Search Results (88)

Claudin 5 (Cldn5) is a critical tight junction protein essential for maintaining paracellular barrier integrity across endothelial and epithelial cells in barrier-forming tissues, including the blood–brain barrier and blood–retinal barrier. Cldn5 plays a central role in regulating vascular permeability, immune responses, and tissue homeostasis. The complex distribution and organ-specific regulation of Cldn5 underscore its potential as a promising therapeutic target. This review comprehensively analyzes the role of Cldn5 in endothelial and epithelial barrier function, its regulation of vascular permeability, and the discrepancies in the literature regarding its expression, regulation, and function in both physiological and pathological conditions across multiple organ systems, including the retina, brain, lung, heart, gut, kidney, liver, skin, and peripheral nerves, while emphasizing its tissue-specific expression patterns. We discuss how both reduced and excessive expressions of Cldn5 can disrupt barrier integrity and contribute to the pathogenesis of ischemic retinopathies, neuroinflammation, cardiovascular injury, and other forms of barrier dysfunction. Furthermore, we explore the dual role of Cldn5 as both a biomarker and a therapeutic target, highlighting emerging strategies such as RNA silencing, pharmacological stabilizers, and transcriptional modulators in controlling barrier leakage in disease conditions. Full article

Background: Despite escalating global pollution from microplastics (MPs) and the concurrent surge in high-fat food consumption, the health impacts of MP exposure on individuals under different dietary patterns remain poorly understood. Methods: This study investigated the differential effects of environmentally relevant concentrations of polystyrene microplastics (5 μm, 8 mg/kg) on gut barrier function in mice fed either a normal chow diet (CD) or a high-fat diet (HFD). Results: Key findings revealed that, in HFD-fed mice, MP exposure significantly reduced (p < 0.05) the transcriptional levels of genes encoding the tight junction proteins (ZO-1, Occludin, and Claudin-1), as well as the mucin protein Muc-2, accompanied by decreased protein expression levels of these markers in both colonic and ileal tissues. In contrast, no significant differences were observed in CD-fed mice exposed to MPs. Analysis of the gut microbiota and measurement of short-chain fatty acid (SCFA) metabolites showed that MPs induced significant alterations in the composition and diversity indices of the gut microbiota, along with a marked decrease (p < 0.05) in the levels of the characteristic metabolite butyrate in HFD-fed mice. Conversely, butyrate levels remained unchanged in CD-fed mice following MP exposure. Quantitative PCR (qPCR) and immunofluorescence staining of colonic tissues demonstrated that MP exposure significantly downregulated (p < 0.05) both the transcription and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) in HFD-fed mice. Again, no significant changes were detected in CD-fed mice. Conclusions: These results collectively indicate that the impact of microplastics on the intestinal barrier differs significantly between mice fed normal and high-fat diets. The gut microbiota and its metabolites, particularly butyrate, may play a critical role, possibly through modulating PPARγ signaling. This study contributes valuable insights into understanding the toxicity profiles of microplastics and establishing crucial links between dietary patterns and the health effects of emerging pollutants. Full article

Background/Objectives: Dilated cardiomyopathy (DCM), defined as dilation and contractile dysfunction of the left or both cardiac ventricles, remains the most common category of primary myocardial disease worldwide. It is the most prevalent cause of chronic heart failure and the most common indication for cardiac transplantation in young subjects. Accumulating evidence increasingly highlights the substantial genetic defects underlying DCM. Nevertheless, the genetic ingredients accountable for DCM in a major percentage of patients remain indefinite. Methods: A multigenerational pedigree suffering from DCM and a total of 276 healthy volunteers employed as controls were recruited from the Chinese Han-ethnicity population. A whole-exome sequencing (WES) assay followed by a Sanger sequencing analysis of the genomic DNAs from the available family members was implemented. Functional characterization of the identified genetic variant was completed by dual-luciferase analysis. Results: A new heterozygous variation in the ETS1 (erythroblast transformation-specific 1) gene, NM_005238.4:c.447T>G;p.(Tyr149*), was identified by WES and validated by Sanger sequencing analysis to co-segregate with DCM in the whole DCM family. This nonsense ETS1 variant was not found in 276 control subjects. Functional examination elucidated that Tyr149*-mutant ETS1 lost the ability to transactivate its downstream target genes CLDN5 (claudin 5) and ALK1 (activin receptor-like kinase 1), two genes crucial for cardiovascular embryonic development and postnatal structural remodeling. Conclusions: The present investigation reveals ETS1 as a new gene predisposed to human DCM and indicates ETS1 haploinsufficiency as an alternative molecular pathogenesis underlying DCM, providing a potential molecular target for genetic counseling and early diagnosis as well as personalized prophylaxis of DCM. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Age-related macular degeneration (AMD) is the main cause of blindness in Western nations. AMD models addressing specific pathological pathways are desired. Through this study, a best-practice protocol for polarized porcine single-eye retinal pigment epithelium (RPE) preparation for AMD-relevant models of RPE barrier and polarity is established. Single-eye porcine primary RPE cells (from one eye for one well) were prepared in 12-well plates including Transwell inserts. Different coatings (laminin (Lam), Poly-ᴅ-Lysine (PDL), fibronectin (Fn) and collagens) and varying serum contents (1%, 5% and 10%) were investigated to determine optimal culture parameters for this model. Success rates of cultures, cell number (trypan-blue exclusion assay), morphology/morphometry (light and fluorescence microscopy), protein secretion/expression (ELISA, Western blot), gene expression (qPCR), transepithelial electric resistance (TEER) and polar location of bestrophin 1 (BEST1) by cryosectioning (IHC-Fr) were assessed. Cells seeded on Lam exhibited the highest level of epithelial cells and confluence properties. Fn resulted in the highest cell number growth. Lam and Fn exhibited the highest culture success rates. TEER values and vascular endothelial growth factor secretion were highest when Lam was used. For the first time, polar (Transwell) porcine single-eye RPE morphometry parameters were determined. RPE on Lam showed bigger cells with a higher variety of cell shapes. CIV displayed the lowest claudin 19 expression. The highest basolateral expression of BEST1 was achieved with Lam coating. The higher the serum, the better the cell number increase and confluence success. A reduction in serum on Lam showed positive results for RPE morphology, while morphometry remained stable. A five percent serum on Lam showed the highest culture success rate and best barrier properties. RPE65 expression was reduced by using 10% serum. Altogether, the most suitable coating of Transwell inserts was Lam, and a reduction in serum to 5% is recommended, as well as a cultivation time of 28 days. A protocol for the use of polar porcine single-eye cultures with validated parameters was established and is provided herein. Full article

Defensins, one of the members of the antimicrobial peptide family, play a vital role in resisting microbial invasion and immune regulation. Porcine β-defensin 2 possesses excellent stability, making it an ideal antibiotic alternative for feed additives. In this study, a total of 15 piglets were used to investigate the effects of supplementing diets with 2.5 mg/kg (LP group) and 5 mg/kg (HP group) of pBD2 to weaned piglets. The results revealed that pBD2 significantly increased the total weight gain and average daily weight gain (p < 0.05), the contents of T-AOC, SOD, IgM, and IL-10 in serum (p < 0.05), the villus-to-crypt ratios, and the expression of tight-junction proteins ZO-1 and claudin-1 (p < 0.05) in the small intestine. Furthermore, pBD2 increased the abundance of beneficial bacteria related to nutrient and energy metabolism while decreasing the abundance of harmful bacteria associated with intestinal inflammation and diarrhea. Alterations in the gut microbiota were closely associated with the levels of T-AOC, SOD, IgM, and IL-10 in serum. pBD2 primarily enhanced the health of weaned piglets by influencing antioxidant capacity, intestinal barrier function, and the intestinal microbiota. Our research provides a novel perspective for addressing the issue of antibiotic residues in feed. Full article

Background: The pathogenesis of neuropsychiatric lupus erythematosus (NPSLE) is very complex and is associated with neuroinflammation and blood–brain barrier compromise. Experimental investigations of NPSLE have classically relied on spontaneous models. Recently, TLR7 agonist-induced lupus has been shown to exhibit similar neuropsychiatric manifestations to spontaneous ones. Cinnamon is a widespread spice and natural flavoring agent. It has been proven to modulate vascular endothelial tight junctions, neuroinflammation, and autoimmunity pathways, but it has never been tested in relation to lupus. Hypothesis/Purpose: In this pilot study, we aimed to explore the disease-modifying effect of Cinnamomum cassia on NPSLE in a TLR7 agonist-induced model. Study Design: An experimental design was followed in this study. Methods: Lupus was induced in C57BL/6J female mice via the direct application of imiquimod, a TLR7 agonist (5% imiquimod cream, 1.25 mg three times weekly), to the skin. Mice were divided into five groups (n = 8 per group): a sham group (S), a sham group supplemented with cinnamon (SC), an imiquimod-treated group (L), an imiquimod-treated group supplemented with cinnamon starting from induction (LC), and an imiquimod-treated group supplemented with cinnamon beginning two weeks prior to induction (CLC). This protocol was followed for six consecutive weeks. Cinnamomum cassia powder was administered orally at 200 mg/kg, 5 days per week. Results: Behavioral alterations were significantly ameliorated in the CLC group compared to lupus mice. Neuronal shrinkage and nuclear chromatin condensation were visible in the hippocampal cornu ammonis and dentate gyrus zones of lupus mice, with an increased expression of TLR7 and NLRP3, versus significantly less neurodegeneration and TLR7 and NLRP3 expression in the CLC group. In addition, the expression of the blood–brain barrier endothelial cell tight junction proteins claudin-1, occludin, and ZO-1 was abnormally modified in lupus mice and was restored in the CLC group. Moreover, while the cell–cell border delocalization of claudin-1 was documented in cultured blood–brain barrier endothelial cells treated with the plasma of lupus mice to a punctate intracytoplasmic fluorescence pattern, only cells treated with the plasma of the CLC group exhibited a complete reversal of this redistribution of claudin-1. Finally, cinnamaldehyde seemed to interact with TLR7 at multiple sites. Conclusions:Cinnamomum cassia seems to alleviate the pathogenesis of NPSLE. Supplementation with Cinnamomum cassia could be of great interest to modulate the activity and severity of the disease. Full article

The deoxynivalenol (DON) mycotoxin poses serious health risks, especially to swine, which are highly susceptible to intestinal damage. Existing strategies to counteract DON toxicity remain insufficient. This study aimed to evaluate the protective effects of cannabidiol (CBD), a phytocannabinoid with anti-inflammatory properties, against DON-induced intestinal toxicity in porcine intestinal epithelial cells. Using differentiated and proliferating porcine intestinal epithelial cells (IPEC-J2), we evaluated CBD (2.5–5 μM) against DON (0.5–50 μM) through viability assays, apoptosis markers (Bax/Bcl-2 ratio), inflammatory mediators (NFκB, IL-6, COX-2), oxidative stress indicators (TXNIP, SOD1, CAT), tight junction gene expression (Claudin-1, Occludin), and barrier permeability. DON exhibited dose- and time-dependent cytotoxicity (IC₅₀ = 2.60 μM at 24 h; 1.07 μM at 48 h). Pre-treatment with 5 μM CBD restored cell viability at low DON concentrations (0.5–2 μM) but failed at ≥8 μM. In differentiated cells, CBD suppressed apoptosis (reduced Bax/Bcl-2 ratio), oxidative stress (downregulated TXNIP; restored CAT expression), and inflammation (decreased IL-6 and COX-2) under high-dose DON (50 μM), while enhancing tight junction protein expression and barrier integrity at 5 μM DON. Conversely, in proliferating cells, CBD exacerbated apoptosis (elevated Bax/Bcl-2 ratio) and inflammatory responses (upregulated IL-6 and COX-2) at subtoxic levels of DON (2 μM). CBD alone induced cytotoxicity at ≥10 μM. Our findings demonstrate that CBD exhibits context-dependent efficacy, providing protection in differentiated epithelia under moderate DON exposure (≤5 μM) but exhibiting detrimental effects in proliferating cells. Its narrow therapeutic window and paradoxical actions necessitate cautious application. These findings position CBD as a potential adjunctive therapy for DON detoxification but highlight critical limitations for standalone use. Full article

Background/Objectives: Research on postbiotics derived from probiotic fermented milk bases require further expansion, and the mechanisms through which they exert their effects have yet to be fully elucidated. This study utilized in vitro cell co-culture, digestion, and fermentation experiments, combined with targeted T500 technology, to elucidate the mechanism by which postbiotic Pa JY062 safeguards intestinal health. Compared to the LPS group, Pa JY062 boosted phagocytic ability in RAW264.7 macrophages, decreased NO levels, and alleviated LPS-induced excessive inflammation. Pa JY062 suppressed pro-inflammatory cytokines (IL-6, IL-17α, and TNF-α) while elevating anti-inflammatory IL-10. It prevented LPS-induced TEER reduction in Caco-2 monolayers, decreased FITC-dextran permeability, restored intestinal microvilli integrity, and upregulated tight junction genes (ZO-1, occludin, claudin-1, and E-cadherin). The hydrolysis rate of Pa JY062 progressively rose in gastrointestinal fluids in 0–120 min. At 5 mg/mL, it enriched gut microbiota diversity and elevated proportions of Limosilactobacillus, Lactobacillus, Pediococcus, and Lacticaseibacillus while augmenting the microbial production of acetic acid (120.2 ± 8.08 μg/mL), propionic acid (9.9 ± 0.35 μg/mL), and butyric acid (10.55 ± 0.13 μg/mL). Pa JY062 incorporated α_s-casein/β-lactoglobulin hydrolysate (L-glutamic acid, alanine, lysine, tyrosine, phenylalanine, histidine, and arginine) to mitigate protein allergenic potential while harboring bioactive components, including tryptophan metabolites, vitamin B6 (VB6), and γ-aminobutyric acid (GABA). Pa JY062 represented a novel postbiotic with demonstrated intestinal health-promoting properties. These findings advance the current knowledge on postbiotic-mediated gut homeostasis regulation and expedite the translational development of dairy-derived postbiotic formulations. Full article

Due to the high mortality rate in chicks caused by pullorum disease (PD) and the drawbacks of antibiotic resistance, the poultry industry is increasingly interested in using natural herbal antimicrobial agents as alternatives, with cinnamaldehyde (CA) being a focus due to its multitarget and synergistic effects. This study aimed to evaluate the effects of oral administration of CA on restoring intestinal physical integrity, intestinal microbial barrier, and intestinal metabolism in a laboratory model of Salmonella pullorum (S. pullorum) infection in chicks. Thirty-six chicks were divided into six groups. The S.P and CA groups were infected with 5 × 10⁸ CFU/mL, 0.5 mL S. pullorum, while the CON group received an equal-volume saline injection. The CA group was treated with 100 mg/kg CA, and the others received phosphate buffer saline (PBS). Samples were collected 24 h after the last treatment. Intestinal physical integrity was assessed by H&E staining, and ELISA was used to measure inflammatory factors. In situ hybridization (ISH) and RT-qPCR were used to measure the expression of tight-junction protein mRNA. The microbiota was analyzed by 16S rRNA gene sequencing of the ileal contents, and metabolite analysis was performed on the intestinal contents. After CA treatment, the expression of IL-1β and TNF-α was reduced, and IL-10 was increased (p < 0.05). H&E staining showed that the intestinal structure was partially restored after treatment. ISH results showed that the fluorescence intensity indicating gene expression status was low in the S.P group and high in the CA group, indicating reduced intestinal permeability. RT-qPCR showed that CA up-regulated the mRNA expression of tight-junction proteins (claudin-1, occludin-1, and zo-1, p < 0.05). The 16S rRNA gene sequence analysis showed that Salmonella was significantly enriched in the S.P group (LDA score > 2.0, p < 0.05), while specific genera were significantly more abundant in the treated groups. Untargeted sequencing of intestinal contents showed that key metabolites (butyrate, alanine, glutamate, cholesterol, and propionate) in the CA group were significantly changed compared with the S.P group (p < 0.05). CA treatment was the most effective method for reducing PD intestinal colonization and maintaining better intestinal homeostasis, possibly by regulating intestinal microbiota and metabolic functions. Full article

Background: Electronic cigarettes (ECIGs) have grown in popularity, particularly among adolescents and young adults. Flavored ECIG-liquids (E-liquids) are aerosolized by these ECIGs and inhaled into the respiratory system. Several studies have shown detrimental effects of E-liquids in airway tissues, revealing that flavoring agents may be the most irritating component. However, research on the effects of E-liquids on biological processes of the oral cavity, which is the first site of aerosol contact, is limited. Hence, this study focuses on the effects of E-liquid flavors on oral epithelial cells using the OKF6/TERT-2 cell line model. Methodology: E-liquid was prepared with and without flavors (tobacco, menthol, cinnamon, and strawberry). OKF6/TERT-2 oral epithelial cells, cultured at 37 °C and 5% CO₂, were exposed to 1% E-liquid ± flavors for 24 h. Outcomes determined include cell morphology, media pH, wound healing capability, oxidative stress, expression of mucin and tight junction genes, glycoprotein release, and levels of inflammatory cytokines (TNFα, IL-6, and IL-8). Results: Exposure to 1% flavored E-liquids negatively affect cellular confluency, adherence, and morphology. E-liquids ± flavors, particularly cinnamon, increase oxidative stress and production of IL-8, curtail wound healing recovery, and decrease glycoprotein release. Gene expression of muc5b is downregulated after exposure to E-liquids. In contrast, E-liquids upregulate occludin and claudin-1. Conclusions: This study suggests that ECIG use is not without risk. Flavored E-liquids, particularly cinnamon, result in pathophysiological responses of OKF6/TERT-2 cells. The dysregulation of inflammatory responses and cellular biology induced by E-liquids may contribute to various oral pathologies. Full article

This article aims to investigate the mechanism by which Bacillus amyloliquefaciens alleviates lipopolysaccharide (LPS)-induced intestinal oxidative stress. The study involved two experimental subjects: human colorectal adenocarcinoma (Caco-2) cells and Arbor Acres broiler chickens. The experiment involving two samples was designed with the same treatment groups, specifically the control (CK) group, lipopolysaccharide (LPS) group, Bacillus amyloliquefaciens (JF) group, and JF+LPS group. In the Caco-2 experiment, we administered 2 μg/mL of LPS and 1 × 10⁶ CFU/mL of JF to the LPS and JF groups, respectively. In the broiler experiment, the LPS group (19–21 d) received an abdominal injection of 0.5 mg/kg BW of LPS, whereas the JF group was fed 1 × 10⁷ CFU/g of JF throughout the entire duration of the experiment (1–21 d). The results indicated the following: (1) JF significantly decreased the DPPH free radical clearance rate and hydrogen peroxide levels (p < 0.05). (2) JF significantly enhanced the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH Px) activity in Caco-2 cells (p < 0.05), while concurrently reducing malondialdehyde (MDA) content (p < 0.05). (3) Compared to the CK group, JF significantly increased the mRNA expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), SOD, catalase (CAT), GSH-Px, interleukin-4 (IL-4), interleukin-10 (IL-10), Claudin, Occludin1, zonula occludens-1 (ZO-1), and mucin 2 (MUC2) in Caco-2 cells (p < 0.05), while concurrently reducing the mRNA expression of Kelch-like ECH-associated protein 1 (Keap1), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-8 (IL-8) (p < 0.05). In comparison to the LPS group, the JF+LPS group demonstrated a significant increase in the mRNA expression of Nrf2, SOD, GSH-Px, and IL-4, as well as Occludin1, ZO-1, and MUC2 in Caco-2 cells (p < 0.05), alongside a decrease in the mRNA expression of Keap1, TNF-α, and IL-1β (p < 0.05). (4) In broiler chickens, the JF group significantly elevated the levels of T-AOC, CAT, and GSH-Px in the jejunum while reducing MDA content (p < 0.05). Furthermore, the CAT level in the JF+LPS group was significantly higher than that observed in the LPS group, and the levels of MDA, TNF-α, and IL-1β were significantly decreased (p < 0.05). (5) In comparison to the CK group, the JF group exhibited a significant increase in Nrf2 levels in the jejunum of broiler chickens (p < 0.05). Notably, the mRNA expression levels of IL-4, IL-10, Claudin, Occludin1, ZO-1, and MUC2 were reduced (p < 0.05), while the mRNA expression levels of Keap1, TNF-α, and IL-1β also showed a decrease (p < 0.05). Furthermore, the mRNA expression levels of Nrf2, Occludin1, ZO-1, and MUC2 in the JF+LPS group were significantly elevated compared to those in the LPS group (p < 0.05), whereas the mRNA expression levels of Keap1 and TNF-α were significantly diminished (p < 0.05). In summary, JF can enhance the intestinal oxidative stress response, improve antioxidant capacity and intestinal barrier function, and decrease the expression of inflammatory factors by regulating the Keap1/Nrf2 signaling pathway. Full article

Malondialdehyde (MDA) is a reactive carbonyl compound produced through lipid peroxidation during feed storage, which poses a significant threat to fish health. This study aimed to evaluate the effects of dietary MDA on the growth rate, gastrointestinal health, and muscle quality of striped catfish (Pangasianodon hypophthalmus). A basal diet (M0) containing 34% crude protein and 10.5% crude lipid was formulated. Each group was sprayed with malondialdehyde solution (0, 5, 10, 20, 40, and 80 mg/kg, on dietary crude lipid basis; 0, 0.53, 1.07, 2.13, 4.26, and 8.52 mg/kg, on dietary basis) before feeding, respectively. Each diet was randomly assigned to triplicates of 30 striped catfish (initial weight 31.38 g) per net cage. After 8 weeks, dietary inclusion of MDA regardless of level significantly depressed the growth rate and feed utilization. The extent of structural damage to the gastrointestinal tract increased progressively with increasing dietary MDA levels. The extent of damage to the intestinal biological barrier (intestinal microbial structure), chemical barrier (trypsin, lipase, amylase, and maltase activity), physical barrier (zonula occludent-2, occludin, claudin 7α, and claudin 12 relative expression), and immune barrier (contents of complement 4, complement 3, immunoglobulin M, and lysozyme activity) was dose-related to dietary MDA. Moreover, a linear decline in the activities of intestinal antioxidant enzymes (catalas, superoxide dismutase, et al.) and anti-inflammatory factor (transforming growth factor beta1, interleukin 10) relative expression was noted alongside an increase in dietary MDA content. In contrast, the relative expression levels of intestinal inflammatory factor (interleukin 8, transcription factor p65, tumor necrosis factor alpha) relative expression displayed an opposing trend. Additionally, dietary MDA exerted a linear influence on muscle color and texture characteristics. In conclusion, high doses of MDA (5–80 mg/kg) reduced the growth performance of striped catfish, attributed to linear damage to the gastrointestinal tract, a linear decrease in antioxidant function, and the occurrence of an inflammatory response. High doses of MDA (>40 mg/kg) were observed to significantly increase dorsal muscle b-value and induce muscle yellowing. Full article

Background/Objectives: Alzheimer’s disease (AD), a leading cause of dementia, lacks effective long-term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Aβ) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut. Given this context, exploring alternative therapeutic interventions capable of addressing the multifaceted components of AD etiology is essential. Methods: This study suggests D-Pinitol (DPIN) as a potential treatment modifier for AD. DPIN, derived from carob pods, demonstrates insulin-sensitizing, tau hyperphosphorylation inhibition, and antioxidant properties. To test this hypothesis, we studied whether chronic oral administration of DPIN (200 mg/kg/day) could reverse the AD-like disease progression in the 5×FAD mice. Results: Results showed that treatment of 5×FAD mice with DPIN improved cognition, reduced hippocampal Aβ and hyperphosphorylated tau levels, increased insulin-degrading enzyme (IDE) expression, enhanced pro-cognitive hormone circulation (such as ghrelin and leptin), and normalized the PI3K/Akt insulin pathway. This enhancement may be mediated through the modulation of cyclin-dependent kinase 5 (CDK5). DPIN also protected the gut barrier and microbiota, reducing the pro-inflammatory impact of the leaky gut observed in 5×FAD mice. DPIN reduced bacterial lipopolysaccharide (LPS) and LPS-associated inflammation, as well as restored intestinal proteins such as Claudin-3. This effect was associated with a modulation of gut microbiota towards a more balanced bacterial composition. Conclusions: These findings underscore DPIN’s promise in mitigating cognitive decline in the early AD stages, positioning it as a potential disease modifier. Full article

Frailty in cirrhosis or advanced chronic liver disease (ACLD) is a relevant prognostic factor. In the present study, we aimed to analyze potential biomarkers associated with frailty and its improvement in patients with ACLD. We analyzed the serum of outpatients with ACLD who participated in a previous study (Román, Hepatol Commun 2024) in which frailty was assessed using the liver frailty index (LFI), and patients who were frail or prefrail were randomized to a multifactorial intervention (home exercise, branched-chain amino acids, and probiotics) or control for 12 months. We determined a biomarker battery of inflammation, bacterial translocation, and liver damage in blood and urine and blood metabolomics by ¹H-NMR. Thirty-seven patients were included. According to the LFI, 32 patients were frail or prefrail, and 5 were robust. At baseline, LFI correlated with LBP, sCD163, mtDNA, FGF-21, urinary NGAL, urinary claudin-3, and the metabolites mannose, ethanol, and isoleucine. During the study, patients in the intervention group showed an improvement in LFI and a decrease in CRP, LBP, sCD163, and ccK18 compared to the control group. Metabolomics showed a decrease in dimethyl sulfone and creatinine and an increase in malonate, ornithine, isoleucine, and valine in the intervention group. We conclude that frailty in patients with ACLD is associated with biomarkers of systemic inflammation, bacterial translocation, and liver damage, and alterations of amino acid and short-chain fatty acid metabolism. Full article