MTHFR C677T polymorphism Increases MTX Sensitivity via the Inhibition of S-adenosylmethionine and De Novo Purine Synthesis
Conclusions.Combining cell models, kinetic studies, and genetic tests in humans, this study gives insight on how MTHFR effects hepatic transmethylation homeostasis during MTX therapy. We provide platforms that help predict the genetic impact on anti-folate drugs, and further delineate tissue-specific target pathway in DMARD therapies. We suggest that genetic factors should be taken into account in clinical practice. (Source: Clinical Science)
Source: Clinical Science - January 17, 2019 Category: Biomedical Science Authors: Wang, Y.-C., Wu, M.-T., Tang, F.-Y., Chen, D.-Y., Ko, H.-A., Shane, B., Huang, W.-N., Chiang, E.-P. Tags: PublishAheadOfPrint Source Type: research
Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure
Activation of the sympathetic nervous system is ahallmark of heart failure and is positively correlated with disease progression. Catecholaminergic (C1) neurons locatedin the rostral ventrolateral medulla (RVLM) are known to modulate sympathetic outflow and are hyperactivated in volume overload heart failure (HF). However, there is no conclusiveevidence showing acontribution of RVLM-C1 neurons to the developmentof cardiac dysfunctionin the setting of HF. Therefore, the aim of this study was to determine the role of RVLM-C1 neurons in cardiac autonomic control and deterioration of cardiac function in HF rats. A surgical art...
Source: Clinical Science - January 9, 2019 Category: Biomedical Science Authors: Andrade, D. C., Toledo, C., Diaz, H. S., Lucero, C., Arce-Alvarez, A., Oliveira, L. M., Takakura, A. C., Moreira, T. S., Schultz, H. D., Marcus, N. J., Alcayaga, J., Del Rio, R. Tags: PublishAheadOfPrint Source Type: research
NLRP3 Activation Induced by Neutrophil Extracellular Traps Sustains Inflammatory Response in the Diabetic Wound
Persistent inflammatory response in the diabetic wound impairs the healing process, resulting in significant morbidity and mortality. Mounting evidence indicates that the activation of Nod-like receptor protein (NLRP) 3 inflammasome in macrophages (M) contributes to the sustained inflammatory response and impaired wound healing associated with diabetes. However, the main trigger of NLRP3 inflammasome in the wounds is not known. Neutrophils, as sentinels of the innate immune system and key stimulators of M, are immune cells that play the main role in the early phase of healing. Neutrophils release extracellular traps (NETs)...
Source: Clinical Science - January 9, 2019 Category: Biomedical Science Authors: Liu, D., Yang, P., Gao, M., Yu, T., Shi, Y., Zhang, M., Yao, M., Liu, Y., Zhang, X. Tags: PublishAheadOfPrint Source Type: research
SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice
This study provides the first evidence that deleted SPARC expression causes diabetes in mice. Thus, SPARC deficient mice constitute a valuable model for studies concerning obesity and its related metabolic complications, including diabetes. (Source: Clinical Science)
Source: Clinical Science - January 9, 2019 Category: Biomedical Science Authors: Atorrasagasti, C., Onorato, A., Gimeno, M. L., Andreone, L., Garcia, M., Malvicini, M., Fiore, E., Bayo, J., Perone, M. J., Mazzolini, G. Tags: PublishAheadOfPrint Source Type: research
ZEB1-AS1 is associated with poor prognosis in non-small-cell lung cancer and influences cell migration and apoptosis by repressing ID1
Long non-coding RNAs (lncRNAs) have been reported to play a vital role in non-small cell lung cancer (NSCLC). ZEB1-AS1 overexpression predicts a poor prognosis in osteosarcoma and colorectal cancers. In the current study, we determined the clinical significance and prognostic value of ZEB1-AS1 in patients with NSCLC. The expression of ZEB1-AS1 and inhibitor of differentiation-1 (ID1) was measured using qRT-PCR and Western blot. Cell growth, migration, and invasion was determined using colony formation assays, Transwell assay, and flow cytometry, respectively. Tumor growth was determined with a xenograft model. ZEB1-AS1 was...
Source: Clinical Science - January 9, 2019 Category: Biomedical Science Authors: Jin, J., Wang, H., Si, J., Ni, R., Liu, Y., Wang, J. Tags: PublishAheadOfPrint Source Type: research
Poldip2 Deficiency Protects Against Lung Edema and Vascular Inflammation in a Model of Acute Respiratory Distress Syndrome
Acute respiratory distress syndrome (ARDS) in a deadly disease that can be brought on by endotoxins such as lipopolysaccharide (LPS). ARDS is characterized by vascular permeability, a severe inflammatory response, lung leukocyte infiltration, and resultant lung edema. Polymerase delta-interacting protein 2 (Poldip2) is a novel regulator of blood-brain barrier permeability; however, its role in regulating lung permeability and vascular inflammation is unknown. Here, the role of Poldip2 in regulating vascular permeability and inflammation in a mouse model of ARDS was assessed. Heterozygous deletion of Poldip2 was found to re...
Source: Clinical Science - January 8, 2019 Category: Biomedical Science Authors: Forrester, S. J., Xu, Q., Kikuchi, D. S., Okwan-Duodu, D., Campos, A. C., Faidley, E. A., Zhang, G., Lassegue, B., Sadikot, R. T., Griendling, K. K., Hernandes, M. S. Tags: PublishAheadOfPrint Source Type: research
USP4 deficiency exacerbates hepatic ischaemia/reperfusion injury via TAK1 signalling
In conclusion, our study demonstrates that USP4 deficiency plays a detrimental role in hepatic I/R injury by promoting activation of the TAK1/JNK signalling pathways. Modulation of this axis may be a novel strategy to alleviate the pathological process of hepatic I/R injury. (Source: Clinical Science)
Source: Clinical Science - January 8, 2019 Category: Biomedical Science Authors: Zhou, J., Qiu, T., Wang, T., Chen, Z., Ma, X., Zhang, L., Zou, J. Tags: PublishAheadOfPrint Source Type: research
Sodium 4-phenylbutyrate treatment protects against renal injury in NZBWF1 mice
Systemic lupus erythematosus (SLE) is an autoimmune disease predominantly affecting women and often leading to lupus nephritis and kidney damage. Endoplasmic reticulum (ER) stress has been implicated in several forms of kidney disease, but whether ER stress contributes to renal injury in SLE is unknown. To investigate this, a small molecule chaperone, sodium 4-phenylbutyrate (4-PBA), was administered to the NZBWF1 mouse model of SLE. In a prevention study, treatment with 4-PBA from 20 weeks of age (prior to the development of renal injury) delayed the onset of albuminuria and significantly reduced additional indices of ren...
Source: Clinical Science - January 7, 2019 Category: Biomedical Science Authors: Bonnemaison, M. L., Marks-Nelson, E. S., Boesen, E. I. Tags: PublishAheadOfPrint Source Type: research
LncRNA DCST1-AS1 functions as a competing endogenous RNA to regulate FAIM2 expression by sponging miR-1254 in hepatocellular carcinoma
In this study, the clinical significance, biological function and regulatory mechanisms of lncRNA DCST1-AS1 in HCC were investigated. Differential lncRNAs in HCC were identified based on The Cancer Genome Atlas (TCGA) database. The biological function and mechanism of DCST1-AS1 were studied in vitro and in vivo. LncRNA DCST1-AS1 was highly expressed in HCC tissues, and the high expression of DCST1-AS1 was significantly correlated with larger tumours and shorter survival time. Moreover, DCST1-AS1 knockout significantly inhibited proliferation, promoted apoptosis and cycle arrest of HCC cells, and inhibited tumour growth in ...
Source: Clinical Science - January 7, 2019 Category: Biomedical Science Authors: Chen, J., Wu, D., Zhang, Y., Yang, Y., Duan, Y., An, Y. Tags: PublishAheadOfPrint Source Type: research
Neutral endopeptidase inhibitors blunt kidney fibrosis by reducing myofibroblast formation
Kidney fibrosis is the common pathophysiological mechanism in end-stage-renal-disease characterized by excessive accumulation of myofibroblast-derived extracellular matrix. Natriuretic peptides have been demonstrated to have cGMP-dependent anti-fibrotic properties likely due to interference with pro-fibrotic TGF-β signaling. However, in vivo , natriuretic peptides are rapidly degraded by neutral endopeptidases (NEP). In a unilateral urether obstruction (UUO) mouse model for kidney fibrosis we assessed the anti-fibrotic effects of SOL1, an orally-active compound that inhibits NEP and endothelin-converting enzyme (ECE)...
Source: Clinical Science - January 7, 2019 Category: Biomedical Science Authors: Bijkerk, R., Aleksinskaya, M. A., Duijs, J. M., Veth, J., Husen, B., Reiche, D., Prehn, C., Adamski, J., Rabelink, T. J., De Mey, J. G. R., van Zonneveld, A. J. Tags: PublishAheadOfPrint Source Type: research
Rare mutations of ADAM17 from TOFs induce hypertrophy in human embryonic stem cell-derived cardiomyocytes via HB-EGF signaling
In this study, we sequenced ADAM10 and ADAM17 in a Han Chinese CHD cohort comprised of 80 TOF patients, 286 other CHD patients, and 480 matched healthy controls. Three missense variants of ADAM17 were only identified in 80 TOF patients, two of which (Y42D and L659P) are novel and not found in the ExAC database. Point mutation knock-in (KI) and ADAM17 KO human embryonic stem cells (hESCs) were generated by CRISPR/Cas9 and programmed to differentiate into cardiomyocytes (CMs). Y42D or L659P KI cells or complete KO cells all developed hypertrophy with disorganized sarcomeres. RNA-seq results showed that PI3K/Akt, whic...
Source: Clinical Science - January 4, 2019 Category: Biomedical Science Authors: Xie, Y., Ma, A., Wang, B., Peng, R., Jing, Y., Wang, D., Finnell, R. H., Qiao, B., Wang, Y., Wang, H., Zheng, Y. Tags: PublishAheadOfPrint Source Type: research
MTHFR C677T polymorphism Increases MTX Sensitivity via the Inhibition of S-adenosylmethionine and De Novo Purine Synthesis
Conclusions.Combining cell models, kinetic studies, and genetic tests in humans, this study gives insight on how MTHFR effects hepatic transmethylation homeostasis during MTX therapy. We provide platforms that help predict the genetic impact on anti-folate drugs, and further delineate tissue-specific target pathway in DMARD therapies. We suggest that genetic factors should be taken into account in clinical practice. (Source: Clinical Science)
Source: Clinical Science - January 3, 2019 Category: Biomedical Science Authors: Wang, Y.-C., Wu, M.-T., Tang, F.-Y., Chen, D.-Y., Ko, H.-A., Shane, B., Huang, W.-N., Chiang, E.-P. Tags: PublishAheadOfPrint Source Type: research
The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig
Liver failure is the major cause of death following liver resection. Post-resection portal venous pressure (PVP) predicts liver failure, is implicated in its pathogenesis and when PVP is reduced, rates of liver dysfunction decrease. The aim of this study was to characterize the hemodynamic, biochemical and histological changes induced by 80% hepatectomy in non-cirrhotic pigs and determine if terlipressin or direct portacaval shunting can modulate these effects.Pigs were randomized (n=8/group) to undergo 80% hepatectomy alone (control); terlipressin (2 mg bolus + 0.5-1 mg/h) + 80% hepatectomy; or portacaval shunt (PCS) + 80...
Source: Clinical Science - January 3, 2019 Category: Biomedical Science Authors: Hammond, J. S., Godtliebsen, F., Steigen, S., Guha, I. N., Wyatt, J., Revhaug, A., Lobo, D. N., Mortensen, K. E. Tags: PublishAheadOfPrint Source Type: research
Elafibranor Interrupts Adipose Dysfunction-mediated Gut and Liver Injury in Mice with Alcoholic Steatohepatitis
Conclusions : Altogether, these findings demonstrated that the PPARα/ agonist, elafibranor, decreased the severity of liver injury by restoration of alcohol-suppressed AT autophagy function and by decreasing the release of apoptotic markers, inflammatory cytokines and FFA, thereby reducing intestinal epithelium disruption and liver inflammation/apoptosis/steatosis in ASH mice. These data suggest that dual PPAR agonists can serve as potential therapeutic agents for the management of ASH. (Source: Clinical Science)
Source: Clinical Science - January 2, 2019 Category: Biomedical Science Authors: Li, T.-H., Yang, Y.-Y., Huang, C.-C., Liu, C.-W., Tsai, H.-C., Lin, M.-W., Tsai, C.-Y., Huang, S.-F., Wang, Y.-W., Lee, T.-Y., Huang, Y.-H., Hou, M.-C., Lin, H.-C. Tags: PublishAheadOfPrint Source Type: research
Upregulated Ferritin in Periodontitis Promotes Inflammatory Cytokine Expression in Human Periodontal Ligament Cells through Transferrin Receptor via ERK/P38 MAPK Pathways
Conclusions:Ferritin is upregulated by inflammation and exhibits cytokine-like activity in HPDLCs inducing a signaling cascade which promote expression of pro-inflammatory cytokines associated with periodontitis. (Source: Clinical Science)
Source: Clinical Science - December 14, 2018 Category: Biomedical Science Authors: Huang, W., Zhan, Y., Zheng, Y., Han, Y., Hu, W., Hou, J. Tags: PublishAheadOfPrint Source Type: research
