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The objective of this study was to determine the effects that increasing doses of encapsulated butyric acid and zinc (BZ) have on feedlot steer growth performance, rumen morphometrics and small intestine histology (data not statistically analyzed), dietary net energy utilization, and carcass characteristics. Steers [n = 272; shrunk body weight (BW) = 360 kg ± 74 kg] were assigned to dietary treatments [0 (CON), 1, 2, or 3 g BZ/kg diet dry matter] in a randomized complete block design (RCBD) with pen (n = 32 total; n = 8 per treatment) as experimental unit. Pens were blocked by cattle source and location within the feedyard. Cattle were fed until visually assessed to have 1.27 cm rib-fat and were shipped for harvest at a commercial beef abattoir. Carcass and liver health data were recorded. A subset of steers (n = 8 total; n = 2 per treatment) was harvested at the SDSU Meat Laboratory to collect empty body measurements, rumen samples for morphometric analysis, and duodenal and ileal samples for histological analysis to provide context to feeding trial outcomes. Feedlot growth performance data was calculated on a carcass-adjusted basis: hot carcass weight (HCW)/0.625. Data were analyzed as a RCBD with fixed effects of BZ inclusion level and block was considered a random effect; pre-planned contrasts for CON vs. BZ, plus linear, and quadratic responses were tested. No differences (P ≥ 0.11) were observed for final BW, dry matter intake, average daily gain (ADG), feed conversion efficiency (G:F), performance calculated dietary net energy, HCW, ribeye area, rib-fat thickness, marbling score, estimated empty body fat, or distribution of USDA yield grade (YG) 1, 3, 4, 5, and USDA quality grade among treatments. A tendency (P = 0.10) was observed for CON vs. BZ for calculated YG. Tendencies were detected for USDA YG 2 carcass distribution (linear; P = 0.07) and for normal and abscessed liver prevalence (quadratic; P = 0.08). Dressed yield tended to be greater (P = 0.08) for BZ vs. CON and increased with dose (linear; P = 0.05). Receiving period shrunk BW, ADG, and G:F were improved (P ≤ 0.02) for BZ supplemented steers compared to CON. Data from this study suggests that the addition of BZ to feedlot finishing diets for improving receiving period growth performance and decreasing the prevalence of abscessed livers should be further investigated.
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INTRODUCTION: Prostate-specific membrane antigen (PSMA) is a promising target for treating metastatic castration-resistant prostate cancer. Our previous report presented 111In- or 225Ac-labeled PSMA-NAT-DA1 (PNT-DA1) as a PSMA-targeted ligand. To improve its therapeutic efficiency, PNT-DA1 contains 4-(p-iodophenyl)butyric acid (IPBA), which is known as an albumin binder (ALB) moiety. However, few reports have examined the relationship between the chemical modification of the ALB moiety and pharmacokinetics of PSMA-targeted radioligands. To assess this relationship, we designed, synthesized, and evaluated four [111In]In-PNT-DA1 analogues with ALB moieties different from IPBA. METHODS: The [111In]In-PNT-DA1 analogues were synthesized from their corresponding precursors through ligand substitution reaction. The stability of [111In]In-PNT-DA1 analogues in mouse plasma, their affinity for human serum albumin (HSA), their binding to mouse plasma proteins, and their affinity for PSMA were evaluated in vitro. The tissue distribution profile of the radioligands was assessed in biodistribution studies using LNCaP tumor-bearing nude mice. RESULTS: All [111In]In-PNT-DA1 analogues were obtained at a high radiochemical yield and purity. These analogues were highly stable in mouse plasma after 24 h. The binding affinity for HSA significantly varied among the different ALB moieties. Moreover, high affinity for mouse plasma proteins was observed for all [111In]In-PNT-DA1 analogues compared with their counterparts without an ALB moiety. The affinity for PSMA was comparable for all radioligands. In the biodistribution assay, the pharmacokinetics of [111In]In-PNT-DA1 analogues varied markedly depending on the type of ALB moiety. In particular, tumor area under the curve (AUC) values were increased for radioligands with higher blood retention, while some previous studies reported that compounds with moderate blood retention exhibited the highest tumor AUC values. CONCLUSION: The introduction of an appropriate ALB moiety into the ligand may lead to the development of more useful PSMA-targeted radioligands with higher tumor accumulation.
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The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to investigate the effect of butyric acid on the proliferation and differentiation of the immortalized chicken preadipocyte 2 (ICP2). ICP2 were treated respectively with 12mM butyric acid for 48h in proliferation trial and 4mM butyric acid plus 200 µM oleic acid for 3 d in differentiation trial. For the proliferation trial, RNA-seq analysis revealed that 2039 genes were significantly up-regulated and 780 genes were significantly down-regulated with 12 mM butyric acid after 48 h treatment. Concurrently, Cell cycle, DNA replication and p53 signaling pathways were down-regulated in Butyric acid group. More importantly, 12 mM butyric acid restrained the expression of cell proliferation genes such as PCNA, CDK1 and CDK2 in Butyric acid group (P < 0.05), and the protein expression levels of PCNA and CDK1 were also significantly decreased (P < 0.05). The Oil red staining revealed a fewer presence of red fat droplets in ICP2 following treatment with 4 mM butyric acid, accompanied by decreased levels of total cholesterol (TC) and triglycerides (TG). RNA-seq analysis shown that the number of up and down-regulated genes were 2095 and 1042 respectively in OAB group (oleic acid+butyric acid) when compared with OA group (oleic acid). Meanwhile the AMPK signaling pathway, FOXO signaling pathway and focal adhesion were significantly enriched in OAB group. Additionally, 4 mM butyric acid inhibited the expression of lipid differentiation genes including FABP4, C/EBPα, PPARγ and LPL in OAB group (P < 0.05), as well as lipogenesis proteins such as FABP4, C/EBP-α and PPARγ (P < 0.05). In conclusion, 12 mM butyric acid effectively inhibited the proliferation of ICP2 by slowing down cell cycle progression, while 4 mM butyric acid alleviated lipid deposition by reducing the production of lipid droplets through inhibiting the expression of lipid differentiation marker genes and proteins.
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Slow transit constipation (STC) is a long-lasting and prevalent intestinal condition, marked by hard, dry feces. The primary cause of STC may be attributed to an imbalance in the gut's microbial community and alterations in its metabolic byproducts. Tongbian formula (TB), a traditional Chinese medicinal formula, has been used to treat STC and shows a great effect on relieving constipation. The role of TB in regulating intestinal microbiota has not been fully elucidated. Herein, we investigated the potential effect of TB on gut microbiota and further explored the potential mechanism behind its effects. Our study demonstrated that TB significantly increased fecal water content and intestinal ink propulsion rate in loperamide (Lope)-induced STC rats. 5-HT signaling was suppressed in STC colon tissue, and the abundance of butyric acid (BA) in colonic contents was significantly down-regulated after Lope treatment. Notably, TB administration led to the restoration of microbial dysbiosis and the up-regulation of BA content, subsequently activating 5-HT signaling pathways. When BA was combined with a tryptophan hydroxylase-1 (TPH1) inhibitor, which is crucial for 5-HT synthesis, its therapeutic efficacy for treating STC was compromised. TB alleviates STC by reversing the intestinal microbiota imbalance and activating the 5-HT signaling in the colon through increasing BA levels. These findings suggest that TB is an ideal candidate for STC treatment.
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Ácido Butírico , Constipação Intestinal , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Serotonina , Transdução de Sinais , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/metabolismo , Animais , Ácido Butírico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos , Serotonina/metabolismo , Masculino , Ratos Sprague-Dawley , Trânsito Gastrointestinal/efeitos dos fármacos , Loperamida , Modelos Animais de Doenças , Colo/metabolismo , Colo/efeitos dos fármacosRESUMO
Conflicting data exist in rheumatoid arthritis and the collagen-induced arthritis (CIA) murine model of autoimmune arthritis regarding the role of bacterial carnitine and choline metabolism into the inflammatory product trimethylamine (TMA), which is oxidized in the liver to trimethylamine-N-oxide (TMAO). Using two published inhibitors of bacterial TMA lyase, 3,3-dimethyl-1-butanol (DMB) and fluoromethylcholine (FMC), we tested if TMA/TMAO were relevant to inflammation in the development of CIA. Surprisingly, DMB-treated mice demonstrated > 50% reduction in arthritis severity compared to FMC and vehicle-treated mice, but amelioration of disease was independent of TMA/TMAO production. Given the apparent contradiction that DMB did not inhibit TMA, we then investigated the mechanism of protection by DMB. After verifying that DMB acted independently of the intestinal microbiome, we traced the metabolism of DMB within the host and identified a novel host-derived metabolite of DMB, 3,3-dimethyl-1-butyric acid (DMBut). In vivo studies of mice treated with DMB or DMBut demonstrated efficacy of both molecules in significantly reducing disease and proinflammatory cytokines in CIA, while in vitro studies suggest these molecules may act by modulating secretion of proinflammatory cytokines from macrophages. Altogether, our study suggests that DMB and/or its metabolites are protective in CIA through direct immunomodulatory effects rather than inhibition of bacterial TMA lyases.
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Objective: To investigate the effects of a high-fat diet (HFD) on the gut bacterium Roseburia intestinalis and butyric acid levels, and to assess their impact on ovarian function and epigenetic markers in mice. Methods: A total of 20 female ICR mice aged 4 weeks were randomly assigned to two groups and fed either a control diet (CD) or an HFD for 36 weeks. Post-intervention, ileal contents were analyzed for the quantification of butyric acid using ELISA, while feces were obtained for Roseburia intestinalis expression assessment via qPCR. Histological evaluations of intestinal and ovarian tissues included H&E and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining, alongside immunohistochemical analysis for F4/80, and immunofluorescent detection of Occludin, ZO-1, 5 mC, and H3K36me3. Ovarian health was assessed through follicle counts and morphological evaluations. Statistical analyses were performed using GraphPad Prism 8.0, with P < 0.05 considered significant. Results: After 36 weeks, the HFD group showed significantly higher body weight compared to the CD group (P < 0.01). The HFD led to a decrease in Roseburia intestinalis and butyric acid levels, a reduction in intestinal goblet cells, and an increase in intestinal inflammation. Histological analyses revealed impaired ovarian follicular development and enhanced inflammation in the HFD mice, with immunofluorescent staining showing downregulation of the ovarian epigenetic markers 5 mC and H3K36me3. Conclusion: Our study demonstrates that long-term HFD negatively impacts ovarian function and epigenetic regulation. We found decreased levels of the gut bacterium Roseburia intestinalis and its metabolite, butyric acid, which contribute to these adverse effects. Additionally, the associated intestinal inflammation and compromised mucosal barrier may contribute to these adverse outcomes on female reproductive health.
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PD-L1 is expressed in many tumors but rarely in normal tissues, therefore, it can be a target of PET imaging. In this work, we developed new peptide-based PET probes [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p with yields of 20-25 % and 40-55 %, respectively. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p were synthesized within 30 min with high molar activities. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p showed good stability in vivo and in vitro. In vitro cell studies showed [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p target PD-L1 specifically, with high uptake of 61.52 ± 4.39 and 19.29 ± 2.17 %ID/1 million cells in B16F10 cells at 60 min, respectively. Biodistribution results showed that both [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p had lower liver accumulation. In vivo PET imaging results showed that [18F]AlF-PAI-PDL1p had a high tumor uptake of 4.23 ± 0.81 %ID/g at 2 h and increased uptake of 6.60 ± 1.01 %ID/g at 12 h. [68Ga]Ga-PAI-PDL1p also showed high tumor uptake of 2.30 ± 0.20 %ID/g at 2 h and slightly increased uptake of 3.80 ± 0.26 %ID/g at 6 h. In conclusion, [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1 seemed to be potential tracers for PET imaging of PD-L1 expression.
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Obesity is a global health concern owing to its association with numerous degenerative diseases and the fact that it may lead to early aging. Various markers of aging, including telomere attrition, epigenetic alterations, altered protein homeostasis, mitochondrial dysfunction, cellular senescence, stem cell disorders, and intercellular communication, are influenced by obesity. Consequently, there is a critical need for safe and effective approaches to prevent obesity and mitigate the onset of premature aging. In recent years, intermittent fasting (IF), a dietary strategy that alternates between periods of fasting and feeding, has emerged as a promising dietary strategy that holds potential in counteracting the aging process associated with obesity. This article explores the molecular and cellular mechanisms through which IF affects obesity-related early aging. IF regulates various physiological processes and organ systems, including the liver, brain, muscles, intestines, blood, adipose tissues, endocrine system, and cardiovascular system. Moreover, IF modulates key signaling pathways such as AMP-activated protein kinase (AMPK), sirtuins, phosphatidylinositol 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR), and fork head box O (FOXO). By targeting these pathways, IF has the potential to attenuate aging phenotypes associated with obesity-related early aging. Overall, IF offers promising avenues for promoting healthier lifestyles and mitigating the premature aging process in individuals affected by obesity.
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Senilidade Prematura , Jejum Intermitente , Obesidade , Animais , Humanos , Envelhecimento , Senilidade Prematura/prevenção & controle , Senescência Celular , Obesidade/prevenção & controle , Transdução de SinaisRESUMO
In this study, our objective was to investigate the impact of dietary butyric acid (BA) on the homeostasis mechanism of Pacific shrimp under cold stress. Specifically, we analyzed its effects on immunity, antioxidant capacity, gene expression, and metabolomics response. To carry out this research, Litopenaeus vannamei were fed a diet supplemented with BA for 8 weeks. Following this feeding period, a total of 180 shrimp, with an average weight of 12.76 ± 0.38 g, were exposed to cold conditions, with the temperature decreasing from 28 °C to 14 °C within an hour. The results of our study revealed survival rates ranging from 90 % to 100 %. Shrimp that were fed a diet containing 1.5 % BA exhibited a significant increase in acid phosphatase (ACP) and alkaline phosphatase (AKP) activity. Conversely, the control groups showed an increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) activity. Shrimp that consumed diets containing 1.5 % BA displayed the lowest malondialdehyde (MDA) levels with the highest superoxide dismutase (SOD) content. The shrimp fed the BA diet exhibited tightly organized hepatic tubules with a star-shaped lumen filled with numerous B and R cells. Furthermore, shrimp fed the BA diet demonstrated a significant increase in caspase 3 (CASP) expression. There were no significant variations in the expression levels of prophenoloxidase (ProPO), manganese superoxide dismutase (MnSOD), and glutathione S-transferase (GST) The metabolites of Dl-carnitine, acetyl-l-carnitine, propionylcarnitine, hexanoylcarnitine, palmitoylcarnitine, decanoylcarnitine, and Dl-carnitine exhibited significantly increased expression in shrimp that were fed BA, suggesting their role in the lipolysis process. Based on the findings, adding 2 % BA to the diet of Pacific shrimp helps reduce inflammation and oxidative stress when they are under cold stress.
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Dependence of the food industry on conventional plastic and the generation of enormous amounts of food waste caused by microbiological spoilage have been imposed as inspiration for this work, to develop active sustainable packaging for sliced cheese using the bi-layer design. Pullulan was modified using a green approach to obtain a polyanionic character in the coating formulation. Chitosan, which has a cationic character in an acidic environment, has been modified using a butyric acid to obtain an amphiphilic character. The formed active bi-layer has demonstrated an improved barrier (decreased permeability for moisture vapor 72.2 and 77.7 times) and mechanical properties (increased tensile strength value up to 3.9 and 9.4 times) compared to the monolayer films. A novel approach to microbiological control of sliced cheese has been established, which implies a synergistic effect of Helichrysum italicum essential oil (EO) and corresponding hydrolate (HY) incorporated in separated layers. This design has ensured avoiding surfactants and preserving cheese's sensory properties, prolonging its shelf-life by 50 % at least. Improvements in cheese storage conditions using this packaging lie in the improved barrier, mechanical and antimicrobial properties, the order of lamination, and a good covering of the cheese surface by spraying.
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Streptococcus pneumoniae (Spn) is the predominant pathogen responsible for community-acquired pneumonia (CAP) in children under five years old, and it can induce over 17% of pregnant women. However, no more effective measures exist to prevent infection induced by Spn in these two special populations. The beneficial microbes can antagonize Spn and provide new targets for preventing pneumococcal infections. This study used 16S rRNA gene sequencing and targeted metabolomics to evaluate the role of the Bacillus aerolatus CX253 (CX253) in alleviating Spn infection. Additionally, the colonization of CX253 was observed in nose, trachea, and lung by using confocal laser scanning microscopy and fluorescent labeling techniques. Compared with the model group, the expression level of interleukin-1ß was dropped 1.81-fold and 2.22-fold, and interleukin-6 was decreased 2.39-fold and 1.84-fold. The express of tumor necrosis factor-α was down 2.30-fold and 3.84-fold in prevention group of childhood and pregnant rats, respectively. The 16S rRNA sequencing results showed that CX253 administration alone significantly increased the abundance of Lactobacillus, Limosilactobacillus, and Prevotella in the gut of childhood and pregnant rats. Furthermore, the CX253 increased propionate in the gut of childhood rats and increased propionate and butyrate in the gut of pregnant rats to inhibit pulmonary inflammation. In summary, CX253 attenuated Spn-induced inflammation by regulating the gut microbiota and SCFAs. The research provides valuable information for the prevention of pneumonia.
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Bacillus , Microbioma Gastrointestinal , Inflamação , Streptococcus pneumoniae , Animais , Feminino , Gravidez , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/microbiologia , Bacillus/metabolismo , Humanos , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Ratos Sprague-Dawley , Masculino , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Pulmão/microbiologia , Pulmão/patologia , Pulmão/metabolismo , Probióticos/farmacologiaRESUMO
Probiotic consumption strongly influences local intestinal immunity and systemic immune status. Heyndrickxia coagulans strain SANK70258 (HC) is a spore-forming lactic acid bacterium that has immunostimulatory properties on peripheral tissues. However, few reports have examined the detailed effectiveness of HC on human immune function and its mechanism of action. Therefore, we conducted a randomized, double-blind, placebo-controlled, parallel-group study to comprehensively evaluate the effects of HC on immunostimulatory capacity, upper respiratory tract infection (URTI) symptoms, and changes in intestinal organic-acid composition. Results of a questionnaire survey of URTI symptoms showed that runny nose, nasal congestion, sneezing, and sore throat scores as well as the cumulative number of days of these symptoms were significantly lower in the HC group than in the placebo group during the study period. Furthermore, the salivary secretory immunoglobulin A (sIgA) concentration was significantly higher, and the natural killer (NK) cell activity tended to be higher in the HC group than in the placebo group. In addition, we performed an exposure culture assay of inactivated influenza virus on peripheral blood mononuclear cells (PBMCs) isolated from the blood of participants in the HC and placebo groups. Gene-expression analysis in PBMCs after culture completion showed that IFNα and TLR7 expression levels were significantly higher in the HC group than in the placebo group. In addition, the expression levels of CD304 tended to be higher in the HC group than in the placebo group. On the other hand, the HC group showed a significantly higher increase in the intestinal butyrate concentration than the placebo group. HC intake also significantly suppressed levels of IL-6 and TNFα produced by PBMCs after exposure to inactivated influenza virus. Collectively, these results suggest that HC activated plasmacytoid dendritic cells expressing TLR7 and CD304 and strongly induced IFNα production, subsequently activating NK cells and increasing sIgA levels, and induced anti-inflammatory effects via increased intestinal butyrate levels. These changes may contribute to the acquisition of host resistance to viral infection and URTI prevention.
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Probióticos , Infecções Respiratórias , Humanos , Infecções Respiratórias/imunologia , Método Duplo-Cego , Masculino , Adulto , Probióticos/administração & dosagem , Feminino , Adulto Jovem , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Microbioma Gastrointestinal/imunologia , Imunoglobulina A Secretora/imunologia , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/imunologia , ImunomodulaçãoRESUMO
AIM OF THE STUDY: This study aimed to determine the effect of Epimedium brevicornu Maxim. (EF) on osteoporosis (OP) and its underlying molecular mechanisms, and to explore the existence of the "Gut-Bone Axis". MATERIAL AND METHODS: The impact of EF decoction (EFD) on OP was evaluated using istopathological examination and biochemical assays. Targeted metabolomics was employed to identify key molecules and explore their molecular mechanisms. Alterations in the gut microbiota (GM) were evaluated by 16S rRNA gene sequencing. The role of the GM was clarified using an antibiotic cocktail and faecal microbiota transplantation. RESULTS: EFD significantly increased the weight (14.06%), femur length (4.34%), abdominal fat weight (61.14%), uterine weight (69.86%), and insulin-like growth factor 1 (IGF-1) levels (59.48%), while reducing serum type I collagen cross-linked carboxy-terminal peptide (CTX-I) levels (15.02%) in osteoporotic mice. The mechanism of action may involve the regulation of the NLRP3/cleaved caspase-1/IL-1ß signalling pathway in improving intestinal tight junction proteins and bone metabolism. Additionally, EFD modulated the abundance of related GM communities, such as Lactobacillus, Coriobacteriaceae, bacteria of family S24-7, Clostridiales, and Prevotella, and increased propionate and butyrate levels. Antibiotic-induced dysbiosis of gut bacteria disrupted OP regulation of bone metabolism, which was restored by the recovery of GM. CONCLUSIONS: Our study is the first to demonstrate that EFD works in an OP mouse model by utilising GM and butyric acid. Thus, EF shows promise as a potential remedy for OP in the future.
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Caspase 1 , Epimedium , Microbioma Gastrointestinal , Interleucina-1beta , Proteína 3 que Contém Domínio de Pirina da Família NLR , Osteoporose , Transdução de Sinais , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Transdução de Sinais/efeitos dos fármacos , Caspase 1/metabolismo , Camundongos , Feminino , Interleucina-1beta/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Transplante de Microbiota FecalRESUMO
Endemic fluorosis has gained increasing attention as a public health concern, and the escalating risk of colitis resulting from excessive fluoride intake calls for effective mitigation strategies. This study aimed to investigate the potential mechanisms underlying the alleviation of fluoride-induced colitis by Tea polysaccharides (TPS). Under conditions of excessive fluoride intake, significant changes were observed in the gut microbiota of rats, leading to aggravated colitis. However, the intervention of TPS exerted a notable alleviating effect on colitis symptoms. Antibiotic intervention and fecal microbiota transplantation (FMT) experiments provided evidence that TPS-mediated relief of fluoride-induced colitis is mediated through its effects on the gut microbiota. Furthermore, TPS supplementation was found to modulate the structure of gut microbiota, enhance the relative abundance of Limosilactobacillus vaginalis in the gut microbiota, and promote the expression of short-chain fatty acid (SCFAs) receptors in colonic tissue. Notably, L. vaginalis played a significant role in alleviating fluoride-induced colitis and facilitating the absorption of butyric acid in the rat colon. Subsequent butyric acid intervention experiments confirmed its remarkable alleviating effect on fluoride-induced colitis. Overall, these findings provide a potential preventive strategy for fluoride-induced colitis by TPS intervention, which is mediated by L. vaginalis and butyric acid.
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Ácido Butírico , Colite , Fluoretos , Microbioma Gastrointestinal , Polissacarídeos , Chá , Animais , Ácido Butírico/metabolismo , Fluoretos/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/prevenção & controle , Polissacarídeos/farmacologia , Masculino , Chá/química , Ratos Sprague-Dawley , Colo/efeitos dos fármacos , Colo/metabolismo , RatosRESUMO
BACKGROUND: Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive. METHODS: The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments. RESULTS: In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon. CONCLUSION: Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice.
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Introduction: Sweet sorghum juice is a typical production feedstock for natural, eco-friendly sweeteners and beverages. Clostridium tyrobutyricum is one of the widely used microorganisms in the food industry, and its principal product, bio-butyric acid is an important food additive. There are no published reports of Clostridium tyrobutyricum producing butyric acid using SSJ as the sole substrate without adding exogenous substances, which could reach a food-additive grade. This study focuses on tailoring a cost-effective, safe, and sustainable process and strategy for their production and application. Methods: This study modeled the enzymolysis of non-reducing sugars via the first/second-order kinetics and added food-grade diatomite to the hydrolysate. Qualitative and quantitative analysis were performed using high-performance liquid chromatography, gas chromatography-mass spectrometer, full-scale laser diffraction method, ultra-performance liquid chromatography-tandem mass spectrometry, the cell double-staining assay, transmission electron microscopy, and Oxford nanopore technology sequencing. Quantitative real-time polymerase chain reaction, pathway and process enrichment analysis, and homology modeling were conducted for mutant genes. Results: The treated sweet sorghum juice showed promising results, containing 70.60 g/L glucose and 63.09 g/L fructose, with a sucrose hydrolysis rate of 98.29% and a minimal sucrose loss rate of 0.87%. Furthermore, 99.62% of the colloidal particles and 82.13% of the starch particles were removed, and the concentrations of hazardous substances were effectively reduced. A food microorganism Clostridium tyrobutyricum TGL-A236 with deep utilization value was developed, which showed superior performance by converting 30.65% glucose and 37.22% fructose to 24.1364 g/L bio-butyric acid in a treated sweet sorghum juice (1:1 dilution) fermentation broth. This titer was 2.12 times higher than that of the original strain, with a butyric acid selectivity of 86.36%. Finally, the Genome atlas view, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and evolutionary genealogy of genes: Non-supervised Orthologous (eggNOG) functional annotations, three-dimensional structure and protein cavity prediction of five non-synonymous variant genes were obtained. Conclusion: This study not only includes a systematic process flow and in-depth elucidation of relevant mechanisms but also provides a new strategy for green processing of food raw materials, improving food microbial performance, and ensuring the safe production of food additives.
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Nanoscale materials are being developed from individual particles to multi-component assemblies, with carbon nanomaterials being particularly useful in bioimaging, sensing, and optoelectronics due to their unique optical properties, enhanced by surface passivation and chemical doping. Noble metals are commonly used in conjunction with carbon-based nanomaterials for the synthesis of nanohybrids. Carbon-based materials can function as photosensitizers and effective carriers in photodynamic therapy, enabling the use of combined treatment approaches. The hydrophobicity and agglomeration tendency of carbon nanoparticles pose a drawback. This study is an attempt to overcome these limitations, which involved the synthesis of iron oxide-doped carbon nanoparticles through the carbonisation of citric acid and hexamethylene tetramine, followed by doping them with iron oxide. The as synthesized iron oxide-doped carbon nanoparticles were stabilised with fluorescently modified hyperbranched polyglycerol. The efficacy of these nanoparticles in photodynamic antibacterial therapy and Cd (II) ion sensing was investigated. The selectivity of stabilised nanoparticles against Cd2+ ion is presented in the current study. The current study also compares the antibacterial efficacy of undoped, iron oxide-doped and stabilised nanoparticle systems. The possible toxic effects of the synthesised nanosystems were investigated in order to assess their suitability for biomedical applications and establish their safety profile.
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The evidence on the role of diets in the production of short-chain fatty acids (SCFAs) was limited. The aim of this study was to assess the potential effects of high-fat high-fructose (HFHF), high-fat, and Western diets on the levels of SCFA. A research experiment employing a post-test-only control group design was carried out from January to April 2022. A total of 27 rats were randomly allocated to each study group. SCFA was measured two weeks after diet administration. Analysis of variance (ANOVA) test was used to analyze the differences among groups, and the effect estimate of each group was analyzed using post hoc Tukey. The concentrations of SCFAs post HFHF diets were recorded as follows: acetic acid at 54.60±10.58 mmol/g, propionic acid at 28.03±8.81 mmol/g, and butyric acid at 4.23±1.68 mmol/g. Following the high-fat diet, acetic acid measured 61.85±14.25 mmol/gr, propionic acid measured 25.19±5.55 mmol/gr, and butyric acid measured 6.10±2.93 mmol/gr. After the administration of Western diet, the levels of SCFA were 68.18±25.73, 29.69±12.76, and 7.48±5.51 mmol/g for acetic acid, propionic acid, and butyric acid, respectively. The level of butyric acid was significantly lower in HFHF diet group compared to the normal diet (mean difference (MD) 6.34; 95%CI: 0.61, 12.04; p=0.026). The levels of acetic acid (p=0.419) and propionic acid (p=0.316) were not statistically different among diet types (HFHF, high-fat, and Western diet). In conclusion, HFHF diet is associated with a lower level of butyric acid than the normal diet in a rat model.
Assuntos
Dieta Hiperlipídica , Dieta Ocidental , Modelos Animais de Doenças , Ácidos Graxos Voláteis , Frutose , Hepatopatia Gordurosa não Alcoólica , Animais , Ratos , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Frutose/administração & dosagem , Dieta Ocidental/efeitos adversos , Masculino , Ratos Sprague-Dawley , Ácido AcéticoRESUMO
Gamma-aminobutyric acid and glycine (GABA/Gly) are predominantly inhibitory neurotransmitters in the mature central nervous system; however, they mediate membrane potential depolarization during development. These differences in actions depend on intracellular Cl- concentrations ([Cl-]i), which are primarily regulated by potassium chloride cotransporter 2 (KCC2). After nerve injury, KCC2 expression markedly decreases and GABA/Gly mediate depolarization. Following nerve regeneration, KCC2 expression recovers and GABA/Gly become inhibitory, suggesting that KCC2 reduction and GABA/Gly excitation may be crucial for axonal regeneration. To directly clarify their involvement in regeneration, we analyzed recovery processes after tibial nerve severance and suturing between heterozygous KCC2 knockout mice (HT), whose KCC2 levels are halved, and their wild-type littermates (WT). Compared with WT mice, the sciatic functional index-indicating lower limb motor function-was significantly higher until 28 days after operation (D28) in HT mice. Furthermore, at D7, many neurofilament-positive fibers were elongated into the distal part of the sutured nerve in HT mice only, and myelinated axonal density was significantly higher at D21 and D28 in HT animals. Electron microscopy and galanin immunohistochemistry indicated a shorter nerve degeneration period in HT mice. Moreover, a less severe decrease in choline acetyltransferase was observed in HT mice. These results suggest that nerve degeneration and regeneration proceed more rapidly in HT mice, resulting in milder motor dysfunction. Via similar microglial activation, nerve surgery may reduce KCC2 levels more rapidly in HT mice, followed by earlier increased [Cl-]i and longer-lasting GABA/Gly excitation. Taken together, reduced KCC2 may accelerate nerve regeneration via GABA/Gly excitation.
Assuntos
Axônios , Cotransportadores de K e Cl- , Regeneração Nervosa , Simportadores , Nervo Tibial , Animais , Feminino , Masculino , Camundongos , Axônios/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismos dos Nervos Periféricos/metabolismo , Simportadores/metabolismo , Simportadores/genética , Nervo Tibial/lesões , Nervo Tibial/metabolismoRESUMO
Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases.