Causal relationship between inflammatory bowel disease and erythema nodosum: A two-sample bidirectional Mendelian randomization study.

BACKGROUND: Previous studies have demonstrated the coexistence of erythema nodosum (EN) and inflammatory bowel disease (IBD), while the exact etiology of the co-occurrence of the two disorders remains uncertain. METHODS: A bidirectional two-sample Mendelian randomization (MR) design was employed to determine the causal link between EN and IBD. Genetic variations associated with Crohn's disease (CD) and ulcerative colitis (UC) were derived from accessible genome-wide association studies pertaining to European ancestry. The FinnGen database was used to find the genetic variations containing EN. In the forward model, IBD was identified as the exposure, whereas in the reverse model, EN was identified as the exposure. The causal link between IBD and EN was examined using a range of different analysis techniques, the primary one being the inverse variance weighted (IVW) method, including inverse variance weighted-fixed effects (IVW-FE) and inverse-variance weighted-multiplicative random effects (IVW-MRE). To strengthen the results, assessments of sensitivity, heterogeneity, and pleiotropy were also conducted. RESULTS: MR results showed that IBD increased the risk of EN (IVW-MRE: OR = 1.242, 95% CI = 1.068-1.443, p = 0.005). Furthermore, there was a strong correlation found between CD and a higher risk of EN (IVW-FE: OR = 1.250, 95% CI = 1.119-1.396, p = 8.036 × 10-5 ). However, UC did not appear to be linked to EN (IVW-FE: OR = 1.104, 95% CI = 0.868-1.405, p = 0.421). The reverse MR analysis findings did not imply that EN was linked to IBD. Horizontal pleiotropy did not appear to exist, and the robustness of these findings was confirmed. CONCLUSION: The current investigation found that in European populations, IBD and its subtype CD could raise the incidence of EN.

An entire recycling of spent Al-bearing cathode powder as giniite sphere and lithiophophate plate with leaching-hydrothermal-precipitation process.

Spent lithium battery is a polymetallic waste, and valuable to be recovered as Li-bearing chemical with the barriers of impurities separation, especially Fe and Al. Here in, Li-rich cathode powder was manually disassembled from spent battery, and then recovered as lithiophosphate plate in consideration of effective separation of impure Fe/Al. The powder comprised of 23.2% Fe, 3.2% Al, 5.5% Li and 19.6% P, and then dissolved by azotic acid as Li-rich solution. When the solution was heated to 190°C for 10 h with the supplementary of saccharose, more than 99.9% Fe and 98.9% Al were removed as spherical giniite particles, in accordance with the rest of Fe/Al at the concentrations of 2.1 and 14 mg/L, whilst the loss of Li was less than 1.5%. But without saccharose, the Fe/Al removals only achieved by 99.2% and 52.1%. It is also found that the Fe/Al/Li removal achieved by 99.6%, 96% and 25.3% after adjusting the solution to pH 2.7 by NaOH. After hydrothermal treatment, the rest Li can be recycled as lithiophosphate plate by pH adjustment, in contrast to the recovery efficiency of 98.5% Li. Such method raised a facile route to effectively separate impure Fe/Al from Li-rich cathode powder, and showed promising application in the industrial recovery of spent battery.

L-citrulline attenuates lipopolysaccharide-induced inflammatory lung injury in neonatal rats.

BACKGROUND: Prenatal or postnatal lung inflammation and oxidative stress disrupt alveolo-vascular development leading to bronchopulmonary dysplasia (BPD) with and without pulmonary hypertension. L-citrulline (L-CIT), a nonessential amino acid, alleviates inflammatory and hyperoxic lung injury in preclinical models of BPD. L-CIT modulates signaling pathways mediating inflammation, oxidative stress, and mitochondrial biogenesis-processes operative in the development of BPD. We hypothesize that L-CIT will attenuate lipopolysaccharide (LPS)-induced inflammation and oxidative stress in our rat model of neonatal lung injury. METHODS: Newborn rats during the saccular stage of lung development were used to investigate the effect of L-CIT on LPS-induced lung histopathology and pathways involved in inflammatory, antioxidative processes, and mitochondrial biogenesis in lungs in vivo, and in primary culture of pulmonary artery smooth muscle cells, in vitro. RESULTS: L-CIT protected the newborn rat lung from LPS-induced: lung histopathology, ROS production, NFκB nuclear translocation, and upregulation of gene and protein expression of inflammatory cytokines (IL-1ß, IL-8, MCP-1α, and TNF-α). L-CIT maintained mitochondrial morphology, increased protein levels of PGC-1α, NRF1, and TFAM (transcription factors involved in mitochondrial biogenesis), and induced SIRT1, SIRT3, and superoxide dismutases protein expression. CONCLUSION: L-CIT may be efficacious in decreasing early lung inflammation and oxidative stress mitigating progression to BPD. IMPACT: The nonessential amino acid L-citrulline (L-CIT) mitigated lipopolysaccharide (LPS)-induced lung injury in the early stage of lung development in the newborn rat. This is the first study describing the effect of L-CIT on the signaling pathways operative in bronchopulmonary dysplasia (BPD) in a preclinical inflammatory model of newborn lung injury. If our findings translate to premature infants, L-CIT could decrease inflammation, oxidative stress and preserve mitochondrial health in the lung of premature infants at risk for BPD.

Recent Advances in Imaging Agents Anchored with pH (Low) Insertion Peptides for Cancer Theranostics.

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.

Relationship between Cholesterol-Related Lipids and Severe Acute Pancreatitis: From Bench to Bedside.

It is well known that hypercholesterolemia in the body has pro-inflammatory effects through the formation of inflammasomes and augmentation of TLR (Toll-like receptor) signaling, which gives rise to cardiovascular disease and neurodegenerative diseases. However, the interaction between cholesterol-related lipids and acute pancreatitis (AP) has not yet been summarized before. This hinders the consensus on the existence and clinical importance of cholesterol-associated AP. This review focuses on the possible interaction between AP and cholesterol-related lipids, which include total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) A1, from the bench to the bedside. With a higher serum level of total cholesterol, LDL-C is associated with the severity of AP, while the persistent inflammation of AP is allied with a decrease in serum levels of cholesterol-related lipids. Therefore, an interaction between cholesterol-related lipids and AP is postulated. Cholesterol-related lipids should be recommended as risk factors and early predictors for measuring the severity of AP. Cholesterol-lowering drugs may play a role in the treatment and prevention of AP with hypercholesterolemia.

Polyketides as Secondary Metabolites from the Genus Aspergillus.

Polyketides are an important class of structurally diverse natural products derived from a precursor molecule consisting of a chain of alternating ketone and methylene groups. These compounds have attracted the worldwide attention of pharmaceutical researchers since they are endowed with a wide array of biological properties. As one of the most common filamentous fungi in nature, Aspergillus spp. is well known as an excellent producer of polyketide compounds with therapeutic potential. By extensive literature search and data analysis, this review comprehensively summarizes Aspergillus-derived polyketides for the first time, regarding their occurrences, chemical structures and bioactivities as well as biosynthetic logics.

Damage associated molecular patterns and neutrophil extracellular traps in acute pancreatitis.

Previous researches have emphasized a trypsin-centered theory of acute pancreatitis (AP) for more than a century. With additional studies into the pathogenesis of AP, new mechanisms have been explored. Among them, the role of immune response bears great importance. Pro-inflammatory substances, especially damage-associated molecular patterns (DAMPs), play an essential role in activating, signaling, and steering inflammation. Meanwhile, activated neutrophils attach great importance to the immune defense by forming neutrophil extracellular traps (NETs), which cause ductal obstruction, premature trypsinogen activation, and modulate inflammation. In this review, we discuss the latest advances in understanding the pathological role of DAMPs and NETs in AP and shed light on the flexible crosstalk between these vital inflammatory mediators. We, then highlight the potentially promising treatment for AP targeting DAMPs and NETs, with a focus on novel insights into the mechanism, diagnosis, and management of AP.

Usefulness of Random Forest Algorithm in Predicting Severe Acute Pancreatitis.

Background and Aims: This study aimed to develop an interpretable random forest model for predicting severe acute pancreatitis (SAP). Methods: Clinical and laboratory data of 648 patients with acute pancreatitis were retrospectively reviewed and randomly assigned to the training set and test set in a 3:1 ratio. Univariate analysis was used to select candidate predictors for the SAP. Random forest (RF) and logistic regression (LR) models were developed on the training sample. The prediction models were then applied to the test sample. The performance of the risk models was measured by calculating the area under the receiver operating characteristic (ROC) curves (AUC) and area under precision recall curve. We provide visualized interpretation by using local interpretable model-agnostic explanations (LIME). Results: The LR model was developed to predict SAP as the following function: -1.10-0.13×albumin (g/L) + 0.016 × serum creatinine (µmol/L) + 0.14 × glucose (mmol/L) + 1.63 × pleural effusion (0/1)(No/Yes). The coefficients of this formula were utilized to build a nomogram. The RF model consists of 16 variables identified by univariate analysis. It was developed and validated by a tenfold cross-validation on the training sample. Variables importance analysis suggested that blood urea nitrogen, serum creatinine, albumin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, calcium, and glucose were the most important seven predictors of SAP. The AUCs of RF model in tenfold cross-validation of the training set and the test set was 0.89 and 0.96, respectively. Both the area under precision recall curve and the diagnostic accuracy of the RF model were higher than that of both the LR model and the BISAP score. LIME plots were used to explain individualized prediction of the RF model. Conclusions: An interpretable RF model exhibited the highest discriminatory performance in predicting SAP. Interpretation with LIME plots could be useful for individualized prediction in a clinical setting. A nomogram consisting of albumin, serum creatinine, glucose, and pleural effusion was useful for prediction of SAP.

A Comparison of XGBoost, Random Forest, and Nomograph for the Prediction of Disease Severity in Patients With COVID-19 Pneumonia: Implications of Cytokine and Immune Cell Profile.

Background and Aims: The aim of this study was to apply machine learning models and a nomogram to differentiate critically ill from non-critically ill COVID-19 pneumonia patients. Methods: Clinical symptoms and signs, laboratory parameters, cytokine profile, and immune cellular data of 63 COVID-19 pneumonia patients were retrospectively reviewed. Outcomes were followed up until Mar 12, 2020. A logistic regression function (LR model), Random Forest, and XGBoost models were developed. The performance of these models was measured by area under receiver operating characteristic curve (AUC) analysis. Results: Univariate analysis revealed that there was a difference between critically and non-critically ill patients with respect to levels of interleukin-6, interleukin-10, T cells, CD4+ T, and CD8+ T cells. Interleukin-10 with an AUC of 0.86 was most useful predictor of critically ill patients with COVID-19 pneumonia. Ten variables (respiratory rate, neutrophil counts, aspartate transaminase, albumin, serum procalcitonin, D-dimer and B-type natriuretic peptide, CD4+ T cells, interleukin-6 and interleukin-10) were used as candidate predictors for LR model, Random Forest (RF) and XGBoost model application. The coefficients from LR model were utilized to build a nomogram. RF and XGBoost methods suggested that Interleukin-10 and interleukin-6 were the most important variables for severity of illness prediction. The mean AUC for LR, RF, and XGBoost model were 0.91, 0.89, and 0.93 respectively (in two-fold cross-validation). Individualized prediction by XGBoost model was explained by local interpretable model-agnostic explanations (LIME) plot. Conclusions: XGBoost exhibited the highest discriminatory performance for prediction of critically ill patients with COVID-19 pneumonia. It is inferred that the nomogram and visualized interpretation with LIME plot could be useful in the clinical setting. Additionally, interleukin-10 could serve as a useful predictor of critically ill patients with COVID-19 pneumonia.

Mechanism of online emotional support accompany group for stress: The role of social support.

Objective: To investigate the effect of social support on stress, and to clarify the effect and mechanism of Online Emotional Support Accompany Group (OESAG). Methods: The group members who signed up for the public welfare project "Psychological Rehabilitation Group Psychological Service under the COVID-19 Pandemic" were divided into the treatment group, the control group, and the blank group with 37 members each. The treatment group received OESAG intervention, the control group received online time management group intervention, and the blank group was the waiting group. The three groups of subjects were synchronously tested before and after the intervention group. Results: After the OESAG intervention, compared with the control group and the blank group, the treatment group showed that perceived social support was improved, and loneliness and stress were decreased. Conclusion: Improving social support can effectively reduce stress. OESAG can effectively improve social support and so too decrease stress. This study could help in designing effective psychological intervention measures to reduce the degree of stress symptoms and enhance both personal and social levels of coping with stressful events.

Adiponectin and the regulation of gastric content volume in the newborn rat.

BACKGROUND: Oral intake is dependent on the gastric ability to accommodate the food bolus. Comparatively, neonates have a smaller gastric capacity than adults and this may limit the volume of their milk intake. Yet, we previously reported that the newborn rat gastric milk volume is greatest after birth and, when normalized to body weight, decreases with postnatal age. Such age-dependent changes are not the result of intake differences, but greater gastric accommodation and reduced emptying rate. AIM: Hypothesizing that breastmilk-derived adiponectin is the factor regulating gastric accommodation in neonates, we comparatively evaluated its effects on the rat fundic muscle tone at different postnatal ages. METHODS: In freshly dispersed smooth muscle cells (SMC), we measured the adiponectin effect on the carbachol-induced length changes. RESULTS: Adiponectin significantly reduced the carbachol-stimulated SMC shortening independently of age. In the presence of the inhibitor iberiotoxin, the adiponectin effect on SMC shortening was suppressed, suggesting that it is mediated via large-conductance Ca2+ sensitive K+ channel activation. Lastly, we comparatively measured the newborn rat gastric milk curd adiponectin content in one- and two-week-old rats and found a 50% lower value in the latter. CONCLUSION: Adiponectin, a major component of breastmilk, downregulates fundic smooth muscle contraction potential, thus facilitating gastric volume accommodation. This rodent's adaptive response maximizes breastmilk intake volume after birth.

MCTR1 Intervention Reverses Experimental Lung Fibrosis in Mice.

PURPOSE: Pulmonary fibrosis (PF) is a progressing lethal disease, effective curative therapies remain elusive and mortality remains high. Maresin conjugates in tissue regeneration 1 (MCTR1) is a DHA-derived lipid mediator promoting inflammation resolution produced in macrophage. However, the effect of MCTR1 on PF remains unknown. MATERIAL AND METHODS: We established a lung fibrosis model in mice induced by intratracheal administration of bleomycin (BLM). On day 7 after lung fibrosis model establishment, treatment with MCTR1 up to day 21. The body weight of each mouse was recorded every day and survival curves were plotted. Histological staining was used to detect pulmonary inflammation and fibrosis. Lung sections were examined with transmission electron microscope to evaluate the ultrastructure of cells and deposit of collagen. Inflammatory cytokines in lung tissues were tested by ELISA. q-PCR and Western blot were used to evaluate the mRNA and the protein levels of EMT-related markers. RESULTS: We found that MCTR1 intervention attenuated BLM-induced lung inflammatory and fibrotic response. Furthermore, MCTR1 protected BLM-induced epithelial cell destroy and reversed epithelial-to-mesenchymal transition phenotype into an epithelial one in lung fibrosis mice. Most importantly, post-treatment with MCTR1 restored BLM-induced lung dysfunction and enhanced survival rate significantly. CONCLUSION: Posttreatment with MCTR1 attenuated BLM-induced inflammation and fibrosis changes in mice, suggested MCTR1 may serve as a novel therapeutic strategy for fibrosis-related diseases.

Unexpected conformational behavior of poly(poly(ethylene glycol) methacrylate)-poly(propylene carbonate)-poly(poly(ethylene glycol) methacrylate) (PPEGMA-PPC-PPEGMA) amphiphilic block copolymers in micellar solution and at the air-water interface.

HYPOTHESIS: This paper investigates the self-assembly behavior of a new amphiphilic block copolymer, PPEGMA-PPC-PPEGMA, in dilute aqueous solution and at the air-water interface. In PPEGMA-PPC-PPEGMA, the hydrophilic PEG moieties exist as side chains attached to the PMA backbone. Because of this unique non-linear architecture, the morphological and conformational properties of self-assembled PPEGMA-PPC-PPEGMA polymers are expected to be different from those of conventional linear PEG-based polymer surfactants. EXPERIMENTS: For this study, three PPEGMA-PPC-PPEGMA samples having an identical PPC molecular weight (5.6 kDa) and different PPEGMA molecular weights (7.2, 2.8 and 2.1 kDa on either side) (named "G7C6G7", "G3C5G3", and "G2C6G2", respectively) were synthesized. The micellar self-assembly behaviors of these materials were investigated by cryo-TEM, rheology, DLS, and visual observation. Langmuir monolayers of these materials were characterized by surface mechanical testing. FINDINGS: PPEGMA-PPC-PPEGMA micelles were found to have a spherical geometry, irrespective of copolymer composition. Interestingly, G2C6G2 and G3C6G3 micelles formed weakly-bound clusters, whereas G7C6G7 micelles predominantly existed as isolated micelles. Detailed analysis suggests that this unexpected trend in micelle morphology originates from the fact that the PPEGMA blocks are only partially hydrated at aqueous interfaces. Detailed features of the surface pressure-area isotherms obtained from Langmuir PPEG-PPC-PPEGMA monolayers further supported this notion.

Enhanced quorum sensing of anode biofilm for better sensing linearity and recovery capability of microbial fuel cell toxicity sensor.

MFC toxicity sensor has major hindrances that limit its practical application, such as the poor concentration-response relationship and inferior recovery capability after high toxicity shock. Till now, the direct influence of intrinsic properties on the performance of MFC toxicity sensor has not been well understood. Quorum sensing (QS) is a cell-to-cell communication strategy that indirectly affects the intrinsic properties of electroactive biofilms. In this work, commercially available QS autoinducers (AHLs) were applied to MFC toxicity sensor to manipulate anode biofilm for better sensing performance. The results showed that the addition of AHLs (C6-HSL, 3-OXO-C12-HSL) led to higher sensing linearity to a wider range of Pb2+. The voltage of MFC sensors with AHLs addition fully recovered even after 10 mg/L Cu2+ shock, indicating an enhanced recovery capability of MFC toxicity sensor. It was found that higher live/dead cells ratio and increased exoelectrogen Geobacter abundance were responsible for the superior sensing linearity and recovery capability of MFC toxicity sensor. Our work presented a novel and effective way to advance the process of MFC toxicity sensor application from the perspective of EABs.

Acetaminophen increases pulmonary and systemic vasomotor tone in the newborn rat.

BACKGROUND: Acetaminophen is widely prescribed to both neonates and young children for a variety of reasons. In adults, therapeutic usage of acetaminophen induces systemic arterial pressure changes and exposure to high doses promotes tissue toxicity. The pulmonary vascular effects of acetaminophen at any age are unknown. Hypothesizing that, early in life, it promotes vasomotor tone changes via oxidative stress, we tested the in vitro acetaminophen effects on intrapulmonary and carotid arteries from newborn and adult rats. METHOD: We measured the acetaminophen dose-response in isometrically mounted arteries and pharmacologically evaluated the factors accounting for its vasomotor effects. RESULTS: Acetaminophen induced concentration- and age-dependent vasomotor tone changes. Whereas a progressive increase in vasomotor tone was observed in the newborn, the adult arteries showed mostly vasorelaxation. Inhibition of endogenous nitric oxide generation with L-NAME and the use of the peroxynitrite decomposition catalyst FeTPPS (Fe(III)5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato chloride) mostly abolished the drug-induced increase in newborn pulmonary vasomotor tone CONCLUSIONS: In newborn rats, acetaminophen increases pulmonary vasomotor tone via peroxynitrite generation. Given its therapeutic usage, further clinical studies are warranted to assess the acetaminophen effects on the newborn pulmonary and systemic vascular resistance.

GLI2 Modulated by SUFU and SPOP Induces Intestinal Stem Cell Niche Signals in Development and Tumorigenesis.

Gut mesenchyme provides key stem cell niche signals such as Wnt ligands, but how these signals are regulated is unclear. Because Hedgehog (Hh) signaling is critical for gut mesenchymal development and tumorigenesis, we investigated Hh-mediated mechanisms by analyzing mice deleted for key negative regulators of Hh signaling, Sufu and/or Spop, in the gut mesenchyme, and demonstrated their dosage-dependent roles. Although these mutants exhibit abnormal mesenchymal cell growth and functionally defective muscle layers, villification is completed with proper mesenchymal clustering, implying a permissive role for Hh signaling. These mesenchymal defects are partially rescued by Gli2 reduction. Consistent with increased epithelial proliferation caused by abnormal Hh activation in development, Sufu reduction promotes intestinal tumorigenesis, whereas Gli2 heterozygosity suppresses it. Our analyses of chromatin and GLI2 binding genomic regions reveal its transcriptional regulation of stem cell niche signals through enhancers, providing mechanistic insight into the intestinal stem cell niche in development and tumorigenesis.

Hydrogen peroxide promotes gastric motility in the newborn rat.

BACKGROUND: When compared with infant formula, human milk enhances gastric emptying in preterm infants. Hydrogen peroxide (H2O2) is present in large quantities in human milk that has an antimicrobial role for the mother and infant. In vitro adult rat studies suggest that H2O2 facilitates gastric motor contraction. Hypothesizing that H2O2 enhances gastric motility, we investigated its effects on the newborn rat stomach tissue. METHODS: Rat newborn and adult gastric fundic segments, or their smooth muscle cells, were used to evaluate the muscle response to H2O2 exposure. Tissue expression of Rho kinase 2 (ROCK-2; Western blot), its catalase activity, and H2O2 content (Amplex Red) were measured. H2O2 gastric mucosal diffusion was evaluated with Ussing chambers. RESULTS: In both newborn and adult rats, H2O2 induced gastric muscle contraction and this response was attenuated by pre-incubation with the antioxidant melatonin. H2O2 passively diffused across the gastric mucosa. Its effect on the muscle was modulated via ROCK-2 activation and inhibited by melatonin. CONCLUSION: H2O2, at a concentration similar to that of human milk, promotes gastric motility in the rat. To the extent that the present findings can be clinically extrapolated, the human milk H2O2 content may enhance gastric emptying in neonates.

The effect of a single anti-Vascular Endothelial Growth Factor injection on neonatal growth and organ development: In-vivo study.

Retinopathy of prematurity (ROP) is one of the leading causes of blindness in preterm Infants. Anti-vascular endothelial growth factor (VEGF) is emerging as a promising treatment, but there is insufficient evidence on their safety. We investigate the effect of systemic anti-VEGF in rat pups with equivalent maturity to a 32 week neonate. A single dose of either anti-VEGF antibody (n = 7) or saline (control group; n = 6) was administered to newborn rats intra-peritoneally on the first day of life. 14 days' post treatment, the serum concentration of anti-VEGF was measured and the brain, lung, heart, kidney and liver were harvested and weighed. The heart was processed to measure the Fulton index (a surrogate for pulmonary hypertension). All other organs were processed for mRNA expression of VEGF and VEGF-receptors (R1&R2). No group differences in body and organ weights were noted. The anti-VEGF was still detected in serum 14 days post Injection and resulted in increase in lung (p < 0.002) and kidney (p < 0.01) VEGF mRNA expressions and the lung (p < 0.02) VEGF-R1 and kidney (P < 0.001) VEGF-R2 mRNA expressions. The treated pups exhibited increased total heart weight (p < 0.01) and Fulton Index (p < 0.05). No changes were seen in the liver and brain. Anti-VEGF antibody did not affect mortality, total body and organ weights, but was associated with pulmonary hypertension. Expression of lung and kidney VEGF and its receptors was increased, whilst the brain and liver did not show changes. Dosing experiments can now be targeted to assess safety threshold and at anti-VEGF dose used in human ROP treatment.

Human milk H2O2 content: does it benefit preterm infants?

BackgroundHuman milk has a high content of the antimicrobial compound hydrogen peroxide (H2O2). As opposed to healthy full-term infants, preterm neonates are fed previously expressed and stored maternal milk. These practices may favor H2O2 decomposition, thus limiting its potential benefit to preterm infants. The goal of this study was to evaluate the factors responsible for H2O2 generation and degradation in breastmilk.MethodsHuman donors' and rats' milk, along with rat mammary tissue were evaluated. The role of oxytocin and xanthine oxidase on H2O2 generation, its pH-dependent stability, as well as its degradation via lactoperoxidase and catalase was measured in milk.ResultsBreast tissue xanthine oxidase is responsible for the H2O2 generation and its milk content is dependent on oxytocin stimulation. Stability of the human milk H2O2 content is pH-dependent and greatest in the acidic range. Complete H2O2 degradation occurs when human milk is maintained, longer than 10 min, at room temperature and this process is suppressed by lactoperoxidase and catalase inhibition.ConclusionFresh breastmilk H2O2 content is labile and quickly degrades at room temperature. Further investigation on breastmilk handling techniques to preserve its H2O2 content, when gavage-fed to preterm infants is warranted.