SUN2 regulates mitotic duration in response to extracellular matrix rigidity.

How cells adjust their growth to the spatial and mechanical constraints of their surrounding environment is central to many aspects of biology. Here, we examined how extracellular matrix (ECM) rigidity affects cell division. We found that cells divide more rapidly when cultured on rigid substrates.

Bronchial smooth muscle cell in asthma: where does it fit?

Asthma is a frequent respiratory condition whose pathophysiology relies on altered interactions between bronchial epithelium, smooth muscle cells (SMC) and immune responses. Those leads to classical hallmarks of asthma: airway hyper-responsiveness, bronchial remodelling and chronic inflammation. Airway smooth muscle biology and pathophysiological implication in asthma are now better understood.

Rac1 as a therapeutic anticancer target: Promises and limitations.

Small molecule inhibitors of GTPases are increasingly considered for the treatment of multiple human pathologies. The GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) plays major roles in vital cellular processes, notably in the control cell motility and dynamic, the regulation of oxidative stress, and in inflammatory and immune surveillance. As such, Rac1 is viewed as a potential target to combat cancers but also diverse inflammatory, metabolic, neurodegenerative, respiratory, cardiovascular, viral, and parasitic diseases.

Why Are Women Predisposed to Intracranial Aneurysm?

Intracranial aneurysm (IA) is a frequent and generally asymptomatic cerebrovascular abnormality characterized as a localized dilation and wall thinning of intracranial arteries that preferentially arises at the arterial bifurcations of the circle of Willis. The devastating complication of IA is its rupture, which results in subarachnoid hemorrhage that can lead to severe disability and death. IA affects about 3% of the general population with an average age for detection of rupture around 50 years.

Smooth muscle Rac1 contributes to pulmonary hypertension.

Background And Purpose: Pulmonary hypertension (PH) is a multifactorial chronic disease characterized by an increase in pulmonary artery (PA) resistance leading to right ventricle (RV) failure. Endothelial dysfunction and alteration of NO/cGMP signalling in PA plays a major role in PH. We recently described the involvement of the Rho protein Rac1 in the control of systemic blood pressure through its involvement in NO-mediated relaxation of arterial smooth muscle cell (SMC).

Structural Design and Analysis of the RHOA-ARHGEF1 Binding Mode: Challenges and Applications for Protein-Protein Interface Prediction.

The interaction between two proteins may involve local movements, such as small side-chains re-positioning or more global allosteric movements, such as domain rearrangement. We studied how one can build a precise and detailed protein-protein interface using existing protein-protein docking methods, and how it can be possible to enhance the initial structures using molecular dynamics simulations and data-driven human inspection. We present how this strategy was applied to the modeling of RHOA-ARHGEF1 interaction using similar complexes of RHOA bound to other members of the Rho guanine nucleotide exchange factor family for comparative assessment.

Essential role of smooth muscle Rac1 in severe asthma-associated airway remodelling.

Background: Severe asthma is a chronic lung disease characterised by inflammation, airway hyperresponsiveness (AHR) and airway remodelling. The molecular mechanisms underlying uncontrolled airway smooth muscle cell (aSMC) proliferation involved in pulmonary remodelling are still largely unknown. Small G proteins of the Rho family (RhoA, Rac1 and Cdc42) are key regulators of smooth muscle functions and we recently demonstrated that Rac1 is activated in aSMC from allergic mice.

Location of intracranial aneurysms is the main factor associated with rupture in the ICAN population.

Background And Purpose: The ever-growing availability of imaging led to increasing incidentally discovered unruptured intracranial aneurysms (UIAs). We leveraged machine-learning techniques and advanced statistical methods to provide new insights into rupture intracranial aneurysm (RIA) risks.

Methods: We analysed the characteristics of 2505 patients with intracranial aneurysms (IA) discovered between 2016 and 2019.

Prediction of Unruptured Intracranial Aneurysm Evolution: The UCAN Project.

Background: Management of small (<7 mm) unruptured intracranial aneurysms (UIA) remains controversial. Retrospective studies have suggested that post gadolinium arterial wall enhancement (AWE) of UIA on magnetic resonance imaging (MRI) may reflect aneurysm wall instability, and hence may highlight a higher risk of UIA growth. This trial aims at exploring wall imaging findings of UIAs with consecutive follow-up to substantiate these assumptions.

Seeds Improve Aging-Related Endothelial Dysfunction in Wistar Rats.

Vascular aging is characterized by functional and structural changes of the vessel wall, including endothelial dysfunction, with decreased endothelial NO bioavailability and elevated vasoconstrictor and inflammatory mediator production, vascular rigidity, and tone impairment. (MOI) is a little tree, and different parts of which are used in traditional medicine in tropical Africa, America, and Asia for therapeutic applications in several disorders including cardiovascular disease. The present study is aimed at assessing the effect of MOI on aging-associated alteration of the endothelial function in Wistar rats.

RRAD mutation causes electrical and cytoskeletal defects in cardiomyocytes derived from a familial case of Brugada syndrome.

Aims: The Brugada syndrome (BrS) is an inherited cardiac disorder predisposing to ventricular arrhythmias. Despite considerable efforts, its genetic basis and cellular mechanisms remain largely unknown. The objective of this study was to identify a new susceptibility gene for BrS through familial investigation.

[New protagonists in asthma pathophysiology].

Asthma is often associated with a Th2-type immune response with well-known cellular and molecular actors such as eosinophils, Th2 lymphocytes and associated cytokines such as interleukin-5 or IL-4. Nevertheless, some of the asthmatic patients show clinical manifestations and characteristics that do not correspond to the current pattern of the pathophysiology of asthma. Thus, recently new cellular and molecular actors in the development of asthma have been demonstrated in animal models and in humans.

Synthesis and biological evaluation of 3-amino-, 3-alkoxy- and 3-aryloxy-6-(hetero)arylpyridazines as potent antitumor agents.

Various 3-amino-, 3-aryloxy- and alkoxy-6-arylpyridazines have been synthesized by an electrochemical reductive cross-coupling between 3-amino-, 3-aryloxy- or 3-alkoxy-6-chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products was evaluated against a representative panel of cancer cell lines (HuH7, CaCo-2, MDA-MB-231, HCT116, PC3, NCI-H727, HaCaT) and oncogenicity prevention of the more efficient derivatives was highlighted on human breast cancer cell line MDA-MB 468-Luc prior establishing their interaction with p44/42 and Akt-dependent signaling pathways.

Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm.

Intracranial aneurysms (IAs) are acquired cerebrovascular abnormalities characterized by localized dilation and wall thinning in intracranial arteries, possibly leading to subarachnoid hemorrhage and severe outcome in case of rupture. Here, we identified one rare nonsense variant (c.1378A>T) in the last exon of ANGPTL6 (Angiopoietin-Like 6)-which encodes a circulating pro-angiogenic factor mainly secreted from the liver-shared by the four tested affected members of a large pedigree with multiple IA-affected case subjects.

Targeting of Rac1 prevents bronchoconstriction and airway hyperresponsiveness.

Background: The molecular mechanisms responsible for airway smooth muscle cells' (aSMCs) contraction and proliferation in airway hyperresponsiveness (AHR) associated with asthma are still largely unknown. The small GTPases of the Rho family (RhoA, Rac1, and Cdc42) play a central role in SMC functions including migration, proliferation, and contraction.

Objective: The objective of this study was to identify the role of Rac1 in aSMC contraction and to investigate its involvement in AHR associated with allergic asthma.

Leukocyte RhoA exchange factor Arhgef1 mediates vascular inflammation and atherosclerosis.

Abnormal activity of the renin-angiotensin-aldosterone system plays a causal role in the development of hypertension, atherosclerosis, and associated cardiovascular events such as myocardial infarction, stroke, and heart failure. As both a vasoconstrictor and a proinflammatory mediator, angiotensin II (Ang II) is considered a potential link between hypertension and atherosclerosis. However, a role for Ang II-induced inflammation in atherosclerosis has not been clearly established, and the molecular mechanisms and intracellular signaling pathways involved are not known.

Seeds Attenuate Vascular Oxidative and Nitrosative Stresses in Spontaneously Hypertensive Rats.

(MOI) is a tree currently used in traditional medicine in tropical Africa, America, and Asia for therapeutic applications in several disorders including arterial hypertension. We previously described a cardiac protective role of a treatment with MOI seeds in spontaneously hypertensive rats (SHR). Here, we investigated the effects of this treatment on oxidative and nitrosative vascular stresses in SHR, with normotensive Wistar Kyoto rats used as controls.

Understanding the Pathophysiology of Intracranial Aneurysm: The ICAN Project.

Background: Understanding the pathophysiologic mechanism of intracranial aneurysm (IA) formation is a prerequisite to assess the potential risk of rupture. Nowadays, there are neither reliable biomarkers nor diagnostic tools to predict the formation or the evolution of IA. Increasing evidence suggests a genetic component of IA but genetics studies have failed to identify genetic variation causally related to IA.

In Vitro and In Vivo Approaches to Assess Rho Kinase Activity.

Increased arterial tone and the resulting rise in peripheral vascular resistance are major determinants of the elevated arterial pressure in hypertension. The RhoA/Rho kinase signaling pathways are now recognized as a major regulator of vascular smooth muscle contraction and arterial tone. Here we describe methods to directly and indirectly assess Rho kinase activity in vitro and in cells and tissues.

Benefit of Mineralocorticoid Receptor Antagonism in AKI: Role of Vascular Smooth Muscle Rac1.

AKI is a frequent complication in hospitalized patients. Unfortunately, there is no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents AKI induced by ischemia-reperfusion (IR).

Cardiac Protective Effects of Moringa oleifera Seeds in Spontaneous Hypertensive Rats.

Background: Hypertension is characterized by a maintained high blood pressure leading to cardiac complications such as left ventricular hypertrophy and fibrosis and an increased risk of heart failure and myocardial infarction. This study investigated the cardiac effects of oral administration of Moringa oleifera (MOI) seed powder in spontaneous hypertensive rats (SHR).

Methods: SHR received food containing MOI seed powder (750mg/d, 8 weeks) or normal food.