexts. The present study aimed to characterize CD8+CD28-T-cells in different phases of chronic HBV infection (CHI)- Immune-tolerance (IT), hepatitis B e-antigen-positive CHB (EP-CHB), Inactive carriers (IC) and hepatitis B e-antigen-negative CHB (EN-CHB), to appraise their contribution in HBV-related disease pathophysiology. Flow cytometry analysis of T-cells in peripheral blood of study subjects revealed enhanc...
Source: Clinical Science - September 1, 2019 Category: Biomedical Science Authors: Nandi, M., Pal, S., Ghosh, S., Chakraborty, B. C., Dey, D., Baidya, A., Shil, A., Chattopadhyaya, S., Banerjee, S., Santra, A., Chowdhury, A., Datta, S. Tags: PublishAheadOfPrint Source Type: research

Adipocytes initiates an adipose-cerebral-peripheral sympathetic reflex to induce insulin resistance during high fat feeding
The underlying mechanism by which amassing of white adipose tissue in obesity regulates sympathetic nerve system (SNS) drive to the tissues responsible for glucose disposal, and causes insulin resistance (IR), remains unknown. We tested the hypothesis that high-fat (HF) feeding increases afferent impulses from white adipose tissue that reflexively elevate efferent nerve activity to skeletal muscle and adipose tissue to impair their local glucose uptake. We also investigated how salt-intake can enhance IR. HF-fed rats received a normal salt (0.4%) or high salt (4%) diet for 3 weeks. High-salt intake in HF fed rats decreased...
Source: Clinical Science - September 1, 2019 Category: Biomedical Science Authors: Cao, W., Shi, M., Wu, L., Li, J., Yang, Z., Liu, Y., Wilcox, C. S., Hou, F. F. Tags: PublishAheadOfPrint Source Type: research

NLRP3 gain-of-function in CD4+ T lymphocytes ameliorates experimental autoimmune encephalomyelitis
NLRP3 inflammasome (NLR Pyrin-domain-containing 3) functions as an innate sensor of several PAMPs and DAMPs (pathogen- and damage-associated molecular patterns). It has been also reported as a transcription factor related to Th2 pattern, although its role in the adaptive immunity has been controversial, mainly because the studies were performed using gene deletion approaches. In the present study we have investigated the NLRP3 gain-of-function in the context of encephalomyelitis autoimmune disease (EAE), considered to be a Th1- and Th17-mediated disease. We took advantage of an animal model with NLRP3 gain-of-function excl...
Source: Clinical Science - August 29, 2019 Category: Biomedical Science Authors: Braga, T. T., Brandao, W. N., Azevedo, H., Terra, F. F., Melo, A. C. L., Pereira, F. V., Andrade-Oliveira, V., Hiyane, M. I., Peron, J. P. S., Camara, N. O. S. Tags: PublishAheadOfPrint Source Type: research

Quantitative reduction of short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease
Chronic kidney disease (CKD) affects 10-15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that required to improve renal function remain unknown. The present study aim to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis...
Source: Clinical Science - August 28, 2019 Category: Biomedical Science Authors: Wang, S., Lv, D., Jiang, S. h., Jiang, J., Liang, M., Hou, F. F., Chen, Y. Tags: PublishAheadOfPrint Source Type: research

The deficiency of miR-214-3p exacerbates cardiac fibrosis via miR-214-3p/NLRC5 axis
In conclusion, our findings show that the deficiency of miR-214-3p exacerbates cardiac fibrosis and reveal a novel miR-214-3p/NLRC5 axis in the regulation of cardiac fibrosis. (Source: Clinical Science)
Source: Clinical Science - August 20, 2019 Category: Biomedical Science Authors: Yang, K., Shi, J., Hu, Z., Hu, X. Tags: PublishAheadOfPrint Source Type: research

Exosomal microRNA-122 mediates obesity-related cardiomyopathy through suppressing mitochondrial ADP-ribosylation factor-like 2
In conclusions, our present study firstly showed that liver-secreted exosomal miR-122 played a critical role in the development of metabolic cardiomyopathy, and miR-122/mitochondrial Arl-2 signaling affected cardiac energy homeostasis. (Source: Clinical Science)
Source: Clinical Science - August 20, 2019 Category: Biomedical Science Authors: Wang, Y., Jin, P., Liu, J., Xie, X. Tags: PublishAheadOfPrint Source Type: research

Synovium-derived stromal cell-induced osteoclastogenesis: A potential osteoarthritis trigger
Conclusions: Osteoclastogenic differentiation capability of PBMCs from OA subjects, also induced by B synoviocytes has been already documented. Here we hypothesized that SDSCs, generally considered for their regenerative potential in cartilage lesions, have also a role in the onset/maintenance of OA. Clinical Relevance: Our observations may represent an interesting opportunity for the development of a holistic approach for OA treatment, that considers the multifaceted capability of MSCs in relation to the environment. (Source: Clinical Science)
Source: Clinical Science - August 14, 2019 Category: Biomedical Science Authors: Dicarlo, M., Teti, G., Cerqueni, G., Iezzi, I., Gigante, A., Falconi, M., Mattioli-Belmonte, M. Tags: PublishAheadOfPrint Source Type: research

In vitro and in vivo investigation of cardiotoxicity associated with anticancer proteasome inhibitors and their combination with anthracycline
In this study, we investigated the toxicity of clinically used PIs alone (bortezomib, carfilzomib) as well as their combinations with an anthracycline (daunorubicin) in both neonatal and adult ventricular cardiomyocytes (NVCMs and AVCMs) and in a chronic rabbit model of daunorubicin-induced HF. Using NVCMs, we found significant cytotoxicity of both PIs around their maximum plasma concentration (cmax) as well as significant augmentation of daunorubicin cytotoxicity. In AVCMs, bortezomib did not induce significant cytotoxicity in therapeutic concentrations, whereas the toxicity of carfilzomib was significant and more profoun...
Source: Clinical Science - August 12, 2019 Category: Biomedical Science Authors: Pokorna, Z., Jirkovsky, E., Hlavackova, M., Jansova, H., Jirkovska, A., Lencova-Popelova, O., Brazdova, P., Kubes, J., Sotakova-Kasparova, D., Mazurova, Y., Adamcova, M., Vostatkova, L., Holzerova, K., Kolar, F., Simunek, T., Sterba, M. Tags: PublishAheadOfPrint Source Type: research

Chemerin-9, a potent agonist of chemerin receptor (ChemR23), prevents atherogenesis
Plasma levels of chemerin,an adipocytokine produced from the adipose tissues and liver,are associated with metabolic syndrome and coronary artery disease (CAD). Chemerin and its analog,chemerin-9,are known to bind to their receptor,ChemR23. However, whether chemerin and chemerin-9 affect atherogenesis remains to be elucidated. We investigated the expression of chemerin and ChemR23 in human coronary arteries and cultured human vascular cells. The effects of chemerin and chemerin-9 on atheroprone phenomena were assessed in human THP1 monocytes, human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle c...
Source: Clinical Science - August 8, 2019 Category: Biomedical Science Authors: Sato, K., Yoshizawa, H., Seki, T., Shirai, R., Yamashita, T., Okano, T., Shibata, K., Wakamatsu, M. J., Mori, Y., Morita, T., Matsuyama, T.-a., Ishibashi-Ueda, H., Hirano, T., Watanabe, T. Tags: PublishAheadOfPrint Source Type: research

BMSCs-derived Exosomes Carrying MicroRNA-122-5p Promote Progression of Osteoblasts in Osteonecrosis of the Femoral Head
Mesenchymal stem cells (MSCs) with multipotential differentiation capacity can differentiate into bone cells under specific conditions and can be used to treat osteonecrosis of the femoral head (ONFH) through cell transplantation. The current study aims to explore the role of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes carrying microRNA-122-5p (miR-122-5p) in ONFH rabbit models. Firstly, rabbit models with ONFH were established. ONFH-related miRNAs were screened using the GEO database. A gain-of-function study was performed to investigate the effect of miR-122-5p on osteoblasts and BMSCs and effects of exos...
Source: Clinical Science - August 5, 2019 Category: Biomedical Science Authors: Liao, W., Ning, Y., Xu, H.-J., Zou, W.-Z., Hu, J., Liu, X.-Z., Yang, Y., Li, Z.-H. Tags: PublishAheadOfPrint Source Type: research