المؤلفون: DiGuilio, Katherine M.¹ (AUTHOR) diguiliok@mlhs.org, Del Rio, Elizabeth A.¹ (AUTHOR) delrioe@mlhs.org, Harty, Ronald N.² (AUTHOR) rharty@vet.upenn.edu, Mullin, James M.^1,3 (AUTHOR) mullinj@mlhs.org

المصدر: International Journal of Molecular Sciences. Mar2024, Vol. 25 Issue 6, p3452. 13p.

مصطلحات موضوعية: *TIGHT junctions, *MICRONUTRIENTS, *FOOD consumption, *VITAMIN D, *CELLULAR signal transduction, *TUMOR necrosis factors

مستخلص: Disease modifiers, whether from cancer, sepsis, systemic inflammation, or microbial pathogens, all appear to induce epithelial barrier leak, with induced changes of the Tight Junctional (TJ) complex being pivotal to the process. This leak—and the ensuant breakdown of compartmentation—plays a central role in disease morbidity on many levels. Accumulation of lung water in the luminal compartment of airways was a major driver of morbidity and mortality in COVID-19 and is an excellent example of the phenomenon. Increasing awareness of the ability of micronutrients to improve basal barrier function and reduce barrier compromise in pathophysiology may prove to be a low-cost, safe, and easily administered prophylactic and/or therapeutic option amenable to large populations. The growing appreciation of the clinical utility of supplemental doses of Vitamin D in COVID-19 is but one example. This narrative review is intended to propose a general theory on how and why micronutrients—at levels above normal dietary intake—successfully remodel TJs and improve barrier function. It discusses the key difference between dietary/Recommended Daily Allowance (RDA) levels of micronutrients versus supplemental levels, and why the latter are needed in disease situations. It advances a hypothesis for why signal transduction regulation of barrier function may require these higher supplemental doses to achieve the TJ remodeling and other barrier element changes that are clinically beneficial. [ABSTRACT FROM AUTHOR]

المؤلفون: DiGuilio, Katherine M., Rybakovsky, Elizabeth, Abdavies, Reza, Chamoun, Romy, Flounders, Colleen A., Shepley-McTaggart, Ariel, Harty, Ronald N., Mullin, James M.

مصطلحات موضوعية: Micronutrient, Tight junction, Claudin, Zinc, Vitamin A, Vitamin D, Barrier function, Inflammation, Sepsis, Virus, COVID, Critical care

الوصف: The published literature makes a very strong case that a wide range of disease morbidity associates with and may in part be due to epithelial barrier leak. An equally large body of published literature substantiates that a diverse group of micronutrients can reduce barrier leak across a wide array of epithelial tissue types, stemming from both cell culture as well as animal and human tissue models. Conversely, micronutrient deficiencies can exacerbate both barrier leak and morbidity. Focusing on zinc, Vitamin A and Vitamin D, this review shows that at concentrations above RDA levels but well below toxicity limits, these micronutrients can induce cell- and tissue-specific molecular-level changes in tight junctional complexes (and by other mechanisms) that reduce barrier leak. An opportunity now exists in critical care—but also medical prophylactic and therapeutic care in general—to consider implementation of select micronutrients at elevated dosages as adjuvant therapeutics in a variety of disease management. This consideration is particularly pointed amidst the COVID-19 pandemic. ; Temple University. College of Science and Technology ; Biology

وصف الملف: 42 pages

العلاقة: MDPI; http://dx.doi.org/10.3390/ijms23062995Test; International Journal of Molecular Sciences, Vol. 23, Iss. 6; Faculty/ Researcher Works; DiGuilio, K.M.; Rybakovsky, E.; Abdavies, R.; Chamoun, R.; Flounders, C.A.; Shepley-McTaggart, A.; Harty, R.N.; Mullin, J.M. Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy. Int. J. Mol. Sci. 2022, 23, 2995. https://doi.org/10.3390/ijms23062995Test; http://hdl.handle.net/20.500.12613/9406Test

الإتاحة: https://doi.org/20.500.12613/9406Test
https://doi.org/10.3390/ijms23062995Test
https://hdl.handle.net/20.500.12613/9406Test

المؤلفون: DiGuilio, Katherine M, Rybakovsky, Elizabeth, Abdavies, Reza, Chamoun, Romy, MD, Flounders, Colleen A, Shepley-McTaggart, Ariel, Harty, Ronald N, Mullin, James M

المصدر: Department of Medicine

مصطلحات موضوعية: Animals, COVID-19, Humans, Inflammatory Bowel Diseases, Intestinal Mucosa, Micronutrients, Pandemics, SARS-CoV-2, Tight Junctions, Vitamin A, Vitamin D, Vitamins, Zinc, Department of Medicine, Department of Medicine Fellows and Residents, Fellows and Residents, Medicine and Health Sciences

الوصف: The published literature makes a very strong case that a wide range of disease morbidity associates with and may in part be due to epithelial barrier leak. An equally large body of published literature substantiates that a diverse group of micronutrients can reduce barrier leak across a wide array of epithelial tissue types, stemming from both cell culture as well as animal and human tissue models. Conversely, micronutrient deficiencies can exacerbate both barrier leak and morbidity. Focusing on zinc, Vitamin A and Vitamin D, this review shows that at concentrations above RDA levels but well below toxicity limits, these micronutrients can induce cell- and tissue-specific molecular-level changes in tight junctional complexes (and by other mechanisms) that reduce barrier leak. An opportunity now exists in critical care-but also medical prophylactic and therapeutic care in general-to consider implementation of select micronutrients at elevated dosages as adjuvant therapeutics in a variety of disease management. This consideration is particularly pointed amidst the COVID-19 pandemic.

العلاقة: https://scholarlyworks.lvhn.org/medicine/4233Test; https://pubmed.ncbi.nlm.nih.gov/35328419Test/

الإتاحة: https://scholarlyworks.lvhn.org/medicine/4233Test
https://pubmed.ncbi.nlm.nih.gov/35328419Test/

المؤلفون: Mullin, James M.¹ mullinj@mlhs.org, Diguilio, Katherine M.¹, Valenzano, Mary C.¹, Deis, Rachael², Thomas, Sunil¹, Zurbach, E. Peter³, Abdulhaqq, Shaheed⁴, Montaner, Luis J.⁴

المصدر: PLoS ONE. 3/9/2017, Vol. 12 Issue 3, p1-18. 18p.

مصطلحات موضوعية: *EPITHELIAL cells, *TRANSFORMING growth factors, *SEMINAL proteins, *SEMEN analysis, *ZINC in the body

مستخلص: 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. Upregulation of claudin-2 by SP also exhibited such variance by SP sample. We characterize individual effects on CACO-2 barrier function of nine factors known to be present abundantly in seminal plasma (zinc, EGF, citrate, spermine, fructose, urea, TGF, histone, inflammatory cytokines) to establish that zinc, spermine and fructose had significant potential to raise CACO-2 transepithelial resistance, whereas inflammatory cytokines and EGF decreased this measure of barrier function. The role of zinc as a dominant factor in determining higher levels of transepithelial resistance and lower levels of paracellular leak were confirmed by zinc chelation and exogenous zinc addition. As expected, SP presentation to the basolateral cell surface also caused a very dramatic yet transient elevation of pErk levels. Results suggest that increased zinc content in SP can compete against the barrier-compromising effect of negative modulators in SP when SP gains access to that epithelium’s basolateral surface. Prophylactic elevation of zinc in an epithelial cell layer prior to contact by SP may help to protect an epithelial barrier from invasion by SP-containing STD microbial pathogens such as HPV or HIV. [ABSTRACT FROM AUTHOR]