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Particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) is a public health risk. We investigate PM2.5 on metabolites in cardiomyocytes and the influence of vitamin C on PM2.5 toxicity. For 24 hours, H9C2 were exposed to various concentrations of PM2.5 (0, 100, 200, 400, 800 μg/ml), after which the levels of reactive oxygen species (ROS) and cell viability were measured using the cell counting kit-8 (CCK-8) and 2′,7′-dichlorofluoresceindiacetate (DCFH2-DA), respectively. H9C2 were treated with PM2.5 (200 μg/ml) in the presence or absence of vitamin C (40 μmol/L). mRNA levels of interleukin 6(IL-6), caspase-3, fatty acid-binding protein 3 (FABP3), and hemeoxygenase-1 (HO-1) were investigated by quantitative reverse-transcription polymerase chain reaction. Non-targeted metabolomics by LC-MS/MS was applied to evaluate the metabolic profile in the cell. Results revealed a concentration-dependent reduction in cell viability, death, ROS, and increased expression of caspase-3, FABP3, and IL-6. In total, 15 metabolites exhibited significant differential expression (FC > 2, p < 0.05) between the control and PM2.5 group. In the PM2.5 group, lysophosphatidylcholines (LysoPC,3/3) were upregulated, whereas amino acids (5/5), amino acid analogues (3/3), and other acids and derivatives (4/4) were downregulated. PM2.5 toxicity was lessened by vitamin C. It reduced PM2.5-induced elevation of LysoPC (16:0), LysoPC (16:1), and LysoPC (18:1). PM2.5 induces metabolic disorders in H9C2 cardiomyocytes that can be ameliorated by treatment with vitamin C. [ABSTRACT FROM AUTHOR]

Background Steatohepatitis is common in persons living with HIV and may be associated with gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis in persons living with HIV. In the Women's Interagency HIV Study, we examined the associations of HIV and circulating biomarkers linked to MT and gut damage using the FibroScan–aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis with advanced fibrosis. Methods Among 883 women with HIV and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut damage (kynurenine and tryptophan ratio, intestinal fatty acid–binding protein, soluble CD14, and soluble CD163) with a log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. Results HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in women with HIV than women without HIV (P <.001 for each). MT biomarkers mediated 13% to 32% of the association of HIV and FAST score. Conclusions Biomarkers linked to MT and gut damage are associated with a higher FAST score and mediate the association of HIV with a higher FAST score. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis. [ABSTRACT FROM AUTHOR]

Objective To analyzing changes of indicators related to intestinal barrier damage, neurotransmitters and inflammatory mediators in patients with irritable bowel syndrome (IBS) in the plateau environment, and explore the underlying pathogenesis of IBS. Methods A prospective cohort observation was conducted on 81 healthy male Han Chinese volunteers who were admitted to Lhasa of Tibe from plain. The study lasted for one year. During the one-year follow-up, 13 patients who developed IBS (Rome IV) were selected as the study subjects. Additionally 11 participants who remained healthy were randomly selected as the control group (named NC). Eleven participants who entered Lhasa from plain within one week and did not develop acute mountain sickness were randomly selected as the NC early group. Serum levels of diamine oxidase (DAO) and intestinal fatty acid-binding protein (I-FABP), 5-hydroxytryptamine (5-HT), interleukin (IL)-6, IL-17A and lipopolysaccharide (LPS) were measured using enzyme-linked immunosorbent assay (ELISA). At the end of the follow-up period, colonoscopy and intestinal mucosal biopsy were performed in 9 cases of IBS, while colonoscopy was performed in 4 cases of NC. Results Colonoscopy and pathological results of IBS patients in plateau environment suggested mild inflammation of intestinal mucosa. Compared to the NC early group, the NC group showed increased levels of 5-HT, DAO, I-FABP, IL-6, IL-17A and LPS at 3 months after entering Lassa, and increased levels of 5-HT, I-FABP, IL-6, and LPS at 6 months (P＜0.05). Compared with the NC group, the IBS group showed decreased levels of 5-HT and LPS at 3 months after entering Lhasa (P＜0.05). Serological indexes of NC group at 6 months were lower than those at 3 months in the NC group (P＜0.05). There were no significant differences in serological indexes at 3 and 6 months of the IBS group. Conclusion Indicators of intestinal mucosal barrier damage, neurotransmitters and inflammatory mediators might be involved in the development of IBS in plateau environment. [ABSTRACT FROM AUTHOR]

This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia has been reported to elicit both beneficial and adverse changes in the cardiovascular system, but its impact on the myocardium during acute exercise and altitude/hypoxic training remains less understood. We aimed to determine how a single bout of intense interval exercise and a four-week period of high-intensity endurance training under normobaric hypoxia affect cardiac marker activity in swimmers. Sixteen young male swimmers were divided into two groups: one undergoing training in hypoxia and the other in normoxia. Cardiac markers, including troponin I and T (cTnI and cTnT), heart-type fatty acid-binding protein (H-FABP), creatine kinase-MB isoenzyme (CK-MB), and myoglobin (Mb), were analyzed to assess the myocardium's response. We found no significant differences in the physiological response of the cardiac muscle to intense physical exertion between hypoxia and normoxia. Four weeks of IHT did not alter the resting levels of cTnT, cTnI, and H-FABP, but it resulted in a noteworthy decrease in the resting concentration of CK-MB, suggesting enhanced cardiac muscle adaptation to exercise. In contrast, a reduction in resting Mb levels was observed in the control group training in normoxia. These findings suggest that IHT at moderate altitudes does not adversely affect cardiac muscle condition and may support cardiac muscle adaptation, affirming the safety and efficacy of IHT as a training method for athletes. [ABSTRACT FROM AUTHOR]

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non‐sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non‐sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non‐sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4–6), p = 0.008]. The serum levels of d‐lactate (p = 0.033), intestinal fatty acid‐binding protein (p = 0.005), interleukin‐6 (p = 0.001), white blood cells (p = 0.007), C‐reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non‐sivelestat group. The sivelestat group also demonstrated longer ICU‐free days [18 (0–22) vs. 13 (0–17), p = 0.004] and ventilator‐free days [22 (1–24) vs. 16 (1–19), p = 0.002] compared with the non‐sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients. [ABSTRACT FROM AUTHOR]

The Amur grayling (Thymallus arcticus grubei Dybowski, 1869), a species of potentially economic and research value, is renowned for its tender meat, exquisite flavor, and high nutritional contents. This study was conducted to investigate the physiological adaptation mechanisms to dietary lipids in Amur grayling fry (with average initial weight 4.64±0.03 g). This study involved a 56-day feeding trial with diets containing varying lipid levels (9.07%, 12.17%, 15.26%, 18.09%, 21.16%, and 24.07%, designated as GL1 through GL6, respectively) to explore the impact of dietary lipids on growth performance, intestinal digestion, liver antioxidative function, and transcriptomic profiles. Results showed that The group receiving 18% dietary lipid exhibited a markedly higher weight gain rate (WGR) and specific growth rate compared to other groups, alongside a reduced feed conversion ratio (FCR), except in comparison to the 15% lipid group. Activities of lipase in pancreatic secretion and amylase in stomach mucosa peaked in the 18% lipid treatment group, indicating enhanced digestive efficiency. The liver of fish in this group also showed increased activities of antioxidative enzymes and higher levels of glutathione and total antioxidative capacity, along with reduced malondialdehyde content compared to the 9% and 24% lipid treatments. Additionally, serum high-density lipoprotein cholesterol levels were highest in the 18% group. Transcriptomic analysis revealed four significant metabolic pathways affected: Cholesterol metabolism, Fat digestion and absorption, PPAR signaling, and Fatty acid degradation, involving key genes such as Lipase, Lipoprotein lipase, Fatty acid-binding protein, and Carnitine palmitoyltransferase I. These findings suggest that the liver of Amur grayling employs adaptive mechanisms to manage excessive dietary lipids. Quadratic regression analysis determined the optimal dietary lipid levels to be 16.62% and 16.52%, based on WGR and FCR, respectively. The optimal dietary lipid level for juvenile Amur grayling appears to be around 18%, as evidenced by improved growth performance, digestive function, balanced serum lipid profile, and enhanced liver antioxidative capacity. Exceeding this lipid threshold triggers both adaptive and potentially detrimental liver responses. [ABSTRACT FROM AUTHOR]

Rho-associated kinases (ROCKs) are crucial during the adipocyte differentiation process. KD025 (Belumosudil) is a newly developed inhibitor that selectively targets ROCK2. It has exhibited consistent efficacy in impeding adipogenesis across a spectrum of in vitro models of adipogenic differentiation. Given the novelty of this treatment, a comprehensive systematic review has not been conducted yet. This systematic review aims to fill this knowledge void by providing readers with an extensive examination of the rationale behind KD025 and its impacts on adipogenesis. Preclinical evidence was gathered owing to the absence of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study's quality was assessed using the Joanna Briggs Institute (JBI) Checklist Critical Appraisal Tool for Systematic Reviews. In various in vitro models, such as 3T3-L1 cells, human orbital fibroblasts, and human adipose-derived stem cells, KD025 demonstrated potent anti-adipogenic actions. At a molecular level, KD025 had significant effects, including decreasing fibronectin (Fn) expression, inhibiting ROCK2 and CK2 activity, suppressing lipid droplet formation, and reducing the expression of proadipogenic genes peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Additionally, KD025 resulted in the suppression of fatty acid-binding protein 4 (FABP4 or AP2) expression, a decrease in sterol regulatory element binding protein 1c (SREBP-1c) and Glut-4 expression. Emphasis must be placed on the fact that while KD025 shows potential in preclinical studies and experimental models, extensive research is crucial to assess its efficacy, safety, and potential therapeutic applications thoroughly and directly in human subjects. [ABSTRACT FROM AUTHOR]

Background: Insomnia has emerged as a major public health issue jeopardizing human wellbeing. Furthermore, insomnia and angina arise concomitantly and exert reciprocal effects. Multiple studies suggest that perimenopausal females are more prone to experiencing both angina and insomnia, consequently substantially compromising their quality of life.Credible evidence suggests that acupuncture exerts a beneficial impact in alleviating insomnia. Nevertheless, the exhaustive investigation into the potential of acupuncture for mitigating insomnia co-occurring with stable angina in perimenopausal females remains a realm yet to be traversed in the realm of randomized controlled trials. Hence, the primary intent of this research protocol was to evaluate the effectiveness and safety profile of acupuncture when administered to perimenopausal subjects grappling with concomitant conditions of stable angina and insomnia. Methods: This study entails a single-center, randomized, double-blind, placebo-controlled clinical trial. A total of 110 patients exhibiting insomnia concomitant with stable angina in the perimenopausal period will be enlisted and randomized to either acupuncture or sham acupuncture. Participants in both arms will undergo 30-minute sessions thrice weekly over a 12-week intervention period, with a 12-week maximum follow-up. The primary outcome measure is the Pittsburgh Sleep Quality Index(PSQI). Secondary outcomes encompass the Health-Related Quality of Life Questionnaire (SF-36), Dosage of sleeping pills, SAP-associated evaluations, including C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2), cardiac fatty acid-binding protein levels (C-FABP), and the Seattle Angina Questionnaire (SAQ). Additionally, the study includes assessments using the Hamilton Depression Inventory (HAMD) and the Generalized Anxiety Disorder Scale (GAD-7). Primary and secondary outcomes will be evaluated at baseline, 4 weeks, 8 weeks, 12 weeks (upon completion of the intervention), and at an additional 12-week follow-up. Any adverse events will be rigorously classified and characterized with respect to time of onset and abatement, therapeutic interventions implemented, impact on the primary morbidity, and regression. Discussion: The current study is poised to furnish pivotal clinical data on the utility of acupuncture for stable angina with concomitant insomnia in perimenopausal women, with the findings to be propagated through academic conferences and peer-reviewed publications. Clinical trial registration: Thai Clinical Trials Registry: TCTR20221121001. Registered 19 November 2022. [ABSTRACT FROM AUTHOR]

Simple Summary: Regulating the lipid nutritional profile of meat by balancing intramuscular fat and backfat is a difficult problem in pork production. In this study, we found that feed supplementation with mulberry leaves increased intramuscular fat while simultaneously reducing backfat. The results of our study suggest that nutritional supplementation with mulberry leaves may be used in pork production to improve the lipid nutrition of meat. Mulberry leaves, a common traditional Chinese medicine, represent a potential nutritional strategy to improve the fat profile, also known as the lipo-nutrition, of pork. However, the effects of mulberry leaves on pork lipo-nutrition and the microorganisms and metabolites in the porcine gut remain unclear. In this study, multi-omics analysis was employed in a Yuxi black pig animal model to explore the possible regulatory mechanism of mulberry leaves on pork quality. Sixty Yuxi black pigs were divided into two groups: the control group (n = 15) was fed a standard diet, and the experimental group (n = 45) was fed a diet supplemented with 8% mulberry leaves. Experiments were performed in three replicates (n = 15 per replicate); the two diets were ensured to be nutritionally balanced, and the feeding period was 120 days. The results showed that pigs receiving the diet supplemented with mulberry leaves had significantly reduced backfat thickness (p < 0.05) and increased intramuscular fat (IMF) content (p < 0.05) compared with pigs receiving the standard diet. Lipidomics analysis showed that mulberry leaves improved the lipid profile composition and increased the proportion of triglycerides (TGs). Interestingly, the IMF content was positively correlated with acyl C18:2 and negatively correlated with C18:1 of differential TGs. In addition, the cecal microbiological analysis showed that mulberry leaves could increase the abundance of bacteria such as UCG-005, Muribaculaceae_norank, Prevotellaceae_NK3B31_group, and Limosilactobacillus. Simultaneously, the relative levels of L-tyrosine-ethyl ester, oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, and mulberrin were increased. Furthermore, we found that mulberry leaf supplementation significantly increased the mRNA expression of lipoprotein lipase, fatty acid-binding protein 4, and peroxisome proliferators-activated receptor γ in muscle (p < 0.01). Mulberry leaf supplementation significantly increased the mRNA expression of diacylglycerol acyltransferase 1 (p < 0.05) while significantly decreasing the expression of acetyl CoA carboxylase in backfat (p < 0.05). Furthermore, mulberry leaf supplementation significantly upregulated the mRNA expression of hormone-sensitive triglyceride lipase and peroxisome proliferator-activated receptor α (p < 0.05) in backfat. In addition, mulberry leaf supplementation led to increased serum leptin and adiponectin (p < 0.01). Collectively, this omic profile is consistent with an increased ratio of IMF to backfat in the pig model. [ABSTRACT FROM AUTHOR]

Background and Purpose: Adipocyte fatty acid‐binding protein (A‐FABP) exacerbates cerebral ischaemia injury by disrupting the blood–brain barrier (BBB) through inducing expression of MMP‐9. Circulating A‐FABP levels positively correlate with infarct size in stroke patients. We hypothesized that targeting circulating A‐FABP by a neutralizing antibody would alleviate ischaemic stroke outcome. Experimental Approach: Monoclonal antibodies (mAbs) against A‐FABP were generated using mouse hybridoma techniques. Binding affinities of a generated mAb named 6H2 towards various FABPs were determined using Biacore. Molecular docking studies were performed to characterize the 6H2‐A‐FABP complex structure and epitope. The therapeutic potential and safety of 6H2 were evaluated in mice with transient middle cerebral artery occlusion (MCAO) and healthy mice, respectively. Key Results: Replenishment of recombinant A‐FABP exaggerated the stroke outcome in A‐FABP‐deficient mice. 6H2 exhibited nanomolar to picomolar affinities to human and mouse A‐FABP, respectively, with minimal cross‐reactivities with heart and epidermal FABPs. 6H2 effectively neutralized JNK/c‐Jun activation elicited by A‐FABP and reduced MMP‐9 production in macrophages. Molecular docking suggested that 6H2 interacts with the "lid" of the fatty acid binding pocket of A‐FABP, thus likely hindering the binding of its substrates. In mice with transient MCAO, 6H2 significantly attenuated BBB disruption, cerebral oedema, infarction, neurological deficits, and decreased mortality associated with reduced cytokine and MMP‐9 production. Chronic 6H2 treatment showed no obvious adverse effects in healthy mice. Conclusion and Implications: These results establish circulating A‐FABP as a viable therapeutic target for ischaemic stroke, and provide a highly promising antibody drug candidate with high affinity and specificity. [ABSTRACT FROM AUTHOR]

Simple Summary: Seaweeds and probiotics are commonly utilized as additives in the diet of aquatic animals. However, limited information exists regarding the effects of Gracilaria lichenoides and Bacillus amyloliquefaciens, either alone or in combination, on Penaeus monodon. In our study, we examined the impact of dietary supplementation with G. lichenoides and B. amyloliquefaciens, both individually and in combination, on the growth performance, antioxidant capacity, and intestinal function of P. monodon. Our findings indicate a beneficial influence of dietary G. lichenoides and B. amyloliquefaciens on P. monodon. These findings offer a theoretical foundation for the judicious utilization of G. lichenoides and B. amyloliquefaciens in the cultivation of black tiger shrimp, as well as for future investigations into their metabolic mechanisms. This research sought to assess the effects of dietary supplements with Gracilaria lichenoides and Bacillus amyloliquefaciens, either individually or combined, on the growth performance, antioxidant capacity, and intestinal function of Penaeus monodon. A total of 840 shrimps were randomly assigned to 28 tanks with an average initial weight of (1.04 ± 0.03) g (30 shrimp per tank) with 7 different treatment groups and 4 replicates per treatment. The control treatment (C) consisted of a basal diet; in contrast, the experimental groups were complement with varying levels of G. lichenoides (3% or 8%), either alone (S3 and S8) or in combination with B.amyloliquefaciens at different concentrations (3% G. lichenoides and 109 CFU/g—S3B9; 8% G. lichenoides and 1011 CFU/g B. amyloliquefaciens—S8B11; 109 CFU/g B. amyloliquefaciens—S9; 1011 CFU/g B. amyloliquefaciens—B11). The results indicated that the maximum values of final body weight (FBW) (10.49 ± 0.90) g, weight gain rate (WGR) (908.94 ± 33.58) g, and specific growth rate (SGR) (4.20 ± 0.06) g were perceived in the 3% G. lichenoide diet treatment, and compared with the control group, the difference was significant (p < 0.05). The whole-body lipid content of shrimp in the B9 group was significantly higher than that in the B11 group (p < 0.05), but no significant difference was observed when compared with shrimp fed other diets (p > 0.05). The ash content of shrimp in the B9 group was found to be significantly higher than that in the S3B9 group (p < 0.05). Furthermore, the lipase activity in the stomach and intestines of the experimental groups exhibited a statistically significantly increase compared to the control (p < 0.05). In comparison to the control group, the hepatopancreas of the S3 group exhibited a significant increase in the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and antioxidant genes [SOD, catalase (CAT), GSH-Px, thioredoxin (Trx), Hippo, and NF-E2-related factor 2 (Nrf2)] expression levels (p < 0.05). Additionally, the activities of total antioxidant capacity (T-AOC), SOD, peroxidase (POD), and antioxidant genes (CAT, GSH-Px, Trx, and Hippo) in the S3B9 treatment of hepatopancreas showed significant improvement (p < 0.05). The inclusion of dietary G. lichenoides and B. amyloliquefaciens resulted in enhanced relative expression of intestinal lipid metabolism genes (fatty acid synthetase (FAS), lipophorin receptor (LR), fatty acid transport protein 1 (FATP1)) and suppressed the expression of the long-chain fatty acid-CoA ligase 4 (LCL4) gene. Analysis of microbiota sequencing indicated improvements in composition and structure, with notable increases in Firmicutes at the phylum level and Vibrio at the genus level in the S3 group, as well as an increase in Tenericutes at the genus level in the S8B11 group. Overall, the inclusion of dietary G. lichenoides and B. amyloliquefaciens positively impacted the growth, antioxidant capacity, and microbial composition of shrimp, with particular enhancement observed in shrimp fed a supplementary 3% G. lichenoides diet. [ABSTRACT FROM AUTHOR]

Cholesterol from low-density lipoprotein (LDL) can be transported to many organelle membranes by non-vesicular mechanisms involving sterol transfer proteins (STPs). Fatty acid-binding protein (FABP) 7 was identified in our previous study searching for new regulators of intracellular cholesterol trafficking. Whether FABP7 is a bona fide STP remains unknown. Here, we found that FABP7 deficiency resulted in the accumulation of LDL-derived cholesterol in lysosomes and reduced cholesterol levels on the plasma membrane. A crystal structure of human FABP7 protein in complex with cholesterol was resolved at 2.7 °A resolution. In vitro, FABP7 efficiently transported the cholesterol analog dehydroergosterol between the liposomes. Further, the silencing of FABP3 and 8, which belong to the same family as FABP7, caused robust cholesterol accumulation in lysosomes. These two FABP proteins could transport dehydroergosterol in vitro as well. Collectively, our results suggest that FABP3, 7, and 8 are a new class of STPs mediating cholesterol egress from lysosomes. [ABSTRACT FROM AUTHOR]

Background: Increasing intestinal permeability causes chronic inflammation, which is one of the etiological factors of many diseases that presently constitute global challenges. Aims: Considering the importance of developing therapies to eliminate the increased intestinal permeability, in this systematic review and meta-analysis, we analyze the impact of bovine colostrum (BC) on the gut barrier and its permeability. Methods: Online databases, including PubMed, ISI Web of Science, and Scopus, were searched to find pertinent articles up to March 2022. Weighted mean difference (WMD) and 95% confidence intervals (CI) were considered as effect sizes. The random-effects model was used to pool the study results. Results: A total of ten articles were included in the meta-analysis. The pooled effect revealed a significant reduction in the 5-h urinary lactulose/rhamnose ratio after BC consumption [mean difference (MD): −0.24; 95% CI −0.43 to −0.04; I2 = 99%] and urinary lactulose/mannitol ratio (MD: −0.01; 95% CI −0.02 to −0.001; I2 = 29.8%). No differences were observed in the plasma intestinal fatty acid-binding protein (I-FABP) between BC and control groups (MD: 2.30; 95% CI −293.9 to 298.5; I2 = 92%). Conclusions: BC supplementation significantly reduced intestinal permeability; however, to confirm the results, more randomized clinical trials considering different quality, dose, and duration are needed. [ABSTRACT FROM AUTHOR]

Purpose: Exertional heat stress can cause damage to the intestinal epithelium and disrupt gastrointestinal barrier integrity, leading to microbial translocation (MT) linked to the development of heat stroke. This study aimed to assess age-related differences in markers of intestinal epithelial injury and MT following non-heat stress and high-heat stress exercise in healthy young and older men. Methods: Markers of intestinal epithelial injury (intestinal fatty acid-binding protein—'IFABP') and MT (soluble cluster of differentiation 14—'sCD14'; and lipopolysaccharide-binding protein—'LBP') were assessed in healthy young (18–30 y, n = 13) and older (50–70 y) men (n = 12). Blood samples were collected before, after 180 min of moderate-intensity (metabolic rate: 200 W/m2) walking and following 60 min recovery in either a non-heat stress [temperate: 21.9 °C, 35% relative humidity (RH)] or high-heat stress (hot: 41.4 °C, 35% RH) environment. Results: There were no differences in IFABP and sCD14 between the young and older groups in the temperate condition, while LBP was greater in the older group (+ 0.66 ug/mL; + 0.08 to + 1.24 ug/mL). In the hot condition, the older group experienced greater increases in IFABP compared to the young group (+ 712 pg/mL/hr; + 269 to + 1154 pg/mL/hr). However, there were no clear between-group differences for sCD14 (+ 0.24 ug/mL/hr, − 0.22 to + 0.70 ug/mL/hr) or LBP (+ 0.86 ug/mL/hr, − 0.73 to + 2.46 ug/mL/hr). Conclusion: While older men may experience greater intestinal epithelial injury following exercise in the heat; this did not lead to a greater magnitude of microbial translocation relative to their younger counterparts. [ABSTRACT FROM AUTHOR]

OBJECTIVES Intestinal ischaemia–reperfusion injury induced by cardiopulmonary bypass causes intestinal epithelial barrier dysfunction, leading to dysbiosis and bacterial translocation. We conducted a randomized prospective study with 2 objectives: (i) to investigate epithelial barrier dysfunction and bacterial translocation induced by cardiopulmonary bypass and changes in the gut microbiota and (ii) to verify whether probiotics can improve these conditions. METHODS Between 2019 and 2020, patients 0–15 years old scheduled to undergo cardiac surgery using cardiopulmonary bypass were enrolled and randomly allocated to 2 groups: the intervention group received probiotics and the control group did not receive probiotics. We analysed the microbiota in faeces and blood, organic acid concentrations in faeces, plasma intestinal fatty acid-binding protein and immunological responses. RESULTS Eighty-two patients were enrolled in this study. The characteristics of the patients were similar in both groups. The total number of obligate anaerobes was higher in the intervention group than in the control group after postoperative day 7. We identified 4 clusters within the perioperative gut microbiota, and cluster changes showed a corrective effect of probiotics on dysbiosis after postoperative day 7. Organic acid concentrations in faeces, incidence of bacterial translocation, intestinal fatty acid-binding protein levels and immunological responses, except for interleukin -17A, were not markedly different between the 2 groups. CONCLUSIONS Administration of probiotics was able to correct dysbiosis but did not sufficiently alleviate the intestinal damage induced by cardiopulmonary bypass. More effective methods should be examined to prevent disturbances induced by cardiac surgery using cardiopulmonary bypass. Clinical trial registration number https://center6.umin.ac.jp/cgi-open-bin/ctr%5fe/ctr%5fview.cgi?recptno=R000037174 UMIN000035556 [ABSTRACT FROM AUTHOR]

This document contains several abstracts related to pediatric dermatology. The first abstract discusses the long-term improvement in sleep observed in pediatric patients with moderate-to-severe atopic dermatitis who were treated with dupilumab over the course of one year. The second abstract presents preliminary results from the IMPEED study, which examines the impact of eczema on educational participation and achievement among children in Ireland. The third abstract focuses on the impact of eczema on social and sporting activities among children in Ireland. The fourth abstract discusses the effectiveness of dupilumab in improving disease severity in children under 12 years old with severe atopic dermatitis. Finally, the fifth abstract describes a phase 2 trial of zabalafin, a novel drug targeting inflammatory and bacterial components of atopic dermatitis, in children. These abstracts provide valuable insights into the understanding and management of atopic dermatitis in pediatric populations. [Extracted from the article]

Previous studies have shown that variations in the CD36 gene may affect phenotypes associated with fat metabolism as the CD36 protein facilitates the transport of fatty acids to the mitochondria for oxidation. However, no previous study has tested whether variations in the CD36 gene are associated with sports performance. We investigated the genotypic and allelic distribution of the single-nucleotide polymorphism (SNP) rs1761667 in the CD36 gene in elite Moroccan athletes (cyclists and hockey players) in comparison with healthy non-athletes of the same ethnic origin. Forty-three Moroccan elite male athletes (nineteen cyclists and twenty-four field hockey players) belonging to the national teams of their respective sports (athlete group) were compared to twenty-eight healthy, active, male university students (control group). Genotyping of the CD36 rs1761667 (G>A) SNP was performed via polymerase chain reaction (PCR) and Sanger sequencing. A chi-square (χ2) test was used to assess the Hardy–Weinberg equilibrium (HWE) and to compare allele and genotype frequencies in the "athlete" and "control" groups. The genotypic distribution of the CD36 rs1761667 polymorphism was similar in elite athletes (AA: 23.81, AG: 59.52, and GG: 16.67%) and controls (AA: 19.23, AG: 69.23, and GG: 11.54%; χ2 = 0.67, p = 0.71). However, the genotypic distribution of the CD36 rs1761667 polymorphism was different between cyclists (AA: 0.00, AG: 72.22, and GG: 27.78%) and hockey players (AA: 41.67, AG: 50.00, and GG: 8.33%; χ2 = 10.69, p = 0.004). Specifically, the frequency of the AA genotype was significantly lower in cyclists than in hockey players (p = 0.02). In terms of allele frequency, a significant difference was found between cyclists versus field hockey players (χ2 = 7.72, p = 0.005). Additionally, there was a predominance of the recessive model in cyclists over field hockey players (OR: 0.00, 95% CI: 0.00–0.35, p = 0.002). Our study shows a significant difference between cyclists and field hockey players in terms of the genotypic and allelic frequency of the SNP rs1761667 of the CD36 gene. This divergence suggests a probable association between genetic variations in the CD36 gene and the type of sport in elite Moroccan athletes. [ABSTRACT FROM AUTHOR]

Membrane transporters playing an important role in the passage of drugs, metabolites and nutrients across the membranes of the brain cells have been shown to be involved in pathogenesis of Alzheimer's disease (AD). However, little is known about sex-specific changes in transporter protein expression at the brain in AD. Here, we investigated sex-specific alterations in protein expression of three ATP-binding cassette (ABC) and five solute carriers (SLC) transporters in the prefrontal cortex of a commonly used model of familial AD (FAD), 5xFAD mice. Sensitive liquid chromatography tandem mass spectrometry-based quantitative targeted absolute proteomic analysis was applied for absolute quantification of transporter protein expression. We compared the changes in transporter protein expressions in 7-month-old male and female 5xFAD mice versus sex-matched wild-type mice. The study revealed a significant sex-specific increase in protein expression of ABCC1 (p = 0.007) only in male 5xFAD mice as compared to sex-matched wild-type animals. In addition, the increased protein expression of glucose transporter 1 (p = 0.01), 4F2 cell-surface antigen heavy chain (p = 0.01) and long-chain fatty acid transport protein 1 (p = 0.02) were found only in female 5xFAD mice as compared to sex-matched wild-type animals. Finally, protein expression of alanine/serine/cysteine/threonine transporter 1 was upregulated in both male (p = 0.02) and female (p = 0.002) 5xFAD mice. The study provides important information about sex-specific changes in brain cortical transporter expression in 5xFAD mice, which will facilitate drug development of therapeutic strategies for AD targeting these transporters and drug delivery research. [ABSTRACT FROM AUTHOR]

Objective: To determine impact of urine liver-type fatty acid binding protein (uL-FABP) and urine neutrophil gelatinase-associated lipocalin (uNGAL), which were biomarkers linked to acute kidney injury (AKI), in AKI diagnosis and prediction of 28-day mortality among hospitalized cirrhotic patients. Materials and Methods: We prospectively enrolled hospitalized cirrhotic patients at a tertiary care university hospital between June 2018 and November 2019. The uL-FABP, uNGAL, and plasma NGAL (pNGAL) were collected within 48 hours of admission. Cutoff values of biomarkers for diagnosing AKI derived from receiver operating characteristic (ROC) curve. Logistic regression analysis was used to identify independent factors for 28-day mortality. Results: We enrolled 109 cirrhotic patients in derivative cohort, 41.3% had AKI. Median uL-FABP, uNGAL, and pNGAL levels in AKI group were higher than non-AKI group: 8.1 vs. 2.8 ng/mL (p=0.002), 40.5 vs. 10.1 ng/mL (p<0.001), and 195.7 vs 81.4 ng/mL (p=0.001), respectively. Areas under the ROC curve of uL-FABP, uNGAL, and pNGAL for AKI diagnosis were 0.68, 0.73 and 0.68, respectively. Also, all biomarkers were significantly higher in mortality group. Multivariate analysis showed that the only independent predictor for 28-day mortality was uLFABP 4.68 ng/mL (odd ratio 4.15, p=0.02). Conclusion: UL-FABP, uNGAL, and pNGAL are associated with AKI in hospitalized cirrhotic patients. Moreover, uL-FABP 4.68 ng/mL was a significant independent predictor for 28-day mortality. [ABSTRACT FROM AUTHOR]

Background: Breast cancer(BC) is currently the fifth largest cause of mortality worldwide and has become the most frequent type of cancer. Fatty acid transport proteins (FATPs) assist cancer cells in meeting their higher metabolic needs by increasing fatty acid uptake, which is a significant source of energy for cancer cells. The phosphoinositide 3‑kinase/protein kinase B/mammalian target of the rapamycin (PI3K/Akt/mTOR) pathway is an important signaling pathway that coordinates the uptake and utilization of various nutrients, including fatty acids. The current study aimed to correlate the FATPs with the PI3K/Akt/mTOR pathway in BC. Methods: Eighty serum samples were collected from BC and control subjects after obtaining an informed consent form. Total ribonucleic acid (RNA) was isolated, and the relative messenger RNA (mRNA) expression of PI3K, Akt, and mTOR was analyzed by a reverse transcriptase‑quantitative polymerase chain reaction. Serum FATPs were estimated using commercially available enzyme‑linked immunoassay kits. P < 0.05 was indicated as statistically significant. Results: The serum FATPs in subjects with BC differed significantly compared to the control. Relative mRNA expression of PI3K, Akt, and mTOR differed significantly between the groups. Further, on correlating the serum FATPs with PI3K‑related signaling molecules showed a significant positive correlation within BC subjects. Conclusion: Significant positive correlation between FATPs and the PI3K, Akt, and mTOR pathway suggests a crucial role of FATPs in promoting BC. [ABSTRACT FROM AUTHOR]

The objective of the study was to assess the expression of proteins responsible for placental lipid transport in term pregnancies complicated by well-controlled gestational (GDM) and type 1 diabetes mellitus (PGDM). A total of 80 placental samples were obtained from patients diagnosed with PGDM (n = 20), GDM treated with diet (GDMG1, n = 20), GDM treated with diet and insulin (GDMG2, n = 20), and a non-diabetic control group (n = 20). Umbilical and uterine artery blood flows were assessed by means of ultrasound in the period prior to delivery and computer-assisted quantitative morphometry of immunostained placental sections was performed to determine the expression of selected proteins. The morphometric analysis performed for the vascular density-matched placental samples demonstrated a significant increase in the expression of fatty acid translocase (CD36), fatty acid binding proteins (FABP1, FABP4 and FABP5), as well as a decrease in the expression of endothelial lipase (EL) and fatty acid transport protein (FATP4) in the PGDM-complicated pregnancies as compared to the GDMG1 and control groups (p < 0.05). No significant differences with regard to the placental expression of lipoprotein lipase (LPL) and FATP6 protein between GDM/PGDM and non-diabetic patients were noted. Maternal pre-pregnancy weight, body mass index, placental weight as well as the expression of LPL and FABP4 were selected by the linear regression model as the strongest contributors to the fetal birth weight. To conclude, in placentas derived from pregnancies complicated by well-controlled PGDM, the expression of several lipid transporters, including EL, CD36, FATP4, FABP1, FABP4 and FABP5, is altered. Nonetheless, only LPL and FABP4 were significant predictors of the fetal birth weight. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the diagnostic potential of serum intestinal fatty acid-binding protein (I-FABP), fecal calprotectin (FC), and fecal human β-defensin 2 (hBD2) in predicting necrotizing enterocolitis (NEC) in preterm infants. Methods: A prospective cohort of neonates with a gestational age < 32 weeks, suspected of NEC, was enrolled between June 2021 and December 2022. Serum I-FABP, FC, and fecal hBD2 levels were measured upon NEC suspicion, and diagnosis was confirmed through radiological examination or surgical intervention. Diagnostic precision of serum I-FABP, FC, and fecal hBD2 was assessed using a logistic regression model with multiple variables. Results: The study included 70 neonates (45 males, 25 females), with 30 developing NEC (40% Stage III, n = 12; 60% Stage II, n = 18) and 40 in the control group. NEC patients exhibited significantly higher serum I-FABP and FC levels (4.76 ng/mL and 521.56 µg/g feces, respectively) than those with other diagnoses (1.38 ng/mL and 213.34 µg/g feces, respectively; p ˂ 0.05 for both biomarkers). Stage II NEC neonates showed elevated fecal hBD2 levels (376.44 ng/g feces) than Stage III NEC neonates and controls (336.87 ng/g and 339.86 ng/g feces, respectively; p ˂ 0.05). No such increase was observed in infants progressing to Stage III NEC. Using a serum I-FABP threshold of > 2.54 ng/mL yielded 76.7% sensitivity, 87.5% specificity, 82.1% positive predictive value (PPV), and 83.3% negative predictive value (NPV). For FC (cutoff > 428.99 µg/g feces), corresponding values were 76.7% sensitivity, 67.5% specificity, 63.9% PPV, and 79.4% NPV. Conclusion: Serum I-FABP and FC levels are valuable for early NEC detection and provide insights into disease severity. Low fecal hBD2 levels suggest an inadequate response to luminal bacteria, potentially rendering these infants more susceptible to NEC development or exacerbation. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication after Percutaneous Coronary Intervention (PCI) for ST segment elevation myocardial infarction (STEMI) and is associated with poor outcomes. AKI is diagnosed by the dynamic change of serum Cr, but it could not predict AKI. This study aimed to evaluate a biomarker array that may fulfill this shortage. Setting: Cardiology Department, Tanta University Hospital. Design: Prospective interventional study included 280 acute STEMI patients who underwent emergency PCI. Serial samples of blood and urine were obtained at the time of admission to the hospital (T0) and PCI unit (T1) and at 12 h and 72 h (T12 and T72) after coronary revascularization to estimate levels of serum Cr, creatine phosphokinase, and heart-type fatty acid-binding protein (H-FABP) and calculation of neutrophil/lymphocyte ratio (NLR) and urinary liver-type FABP (L-FABP). AKI was diagnosed according to the recommendations of the European Renal Best Practice as the times of increased serum Cr concerning baseline level. 85 patients developed AKI. Regression analyses defined a high NLR ratio in the T0 sample as the most significant predictor for early AKI diagnosed at T1 time, while high NLR and serum H-FABP levels in T1 samples as the significant predictors for AKI defined at T12 time. However, high urinary L-FABP levels in T12 samples and high NLR are significant predictors for AKI at T72 time. Combined estimations of serum H-FABP and urinary L-FABP with the calculation of NLR could predict the oncoming AKI and discriminate its pathogenesis. The study protocol was approved by the Local Ethical Committee at Tanta Faculty of Medicine by approval number: 35327/3/22. For blindness purposes, the authors will be blinded about the laboratory results till the end of 72 h after revascularization and the clinical pathologist will be blinded about the indication for the requested investigations. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine fatty acid binding protein‐4 (FABP‐4) concentrations in maternal serum of fetal growth restriction (FGR) pregnancies and controls of normal pregnancies. Furthermore, we hypothesized that the alterations in FABP‐4 levels might correlate with FGR severity. Methods: We performed this prospective case–control study with 83 pregnant women. The study groups included 26 FGR pregnancies without abnormal fetal Doppler flow patterns and 25 pregnancies complicated with FGR accompanied by abnormal fetal Doppler flow patterns. Results: The median serum FABP‐4 concentrations were significantly higher in the FGR cases with abnormal Doppler flow pattern group (2.09 ng/mL) than in the FGR cases without abnormal Doppler flow pattern group (1.62 ng/mL) and the control group (1.20 ng/mL, p < 0.001). A significant negative correlation was observed between maternal serum FABP‐4 levels and time to birth from blood sample collection (r = −0.356 and p = 0.001), gestational week at birth (r = −0.386 and p < 0.001), and birth weight (r = −0.394 and p < 0.001). A 1.35 ng/mL cut‐off value of serum FABP‐4 level could be used to discriminate FGR cases with a 78.4% sensitivity and 60.6% specificity. The optimal cut‐off value of FABP‐4 levels as an indicator for the diagnosis of FGR with abnormal Doppler flow pattern was estimated to be 1.76 ng/mL, which yielded a sensitivity of 84.0% and a specificity of 75.8%. Conclusion: FABP‐4 is a crucial biomarker in the diagnosis and determining the severity of pregnancies with restricted fetal growth. We consider that FABP‐4 is a powerful, reliable, and unique biomarker to diagnose FGR pregnancies. [ABSTRACT FROM AUTHOR]

Background: Recently, the hypothesis that pathological α-Synuclein propagates from the gut to the brain has gained attention. Although results from animal studies support this hypothesis, the specific mechanism remains unclear. This study focused on the intestinal fatty acid-binding protein (FABP2), which is one of the subtypes of fatty acid binding proteins localizing in the gut, with the hypothesis that FABP2 is involved in the gut-to-brain propagation of α-Synuclein. The aim of this study was to clarify the pathological significance of FABP2 in the pathogenesis and progression of synucleinopathy. Methods: We examined the relationship between FABP2 and a-Synuclein in the uptake of α-Synuclein into enteric neurons using primary cultured neurons derived from mouse small intestinal myenteric plexus. We also quantified disease-related protein concentrations in the plasma of patients with synucleinopathy and related diseases, and analyzed the relationship between plasma FABP2 level and progression of the disease. Results: Experiments on α-Synuclein uptake in primary cultured enteric neurons showed that following uptake, α-Synuclein was concentrated in areas where FABP2 was localized. Moreover, analysis of the plasma protein levels of patients with Parkinson's disease revealed that the plasma FABP2 and α-Synuclein levels fluctuate with disease duration. The FABP2/α-Synuclein ratio fluctuated more markedly than either FABP2 or α-Synuclein alone, depending on the duration of disease, indicating a higher discriminant ability of early Parkinson's disease patients from healthy patients. Conclusions: These results suggest that FABP2 potentially contributes to the pathogenesis and progression of α-Synucleinopathies. Thus, FABP2 is an important molecule that has the potential to elucidate the consistent mechanisms that lead from the prodromal phase to the onset and subsequent progression of synucleinopathies. [ABSTRACT FROM AUTHOR]

Background. Colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality worldwide. Recently, the pathogenesis of CRC among other cancer types has been linked to lipid metabolism. Fatty acid-binding proteins (FABPs) are a protein-family expressed in multiple tissues and play a crucial role in lipid metabolism. A few recent studies have examined FABPs role in CRC. Our aims are to explore the immunohistochemical expression of fatty acid binding proteins (FABP) 4 and 7 in colorectal cancer, and correlate their expression levels with clinical, histopathological features, and survival. Methods. A retrospective review of colorectal cancer biopsies over a 5-year period was conducted in our institute. Clinical and histological data were collected. Immunohistochemical staining for FABP 4 and 7 was performed using microarray and their expression was evaluated using the Histologic score (HS). The correlations between the expression of FABP 4 and 7 and clinicopathological parameters were determined by Fisher’s exact test. The impact of the expression on the overall survival was determined using Kaplan–Meier survival analysis. Results. 125 CRC tissue biopsy blocks were included. Median follow-up time was 35 months. High FABP4 expression was observed in 107 (85.60%). For FABP7, only 8.8% of cases (11/125) showed high expression. Co-expression of FABP4 and FABP7 occurred in 11 cases (8.8%). FABP7 expression correlated with age (p = 0.001). The median overall survival of patients with high expression of FABP4 was 43.00 ± 3.01 months, whereas patients showing low/negative expression reported a survival of 24.00 ± 6.24 months(p =0.041). No statistically significant association between FABP7 high expression and the overall survival was detected (Log-Rank test, p = 0.086). Conclusion. FABP4 expression in CRC is higher than that of FABP7. FABP7 expression levels negatively correlate with the age of CRC patients. FABP4 expression is associated with a better survival in CRC. No significant association between FABP4 and 7 with tumor grade, stage, or other clinicopathological criteria has been found in this study. [ABSTRACT FROM AUTHOR]

Background: Fatty acid-binding protein 4 (FABP4) has been associated with cardiovascular disease and diabetes. Acute aerobic exercise increases circulating FABP4 concentrations, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of inhibition of lipolysis by carbohydrate ingestion on circulating FABP4 concentrations during and after acute aerobic exercise in healthy men. Methods: Men aged between 20 and 40, with no exercise habits and no metabolic diseases, were recruited. In a randomized crossover design, the participants underwent a carbohydrate-ingestion exercise (CE) and a fasted exercise (FE) trial. The CE trial consisted of 40-min acute aerobic exercise with ingestion of carbohydrates and 60-min bed rest. The FE trial followed the same protocol as the CE trial but without carbohydrate ingestion. Venous blood samples were collected to measure hormones (adrenaline, noradrenaline, and insulin) metabolites (glycerol, free fatty acids, and glucose), and FABP4 concentrations. Ventilation and gas exchange were also collected to measure substrate oxidation. Results: Thirteen healthy men participated in and completed both the CE and FE trials. The insulin concentration was more than 4 times higher in the CE trial than in the FE trial (p < 0.004, effect size [ES] > 2.00). Free fatty acid concentrations were more than 4 times lower in the CE trial than in the FE trial (p < 0.02, ES > 2.04). However, there was no significant difference in the changes in circulating FABP4 concentrations between the CE and FE trials (p = 0.108), which did not change during aerobic exercise and significantly increased post-aerobic exercise in both trials (p < 0.002, ES > 1.212). Changes in FABP4 concentrations following aerobic exercise were not significantly correlated with changes in glycerol or free fatty acid concentrations during aerobic exercise. Conclusions: The results suggest that suppression of lipolysis and elevation of insulin are not strongly involved in increases in FABP4 secretion following acute aerobic exercise. [ABSTRACT FROM AUTHOR]

Background: Lipid metabolism related factors, such as angiopoietin‐like protein 3 (ANGPTL3), angiopoietin‐like 4 (ANGPTL4), fatty acid‐binding protein 4 (FABP4) are newly discovered factors that can affect coronary artery disease (CAD). In this study, we aimed to investigate the relationship between CAD and these lipid metabolism factors. Hypothesis: ANGPTL3, ANGPTL4, and FABP4 may provide a new method for the control of CAD risk factors and the prevention and treatment of CAD. Methods: We enrolled 284 consecutive inpatients with suspected CAD and divided them into CAD and non‐CAD groups based on the coronary angiography results. Serum ANGPTL3, ANGPTL4, FABP4, and tumor necrosis factor‐α (TNF‐α) levels were estimated using the enzyme‐linked immunosorbent assay. Multivariate logistic regression was used to assess the risk factors for CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. Results: The serum TNF‐α, FABP4, ANGPTL3, and ANGPTL4 values showed a significant difference between the CAD and non‐CAD groups (p <.05). After adjusting for confounding factors, the FABP4, ANGPTL3, and ANGPTL4 levels were independently associated with CAD (p <.05). The ANGPTL3 expression level was an independent risk factor for CAD in patients with hypertension, but not in those without hypertension. The ANGPTL3 > 67.53 ng/mL, ANGPTL4 > 29.95 ng/mL, and FABP4 > 1421.25 ng/L combination had the highest diagnostic value for CAD. Conclusion: ANGPTL3, ANGPTL4, and FABP4 were identified as independent risk factors for CAD and have valuable clinical implications for the diagnosis and treatment of CAD. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common condition in severely ill patients associated with poor outcomes. We assessed the associations between urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary liver-type fatty acid-binding protein (uLFABP), and urinary cystatin C (uCysC) concentrations and patient outcomes. Methods: We assessed the predictive performances of uNGAL, uLFABP, and uCysC measured in the early phase of intensive care unit (ICU) management and at discharge from the ICU in severely ill patients for short- and long-term outcomes. The primary outcome was the occurrence of AKI during ICU stay; secondary outcomes were 28-day and 1-yr allcause mortality. Results: In total, 1,759 patients were admitted to the ICU, and 728 (41.4%) developed AKI. Median (interquartile range, IQR) uNGAL, uLFABP, and uCysC concentrations on admission were 147.6 (39.9-827.7) ng/mL, 32.4 (10.5-96.0) ng/mL, and 0.33 (0.12-2.05) mg/L, respectively. Biomarker concentrations on admission were higher in patients who developed AKI and associated with AKI severity. Three hundred fifty-six (20.3%) and 647 (37.9%) patients had died by 28 days and 1-yr, respectively. Urinary biomarker concentrations at ICU discharge were higher in non-survivors than in survivors. The areas under the ROC curve (95% confidence interval) of uLFABP for the prediction of AKI, 28-day mortality, and 1-yr mortality (0.70 [0.67-0.72], 0.63 [0.59-0.66], and 0.57 [0.51-0.63], respectively) were inferior to those of the other biomarkers. Conclusions: uNGAL, uLFABP, and uCysC concentrations on admission were associated with poor outcomes. However, their predictive performance, individually and in combination, was limited. Further studies are required to confirm our results. [ABSTRACT FROM AUTHOR]

This study investigated the effects of 7 days of 600 mg/day anthocyanin-rich blackcurrant extract intake on small intestinal permeability, enterocyte damage, microbial translocation, and inflammation following exertional heat stress. Twelve recreationally active men (maximal aerobic capacity = 55.6 ± 6.0 ml·kg−1·min−1) ran (70% VO2max) for 60 min in an environmental chamber (34 °C, 40% relative humidity) on two occasions (placebo/blackcurrant, randomized double-blind crossover). Permeability was assessed from a 4-hr urinary excretion of lactulose and rhamnose and expressed as a ratio of lactulose/rhamnose. Venous blood samples were taken at rest and 20, 60, and 240 min after exercise to measure enterocyte damage (intestinal fatty acid-binding protein); microbial translocation (soluble CD14, lipopolysaccharide-binding protein); and interleukins 6, interleukins 10, and interleukins 1 receptor antagonist. Exercise increased rectal temperature (by ∼2.8 °C) and heart rate (by ∼123 beats/min) in each condition. Blackcurrant supplementation led to a ∼12% reduction in lactulose/rhamnose ratio (p <.0034) and enterocyte damage (∼40% reduction in intestinal fatty acid-binding protein area under the curve; p <.0001) relative to placebo. No between-condition differences were observed immediately after exercise for lipopolysaccharide-binding protein (mean, 95% confidence interval [CI]; +80%, 95% CI [+61%, +99%]); soluble CD14 (+37%, 95% CI [+22%, +51%]); interleukins 6 (+494%, 95% CI [+394%, +690%]); interleukins 10 (+288%, 95% CI [+105%, +470%]); or interleukins 1 receptor antagonist (+47%, 95% CI [+13%, +80%]; all time main effects). No between-condition differences for these markers were observed after 60 or 240 min of recovery. Blackcurrant extract preserves the GI barrier; however, at subclinical levels, this had no effect on microbial translocation and downstream inflammatory processes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Clinical management of shrimp allergy is hampered by the lack of accurate tests. Molecular diagnosis has been shown to more accurately reflect the clinical reactivity but the full spectrum of shrimp allergens and their clinical relevance are yet to be established. We therefore sought to comprehend the allergen repertoire of shrimp, investigate and compare the sensitization pattern and diagnostic value of the allergens in allergic subjects of two distinct populations. METHODS: Sera were collected from 85 subjects with challenge-proven or doctor-diagnosed shrimp allergy in Hong Kong and Thailand. The IgE-binding proteins of Penaeus monodon were probed by Western blotting and identified by mass spectrometry. Recombinant shrimp allergens were synthesized and analyzed for IgE sensitization by ELISA. RESULTS: Ten IgE-binding proteins were identified, and a comprehensive panel of 11 recombinant shrimp allergens was generated. The major shrimp allergens among Hong Kong subjects were troponin C (Pen m 6) and glycogen phosphorylase (Pen m 14, 47.1%), tropomyosin (Pen m 1, 41.2%) and sarcoplasmic-calcium binding protein (Pen m 4, 35.3%), while those among Thai subjects were Pen m 1 (68.8%), Pen m 6 (50.0%) and fatty acid-binding protein (Pen m 13, 37.5%). Component-based tests yielded significantly higher area under curve values (0.77-0.96) than shrimp extract-IgE test (0.70-0.75). Yet the best component test differed between populations; Pen m 1-IgE test added diagnostic value only in the Thai cohort, whereas sensitizations to other components were better predictors of shrimp allergy in Hong Kong patients. CONCLUSION: Pen m 14 was identified as a novel shrimp allergen predictive of challenge outcome. Molecular diagnosis better predicts shrimp allergy than conventional tests, but the relevant component is population dependent.

Objective To explore the relationship between urinary fatty acid binding protein-1 （u-FABP1） and a rapid decline of renal function in elders with type 2 diabetes mellitus （T2DM）. Methods From January to December 2017, 430 T2DM elders with preserved renal function were recruited for this prospective observational study. During a follow-up period of at least 5 years, they underwent a serial detection of estimated glomerular filtration rate （eGFR）. Rapid decline in renal function was defined as an annual decline of eGFR＞3 mL·min−1·（1.73m2）−1. The relationship between baseline serum level of u-FABP1 and an annual decline rate of eGFR was examined. Results During 5-year follow-ups, 70 patients （16.28%） had a rapid decline in renal function. As compared with non-rapid decline group, baseline u-FABP1 level [corrected with urinary creatinine （uCr）] of patients was significantly higher in rapid decline group [27.29（21.20, 34.03） μg/g uCr vs 39.61 （34.06, 50.0） μg/g uCr, Z = −12.240, P＜0.001]. After adjusting for such risk factors as age, gender, body mass index （BMI）, glycated hemoglobin A1c （HbA1c） and baseline eGFR, annual eGFR decline rate （%） was correlated negatively with baseline u-FABP1 （rs = −0.150, P = 0.005）. Futhermore, univariate and multivariate Logistic regression analyses indicated that age＞75 year and baseline u-FABP1≥16.76 ng/mg uCr were independent predictors of a rapid decline of renal function （P＜0.05）. When baseline level of u-FABP1 was≥22.45 ng/mg uCr, it could well predict the risk of a rapid decline of renal function. Area under receiver operating characteristic curve was 0.962 （95%CI：0.943-0.981） with a specificity of 97.10% and a sensitivity of 77.70%. Conclusions In T2DM elders with preserved renal function, elevated baseline level of u-FABP1 is associated with a high risk of rapid decline of renal function. It hints that u-FABP may play a role in the progression of early diabetic kidney disease.

The article discusses the endocannabinoid system (ECS), which is involved in various aspects of health and disease. It reviews recent research on the pharmacology of the ECS, its role in development and synaptic function, and its signaling in pathological conditions. The article also highlights the cellular, molecular, and functional specificity, heterogeneity, and diversity of (endo)cannabinoid action. It provides examples of how data mining strategies and data profiling can help identify critical molecules in the ECS. The article concludes by discussing methodological tools for data generation and analysis, such as single-cell RNA sequencing and dimensionality reduction techniques. It encourages further applications of these techniques in the study of the ECS. [Extracted from the article]

Exogenous supplementation of guanidinoacetic acid can mechanistically regulate the energy distribution in muscle cells. This study aimed to investigate the effects of guanidinoacetic acid supplementation on liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks. We randomly divided 480 42 days-old female Jiaji ducks into four groups with six replicates and 20 ducks for each replicate. The control group was fed the basal diet, and the experimental groups were fed the basal diet with 400, 600, and 800 mg/kg (GA400, GA600, and GA800) guanidinoacetic acid, respectively. Compared with the control group, (1) the total cholesterol (p = 0.0262), triglycerides (p = 0.0357), malondialdehyde (p = 0.0452) contents were lower in GA400, GA600 and GA800 in the liver; (2) the total cholesterol (p = 0.0365), triglycerides (p = 0.0459), and malondialdehyde (p = 0.0326) contents in breast muscle were decreased in GA400, GA600 and GA800; (3) the high density lipoprotein (p = 0.0356) and apolipoprotein-A1 (p = 0.0125) contents were increased in GA600 in the liver; (4) the apolipoprotein-A1 contents (p = 0.0489) in breast muscle were higher in GA600 and GA800; (5) the lipoprotein lipase contents (p = 0.0325) in the liver were higher in GA600 and GA800; (6) the malate dehydrogenase contents (p = 0.0269) in breast muscle were lower in GA400, GA600, and GA800; (7) the insulin induced gene 1 (p = 0.0326), fatty acid transport protein 1 (p = 0.0412), and lipoprotein lipase (p = 0.0235) relative expression were higher in GA400, GA600, and GA800 in the liver; (8) the insulin induced gene 1 (p = 0.0269), fatty acid transport protein 1 (p = 0.0234), and lipoprotein lipase (p = 0.0425) relative expression were increased in GA400, GA600, and GA800 in breast muscle. In this study, the optimum dosage of 600 mg/kg guanidinoacetic acid improved the liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks. [ABSTRACT FROM AUTHOR]

Severe acute malnutrition (SAM) is the most high-risk form of undernutrition, particularly when children require hospitalization for complications. Complicated SAM is a multisystem disease with high inpatient and postdischarge mortality, especially in children with comorbidities such as HIV; however, the underlying pathogenesis of complicated SAM is poorly understood. Targeted multiplex biomarker analysis in children hospitalized with SAM (n = 264) was conducted on plasma samples, and inflammatory markers were assessed on stool samples taken at recruitment, discharge, and 12 to 24 and 48 weeks after discharge from three hospitals in Zimbabwe and Zambia. Compared with adequately nourished controls (n = 173), we found that at baseline, complicated SAM was characterized by systemic, endothelial, and intestinal inflammation, which was exacerbated by HIV infection. This persisted over 48 weeks despite nutritional recovery and was associated with children's outcomes. Baseline plasma concentrations of vascular endothelial growth factor, glucagon-like peptide-2, and intestinal fatty acid–binding protein were independently associated with lower mortality or hospital readmission over the following 48 weeks. Following principal components analysis of baseline biomarkers, higher scores of a component representing growth factors was associated with greater weight-for-height z score recovery and lower mortality or hospital readmission over the 48 weeks. Conversely, components representing higher gut and systemic inflammation were associated with higher mortality or hospital readmission. These findings highlight the interplay between inflammation, which damages tissues, and growth factors, which mediate endothelial and epithelial regeneration, and support further studies investigating interventions to reduce inflammation and promote epithelial repair as an approach to reducing mortality and improving nutritional recovery. Editor's summary: Complicated severe acute malnutrition (SAM) is associated with high mortality even after recovery of nutrition, but the underlying pathophysiology is still poorly understood. Here, Sturgeon and colleagues studied blood, urine, and stool samples from 264 children with SAM from hospitalization to 48 weeks after hospital discharge to better understand the disease. Principal components analyses and structural equation modeling revealed that SAM was characterized by inflammation, endothelial activation, and enteropathy that persisted over the 48 weeks after discharge and that were associated with higher mortality and hospital readmission. Conversely, growth factors indicative of endothelial and epithelial repair were associated with reduced mortality and hospital readmission over 48 weeks. These findings suggest that interventions to decrease inflammation and promote epithelial repair may be beneficial for the treatment of SAM. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Lipid alterations in the brain are well-documented in disease and aging, but our understanding of their pathogenic implications remains incomplete. Recent technological advances in assessing lipid profiles have enabled us to intricately examine the spatiotemporal variations in lipid compositions within the complex brain characterized by diverse cell types and intricate neural networks. In this study, we coupled time-of-flight secondary ion mass spectrometry (ToF-SIMS) to an amyotrophic lateral sclerosis (ALS) Drosophila model, for the first time, to elucidate changes in the lipid landscape and investigate their potential role in the disease process, serving as a methodological and analytical complement to our prior approach that utilized matrix-assisted laser desorption/ionization mass spectrometry. The expansion of G4C2 repeats in the C9orf72 gene is the most prevalent genetic factor in ALS. Our findings indicate that expressing these repeats in fly brains elevates the levels of fatty acids, diacylglycerols, and ceramides during the early stages (day 5) of disease progression, preceding motor dysfunction. Using RNAi-based genetic screening targeting lipid regulators, we found that reducing fatty acid transport protein 1 (FATP1) and Acyl-CoA-binding protein (ACBP) alleviates the retinal degeneration caused by G4C2 repeat expression and also markedly restores the G4C2-dependent alterations in lipid profiles. Significantly, the expression of FATP1 and ACBP is upregulated in G4C2-expressing flies, suggesting their contribution to lipid dysregulation. Collectively, our novel use of ToF-SIMS with the ALS Drosophila model, alongside methodological and analytical improvements, successfully identifies crucial lipids and related genetic factors in ALS pathogenesis. [ABSTRACT FROM AUTHOR]

In terms of medicine, the prevention, diagnosis, and assessment of acute myocardial infarction (AMI) as well as the effectiveness of therapy all depend on the sensitive and early detection of human heart-type fatty acid–binding protein (H-HABP). The synthetic material used in this study, Ni-TCPP(Fe), has a unique structure that resembles a rifter with many thorns. When exposed to PSS-Gr, Ni-TCPP(Fe) would unfold into a sheet structure, exposing a lot of active sites and improving the catalytic active surface area, making it easier to detect H-FABP. We have successfully synthesized an electrochemical immunosensor based on Ni-TCPP(Fe)@PSS-Gr and Ag@Au/Pt as a signal label which demonstrated excellent sensor performance. A broad linear range of 10 fg/mL to 100 ng/mL with a low detection limit of 5.75 fg/mL (S/N = 5) for detecting H-FABP was obtained under ideal conditions. Furthermore, the detection results from the human serum samples were positive, suggesting that the made-up immunosensor could be useful for early clinical analysis. [ABSTRACT FROM AUTHOR]

The article aims to find potential biomarker for the detection of tubular damage in pediatric neurogenic bladder (NB) by investigating urinary levels of liver-type fatty acid-binding protein (uL-FABP). This prospective analysis was conducted on two groups: 42 children with NB and 18 healthy children. The uL-FABP concentrations were measured using ELISA methods. The medical charts of the children were examined to determine age, sex, anthropometric measurements, activity assessment using Hoffer's scale, and renal function parameters. The results revealed that the uL-FABP/creatinine ratio was higher in the study group compared with the reference group, but the difference was not statistically significant (p = 0.52, p > 0.05). However, the uL-FABP/creatinine ratio exhibited a wider range in NB patients compared to the reference group. NB children with proteinuria and the history of high-grade vesicoureteral reflux (VUR) tended to have the highest uL-FABP concentrations. In conclusion, uL-FABP may be considered a potential tubular damage biomarker in children with NB. Proteinuria and the history of VUR may be the factors influencing the uL-FABP. [ABSTRACT FROM AUTHOR]

Background and Aim: Liver injury results in the production of free radicals that can lead to hepatocytic degeneration, cirrhosis, and hepatocellular carcinoma (HCC). Liver-fatty acid-binding protein (L-FABP) is highly expressed in hepatocytes and is a key regulator of hepatic lipid metabolism and antioxidant characteristics. Interestingly, the increase in L-FABP expression could be used as a novel marker of liver injury. Therefore, this study aimed to use immunohistochemical techniques to investigate the expression of L-FABP in dogs with liver injury compared with dogs with non-pathological liver. Materials and Methods: Liver tissue samples were collected from dog biopsy specimens at the Veterinary Diagnostic Laboratory at the Faculty of Veterinary Medicine, Chiang Mai University. The tissues were prepared for immunohistochemistry and the expression and localization of L-FABP were investigated using one-way analysis of variance. Results: Immunohistochemical analysis showed that L-FABP was strongly expressed in the hepatocytes of dogs with lipidosis and HCC when compared with that in normal liver. Semi-quantitative immunohistochemistry evaluation showed the percentage of protein expression of L-FABP 0.023 ± 0.027 in the non-pathological liver. The percentage of L-FABP protein expression in lipidosis and HCC was found to be 8.517 ± 1.059 and 17.371 ± 4.026, respectively. Conclusion: L-FABP expression in dogs with liver injuries was significantly higher than that in dogs with non-pathological liver injury (p = 0.05). These results suggest that L-FABP has the potential as a novel marker for specific diagnosis and prognosis of dogs with liver injury. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies have documented the cardiovascular consequences of acute coronavirus disease 2019 (COVID-19), although one of the early cardiac markers that can be used for diagnosis, the heart-type fatty acid-binding protein (H-FABP), has not been covered. Through the evaluation of H-FABP levels, we aim to contribute to the early diagnosis and treatment of cardiac problems in COVID-19 infection patients. Methodology: Seventy-five patients who were admitted to the emergency department of Mehmet Akif Ersoy Hospital with a complaint of chest pain in the last 6 hours and whose corona PCR tests were positive, were included in our study as the case group and 60 healthy volunteers as the control group. The routine cardiac markers such as creatine kinase MB (CK-MB) cardiac troponin T (cTnT), and H-FABP levels were analyzed by routine laboratory methods. Results: The mean age and gender distributions of the groups did not differ statistically (p > 0.05). CK-MB, cTnT, and H-FABP measurements were statistically different between the groups (p = 0.001; p < 0.01). Conclusions: The relationship between AMI and COVID-19 with routine cardiac markers is already supported by recent studies. We also evaluated H-FABP levels in our study, as it affects the prognosis of the disease independent of the chronic disease history. At the same time, we showed that H-FABP levels increase earlier than routine cardiac markers, so it will be useful for COVID-19 patients with cardiac complaints. [ABSTRACT FROM AUTHOR]

Perfluorooctanesulfonate (PFOS) is a widespread environmental pollutant with a long half-life and clearly negative outcomes on metabolic diseases such as fatty liver disease and diabetes. Male and female Cyp2b-null and humanized CYP2B6-transgenic (hCYP2B6-Tg) mice were treated with 0, 1, or 10 mg/kg/day PFOS for 21 days, and surprisingly it was found that PFOS was retained at greater concentrations in the serum and liver of hCYP2B6-Tg mice than those of Cyp2b-null mice, with greater differences in the females. Thus, Cyp2b-null and hCYP2B6-Tg mice provide new models for investigating individual mechanisms for PFOS bioaccumulation and toxicity. Overt toxicity was greater in hCYP2B6-Tg mice (especially females) as measured by mortality; however, steatosis occurred more readily in Cyp2b-null mice despite the lower PFOS liver concentrations. Targeted lipidomics and transcriptomics from PFOS-treated Cyp2b-null and hCYP2B6-Tg mouse livers were performed and compared to PFOS retention and serum markers of toxicity using PCA. Several oxylipins, including prostaglandins, thromboxanes, and docosahexaenoic acid metabolites, are associated or inversely associated with PFOS toxicity. Both lipidomics and transcriptomics indicate PFOS toxicity is associated with PPAR activity in all models. GO terms associated with reduced steatosis were sexually dimorphic with lipid metabolism and transport increased in females and circadian rhythm associated genes increased in males. However, we cannot rule out that steatosis was initially protective from PFOS toxicity. Moreover, several transporters are associated with increased retention, probably due to increased uptake. The strongest associations are the organic anion transport proteins (Oatp1a4-6) genes and a long-chain fatty acid transport protein (fatp1), enriched in female hCYP2B6-Tg mice. PFOS uptake was also reduced in cultured murine hepatocytes by OATP inhibitors. The role of OATP1A6 and FATP1 in PFOS transport has not been tested. In summary, Cyp2b-null and hCYP2B6-Tg mice provided unique models for estimating the importance of novel mechanisms in PFOS retention and toxicity. [ABSTRACT FROM AUTHOR]

Aims: This study aims to provide insight into sex‐specific cardiovascular protein profiles and their associations with adverse outcomes, which may contribute to a better understanding of heart failure (HF) pathophysiology and the optimal use of circulating proteins for prognostication in women and men. Methods and results: In 250 stable patients with HF with reduced ejection fraction (HFrEF), we performed trimonthly blood sampling (median follow‐up: 26 [17–30] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or one sample closest to censoring and applied the Olink Cardiovascular III panel. We used linear regression to study sex‐based differences in baseline levels and joint models to study differences in the prognostic value of serially measured proteins. In 66 women and 184 men (mean age of 66 and 67 years, respectively), 21% and 28% reached the PEP, respectively. Mean baseline levels of fatty acid‐binding protein 4, secretoglobin family 3A member 2, paraoxonase 3, and trefoil factor 3 were higher in women (Pinteraction: 0.001, 0.007, 0.018, and 0.049, respectively), while matrix metalloproteinase‐3, interleukin 1 receptor‐like 1, and myoglobin were higher in men (Pinteraction: <0.001, 0.001, and 0.049, respectively), independent of clinical characteristics. No significant differences between sexes were observed in the longitudinal associations of proteins with the PEP. Only peptidoglycan recognition protein 1 showed a suggestive interaction with sex for the primary outcome (Pinteraction = 0.028), without multiple testing correction, and was more strongly associated with adverse outcome in women {hazard ratio [HR] 3.03 [95% confidence interval (CI), 1.42 to 6.68], P = 0.008} compared with men [HR 1.18 (95% CI, 0.84 to 1.66), P = 0.347]. Conclusions: Although multiple cardiovascular‐related proteins show sex differences at baseline, temporal associations with the adverse outcome do not differ between women and men with HFrEF. [ABSTRACT FROM AUTHOR]

The effects of monolaurin (ML) on the health of piglets infected with porcine epidemic diarrhoea virus (PEDV) have not been fully understood. This study aimed to investigate its role in blood biochemical profile, intestinal barrier function, antioxidant function and the expression of antiviral genes in piglets infected with PEDV. Thirty-two piglets were randomly divided into four groups: control group, ML group, PEDV group and ML + PEDV group. Piglets were orally administrated with ML at a dose of 100 mg/kg·BW for 7 d before PEDV infection. Results showed that PEDV infection significantly decreased D-xylose content and increased intestinal fatty acid-binding protein content, indicating that PEDV infection destroyed intestinal barrier and absorption function. While it could be repaired by ML administration. Moreover, ML administration significantly decreased plasma blood urea nitrogen and total protein content upon PEDV infection. These results suggested ML may increase protein utilisation efficiency. ML administration significantly decreased the number of large unstained cells and Hb and increased the number of leucocytes and eosinophils in the blood of PEDV-infected piglets, indicating ML could improve the immune defense function of the body. In the presence of PEDV infection, ML administration significantly increased superoxide dismutase and catalase activities in blood and colon, respectively, indicating ML could improve antioxidant capacity. Besides, ML administration reversed the expression of ISG15, IFIT3 and IL-29 throughout the small intestine and Mx1 in jejunum and ileum, indicating the body was in recovery from PEDV infection. This study suggests that ML could be used as a kind of feed additive to promote swine health upon PEDV infection. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia affecting millions of individuals worldwide and posing significant challenges to healthcare systems. The growing body of research has uncovered sex-related differences in AF pathophysiology, including the role of fatty acid-binding protein 4 (FABP4) and leptin as potential biomarkers. FABP4 and leptin, key adipokines involved in cardiovascular health, have been linked to inflammation, oxidative stress, and endothelial dysfunction, all of which may contribute to AF development. These adipokines exhibit sex-specific differences in their concentrations, with females generally showing higher FABP4 levels and males displaying distinct leptin profiles. Furthermore, hormonal influences, particularly estrogen, and testosterone, play significant roles in shaping AF risk and atrial remodeling. Estrogen is associated with cardioprotective effects, while testosterone may exert proarrhythmic effects. Understanding these sex-specific mechanisms could lead to more tailored and effective clinical management of AF. The future of AF research holds promise for precision medicine, novel therapeutic targets, artificial intelligence integration, and personalized care approaches. Emphasizing patient-centered care, telemedicine, and multidisciplinary collaboration can further enhance AF management and improve patient outcomes. In conclusion, recognizing and addressing sex-related factors in AF pathophysiology offer opportunities for gender-responsive interventions and advancements in AF management. Implementing these insights may pave the way for targeted therapies and improved quality of life for individuals affected by AF. [ABSTRACT FROM AUTHOR]

The article discusses the use of nuclear magnetic resonance (NMR) spectroscopy in studying the structures and dynamics of bioactive proteins. NMR spectroscopy provides detailed information on the atomic-level structure and motion of molecules, including proteins. It is particularly useful in understanding protein interactions, folding, and stability. The article highlights several studies that utilize NMR spectroscopy to investigate protein-protein interactions, protein-nucleotide interactions, protein dynamics, ligand binding, and protein folding. The findings from these studies contribute to our understanding of biological processes and have implications for the development of new therapies. [Extracted from the article]

Blood biomarkers have been studied to improve the clinical assessment and prognostication of patients with moderate-severe traumatic brain injury (mo/sTBI). To assess their clinical usability, one needs to know of potential factors that might cause outlier values and affect clinical decision making. In a prospective study, we recruited patients with mo/sTBI (n = 85) and measured the blood levels of eight protein brain pathophysiology biomarkers, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), neurofilament light (Nf-L), heart-type fatty acid-binding protein (H-FABP), interleukin-10 (IL-10), total tau (T-tau), amyloid β40 (Aβ40) and amyloid β42 (Aβ42), within 24 h of admission. Similar analyses were conducted for controls (n = 40) with an acute orthopedic injury without any head trauma. The patients with TBI were divided into subgroups of normal versus abnormal (n = 9/76) head computed tomography (CT) and favorable (Glasgow Outcome Scale Extended [GOSE] 5–8) versus unfavorable (GOSE <5) (n = 38/42, 5 missing) outcome. Outliers were sought individually from all subgroups from and the whole TBI patient population. Biomarker levels outside Q1 − 1.5 interquartile range (IQR) or Q3 + 1.5 IQR were considered as outliers. The medical records of each outlier patient were reviewed in a team meeting to determine possible reasons for outlier values. A total of 29 patients (34%) combined from all subgroups and 12 patients (30%) among the controls showed outlier values for one or more of the eight biomarkers. Nine patients with TBI and five control patients had outlier values in more than one biomarker (up to 4). All outlier values were > Q3 + 1.5 IQR. A logical explanation was found for almost all cases, except the amyloid proteins. Explanations for outlier values included extremely severe injury, especially for GFAP and S100B. In the case of H-FABP and IL-10, the explanation was extracranial injuries (thoracic injuries for H-FABP and multi-trauma for IL-10), in some cases these also were associated with abnormally high S100B. Timing of sampling and demographic factors such as age and pre-existing neurological conditions (especially for T-tau), explained some of the abnormally high values especially for Nf-L. Similar explanations also emerged in controls, where the outlier values were caused especially by pre-existing neurological diseases. To utilize blood-based biomarkers in clinical assessment of mo/sTBI, very severe or fatal TBIs, various extracranial injuries, timing of sampling, and demographic factors such as age and pre-existing systemic or neurological conditions must be taken into consideration. Very high levels seem to be often associated with poor prognosis and mortality (GFAP and S100B). [ABSTRACT FROM AUTHOR]

This article discusses the role of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in tumor progression and resistance to therapy. PMN-MDSCs are a subset of neutrophils that exhibit immune suppressive activity and contribute to the tumor microenvironment. The article highlights the mechanisms by which PMN-MDSCs promote tumor growth and limit anti-cancer immune responses. It also explores the potential of targeting PMN-MDSCs for cancer immunotherapy, with several drugs showing promising results in combination with checkpoint inhibitors. The study identifies CD300ld as a specific surface marker and critical immune suppressor on PMN-MDSCs, providing a potential target for cancer treatment. [Extracted from the article]

Introduction: Large-scale clinical trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrate proteinuria-reducing effects in diabetic kidney disease, even after treatment with renin–angiotensin inhibitors. The precise mechanism for this favorable effect remains unclear. This prospective open-label single-arm study investigated factors associated with a reduction in proteinuria after SGLT2i administration. Methods: Patients with type 2 diabetes (T2DM) who had glycated hemoglobin (HbA1c) levels ≥ 6.5% despite dietary and/or oral hypoglycemic monotherapy were recruited and administered the recommended daily dose of SGLT2i for 4 months. Dual primary outcomes were changes in the urine albumin-to-creatinine ratio (uACR) and urine liver-type fatty acid-binding protein (L-FABP)-to-creatinine ratio (uL-FABPCR) at month 4 from baseline. Changes in kidney injury, inflammation, and oxidative stress biomarkers were investigated as secondary endpoints to examine the effects of this treatment on the kidney. The correlation between renal outcomes and clinical indicators, including circulating tumor necrosis factor receptors (TNFR) 1 and 2, was evaluated using univariate and multivariate analyses. Results: Participants (n = 123) had a mean age of 64.1 years (SD 13.4), with 50.4% being male. The median BMI was 25.8 kg/m2 (interquartile range (IQR) 23.1–28.9), and the median HbA1c level was 7.3% (IQR 6.9–8.3). After SGLT2i administration, the uACR declined from 19.2 mg/gCr (IQR 7.1–48.7) to 13.3 mg/gCr (IQR 7.5–31.6), whereas the uL-FABPCR was not influenced. In univariate analysis, the change in log-transformed uACR due to SGLT2i administration showed a positive correlation with the change in serum TNFR1 level (R = 0.244, p < 0.01). Multivariate regression analysis, including confounding factors, showed that the changes in serum TNFR1 level were independently associated with the changes in the log-transformed uACR (independent t = 2.102, p < 0.05). Conclusion: After the 4-month SGLT2i administration, decreased albuminuria level was associated with decreased serum TNFR level in patients with T2DM. Trial Registration Number: UMIN000031947. Plain Language Summary: Previous studies have demonstrated the synergistic proteinuria-reducing effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in combination therapy with renin–angiotensin system blockers; however, the underlying mechanisms of this effect are poorly understood. This study was based on our hypothesis that the proteinuria-reducing effect is associated with the anti-inflammatory effects of SGLT2i beyond the effect on glycemic control. In total, 123 patients with type 2 diabetes mellitus (T2DM) were administered the recommended daily dose of SGLT2i for 4 months. Dual primary outcomes were changes in the urine albumin-to-creatinine ratio (uACR) and urine liver-type fatty acid-binding protein (L-FABP)-to-creatinine ratio (uL-FABPCR) as markers of glomerular and proximal tubular damage at 4 months from the baseline. Secondary outcomes included changes in kidney injury biomarkers, inflammation, and oxidative stress to examine the effects of treatment on the kidneys. The correlation between renal outcomes and clinical indicators, including circulating tumor necrosis factor receptors (TNFR) 1 and 2, was evaluated using univariate and multivariate analyses. We found that administration of SGLT2i decreased the urine albumin-to-creatinine ratio but did not affect the urine liver-type fatty acid-binding protein-to-creatinine ratio. Further, SGLT2i may exert a proteinuria-reducing effect dependent on the anti-inflammatory effect in patients with T2DM. The inflammation-reducing and renoprotective mechanisms of SGLT2i remain to be fully clarified, but this study provides novel evidence regarding the mechanism. The study findings can help in developing anti-inflammatory agents for metabolic diseases. [ABSTRACT FROM AUTHOR]

Background Vitiligo is an acquired depigmentary disorder characterized by destruction of melanocytes. The activity of vitiligo influences the clinical outcome and alters the choice of treatment modality. Intestinal fatty acid binding protein (I-FABP), also called FABP-2, is solely expressed in intestinal enterocytes of mammals. Objective To evaluate the serum and tissue levels of I-FABP in vitiligo patients and its relation to healthy controls. Patients and methods The present study is a case-control study that was carried out on 44 subjects subdivided into two equal groups, vitiligo, and matched controls. The clinical study was done as well and I-FABP levels in both serum and tissue were measured by Enzyme-linked immunosorbent assay (ELISA). Results There were significant elevations in I-FABP levels in both serum with a median of 7.16 and 5.29 (P=0.011) and in tissue with a median of 707.3 and 274.9 (P=0.014) for vitiligo patients in comparison with controls, respectively. Positive correlation between I-FABP levels in serum and in tissue was detected (r=0.488, P=0.021). Sensitivity for diagnosis vitiligo for serum and tissue I-FABP were 77.3 and 86.36%, respectively and specificity were 54.5 and 95.5%, respectively. Conclusion I-FABP can play a vital role in vitiligo and may be a marker that helps in early diagnosis of vitiligo, but it does not appear to be useful for determining vitiligo activity, severity. [ABSTRACT FROM AUTHOR]