Unveiling cofactor inhibition mechanisms in horse liver alcohol dehydrogenase: An allosteric driven regulation.

Horse Liver Alcohol Dehydrogenase (HLADH) is an extensively studied enzyme isolated from equine liver tissue, and holds a central role in numerous enzymatic processes, underscoring the need for thorough investigation. This study delves into the kinetic behavior and structural dynamics of HLADH, shedding light on complex mechanisms governing its catalytic activity and interactions with the cofactor. Notably, deviations from traditional Michaelis-Menten kinetics are observed, manifesting as a slowdown in catalytic rate under high NADH concentrations.

Prevention of Swelling Phenomenon of Alginate Beads To Improve the Stability and Recyclability of Encapsulated Horse Liver Alcohol Dehydrogenase.

Horse Liver Alcohol Dehydrogenase (HLADH) has been immobilized on calcium-alginate beads and used for both oxidation and reduction reactions. To avoid swelling of the beads and their subsequent breakage, calcium ions were added to both reaction and storage solutions, allowing the beads to maintain the initial structural features. The techniques used for this purpose revealed that 2 mM Ca is the optimal concentration, which does not significantly change the weight of the beads, the amount of water in them, and their external and internal structure.

Rationale and design of the pragmatic clinical trial tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT).

Aims: There is a lack of evidence regarding the benefits of β-blocker treatment after invasively managed acute myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF).

Methods And Results: The tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT) trial is a pragmatic, controlled, prospective, randomized, open-label blinded endpoint (PROBE design) clinical trial testing the benefits of β-blocker maintenance therapy in patients discharged after MI with or without ST-segment elevation. Patients eligible for participation are those managed invasively during index hospitalization (coronary angiography), with LVEF >40%, and no history of heart failure (HF).

Analysis of six pyrethroid insecticide metabolites in cord serum using a novel gas chromatography-ion trap mass spectrometry method.

Pyrethroid insecticides are commonly used for residential and commercial pest control in the US. Pregnant women and their fetuses are vulnerable to pesticide exposures during critical windows of neurodevelopment. Biomonitoring for exposure requires accurate and sensitive methods to assess exposures during pregnancy.

Low oxygen tension differentially regulates the expression of placental solute carriers and ABC transporters.

Low oxygen concentration, or hypoxia, is an important physiological regulator of placental function including chemical disposition. Here, we compared the ability of low oxygen tension to alter the expression of solute carriers (SLC) and ABC transporters in two human placental models, namely BeWo cells and term placental explants. We found that exposure to low oxygen concentration differentially regulates transporter expression in BeWo cells, including downregulation of ENT1, OATP4A1, OCTN2, BCRP, and MRP2/3/5, and upregulation of CNT1, OAT4, OATP2B1, SERT, SOAT, and MRP1.

Derivatives of 1,2,4-triazole imines acting as dual iNOS and tumor cell growth inhibitors.

A set of 4-(R-imino)-3-mercapto-5-(R)-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and growth inhibition cytotoxicity. Noticeably, the compounds designed to be nitrofurantoin mimics were the most potent anti-neoplastic agents.

Insulin-Induced Skin Lipohypertrophy in Type 2 Diabetes: a Multicenter Regional Survey in Southern Italy.

Introduction: Lipohypertrophies (LHs) due to incorrect insulin injection techniques have been described in the literature for decades. Their rate averages 38%, but this is still controversial because of the vast range reported by different publications, most of which fail to describe the selected detection protocol and therefore are not entirely reliable. We still need to identify the real LH rate, and only consistently using a standardized method in a large cohort of insulin-treated (IT) patients make this possible.

Exhaled breath condensate nitrite in premature infants with bronchopulmonary dysplasia.

Background: Tracheal aspirate is the conventional method to measure biomarkers of inflammation and oxidation from premature infants on mechanical ventilation at risk for bronchopulmonary dysplasia (BPD), but this method is invasive. Exhaled breath condensate (EBC) is a novel, non-invasive method that has been used in older populations. Nitrite, a stable metabolite of nitric oxide (NO), is elevated in inflammatory conditions.

Interindividual Regulation of the Breast Cancer Resistance Protein/ Transporter in Term Human Placentas.

The breast cancer resistance protein (BCRP/) is a maternally-facing efflux transporter that regulates the placental disposition of chemicals. Transcription factors and gene variants are important regulatory factors that influence transporter expression. In this study, we sought to identify the genetic and transcriptional mechanisms underlying the interindividual expression of BCRP mRNA and protein across 137 term placentas from uncomplicated pregnancies.

Antiplatelet Therapy for Non-ST-Segment Elevation Myocardial Infarction in Complex "Real" Clinical Scenarios: A Consensus Document of the "Campania NSTEMI Study Group".

The incidence of ST-segment elevation myocardial infarction (STEMI) has significantly decreased. Conversely, the rate of non-STEMI (NSTEMI) has increased. Patients with NSTEMI have lower short-term mortality compared to patients with STEMI, whereas at long-term follow-up, the mortality becomes comparable.

Localization of the placental BCRP/ABCG2 transporter to lipid rafts: Role for cholesterol in mediating efflux activity.

Introduction: The breast cancer resistance protein (BCRP/ABCG2) is an efflux transporter in the placental barrier. By transporting chemicals from the fetal to the maternal circulation, BCRP limits fetal exposure to a range of drugs, toxicants, and endobiotics such as bile acids and hormones. The purpose of the present studies was to 1) determine whether BCRP localizes to highly-ordered, cholesterol-rich lipid raft microdomains in placenta microvillous membranes, and 2) determine the impact of cholesterol on BCRP-mediated placental transport in vitro.

Genetic and Dietary Regulation of Glyburide Efflux by the Human Placental Breast Cancer Resistance Protein Transporter.

Glyburide is frequently used to treat gestational diabetes owing to its low fetal accumulation resulting from placental efflux by the breast cancer resistance protein (BCRP)/ABCG2 transporter. Here we sought to determine how exposure to the dietary phytoestrogen genistein and expression of a loss-of-function polymorphism in the ABCG2 gene (C421A) impacted the transport of glyburide by BCRP using stably transfected human embryonic kidney 293 (HEK) cells, human placental choriocarcinoma BeWo cells, and human placental explants. Genistein competitively inhibited the BCRP-mediated transport of (3)H-glyburide in both wild-type (WT) and C421A-BCRP HEK-expressing cells, with greater accumulation of (3)H-glyburide in cells expressing the C421A variant.

Mono-(2-Ethylhexyl) Phthalate Promotes Pro-Labor Gene Expression in the Human Placenta.

Women exposed to phthalates during pregnancy are at increased risk for delivering preterm, but the mechanism behind this relationship is unknown. Placental corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2) are key mediators of parturition and are regulated by the non-canonical NF-kB (RelB/p52) signaling pathway. In this study, we demonstrate that one of the major phthalate metabolites, mono-(2-ethylhexyl)-phthalate (MEHP), increased CRH and COX-2 mRNA and protein abundance in a dose-dependent manner in primary cultures of cytotrophoblast.

Association of prenatal perchlorate, thiocyanate, and nitrate exposure with neonatal size and gestational age.

Background: Perchlorate and similar anions compete with iodine for uptake into the thyroid by the sodium iodide symporter (NIS). This may restrict fetal growth via impaired thyroid hormone production.

Methods: We collected urine samples from 107 pregnant women and used linear regression to estimate differences in newborn size and gestational age associated with increases in perchlorate, thiocyanate, nitrate, and perchlorate equivalence concentrations (PEC; measure of total NIS inhibitor exposure).

Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils.

Background: Mesenchymal stem cells (MSCs) have been proposed as autologous therapy for inflammatory diseases in neonates. MSCs from umbilical cord Wharton's jelly (WJ-MSCs) are accessible, with high proliferative capacity. The effects of WJ-MSCs on neutrophil activity in neonates are not known.

Biodiversity conservation: an example of a multidisciplinary approach to marine dispersal.

The general aim of this paper is to present a possible multidisciplinary approach to the problem of connectivity among marine protected areas (MPAs) describing some of the mechanisms and vectors that control the dispersal of propagules among spatially distributed marine communities of MPAs in the Southern Adriatic Sea. A joint approach is described that focuses on (a) measurements of surface water current and model data integrated with a dedicated software (LAVA, LAgrangian Variational Analysis), (b) measurements of rafting objects and their evaluation as an alternative way to species dispersal, and (c) a tool to automatically monitor propagules and plankton species in the water column. Studies on the dynamics of water currents demonstrated that the Gargano area has the potential to supply dispersal propagules to the Southern Adriatic both along the Italian coastline and offshore across the basin, thus providing important services to the dispersal processes and the connectivity routes among MPAs.

Regional expression of the BCRP/ABCG2 transporter in term human placentas.

The breast cancer resistance protein (BCRP, ABCG2) is an efflux transporter that removes xenobiotics that cross the placenta back to the maternal circulation, thereby limiting exposure of the fetus to drugs and chemicals. Currently, variability of BCRP expression within the placenta is not known. Ten placentas were collected from healthy women undergoing elective Cesarean sections at term.

Effects of maternal exposure to phthalates and bisphenol A during pregnancy on gestational age.

Objective: Phthalates and bisphenol A (BPA) are ubiquitous environmental toxicants, present in high concentrations in numerous consumer products. We hypothesized that maternal exposure to phthalates and BPA in pregnancy is associated with shortened gestation.

Methods: Urinary phthalate and BPA metabolites from 72 pregnant women were measured at the last obstetric clinic visit prior to delivery.

Effects of bilirubin on neutrophil responses in newborn infants.

Background: Newborns are susceptible to inflammatory diseases due to defects in clearing activated immune cells from tissues. Therefore, mechanisms have likely evolved to protect neonates from leukocyte-mediated cytotoxicity. Bilirubin has antioxidant activity, and it is possible that it also exerts effects on cellular immune responses in jaundiced infants.

Decreased anti-inflammatory responses to vitamin D in neonatal neutrophils.

Neutrophil activity is prolonged in newborns, suggesting decreased exposure and/or responses to immunosuppressive modulators, such as 1,25-hydroxyvitamin D(3) (1,25-vit D(3)). We hypothesized that 1,25-vit D(3) suppresses neutrophil activation and that this response is impaired in newborns. Consistent with this, 1,25-vit D(3) decreased LPS-induced expression of macrophage inflammatory protein-1β and VEGF in adult, but not neonatal, neutrophils.

Investigation of anticholinergic and non-steroidal anti-inflammatory prodrugs which reduce chemically induced skin inflammation.

As part of a continuous effort to develop efficient counter measures against sulfur mustard injuries, several unique NSAID prodrugs have been developed and screened for anti-inflammatory properties. Presented herein are three classes of prodrugs which dually target inflammation and cholinergic dysfunction. Compounds 1-28 contain common NSAIDs linked either to choline bioisosteres or to structural analogs of acetylcholinesterase (AChE) inhibitors.

Mechanisms of oxidant generation by catalase.

The enzyme catalase converts solar radiation into reactive oxidant species (ROS). In this study, we report that several bacterial catalases (hydroperoxidases, HP), including Escherichia coli HP-I and HP-II also generate reactive oxidants in response to ultraviolet B light (UVB). HP-I and HP-II are identical except for the presence of NADPH.

Inflammatory effects of phthalates in neonatal neutrophils.

Hospitalized infants are exposed to numerous devices containing the plasticizer di-(2-ethylhexyl) phthalate. Urinary levels of the phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), are markedly elevated in premature infants. Phthalates inactivate peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear transcription factor that mediates the resolution of inflammation, a process impaired in neonates.

IL-10 modulates placental responses to TLR ligands.

Problem: Intra-uterine infections increase production of pro-inflammatory cytokines. It is unclear whether different infectious agents determine the relative expression of pro-and anti-inflammatory cytokines.

Methods Of Study: We compared the placental inflammatory response induced by bacterial lipopolysaccharide (LPS, endotoxin from Gram-negative bacteria) with those induced by lipoteichoic acid (LTA, a cell wall component of Gram-positive bacteria).