Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis

Previous work has reported the important links between cellular bioenergetics and the development of chronic kidney disease, highlighting the potential for targeting metabolic functions to regulate disease progression. More recently, it has been shown that alterations in fatty acid oxidation (FAO) can have an important impact on the progression of kidney disease. In this work, we demonstrate that loss of miR-33, an important regulator of lipid metabolism, can partially prevent the repression of FAO in fibrotic kidneys and reduce lipid accumulation. These changes were associated with a dramatic reduction in the extent of fibrosis induced in 2 mouse models of kidney disease. These effects were not related to changes in circulating leukocytes because bone marrow transplants from miR-33–deficient animals did not have a similar impact on disease progression. Most important, targeted delivery of miR-33 peptide nucleic acid inhibitors to the kidney and other acidic microenvironments was accomplished using pH low insertion peptides as a carrier. This was effective at both increasing the expression of factors involved in FAO and reducing the development of fibrosis. Together, these findings suggest that miR-33 may be an attractive therapeutic target for the treatment of chronic kidney disease

Endometriosis: New Perspective for the Diagnosis of Certain Cytokines in Women and Adolescent Girls, as Well as the Progression of Disease Outgrowth: A Systematic Review

Endometriosis is a common chronic gynecological disorder that undoubtedly impacts on quality of life, and is one of the more complex and mysterious illnesses of our century, which is associated with the improper growth of endometrial tissue outside of the uterine cavity. This pathologically implanted tissue can be found most frequently in the minor pelvis, but also in the peritoneal cavity, and can affect many organs, leading to chronic pelvic pain syndrome, infertility, and dysmenorrhea. Endometrial tissue is a particularly dynamic tissue that has a direct impact on the progression of the disease, with altered immunity, as well as cytokine storms within the metaplastic endometriotic site, as possible key factors. Currently, diagnosis of this mysterious chronic illness relies on performing a laparoscopic procedure with tissue sampling. One of the most troublesome outcomes of this unintended progression is that we lack any specific, sensitive, non-invasive diagnostic tools. Currently, the vast majority of regime stewardship options rely on anti-contraceptive drugs, or other remedies that suppress the release of estrogen through the gonads—although in most clinical trials, endometriosis is a chronic progressive disorder that depends mostly on the high concentration of estrogen. Moreover, many specific trials have demonstrated that the eutopic endometrial cells in individuals with endometriosis remain much more resistant to the immunological annihilation process caused by certain elements of the immune system. Nevertheless, eutopic endometrial cells have the potential to similarly escalate the expression of aromatase receptors on the surface of the pathological cells, which in the final cascade cause an increase in the concentration of estrogen, as well as other inflammatory proteins that contribute to pathological outgrowth. Data reveal occurrence among first-degree relatives, suggesting that the specific cascade could be related to inherited as well as epigenetic (acquired) mechanisms. In women with the disease, confirmed by laparoscopic procedures, diagnosis of endometriosis can be established also via detection by gene polymorphism in the genes which are responsible for responsible for the detoxification phase of estrogen receptors and other immunomodulator components. A recent publication aims to reveal a new prospect for the non-invasive diagnosis, detection, and estimation of certain biomarkers for much more specific investigation of the disease’s progression

Caractérisation et imagerie moléculaire de la plaque d'athérome : études pré-cliniques

Coronary artery disease is a major healthcare issue. Acute coronary syndrome is mainly caused by the rupture of vulnerable coronary plaques. This thesis focused on the preclinical study of atherosclerosis in a mouse model: the apolipoprotein E-deficient mouse (apoE-/-).Vulnerable plaque rupture is caused by an elevation of mechanical stress in the fibrous cap of atherosclerotic plaques. The first part of this thesis focused on the parietal stress evaluation in atheromatous lesions from apoE-/- mouse vessels. Atherosclerotic tissue showed low stiffness resulting in low levels of mechanical stress in atheromatous lesions. The low level of mechanical stress might account for the atherosclerotic plaque stability in this animal model.Rupture-prone vulnerable atheromatous plaques are highly inflammatory; vascular inflammation imaging appears therefore as a relevant strategy for vulnerable plaque imaging. The second part of this thesis dealt with atherosclerosis imaging in the apoE-/- mouse model, firstly with the evaluation of original peptidic radiotracers described as a VCAM-1 binders, an adhesion molecule over-expressed during inflammation, and secondly with the evaluation of [18F]-fluorodeoxyglucose (FDG), which was shown to accumulate in inflammatory cells and in the brown adipose tissue (BAT). Advanced evaluation of peptides revealed a lack of robustness in their biological behavior. A similar FDG uptake was observed in the atherosclerotic lesions and in the periaortic brown adipose tissue of apoE-/- mouse found in the vicinity. This potential confounding factor emphasizes the need to carefully design preclinical studies using FDG for the evaluation of lesion inflammation in this animal model.La maladie coronaire représente un problème majeur de santé publique. Sa manifestation la plus sévère, le syndrome coronarien aigu, est en grande majorité lié à la rupture de plaques d'athérome vulnérables. Les travaux effectués dans le cadre de cette thèse portent sur l'étude pré-clinique de la plaque d'athérome dans un modèle murin : la souris déficiente en apolipoprotéine E (apoE-/-).La rupture des plaques d'athérome vulnérables survient à la suite d'une élévation des contrainte mécaniques au niveau de la capsule fibreuse. Une première partie de ce travail de thèse porte sur l'évaluation de la contrainte présente dans la paroi des vaisseaux de souris apoE-/- porteuses de lésions athéromateuses. Ces lésions présentent une faible rigidité et en conséquence de faibles contraintes. Ces observations donnent un élément d'explication de l'absence de rupture dans ce modèle animal.Les plaques d'athérome vulnérables présentent une inflammation importante ; l'imagerie de l'inflammation vasculaire est une approche pertinente pour l'identification des plaques d'athérome vulnérables. Une seconde partie de ce travail de thèse porte sur l'imagerie de l'athérosclérose en ciblant le processus inflammatoire chez la souris apoE-/- avec d'une part l'évaluation de radiotraceurs peptidiques développés au sein du laboratoire et décrits comme ligands de la molécule d'adhésion VCAM-1, surexprimée dans le contexte inflammatoire, et d'autre part l'évaluation du [18F]-fluorodésoxyglucose (FDG), décrit pour s'accumuler dans les cellules inflammatoires et le tissu adipeux brun. L'évaluation poussée des peptides originaux a mis en évidence un manque de robustesse dans leur comportement biologique. D'autre part, une captation similaire de FDG a été observée dans les lésions athéromateuses et du tissu le brun péri-aortique se trouvant à proximité chez la souris apoE-/- . Cette limitation souligne la nécessité de l'optimisation des procédés expérimentaux destinés à l'évaluation de l'inflammation des lésions d'athérosclérose avec le FDG dans ce modèle animal

Characterization and Molecular Imaging and Atherosclerotic Plaque : Preclinical Studies

La maladie coronaire représente un problème majeur de santé publique. Sa manifestation la plus sévère, le syndrome coronarien aigu, est en grande majorité lié à la rupture de plaques d'athérome vulnérables. Les travaux effectués dans le cadre de cette thèse portent sur l'étude pré-clinique de la plaque d'athérome dans un modèle murin : la souris déficiente en apolipoprotéine E (apoE-/-).La rupture des plaques d'athérome vulnérables survient à la suite d'une élévation des contrainte mécaniques au niveau de la capsule fibreuse. Une première partie de ce travail de thèse porte sur l'évaluation de la contrainte présente dans la paroi des vaisseaux de souris apoE-/- porteuses de lésions athéromateuses. Ces lésions présentent une faible rigidité et en conséquence de faibles contraintes. Ces observations donnent un élément d'explication de l'absence de rupture dans ce modèle animal.Les plaques d'athérome vulnérables présentent une inflammation importante ; l'imagerie de l'inflammation vasculaire est une approche pertinente pour l'identification des plaques d'athérome vulnérables. Une seconde partie de ce travail de thèse porte sur l'imagerie de l'athérosclérose en ciblant le processus inflammatoire chez la souris apoE-/- avec d'une part l'évaluation de radiotraceurs peptidiques développés au sein du laboratoire et décrits comme ligands de la molécule d'adhésion VCAM-1, surexprimée dans le contexte inflammatoire, et d'autre part l'évaluation du [18F]-fluorodésoxyglucose (FDG), décrit pour s'accumuler dans les cellules inflammatoires et le tissu adipeux brun. L'évaluation poussée des peptides originaux a mis en évidence un manque de robustesse dans leur comportement biologique. D'autre part, une captation similaire de FDG a été observée dans les lésions athéromateuses et du tissu le brun péri-aortique se trouvant à proximité chez la souris apoE-/- . Cette limitation souligne la nécessité de l'optimisation des procédés expérimentaux destinés à l'évaluation de l'inflammation des lésions d'athérosclérose avec le FDG dans ce modèle animal.Coronary artery disease is a major healthcare issue. Acute coronary syndrome is mainly caused by the rupture of vulnerable coronary plaques. This thesis focused on the preclinical study of atherosclerosis in a mouse model: the apolipoprotein E-deficient mouse (apoE-/-).Vulnerable plaque rupture is caused by an elevation of mechanical stress in the fibrous cap of atherosclerotic plaques. The first part of this thesis focused on the parietal stress evaluation in atheromatous lesions from apoE-/- mouse vessels. Atherosclerotic tissue showed low stiffness resulting in low levels of mechanical stress in atheromatous lesions. The low level of mechanical stress might account for the atherosclerotic plaque stability in this animal model.Rupture-prone vulnerable atheromatous plaques are highly inflammatory; vascular inflammation imaging appears therefore as a relevant strategy for vulnerable plaque imaging. The second part of this thesis dealt with atherosclerosis imaging in the apoE-/- mouse model, firstly with the evaluation of original peptidic radiotracers described as a VCAM-1 binders, an adhesion molecule over-expressed during inflammation, and secondly with the evaluation of [18F]-fluorodeoxyglucose (FDG), which was shown to accumulate in inflammatory cells and in the brown adipose tissue (BAT). Advanced evaluation of peptides revealed a lack of robustness in their biological behavior. A similar FDG uptake was observed in the atherosclerotic lesions and in the periaortic brown adipose tissue of apoE-/- mouse found in the vicinity. This potential confounding factor emphasizes the need to carefully design preclinical studies using FDG for the evaluation of lesion inflammation in this animal model

Benefit of Silver and Gold Nanoparticles in Wound Healing Process after Endometrial Cancer Protocol

It is intractable to manage the vast majority of wounds in a classical surgical manner, however if silver, likewise gold and its representative nanoparticles, can lead to the amelioration of the wound healing process after extensive procedures, they should be employed in the current gynecological practice as promptly as possible. Most likely due to its antimicrobial properties, silver is usually applied as an additional component in the wound healing process. In wound management, we obtained various aspects that can lead to impaired wound healing; the crucial aspect for the wound milieu is to prevent the offending agents from occurring. The greatest barrier to healing is represented by the bacterial biofilm, which can occur naturally or in other ways. Biofilm bacteria can produce extracellular polymers, which can then resist concentrated anti-bacterial treatment. The published literature on the use of silver nanoparticles’ utilization in wound healing becomes slightly heterogenous and requires us in difficult moments to set up proper treatment guidelines

Pozytywny wpływ późnego odpępniania na stan urodzeniowy wcześniaków z perspektywy położniczej

Wybór techniki wczesnego czy późnego odpępniania w obecnej praktyce położniczej jest tematem wielu dyskusji.Sposób odpępniania noworodka zależy w głównej mierze od jego kondycji życiowej, wieku ciążowego oraz stanuzdrowia matki. Późne odpępnianie (DCC) prowadzi do zwiększonego przepływu krwi przez łożysko, a tym samymdo znacznego zwiększenia objętości krwi w łożysku naczyniowym noworodka, zwiększenia zasobów żelaza biodostępnegooraz zwiększenia koncentrację krwinek czerwonych w krwi obwodowej. U przedwcześnie urodzonegonoworodka DCC może zmniejszyć zapotrzebowanie na transfuzję krwi, obniżyć ryzyko występowania wylewów dokomorowychoraz późnej sepsy. Zalety DCC obejmują również zmniejszenie alloimmunizacji u RH ujemnej kobiety.Zebrane dotychczas dowody na temat pozytywnego wpływu późnego odpępniania przemawiają za lepszą kondycjąpo porodzie noworodka przedwcześnie urodzonego

Identifying the leukocyte uptake pattern of inflammation imaging agents: Current limitations and potential impact

International audienc

Elucidating atherosclerotic vulnerable plaque rupture by modeling cross substitution of ApoE-/- mouse and human plaque components stiffnesses.

International audienceThe structure of mouse atherosclerotic lesions may differ from that of humans, and mouse atherosclerotic plaques do not rupture except in some specific locations such as the brachiocephalic artery. Recently, our group was the first to observe that the amplitudes of in vivo stresses in ApoE-/- mouse aortic atherosclerotic lesions were much lower and differed from those found in a previous work performed on human lesions. In this previous preliminary work, we hypothesized that the plaque mechanical properties (MP) may in turn be responsible for such species differences. However, the limited number of human samples used in our previous comparative study was relevant but not sufficient to broadly validate such hypothesis. Therefore, in this study, we propose an original finite element strategy that reconstructs the in vivo stress/strain (IVS/S) distributions in ApoE-/- artherosclerotic vessels based on cross substitution of ApoE-/- mouse and human plaque components stiffnesses and including residual stress/strain (RS/S). Our results: (1) showed that including RS/S decreases by a factor 2 the amplitude of maximal IVS/S, and more importantly, (2) demonstrated that the MP of the ApoE-/- plaque constituents are mainly responsible for the low level-compared with human-of intraplaque stress in ApoE-/- mouse aortic atherosclerotic lesions (8.36 ± 2.63 kPa vs. 182.25 ± 55.88 kPa for human). Our study highlights that such differences in the distribution and amplitude of vessel wall stress might be one key feature for explaining for the difference in lesion stability between human coronary and mouse aortic lesions

Assessing low levels of mechanical stress in aortic atherosclerotic lesions from apolipoprotein E-/- mice--brief report.

International audienceOBJECTIVE: Despite the fact that mechanical stresses are well recognized as key determinants for atherosclerotic plaque rupture, very little is known about stress amplitude and distribution in atherosclerotic lesions, even in the standard apolipoprotein E (apoE)-/- mouse model of atherosclerosis. Our objectives were to combine immunohistology, atomic force microscopy measurements, and finite element computational analysis for the accurate quantification of stress amplitude and distribution in apoE-/- mouse aortic atherosclerotic lesions. METHODS AND RESULTS: Residual stresses and strains were released by radially cutting aortic arch segments from 7- to 30-week-old pathological apoE-/- (n=25) and healthy control mice (n=20). Immunohistology, atomic force microscopy, and biomechanical modeling taking into account regional residual stresses and strains were performed. Maximum stress values were observed in the normal arterial wall (276±71 kPa), whereas low values (<20 kPa) were observed in all plaque areas. Stress distribution was not correlated to macrophage infiltration. CONCLUSIONS: Low mechanical stress amplitude was observed in apoE-/- mouse aortic atherosclerotic lesions. This original study provides a basis for further investigations aimed at determining whether low stress levels are responsible for the apparently higher stability of murine aortic atherosclerotic lesions