Microvascular alterations in hypertension and vascular aging

Hypertension and aging are characterized by vascular remodelling and stiffness as well as endothelial dysfunction. Endothelial function declines with age, since aging is associated with senescence of the endothelium due to increased rate of apoptosis and reduced regenerative capacity of the endothelium. Different phenotypes of hypertension have been described in younger and adult subjects with hypertension. In younger patients functional and structural alterations of resistance arteries occur as the earliest vascular alterations which have prognostic significance and may contribute to stiffness of large arteries through wave reflection. In individuals above age of 50 years as well as in subjects with long-lasting elevated blood pressure, vascular changes occur predominantly in conduit arteries which become stiffer. Activation of renin-angiotensin-aldosterone and endothelin systems plays a key role in endothelial dysfunction, vascular remodelling, and aging by inducing reactive oxygen species production, and promoting inflammation and cell growth

Hepatitis B virus preS2Δ38-55 variants: A newly identified risk factor for hepatocellular carcinoma.

BACKGROUND & AIMS: Although HBV is a major cause of death in Africa, its genetic variability has been poorly documented. This study aimed to address whether HBV genotype and surface gene variants are associated with HBV-related liver disease in The Gambia. METHODS: We conducted a case-control study nested in the Prevention of Liver Fibrosis and Cancer in Africa programme. Consecutive treatment-naive patients with chronic HBV infection and detectable viral load were recruited: 211 controls with no significant liver disease and 91 cases (56 cirrhosis and 35 HCC cases). HBV genotypes and surface gene variants were determined by Sanger sequencing or next-generation sequencing (NGS) in serum DNA. Aflatoxin B1 (AFB1)-specific codon 249 TP53 mutation was determined by NGS in circulating cell-free plasma DNA. RESULTS: In phylogenetic analysis, 85% of individuals carried HBV genotype E, 14% genotype A, and 1% A/E recombinant viruses. Surface gene variants were more frequently observed in cases (43% and 57% in cirrhosis and HCC cases, respectively) than controls (25%; p 2,000 IU/ml (OR 22.7 [8.0-64.9]), HBsAg levels <10,000 IU/ml (OR 19.0 [5.5-65.3]), and AFB1 exposure (OR 29.3 [3.7-230.4]) on HCC risk. CONCLUSIONS: This study identified a hotspot for HBV preS2 deletions as a strong independent factor for HCC in The Gambia, with HBV genotypes and AFB1 exposure contributing to the high liver cancer risk. LAY SUMMARY: Although HBV-related liver disease is highly prevalent in sub-Saharan Africa, the associated virological characteristics are poorly studied. Using clinical data from African patients chronically infected with HBV, an assessment of the virological variability (genotypes and mutations) and exposure to AFB1, a toxin often contaminating food, was carried out. Our results show that HBV genotypes, the presence of a highly prevalent mutant form of HBV, and AFB1 exposure contribute to the high liver cancer risk in this population

Hypertension and COVID-19. Current Evidence and Perspectives

Coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a real challenge for health-care systems worldwide. Male sex, older age and the coexistence of chronic comorbidities have been described as the most relevant conditions associated with a worse prognosis. Early reports suggested that hypertension might represent a risk factor for susceptibility to SARS-CoV-2 infection, a more severe course of COVID-19 and increased COVID-19-related deaths. Nevertheless, the independent role of hypertension remains under debate, since hypertension is often associated with the older age and other cardiovascular (CV) risk factors in the general population, which may also contribute to the SARS-Cov-2 infection and COVID-19. Moreover, the role of antihypertensive drugs, primarily angiotensin-converting inhibitors (ACEIs) and ARBs (angiotensin receptor blockers) in COVID-19 development and outcome appears controversial. Indeed, preclinical studies using these classes of drugs have suggested a potential upregulation of angiotensin-converting-enzyme 2 (ACE2) which is the key binding receptor promoting cell entry of SARS-CoV-2 in the organism. Renin-angiotensin system (RAS) blockers may potentially upregulate ACE2, hence, it has been initially hypothesized that these agents might contribute to a higher risk of SARS-CoV-2 infection and progressive course of COVID-19. However, several clinical reports do not support a detrimental role of RAS blockers in COVID-19, and an intense debate about the withdrawal or maintenance of chronic therapy with ACEi/ARB has been developed. In this review we will discuss the available evidence on the role of hypertension and antihypertensive drugs on SARS-CoV-2 infection and COVID-19 development

Kaposi’s Sarcoma-Associated Herpesvirus, the Etiological Agent of All Epidemiological Forms of Kaposi’s Sarcoma

International audienceSimple SummaryKaposi’s sarcoma-associated herpesvirus (KSHV) is one of the seven oncogenic viruses currently recognized by the International Agency for Research on Cancer. Its presence for Kaposi’s sarcoma development is essential and knowledge on the oncogenic process has increased since its discovery in 1994. However, some uncertainties remain to be clarified, in particular on the exact routes of transmission and disparities in KSHV seroprevalence and the prevalence of Kaposi’s sarcoma worldwide. Here, we summarized the current data on the KSHV viral particle’s structure, its genome, the replication, its seroprevalence, the viral diversity and the lytic and latent oncogenesis proteins involved in Kaposi’s sarcoma. Lastly, we reported the environmental, immunological and viral factors possibly associated with KSHV transmission that could also play a role in the development of Kaposi’s sarcoma.AbstractKaposi’s sarcoma-associated herpesvirus (KSHV), also called human herpesvirus 8 (HHV-8), is an oncogenic virus belonging to the Herpesviridae family. The viral particle is composed of a double-stranded DNA harboring 90 open reading frames, incorporated in an icosahedral capsid and enveloped. The viral cycle is divided in the following two states: a short lytic phase, and a latency phase that leads to a persistent infection in target cells and the expression of a small number of genes, including LANA-1, v-FLIP and v-cyclin. The seroprevalence and risk factors of infection differ around the world, and saliva seems to play a major role in viral transmission. KSHV is found in all epidemiological forms of Kaposi’s sarcoma including classic, endemic, iatrogenic, epidemic and non-epidemic forms. In a Kaposi’s sarcoma lesion, KSHV is mainly in a latent state; however, a small proportion of viral particles (<5%) are in a replicative state and are reported to be potentially involved in the proliferation of neighboring cells, suggesting they have crucial roles in the process of tumorigenesis. KSHV encodes oncogenic proteins (LANA-1, v-FLIP, v-cyclin, v-GPCR, v-IL6, v-CCL, v-MIP, v-IRF, etc.) that can modulate cellular pathways in order to induce the characteristics found in all cancer, including the inhibition of apoptosis, cells’ proliferation stimulation, angiogenesis, inflammation and immune escape, and, therefore, are involved in the development of Kaposi’s sarcoma

Mechanical Alloying and Molding by Spark Plasma Sintering of Telluride based glasses

International audienceAlternative way of synthesis for high refractive index tellurides based glasses has been experimented, in addition to low temperature Spark Plasma Sintering. The composition tested, Ge25Se10Te65, has been chose in the Ge-Se-Te system and characterized. Its index refractive index of 3.12 and overall optical, thermal and mechanical properties makes it the perfect candidate for IR application. However, due to its relative instability regarding crystallization, formation of GeTe crystals occurs during mechanical alloying using raw elements. Transparency has not been achieved in the sintered samples using this powder, as the crystallization rate is accelerated by the pressure during the process. In parallel, glass samples synthesized by melt-quenching have been used to determine optimal sintering parameters for this composition. The main issue met during those tests has been the carbon contamination, reducing overall transparency of the samples through scatterings. As such, it has been shown that the critical parameter to consider to limiting this pollution is the powder granulometry, needing to be above 100 mu m for optimal performance. This shows the potential for this method to produce high refractive index IR optics, using even unstable glasses

Epidemiology and Characteristics of SARS-CoV-2 Variants of Concern: The Impacts of the Spike Mutations

SARS-CoV-2 expresses on its surface the Spike protein responsible for binding with the ACE2 receptor and which carries the majority of immunodominant epitopes. Mutations mainly affect this protein and can modify characteristics of the virus, giving each variant a unique profile concerning its transmissibility, virulence, and immune escape. The first lineage selected is the B.1 lineage characterized by the D614G substitution and from which all SARS-CoV-2 variants of concern have emerged. The first three variants of concern Alpha, Beta, and Gamma spread in early 2021: all shared the N501Y substitution. These variants were replaced by the Delta variant in summer 2021, carrying unique mutations like the L452R substitution and associated with higher virulence. It was in turn quickly replaced by the Omicron variant at the end of 2021, which has predominated since then, characterized by its large number of mutations. The successive appearance of variants of concern showed a dynamic evolution of SARS-CoV-2 through the selection and accumulation of mutations. This has not only allowed progressive improvement of the transmissibility of SARS-CoV-2, but has also participated in a better immune escape of the virus. This review brings together acquired knowledge about SARS-CoV-2 variants of concern and the impacts of the Spike mutations

Harnessing Redox Disruption to Treat Human Herpesvirus 8 (HHV-8) Related Malignancies

Reprogrammed metabolism is regarded as a hallmark of cancer and offers a selective advantage to tumor cells during carcinogenesis. The redox equilibrium is necessary for growth, spread and the antioxidant pathways are boosted following Reactive Oxygen Species (ROS) production to prevent cell damage in tumor cells. Human herpesvirus 8 (HHV-8), the etiologic agent of Kaposi sarcoma KS and primary effusion lymphoma (PEL), is an oncogenic virus that disrupts cell survival-related molecular signaling pathways leading to immune host evasion, cells growths, angiogenesis and inflammatory tumor-environment. We recently reported that primaquine diphosphate causes cell death by apoptosis in HHV-8 infected PEL cell lines in vivo and exhibits therapeutic anti-tumor activity in mice models and advanced KS. Our findings also suggest that the primaquine-induced apoptosis in PEL cells is mostly influenced by ROS production and targeting the redox balance could be a new approach to treat HHV-8 related diseases. In this review, we summarized the knowledge about the influence of ROS in cancer development; more specifically, the proof of evidence from our work and from the literature that redox pathways are important for the development of HHV-8 pathologies

Évaluation du potentiel des lentilles en chalcogénure à haut indice de réfraction pour l'application automobile

International audienceInfrared cameras could serve automotive applications by delivering breakthrough perception systems for both in-cabin passengers monitoring and car surrounding. However, low-cost and high-throughput manufacturing methods are essential to sustain the growth in thermal imaging markets for automotive applications, and for other close-to-consumer applications, which have a fast growth potential. With the reduction of the pixel pitch of microbolometer detectors, their cost has decreased considerably and now the optical part represents a significant part of the system cost. Fast low cost infrared lenses suitable for microbolometers are already sold by companies like Umicore, Lightpath, FLIR… Chalcogenide glasses are widely used as materials for optics because they have many cost advantages, especially due to the possibility of mass molding the optics. However, with the reduction of the pixel pitch, it is more and more difficult to design high performance lenses with a limited number of optics. The possibility of molding the optics allows us to use many highly aspherical surfaces at affordable costs. However, Chalcogenide glasses have usually a lower refractive index than other more expensive infrared materials such as Germanium. Indeed, high refractive index materials are known to be effective in attenuating the amplitude of many geometric aberrations. In this presentation, we evaluate the interest of high index Chalcogenide lenses, especially TGG and TGS, to design optical systems meeting the needs of the automobile with a limited number of optics. TGG glass has an index of refraction of 3.396 at a wavelength of 10µm, i.e. its index of refraction is close to the Silicon one and was initially studied for space applications. TGS has a lower index of refraction (3.12@10µm) but can be used in a cost effective manufacturing process by using flash spark plasma sintering (SPS) on raw powder. Demonstrators with TGG glass have been made and their performance evaluated.Les caméras infrarouges pourraient servir les applications automobiles en fournissant des systèmes de perception révolutionnaires, tant pour la surveillance des passagers à l'intérieur de la cabine que pour l'entourage de la voiture. Cependant, des méthodes de fabrication à faible coût et à haut rendement sont essentielles pour soutenir la croissance des marchés de l'imagerie thermique pour les applications automobiles, et pour d'autres applications proches du consommateur, qui ont un potentiel de croissance rapide. Avec la réduction du pas des pixels des détecteurs microbolométres, leur coût a considérablement diminué et la partie optique représente désormais une part importante du coût du système. Des lentilles infrarouges très ouvertes et peu coûteuses adaptées aux microbolomètres sont déjà vendues par des sociétés comme Umicore, Lightpath, FLIR... Les verres de chalcogénure sont largement utilisés comme matériaux pour les optiques car ils présentent de nombreux avantages en termes de coût, notamment en raison de la possibilité de mouler les optiques en grande quantité. Cependant, avec la réduction du pas des pixels, il est de plus en plus difficile de concevoir des lentilles de haute performance avec un nombre limité d'optiques. La possibilité de mouler les optiques nous permet d'utiliser de nombreuses surfaces hautement asphériques à des coûts abordables. Cependant, les verres en Chalcogénure ont généralement un indice de réfraction plus faible que d'autres matériaux infrarouges plus coûteux comme le Germanium. En effet, les matériaux à haut indice de réfraction sont connus pour leur efficacité à atténuer l'amplitude de nombreuses aberrations géométriques. Dans cette présentation, nous évaluons l'intérêt des verres en Chalcogénure à haut indice, notamment TGG et TGS, pour concevoir des systèmes optiques répondant aux besoins de l'automobile avec un nombre limité d'optiques. Le verre TGG a un indice de réfraction de 3,396 à une longueur d'onde de 10µm, c'est-à-dire que son indice de réfraction est proche de celui du Silicium et a été initialement étudié pour des applications spatiales. Le TGS a un indice de réfraction plus faible (3,12@10µm) mais peut être utilisé dans un processus de fabrication rentable en utilisant le frittage par plasma à étincelles (SPS) sur la poudre brute. Des démonstrateurs avec du verre TGG ont été fabriqués et leurs performances évaluées

Seroprevalence and molecular diversity of Human Herpesvirus 8 among people living with HIV in Brazzaville, Congo

International audienceHuman herpesvirus 8 (HHV8) is endemic in Africa, although studies of this infection are rare in Congo. We evaluated seroprevalence and HHV-8 diversity among people living with HIV. We included 353 patients receiving highly active antiretroviral therapy. Antibodies against HHV-8 latency-associated nuclear antigen were detected by indirect immunofluorescence. In HHV-8 positive patients, we performed HHV-8 quantification in blood and saliva by real-time PCR and typing by Sanger sequencing of K1 open reading frame. HHV-8 seroprevalence was 19%, being male (odd ratio [OR] = 1.741, [95% Confidence interval {CI}, 0.97–3.07]; p = 0.0581) and having multiple sex partners before HIV diagnosis (OR = 1.682, [CI 95%, 0.97–2.92]; p = 0.0629) tended to be associated with HHV-8 seropositivity. Of the 64 HHV-8 seropositive patients, HHV-8 DNA was detected in 10 (16%) in saliva, 6 (9%) in whole-blood and in 2 (3%) in both whole-blood and saliva. Three out of 6 HHV-8 strains were subtypes A5, 2 subtype B1 and 1 subtype C. HHV-8 seroprevalence was relatively low with more frequent carriage in men, associated with asymptomatic oral excretion and a predominance of subtype A5. These data tend to support the hypothesis of horizontal transmission in people living with HIV in Brazzaville