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Aberrant Metabolism as Inductor involving Epigenetic Modifications in Breast cancers: Beneficial Opportunities.
It is demonstrated that the choice of crosslinking technique has a significant influence on the biocompatibility, mechanical properties and chemical structure of hydrogels that may be suitable for corneal tissue engineering and regenerative applications.Respiratory exposure of humans to environmental and therapeutic nanoparticles repeatedly occurs at relatively low concentrations. To identify adverse effects of particle accumulation under realistic conditions, monocultures of Calu-3 and A549 cells and co-cultures of A549 and THP-1 macrophages in the air-liquid interphase culture were exposed repeatedly to 2 µg/cm2 20 nm and 200 nm polystyrene particles with different functionalization. Particle accumulation, transepithelial electrical resistance, dextran (3-70 kDa) uptake and proinflammatory cytokine secretion were determined over 28 days. Calu-3 cells showed constant particle uptake without any change in barrier function and cytokine release. A549 cells preferentially ingested amino- and not-functionalized particles combined with decreased endocytosis. Cytokine release was transiently increased upon exposure to all particles. Carboxyl-functionalized demonstrated higher uptake and higher cytokine release than the other particles in the A549/THP-1 co-cultures. The evaluated respiratory cells and co-cultures ingested different amounts and types of particles and caused small (partly transient) effects. The data suggest that the healthy cells can adapt to low doses of non-cytotoxic particles.Progenitor Biological Bandages (PBB) have been continuously applied clinically in the Lausanne Burn Center for over two decades. Vast translational experience and hindsight have been gathered, specifically for cutaneous healing promotion of donor-site grafts and second-degree pediatric burns. PBBs constitute combined Advanced Therapy Medicinal Products, containing viable cultured allogeneic fetal dermal progenitor fibroblasts. Such constructs may partly favor repair and regeneration of functional cutaneous tissues by releasing cytokines and growth factors, potentially negating the need for subsequent skin grafting, while reducing the formation of hypertrophic scar tissues. This retrospective case-control study (2010-2018) of pediatric second-degree burn patients comprehensively compared two initial wound treatment options (i.e., PBBs versus Aquacel® Ag, applied during ten to twelve days post-trauma). Results confirmed clinical safety of PBBs with regard to morbidity, mortality, and overall complications. No difference was detected between groups for length of hospitalization or initial relative burn surface decreasing rates. Nevertheless, a trend was observed in younger patients treated with PBBs, requiring fewer corrective interventions or subsequent skin grafting. Importantly, significant improvements were observed in the PBB group regarding hypertrophic scarring (i.e., reduced number of scar complications and related corrective interventions). Such results establish evidence of clinical benefits yielded by the Swiss fetal progenitor cell transplantation program and favor further implementation of specific cell therapies in highly specialized regenerative medicine.The aim of this study was to present molecular and antimicrobial resistance characteristics of methicillin-resistant Staphylococcus aureus (MRSA) clonal complex (CC) 398 isolated from diseased dogs and cats in Thailand. A total of 20 MRSA isolates of 134 Staphylococcus aureus isolated from canine and feline clinical samples during 2017-2020 were CC398, consisting of sequence type (ST) 398 (18 isolates), ST5926 (1 isolate), and ST6563 (1 isolate) by multilocus sequence typing. spa t034 and staphylococcal cassette chromosome mec (SCCmec) V were predominantly associated with ST398. Intraclonal differentiation was present by additional spa (t1255, t4653), non-detectable spa, composite SCCmec with a hybrid of ccrA1B1+ccrC and class A mec complex, and DNA fingerprints by pulsed-field gel electrophoresis. The isolates essentially carried antimicrobial resistance genes, mediating multiple resistance to β-lactams (mecA, blaZ), tetracyclines [tet(M)], aminoglycosides [aac(6')-Ie-aph(2')-Ia], and trimethoprim (dfr). Livestock-associated MRSA ST398 resistance genes including lnu(B), lsa(E), spw, fexA, and tet(L) were heterogeneously found and lost in subpopulation, with the absence or presence of additional erm(A), erm(B), and ileS2 genes that corresponded to resistance phenotypes. As only a single CC398 was detected with the presence of intraclonal variation, CC398 seems to be the successful MRSA clone colonizing in small animals as a pet-associated MRSA in Thailand.Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol.The conjunctiva, an under-researched yet incredibly important tissue, plays key roles in providing protection to the eye and maintaining homeostasis of its ocular surface. Multiple diseases can impair conjunctival function leading to severe consequences that require surgical intervention. Small conjunctival defects can be repaired relatively easily, but larger defects rely on tissue grafts which generally do not provide adequate healing. A tissue engineering approach involving a biomaterial substrate capable of supporting a stratified epithelium with embedded, mucin-secreting goblet cells offers a potential solution. As a first step, this study aimed to induce stratification of human conjunctival epithelial cells cultured on electrospun scaffolds composed from poly(ε-caprolactone) (PCL) and decellularised tissue matrix (small intestinal submucosa (SIS) or urinary bladder matrix (UBM)) and held at the air/liquid interface. Stratification, up to 5 cell layers, occurred more frequently on scaffolds containing PCL + UBM. Incorporation of these decellularised tissue matrices also impacted material properties, with significant changes occurring to their fibre diameter, tensile properties, and chemical composition throughout the scaffold structure compared to PCL alone. These matrix containing scaffolds warrant further long-term investigation as a potential advanced therapy medicinal product for conjunctiva repair and regeneration.The mutual impact of low-quality lignite and high-density polyethylene (HDPE) during open system pyrolysis was investigated, aiming to improve utilization of lignite with simultaneous treatment of HDPE waste. Pyrolysis of lignite, HDPE, and their mixture (mass ratio, 11) was performed at temperatures 400, 450, 500, 550, and 600 °C. Initial substrates and pyrolysis products were characterized by thermogravimetric analysis (TGA), gas chromatography-mass spectrometry (GC-MS), specific carbon isotope analysis of individual hydrocarbons (δ13C), Rock-Eval pyrolysis, and elemental analysis. The positive synergetic effect during co-pyrolysis of lignite/HDPE mixture was observed at temperatures ≥450 °C, with the greatest being at 500 °C. The highest yield of liquid co-pyrolysis products with a similar composition to that of crude oils is also noticed at 500 °C. The yields of liquid and gaseous products and quality of pyrolytic products obtained by co-pyrolysis of lignite/HDPE mixture are notably improved compared with pyrolysis of lignite alone. On the other hand, data obtained from pyrolysis of HDPE alone indicate that it cannot be concurrent to well-developed catalytic thermal processes for polymer recycling. However, concerning the huge amount of produced HDPE, at least part of this plastic material can be reused for advanced thermal treatment of lignite, particularly in countries where this low-rank coal represents the main source of energy.Heme oxygenase catalyzes the rate-limiting step in heme degradation in order to generate biliverdin, carbon monoxide (CO), and iron. The inducible form of the enzyme, heme oxygenase-1 (HO-1), exerts a central role in cellular protection. The substrate, heme, is a potent pro-oxidant that can accelerate inflammatory injury and promote cell death. HO-1 has been implicated as a key mediator of inflammatory cell and tissue injury, as validated in preclinical models of acute lung injury and sepsis. A large body of work has also implicated HO-1 as a cytoprotective molecule against various forms of cell death, including necrosis, apoptosis and newly recognized regulated cell death (RCD) programs such as necroptosis, pyroptosis, and ferroptosis. While the antiapoptotic potential of HO-1 and its reaction product CO in apoptosis regulation has been extensively characterized, relatively fewer studies have explored the regulatory role of HO-1 in other forms of necrotic and inflammatory RCD (i.e., pyroptosis, necroptosis and ferroptosis). HO-1 may provide anti-inflammatory protection in necroptosis or pyroptosis. In contrast, in ferroptosis, HO-1 may play a pro-death role via enhancing iron release. HO-1 has also been implicated in co-regulation of autophagy, a cellular homeostatic program for catabolic recycling of proteins and organelles. While autophagy is primarily associated with cell survival, its occurrence can coincide with RCD programs. This review will summarize the roles of HO-1 and its reaction products in co-regulating RCD and autophagy programs, with its implication for both protective and detrimental tissue responses, with emphasis on how these impact HO-1 as a candidate therapeutic target in disease.The mean age of lung transplant recipients has significantly increased in recent decades. Elderly recipients have a higher risk of developing herpes zoster (HZ), and they have in general a worse response to vaccination than younger persons do. see more We investigated the relationship between the humoral and cellular immune response to a live-attenuated HZ vaccine (Zostavax®, Merck Sharp and Dohme) and the frequencies of T and B cell subsets, especially aged cell subsets (CD28-T cells and age associated B cells, ABCs). In total, 37 patients awaiting lung transplantation received one dose of Zostavax®, and peripheral blood was collected before and within 6 months after vaccination. We observed a robust immune response after vaccination. The frequencies of CD28-T cells before vaccination had no impact on the subsequent immune response to HZ vaccination. However, a higher frequency of ABCs before vaccination correlated with a lower immune response especially regarding the cellular immune response. Cytomegalovirus seropositivity was associated with increased frequencies of CD28-T cells but not with frequencies of ABCs in the patients.
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