9,949 results match your criteria Clinical Science[Journal]


MKP2 suppresses TGF-β1-induced epithelial-to-mesenchymal transition through JNK inhibition.

Authors:
Ivonne Loeffler

Clin Sci (Lond) 2019 Feb 13;133(3):545-550. Epub 2019 Feb 13.

Department of Internal Medicine III, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany

Interstitial fibrosis is a typical feature of end-stage renal diseases, regardless of the initial cause of kidney injury. Epithelial-to-mesenchymal transition (EMT) is a mechanism that is thought to play a role in generating the interstitial matrix-producing myofibroblasts and is prominently induced by the transforming growth factor-β 1 (TGF-β1). TGF-β1 signals through a variety of Smad and non-Smad signaling pathways, including the mitogen-activated protein kinase (MAPK) pathways. Read More

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http://dx.doi.org/10.1042/CS20180881DOI Listing
February 2019
1 Read

Emerging awareness on the importance of skeletal muscle in liver diseases: time to dig deeper into mechanisms!

Clin Sci (Lond) 2019 Feb 12;133(3):465-481. Epub 2019 Feb 12.

Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium

Skeletal muscle is a tissue that represents 30-40% of total body mass in healthy humans and contains up to 75% of total body proteins. It is thus the largest organ in non-obese subjects. The past few years have seen increasing awareness of the prognostic value of appreciating changes in skeletal muscle compartment in various chronic diseases. Read More

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http://dx.doi.org/10.1042/CS20180421DOI Listing
February 2019

The first identified heterozygous nonsense mutations in podocalyxin offer new perspectives on the biology of podocytopathies.

Clin Sci (Lond) 2019 Feb 8;133(3):443-447. Epub 2019 Feb 8.

The Biomedical Research Centre, University of British Columbia, Vancouver, Canada

In the last two decades, our understanding of the genetic underpinnings of inherited podocytopathies has advanced immensely. By sequencing the genomes of a large pool of families affected by focal segmental glomerulosclerosis (FSGS), researchers have identified a common theme: familial podocytopathies are frequently caused by genes selectively expressed in podocytes. Podocalyxin is a podocyte-specific surface sialomucin that has long been known to play important roles in podocyte morphogenesis and function. Read More

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http://dx.doi.org/10.1042/CS20181067DOI Listing
February 2019
1 Read

Alamandine attenuates arterial remodelling induced by transverse aortic constriction in mice.

Clin Sci (Lond) 2019 Feb 8. Epub 2019 Feb 8.

Federal University of Minas Gerais, Belo Horizonte, Brazil.

Aims - The renin-angiotensin system (RAS) plays an important role in the pathophysiology of vascular diseases, especially as a mediator of inflammation and tissue remodelling. Alamandine is a new biologically active peptide from the RAS, interacting with Mas-related G-protein-coupled receptor member D. Although a growing number of studies reveal the cardioprotective effects of alamandine, there is a paucity of data on its participation in vascular remodelling associated events. Read More

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http://dx.doi.org/10.1042/CS20180547DOI Listing
February 2019

Matrine reduces cigarette smoke-induced airway neutrophilic inflammation by enhancing neutrophil apoptosis.

Clin Sci (Lond) 2019 02 7. Epub 2019 Feb 7.

School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia

Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and will become the third largest cause of death in the world by 2030. It is well established that an exaggerated inflammatory and oxidative stress response to cigarette smoke (CS) leads to, emphysema, small airway fibrosis, mucus hypersecretion and progressive airflow limitation. Current treatments have limited efficacy in inhibiting chronic inflammation and consequently do not reverse the pathology that initiate and drive the long-term progression of disease. Read More

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http://dx.doi.org/10.1042/CS20180912DOI Listing
February 2019
1 Read

Activation of G protein-coupled estrogen receptor protects intestine from ischemia/reperfusion injury in mice by protecting the crypt cell proliferation.

Clin Sci (Lond) 2019 Feb 8;133(3):449-464. Epub 2019 Feb 8.

Department of Physiology and Pathohysiology, School of Basic Medical Science, Shandong University, Jinan 250012, China

The intestinal ischemia/reperfusion (I/R) injury is a common clinical event related with high mortality in patients undergoing surgery or trauma. Estrogen exerts salutary effect on intestinal I/R injury, but the receptor type is not totally understood. We aimed to identify whether the G protein-coupled estrogen receptor (GPER) could protect the intestine against I/R injury and explored the mechanism. Read More

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http://dx.doi.org/10.1042/CS20180919DOI Listing
February 2019
2 Reads
5.598 Impact Factor

Balancing mitochondrial dynamics via increasing mitochondrial fusion attenuates infarct size and left ventricular dysfunction in rats with cardiac ischemia/reperfusion injury.

Clin Sci (Lond) 2019 Feb 12;133(3):497-513. Epub 2019 Feb 12.

Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand

An uncontrolled balance of mitochondrial dynamics has been shown to contribute to cardiac dysfunction during ischemia/reperfusion (I/R) injury. Although inhibition of mitochondrial fission could ameliorate cardiac dysfunction, modulation of mitochondrial fusion by giving a fusion promoter at different time-points during cardiac I/R injury has never been investigated. We hypothesized that giving of a mitochondrial fusion promoter at different time-points exerts cardioprotection with different levels of efficacy in rats with cardiac I/R injury. Read More

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http://dx.doi.org/10.1042/CS20190014DOI Listing
February 2019

Omeprazole prevents CDX2 and SOX9 expression by inhibiting hedgehog signaling in Barrett's esophagus cells.

Clin Sci (Lond) 2019 Feb 12;133(3):483-495. Epub 2019 Feb 12.

State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

Activation of hedgehog (Hh) signaling contributes to the progression of Barrett's esophagus (BE), which increases the risk of esophageal adenocarcinoma. Recent clinical studies revealed that proton-pump inhibitors (PPIs) but not H2 receptor antagonists (H2RAs) were associated with a decreased risk of esophageal adenocarcinoma. We would like to know whether PPIs interfere with BE progression during BE treatment. Read More

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http://dx.doi.org/10.1042/CS20180828DOI Listing
February 2019
4 Reads

Involvement of serum amyloid A1 in the rupture of fetal membranes through induction of collagen I degradation.

Clin Sci (Lond) 2019 Feb 12;133(3):515-530. Epub 2019 Feb 12.

Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China

The synthesis of serum amyloid A1 (SAA1) is augmented in human fetal membranes at parturition. However, its role in parturition remains largely unknown. Here, we investigated whether SAA1 was involved in the rupture of fetal membranes, a crucial event in parturition accompanied with extensive degradation of collagens. Read More

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http://dx.doi.org/10.1042/CS20180950DOI Listing
February 2019

Micromanaging human placental function: differential microRNA expression in feto-placental endothelial cells of gestational diabetes pregnancies.

Clin Sci (Lond) 2019 Jan 25;133(2):315-319. Epub 2019 Jan 25.

Epigenetics Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, VIC, 3052, Australia and Department of Paediatrics, University of Melbourne, Parkville, VIC, 3052, Australia

Healthy development in utero relies on the appropriate exchange of nutrients and other signalling between the maternal and fetal circulations. Disruption to this fine balance is associated with several pregnancy and adverse birth outcomes, including gestational diabetes mellitus (GDM). This is a complex condition influenced by genetic, environment and potentially epigenetic factors in association with a range of altered developmental outcomes. Read More

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http://dx.doi.org/10.1042/CS20180901DOI Listing
January 2019
1 Read
5.598 Impact Factor

Transforming growth factor β (TGFβ) and related molecules in chronic kidney disease (CKD).

Clin Sci (Lond) 2019 Jan 25;133(2):287-313. Epub 2019 Jan 25.

Pathophysiology of Diabetic Complications Laboratory, Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia

The incidence of chronic kidney diseases (CKDs) is expected to rise, fuelled by the ever increasing epidemic of Type 2 diabetes. Despite extensive research in this area, there are currently no effective treatments available to sufficiently halt the progression of CKD towards renal failure. This is largely due to ongoing secondary pathological processes generally elicited by the onset of disease. Read More

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http://dx.doi.org/10.1042/CS20180438DOI Listing
January 2019
3 Reads

Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7).

Clin Sci (Lond) 2019 Jan 25;133(2):269-286. Epub 2019 Jan 25.

Philips Research Europe, High Tech Campus 34, 5656AE Eindhoven, The Netherlands

Increased PSA-based screening for prostate cancer has resulted in a growing number of diagnosed cases. However, around half of these are 'indolent', neither metastasizing nor leading to disease specific death. Treating non-progressing tumours with invasive therapies is currently regarded as unnecessary over-treatment with patients being considered for conservative regimens, such as active surveillance (AS). Read More

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http://dx.doi.org/10.1042/CS20180519DOI Listing
January 2019
1 Read

Suppression of miRNA let-7i-5p promotes cardiomyocyte proliferation and repairs heart function post injury by targetting CCND2 and E2F2.

Clin Sci (Lond) 2019 Feb 5;133(3):425-441. Epub 2019 Feb 5.

State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

MiRNAs regulate the cardiomyocyte (CM) cell cycle at the post-transcriptional level, affect cell proliferation, and intervene in harmed CM repair post-injury. The present study was undertaken to characterize the role of let-7i-5p in the processes of CM cell cycle and proliferation and to reveal the mechanisms thereof. In the present study, we used real-time qPCR (RT-qPCR) to determine the up-regulated let-7i-5p in CMs during the postnatal switch from proliferation to terminal differentiation and further validated the role of let-7i-5p by loss- and gain-of-function of let-7i-5p in CMs and We found that the overexpression of let-7i-5p inhibited CM proliferation, whereas the suppression of let-7i-5p significantly facilitated CM proliferation. Read More

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http://dx.doi.org/10.1042/CS20181002DOI Listing
February 2019

PCSK9 inhibition 2018: riding a new wave of coronary prevention.

Clin Sci (Lond) 2019 Jan 22;133(2):205-224. Epub 2019 Jan 22.

School of Medicine, University of Western Australia, Perth, Australia

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic enzyme that regulates the low-density lipoprotein cholesterol (LDL-c) receptor and thus circulating LDL-c levels. With overwhelming evidence now supporting the reduction in LDL-c to lower the risk of cardiovascular disease, PCSK9 inhibitors represent an important therapeutic target, particularly in high-risk populations. Here, we summarise and update the science of PCSK9, including its discovery and the development of various inhibitors, including the now approved monoclonal antibodies. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20171300
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http://dx.doi.org/10.1042/CS20171300DOI Listing
January 2019
11 Reads

Trained immunity and diabetic vascular disease.

Clin Sci (Lond) 2019 Jan 18;133(2):195-203. Epub 2019 Jan 18.

Department of Internal Medicine (463), Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, the Netherlands

Trained immunity is a recently described phenomenon whereby innate immune cells undergo functional reprogramming in response to microbial products, vaccines, or other stimuli, leading them to mount a sensitized nonspecific response to subsequent stimulation. While it is essential for the host response to pathogens, many diseases are the product of excessive or chronic inflammation. Atherosclerosis is a disease characterized by chronic low-grade inflammation of the arterial wall leading to plaque formation, where macrophages are the most abundant cell regulating plaque progression and stability. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180905
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http://dx.doi.org/10.1042/CS20180905DOI Listing
January 2019
6 Reads
5.598 Impact Factor

Immunotherapy: enhancing the efficacy of this promising therapeutic in multiple cancers.

Clin Sci (Lond) 2019 Jan 18;133(2):181-193. Epub 2019 Jan 18.

Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, United Kingdom

Cancer treatments often reach a refractory period leading to treatment failure and patients developing disease recurrence. This can be due to tumour cells escaping the immune response and creating an immunosuppressive microenvironment enhancing cancer progression. Immunotherapy has become a promising tool for cancer treatment as it restores the anti-tumour response of the patient's immune system. Read More

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http://dx.doi.org/10.1042/CS20181003DOI Listing
January 2019
4 Reads

ADAM8 in invasive cancers: links to tumor progression, metastasis, and chemoresistance.

Clin Sci (Lond) 2019 Jan 11;133(1):83-99. Epub 2019 Jan 11.

Department of Neurosurgery, Philipps University Marburg, Baldingerstrasse, Marburg D-35033, Germany

Ectodomain shedding of extracellular and membrane proteins is of fundamental importance for cell-cell communication in neoplasias. A Disintegrin And Metalloproteinase (ADAM) proteases constitute a family of multifunctional, membrane-bound proteins with traditional sheddase functions. Their protumorigenic potential has been attributed to both, essential (ADAM10 and ADAM17) and 'dispensable' ADAM proteases (ADAM8, 9, 12, 15, and 19). Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180906
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http://dx.doi.org/10.1042/CS20180906DOI Listing
January 2019
7 Reads

NLRP3 Activation Induced by Neutrophil Extracellular Traps Sustains Inflammatory Response in the Diabetic Wound.

Clin Sci (Lond) 2019 Jan 9. Epub 2019 Jan 9.

burn and plastic surgery, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

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 (Mϕ) 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. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180600
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http://dx.doi.org/10.1042/CS20180600DOI Listing
January 2019
4 Reads

Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure.

Clin Sci (Lond) 2019 Feb 5;133(3):393-405. Epub 2019 Feb 5.

Laboratory of Cardiorespiratory Control, Department of Physiology, Pontificia Universidad Católica de Chile, Santiago, Chile.

Activation of the sympathetic nervous system is a hallmark of heart failure (HF) and is positively correlated with disease progression. Catecholaminergic (C1) neurons located in the rostral ventrolateral medulla (RVLM) are known to modulate sympathetic outflow and are hyperactivated in volume overload HF. However, there is no conclusive evidence showing a contribution of RVLM-C1 neurons to the development of cardiac dysfunction in the setting of HF. Read More

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http://dx.doi.org/10.1042/CS20180589DOI Listing
February 2019
5 Reads
5.598 Impact Factor

ZEB1-AS1 is associated with poor prognosis in non-small-cell lung cancer and influences cell migration and apoptosis by repressing ID1.

Clin Sci (Lond) 2019 Jan 30;133(2):381-392. Epub 2019 Jan 30.

Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China

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. Read More

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http://dx.doi.org/10.1042/CS20180983DOI Listing
January 2019
2 Reads

SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice.

Clin Sci (Lond) 2019 Jan 30;133(2):351-365. Epub 2019 Jan 30.

Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, CONICET- Universidad Austral, Av. Pte. Perón 1500 (B1629AHJ) Derqui-Pilar, Buenos Aires, Argentina

Obesity, metabolic syndrome, and type 2 diabetes, three strongly interrelated diseases, are associated to increased morbidity and mortality worldwide. The pathogenesis of obesity-associated disorders is still under study. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein expressed in many cell types including adipocytes, parenchymal, and non-parenchymal hepatic cells and pancreatic cells. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180714
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http://dx.doi.org/10.1042/CS20180714DOI Listing
January 2019
10 Reads

USP4 deficiency exacerbates hepatic ischaemia/reperfusion injury via TAK1 signalling.

Clin Sci (Lond) 2019 Jan 30;133(2):335-349. Epub 2019 Jan 30.

Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430060, China.

Ubiquitin-specific peptidase 4 (USP4) protein is a type of deubiquitination enzyme that is correlated with many important biological processes. However, the function of USP4 in hepatic ischaemia/reperfusion (I/R) injury remains unknown. The aim of the present study was to explore the role of USP4 in hepatic I/R injury. Read More

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http://dx.doi.org/10.1042/CS20180959DOI Listing
January 2019
1 Read

Poldip2 deficiency protects against lung edema and vascular inflammation in a model of acute respiratory distress syndrome.

Clin Sci (Lond) 2019 Jan 25;133(2):321-334. Epub 2019 Jan 25.

Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA 30322, U.S.A.

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 δ-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. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180944
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http://dx.doi.org/10.1042/CS20180944DOI Listing
January 2019
7 Reads

Electrolyte transport in the renal collecting duct and its regulation by the renin-angiotensin-aldosterone system.

Clin Sci (Lond) 2019 Jan 8;133(1):75-82. Epub 2019 Jan 8.

Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan

Distal nephron of the kidney plays key roles in fluid volume and electrolyte homeostasis by tightly regulating reabsorption and excretion of Na, K, and Cl Studies to date demonstrate the detailed electrolyte transport mechanisms in principal cells of the cortical collecting duct, and their regulation by renin-angiotensin-aldosterone system (RAAS). In recent years, however, accumulating data indicate that intercalated cells, another cell type that is present in the cortical collecting duct, also play active roles in the regulation of blood pressure. Notably, pendrin in β-intercalated cells not only controls acid/base homeostasis, but is also one of the key components controlling salt and K transport in distal nephron. Read More

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http://dx.doi.org/10.1042/CS20180194DOI Listing
January 2019
1 Read

Fetal programming and the angiotensin-(1-7) axis: a review of the experimental and clinical data.

Clin Sci (Lond) 2019 Jan 8;133(1):55-74. Epub 2019 Jan 8.

Cardiovascular Sciences Center, Wake Forest School of Medicine, 526 Vine Street, Winston Salem, NC 27157, U.S.A.

Hypertension is the primary risk factor for cardiovascular disease that constitutes a serious worldwide health concern and a significant healthcare burden. As the majority of hypertension has an unknown etiology, considerable research efforts in both experimental models and human cohorts has focused on the premise that alterations in the fetal and perinatal environment are key factors in the development of hypertension in children and adults. The exact mechanisms of how fetal programming events increase the risk of hypertension and cardiovascular disease are not fully elaborated; however, the focus on alterations in the biochemical components and functional aspects of the renin-angiotensin (Ang) system (RAS) has predominated, particularly activation of the Ang-converting enzyme (ACE)-Ang II-Ang type 1 receptor (ATR) axis. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20171550
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http://dx.doi.org/10.1042/CS20171550DOI Listing
January 2019
2 Reads

Neutral endopeptidase inhibitors blunt kidney fibrosis by reducing myofibroblast formation.

Clin Sci (Lond) 2019 Jan 22;133(2):239-252. Epub 2019 Jan 22.

Department of Internal Medicine (Nephrology) and the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands

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 cyclic guanosine monophosphate (cGMP)-dependent anti-fibrotic properties likely due to interference with pro-fibrotic tissue growth factor β (TGF-β) signaling. However, , natriuretic peptides are rapidly degraded by neutral endopeptidases (NEP). Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180882
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http://dx.doi.org/10.1042/CS20180882DOI Listing
January 2019
4 Reads

LncRNA DCST1-AS1 functions as a competing endogenous RNA to regulate FAIM2 expression by sponging miR-1254 in hepatocellular carcinoma.

Clin Sci (Lond) 2019 Jan 30;133(2):367-379. Epub 2019 Jan 30.

Department of Hepato-Pancreato-Biliary Surgery, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, P.R. China

Long non-coding RNAs (lncRNAs) play important roles in a variety of tumours; however, their biological function and clinical significance in hepatocellular carcinoma (HCC) are still unclear. In the present 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. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180814
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http://dx.doi.org/10.1042/CS20180814DOI Listing
January 2019
5 Reads
5.598 Impact Factor

Sodium 4-phenylbutyrate treatment protects against renal injury in NZBWF1 mice.

Clin Sci (Lond) 2019 Jan 18;133(2):167-180. Epub 2019 Jan 18.

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, U.S.A.

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 New Zealand Black x New Zealand White F hybrid (NZBWF1) mouse model of SLE. Read More

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http://dx.doi.org/10.1042/CS20180562DOI Listing
January 2019
2 Reads

Rare mutations of from TOFs induce hypertrophy in human embryonic stem cell-derived cardiomyocytes via HB-EGF signaling.

Clin Sci (Lond) 2019 Jan 22;133(2):225-238. Epub 2019 Jan 22.

Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China

Tetralogy of Fallot (TOF) is the most common cyanotic form of congenital heart defects (CHDs). The right ventricular hypertrophy is associated with the survival rate of patients with repaired TOF. However, very little is known concerning its genetic etiology. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180842
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http://dx.doi.org/10.1042/CS20180842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365624PMC
January 2019
8 Reads

C677T polymorphism increases MTX sensitivity via the inhibition of -adenosylmethionine and purine synthesis.

Clin Sci (Lond) 2019 01 25;133(2):253-267. Epub 2019 Jan 25.

Food Science and Biotechnology, National Chung Hsing University (NCHU), Taichung, Taiwan

Currently, no guidelines are established for pharmacogenomic testing involving folate metabolic genes in long-term disease-modifying antirheumatic drugs' (DMARD) therapies. We carefully investigated how common genetic variations in methylenetetrahydrofolate reductase () influence cellular metabolic kinetics in response to methotrexate (MTX). Two distinct cell models: HepG2 with stabilized inhibition using shRNA delivered by a Lentiviral vector; and Epstein-Barr virus transformed human lymphoblasts expressing polymorphic allele 677C and 677T were used. Read More

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http://dx.doi.org/10.1042/CS20180932DOI Listing
January 2019
3 Reads

The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig.

Clin Sci (Lond) 2019 Jan 15;133(1):153-166. Epub 2019 Jan 15.

Surgical Research Laboratory, Institute of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway.

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 the present 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. Read More

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http://dx.doi.org/10.1042/CS20180858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331658PMC
January 2019
4 Reads

Histamine and diabetic nephropathy: an up-to-date overview.

Clin Sci (Lond) 2019 Jan 3;133(1):41-54. Epub 2019 Jan 3.

Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, Turin 10125, Italy

The classification of diabetic nephropathy (DN) as a vascular complication of diabetes makes the possible involvement of histamine, an endogenous amine that is well known for its vasoactive properties, an interesting topic for study. The aim of the present review is to provide an extensive overview of the possible involvement of histamine in the onset and progression of DN. The evidence collected on the role of histamine in kidney function together with its well-known pleiotropic action suggest that this amine may act simultaneously on glomerular hyperfiltration, tubular inflammation, fibrosis development and tubular hypertrophy. Read More

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http://dx.doi.org/10.1042/CS20180839DOI Listing
January 2019
2 Reads

MicroRNAs and other non-coding RNAs in adipose tissue and obesity: emerging roles as biomarkers and therapeutic targets.

Clin Sci (Lond) 2019 Jan 3;133(1):23-40. Epub 2019 Jan 3.

Department of Nutrition, Food Science and Physiology/Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain.

Obesity is a metabolic condition usually accompanied by insulin resistance (IR), type 2 diabetes (T2D), and dyslipidaemia, which is characterised by excessive fat accumulation and related to white adipose tissue (WAT) dysfunction. Enlargement of WAT is associated with a transcriptional alteration of coding and non-coding RNAs (ncRNAs). For many years, big efforts have focused on understanding protein-coding RNAs and their involvement in the regulation of adipocyte physiology and subsequent role in obesity. Read More

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http://dx.doi.org/10.1042/CS20180890DOI Listing
January 2019
1 Read

The vermiform appendix: an immunological organ sustaining a microbiome inoculum.

Clin Sci (Lond) 2019 Jan 3;133(1):1-8. Epub 2019 Jan 3.

Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney 2006, Australia.

The hominoid vermiform appendix has been characterized as a diverticulum of the caecum and describes an entity at the juxtaposition of the colon in the confluence of tanias. The independent development of the lymphoid follicle centres of the appendix is progressed at birth in the presence of the intestinal commensal microbiome, an obligatory prompt for the diversification of intestinal and extra-intestinal mucosal immunological tissue. In the vermiform appendix, this activity is centred on further developing the inventory of primary antibodies and the maturation of T- and B-lymphocyte cells in the follicles within the lymphoid tissue. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180956
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http://dx.doi.org/10.1042/CS20180956DOI Listing
January 2019
8 Reads

Elafibranor interrupts adipose dysfunction-mediated gut and liver injury in mice with alcoholic steatohepatitis.

Clin Sci (Lond) 2019 Feb 13;133(3):531-544. Epub 2019 Feb 13.

Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan

Reversal of alcohol-induced peroxisome proliferator-activated receptor (PPAR) α (PPARα) and PPARδ dysfunction has been reported to decrease the severity of alcoholic steatohepatitis (ASH). Autophagy is essential for cell survival and tissue energy homeostasis. Emerging evidence indicates that alcohol-induced adipose tissue (AT) autophagy dysfunction contributes to injury in the intestine, liver, and AT of ASH. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180873
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http://dx.doi.org/10.1042/CS20180873DOI Listing
February 2019
5 Reads

Up-regulated ferritin in periodontitis promotes inflammatory cytokine expression in human periodontal ligament cells through transferrin receptor via ERK/P38 MAPK pathways.

Clin Sci (Lond) 2019 Jan 11;133(1):135-148. Epub 2019 Jan 11.

Department of Periodontology, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, P.R. China

Objective: Ferritin, an iron-binding protein, is ubiquitous and highly conserved; it plays a crucial role in inflammation, which is the main symptom of periodontitis. Full-length cDNA library analyses have demonstrated abundant expression of ferritin in human periodontal ligament. The aims of the present study were to explore how ferritin is regulated by local inflammation, and to investigate its functions and mechanisms of action in the process of periodontitis. Read More

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http://dx.doi.org/10.1042/CS20180679DOI Listing
January 2019
2 Reads

Much Ado about N…atrium: modelling tissue sodium as a highly sensitive marker of subclinical and localized oedema.

Clin Sci (Lond) 2018 Dec 13;132(24):2609-2613. Epub 2018 Dec 13.

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K.

Hypertonic Na accumulation in peripheral tissues is a recently described phenomenon: it has been associated with ageing, hypertension, diabetes, chronic kidney disease and heart failure, but its clinical meaning has yet to be determined. This concept conflicts with the classic physiological paradigm of constant balance between salt intake and excretion, and its water-independent nature is still a matter of debate.We developed a theoretical model explaining changes in the chemical composition of tissues as a function of extracellular volume fraction and excess extracellular fluid, i. Read More

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http://dx.doi.org/10.1042/CS20180575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365627PMC
December 2018
3 Reads

Possible role of phytoestrogens in breast cancer via GPER-1/GPR30 signaling.

Clin Sci (Lond) 2018 Dec 13;132(24):2583-2598. Epub 2018 Dec 13.

Laboratory of Cellular Pathology, Institute of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia, Chile

Estrogens generated within endocrine organs and the reproductive system act as ligands for at least three types of estrogen receptors. Estrogen receptors α (ERα) and β (ERβ) belong to the so-called classical family of estrogen receptors, whereas the G protein-coupled receptor GPR30, also known as GPER-1, has been described as a novel estrogen receptor sited in the cell membrane of target cells. Furthermore, these receptors are under stimulation of a family of exogenous estrogens, known as phytoestrogens, which are a diverse group of non-steroidal plant compounds derived from plant food consumed by humans and animals. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180885
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http://dx.doi.org/10.1042/CS20180885DOI Listing
December 2018
10 Reads

First identification of nonsense mutations in autosomal dominant focal segmental glomerulosclerosis.

Clin Sci (Lond) 2019 Jan 3;133(1):9-21. Epub 2019 Jan 3.

Department of Nephrology, 97th Hospital of PLA, Xuzhou 221004, Jiangsu Province, China

Recently, a novel heterozygous missense mutation c.T1421G (p. L474R) in the gene encoding podocalyxin was identified in an autosomal dominant focal segmental glomerulosclerosis (AD-FSGS) pedigree. Read More

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http://dx.doi.org/10.1042/CS20180676DOI Listing
January 2019
3 Reads

GPR120 protects lipotoxicity-induced pancreatic β-cell dysfunction through regulation of PDX1 expression and inhibition of islet inflammation.

Clin Sci (Lond) 2019 Jan 11;133(1):101-116. Epub 2019 Jan 11.

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China

G-protein coupled receptor 120 (GPR120) has been shown to act as an omega-3 unsaturated fatty acid sensor and is involved in insulin secretion. However, the underlying mechanism in pancreatic β cells remains unclear. To explore the potential link between GPR120 and β-cell function, its agonists docosahexaenoic acid (DHA) and GSK137647A were used in palmitic acid (PA)-induced pancreatic β-cell dysfunction, coupled with GPR120 knockdown (KD) in MIN6 cells and GPR120 knockout (KO) mice to identify the underlying signaling pathways. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180836
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http://dx.doi.org/10.1042/CS20180836DOI Listing
January 2019
9 Reads

Heme oxygenase-1 induction by hemin prevents oxidative stress-induced acute cholestasis in the rat.

Clin Sci (Lond) 2019 Jan 11;133(1):117-134. Epub 2019 Jan 11.

Instituto de Fisiología Experimental (IFISE-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (U.N.R.), Rosario, Argentina

We previously demonstrated in and models that physiological concentrations of unconjugated bilirubin (BR) prevent oxidative stress (OS)-induced hepatocanalicular dysfunction and cholestasis. Here, we aimed to ascertain, in the whole rat, whether a similar cholestatic OS injury can be counteracted by heme oxygenase-1 (HO-1) induction that consequently elevates endogenous BR levels. This was achieved through the administration of hemin, an inducer of HO-1, the rate-limiting step in BR generation. Read More

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http://dx.doi.org/10.1042/CS20180675DOI Listing
January 2019
2 Reads

Investigating the RAS can be a fishy business: interdisciplinary opportunities using Zebrafish.

Clin Sci (Lond) 2018 Dec 5;132(23):2469-2481. Epub 2018 Dec 5.

University of Edinburgh/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, The University of Edinburgh, 47, Little France Crescent, Edinburgh EH16 4TJ, U.K.

The renin-angiotensin system (RAS) is highly conserved, and components of the RAS are present in all vertebrates to some degree. Although the RAS has been studied since the discovery of renin, its biological role continues to broaden with the identification and characterization of new peptides. The evolutionarily distant zebrafish is a remarkable model for studying the kidney due to its genetic tractability and accessibility for imaging. Read More

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http://dx.doi.org/10.1042/CS20180721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279434PMC
December 2018
1 Read

Functional cardiac orexin receptors: role of orexin-B/orexin 2 receptor in myocardial protection.

Clin Sci (Lond) 2018 Dec 13;132(24):2547-2564. Epub 2018 Dec 13.

Translational and Experimental Medicine, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, U.K.

Orexins/hypocretins exert cardiovascular effects which are centrally mediated. In the present study, we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative reverse transcription-PCR (RT-PCR), immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors (OXR). Read More

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http://dx.doi.org/10.1042/CS20180150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365625PMC
December 2018
11 Reads
5.600 Impact Factor

Type 3 innate lymphoid cell: a new player in liver fibrosis progression.

Clin Sci (Lond) 2018 Dec 13;132(24):2565-2582. Epub 2018 Dec 13.

Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China

Type 3 innate lymphoid cell (ILC3) has recently emerged as a crucial effector in inflammatory and fibrotic diseases. The present study was designed to determine the roles of ILC3 in liver fibrosis. By flow cytometry, we documented increased frequencies of peripheral ILC3 (LinCD127CD117CD294 lymphocytes) in patients, especially at the advanced stage of hepatitis B virus (HBV)-related chronic liver diseases, and demonstrated their correlations with disease progression. Read More

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http://dx.doi.org/10.1042/CS20180482DOI Listing
December 2018
11 Reads

Impact of the gut microbiome in cardiovascular and autoimmune diseases.

Authors:
Michael Weis

Clin Sci (Lond) 2018 Nov 19;132(22):2387-2389. Epub 2018 Nov 19.

Hospital Neuwittelsbach of the Sisters of Mercy, Renatastrasse 71a, 80639, Munich, Germany

The gut microbiome functions like an endocrine organ, generating enzymes and bioactive metabolites, which affect host physiology. In addition metabolism-independent processes like impaired intestinal barrier function may result in bacterial translocation and an increased inflammation. Specific microbe-associated molecular patterns (MAMPs) have been detected that induce immune activation via cognate pattern-recognition receptors on host immune cells, with subsequent consequences on inflammatory-induced endothelial dysfunction. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180410
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http://dx.doi.org/10.1042/CS20180410DOI Listing
November 2018
8 Reads

Changes in cell fate determine the regenerative and functional capacity of the developing kidney before and after release of obstruction.

Clin Sci (Lond) 2018 Dec 5;132(23):2519-2545. Epub 2018 Dec 5.

Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, U.S.A.

Congenital obstructive nephropathy is a major cause of chronic kidney disease (CKD) in children. The contribution of changes in the identity of renal cells to the pathology of obstructive nephropathy is poorly understood. Using a partial unilateral ureteral obstruction (pUUO) model in genetically modified neonatal mice, we traced the fate of cells derived from the renal stroma, cap mesenchyme, ureteric bud (UB) epithelium, and podocytes using , and mice respectively, crossed with double fluorescent reporter (membrane-targetted tandem dimer Tomato (mT)/membrane-targetted GFP (mG)) mice. Read More

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http://clinsci.org/lookup/doi/10.1042/CS20180623
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http://dx.doi.org/10.1042/CS20180623DOI Listing
December 2018
12 Reads

Urinary angiotensinogen as a biomarker for acute to chronic kidney injury transition - prognostic and mechanistic implications.

Clin Sci (Lond) 2018 Nov 13;132(21):2383-2385. Epub 2018 Nov 13.

Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, U.K.

Accurate biomarkers that both predict the progression to, and detect the early stages of chronic kidney disease (CKD) are lacking, resulting in difficulty in identifying individuals who could potentially benefit from targeted intervention. In a recent issue [ (2018) , 2121-2133], Cui et al. examine the ability of urinary angiotensinogen (uAGT) to predict the progression of acute kidney injury (AKI) to CKD. Read More

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http://dx.doi.org/10.1042/CS20180795DOI Listing
November 2018
2 Reads