The Fate of Epidermal Tight Junctions in the stratum corneum: Their Involvement in the Regulation of Desquamation and Phenotypic Expression of Certain Skin Conditions.

We evaluated the presence of tight junction (TJ) remnants in the stratum corneum (SC) of in vitro reconstructed human epidermis and human skin explants subjected or not to an aggressive topical treatment with beta-lipohydroxy salicylic acid (LSA) for 24 h. LSA-treated samples showed an increased presence of TJ remnants in the two lowermost layers of the SC, as quantified with standard electron microscopy. The topical aggression-induced overexpression of TJ-like cell-cell envelope fusions may influence SC functions: (1) directly, through an enhanced cohesion, and (2) indirectly, by impeding accessibility of peripheral corneodesmosomes to extracellular hydrolytic enzymes and, thus, slowing down desquamation. Observations of ichthyotic epidermis in peeling skin disease (PSD; corneodesmosin deficiency; two cases) and ichthyosis hypotrichosis sclerosing cholangitis syndrome (IHSC/NISCH; absence of claudin-1; two cases) also demonstrated increased persistence of TJ-like intercellular fusions in pathological SC and contributed to the interpretation of the diseases' pathological mechanisms

Implication of glycans and junctional elements in the stratum corneum barrier function

La barrière épidermique du stratum corneum (SC) est doublée par une barrière secondaire des jonctions serrées (JS) qui influent sur la formation de barrière principale. Dans mes travaux, je me suis concentré sur l'étude de la présence et l'évolution des éléments jonctionnelles composants ces deux barrières ; les cornéodesmosomes au niveau du SC et les JSs au niveau de la granuleuse. En plus, je me suis intéressé à l'implication des glycanes dans la fonction barrière épidermique. Ces travaux ont été réalisés soit dans un contexte physiologique soit par la modulation de la barrière épidermique par des facteurs intrinsèques et extrinsèques. Nos résultats confirment que les JSs jouent un rôle subalterne par rapport à la barrière du SC et montrent que les glycanes persistent à la surface des cornéocytes humains. La composition et la répartition utlrastructurale des glycanes évoluent à travers les assises du SC jusqu'à la desquamation d'une manière concordante avec la répartition des cornéodesmosomes. Certaines modifications intrinsèques naturelles lors du vieillissement ou pathologiques notamment l'état pelliculaire et la dermatite atopique, ont permis d'appréhender le rôle de ces composants dans la cohésion du SC et la prestance d'une barrière fonctionnelle. Les modifications extrinsèques de la barrière par l'application de solvants, d'excipients ou de formulations perméabilisantes montrent l'importance de l'organisation utlrastructurale des composants jonctionnelles et non jonctionnelles du SC dans le maintien d'une barrière efficaceThe stratum corneum (SC) barrier is doubled by the secondary barrier of tight junctions which influences the formation of the main barrier. In my work, I focused on the study of the junctional elements composing those two barriers; corneodesmosomes in the SC and the tight junction at the granular layer level. In addition, I got interested in the involvement of glycans in the epidermal barrier function. This work was carried out either in skin physiological conditions or by the modulation of the epidermal barrier by intrinsic or extrinsic factors. Our results confirm that tight junctions play a subordinate role compared to the SC barrier and that glycans remain present at the surface of human corneocytes. The composition and the ultrastructure distribution of glycans evolve from the SC compactum to the SC disjunctum, towards desquamation in a comparable manner to the repartition of corneodesmosomes. Natural intrinsic changes during aging and pathological changes, including dandruff and atopic dermatitis, helped us to understand the role of those components in the cohesion of the SC and the conservation of functional barrier. Extrinsic modulation of the barrier by the application of solvents, excipients or topical formulations shows the importance of the ultrastructural organization of junctional and non-junctional SC components in maintaining an effective barrie

Elaboration of a sustainable bottom ash geopolymer material

The use of Ordinary Portland Cement (OPC) has been the primary material used in the construction industry. Its production leads to 5% to 7% of total CO2 emissions and 14% of the total global energy emissions [1,2]. The pollution caused by OPC production has encouraged researchers to discover new environmental and sustainable materials such as geopolymers [2]. The main objective of this study is to investigate the mechanical properties of metakaolin-based geopolymers made with bottom ash to produce an eco-friendly material while reducing waste generation. The following research determines the mechanical properties of French metakaolin-based geopolymer produced with bottom ash at different mass substitution rates ranging from 0% to 15%. The solid powders were mixed with a sodium-based alkali activator and poured into 4x4 cubical molds. The four different mix designs were cured at ambient temperature and varied according to the different percentages of bottom ash (0%, 5%, 10%, and 15%) inserted. The mechanical properties of the several mixes were assessed by the use of a UTM compression test machine on the respective days of testing: 7, 28, and 90 days. Results demonstrated that the geopolymer mortars produced with bottom ash gave promising mechanical properties regardless of the mass substitution rates inserted in the mixes. This behavior has induced the potential for incorporating such waste in producing a sustainable and eco-friendly cementitious material. In conclusion, the use of bottom ash as a recyclable source material in geopolymer mortar formulation has highlighted the importance of this development as a sustainable solution. The effectiveness of a study where the compressive strength showed high results when compared to OPC is encouraging

Targeting HER2 in non-small-cell lung cancer (NSCLC) : a glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations

Non-small-cell lung cancer (NSCLC) harbouring HER2 alterations is now considered a distinct molecular subtype. The activation of HER2 in NSCLC occurs via three mechanisms, i.e. gene mutation (1%-4% of cases), gene amplification (2%-5%) and protein overexpression (2%-30%), with different prognostic and predictive outcomes. So far, non-selective tyrosine kinase inhibitors (TKIs) have shown a minor benefit in HER2-mutant NSCLC patients with objective response rates (ORRs) ranging from 0% to 19%. Trastuzumab-based chemotherapy was not found to be superior to chemotherapy alone [median progression-free survival (PFS) 6.1 versus 7 months, respectively] and dual HER2 antibody blockade with trastuzumab and pertuzumab had limited efficacy (ORR 13%-21%). In contrast, novel more selective HER2 TKIs such as poziotinib and pyrotinib have shown a promising activity in HER2-mutant pre-treated NSCLC patients, with response rates up to 38% and 44%, respectively. The most encouraging data come from phase II studies that evaluated the antibody-drug conjugates (ADCs) ado-trastuzumab-emtansine and trastuzumab-deruxtecan in patients with HER2-mutant NSCLC, with response rates of 50% and 62%, respectively. These agents are bringing hope to the management of HER2-altered NSCLC. Moreover, a paradigm shift from monotherapies towards combinations of agents with distinct mechanisms of action, such as ADCs with irreversible TKIs or immune checkpoint inhibitors, is already taking place and will change the therapeutic landscape of HER2-driven NSCLC. This paper provides a practical, concise and updated review on the therapeutic strategies in NSCLC with HER2 molecular alterations

Skin Minerals: Key Roles of Inorganic Elements in Skin Physiological Functions

As odd as it may seem at first glance, minerals, it is what we are all about…or nearly. Although life on Earth is carbon-based, several other elements present in the planet’s crust are involved in and often indispensable for functioning of living organisms. Many ions are essential, and others show supportive and accessory qualities. They are operative in the skin, supporting specific processes related to the particular situation of this organ at the interface with the environment. Skin bioenergetics, redox balance, epidermal barrier function, and dermal remodeling are amongst crucial activities guided by or taking advantage of mineral elements. Skin regenerative processes and skin ageing can be positively impacted by adequate accessibility, distribution, and balance of inorganic ions

Caratterizzazione chimico-fisica di reflui oleari da processi di estrazione a due fasi e di loro sottoprodotti dopo recupero energetico.

Scopo della presente ricerca, inserita nel progetto europeo BIOTROLL , \ue8 quello della caratterizzazione chimico-fisica delle polpe di olive (OP) e degli effluenti provenienti dal loro trattamento biologico per la produzione di idrogeno (EH2) e di metano (ECH4). I risultati preliminari ottenuti mostrano che gli effluenti analizzati contengono: i) il 28,4 % (OP), il 7,8 % (EH2) e il 4,6 % (ECH4) di sostanza secca; ii) circa il 60 % (sul secco) di carbonio organico e iii) apprezzabili quantit\ue0 di macro (in particolare N organico e K2O) e di microelementi. La quantit\ue0 di metalli pesanti \ue8 trascurabile, mentre il pH e la conduttivit\ue0 elettrica (CE) sono nella norma. I risultati confermano che i prodotti saggiati presentano caratteristiche chimico-fisiche compatibili con il loro possibile impiego in agricoltura

Mineralizzazione nel suolo di farine sgrassate di semi di piante ad alto contenuto in glucosinolati: effetto sulla disponibilit\ue0 dell\u2019azoto e del fosfato

In questo lavoro sono riportati i risultati ottenuti dallo studio della mineralizzazione nel suolo di farine sgrassate ad alto contenuto in glucosinolati. La mineralizzazione apparente dell\u2019azoto e del fosfato aggiunti con le farine \ue8 stata intensa nelle prime settimane per poi stabilizzarsi dopo circa 6-8 settimane d\u2019incubazione, con valori pari a circa il 50-60% dell\u2019azoto e il 20-30 % del fosfato aggiunti. I risultati ottenuti dimostrano che questi prodotti possono essere assimilati a tutti gli effetti a concimi organici NP. Abstract In this research, we have studied the soil mineralisation of several defatted meals from glucosinolates-rich plants. The results showed that the nitrogen and phosphate apparent mineralisation was very high for the first 6-8 weeks, while in the remaining 8-10 weeks the process was negligible. The 50-60 % of added nitrogen, and 20-30 % of phosphate was apparently mineralised at the end of the incubation time. The results obtained have demonstrated that this products are potentially good organic NP fertilisers

Mineralizzazione nel suolo di farine sgrassate di semi di piante ad alto contenuto in glucosinolati: effetto sulla disponibilit\ue0 dell\u2019azoto e del fosfato.

Sommario In questo lavoro sono riportati i risultati ottenuti dallo studio della mineralizzazione nel suolo di farine sgrassate ad alto contenuto in glucosinolati. La mineralizzazione apparente dell\u2019azoto e del fosforo aggiunti con le farine \ue8 stata intensa nelle prime settimane per poi stabilizzarsi dopo circa 6-8 settimane d\u2019incubazione, con valori pari a circa il 50-60% dell\u2019azoto e il 20-30 % del fosfato aggiunti. I risultati ottenuti dimostrano che questi prodotti possono essere assimilati a tutti gli effetti a concimi organici NP. Abstract In this research, we have studied the soil mineralisation of several defatted meals from glucosinolates-rich plants. The results showed that the nitrogen and phosphate apparent mineralisation was very high for the first 6-8 weeks, while in the remaining 8-10 weeks the process was negligible. The 50-60 % of added nitrogen, and 20-30 % of phosphate was apparently mineralised at the end of the incubation time. The results obtained have demonstrated that this products are potentially good organic NP fertilisers