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共有 212 条符合本次的查询结果, 用时 2.3042174 秒

21. [Orally active aminopeptidase A inhibitors reduce blood pressure: a new strategy for treating hypertension].

作者: Catherine Llorens-Cortès.
来源: Biol Aujourdhui. 2014年208卷3期217-24页
The hyperactivity of the brain renin-angiotensin system (RAS) has been implicated in the development and maintenance of hypertension in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III display the same affinity for type 1 and type 2 Ang II receptors. Both peptides, injected intracerebroventricularly, similarly increase arginine vasopressin release and blood pressure (BP); however, because Ang II is converted in vivo to Ang III, the identity of the true effector is unknown. We first identified the enzymes involved in the metabolism of brain angiotensins and developed specific and selective inhibitors. Here we review new insights into the predominant role of brain Ang III in the control of BP, underlining the fact that brain aminopeptidase A (APA), the enzyme generating brain Ang III, may therefore be an interesting candidate target for the treatment of hypertension. This justifies the development of potent systemically active APA inhibitors, such as RB150, as prototypes of a new class of antihypertensive agents for the treatment of certain forms of hypertension.

22. [Implication of PML nuclear bodies in intrinsic and innate immunity].

作者: Mohamed Ali Maroui.;Faten El Asmi.;Jacques Dutrieux.;Mounira K Chelbi-Alix.;Sébastien Nisole.
来源: Med Sci (Paris). 2014年30卷8-9期765-71页
PML/TRIM19 is the organizer of PML nuclear bodies (NB), large multiprotein structures associated to the nuclear matrix, which recruit a great number of proteins and which are implicated in various cellular processes including antiviral defense. The conjugation of PML to SUMO is required for the formation and function of PML NB. Alternative splicing from a single PML gene generates several PML isoforms (PMLI to PMLVIIb), each harboring a specific carboxy-terminal region. This variability allows each isoform to recruit different partners and thus confers them specific functions. PML gene is directly induced by interferon and certain PML isoforms are implicated in its antiviral properties, as they display intrinsic antiviral activities against RNA or DNA viruses. One isoform, PMLIV, is also implicated in innate immunity by enhancing IFN-β production during a viral infection. Here we review recent findings on PML/TRIM19 implication in interferon response and antiviral defense, at the interface between intrinsic and innate immunity.

23. [Current therapeutic strategies in lysosomal disorders].

作者: Pierre Kaminsky.;Olivier Lidove.
来源: Presse Med. 2014年43卷11期1174-84页
The lysosomal storage disorders (LSD) comprise a heterogeneous group of inborn errors of metabolism. The resulting enzymatic defect leads to accumulation of its substrate in the lysosome. Their clinical patterns reflect the site of substrate storage. Central nervous system involvement is often present in the younger patients affected by the most severe phenotypes. Substantial progress has been made in the pathophysiological knowledge, leading to new therapeutic options in LSD. Enzyme replacement therapy (ERT) is the dominant approach and is actually proposed in six LSD: Gaucher disease, Fabry disease, Pompe disease and mucopolysaccharidoisis (MPS) I (Hurler disease), II (Hunter disease) and VI (Maroteaux-Lamy disease). This treatment reduces lysosomal storage, and sometimes reduces, but most often limits the progression of visceral involvement and of its clinical consequences. However, ERT does not cross the blood-brain barrier and is ineffective on neurological symptoms. In the younger patients with MPS I (Hurler disease) and with selected cases of other LSD, haematopoietic stem cell transplantation remains the optimal option. Other strategies using small molecules are being explored in order to cross the blood-brain barrier. This includes substrate reduction or depletion therapies, which decrease the amount of substrate, and the use of pharmacological chaperones, which enhance the residual activity of the mutant enzyme. Miglustat is the proposed substrate reduction therapy in Niemann-Pick C disease and clinical trials are actually performed in several LSD using other substrate reduction or chaperone drugs.

24. [Xenobiotics and the active gut microbiome: unknown effects unveiled].

作者: Corinne F Maurice.
来源: Med Sci (Paris). 2013年29卷10期846-8页

25. [Endoplasmic reticulum stress: from physiology to pathogenesis of type 2 diabetes].

作者: Mélissa Flamment.;Fabienne Foufelle.
来源: Med Sci (Paris). 2013年29卷8-9期756-64页
Type 2 diabetes is characterized by a dysfunction of pancreatic β cells producing insulin and by impaired insulin responses in liver and skeletal muscle. This dysregulation of insulin secretion and action leads to chronic hyperglycaemia. The main causes that have been proposed to explain the pathogenesis of type 2 diabetes are lipotoxicity, glucotoxicity, oxidative stress and inflammation. Interestingly, these alterations converge towards the activation of a cellular pathway called "Unfolded Protein Response" which is set up in β cells and insulin-sensitive tissues. This cellular pathway is central to the pathogenesis of type 2 diabetes and emerges as an important therapeutic target in the treatment of this disease.

26. [Mechanisms of action of glucocorticoids].

作者: C Dejean.;D Richard.
来源: Rev Med Interne. 2013年34卷5期264-8页
Glucocorticoids exert their actions at nuclear levels through genomic mechanisms including both transcriptional activation (transactivation) and gene expression repression (transrepression). Transactivation mechanisms are mediated by transcription factors, the main one being the activated glucocorticoid receptor (GR). These mechanisms contribute to both powerful therapeutic effects of glucocorticoids on inflammatory and immune diseases, and adverse effects than can be harmful on vital functions. Non-genomic mechanisms, which act faster than genomic ones, have also been explored. They also involve the GR in different membranous and cytosolic sites. The phenomenon of glucocorticoid resistance is also complex and several different mechanisms may mediate this phenomenon. Among them are alterations in number, binding affinity or phosphorylation status of the GR, changes in capacity of cellular apoptosis, polymorphic changes or expression of proteins involved in the genomic actions of glucocorticoids. Finally, some proteins, which mediate glucocorticoid activity could be therapeutic targets for reducing glucocorticoid-induced adverse effects.

27. [Thyroid hormone signalling favors neural stem cell commitment].

作者: Sylvie Remaud.;Ghislaine Morvan-Dubois.;Barbara A Demeneix.
来源: Med Sci (Paris). 2012年28卷12期1050-2页

28. [Masculine fertility threatened by the presence of endocrine disruptors in environment?].

作者: L Dewalque.;C Charlier.
来源: Rev Med Liege. 2012年67卷5-6期243-9页
Endocrine disruptors are chemicals substances interfering with the hormonal system. These pollutants, present in environment, can lead to diseases in human being. In this article, we take an interest to some endocrine disrupting substances linked to decrease in sperm quality and testicular dysgenesis syndrome, two pathologies involve in masculine fertility decline. The role of environment in complex diseases as male hypofertility is questioned.

29. [A new Topo to targeted management of Angelman syndrome?].

作者: Bernard Dan.;Karine Pelc.;Guy Chéron.
来源: Med Sci (Paris). 2012年28卷6-7期572-4页

30. [New painkillers inhibiting the physiological breakdown of endogenous opioids].

作者: Bernard P Roques.;Marie-Claude Fournié-Zaluski.;Michel Wurm.
来源: Med Sci (Paris). 2012年28卷5期476-8页

31. [Resistance acquisition via the bacterial SOS response: the inducive role of antibiotics].

作者: Sandra Da Re.;Marie-Cécile Ploy.
来源: Med Sci (Paris). 2012年28卷2期179-84页
After the euphoria of the antibiotic discovery and their tremendous action on bacterial infections outcomes, arrives a period of fear with the continuous emergence of bacteria that are resistant to almost all antibiotic treatments. It is becoming essential to better understand antibiotic resistance mechanisms to find new approaches to prevent the worldwide problem of multiresistance. The role of antibiotics on the direct induction of resistance acquisition is known. Recent studies have shown that some antibiotics, by inducing the bacterial SOS response, global repair response after DNA damages, are involved on a broader level in the induction, acquisition and dissemination of resistances in bacteria. We discuss here the role of antibiotics in resistance acquisition via the SOS response through several examples and the interest of identifying the SOS response regulators as the future targets of new families of antimicrobial molecules.

32. [The second (main) phase of an open, randomised, multicentre study to investigate the effectiveness of an INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2): protocol and baseline characteristics of patients included in France].

作者: C Delcourt.;C Stapf.;C Tzourio.;S Héritier.;C Anderson.
来源: Rev Neurol (Paris). 2012年168卷4期321-7页
The INTERACT pilot study demonstrated the feasibility of the protocol, safety of early intensive blood pressure (BP) lowering, and effects on hematoma expansion within 6hours of onset of intracerebral hemorrhage (ICH). This article describes the design of the second, main phase, INTERACT2. INTERACT2 aims to compare the effects of a management strategy of early intensive BP lowering with a more conservative guideline-based BP management policy in patients with acute ICH. This article also compares the baseline characteristics of the patients included in France with the baseline characteristics of the patients included in the pilot study INTERACT1.

33. [Histone methyltransferases: a new class of therapeutic targets in cancer treatment?].

作者: Hassiba Chaib.;Thomas Prébet.;Norbert Vey.;Yves Collette.
来源: Med Sci (Paris). 2011年27卷8-9期725-32页
Epigenetic gene regulation contributes, together with genetic alterations, to cancer development and progression. In contrast to genetic disorders, the possibility of reversing epigenetic alterations has provided original targets for therapeutic application. In the last years, work has been focused on the pharmacological restoration of epigenetic regulation balance using epidrugs which yield hopes for novel strategy in cancer therapy. Histone acetylation and DNA methylation are epigenetic modifications which have been closely linked to the pathology of human cancers, and inhibitors of both enzyme classes for clinical use are at hands. Novel findings accumulated during the last years both in chemistry and biomedical applications give rise to new targeted treatments against cancer. Since their links with pathogenesis and progression of cancer were recognized, histone methyltransferases emerge as promising therapeutic targets in cancer treatment.

34. [The IKKε kinase in breast cancer: from oncogenesis to treatment resistance].

作者: Nathalie Grandvaux.
来源: Med Sci (Paris). 2011年27卷6-7期619-25页
The IKKε kinase, an atypical member of the IKK family of kinases, was recently identified as an oncogene overexpressed in over 30% of breast cancers. Besides its role in the regulation of the NF-κB transcription factor, which is well recognized for its implication in the development of breast cancers, IKKε was shown to phosphorylate numerous targets. Analysis of the phosphorylation of some of these substrates in the context of breast cancer highlighted new oncogenic signaling pathways that constitute potential targets for new therapies. Interestingly, IKKε is involved in the development of resistance to Tamoxifène. Thus, IKKε is a promising therapeutic target for newly developed breast cancer treatment.

35. [Rescue of nonsense mutated p53 by readthrough leads to apoptosis in cancers cells].

作者: Célia Floquet.;Jean-Pierre Rousset.;Laure Bidou.
来源: Med Sci (Paris). 2011年27卷6-7期585-6页

36. [DNA methylation, a key player in pluripotency].

作者: Michaël Weber.
来源: Med Sci (Paris). 2011年27卷5期483-5页

37. [A simple view on lung cancer biology: The EGFR pathway].

作者: A-M Ruppert.;M Wislez.;V Poulot.;R Lacave.;M Antoine.;J Cadranel.
来源: Rev Mal Respir. 2011年28卷4期565-77页
Epidermal growth factor receptor (EGFR) is a cell membrane tyrosine kinase receptor. Activating mutations at exon 19 and 21 of the EGFR gene are associated with the occurrence and development of lung adenocarcinoma. These gain of function mutations predict responsiveness to EGFR tyrosine kinase inhibitors (TKis), erlotinib or gefitinib and are also a favorable prognostic factor in lung cancer. Sequencing is the recommended technique to detect the mutations, but other more sensitive technics are under evaluation. Treatment as first line therapy by gefitinib is limited to lung cancer patients harboring an EGFR mutation. Erlotinib can be given regardless of the EGFR status as second or third line therapy, as well as maintenance therapy in patients with a stable disease after platinum based chemotherapy. In EGFR mutated tumors, most patients present a recurrence of the disease, despite an initial response on EGFR TKis. Two mechanisms of secondary resistance have been identified, the selection of the T790M mutation in EGFR exon 20 and the MET amplification. Other molecular anomalies as the ras mutations or the EMLA-ALK protein fusion are mutually exclusive with the EGFR mutations and are associated with primary resistance to EGFR TKis.

38. [Curing mental retardation: searching for balance].

作者: Sharon Harel.;Sarah Jenna.
来源: Med Sci (Paris). 2011年27卷1期70-6页
Mental retardation (MR) occurs in 2 to 3 % of the general population and is still not therapeutically addressed. Milder forms of MR result from deficient synaptogenesis and/or impaired synaptic plasticity during childhood. These alterations would result from disequilibrium in signalling pathways regulating the balance between long term potentiation (LTP) and long term depression (LTD) in certain neurons such as hippocampus neurons. To provide mentally retarded children with increased cognitive abilities, novel experimental approaches are currently being developed to characterize signalling status associated with MR and to identify therapeutic targets that would restore lost equilibrium. Several studies also highlighted the major role played by molecular switches like kinases, phosphatases, small G proteins and their regulators in the coordination and integration of signalling pathways associated with synaptic plasticity. These proteins may therefore constitute promising therapeutic targets for a number of cognitive deficiencies.

39. [Resveratrol acts by modulating miRNAs].

作者: Norbert Latruffe.
来源: Med Sci (Paris). 2011年27卷1期31-3页

40. [CDK4, a specific target in the treatment of lung adenocarcinomas mutated for KRAS].

作者: Pierre Dubus.
来源: Med Sci (Paris). 2010年26卷12期1023-5页
共有 212 条符合本次的查询结果, 用时 2.3042174 秒