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 16, 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 13, 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 13, 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 9, 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 enhanced CD8...
Source: Clinical Science - September 2, 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 2, 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 30, 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 29, 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 21, 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 21, 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 15, 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 13, 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 9, 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 6, 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

Preclinical effects of highly potent MEK1/2 inhibitors on rat cerebral vasculature after organ culture and subarachnoid haemorrhage
Conclusion: The PD0325901 treatment did not improve the neurological score after SAH, nor showed any beneficial therapeutic effect on the contractility, contrasting with the reduction in neurological deficits seen after trametinib treatment. These data show that trametinib might be a potential candidate for treatment of SAH. (Source: Clinical Science)
Source: Clinical Science - August 6, 2019 Category: Biomedical Science Authors: Christensen, S. T., Haanes, K. A., Spray, S., Grell, A.-S., Warfvinge, K., Edvinsson, L., Johansson, S. E. Tags: PublishAheadOfPrint Source Type: research

Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition
Macrophage polarization towards the M1 phenotype and its subsequent inflammatory response have been implicated in the progression of diabetic complications. Despite adverse consequences of autophagy impairment on macrophage inflammation, the regulation of macrophage autophagy under hyperglycemic conditions is incompletely understood. Here, we report that the autophagy-lysosome system and mitochondrial function are impaired in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-stimulated RAW 264.7 cells. Mitochondrial dysfunction promotes reactive oxygen species (ROS) production and blocks autophagic flux by i...
Source: Clinical Science - August 5, 2019 Category: Biomedical Science Authors: Yuan, Y., Chen, Y., Peng, T., Li, L., Zhu, W., Liu, F., Liu, S., An, X., Luo, R., Cheng, J., Liu, J., Lu, Y. Tags: PublishAheadOfPrint Source Type: research

Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPAR{gamma}-mediated pathway in bladder cancer
Tumor cells rely on aerobic glycolysis as their main energy resource (Warburg effect). Recent researches highlighted the importance of lipid metabolism in tumor progression and certain cancers even turn to fatty acids as main fuel. Related studies have identified alterations of fatty acid metabolism in human bladder cancer (BCa). Our microarray analysis showed that fatty acid metabolism was activated in BCa compared with normal bladder. And the free fatty acid (FFA) level was increased in BCa compared with paracancerous tissues. Inhibition of FAO with etomoxir caused lipid accumulation, decreased adenosine triphosphate (AT...
Source: Clinical Science - July 29, 2019 Category: Biomedical Science Authors: Cheng, S., Wang, G., Wang, Y., Cai, L., Qian, K., Ju, L., Liu, X., Xiao, Y., Wang, X. Tags: PublishAheadOfPrint Source Type: research

Effect of Mycophenolate and Rapamycin on Renal Fibrosis in Lupus Nephritis
Lupus nephritis (LN) leads to chronic kidney disease through progressive fibrosis. Mycophenolate inhibits inosine monophosphate dehydrogenase and is a standard treatment for LN. The mammalian or mechanistic target of rapamycin (mTOR) pathway is activated in LN. Rapamycin inhibits mTOR and is effective in preventing kidney transplant rejection, with the additional merits of reduced incidence of malignancies and viral infections. The effect of mycophenolate or rapamycin on kidney fibrosis in LN has not been investigated. We investigated the effects of mycophenolate and rapamycin in NZB/W F1 murine LN and human mesangial cell...
Source: Clinical Science - July 29, 2019 Category: Biomedical Science Authors: Zhang, C., Chan, C. C., Cheung, K. F., Chau, M. K., Yap, D. Y., Ma, M. K., Chan, K. W., Yung, S., Chan, T. M. Tags: PublishAheadOfPrint Source Type: research

Empagliflozin prevents cardiomyopathy via sGC-cGMP-PKG pathway in type 2 diabetes mice
Cardiovascular complications contribute to the major mortality and morbidity in type 2 diabetes. Diabetic cardiomyopathy (DCM) is increasingly recognized as an important cause of heart failure. EMPA-REG OUTCOME trial has reported that empagliflozin, the sodium-glucose cotransporter 2 inhibitor, exerts cardiovascular benefits on diabetic population. However, the mechanism by which empagliflozin alleviates DCM still remains unclear. In the current study, we investigated the cardiac protective effects of empagliflozin on spontaneous type 2 diabetes db/db mice and its potential mechanism. 8 weeks of empagliflozin treatment (10...
Source: Clinical Science - July 23, 2019 Category: Biomedical Science Authors: Xue, M., Li, T., Wang, Y., Chang, Y., Cheng, Y., Lu, Y., Liu, X., Xu, L., Li, X., Yu, X., Sun, B., Chen, L. Tags: PublishAheadOfPrint Source Type: research

Endothelial progenitor cell-derived exosomes facilitate vascular endothelial cell repair through shuttling miR-21-5p to modulate Thrombospondin-1 expression
CONCLUSIONS: The present work highlights a critical event for the regulation of EC behavior by EPC-exosomes, which EPC-exosomes may deliver miR-21-5p and inhibit THBS1 expression to promote endothelial cell repair. (Source: Clinical Science)
Source: Clinical Science - July 17, 2019 Category: Biomedical Science Authors: Hu, H., Wang, B., Jiang, C., Li, R., Zhao, J. Tags: PublishAheadOfPrint Source Type: research

RIPK1 inhibitor Cpd-71 attenuates renal dysfunction in cisplatin-treated mice via attenuating necroptosis, inflammation and oxidative stress
In this study, we evaluated the treatment effects of Cpd-71, a novel RIPK1 inhibitor, by comparing with Necrostatin-1 (Nec-1), a classic RIPK1 inhibitor, which has several drawbacks like the narrow structure activity relationship (SAR) profile, moderate potency and non-ideal pharmacokinetic properties, in vivo and in vitro . Our results showed that pretreatment of Cpd-71 attenuated cisplatin-induced renal injury, restored renal function, and suppressed renal inflammation, oxidative stress and cell necroptosis. In addition, Cpd-71 inhibited renal damage while reducing the upregulated serum creatinine and BUN levels in estab...
Source: Clinical Science - July 17, 2019 Category: Biomedical Science Authors: Wang, J.-n., Liu, M.-m., Wang, F., Wei, B., Yang, Q., Cai, Y.-t., Chen, X., Liu, X.-q., Jiang, L., Li, C., Hu, X.-w., Yu, J.-t., Ma, T.-t., Jin, J., Wu, Y.-g., Li, J., Meng, X.-M. Tags: PublishAheadOfPrint Source Type: research

PBI-4050 via GPR40 activation improves adenine-induced kidney injury in mice
PBI-4050, a novel first-in-class orally active compound that has completed clinical phases Ib and II in subjects with CKD and metabolic syndrome respectively, exerts antifibrotic effects in several organs via a novel mechanism of action, partly through activation of the GPR40 receptor. Here we evaluate the effects of PBI-4050 in both WT and Gpr40-/- mice on adenine-induced tubulointerstitial injury, anemia and activation of the unfolded protein response pathway. Adenine-induced CKD was achieved in eight-week old C57BL/6 mice fed a diet supplemented with 0.25% adenine. After 1 week, PBI-4050 or vehicle was administered dail...
Source: Clinical Science - July 15, 2019 Category: Biomedical Science Authors: Thibodeau, J.-F., Simard, J.-C., Holterman, C. E., Blais, A., Cloutier, M.-P., Medeiros, T., Leduc, M., Grouix, B., Leblond, F. A., Burger, D., Hebert, R. L., Kennedy, C. R. J., Gagnon, L. Tags: PublishAheadOfPrint Source Type: research

Downregulation of LncRNA XIST Inhibits Cell Proliferation via Regulating miR-744/RING1 Axis in Non-small Cell Lung Cancer
Conclusion:Taken together, it was confirmed here that XIST overexpression is associated with tumor progression phenotype and the newly discovered XIST/miR-744/RING1 axis, which could serve as a potential biomarker and therapeutic target for NSCLC. (Source: Clinical Science)
Source: Clinical Science - July 10, 2019 Category: Biomedical Science Authors: Wang, J., Cai, H., Dai, Z., Wang, G. Tags: PublishAheadOfPrint Source Type: research

Soluble ST2 promotes oxidative stress and inflammation in cardiac fibroblasts: An in vitro and in vivo study in aortic stenosis
Conclusions: sST2 affected mitochondrial fusion in human cardiac fibroblasts, increasing oxidative stress production and inflammatory markers secretion. The blockade of NFkB or mitochondrial reactive oxygen species restored MFN-1 expression, improving oxidative stress status and reducing inflammatory markers secretion. In human AS, cardiac sST2 levels associated with oxidative stress and inflammation. The present study reveals a new pathogenic pathway by which sST2 promotes oxidative stress and inflammation contributing to cardiac damage. (Source: Clinical Science)
Source: Clinical Science - July 8, 2019 Category: Biomedical Science Authors: Matilla, L., Ibarrola, J., Arrieta, V., Garcia-Pena, A., Martinez-Martinez, E., Sadaba, R., Alvarez, V., Navarro, A., Fernandez-Celis, A., Gainza, A., Santamaria, E., Fernandez-Irigoyen, J., Bayes-Genis, A., Rossignol, P., Lopez-Andres, N. Tags: PublishAheadOfPrint Source Type: research

HEG1 indicates poor prognosis and promotes hepatocellular carcinoma invasion, metastasis, and EMT by activating Wnt/{beta}-catenin signaling
In conclusion, HEG1 indicates poor prognosis; plays important roles in HCC invasion, metastasis, and EMT by activating Wnt/β-catenin signaling; and can serve as a potentially valuable prognostic biomarker and therapeutic target for HCC. (Source: Clinical Science)
Source: Clinical Science - July 5, 2019 Category: Biomedical Science Authors: Zhao, Y.-r., Wang, J.-l., Xu, C., Li, Y.-m., Sun, B., Yang, L.-y. Tags: PublishAheadOfPrint Source Type: research

CircRNA-104718 acts as competing endogenous RNA and promotes hepatocellular carcinoma progression through microRNA-218-5p/TXNDC5 signaling pathway
This study aims at investigating the role of circRNA-104718 in HCC progression, which has been observed to be significantly up-regulated in HCC tissues. We found that, higher expression of circRNA-104718 also led to a poor prognosis in HCC patients. Using luciferase binding assays and RNA immunoprecipitation studies, we identified circRNA-104718 is physically associated and co-expressed with microRNA-218-5p in HCC. Mechanistically, we demonstrated that circRNA-104718 functions as a competing endogenous RNAs (ceRNAs) and competes with thioredoxin domain-containing protein 5 (TXNDC5) mRNA and directly binds to miR-218-5p. Fu...
Source: Clinical Science - July 5, 2019 Category: Biomedical Science Authors: Yu, J., Yang, M., Zhou, B., Luo, J., Zhang, Z., Zhang, W., Yan, Z. Tags: PublishAheadOfPrint Source Type: research

Impact of ET-1 and sex in glomerular hyperfiltration in humanized sickle cell mice
Hyperfiltration, highly prevalent early in sickle cell disease (SCD), is in part driven by an increase in ultrafiltration coefficient (Kf). The increases in Kf may be due to enlarged filtration surface area and/or increased glomerular permeability (Palb). Previous studies have demonstrated that endothelin-1 (ET-1) contributes to Palb changes in models of diabetes and SCD.  Thus, we performed longitudinal studies of renal function to determine the relationship between ET-1 and glomerular size and Palb that may contribute to hyperfiltration in humanized sickle cell (HbSS) and control (HbAA) mice 8 to 32 weeks of age. Hb...
Source: Clinical Science - July 4, 2019 Category: Biomedical Science Authors: Kasztan, M., Pollock, D. M. Tags: PublishAheadOfPrint Source Type: research

Ergosterol attenuates cigarette smoke extract-induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo
The objective of this work was to investigate the effects of ergosterol on anti- inflammatory and anti-oxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both in vitro and in vivo . Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the NF-B/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of NO, IL-6, TNF-α, MDA, and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-PARP both in vitro and in vivo , where...
Source: Clinical Science - July 3, 2019 Category: Biomedical Science Authors: Sun, X., Feng, X., Zheng, D., Li, A., Li, C., Li, S., Zhao, Z. Tags: PublishAheadOfPrint Source Type: research

Nicotinamide riboside promotes autolysosome clearance in preventing doxorubicin-induced cardiotoxicity
This study investigated whether nicotinamide riboside, a precursor of NAD+, prevents doxorubicin cardiotoxicity by improving autophagic flux. We report that administration of nicotinamide riboside elevated NAD+ levels, and reduced cardiac injury and myocardial dysfunction in doxorubicin-injected mice. These protective effects of nicotinamide riboside were recapitulated in cultured cardiomyocytes upon doxorubicin treatment. Mechanistically, nicotinamide riboside prevented the blockage of autophagic flux, accumulation of autolysosomes and oxidative stress in doxorubicin-treated cardiomyocytes, the effects of which were assoc...
Source: Clinical Science - July 2, 2019 Category: Biomedical Science Authors: Zheng, D., Zhang, Y., Zheng, M., Cao, T., Wang, G., Zhang, L., Ni, R., Brockman, J., Zhong, H., Fan, G.-C., Peng, T. Tags: PublishAheadOfPrint Source Type: research

A novel lncRNA NR4A1AS upregulates orphan nuclear receptor NR4A1 expression by blocking UPF1-mediated mRNA destabilization in colorectal cancer
Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and cancer progression. The orphan nuclear receptor NR4A1 acts as an oncogene, and is involved in colorectal cancer (CRC) development. However, the mechanism through which lncRNA regulates NR4A1 expression remains unknown. We aimed to identify lncRNAs that regulate NR4A1 and assess their underlying mechanisms in CRC. We first identified an antisense lncRNA of NR4A1 that was upregulated in CRC tissues and cells with rapid amplification of cDNA ends, and designated it as NR4A1AS. Spearman correlation analysis showed that NR4A1AS was positively correlated wi...
Source: Clinical Science - June 28, 2019 Category: Biomedical Science Authors: Xie, X., Lin, J., Liu, J., Huang, M., Zhong, Y., Liang, B., Song, X., Gu, S., Chang, X., Huang, D., Tang, A. Tags: PublishAheadOfPrint Source Type: research

MicroRNA-302d promotes the proliferation of human pluripotent stem cell-derived cardiomyocytes by inhibiting LATS2 in the Hippo pathway
In this study, we demonstrate that i) expression of microRNA-302d (miR-302d) decreased significantly during CM differentiation from human pluripotent stem cells (hPSCs) from day 4 to day 18; ii) miR-302d efficiently promoted proliferation of hPSC-derived CMs; iii) miR-302d promoted CM proliferation by targeting LATS2 in the Hippo pathway; and iv) RNA-seq analysis revealed that overexpression of miR-302d induced changes in gene expression, which mainly converged on the cell cycle. Our study provides further evidence for the therapeutic potential of miR-302d. (Source: Clinical Science)
Source: Clinical Science - June 25, 2019 Category: Biomedical Science Authors: Xu, F., Yang, J., Shang, J., Lan, F., Li, M., Shi, L., Shen, L., Wang, Y., Ge, J. Tags: PublishAheadOfPrint Source Type: research

Enhanced endoplasmic reticulum and mitochondrial stress in abdominal aortic aneurysm.
Abdominal aortic aneurysm (AAA) is a degenerative vascular disease with a complex aetiology that remains to be fully elucidated. Clinical management of AAA is limited to surgical repair, while an effective pharmacotherapy is still awaited. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction have been involved in the pathogenesis of cardiovascular diseases, although their contribution to AAA development is uncertain. Therefore, we aimed to determine their implication in AAA and investigated the profile of oxysterols in plasma, specifically 7-ketocholesterol (7-KC), as an ER stress inducer. In the present study, ...
Source: Clinical Science - June 25, 2019 Category: Biomedical Science Authors: Navas-Madronal, M., Rodriguez, C., Kassan, M., Fite, J., Escudero, J. R., Canes, L., Martinez-Gonzalez, J., Camacho, M., Galan, M. Tags: PublishAheadOfPrint Source Type: research

The pseudogene PTENP1 regulates smooth muscle cells as a competing endogenous RNA
The lncRNA PTENP1 is a pseudogene of phosphatase and tensin homolog deleted on chromosome ten (PTEN), has been implicated in smooth muscle cell (SMC) proliferation and apoptosis. PTENP1 is the pseudogene of PTEN. However, it is unclear whether and how PTENP1 functions in the proliferation and apoptosis of human aortic smooth muscle cells (HASMCs). Here, we hypothesized that PTENP1 inhibits HASMC proliferation and enhances apoptosis by promoting PTEN expression. PCR analysis and Western blot assays respectively showed that both PTENP1 and PTEN were upregulated in human aortic dissection(AD) samples. PTENP1 ov...
Source: Clinical Science - June 24, 2019 Category: Biomedical Science Authors: Lai, Y., Li, J., Zhong, L., He, X., Si, X., Sun, Y., Chen, Y., Zhong, J., Hu, Y., Li, B., Liao, W., Liu, C., Liao, Y., Xiu, J., Bin, J. Tags: PublishAheadOfPrint Source Type: research

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons
Type 2 diabetes (T2D) hampers stroke recovery though largely undetermined mechanisms. Few preclinical studies have investigated the effect of genetic/toxin-induced diabetes on long-term stroke recovery. However, the effects of obesity-induced T2D are mostly unknown. We aimed to investigate whether obesity-induced T2D worsens long-term stroke recovery through the impairment of brain's self-repair mechanisms - stroke-induced neurogenesis and parvalbumin (PV)+ interneurons-mediated neuroplasticity. To mimic obesity-induced T2D in the middle-age, C57bl/6j mice were fed 12 months with high-fat diet and subjected to transient mi...
Source: Clinical Science - June 24, 2019 Category: Biomedical Science Authors: Pintana, H., Lietzau, G., Augestad, I. L., Chiazza, F., Nystrom, T., Patrone, C., Darsalia, V. Tags: PublishAheadOfPrint Source Type: research

Ovarian cancer-derived exosomes promote tumor metastasis in vivo an effect modulated by the invasiveness capacity of their originating cells
Exosomes are small nanovesicles that carry bioactive molecules which can be delivered to neighbouring cells to modify their biological functions. Interestingly, exosomes from ovarian cancer (OVCA) cells can alter the cell migration and proliferation of cells within the tumour microenvironment, an effect modulated by the invasiveness capacity of their originating cells. Using a OVCA cell line xenograph mouse model, we showed that exosomes derived from a high invasiveness capacity cell line (exo-SKOV-3) promoted metastasis in vivo compared to exosomes from a low invasiveness capacity cell line (exo-OVCAR-3). Analysis from an...
Source: Clinical Science - June 21, 2019 Category: Biomedical Science Authors: Alharbi, M., Lai, A., Guanzon, D., Palma, C., Zuniga, F., Perrin, L., He, Y., Hooper, J. D., Salomon, C. Tags: PublishAheadOfPrint Source Type: research

Overexpression of the aryl hydrocarbon receptor nuclear translocator (ARNT) partially rescues fetoplacental angiogenesis in severe fetal growth restriction
Pregnancies complicated by severe fetal growth restriction with abnormal umbilical artery Doppler velocimetry (FGRadv) are at substantial risk for adverse perinatal and long-term outcomes. Impaired angiogenesis of the placental vasculature in these pregnancies results in a sparse, poorly branched vascular tree, which structurally contributes to the abnormally elevated fetoplacental vascular resistance that is clinically manifested by absent or reversed umbilical artery Doppler indices. Previous studies have shown that aryl hydrocarbon receptor nuclear translocator (ARNT) is a key mediator of proper placental angiogenesis, ...
Source: Clinical Science - June 12, 2019 Category: Biomedical Science Authors: Ji, S., Xin, H., Su, E. J. Tags: PublishAheadOfPrint Source Type: research

G-CSF partially mediates the bone loss induced by Staphylococcus aureus infection in mice
This study aimed to elucidate how S. aureus infection in bone might induce bone loss. The C57BL/6 mice were injected with S. aureus (106 CFU/ml, 100 μl) or with the same amount of vehicle (control) via the tail vein. MicroCT analysis showed bone loss progressing from week 1 to week 5 after infection, accompanied by a decreased number of osteocalcin-positive stained osteoblasts and the suppressed mRNA expression of Runx2 and osteocalcin. Transcriptome profiles of GSE30119 were downloaded and analyzed to determine the differences in expression of inflammatory factors between patients with S. aureus infected osteomyelitis ...
Source: Clinical Science - June 7, 2019 Category: Biomedical Science Authors: Hou, Y., Qin, H., Jiang, N., Liu, G., Wu, H., Bai, L., Yu, B., Zhang, X. Tags: PublishAheadOfPrint Source Type: research

Association of functional variant in GDF1 promoter with risk of congenital heart disease and its regulation by Nkx2.5
GDF1 plays an important role in left-right patterning and genetic mutations in the coding region of GDF1 are associated with congenital heart disease (CHD). However, the genetic variation in the promoter of GDF1 with sporadic CHD and its expression regulation is little known. The association of the genetic variation in GDF1 promoter with CHD was examined in two case-control studies, including 1084 cases and 1198 controls in the first study and 582 cases and 615 controls in the second study. We identified one single nucleotide polymorphism (SNP) rs181317402 and two novel genetic mutations located in the promoter region of G...
Source: Clinical Science - June 6, 2019 Category: Biomedical Science Authors: Gao, X., Zheng, P., Yang, L., Luo, H., Zhang, C., Qiu, Y., Huang, G., Sheng, W., Ma, X., Lu, C. Tags: PublishAheadOfPrint Source Type: research

Lipid Metabolism Participates in Human Membranous Nephropathy Identified by Whole-genome Gene Expression Profiling
In this study, gene expression profiling using renal cortex tissue from iMN patients and healthy controls was conducted; differentially expressed genes (DEGs) were filtered out, and 167 up- and 291 downregulated genes were identified as overlapping differentially expressed genes (ODEGs). Moreover, enrichment analysis and protein-protein network construction were performed, revealing enrichment of genes mainly in cholesterol metabolism and arachidonic acid metabolism, among others, with 38 hub genes obtained. Furthermore, we found several associations between circulating lipid concentrations and hub gene signal intensities ...
Source: Clinical Science - June 3, 2019 Category: Biomedical Science Authors: Wu, D., Yu, Z., Zhao, S., Qu, Z., Sun, W., Jiang, Y. Tags: PublishAheadOfPrint Source Type: research

Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression
Circular RNA (circRNA) plays an important role in the development of human malignant tumors. Recently, an increasing number of circRNAs have been identified and investigated in various tumors. However, the expression pattern and biological function of circRNAs in colorectal cancer (CRC) still remain largely unexplored. In the present study, hsa_circ_0009361 was significantly downregulated in CRC tissues and cells. Low expression level of hsa_circ_0009361 promoted the proliferation, epithelial-mesenchymal transition (EMT), migration and invasion of CRC cells. Hsa_circ_0009361 was identified as the sponge of miR-582 by fluor...
Source: Clinical Science - May 20, 2019 Category: Biomedical Science Authors: Geng, Y., Zheng, X., Hu, W., Wang, Q., Xu, Y., He, W., Wu, C., Zhu, D., Wu, C., Jiang, J. Tags: PublishAheadOfPrint Source Type: research

Silencing of Junctional Adhesion Molecule-Like Protein Attenuates Atherogenesis and Enhances Plaque Stability in ApoE-/- Mice
Conclusions: Our results demonstrated that therapeutic drugs which antagonize the function of JAML may be a potentially effective approach to attenuate atherogenesis and enhance plaque stability. (Source: Clinical Science)
Source: Clinical Science - May 17, 2019 Category: Biomedical Science Authors: Sun, Y., Guan, J., Hou, Y., Xue, F., Huang, W., Zhang, W., Zhang, Y., Zhang, C., Yang, J. Tags: PublishAheadOfPrint Source Type: research

Postnatal inflammation following intrauterine inflammation exacerbates the development of atherosclerosis in ApoE-/- mice
In conclusion, pre- and postnatal inflammation have additive and deleterious effects on the development of atherosclerosis in ApoE knockout mice. The findings are particularly relevant to preterm human infants, whose gestations are frequently complicated by chorioamnionitis and who are particularly susceptible to repeated postnatal infections. Human and mechanistic studies are warranted to guide preventative strategies. (Source: Clinical Science)
Source: Clinical Science - May 14, 2019 Category: Biomedical Science Authors: Bekkering, S., Limawan, A. P., Nguyen, M. U., Widiasmoko, L. K., Lu, H., Pepe, S., Cheung, M. M., Menheniott, T. R., Wallace, M. J., Burgner, D. P., Moss, T. J. Tags: PublishAheadOfPrint Source Type: research

Mucin O-glycosylating enzyme GALNT2 facilitates the malignant character of glioma by activating the EGFR/PI3K/Akt/mTOR axis
N-Acetylgalactosaminyltransferase 2 (GALNT2), the enzyme that regulates the initial step of mucin O-glycosylation, has been reported to play a role in influencing the malignancy of various cancers. However, the mechanism through which it influences gliomas is still unknown. In the current study, the Cox proportional hazards model was used to select genes. Data obtained from The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) of clinical specimens showed that increased GALNT2 expression levels were associated with an unfavorable prognosis and a higher tumor grade in human gliomas. Then, GALNT2 knockdown a...
Source: Clinical Science - May 10, 2019 Category: Biomedical Science Authors: Sun, Z., Xue, H., Wei, Y., Wang, C., Yu, R., Wang, C., Wang, S., Xu, J., Qian, M., Meng, Q., Li, G. Tags: PublishAheadOfPrint Source Type: research

NSD2 silencing alleviates pulmonary arterial hypertension by inhibiting trehalose metabolism and autophagy
In conclusion, we reveal a new role of NSD2 in the pathogenesis of PAH related to the regulation of trehalose metabolism and autophagy via increasing the di-methylation level of H3K36 (H3K36me2). NSD2 is a promising target for PAH therapy. (Source: Clinical Science)
Source: Clinical Science - April 30, 2019 Category: Biomedical Science Authors: Zhou, X.-l., Liu, Z.-b., Zhu, R.-r., Huang, H., Xu, Q.-r., Xu, H., Zeng, L., Li, Y.-y., Huang, C.-h., Wu, Q.-c., Liu, J.-c. Tags: PublishAheadOfPrint Source Type: research

Mitochondrial protein 18 is a positive apoptotic regulator in cardiomyocytes under oxidative stress
This study aimed to detect the role of Mtp18 in H2O2-induced mitochondrial fission and apoptosis in cardiomyocytes. We studied the effect of Mtp18 in cardiomyocytes by modulating its expression with lentiviral construct of Mtp18-shRNA and Mtp18 c-DNA, respectively. We then analyzed mitochondrial morphological dynamics with MitoTracker Red staining; apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) and cell death detection assays; and protein expression with immunoblotting. Here, we observed that Mtp18 could regulate oxidative stress-mediated mitochondrial fission and apoptosis in ...
Source: Clinical Science - April 23, 2019 Category: Biomedical Science Authors: Aung, L. H. H., Li, Y.-Z., Yu, H., Chen, X., Yu, Z., Gao, J., Li, P. Tags: PublishAheadOfPrint Source Type: research

Prenatal Cold Exposure Causes Hypertension in Offspring by Hyperactivity of the Sympathetic Nervous System
This study provides evidence for overactive peripheral and central sympathetic nervous systems in the pathogenesis of prenatal cold-induced hypertension. Central AT1 receptor blockade in the PVN may be a key step for treatment of this type hypertension. (Source: Clinical Science)
Source: Clinical Science - April 23, 2019 Category: Biomedical Science Authors: Chen, K., Sun, D., Qu, S., Chen, Y., Wang, J., Zhou, L., Jose, P. A., Yang, Y., Zeng, C. Tags: PublishAheadOfPrint Source Type: research

circRASSF2 promotes laryngeal squamous cell carcinoma progression by regulating the miR-302b-3p/ IGF-1R axis
Conclusion: In conclusion, these data suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via a miR-302b-3p / IGF-1R axis. (Source: Clinical Science)
Source: Clinical Science - April 16, 2019 Category: Biomedical Science Authors: Tian, L., Cao, J., Jiao, H., Zhang, J., Ren, X., Liu, X., Liu, M., Sun, Y. Tags: PublishAheadOfPrint Source Type: research

Pharmacological inhibition of TRPV4 channels protects against ischemia-reperfusion-induced renal insufficiency in neonatal pigs
In this study, we show that pharmacological activation of TRPV4 channels constricted preglomerular microvessels and elicited renal hypoperfusion in neonatal pigs. Bilateral renal ischemia followed by short-term reperfusion increased TRPV4 protein expression in resistance size renal vessels and TRPV4-dependent cation currents in renal vascular smooth muscle cells (SMCs). Selective TRPV4 channel blockers attenuated IR-induced reduction in total renal blood flow, cortical perfusion, and glomerular filtration rate. TRPV4 inhibition also diminished renal IR-induced increase in AKI biomarkers. Furthermore, the level of angiotens...
Source: Clinical Science - April 15, 2019 Category: Biomedical Science Authors: Soni, H., Peixoto-Neves, D., Olushoga, M. A., Adebiyi, A. Tags: PublishAheadOfPrint Source Type: research

The human duodenal mucosa harbours all components for a local renin angiotensin system
Conclusion: Immunostaining and pharmacological data demonstrate the presence of a local RAS in the human duodenal mucosa with capacity to influence epithelial ion transport by way of particulary the AT2R. (Source: Clinical Science)
Source: Clinical Science - April 15, 2019 Category: Biomedical Science Authors: Spak, E., Hallersund, P., Edebo, A., Casselbrant, A., Fandriks, L. Tags: PublishAheadOfPrint Source Type: research