COMT Variants are Associated With Breast and Nipple Pain.

Estimates suggest that only 24.9% of infants born in 2019 were exclusively breastfed before 6 months of age, despite the known health benefits of exclusive breastfeeding. Breast and nipple pain is one of the primary determinants of exclusive breastfeeding.

Polyphenols and Lactation: Molecular Evidence to Support the Use of Botanical Galactagogues.

Botanicals and herbal supplements contain a diverse array of polyphenols that may affect mammary gland function and promote galactagogue activity. This scoping review is conducted to identify scientific literature elucidating how polyphenols affect mammary gland biology and cellular mechanisms critical for lactation. A literature search of PubMed and Medline reviews relevant studies in dairy animals, rodent models, and cultured mammary epithelial cells that are published from January 2010 until July 2023, to ascertain effects of polyphenols on mechanisms regulating milk production and composition.

Stool titanium dioxide is positively associated with stool alpha-1 antitrypsin and calprotectin in young healthy adults.

Titanium dioxide (TiO2/E171) is used widely in foods, primarily as a food additive. Animal models have shown that chronic TiO exposure may disturb homeostasis of the gastrointestinal tract by increasing gut permeability, inducing gut inflammation, and increasing the likelihood of microbial infection. Adults have a wide range of ingested TiO,which span two to three orders of magnitude, with a small portion of individuals consuming near gram quantities of TiO2/day.

The ins and outs of mammary gland calcium and zinc transport: A brief review.

Milk is an excellent source of all macrominerals and trace elements, which are essential for proper function of a wide variety of vital processes. The concentrations of minerals in milk are influenced by numerous factors, including stage of lactation, time of day, nutritional and health status of the mother, as well as maternal genotype and environmental exposures. Additionally, tight regulation of mineral transport within the secretory mammary epithelial cell itself is critical for the production and secretion of milk.

ZnT2 Is Critical for TLR4-Mediated Cytokine Expression in Colonocytes and Modulates Mucosal Inflammation in Mice.

A wide range of microbial pathogens can enter the gastrointestinal tract, causing mucosal inflammation and infectious colitis and accounting for most cases of acute diarrhea. Severe cases of infectious colitis can persist for weeks, and if untreated, may lead to major complications and death. While the molecular pathogenesis of microbial infections is often well-characterized, host-associated epithelial factors that affect risk and severity of infectious colitis are less well-understood.

Estimation of Titanium Dioxide Intake by Diet and Stool Assessment among US Healthy Adults.

Background: Titanium dioxide (TiO2/E171) is used in foods primarily as a whitening agent. Little is known regarding TiO2 exposure in the United States.

Objectives: To quantify stool TiO2 content among US adults and evaluate its association with estimated intake.

Loss-of-function mutants are associated with gut dysbiosis and alterations in intestinal gene expression in preterm infants.

Loss of Paneth cell (PC) function is implicated in intestinal dysbiosis, mucosal inflammation, and numerous intestinal disorders, including necrotizing enterocolitis (NEC). Studies in mouse models show that zinc transporter ZnT2 () is critical for PC function, playing a role in granule formation, secretion, and antimicrobial activity; however, no studies have investigated whether loss of ZnT2 function is associated with dysbiosis, mucosal inflammation, or intestinal dysfunction in humans. was sequenced in healthy preterm infants (26-37 wks; n = 75), and structural analysis and functional assays determined the impact of mutations.

Zinc Exposure Promotes Commensal-to-Pathogen Transition in Leading to Mucosal Inflammation and Illness in Mice.

The opportunistic pathogen () is associated gastrointestinal (GI) inflammation and illness; however, factors motivating commensal-to-pathogen transition are unclear. Excessive zinc intake from supplements is common in humans. Due to the fact that zinc exposure enhances colonization in vitro, we hypothesized zinc exposure broadly activates virulence mechanisms, leading to inflammation and illness.

Early-life formula feeding is associated with infant gut microbiota alterations and an increased antibiotic resistance load.

Background: Infants are at a high risk of acquiring fatal infections, and their treatment relies on functioning antibiotics. Antibiotic resistance genes (ARGs) are present in high numbers in antibiotic-naive infants' gut microbiomes, and infant mortality caused by resistant infections is high. The role of antibiotics in shaping the infant resistome has been studied, but there is limited knowledge on other factors that affect the antibiotic resistance burden of the infant gut.

Macrolets: Outsized Extracellular Vesicles Released from Lipopolysaccharide-Stimulated Macrophages that Trap and Kill Escherichia coli.

Macrophages release a variety of extracellular vesicles (EVs). Here we describe a previously unreported class of EVs that are released from macrophages in response to Escherichia coli endotoxin, lipopolysaccharide (LPS), that we have named "macrolets" since they are extruded as large "droplets" released from macrophages. Morphologically, macrolets are anuclear, bounded by a single lipid membrane and structurally dependent on an actin cytoskeleton.

A common genetic variant in zinc transporter ZnT2 (Thr288Ser) is present in women with low milk volume and alters lysosome function and cell energetics.

Suboptimal lactation is a common, yet underappreciated cause for early cessation of breastfeeding. Molecular regulation of mammary gland function is critical to the process lactation; however, physiological factors underlying insufficient milk production are poorly understood. The zinc (Zn) transporter ZnT2 is critical for regulation of mammary gland development and maturation during puberty, lactation, and postlactation gland remodeling.

Milk-derived miRNA profiles elucidate molecular pathways that underlie breast dysfunction in women with common genetic variants in SLC30A2.

Studies in humans and pre-clinical animal models show milk-derived miRNAs reflect mammary gland function during lactation. The zinc transporter SLC30A2/ZnT2 plays a critical role in mammary gland function; ZnT2-null mice have profound defects in mammary epithelial cell (MEC) polarity and secretion, resulting in sub-optimal lactation. Non-synonymous genetic variation in SLC30A2 is common in humans, and several common ZnT2 variants are associated with changes in milk components that suggest breast dysfunction in women.

The Role of Genetic Variant rs13266634 in SLC30A8/ZnT8 in Postoperative Hyperglycemia After Major Abdominal Surgery.

Context: Following major surgery, postoperative hyperglycemia (POHG) is associated with suboptimal outcomes among patients with diabetes and nondiabetic patients. A specific genetic variant, rs13266634 (c.973C>T; p.

Increased early enteral zinc intake improves weight gain in hospitalised preterm infants.

Aim: To test the hypothesis that enteral zinc intake is associated with improved preterm infant growth during neonatal intensive care unit (NICU) hospitalisation.

Methods: This prospective cohort study enrolled 105 preterm infants at a tertiary referral centre. Enteral zinc intake was calculated at day of life 14, and growth was measured as change in weight, length and head circumference from birth to discharge.

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host-Microbe Interactions.

Scope: Greater than 68% of young infants are exposed to dietary zinc (Zn) levels that are higher than the Tolerable Upper Intake Limit. However, the consequences of excess dietary Zn during early life on intestinal function and host-microbe interactions are unknown.

Methods And Results: Neonatal mice are gavaged with 100 Zn µg d from postnatal day (PN) 2 through PN10 and indices of intestinal function and host-microbe interactions are compared to unsupplemented mice.

ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution.

Mammary gland involution, a tightly regulated process of tissue remodeling by which a lactating mammary gland reverts to the prepregnant state, is characterized by the most profound example of regulated epithelial cell death in normal tissue. Defects in the execution of involution are associated with lactation failure and breast cancer. Initiation of mammary gland involution requires upregulation of lysosome biogenesis and acidification to activate lysosome-mediated cell death; however, specific mediators of this initial phase of involution are not well described.

A genetic variant in SLC30A2 causes breast dysfunction during lactation by inducing ER stress, oxidative stress and epithelial barrier defects.

SLC30A2 encodes a zinc (Zn) transporter (ZnT2) that imports Zn into vesicles in highly-specialized secretory cells. Numerous mutations and non-synonymous variants in ZnT2 have been reported in humans and in breastfeeding women; ZnT2 variants are associated with abnormally low milk Zn levels and can lead to severe infantile Zn deficiency. However, ZnT2-null mice have profound defects in mammary epithelial cell (MEC) polarity and vesicle secretion, indicating that normal ZnT2 function is critical for MEC function.

Zinc transporter 2 interacts with vacuolar ATPase and is required for polarization, vesicle acidification, and secretion in mammary epithelial cells.

An important feature of the mammary gland is its ability to undergo profound morphological, physiological, and intracellular changes to establish and maintain secretory function. During this process, key polarity proteins and receptors are recruited to the surface of mammary epithelial cells (MECs), and the vesicle transport system develops and matures. However, the intracellular mechanisms responsible for the development of secretory function in these cells are unclear.

Peripheral zinc and neopterin concentrations are associated with mood severity in bipolar disorder in a gender-specific manner.

Bipolar disorder (BD) is a recurrent, episodic mood disorder for which there are no current diagnostic, prognostic or theranostic biomarkers. Two peripheral markers of the acute phase immune response, zinc and neopterin, are consistently associated with severity of depression in literature. Given gender differences in clinical presentation of BD and in inflammatory processes, we aimed to explore the interaction between gender and immune biomarkers to predict mood severity in BD.

Immune and metabolic responses in early and late sepsis during mild dietary zinc restriction.

Background: Mild dietary zinc (Zn) deficiency is widespread in human populations, but its influence on recovery after acute illness is poorly understood. In a mouse model of abdominal sepsis (cecal ligation puncture), systemic immune responses and liver metabolism were monitored in early (24 h) and late (5 d) phases, under control conditions and during mild dietary Zn restriction.

Methods: Mice were fed diets adequate or marginally deficient (ZM) in Zn (30 versus 10 mg zinc/kg diet) for 4 wk, before undergoing laparotomy alone (nonseptic control) or cecal ligation puncture (septic).

ZnT2-Mediated Zinc Import Into Paneth Cell Granules Is Necessary for Coordinated Secretion and Paneth Cell Function in Mice.

Background & Aims: Defects in Paneth cell (PC) function are associated with microbial dysbiosis and intestinal inflammation. PC granules contain antimicrobial peptides, cytokines, and substantial stores of zinc (Zn). We hypothesized that Zn, transported into the granule through the Zn transporter (ZnT)2, is critical for signature PC functions.

Oral omega-3 fatty acids promote resolution in chemical peritonitis.

Background: Recent studies suggest that purified omega-3 fatty acids may attenuate acute inflammation and hasten the transition to healing. In this study, we tested the hypothesis that pretreatment with omega-3-rich fish oil (FO) would promote resolution of peritoneal inflammation through production of specific lipid mediators.

Methods: C57/BL6 mice were given a daily 200-μL oral gavage of saline (CTL) or FO (1.

Marginal dietary zinc deprivation augments sepsis-induced alterations in skeletal muscle TNF-α but not protein synthesis.

Severe zinc deficiency is associated with an increased systemic inflammatory response and mortality after sepsis. However, the impact of mild zinc deficiency, which is more common in populations with chronic illnesses and sepsis, is unknown. In this study, we hypothesized that marginal dietary Zn deprivation (ZM) would amplify tissue inflammation and exacerbate the sepsis-induced decrease in muscle protein synthesis.

Biological underpinnings of breastfeeding challenges: the role of genetics, diet, and environment on lactation physiology.

Lactation is a dynamic process that has evolved to produce a complex biological fluid that provides nutritive and nonnutritive factors to the nursing offspring. It has long been assumed that once lactation is successfully initiated, the primary factor regulating milk production is infant demand. Thus, most interventions have focused on improving breastfeeding education and early lactation support.