Mitigate Weight Loss Research Articles

Lactobacillus fermentum 016 Alleviates Mice Colitis by Modulating Oxidative Stress, Gut Microbiota, and Microbial Metabolism

Ulcerative colitis (UC) is a chronic and progressive inflammatory gastrointestinal disease closely associated with gut microbiota dysbiosis and metabolic homeostasis disruption. Although targeted microbial therapies are an emerging intervention strategy for inflammatory bowel disease (IBD), the mechanisms by which specific probiotics, such as Lactobacillus fermentum 016 (LF), alleviate UC remain unclear. The current study evaluated the effects of LF supplementation on gut health in a basal model using C57BL/6 mice. Subsequently, the preventive effects and mechanisms of LF supplementation on DSS-induced UC were systematically investigated. According to our findings, LF supplementation revealed immunoregulatory capabilities with significantly altered gut the composition of microbiota and metabolic activities, particularly enhancing tryptophan metabolism. In the UC model, LF supplementation effectively mitigated weight loss, increased the disease activity index (DAI), and alleviated diarrhea, rectal bleeding, and colon shortening. Moreover, it reduced colonic pathological damage and histological injury scores. LF intervention improved antioxidant markers and intestinal mucosal barrier function with the activation of the Nrf2–Keap1 signaling pathway and regulation of systemic inflammatory markers, i.e., IL-1β, IL-6, TNF-α, IFN-γ, IL-4, and IL-10. Importantly, LF supplementation reversed metabolic disturbances by significantly increasing the abundance of beneficial genera (e.g., g_Dubosiella, g_Faecalibaculum, g_Odoribacter, g_Candidatus_saccharimonas, g_Roseburia, and g_Eubacterium_xylanophilum_group) and elevating tryptophan metabolites (e.g., melatonin, kynurenic acid, 3-indoleacetic acid, 5-methoxytryptophan, and 5-hydroxyindoleacetic acid). In conclusion, Lactobacillus fermentum 016 exhibits potential for regulating gut microbiota homeostasis, enhancing tryptophan metabolism, and alleviating UC, providing critical insights for developing probiotic-based precision therapeutic strategies for IBD.

DOP032 Extracellular vesicles from Bifidobacterium longum Subspecies infantis attenuate intestinal inflammation via macrophage polarization

Abstract Background Inflammatory Bowel Disease (IBD) is characterized by chronic intestinal inflammation driven by a complex interplay of genetic, environmental, and immune interactions1. Despite significant advancements in IBD therapies, many patients still face challenges in achieving complete remission or maintaining long-term treatment efficacy. We hypothesize that extracellular vesicles from Bifidobacterium longum subspecies infantis (B. infantis-EVs) can regulate immune responses, promote balanced macrophage polarization, and modulate the gut microbiota, ultimately attenuating intestinal inflammation. Methods B. infantis-EVs were isolated via tangential flow filtration (TFF)2. In vitro studies examined cellular morphology, expression of inflammatory cytokines, and immunofluorescence staining of activated RAW 264.7 macrophage cells34. In a 3% dextran sulfate sodium (DSS) mouse model, disease severity was assessed using the Disease Activity Index (DAI), colon length, survival rate, and metagenome analysis. To confirm the targeting capability of B. infantis-EVs for inflamed lesions, cellular uptake was analyzed using confocal microscopy, and biodistribution was assessed with an In Vivo Imaging System (IVIS). Results To investigate the effects of B. infantis-EVs on macrophage polarization, we examined the cellular morphology and macrophage markers of RAW 264.7 cells. B. infantis-EVs suppress macrophage cells from driving an M1-like phenotype, and downregulated M1 markers (iNOS and CD86) while upregulating M2 markers (Arg1 and CD200R) (Fig. 1a-c). They also decreased the expression of LPS-induced pro-inflammatory cytokines (IL-1β, IL-2, IL-6, and TNF-α) while increasing anti-inflammatory cytokines (IL-10 and TGF-β) (Fig. 1d). In vivo, oral administration of B. infantis-EVs mitigated weight loss (p=0.0120), preserved colon length (p=0.0018), reduced DAI (p=0.0079), lowered histological score (p=0.0003), and modulated gut microbiota composition in DSS-treated mice compared to the DSS + PBS groups. Additionally, fluorescence intensities were stronger in the inflamed group treated with Cy5-labeled B. infantis-EVs compared to non-inflamed group at all-time points tested both cellular uptake and biodistribution (Fig. 1e). These findings suggest that B. infantis-EVs have the capability to target inflamed lesions and exhibit significant anti-inflammatory effects. Conclusion In this study, B. infantis-EVs attenuated intestinal inflammation via the modulation of macrophage polarization with its targeting capability to inflamed lesions. B. infantis-EVs could emerge as an innovative and promising therapeutic option for future IBD treatment.

Exploring the efficacy of Transcutaneous Auricular Vagus nerve stimulation (taVNS) in modulating local and systemic inflammation in experimental models of colitis

BackgroundCurrent inflammatory bowel disease (IBD) treatments often fail to achieve lasting remission and have adverse effects. Vagus nerve stimulation (VNS) offers a promising therapy due to its anti-inflammatory effects. Its invasive nature, however, has led to the development of non-invasive methods like transcutaneous auricular VNS (taVNS). This study assesses taVNS’s impact on acute colitis progression, inflammatory, anti-inflammatory, and apoptosis-related markers.MethodsMale C57BL/6 mice (11–12 weeks) were used for dextran sulfate sodium (DSS)- and dinitrobenzene sulfonic acid (DNBS)-induced colitis studies. The administration of taVNS or no stimulation (anesthesia without stimulation) for 10 min per mouse began one day before colitis induction and continued daily until sacrifice. Ulcerative colitis (UC)-like colitis was induced by administering 5% DSS in drinking water for 5 days, after which the mice were sacrificed. Crohn’s disease (CD)-like colitis was induced through a single intrarectal injection of DNBS/ethanol, with the mice sacrificed after 3 days. Disease activity index (DAI), macroscopic evaluations, and histological damage were assessed. Colon, spleen, and blood samples were analyzed via qRT-PCR and ELISA. One-way or two-way ANOVA with Bonferroni and Šídák tests were applied.ResultstaVNS improved DAI, macroscopic, and histological scores in DSS colitis mice, but only partially mitigated weight loss and DAI in DNBS colitis mice. In DSS colitis, taVNS locally decreased colonic inflammation by downregulating pro-inflammatory markers (IL-1β, TNF-α, Mip1β, MMP 9, MMP 2, and Nos2) at the mRNA level and upregulating anti-inflammatory TGF-β in non-colitic conditions at both mRNA and protein levels and IL-10 mRNA levels in both non-colitic and colitic conditions. Systemically, taVNS decreased splenic TNF-α in non-colitic mice and increased serum levels of TGF-β in colitic mice and splenic levels in non-colitic and colitic mice. Effects were absent in DNBS-induced colitis. Additionally, taVNS decreased pro-apoptotic markers (Bax, Bak1, and caspase 8) in non-colitic and colitic conditions and increased the pro-survival molecule Bad in non-colitic mice.ConclusionsThis study demonstrates that taVNS has model-dependent local and systemic effects, reducing inflammation and apoptosis in UC-like colitis while offering protective benefits in non-colitic conditions. These findings encourage further research into underlying mechanisms and developing adjunct therapies for UC.

Exploring critical animal-based traits as potential predictors of production diseases in dairy cattle: a systematic review and meta-analysis

This meta-analysis comprehensively evaluates the impact of production diseases on dairy cattle, examining a variety of physiological, metabolic, and behavioral traits. From an initial set of 3 349 records, a rigorous selection process resulted in 56 relevant articles, highlighting the strict criteria employed. The low inclusion rate of 1.67% underscores the dedication to studying quality and significance. Common reasons for exclusion, such as statistical methodology and the lack of a negative control group, emphasize the necessity for robust scientific investigation. The study reveals key indicators of production diseases, such as decreased milk production, weight loss, a low body condition score, digestive disorders, lameness, and respiratory distress. These findings align with existing knowledge, emphasizing the multifaceted nature of production diseases and their broad impact on dairy cattle health. Diseased animals consistently exhibit higher parameter values, supported by confidence intervals that indicate result precision. Subgroup analyses offer nuanced insights into the specific effects of diseases and interventions on different characteristics. Metritis and Mastitis significantly affect milk production, highlighting the economic implications for dairy farmers. Interventions such as improved milking techniques show promise. Similarly, interventions involving veterinary medications and controlled energy diets effectively mitigate weight loss, a low body condition score, and digestive disorders. The analysis underscores the vulnerability of dairy cattle to reproductive issues, metabolic imbalances, and increased susceptibility to infections. Interventions addressing these challenges include hormone therapy, balanced diets, and vaccination programs. Behavioral changes and feeding habits emerge as significant indicators of dairy cattle well-being. Ovarian cysts are identified as a major contributor to behavioral changes, necessitating targeted interventions. In conclusion, this meta-analysis provides valuable contributions to the field of dairy cattle health, offering specific insights into the effects of diseases and the effectiveness of interventions. These findings inform evidence-based practices for dairy stakeholders, ultimately enhancing animal welfare and promoting sustainable dairy production. However, establishing precise reference values presents challenges, warranting further investigation.

Fuzheng Jiedu decoction alleviates H1N1 virus-induced acute lung injury in mice by suppressing the NLRP3 inflammasome activation.

Severe influenza, marked by excessive cytokine production, is a major contributor to death in hospitalized individuals. Fuzheng Jiedu decoction (FZJDD), an effective traditional Chinese herbal recipe, has demonstrated promising results in combating the COVID-19 pandemic by reducing mortality and improving Symptoms, and has exhibited anti-inflammatory properties in both clinical trials and laboratory research. Given that pneumonia is a common outcome of SARS-CoV-2 and H1N1 virus infections, we hypothesized that FZJDD may also have therapeutic effects on influenza-related pneumonia and acute lung injury (ALI). This research sought to explore the impact and underlying mechanisms of FZJDD on ALI caused by the H1N1 virus in mice. FZJDD was characterized using UHPLC-MS/MS. A mouse model infected with H1N1 virus was used to examine the therapeutic and protective benefits of FZJDD in a living organism, by monitoring body weight fluctuations, lung index, histopathological changes, lung injury scores, and survival rates. Lung tissues underwent haematoxylin-eosin staining, western blotting, qRT-PCR and plaque reduction assay. Blood serum was gathered to assess levels of IL-1β, IL-6, TNF-α through ELISA testing. The impact of FZJDD on the NLRP3 inflammasome was further evaluated in macrophages. FZJDD treatment significantly mitigated weight loss, reduced lung index, alleviated histopathological injury, and improved the survival rates in mice with H1N1 virus-induced ALI, demonstrating a protective effect against influenza virus infection. qRT-PCR and Western blot assays revealed that FZJDD treatment ameliorated the hyperinflammatory response caused by the H1N1 virus in lung tissue by suppressing NLRP3 inflammasome activation, without impacting viral replication. In vitro experiments additionally verified that FZJDD treatment can suppress the activation of the NLRP3 inflammasome triggered by the H1N1 virus. Our findings demonstrate that FZJDD treatment can mitigate ALI caused by H1N1 virus and enhance the survival rate in mice, while it doesn't lower viral titers in the lungs. FZJDD achieves these outcomes by curbing excessive inflammation and blocking the activation of NLRP3 inflammasome.

Postbiotic Effect of Escherichia coli CEC15 and Escherichia coli Nissle 1917 on a Murine Model of 5-FU-induced Intestinal Mucositis.

Probiotics are live microorganisms that, when administered in adequate amounts, can bring health benefits to the host. Most of these organisms are found naturally in the human gastrointestinal tract. Escherichia coli strains Nissle 1917 (EcN), and CEC15 have shown beneficial effects in murine models of intestinal inflammation, such as colitis and mucositis. The present study evaluated the effects as postbiotic of heat-inactivated and cell-free supernatant preparations of EcN and CEC15 in attenuating 5-fluorouracil (5-FU)-induced intestinal mucositis in mice and compared them with the probiotic effects of the live preparations. BALB/c mice were fed, by daily gavage, with 1010 CFU of live or inactivated bacteria or with 300 µL of cell-free supernatant for 12 days. On the 10th day, all animals, except for the control group, received an intraperitoneal injection of 5-FU (300mg/kg). After 72h of 5-FU administration, animals were euthanized, and the ileum and blood were collected for analysis. Treatments with live and heat-inactivated CEC15 mitigated weight loss, preserved intestinal length, reduced histological damage, maintained goblet cells, decreased neutrophil infiltration, and modulated expression of inflammatory and barrier genes when compared to 5-FU mucositis controls. EcN showed more limited effects. CEC15 upregulated mRNA expression of the mucin MUC2 and tight junction protein TJP1. CEC15 demonstrated protective effects against 5-FU-induced mucositis, whether administered with live, heat-inactivated, or cell-free supernatant. This suggests that CEC15 mediates a protective response via secreted metabolites and does not require viability. The postbiotic forms of CEC15 present advantages for use in immunocompromised patients. This study elucidates the anti-inflammatory and barrier-protective effects of CEC15 against intestinal mucositis.

4-Hexylresorcinol Enhances Glut4 Expression and Glucose Homeostasis via AMPK Activation and Histone H3 Acetylation.

This study investigates the potential of 4-hexylresorcinol (4HR) as a novel antidiabetic agent by assessing its effects on blood glucose levels, Glut4 expression, AMPK phosphorylation, and Histone H3 acetylation (Ac-H3) in the liver. In vitro experiments utilized Huh7 and HepG2 cells treated with varying concentrations of 4HR. Glut4, p-AMPK, and Ac-H3 expression levels were quantified via Western blotting. Additionally, GAPDH activity and glucose uptake were evaluated. In vivo experiments employed streptozotocin (STZ)-induced diabetic rats, with or without 4HR treatment, monitoring blood glucose, body weight, and hepatic levels of Glut4, p-AMPK, and Ac-H3. In vitro, 4HR treatment increased GAPDH activity and glucose uptake. Elevated Glut4, p-AMPK, and Ac-H3 levels were observed 8 h after 4HR administration. Inhibition of p-AMPK using compound C reduced 4HR-mediated Glut4 expression. In STZ-induced diabetic rats, 4HR significantly upregulated Glut4, p-AMPK, and Ac-H3 expression in the liver. Periodic 4HR injections mitigated weight loss and lowered blood glucose levels in STZ-injected animals. Histological analysis revealed increased glycogen storage in hepatocytes of the 4HR-treated group. Overall, 4HR enhanced Glut4 expression through upregulation of AMPK activity and histone H3 acetylation in vitro and in vivo, improving hepatic glucose homeostasis and suggesting potential as a candidate for diabetes treatment.

Hypoglycemic and intestinal microbiota-regulating effects of melanoidins in diabetic mice.

The aqueous extraction of sesame oil is a traditional process that generates a large amount of melanoidins. However, little is known about the characteristics and bioactive functions of these melanoidins. Electronic tongue, fluorescence emission spectroscopy, and Fourier transform infrared spectroscopy analyses indicated that melanoidins from sesame residues (MELs) are brown macromolecular compounds with protein skeletons and heteroaromatic ring structures, a bitter taste, and instability in strong oxidative and reductive environments. The MELs demonstrated inhibitory effects on α-glucosidase, α-amylase and pancreatic lipase in vitro. These MELs mitigated weight loss in mice with type 2 diabetes (T2DM), reduced their fasting blood glucose to 54.73% (500 mg kg-1 day-1) of the initial value, increased the glycogen levels in the liver and skeletal muscles, lowered blood lipid levels, and protected the liver. Western blot analysis revealed that MELs inhibited the activities of enzymes such as PEPCK, FBPase, and G6Pase through the IRS-1/PI3K/Akt and AMPK pathways, increased the activity of the enzymes hexokinase (HK) and pyruvate kinase (PK), enhanced liver glycolytic ability, and promoted liver glycogen synthesis, thereby reducing blood glucose levels in T2DM mice. Moreover, MELs reduced the ratio of Firmicutes to Bacteroides (F/B) in the intestines of T2DM mice, increased the relative abundance of beneficial bacteria such as Lactobacillus, Coprococcus, and Ruminococcus, and reduced the propionic acid content. Melanoidins can regulate T2DM by activating the IRS-1/PI3K/Akt and AMPK-signaling pathways and ameliorating gut microbiota imbalances in T2DM mice. © 2024 Society of Chemical Industry.

Influenza A virus-induced glycolysis facilitates virus replication by activating ROS/HIF-1α pathway

As a highly contagious acute respiratory disease, influenza A virus (A/WSN/1933) poses a huge threat to human health and public health. influenza A virus proliferation relies on glucose metabolism in host cells, yet the effects of influenza A virus on glucose metabolism and the underlying molecular mechanisms remain unclear. Here, we created models of WSN virus-infected mice and A549 cells, along with analyzing metabolomics and transcriptomics data, to investigate how WSN virus infection affects host cell glucose metabolism and specific mechanisms. Analysis of metabolites and gene expression showed that WSN virus infection triggers glycolysis in A549 cells, with notable upregulation of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), hypoxia-inducible factor-1 alpha (HIF-1α), and elevated lactate levels. Additionally, it leads to mitochondrial impairment and heightened reactive oxygen species (ROS) generation. Elevated levels of glucose may enhance the replication of WSN virus, whereas inhibitors of glycolysis can reduce it. Enhancement of HIF-1α activation facilitated replication of WSN virus through stimulation of lactate synthesis, with the primary influence of glycolysis on WSN virus replication being mediated by ROS/HIF-1α signaling. Mice given HIF-1α inhibitor PTX-478 or glycolysis inhibitor 2-Deoxyglucose (2-DG) exhibited reduced lactate levels and decreased WSN virus replication, along with mitigated weight loss and lung damage. In summary, WSN virus-induced glycolysis has been demonstrated to enhance virus replication through the activation of the ROS/HIF-1α pathway, suggesting potential new targets for combating the virus.

Development of interleukin-27 recombinant Lactococcus lactis and its efficacy in treating psoriasis and colitis in mice

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD.

Neurohistopathological Alterations Induced by Clitoria Ternatea and Emblica Officinalis Extracts in Diabetic Male Wistar Rats.

Background Diabetes mellitus is a chronic condition that can lead to significant neurodegenerative complications. The extracts of traditional medicinal plants such as Clitoria ternatea and Emblica officinalis have neuroprotective properties. This study investigates the neurohistopathological alterations in diabetic male Wistar rats treated with these extracts. Objective This study aimed to assess the neuroprotective potential of Clitoria ternatea and Emblica officinalis extracts in mitigating neurohistopathological alterations in streptozotocin-induced diabetic male Wistar rats Methods In this experimental investigation, 48 male Wistar rats, aged 8-12 weeks and weighing 200-250g, were randomly allocated into eight groups (n=6): control, diabetic model, metformin treatment, Clitoria ternatea extract treatment, Emblica officinalis extract treatment, diabetic model + Clitoria ternatea extract treatment, diabetic model + Emblica officinalis extract treatment, and diabetic model + combined extract treatment.Streptozotocin 40 mg/kg was used to induce diabetes. Treatments included 100 mg/kg metformin, 300 mg/kg Clitoria ternatea extract, and 250 mg/kg Emblica officinalis extract. After three weeks, blood glucose levels, body weight, and neurohistopathological parameters (neuronal degeneration, gliosis, and vacuolation) were evaluated. Results The diabetic rats had much higher blood sugar levels (320.4 ± 15.3 mg/dL) and lost a lot of weight (180.7 ± 9.5 g) compared to the control group, which had normal blood sugar levels (92.3 ± 4.8 mg/dL) and stable body weight (225.4 ± 12.1 g) (p < 0.001). Treatment with Clitoria ternatea extract reduced blood glucose to 160.3 ± 12.1 mg/dL, while Emblica officinalis extract lowered it to 155.4 ± 11.8 mg/dL. The combined treatment brought glucose levels closer to normal (110.5 ± 8.9 mg/dL). Similarly, both extracts mitigated weight loss, with the combined treatment maintaining body weight at 220.4 ± 12.0 g, close to the control group (p < 0.05). The study of diabetic rats that had not been treated showed severe neuronal degeneration (4.2±0.4), gliosis (4.5±0.5), and vacuolation (4.7±0.5). Treatment groups showed marked reductions in these parameters, with the combined treatment producing the greatest neuroprotective effects, comparable to controls (p < 0.001). Conclusions Extracts from Clitoria ternatea and Emblica officinalis, particularly when combined, provide significant neuroprotective advantages in male Wistar diabetic rats, significantly lowering hyperglycemia and related neurohistopathological changes. These findings support the potential use of these extracts as complementary or alternative therapies in managing diabetic complications.

Development and preservative applications of polysaccharide-based bilayer packaging films: Enhanced functional properties through metal-phenolic network-coated zein nanoparticles and biomimetic hydrophobic surfaces

This study develops an innovative bilayer biomimetic hydrophobic film, tailored to provide a sustainable and eco-friendly packaging solution for fresh produce. The outer layer, crafted from chitosan, utilized polydimethylsiloxane templating to mimic the ultra-hydrophobic surface of a lotus leaf, achieving a water contact angle exceeding 130°. The inner layer comprised sodium alginate and zein nanoparticles, enriched with citral and fortified by a metal-phenolic network to facilitate uniform dispersion and controlled release of bioactive agents. The structural design of the film significantly improved mechanical properties, evidenced by a maximum tensile strength of 29.3 ± 3.6 MPa, and enhanced hydrophobicity, reducing water solubility to 28.3 ± 1.5% and substantially decreasing water absorption. The barrier functionality of film was also strengthened, demonstrated by a lowered water vapor transmission rate of 289.3 ± 1.5 g m−2 24 h−1, and it supported extended citral release in acidic media up to 70 h. Moreover, the film exhibited robust antioxidant and antibacterial properties. In practical tests, it effectively mitigated weight loss, browning, and hardness degradation in fresh-cut apples and lotus roots, concurrently inhibiting microbial growth and extending shelf life. This study presents an effective strategy for enhancing the hydrophobicity and bioactivity of bio-based films, contributing valuable insights to the field of sustainable food packaging.

The Role of Oral Nutritional Supplements in Head and Neck Cancer Patients Undergoing Chemoradiotherapy.

This study aimed to assess the impact of oral nutritional supplements (ONS) on nutritional intake, body weight, and body composition in head and neck cancer (HNC) patients undergoing chemoradiotherapy. The study evaluated whether ONS could prevent treatment-related nutritional deterioration. This prospective observational pilot study included 30 HNC patients randomized into two groups: ONS (n = 15) and No ONS (n = 15). All participants underwent chemoradiotherapy, with the ONS group receiving 200 mL of a high-calorie, high-protein supplement twice daily. Nutritional status, including body weight, BMI, fat mass, fat-free mass, and bone mass, was assessed at three time points: baseline, mid-treatment, and end of treatment. Data were analyzed using the Mann-Whitney U test, with a p-value of ≤0.05 considered statistically significant. At baseline, there were no significant differences between the two groups in body weight, BMI, or body composition. By the end of radiotherapy, the No ONS group showed significant reductions in body weight (p < 0.001), BMI (p < 0.001), fat mass (p < 0.001), and fat-free mass (p < 0.001), while the ONS group maintained more stable nutritional parameters. Acute radiotherapy toxicities, including nausea, dysphagia, and oral mucositis, were not significantly different between the two groups. ONS effectively mitigates weight loss and preserves body composition in HNC patients undergoing chemoradiotherapy. While no significant reduction in radiation-induced toxicities was observed, the nutritional benefits of ONS support its use in preventing malnutrition in this patient population. Larger studies are needed to further validate these findings.

Glycosylation of chrysin with β-d-glucose tetraacetate (LQFM280) enhances its in vitro and in vivo neuroprotective effects against the toxicity induced by 3-nitropropionic acid.

Chrysin (CHR) is a naturally occurring flavonoid found in the human diet, recognized for its potential in preventing neurodegenerative diseases. However, its limited water solubility restricts its bioavailability and therapeutic applications. To address this issue and bolster the neuroprotective properties of CHR for potential nutraceutical or medicinal use, we investigated a novel compound, LQFM280, formed by conjugating CHR with β-d-glucose tetraacetate. We conducted both in vitro (using SH-SY5Y cells, mutant STHdhQ111/Q111 cells, and wild-type STHdhQ7/Q7 cells), and in vivo (mice) neurotoxicity experimental model induced by 3-nitropropionic acid, which mimic biological changes akin to Huntington's disease in humans. Compared to non-glycosylated CHR, LQFM280 showed superior in vitro effects in preventing neurotoxicity caused by increased mitochondrial vulnerability due to mutant huntingtin. In vivo findings demonstrated that LQFM280 has heightened efficacy in mitigating weight loss, memory and locomotor impairment, oxidative stress, and disruptions in the antioxidant defense system, as well as succinate dehydrogenase, and cholinesterase activities induced by 3-nitropropionic acid. These findings underscore the significant enhancement of chrysin's neuroprotective effects through glycosylation with β-d-glucose tetraacetate, positioning it as a promising candidate for use as a nutraceutical or food supplement to promote health benefits.

Oleanolic acid 28-O-β-D-glucopyranoside: A novel therapeutic agent against ulcerative colitis via anti-inflammatory, barrier-preservation, and gut microbiota-modulation

Ulcerative colitis (UC), an incurable and recurrent inflammatory bowel disease, presents a significant threat to health and highlights the need for novel therapeutic strategies. Oleanolic acid 28-O-β-D-glucopyranoside (OAG) is a naturally occurring pentacyclic triterpenoid found in ginseng. In this study, we demonstrated that OAG exhibited remarkable anti-UC activity in LPS-induced Caco-2 cells and DSS-induced model mice. First, OAG alleviated the symptoms of UC by mitigating weight loss, reducing the DAI score, and increasing colon length. Second, the inflammatory response was inhibited after OAG intervention, evidenced decreases in the spleen coefficient, cytokine levels, and inflammatory cell infiltration in colon tissue. Thirdly, OAG also enhanced intestinal epithelial barrier function, as evidenced by elevated TEER values, increased expression of tight junction proteins, diminished bacterial translocation, and maintained intact ultrastructure of colonic mucosal cells. Notably, compared with 5-aminosalicylic acid, OAG demonstrated superior efficacy in enhancing mucosal barrier function. Fourth, OAG increased microbial diversity, promoted the abundance of beneficial bacteria, reduced the abundance of harmful bacteria, and rebalanced the gut microbiome. Finally, the PI3K-AKT and MAPK signaling pathways were identified as crucial mechanisms underlying the therapeutic effects of OAG against UC through multi-omics. In summary, we identified OAG as a novel therapeutic agent against UC, demonstrating anti-inflammatory, barrier-preserving, and gut microbiota-modulating effects, highlighting its promising potential as a candidate UC drug.

Tea polyphenols coating improves physiological properties, microstructure and chemical composition of cuticle to suppress quality deterioration of passion fruit during cold storage

The plant cuticle plays a crucial role in modulating postharvest quality and extending shelf life of horticultural crops. Passion fruit often suffers from quality degradation primarily due to peel wrinkling after harvest. Tea polyphenols (TPs) hold potential for enhancing postharvest preservation. However, the specific effects of TPs coating on preservation of passion fruit, as well as the underlying mechanisms involving cuticle regulation, have not been thoroughly investigated. This study demonstrated that treating ‘Qinmi no.9’ passion fruit with TPs at a concentration of 0.1 g L−1 significantly mitigates weight loss, maintains firmness, and reduces cell membrane permeability during storage at 10 °C. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that TPs treatment notably enhances cuticle thickness and structural integrity. Furthermore, gas chromatography–mass spectrometry (GC–MS) and metabolomics analyses indicated that TPs treatment obviously promotes the accumulation of palmitic acid, stearic acid, and their derivatives—primarily 12-Octadecenoic acid and 10(E)-Octadecenoic acid—as well as increases the levels of 11-Octadecenoic acid, primary alcohols such as 1-Eicosanol, and long-chain alkanes (including C31 and C32 alkanes) in the fruit peel cuticle. These biochemical changes contribute to the quality maintenance of passion fruit during cold storage. The findings suggest that TPs treatment is a promising biological strategy for extending shelf life and mitigating quality degradation by regulating cuticle metabolism in postharvest passion fruit.

The impact of oncology nutrition services on weight change among patients with head and neck or pancreatic cancers.

86 Background: Weight loss is prevalent among cancer patients and correlates with lower health-related quality of life and overall survival rates. Individuals diagnosed with head and neck (HN) and pancreatic cancers face a heightened risk of weight loss due to tumor location and treatment-related side effects. Although guidelines advocate early interventions such as referral to a dietitian for tailored nutritional support, the precise impact of oncology nutrition services (ONS) on weight loss remains unclear. In this study, we investigated the longitudinal association between weight change and ONS among patients diagnosed with HN or pancreatic cancers. Methods: A retrospective chart review was conducted for patients diagnosed with HN or pancreatic cancers visited between January 2019 and December 2023. Inclusion criteria encompassed patients who had weight measurements taken within 30 days of their cancer diagnosis. Patient demographics, clinical characteristics, all recorded body weights, and receipt of ONS were extracted from electronic health records. Weight change (%) from the baseline was calculated at each measurement by subtracting the initial weight value. A mixed-effects model was employed to evaluate the impact of ONS on weight change, with time to weight measurement and ONS serving as interaction terms, after adjusting for demographics and clinical characteristics. Results: A cohort of 1305 patients was identified, predominantly comprising males (n=1014, 63%) and individuals of White race (n=1358, 85%), with a diverse ethnic distribution (Hispanic: n=620, 39%). Of these patients, 947 (73%) received ONS at any point following cancer diagnosis. Significant weight loss over time was noted among all patients (-0.53% per 6 months, p&lt;0.001). Baseline weight, sex, ethnicity, receipt of percutaneous endoscopic gastrostomy, total parenteral nutrition, radiation, chemotherapy, and ONS were significantly associated with weight loss. Following adjustment for the covariates, patients receiving ONS showed significantly less weight loss compared to those without ONS (-0.06% [95% confidence interval (CI): -0.10, -0.03] vs. -0.04% [95% CI: -0.38, -0.23] per 6 months, p&lt;0.001). Conclusions: The findings indicate that ONS plays a significant role in attenuating weight loss among patients diagnosed with HN or pancreatic cancer, irrespective of baseline demographics or clinical status. While the magnitude of weight change may appear modest, its implications are substantial long term. Early referrals to ONS should be recommended for HN or pancreatic cancer patients to mitigate weight loss.

Isatidis Folium Represses Dextran Sulfate Sodium-Induced Colitis and Suppresses the Inflammatory Response by Inhibiting Inflammasome Activation

Background/Objectives: Isatidis Folium (IF) has been used in traditional medicine for various ailments, and recent research highlights its anti-inflammatory, antiviral, and detoxifying properties. This study investigated the anti-inflammatory effects of a hydroethanolic extract of IF (EIF) on inflammasomes and colitis. Methods: Dextran sulfate sodium (DSS)-induced colitis model C57BL/6 mice were treated with DSS, mesalamine, or EIF (200 mg/kg). Parameters such as daily disease activity index (DAI), spleen weight, colon length, and histopathology were evaluated. Intestinal fibrosis, mucin, and tight junction proteins were assessed using Masson’s trichrome, periodic acid–Schiff, and immunohistochemistry staining. RAW264.7 and J774a.1 macrophages were treated with EIF and lipopolysaccharide, with cell viability assessed via the cell counting kit-8 assay, nitric oxide (NO) production with Griess reagent, and cytokine levels with the enzyme-linked immunosorbent assay. NF-κB inhibition was analyzed using the luciferase assay, and phytochemical analysis was performed using UPLC-MS/MS. Results: EIF mitigated weight loss, reduced DAI scores, prevented colon shortening, and attenuated mucosal damage, fibrosis, and goblet cell loss while enhancing the tight junction protein occludin. The anti-inflammatory effects of EIF in RAW264.7 cells included reduced NO production, pro-inflammatory cytokines, and NF-κB activity, along with inhibition of NLRP3 inflammasome responses in J774a.1 cells. The key constituents identified were tryptanthrin, indigo, and indirubin. Conclusions: Animal studies demonstrated the efficacy of EIF in alleviating colitis, suggesting its potential for treating inflammatory diseases.

FGF20 modulates gut microbiota to mitigate dextran sodium sulfate-induced ulcerative colitis in mouse models

Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), presents a significant clinical challenge due to the lack of optimal therapeutic strategies. Emerging evidence suggests that fibroblast growth factor 20 (FGF20) may play a crucial role in mitigating UC symptoms, though the mechanistic underpinnings remain elusive. In this study, a mouse model of UC was established using dextran sodium sulfate (DSS) to investigate the potential role of FGF20. Our findings revealed a marked reduction in FGF20 expression in the serum and colonic tissues of DSS-treated mice. Furthermore, FGF20 knockout did not exacerbate colonic damage in these mice. Conversely, overexpression of FGF20 via adeno-associated virus (AAV) significantly alleviated UC-associated symptoms. This alleviation was evidenced by attenuated intestinal shortening, mitigated weight loss, increased colonic goblet cell density and crypt formation, reduced inflammation severity and inflammatory cell infiltration, and enhanced expression of tight junction and mucin proteins. Moreover, FGF20 significantly ameliorated the dysbiosis of gut microbiota in DSS-treated mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. The beneficial effects of FGF20 were notably attenuated following gut microbiota depletion with an antibiotic regimen. Fecal microbiota transplantation experiments further supported the critical role of gut microbiota in mediating the effects of FGF20 on DSS-treated mice. In conclusion, these findings highlight the potential involvement of gut microbiota in the therapeutic effects of FGF20 in UC.

Mechanism of Takifugu bimaculatus Skin Peptides in Alleviating Hyperglycemia in Rats with Type 2 Diabetic Mellitus Based on Microbiome and Metabolome Analyses.

In this study, we aimed to explore the hypoglycemic effects of a hydrolysate on Takifugu bimaculatus skin (TBSH). The effect of the dipeptidyl peptidase-IV (DPP-IV) inhibitory activities from different TBSH fractions was investigated on basic indexes, gut hormones, blood lipid indexes, viscera, and the gut microbiota and its metabolites in rats with type 2 diabetes mellitus (T2DM). The results showed that the <1 kDa peptide fraction from TBSH (TBP) exhibited a more potent DPP-IV inhibitory effect (IC50 = 0.45 ± 0.01 mg/mL). T2DM rats were induced with streptozocin, followed by the administration of TBP. The 200 mg/kg TBP mitigated weight loss, lowered fasting blood glucose levels, and increased insulin secretion by 20.47%, 25.23%, and 34.55%, respectively, rectified irregular hormonal fluctuations, lipid metabolism, and tissue injuries, and effectively remedied gut microbiota imbalance. In conclusion, TBP exerts a hypoglycemic effect in rats with T2DM. This study offers the potential to develop nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus. It will provide information for developing nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus.