Search results for "genetics [Transcriptome]"

Expression of WISPs and of their novel alternative variants in human hepatocellular carcinoma cells

2005

WISPs (Wnt-induced secreted proteins) are members of the CCN (CTGF/Cyr61/Nov) family involved in fibrotic disorders and tumorigenesis. They have a typical structure composed of four conserved cysteine-rich modular domains, but variants of CCN members lacking one or more modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. WISP genes were first described as downstream targets of the Wnt signaling pathway, which is frequently altered in human hepatocellular carcinoma (HCC). In the present study, WISP mRNA expression was analyzed by RT-PCR in four human HCC cell lines (HepG2, HuH-6, HuH-7, HA22T/VGH). Our results show for the fir…

Can Hepatoma Cell Lines be Re-differentiated to be Used in Drug Metabolism Studies?

2013

Knowledge of metabolism, enzymes so far involved, and potential enzyme-inhibiting or enzyme-inducing properties of new compounds is a key issue in drug development. Primary cultured hepatocytes, cytochrome P450 (CYP)-engineered cells and hepatoma cell lines are currently being used for this purpose, but only primary cultures can produce a metabolic profile of a drug similar to that found in vivo and can respond to inducers. Because of their limited accessibility, alternatives to replace human hepatocytes are currently being explored, including the immortalisation of hepatocytes by using different strategies (i.e. SV40 T-large antigen, conditionally immortalised hepatocytes, transfection wi…

Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac f…

2021

Abstract Aims Doxorubicin (DOX) is an important drug for the treatment of various tumor entities. However, the occurrence of heart failure limits its application. This study investigated differential gene expression profiles in the left and right ventricles of DOX treated mice with either preserved or impaired myocardial function. We provide new mechanistic insights into the pathophysiology of DOX-induced heart failure and have discovered pathways that counteract DOX-induced cardiotoxicity. Main methods We used in total 48 male mice and applied a chronic low dose DOX administration (5 mg/kg per injection, in total 20 mg/kg over 4 weeks) to induce heart failure. Echocardiographic parameters …

Ocular Comorbidities and the Relationship between Eye Diseases and Systemic Disorders

2016

Patients with ocular disorders may have additional ophthalmic problems that can have an impact on both morbidity and vision. Ocular comorbidities are commonly associated with vision-related disability and decreased quality of life related to visual impairment. The majority of studies on this topic deal with cataracts, glaucoma, uveitis, and/or retinopathies. It is important to summarize the available evidence to date on the association of one or several ocular diseases and the implications these comorbidities have on prognosis and therapy. The relationship between eye disorders and systemic diseases has recently drawn special interest. The increasing prevalence of neurodegenerative disorder…

PREDICTION OF CEREBROVASCULAR AND CARDIOVASCULAR EVENTS IN PATIENTS WITH SUBLINICAL CAROTID ATHEROSCLEROSIS: THE ROLE OF C-REACTIVE PROTEIN

2008

Background Several studies have suggested that inflammation and infection may be important for accelerated progression of atherosclerosis, but few data are available on subjects with early stages of atherosclerosis. Methods and Results We included, in a prospective 5-year follow-up study, 150 patients with subclinical carotid atherosclerosis, evaluating at baseline all established traditional cardiovascular risk factors (eg, older age, male sex, obesity, hypertension, diabetes, smoking, family history of coronary artery disease, and dyslipidemia); 2 markers of inflammation, fibrinogen, and high-sensitivity C-reactive protein (CRP); and the seropositivity to Helicobacter pylori, Chlamydia pn…

Centriolar satellites expedite mother centriole remodeling to promote ciliogenesis

2023

Centrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by Pericentriolar material 1 (PCM1). To study the requirement for centriolar satellites, we generated mice lacking PCM1, a crucial component of satellites. Pcm1−/− mice display partially penetrant perinatal lethality with survivors exhibiting hydrocephalus, oligospermia, and cerebellar hypoplasia, and variably expressive phenotypes such as hydronephrosis. As many of these phenotypes have been observed in human ciliopathies and satellites are implicated in cilia biology, we investigated whether cilia were affected. PCM1 was dispensable for ciliogenesis in many cell types, whereas Pcm1−/− multiciliated…

Electrophoresis of Unlabeled Proteins in a Sequencing Gel Apparatus

2000

Cryopreservation of Escherichia coli K12TG1: Protection from the damaging effects of supercooling by freezing

2015

Injuries in living cells caused by water freezing during a freeze-thaw process have been extensively reported. In particular, intracellular water freezing has long been incriminated in cell death caused by a high cooling rate, but this supposition could not always be demonstrated. This work aims to discriminate the role of water freezing, dehydration and cold-induced injuries in cellular damage occuring during cryopreservation. For this purpose, Escherichia coli K12TG1 suspensions were maintained in a supercooled or frozen state at -20°C for times ranging from 10 min to 5 h. The supercooled state was maintained for a long period at -20°C by applying a non-injurious isostatic pressure (P<40 …

Assembly mechanism of the oligomeric streptolysin O pore: the early membrane lesion is lined by a free edge of the lipid membrane and is extended gra…

1998

Streptolysin O (SLO) is a bacterial exotoxin that binds to cell membranes containing cholesterol and then oligomerizes to form large pores. Along with rings, arc-shaped oligomers form on membranes. It has been suggested that each arc represents an incompletely assembled oligomer and constitutes a functional pore, faced on the opposite side by a free edge of the lipid membrane. We sought functional evidence in support of this idea by using an oligomerization-deficient, non-lytic mutant of SLO. This protein, which was created by chemical modification of a single mutant cysteine (T250C) with N-(iodoacetaminoethyl)-1-naphthylamine-5-sulfonic acid, formed hybrid oligomers with active SLO on memb…

Kinetic models for nucleocytoplasmic transport of messenger RNA

1995

Abstract Much is known about the mechanism by which mRNAs cross the nuclear envelope (the translocation stage of nucleocytoplasmic transport), but far less is known about the preceding (intranuclear migration/release) and succeeding (cytoplasmic binding) stages. Therefore, existing information suffices for articulating detailed kinetic models of translocation, but not models for the overall mRNA transport process. In this paper, we show that simple kinetic models of translocation can (i) accommodate date about nucleocytoplasmic distributions of endogenous transcripts; (ii) predict the overall effects on these distributions of effectors such as insulin and epidermal growth factor; (iii) thro…