Search Results (1,851)

Background/Objectives: Innovative intranasal delivery systems have emerged as a strategy to overcome the limitations of conventional COVID-19 vaccines, including suboptimal mucosal immunity, limited antigen retention, and vaccine hesitancy. This study aimed to evaluate physicochemical properties and murine safety of a novel COVID-19 intranasal vaccine candidate based on CHIVAX 2.1 (CVX)-loaded chitosan nanoparticles (CNPs). Methods: The CVX recombinant protein was encapsulated into CNPs using the ionic gelation method. The nanoparticles were characterized by their physicochemical properties (mean size, zeta potential, morphology, and encapsulation efficiency) and spectroscopic profiles. Mucin adsorption and in vitro release profiles in simulated nasal fluid were also assessed. In vivo compatibility was evaluated through histopathological analysis of tissues in male C-57BL/6J mice following intranasal administration. Results: CNPs exhibited controlled size distribution (38.5–542.5 nm) and high encapsulation efficiency (65.4–92.2%). Zeta potential values supported colloidal stability. TEM analysis confirmed spherical morphology and successful CVX encapsulation, and immunogenic integrity was also demonstrated. Mucin adsorption analysis demonstrated effective nasal retention, particularly in particles ≈90 nm. In vitro release studies revealed a biphasic protein profile, where ≈80% of the recombinant protein was released within 2 h. Importantly, histopathological analyses and weight monitoring of intranasally immunized mice revealed no signs of adverse effects related to toxicity. Conclusions: The ionic gelation encapsulation process preserved the physical and immunological integrity of CVX antigen. Furthermore, the intranasal administration of the CVX-loaded CNPs demonstrated a favorable safety profile in vivo. These findings support the potential of the CVX intranasal vaccine formulation for further immunogenicity studies, with no apparent biosafety concerns. Full article

Objective: Hexafluoropropylene oxide dimer acid (HFPO-DA), also known as GenX, is widely used globally, raising concerns about its safety and public health implications. However, its toxicity mechanism remains unclear. The purpose of this study was to develop a reliable method for detecting HFPO-DA in mice and to investigate its absorption, distribution, and impact on hepatic lipid metabolism. Method: HFPO-DA levels were measured in the serum and eight tissues of C57BL/6J mice after oral administration using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Lipid metabolites in the liver were also detected and analyzed. Results: HFPO-DA was rapidly absorbed into the bloodstream and widely distributed throughout all tested tissues. It penetrated the blood–brain barrier, with the highest concentration in the liver; however, long-term effects on the lungs also warrant attention. HFPO-DA disrupted liver lipid metabolism, leading to acylcarnitine accumulation while lowering triglycerides and cholesterol. Conclusion: This study on the pharmacokinetics and tissue distribution of HFPO-DA in mice following oral exposure revealed that HFPO-DA exacerbates liver injury by altering hepatic lipid metabolism. These findings provide theoretical support for toxicological studies on the emerging environmental pollutant HFPO-DA. Full article

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus, Romboutsia, and Enterobacter. Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC. Full article

Background/Objectives: The prevalence of obesity globally has increased steadily in the past decades. Obesity, sarcopenic obesity (SO) and nonalcoholic fatty liver disease (NAFLD) commonly coexist. Ursolic acid (UA), a natural pentacyclic triterpenoid, has demonstrated potential anti-obesity properties. This study was designed to evaluate the anti-obesity efficacy of UA in a mouse model of high-fat diet (HFD)-induced obesity, with a particular focus on its impact on muscle function and NAFLD. Methods: Male C57BL/6J mice (6 weeks old) were randomly assigned to three groups (n = 20 per group): a control group (CON) fed a normal chow diet, a high-fat diet group (HFD), and a UA treatment group (UA). The HFD and UA groups received a high-fat diet for 10 weeks to induce obesity. Thereafter, mice in the UA group were administered UA orally once daily for 6 weeks. Results: In HFD-induced obese mice, UA administration significantly reduced body weight (BW), abdominal fat weight and liver weight; improved grip strength and muscle weight; and enhanced lipid profiles, including triglycerides, total cholesterol, low-density lipoprotein cholesterol and free fatty acid levels in serum. UA also improved histological changes in the liver and abdominal adipose tissues, regulated serum GH, IGF-1, T3, T4 and leptin levels and downregulated the inflammation-associated gene expression of TNF-α and IL-1β in abdominal adipose tissue. Conclusions: UA could enhance muscle strength, improve lipid metabolism and hepatic steatosis and might be considered a potential therapeutic agent for managing obesity and related metabolic diseases. Full article

Cranberry juice (CJ), a natural source of anthocyanins, may provide additional health benefits when enriched, as anthocyanins have been shown to influence gut microbiota composition. This study investigated the effects of varying anthocyanin and mineral concentrations in CJ on gut microbiota in mice. Using electrodialysis with filtration membranes (EDFM), five CJ samples with different anthocyanin/mineral enrichment levels (0/0, −31/−85%, −19/−70%, 26/−32%, and 44/−60%) were produced and administered to C57BL/6J mice for four weeks. Gut microbiota composition was analyzed via 16S rRNA sequencing, and inflammation was determined in macroscopic observations of intestinal tissues. While α and β diversity remained unchanged, differential abundance analysis revealed that gut microbiota changes were influenced by anthocyanin and mineral concentrations. Synergistic trends were observed for Colidextribacter and Oscillibacter (increasing with both compounds) and for Turicibacter, Romboutsia, Enterorhabdus, and Bifidobacterium (decreasing with both compounds). Antagonistic trends emerged for Dubosiella, Acetatifactor, A2, Ruminococcus, and Intestinimonas (decreasing with anthocyanins and increasing with minerals), and the reverse was found for Ligilactobacillus. The most significant microbiota shifts occurred with the −31/−85% CJ, suggesting a strong effect of its low anthocyanin and mineral content. But further analysis is needed to assess their metabolic effects and impact on intestinal health. Full article

Background/Objectives: Aging and metabolic disorders are associated with a decline in muscle function, referred to as age-related sarcopenia. The underlying mechanisms of sarcopenia include cellular senescence, imbalanced protein homeostasis, accumulation of oxidative and inflammatory stressors, and mitochondrial dysfunction. Probiotic supplementation improves the gut microbiome and enhances muscle function via the gut–muscle axis. However, details of molecular mechanisms and the development of an appropriate treatment are under active investigation. Methods: We have examined the effects of Lactiplantibacillus plantarum LM1001, a probiotic that reportedly improves the digestibility of branched-chain amino acids in myocyte cultures, but exactly how it contributes to muscle structure and function remains unclear. Results: We show that aged mice (male C57BL6/J) fed a high-fat diet (HFD) exhibit weak muscle strength, as reflected by a reduction in grip strength. LM1001 supplementation increases muscle strength and restores myofibril size, which has been altered by HFD in aged mice. Expression of myogenic proteins is increased, while protein markers for muscle atrophy are downregulated by LM1001 treatment via the IGF-1/Akt/FoxO3a pathway. LM1001 improves gut microbiota that are altered in aged HFD-fed mice, by increasing their abundance in beneficial bacteria, and efficiently maintains the epithelial lining integrity of the large intestine. Conclusions: We conclude that LM1001 supplementation serves a beneficial role in patients suffering from sarcopenia and metabolic disorders, improving their muscle function, gut microbiota, and intestinal integrity. Full article

Erebosis is a newly described form of cell death but has been reported only in the gut enterocytes of Drosophila, a group of fast turnover cells. Angiotensin-converting enzyme 2 (ACE2) accumulation in cells is a biomarker for erebotic cells. Brain cell loss is a characteristic of patients with Alzheimer’s disease (AD), the leading neurodegenerative disease. The objectives of this study are to determine whether there is erebosis in the mammalian brain. Here we show that there is more ACE2 staining in the hippocampus of old wild-type (C57BL/6J) male mice, female mice with AD neuropathology (3xTg-AD mice), and human AD sufferers. Some ACE2 positive cells have fragmented or small nuclei, lose NeuN staining and are positive for TUNEL staining, indicators for cell injury/dying. ACE2 positive cells are neurons in the hippocampus and are often positive for phospho-tau in the mice with AD neuropathology. Phospho-tau injected into the hippocampus of wild-type young adult mice increases its ACE2 expression. Some ACE2 staining is extracellular. Our results suggest that erebosis may exist in the mammalian brain and may be increased with aging and AD neuropathology. This form of death may occur in the long-lasting cells like neurons and can be activated by phospho-tau in the brain. Our findings highlight the therapeutic potential of regulating erebosis for attenuating brain aging and AD neuropathology. Full article

Background: Glutamate transporter 1 (GLT-1) plays a vital role in maintaining glutamate homeostasis in the body. A decreased GLT-1 expression in astrocytes can heighten neuronal sensitivity to glutamate excitotoxicity after traumatic brain injury (TBI). Despite its significance, the mechanisms behind the reduced expression of GLT-1 following TBI remain poorly understood. After TBI, the endocannabinoid 2-arachidonoyl glycerol (2-AG) is elevated several times. 2-AG is known to inhibit key positive transcriptional regulators of GLT-1. This study aims to investigate the role of 2-AG in regulating GLT-1 expression and to uncover the underlying mechanisms involved. Methods: A controlled cortical impact (CCI) model was used to establish a TBI model in C57BL/6J mice. The CB1 receptor antagonist (referred to as AM281) and the monoacylglycerol lipase (MAGL) inhibitor (referred to as JZL184) were administered to investigate the role and mechanism of 2-AG in regulating GLT-1 expression following TBI. Behavioral tests were conducted to assess neurological functions, including the open field, Y-maze, and novel object recognition tests. Apoptotic cells were identified using the TUNEL assay, while Western blot analysis and immunofluorescence were employed to determine protein expression levels. Results: The expression of GLT-1 in the contused cortex and hippocampus following TBI showed an initial decrease, followed by a gradual recovery. It began to decrease within half an hour, reached its lowest level at 2 h, and then gradually increased, returning to normal levels by 7 days. The administration of AM281 alleviated neuronal death, improved cognitive function, and reversed the reduction of GLT-1 caused by TBI in vivo. Furthermore, 2-AG decreased GLT-1 expression in astrocytes through the CB1-CREB signaling pathway. Mechanistically, 2-AG activated CB1, which inhibited CREB phosphorylation in astrocytes. This decreased GLT-1 levels and ultimately increased neuronal sensitivity to glutamate excitotoxicity. Conclusions: Our research demonstrated that the upregulation of GLT-1 expression effectively mitigated neuronal apoptosis and cognitive dysfunction by inhibiting the CB1-CREB signaling pathway. This finding may offer a promising therapeutic strategy for TBI. Full article

Background/Objectives: Aging is characterized by progressive physiological and metabolic decline. Aerobic exercise mitigates age-related impairments, and nicotinamide mononucleotide (NMN), a precursor in the NAD⁺ salvage pathway, has emerged as a nutritional intervention to promote healthy aging. This study investigated whether NMN supplementation combined with aerobic exercise provides synergistic benefits on physical performance and metabolic regulation in aged mice. Methods: Forty male C57BL/6J mice, including eight young (8 weeks) and thirty-two aged (85 weeks) mice, were randomly assigned to five groups: young sedentary (YS), aged sedentary (AS), aged with exercise (AE), aged with NMN (ASNMN; 300 mg/kg/day), and aged with combined NMN and exercise (AENMN). Interventions lasted six weeks. Assessments included grip strength, muscle endurance, aerobic capacity, oral glucose tolerance test (OGTT), and indirect calorimetry, followed by biochemical and molecular analyses of NAMPT and SirT1 expression. Results: The AENMN group demonstrated significant improvements in maximal strength and aerobic endurance compared with the AS group (p < 0.05). Both NMN and exercise interventions increased blood NAMPT concentrations, with the highest levels observed in the AENMN group (p < 0.05). SirT1 expression was elevated in the ASNMN and AENMN groups relative to YS (p < 0.05). Glucose tolerance improved in the ASNMN and AENMN groups (p < 0.05). Enhanced energy metabolism in the AENMN group was indicated by increased oxygen consumption, elevated energy expenditure, and reduced respiratory quotient. Conclusions: NMN supplementation, particularly when combined with aerobic exercise, effectively improved aerobic performance, glucose regulation, and systemic energy metabolism in aged mice. These findings suggest that NMN, in synergy with exercise, may serve as a promising nutritional strategy to counteract age-associated metabolic and functional decline. Full article

Background/Objectives: The consumption of highly palatable ultra-processed foods (UPFs), enriched in sugar, saturated fat, and salt, increases the risk of morbidity and mortality by inducing obesity, type 2 diabetes (T2DM), cardiovascular disease, and cancer. The present study aimed to investigate the impact of a UPF-rich diet on adiposity, feeding behavior, glucose homeostasis, intestinal barrier markers, expression of inflammatory cytokines, and microbiota in male and female C57BL/6J mice. Methods: Animals received a chow diet or a UPF diet for 10 (UPF10) or 30 days (UPF30). UPF10 induced greater calorie intake as early as 10 days on a UPF diet. Fat accumulation occurs in both sexes, specifically after 30 days of exposure. Results: The duration of UPF exposure significantly influenced glucose metabolism and insulin sensitivity. A 10-day UPF diet was associated with lower fasting blood glucose levels, without higher insulin levels, in both sexes. Females showed early impairment in glucose tolerance. Male mice on UPF30 exhibited elevated systemic IL-6 levels, as well as reduced intestinal expression of Occludin and E-cadherin genes. In females, UPF30 increased TNF-α expression in the gut and increased microbial diversity. Both sexes displayed dysbiosis, with females showing pronounced changes in the proportion between predominant phyla, and males showing more specific changes in bacterial genera. Conclusions: A diet high in UPFs promoted metabolic, inflammatory, and gut microbiota alterations, with effects varying according to exposure duration and biological context, and becoming more pronounced after 30 days. Full article

Background/Objectives: Infant diarrhea is a major global cause of morbidity and mortality. While Bifidobacterium is linked to diarrhea, its preventive effects, underlying mechanisms, and potential synergistic benefits with prebiotics remain unclear. The objective of this study was to explore the efficacy of a synbiotic composed of Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and 2′-fucosyllactose (2′-FL) in alleviating infant diarrhea. Methods: One-week-old C57BL/6J mice were used to construct a model of infant diarrhea via infection with enteropathogenic Escherichia coli (EPEC) O127. Mice were administered BB-12 (10⁸ CFU per mouse), 2′-FL (1 g/kg), or their combination (synbiotic) for three consecutive weeks. Results: Administration of the synbiotic not only markedly improved diarrhea, anxiety-like behavior, colon inflammation, and gut barrier function but also positively reshaped the microbial community. This was achieved through a significant rise in short-chain fatty acid (SCFA)-producing bacteria (e.g., Akkermansia and Paraprevotella), a rise in fecal SCFAs, and a reduction in harmful bacteria such as Escherichia. Conclusions: The synbiotic effectively relieves EPEC-induced infant diarrhea by regulating gut microbiota composition and metabolic functions. These findings highlight its potential as a dietary intervention in infant diarrhea and provide new insights into infant health applications. Full article

This study was designed to first investigate the effects of zinc phytate (ZnPA) from wheat bran in alleviating high-fat diet (HFD)-induced hepatic inflammation and metabolic disorders and its underlying mechanism. C57BL/6J mice were randomly assigned to five groups including normal diet (ND), HFD, HFD+low-dose ZnPA (100 mg/kg), HFD+high-dose ZnPA (200 mg/kg), and HFD+wheat bran (100 mg/kg). All interventions were administered orally for 12 weeks. The results indicated that ZnPA significantly mitigated HFD-induced weight gain, dyslipidemia, pathoglycemia, hepatic steatosis and inflammation (p < 0.05). ZnPA effectively corrected HFD-induced microbial dysbiosis, in which the relative abundance of the Ruminococcus torques group decreased from 11.0% to 0.75%, and Coriobacteriaceae_UCG-002 dropped from 2.47% to 0.087% (p < 0.05). Conversely, ZnPA increased the abundance of Ileibacterium from 0.32% to 17.76% and Dubosiella from 1.03% to 4.24% (p < 0.05). Meanwhile, ZnPA could be metabolized by the gut microbiota to release IP6, which was further converted into secondary inositol phosphates (InsP_3–5), resulting in increases of 52.1%, 83.3%, 62.5%, and 96.2% in the colonic contents of InsP₆, InsP₅, InsP₄, and InsP₃ (p < 0.05), respectively. In addition, ZnPA increased levels of secondary bile acids and short-chain fatty acids, especially deoxycholic acid and taurocholic acid, which were elevated by 1.95-fold and 1.88-fold (p < 0.05), respectively. Interestingly, ZnPA enhanced hepatic expressions of histone deacetylase 3, bile acid receptor FXR, and lipid metabolism coactivator PGC-1α (p < 0.05). Collectively, these results indicated that ZnPA might alleviate obesity-related hepatic inflammation and metabolic disorders by reshaping microbial composition and increasing the production of microbial metabolism such as secondary bile acids, thereby triggering FXR–PGC1α axis activation. Full article

Background/Objectives: Diabetic nephropathy (DN) is a major complication of diabetes and a leading cause of end-stage renal disease, a condition associated with high mortality risks. Recently, supplementation with probiotics and postbiotics has been attracting attention. Especially, metabolites of natural products bioconverted by beneficial bacteria have emerged as a novel therapeutic intervention for metabolic diseases, including diabetes, due to the enhanced bioavailability of their metabolites. This study investigated the alleviating effects of metabolites derived from guava leaf extract bioconverted by Limosilactobacillus fermentum (GBL) on renal inflammation in type 2 diabetic mice. Methods: For this purpose, diabetes was induced in male C57BL/6J mice by a high-fat diet and streptozotocin injection (80 mg/kg BW) twice. Subsequently, mice with fasting blood glucose levels higher than 300 mg/dL were administered metabolites of L. fermentum (LF) (50 mg/kg BW/day) or guava leaf extract bioconverted by L. fermentum (GBL) (50 mg/kg BW/day) by oral gavage for 15 weeks. Results: GBL demonstrated potential in alleviating hyperglycemia-induced DN in diabetic mice. It markedly improved hyperglycemia, glucose tolerance, and morphological alterations, which might stem from activation of key regulators of energy metabolism. GBL uniquely reduced advanced glycation end products (AGEs) and suppressed nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-driven inflammatory pathways, which significantly alleviated oxidative stress and apoptosis. Conclusions: This highlights the distinct therapeutic efficacy of GBL in addressing DN, primarily through its effects on renal inflammation. Taken together, GBL can be used as a promising nutraceutical to mitigate hyperglycemia and its associated renal inflammation, thereby alleviating the progression of DN. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent and progressive liver disorder linked to metabolic syndrome affecting over 30% of global population, currently lacking effective pharmacological treatment. Natural compounds like quercetin, silibinin, and crocetin have shown hepatoprotective potential. This study investigates their therapeutic effect in a high-fat diet (HFD)-induced mouse model of MASLD. Methods: Ninety-five C57BL/6J (wild type) mice were fed an HFD for 12 weeks to induce hepatic steatosis and were then randomized into eight groups for a 4-week therapeutic intervention. Liver histopathology was assessed using the NAFLD Activity Score (NAS), and immunohistochemistry was conducted to quantify CD36 and PLIN3 expressions. Results: Both quercetin groups significantly reduced the prevalence of steatohepatitis (p-value < 0.05) and showed an increased PLIN3 expression. Silibinin also improved steatohepatitis, with the high-dose group reaching statistical significance (p-value 0.020), and demonstrated upregulation of PLIN3 along with significant CD36 downregulation. Crocetin groups markedly improved disease severity and showed the highest PLIN3 expression, though without significant changes in CD36. Conclusions: Quercetin, silibinin, and crocetin mitigate MASLD progression by reducing steatohepatitis. These effects are associated with distinct modulations of CD36 and PLIN3 protein expression, suggesting that these pathways are promising therapeutic targets in MASLD management. Natural compounds offer a multi-targeted hepatoprotective approach warranting further clinical investigation. Full article

This study aimed to evaluate the effects of different dosimetric parameters of photobiomodulation therapy (PBMT) in an experimental model of chronic obstructive pulmonary disease (COPD). C57BL/6 mice were assigned to the following groups: Baseline, COPD, and COPD treated with PBMT at doses of 1 J, 3 J, 5 J, and 7.5 J. Treatment was performed using a diode laser (660 nm, 100 mW) applied for 10 s, 30 s, 50 s, and 120 s, respectively, over 15 consecutive days. COPD was induced by orotracheal instillation of cigarette smoke extract twice weekly for 45 days. Analyses included total cell count, immune cell profiling by flow cytometry, pulmonary infiltration of inflammatory markers, necrosis, apoptosis, and reactive oxygen species (ROS) production. Data were analyzed using one-way ANOVA followed by the Newman–Keuls post hoc test, with statistical significance set at p < 0.05. PBMT significantly reduced inflammatory cell infiltration, with the most pronounced anti-inflammatory effects observed at doses of 1 J and 3 J, highlighting the importance of appropriate dosimetry in optimizing the therapeutic outcomes of PBMT for COPD. Full article