Quercetin improves and protects Calu-3 airway epithelial barrier function.

In light of the impact of airway barrier leaks in COVID-19 and the significance of vitamin D in COVID-19 outcomes, including airway barrier protection, we investigated whether the very common dietary flavonoid quercetin could also be efficacious in supporting airway barrier function. To address this question, we utilized the widely used airway epithelial cell culture model, Calu-3. We observed that treating Calu-3 cell layers with quercetin increased transepithelial electrical resistance while simultaneously reducing transepithelial leaks of 14C-D-mannitol (Jm) and 14C-inulin.

Calcitriol modifies tight junctions, improves barrier function, and reduces TNF-α-induced barrier leak in the human lung-derived epithelial cell culture model, 16HBE 14o.

Using the 16HBE 14o- human airway epithelial cell culture model, calcitriol (Vitamin D) was shown to improve barrier function by two independent metrics - increased transepithelial electrical resistance (TER) and reduced transepithelial diffusion of C-D-mannitol (J ). Both effects were concentration dependent and active out to 168 h post-treatment. Barrier improvement associated with changes in the abundance of specific tight junctional (TJ) proteins in detergent-soluble fractions, most notably decreased claudin-2.

The multiphasic TNF-α-induced compromise of Calu-3 airway epithelial barrier function.

Airway epithelial barrier leak and the involvement of proinflammatory cytokines play a key role in a variety of diseases. This study evaluates barrier compromise by the inflammatory mediator Tumor Necrosis Factor-α (TNF-α) in the human airway epithelial Calu-3 model. We examined the effects of TNF-α on barrier function in Calu-3 cell layers using Transepithelial Electrical Resistance (TER) and transepithelial diffusion of radiolabeled probe molecules.

A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in mice.

In the intraerythrocytic protozoan parasites of the genus Babesia both innate and adaptive immune responses are necessary to confer protection against clinical disease. In particular, the adaptive immune response involves the production of neutralizing antibodies as well as the presentation of parasite antigens to CD4+ T lymphocytes by professional antigen-presenting cells. Therefore, the development of alternative vaccines that replace the use of live attenuated strains should include relevant epitopes targeting both B and T cell responses.

Predicting Glycated Hemoglobin Through Continuous Glucose Monitoring in Real-Life Conditions: Improved Estimation Methods.

Background: The adoption of continuous glucose monitoring (CGM) already helps to improve glycemic control in diabetes. When coupled with appropriate data analysis techniques, CGM also provides dependable estimates for significant metrics, like glycated hemoglobin (HbA1c). Findings from the REALISM-T1D study can boost HbA1c estimation methods in diabetes care and stimulate their use in clinical practice.

Diversity of the BoLA-DRB3 gene in cattle breeds from tropical and subtropical regions of Argentina.

Bovine leukocyte antigens (BoLA) have been widely studied because of their primary function in the recognition of pathogens by the immune system. To date, however, the characterization of the BoLA-DRB3 gene in Latin American Zebu and mixed zebuine breeds is scarce. By a sequence-based typing method, here we sequenced exon 2 of BoLA class II DRB3 gene in 264 animals from the five most commonly used breeds in northern Argentina (Creole, Brahman, Braford, Brangus, and Nellore).

Time in range-A1c hemoglobin relationship in continuous glucose monitoring of type 1 diabetes: a real-world study.

Introduction: The availability of easily accessible continuous glucose monitoring (CGM) metrics can improve glycemic control in diabetes, and they may even become a viable alternative to hemoglobin A1c (HbA1c) laboratory tests in the next years. The REALISM-T1D study (REAl-Life glucoSe Monitoring in Type 1 Diabetes) was aimed at contributing, with real-world data, to a deeper understanding of these metrics, including the time in range (TIR)-HbA1c relationship, to facilitate their adoption by diabetologists in everyday practice.

Research Design And Methods: 70 adults affected by type 1 diabetes were monitored for 1 year by means of either flash (FGM) or real-time (rtCGM) glucose monitoring devices.

Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

Background: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans.

Aims: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia.

Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection.

Protection against the intraerythrocytic protozoan parasite Babesia bovis depends on both strong innate and adaptive immune response, this latter involving the presentation of parasite antigens to CD4 T-lymphocytes by professional antigen-presenting cells. Secretion of Th1 cytokines by CD4 T cell is also very important for isotype switching to IgG, the best opsonising antibody isotype in cattle, to target extracellular parasites and parasite antigens displayed at the erythrocyte surface. In the field of vaccinology, heterologous prime-boost schemes combining protein-adjuvant formulations with a modified vaccinia Ankara vector expressing the same antigen have demonstrated the induction of both humoral and cellular immune responses.

Helicobacter pylori and diabetes mellitus: a controversial relationship.

Research on Helicobacter pylori (H. pylori), a pathogenic bacterium that is widespread among humans, is investigating the medical implications of the infection in many fields beyond gastroenterology. Because of the ubiquitous presence of the infection, there is an increasing interest in finding a relationship between this bacterium and diabetes mellitus (DM).

Improving Transient Transfection Efficiency in a Differentiated, Polar Epithelial Cell Layer.

Polar, differentiated epithelial cell culture models (especially at confluence) are difficult to transfect compared with the higher transfection efficiencies that one obtains with relatively less differentiated, nonpolar cell culture models. Here, we sought to develop a strategy to enhance the efficiency of transfecting polar, differentiated epithelial cells. We found that chemically abrading the differentiated CACO-2 human intestinal epithelial cell layer by a trypsin and EDTA pretreatment (before the use of detergent-like transfection reagents) dramatically improved transfection efficiency in this polar, differentiated model.

Cobalt chloride compromises transepithelial barrier properties of CaCo-2 BBe human gastrointestinal epithelial cell layers.

Background: Elevation of the transcription factor HIF-1 is a prominent mediator of not only processes that accompany hypoxia, but also the tumor microenvironment and tissue regeneration. This study uses mediators of "chemical hypoxia" to ask the question whether HIF-1α elevation in a healthy epithelial cell layer leads to leakiness in its tight junctional seals.

Methods: Transepithelial electrical resistance and transepithelial diffusion of C-D-mannitol and other radiolabeled probes are used as indicators of transepithelial barrier function of CaCo-2 BBe human gastrointestinal epithelial cell layers cultured on permeable supports.

Improvement of Human-Oral-Epithelial-Barrier Function and of Tight Junctions by Micronutrients.

The oral epithelium represents a major interface between an organism and its external environment. Improving this barrier at the molecular level can provide an organism added protection from microbial-based diseases. Barrier function of the Gie-3B11-human-gingival-epithelial-cell-culture model is enhanced by the micronutrients zinc, quercetin, retinoic acid, and acetyl-11-keto-β-boswellic acid, as observed by a concentration-dependent increase in transepithelial electrical resistance and a decrease in transepithelial C-d-mannitol permeability.

Zinc reduces epithelial barrier compromise induced by human seminal plasma.

Human semen has the potential to modulate the epithelial mucosal tissues it contacts, as seminal plasma (SP) is recognized to contain both pro- and anti-barrier components, yet its effects on epithelial barrier function are largely unknown. We addressed the role of human SP when exposed to the basal-lateral epithelial surface, a situation that would occur clinically with prior mechanical or disease-related injury of the human epithelial mucosal cell layers in contact with semen. The action of SP on claudins-2, -4, -5, and -7 expression, as well as on a target epithelium whose basolateral surface has been made accessible to SP, showed upregulation of claudins-4 and -5 in CACO-2 human epithelial cell layers, despite broad variance in SP-induced modulation of transepithelial electrical resistance and mannitol permeability.

Skin cancer risk assessment in dark skinned immigrants: the role of social determinants and ethnicity.

Objectives: Dark-skinned people have a lower incidence rate of skin cancer, in particular melanoma, which is detected at more advanced stages leading to poorer prognoses and long-term outcomes compared to whites. The gap in survival is due to some difficulty in melanoma detection, lack of attention from doctors and awareness by patients. This study aims to assess skin cancer risk awareness in dark-skinned immigrants and to determine the influence of socioeconomic factors and ethnic origin on behaviors.

LYMPHA Technique to Prevent Secondary Lower Limb Lymphedema.

Background: Inguinofemoral lymphadenectomy carries a high risk of lower limb lymphedema. This report describes the feasibility of performing multiple lymphatic-venous anastomoses (MLVA) after inguinofemoral lymph node completion (LYMPHA technique) and the possible benefit of LYMPHA for preventing lymphedema.

Methods: Between February, 2011 and October, 2014, 11 patients with vulvar cancer and 16 patients with melanoma of the trunk requiring inguinofemoral lymphadenectomy underwent lymph node dissection and the LYMPHA technique.

Sieving characteristics of cytokine- and peroxide-induced epithelial barrier leak: Inhibition by berberine.

Aim: To study whether the inflammatory bowel disease (IBD) colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak.

Methods: We examined the effects of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1-β (IL1β) and hydrogen peroxide (H2O2) - singly and in combinations - on barrier function of CACO-2 cell layers. Our focus was on the type (not simply the magnitude) of transepithelial leak generated by these agents as measured by transepithelial electrical resistance (TER) and transepithelial flux of (14)C-D-mannitol, (3)H-Lactulose and (14)C-Polyethylene glycol as radiolabeled probe molecules.

Methionine restriction fundamentally supports health by tightening epithelial barriers.

Dietary methionine restriction (MR) has been found to affect one of the most primary tissue-level functions of an organism: the efficiency with which the epithelial linings of major organs separate the fluid compartments that they border. This process, epithelial barrier function, is basic for proper function of all organs, including the lung, liver, gastrointestinal tract, reproductive tract, blood-brain barrier, and kidney. Specifically, MR has been found to modify the protein composition of tight junctional complexes surrounding individual epithelial cells in a manner that renders the complexes less leaky.

Remodeling of Tight Junctions and Enhancement of Barrier Integrity of the CACO-2 Intestinal Epithelial Cell Layer by Micronutrients.

The micronutrients zinc, quercetin, butyrate, indole and berberine were evaluated for their ability to induce remodeling of epithelial tight junctions (TJs) and enhance barrier integrity in the CACO-2 gastrointestinal epithelial cell culture model. All five of these chemically very diverse micronutrients increased transepithelial electrical resistance (Rt) significantly, but only berberine also improved barrier integrity to the non-electrolyte D-mannitol. Increases of Rt as much as 200% of untreated controls were observed.

Drug delivery of zinc to Barrett's metaplasia by oral administration to Barrett's esophagus patients.

Background: Delivery of a pharmacologically effective drug dosage to a target tissue is critical. Barrett's epithelia are a unique challenge for drug delivery of orally administered zinc due to rapid transit down the esophageal lumen, incomplete absorptive differentiation of these epithelia, and the use of proton-pump inhibitor drugs abrogating intestinal uptake of supplemental zinc.

Methods: Barrett's esophagus patients were administered oral zinc gluconate (26 mg zinc twice daily) for 14 days prior to biopsy procurement.