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The role of Auricularia auricula polysaccharide (AP) in the regulation of glycolipid metabolism was investigated using a high-fat-diet-induced hyperlipidemic mouse model. In a further step, its potential mechanism of action was investigated using microbiome analysis and widely targeted lipidomics. Compared to high-fat mice, dietary AP supplementation reduced body weight by 13.44%, liver index by 21.30%, epididymal fat index by 50.68%, fasting blood glucose (FBG) by 14.27%, serum total cholesterol (TC) by 20.30%, serum total triglycerides (TGs) by 23.81%, liver non-esterified fatty acid (NEFA) by 20.83%, liver TGs by 20.00%, and liver malondialdehyde (MDA) by 21.05%, and increased liver glutathione oxidase (GSH-PX) activity by 52.24%, total fecal bile acid (TBA) by 46.21%, and fecal TG by 27.16%, which significantly regulated glucose and lipid metabolism. Microbiome analysis showed that AP significantly downregulated the abundance of the Desulfobacterota phylum, as well as the genii Desulfovibrio, Bilophila, and Oscillbacter in the cecum of hyperlipidemic mice, which are positively correlated with high lipid indexes, while it upregulated the abundance of the families Eubacterium_coprostanoligenes_group and Ruminococcaceae, as well as the genii Eubacterum_xylanophilum_group, Lachnospiraceae_NK4A136_group, Eubacterium_siraeum_group, and Parasutterella, which were negatively correlated with high lipid indexes. In addition, AP promoted the formation of SCFAs by 119.38%. Widely targeted lipidomics analysis showed that AP intervention regulated 44 biomarkers in metabolic pathways such as sphingolipid metabolism and the AGE-RAGE signaling pathway in the hyperlipidemic mice (of which 15 metabolites such as unsaturated fatty acids, phosphatidylserine, and phosphatidylethanolamine were upregulated, and 29 metabolites such as phosphatidylcholine, ceramide, carnitine, and phosphatidylinositol were downregulated), thereby correcting glucose and lipid metabolism disorders.
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Yam is a dual-purpose crop used in both medicine and food that is commonly used as a dietary supplement in food processing. Since yam proteins are often lost during the production of yam starch, elucidating the functionally active value of yam proteins is an important guideline for fully utilizing yam in industrial production processes. This study aimed to explore the potential protective effect of yam protein (YP) on cyclophosphamide (CTX)-induced immunosuppression in mice. The results showed that YP can reduce immune damage caused by CTX by reversing immunoglobulins (IgA, IgG and IgM), cytokines (TNF-α, IL-6, etc.) in the intestines of mice. Moreover, YPs were found to prevent CTX-induced microbiota dysbiosis by enhancing the levels of beneficial bacteria within the microbiome, such as Lactobacillus, and lowering those of Desulfovibrio_R and Helicobacter_A. Metabolomics analyses showed that YP significantly altered differential metabolites (tryptophan, etc.) and metabolic pathways (ABC transporter protein, etc.) associated with immune responses in the gut. Furthermore, important connections were noted between particular microbiomes and metabolites, shedding light on the immunoprotective effects of YPs by regulating gut flora and metabolism. These findings deepen our understanding of the functional properties of YPs and lay a solid foundation for the utilization of yam.
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Objective: Pulmonary artery hypertension (PAH) poses a significant challenge due to its limited therapeutic options and high mortality rates. The ACE2-Ang-(1-7)-Mas axis plays a pivotal role in regulating blood pressure and inhibiting myocardial remodeling. However, the precise mechanistic links between the ACE2-Ang-(1-7)-Mas axis and PAH remain poorly understood. This study aimed to elucidate the involvement of the ACE2-Ang-(1-7)-Mas axis in the development of PAH. Methods: PAH was induced in mice using Sugen5416/hypoxia, PAAT/PET ratio and PA were detected using cardiac ultrasound; inflammation related factors such as MCP-1, TNF, IL-10and IL-12p70 were detected in intestines using cytometric bead array (CBA) kits; histopathological and morphological changes in lung and intestinal tissues were assessed via HE staining and Masson staining to evaluate the progression of PAH. Immunohistochemistry and western blotting were employed to determine the expression levels of two tight junction proteins, occludin and ZO-1, in intestinal tissues. Additionally, 16rRNA sequencing and non-targeted metabolomics by LC-MS/MS techniques were utilized to investigate the impact of the ACE2-Ang-(1-7)-Mas axis on microbial diversity and metabolomics of intestinal contents. Results: Activation of the ACE2-Ang-(1-7)-Mas axis improves heart function, reduces intestines inflammatory factors and ameliorates pathological and histological alterations in SuHx mice. This activation notably upregulated the expression of occludin and ZO-1 proteins in intestinal tissues and promoted the proliferation of SCFA-producing bacteria genera, such as g_Candidatus_Saccharimonas. Furthermore, it enhanced the abundance of beneficial metabolites, including tryptophan and butyric acid. Conclusion: The findings suggest that modulation of the ACE2-Ang-(1-7)-Mas axis can alleviate PAH by regulating intestinal microbes and metabolites. These results highlight the potential of the ACE2-Ang-(1-7)-Mas axis as a promising therapeutic target for clinical management of PAH.
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Gut microecology,the complex community consisting of microorganisms and their microenvironments in the gastrointestinal tract, plays a vital role in maintaining overall health and regulating various physiological and pathological processes. Recent studies have highlighted the significant impact of gut microecology on the regulation of uric acid metabolism. Natural products, including monomers, extracts, and traditional Chinese medicine formulations derived from natural sources such as plants, animals, and microorganisms, have also been investigated for their potential role in modulating uric acid metabolism. According to research, The stability of gut microecology is a crucial link for natural products to maintain healthy uric acid metabolism and reduce hyperuricemia-related diseases. Herein, we review the recent advanced evidence revealing the bidirectional regulation between gut microecology and uric acid metabolism. And separately summarize the key evidence of natural extracts and herbal formulations in regulating both aspects. In addition,we elucidated the important mechanisms of natural products in regulating uric acid metabolism and secondary diseases through gut microecology, especially by modulating the composition of gut microbiota, gut mucosal barrier, inflammatory response, purine catalyzation, and associated transporters. This review may offer a novel insight into uric acid and its associated disorders management and highlight a perspective for exploring its potential therapeutic drugs from natural products.
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Hypertensive disorders of pregnancy (HDP) are severe complications of pregnancy with high morbidity and are a major cause of increased maternal and infant morbidity and mortality. Currently, there is a lack of effective early diagnostic indicators and safe and effective preventive strategies for HDP in clinical practice, except for monitoring maternal blood pressure levels, the degree of proteinuria, organ involvement and fetal conditions. The intestinal microbiota consists of the gut flora and intestinal environment, which is the largest microecosystem of the human body and participates in material and energy metabolism, gene expression regulation, immunity regulation, and other functions. During pregnancy, due to changes in hormone levels and altered immune function, the intestinal microecological balance is affected, triggering HDP. A dysregulated intestinal microenvironment influences the composition and distribution of the gut flora and changes the intestinal barrier, driving beneficial or harmful bacterial metabolites and inflammatory responses to participate in the development of HDP and promote its malignant development. When the gut flora is dysbiotic and affects blood pressure, supplementation with probiotics and dietary fiber can be used to intervene. In this review, the interaction between the intestinal microbiota and HDP was investigated to explore the feasibility of the gut flora as a novel biomarker of HDP and to provide a new strategy and basis for the prevention and treatment of clinical HDP.
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Biomarcadores , Microbioma Gastrointestinal , Probióticos , Humanos , Embarazo , Femenino , Probióticos/uso terapéutico , Hipertensión Inducida en el Embarazo/microbiología , Disbiosis , Animales , Fibras de la DietaRESUMEN
Heart failure is a multifactorial disease, the percentage of patients with heart failure caused by metabolic syndrome is increasing year by year. The effect of gut flora dysbiosis on metabolic syndrome and heart failure has received widespread attention in recent years. Drugs to treat the condition urgently need to be discovered. C20DM, as a precursor compound of ginsenoside, is a small molecule compound obtained by biosynthetic means and is not available in natural products. In this project, we found that C20DM could improve the diversity of gut flora and elevate the expression of intestinal tight junction proteins-Occludin, Claudin, ZO-1, which inhibited the activity of the TLR4-MyD88-NF-kB pathway, and as a result, reduced myocardial inflammation and slowed down heart failure in metabolic syndrome mice. In conclusion, our study suggests that C20DM can treat heart failure by regulating gut flora, and it may be a candidate drug for treating metabolic syndrome-induced heart failure.
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Microbioma Gastrointestinal , Insuficiencia Cardíaca , Síndrome Metabólico , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Síndrome Metabólico/metabolismo , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/microbiología , Síndrome Metabólico/complicaciones , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/microbiología , Ratones , Masculino , Ratones Endogámicos C57BL , Receptor Toll-Like 4/metabolismo , FN-kappa B/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Transducción de Señal/efectos de los fármacos , Ginsenósidos/farmacología , Ginsenósidos/uso terapéuticoRESUMEN
Ulcerative colitis (UC) is a chronic inflammatory condition with recurrent and challenging symptoms. Effective treatments are lacking, making UC management a critical research area. Morin (MO), a flavonoid from the Moraceae family, shows potential as an anti-UC agent, but its mechanisms are not fully understood. Using a dextran sulfate sodium (DSS)-induced UC mouse model, we employed network pharmacology to predict MO's therapeutic effects. Assessments included changes in body weight, disease activity index (DAI), and colon length. Immunofluorescence, hematoxylin and eosin (H&E), and PAS staining evaluated colon damage. ELISA and western blot analyzed inflammatory factors, tight junction (TJ)-associated proteins (Claudin-3, Occludin, ZO-1), and Mitogen-Activated Protein Kinase (MAPK)/ Nuclear Factor kappa B (NF-κB) pathways. 16S rRNA sequencing assessed gut microbiota diversity, confirmed by MO's modulation via Fecal Microbial Transplantation (FMT). Early MO intervention reduced UC severity by improving weight, DAI scores, and colon length, increasing goblet cells, enhancing barrier function, and inhibiting MAPK/NF-κB pathways. MO enriched gut microbiota, favoring beneficial bacteria like Muribaculaceae and Erysipelotrichaceae while reducing harmful Erysipelotrichaceae and Muribaculaceae. This study highlights MO's potential in UC management through inflammation control, mucosal integrity maintenance, and gut flora modulation.
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Colitis Ulcerosa , Sulfato de Dextran , Flavonoides , Microbioma Gastrointestinal , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/patología , Microbioma Gastrointestinal/efectos de los fármacos , Flavonoides/farmacología , Flavonoides/uso terapéutico , Ratones , Masculino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Colon/patología , Colon/efectos de los fármacos , Colon/microbiología , Colon/inmunología , FN-kappa B/metabolismo , Trasplante de Microbiota Fecal , Humanos , FlavonasRESUMEN
BACKGROUND: Prolonged alcohol consumption may lead to gastrointestinal tract dysfunction and cause abnormalities in the associated nervous system activity, thereby increasing the body's craving for alcohol. Lactobacillus casei is a probiotic that has been shown to reduce the incidence of alcohol-related diseases. However, it is unclear whether Lactobacillus casei can delay the development of alcohol dependence. METHODS: The chronic intermittent active drinking method was used to establish a mouse alcohol dependence model. The mice were randomly divided into 4 treatment groups, as follows: (1) Control group: two bottles of distilled water alternately, 0.2 mL/d saline gavage. (2) Alcohol group: alternating water and alcohol, 0.2 mL/d saline gavage. (3) Low group: alternating water and alcohol, 0.2 mL/d 1 × 108CFU of Lactobacillus casei by gavage. (4) High group: alternating water and alcohol, 0.2 mL/d 1 × 109CFU of Lactobacillus casei by gavage. The daily water consumption (mL), alcohol consumption (mL) and body weight of each mouse were recorded. After that, pathological changes in the intestines, brain tissues and serum of the experimental animals were detected, while changes in the intestinal flora of the mice were analysed by 16S rRNA sequencing. RESULTS: The Lactobacillus casei intervention did not produce a significant effect on body weight in alcohol-exposed mice (P>0.05), but significantly reduced alcohol preference in alcohol-exposed mice (P<0.05). Subsequent analyses showed that Lactobacillus casei significantly ameliorated intestinal, brain tissue, and systemic inflammatory responses in alcohol-exposed mice (P<0.05). 16S rRNA sequencing showed that alcohol-exposed mice treated with Lactobacillus casei exhibited a richer composition of intestinal microorganisms, such as f__Rikenellaceae, g__Alistipes_A_871400, and g__Bacteroides_H genera showed relative enrichment in the High group. CONCLUSION: By showing that Lactobacillus casei slows down alcohol preference and alleviates gut and brain tissue inflammation in alcohol-exposed mice, our findings provide a possible strategy: Lactobacillus casei may be able to serve as a potential target for the prevention and treatment of alcohol dependence.
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Alcoholismo , Microbioma Gastrointestinal , Lacticaseibacillus casei , Probióticos , Animales , Probióticos/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Consumo de Bebidas Alcohólicas , Encéfalo/patología , Intestinos/microbiología , Intestinos/patología , EtanolRESUMEN
Hyperuricemia (HUA) is one of the most common chronic diseases today, with a prevalence exceeding 14 % in both the United States and China. Current clinical treatments for HUA focus on promoting uric acid (UA) excretion and inhibiting UA production, but often neglect the strain on the liver and kidneys. The fruit of Alpinia oxyphylla (A. oxyphylla) is known to improve renal function, regulate metabolism, and exhibit anti-inflammatory effects; however, its effectiveness and mechanisms in treating HUA are not well understood. In this study, HUA mice induced by potassium oxonate and adenine were treated with A. oxyphylla polysaccharide (AFP) for 21 days. The levels associated with HUA were quantified using assay kits to evaluate the impact of AFP on HUA. Serum metabolomics and 16S rRNA sequencing were used to investigate the mechanisms by which AFP ameliorates HUA. The results showed that AFP treatment reduced abnormal biochemical levels, including UA, blood urea nitrogen, and creatinine, in HUA mice. AFP inhibited UA synthesis by regulating pyrimidine metabolism and the metabolism of alanine, aspartate and glutamate, reduced kidney inflammation, and promoted UA excretion by regulating intestinal flora. Thus, AFP appears to be an effective agent for alleviating HUA symptoms.
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Alpinia , Frutas , Microbioma Gastrointestinal , Hiperuricemia , Polisacáridos , Ácido Úrico , Animales , Alpinia/química , Hiperuricemia/tratamiento farmacológico , Ácido Úrico/sangre , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Frutas/química , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , ARN Ribosómico 16S/genética , Nitrógeno de la Urea Sanguínea , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , PirimidinasRESUMEN
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Saccharomyces cerevisiae CNCM I-1079 as a zootechnical feed additive for dogs and all other Canidae. The additive is intended for use in feed for dogs and all other Canidae at a proposed minimum inclusion level of 1 × 109 CFU per kg of complete feed. Saccharomyces cerevisiae is considered by EFSA to be suitable for the qualified presumption of safety approach to safety assessment. Since the identity of the active agent has been clearly established and no concerns are expected from other components of the product, the additive is considered safe for the target species. Since the additive is intended to be used only in feed for dogs and other non-food-producing animals, an assessment of the safety for the consumer and the environment is not needed. The non-coated form of the additive was shown to be non-irritant to skin and eyes. No conclusion can be drawn on the eye irritation potential of the coated form of the additive due to the lack of data. The additive in both forms, should be considered a skin and respiratory sensitiser and any exposure through skin and respiratory tract is considered a risk. The Panel was not in the position to conclude on the efficacy of Saccharomyces cerevisiae CNCM I-1079 at the proposed conditions of use.
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This study aimed to explore the mechanism of Xiaoyu Xiezhuo decoction (XXD) on ischemia-reperfusion-induced acute kidney injury (IRI-AKI) using network pharmacology methods and gut microbiota analysis. A total of 1778 AKI-related targets were obtained, including 140 targets possibly regulated by AKI in XXD, indicating that the core targets were mainly enriched in inflammatory-related pathways, such as the IL-17 signaling pathway and TNF signaling pathway. The unilateral IRI-AKI animal model was established and randomly divided into four groups: the sham group, the AKI group, the sham + XXD group, and the AKI + XXD group. Compared with the rats in the AKI group, XXD improved not only renal function, urinary enzymes, and biomarkers of renal damage such as Kim-1, cystatin C, and serum inflammatory factors such as IL-17, TNF-α, IL-6, and IL 1-ß, but also intestinal metabolites including lipopolysaccharides, d-lactic acid, indoxyl sulfate, p-cresyl sulfate, and short-chain fatty acids. XXD ameliorated renal and colonic pathological injury as well as inflammation and chemokine gene abundance, such as IL-17, TNF-α, IL-6, IL-1ß, ICAM-1, and MCP-1, in AKI rats via the TLR4/NF-κB/NLRP3 pathway, reducing the AKI score, renal pathological damage, and improving the intestinal mucosa's inflammatory infiltration. It also repaired markers of the mucosal barrier, including claudin-1, occludin, and ZO-1. Compared with the rats in the AKI group, the α diversity was significantly increased, and the Chao1 index was significantly enhanced after XXD treatment in both the sham group and the AKI group. The treatment group significantly reversed this change in microbiota.
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Lesión Renal Aguda , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Riñón , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Lesión Renal Aguda/etiología , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/metabolismo , Daño por Reperfusión/complicaciones , Daño por Reperfusión/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Ratas , Masculino , Riñón/patología , Riñón/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Farmacología en Red , Receptor Toll-Like 4/metabolismoRESUMEN
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of a preparation of dried cells of Saccharomyces cerevisiae CNCM I-4407 (Actisaf® Sc 47) as a zootechnical additive for rabbits for fattening and non-food producing rabbits. The applicant provided evidence that the additive currently in the market complies with the existing terms of the authorisation. The Panel concluded that the additive remains safe for the target species, consumers and the environment. Regarding the safety for the user, the additive is not a skin or eye irritant. However, it should be considered as a potential skin and respiratory sensitiser, and any exposure through skin and respiratory tract is considered a risk. The present application for renewal of the authorisation did not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive. Therefore, there was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.
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Orally administered crocin rapidly and efficiently rescues depressive-like behaviors in depression models; however, crocin levels in the circulatory and central nervous systems are rather low. The underlying mechanism responsible for the inconsistency between pharmacokinetics and pharmacodynamics is unknown. To identify the active metabolites and clarify the underlying mechanisms, the pharmacokinetics and metabolic effects of the gut flora and hepatic and intestinal microsomes on crocin were examined, and the pharmacodynamics of crocin and its major metabolite, crocetin, were also evaluated in both normal and pseudo germ-free mice subjected to chronic social defeat stress. The results showed that oral administration of 300 mg/kg crocin significantly improved the depression-like behaviors of chronic social defeat stress mice, although the levels of crocin in the circulatory system were rather low (Cmax = 43.5 ± 8.6 µg/L; AUC = 151 ± 20.8 µg·h/L). However, the primary metabolite of crocetin was much more abundant in vivo (Cmax = 4662.5 ± 586.1 µg/L; AUC = 33,451.9 ± 3323.6 µg·h/L). Orally administered crocin was primarily metabolized into crocetin by the gut flora instead of hepatic or intestinal microsomal enzymes, and less than 10% of crocin was transformed into crocetin in the liver or intestinal microsomes. Inhibition of the gut flora dramatically reduced the production of and in vivo exposure to crocetin, and the rapid antidepressant effect of crocin disappeared. Moreover, crocetin showed rapid antidepressant effects similar to those of crocin, and the effects were independent of the gut flora. In conclusion, the metabolic transformation of crocin to crocetin primarily contributes to the rapid antidepressant effects of crocin and is dependent on the gut flora.
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Colorectal cancer (CRC) is one of the most common cancers diagnosed in the world. Although environmental and genetic factors play a major role in the pathogenesis of CRC, extensive research has suggested that vitamin D may play a pivotal role in the development of CRC. Vitamin D, primarily obtained through sunlight exposure, dietary sources, and supplements, has long been recognized for its essential functions in maintaining health, including immune regulation. This article delves into the intricate relationship between vitamin D, the immune system, gut flora, and the prevention of CRC. It presents a synthesis of epidemiological data, experimental studies, and clinical trials, highlighting the mechanisms by which vitamin D influences immune cell function, cytokine production, and inflammation. By enhancing the immune system's surveillance and anti-tumor activity, vitamin D may offer a promising avenue for CRC prevention. Furthermore, this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain. Additionally, the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC, emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms, encompassing antineoplastic mechanisms, influences on the immune system, and modulation of the gut microbiome.
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To investigate the effects of rapeseed diacylglycerol oil (RDG) intake on lipid accumulation and metabolism in C57BL/6J mice, obese mice were fed a high-fat diet in which 45% of the total energy content came from RDG (RDGM group) or rapeseed triacylglycerol oil (RTGM group). This diet intervention was conducted for 12 weeks following the establishment of the obese mouse model. By the end of the experiment, the serum glucose levels of the mice in the RTGM and RDGM groups were 13.0 ± 1.3 mmol/L and 9.7 ± 1.5 mmol/L, respectively. Meanwhile, the serum triglyceride level in the RDGM group was 26.3% lower than that in the RTGM group. The weight-loss effect in the RDGM group was accompanied by a significant decrease in the white adipose tissue (WAT) index. The RDG intervention did not significantly change the antioxidant and anti-inflammatory properties of the rapeseed oil in vivo. The RDG diet improved the liver lipid metabolism abnormalities induced by a high-fat diet, leading to decreased liver damage index values (AST and ALT). Additionally, compared to that in the RTGM group, the expression of the adipogenic genes PPAR-γ and DGAT decreased in both the liver and intestine by 21.7% and 16.7% and by 38.7% and 47.2%, respectively, in the RDGM group. Further, most lipolytic genes in BAT showed no significant change after the RDG intervention. This implies that RDG regulates lipid metabolism by altering the expression of adipogenic genes in the liver, intestine, and adipose tissue, thereby reducing the accumulation of WAT. Furthermore, the RDG diet enhanced gut flora diversity, increasing the relative levels of unclassified Muribaculaceae and decreasing the levels of Dubosiella and Faecalibaculum in the mouse gut, potentially accelerating lipid metabolism. Thus, a three-month RDG diet intervention in obese mice exhibited benefits in regulating the somatotype, serum obesity-related indices, gut flora structure, and lipid metabolism in the adipose tissue, liver, and intestine.
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Fármacos Antiobesidad , Dieta Alta en Grasa , Diglicéridos , Metabolismo de los Lípidos , Hígado , Ratones Endogámicos C57BL , Obesidad , Aceite de Brassica napus , Animales , Metabolismo de los Lípidos/efectos de los fármacos , Obesidad/metabolismo , Diglicéridos/farmacología , Dieta Alta en Grasa/efectos adversos , Masculino , Aceite de Brassica napus/farmacología , Hígado/metabolismo , Hígado/efectos de los fármacos , Ratones , Fármacos Antiobesidad/farmacología , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Triglicéridos/sangre , Diacilglicerol O-Acetiltransferasa/metabolismo , Diacilglicerol O-Acetiltransferasa/genética , Microbioma Gastrointestinal/efectos de los fármacos , PPAR gamma/metabolismo , Ratones ObesosRESUMEN
Helicobacter pylori (H. pylori) is one of the major causes of gastrointestinal diseases, including gastric cancer. However, the acidic environment of the stomach and H. pylori resistance severely impair the antimicrobial efficacy of oral drugs. Here, a biocompatible chitosan-modified molybdenum selenide (MoSe2@CS) was designed for the simultaneous photothermal treatment of H. pylori infection and gastric cancer. MoSe2@CS showed a photothermal conversion efficiency was as high as 45.7 %. In the H. pylori-infected mice model, MoSe2@CS displayed a high bacteriostasis ratio of 99.9 % upon near-infrared irradiation. The antimicrobial functionality was also proved by transcriptomic sequencing study, which showed that MoSe2@CS combined with NIR laser irradiation modulated the gene expression of a variety of H. pylori bioprocesses, including cell proliferation and inflammation-related pathways. Further gut flora analysis results indicated that MoSe2@CS mediated PTT of H. pylori did not affect the homeostasis of gut flora, which highlights its advantages over traditional antibiotic therapy. In addition, MoSe2@CS exhibited a good photothermal ablation effect and significantly inhibited gastric tumor growth in vitro and in vivo. The comprehensive application of MoSe2@CS in the PTT of H. pylori infection and gastric cancer provides a new avenue for the clinical treatment of H. pylori infection and related diseases.
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Quitosano , Infecciones por Helicobacter , Helicobacter pylori , Molibdeno , Neoplasias Gástricas , Helicobacter pylori/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Animales , Ratones , Molibdeno/química , Molibdeno/farmacología , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Línea Celular Tumoral , Terapia FototérmicaRESUMEN
BACKGROUND: Intestinal barrier dysfunction is a significant contributor to the recurrence and refractory of ulcerative colitis (UC). Promoting the interaction between group 3 innate lymphoid cells (ILC3s) and gut flora is a valuable strategy for mucosal repair. Paeoniae decoction (PD) is a compound commonly used in clinical treatment of UC, but its exact mechanism remains unclear. PURPOSE: We aimed to investigate the protective effect of PD on intestinal mucosal injury induced by dextran sulfate sodium (DSS) in chronic colitis, as well as to elucidate its potential mechanism. METHODS: C57BL/6 mice were induced with chronic colitis by 2 % DSS and divided into four groups: control group, model group, PD low dose (4 g/kg), and high dose (8 g/kg) group. The effectiveness of PD in treating chronic colitis mice was evaluated based on changes in body weight, colon length, colon pathological tissue scores, and the mRNA levels of inflammatory factors IL-6 and IL-1ß. The expressions of intestinal epithelial tight junction proteins (ZO-1 and Occludin), IL-22, and MUC2 were observed using immunofluorescence and RT-PCR. Additionally, the proportion of ILC3 and natural cytotoxicity receptor (NCR)+ ILC3 in the colon were detected using flow cytometry. Furthermore, UHPLC-QE-MS was utilized to identify chemical components of PD and network pharmacology was employed to predict potential pathways for PD intervention in UC. Subsequently, MNK-3 cells (ILC3 in vitro cell line) and NCM460 cells were used to verify the network pharmacology results. Finally, the effects of PD on UC gut flora have been explored using in vitro fermentation and 16S rDNA techniques. RESULTS: The results showed that PD significantly restored body weight and colon length in mice with chronic colitis, while also reducing colon inflammatory cell infiltration and the expression of IL-6 and IL-1ß. Additionally, PD notably promoted the expression of MUC2, ZO-1, Occludin, and IL-22, as well as increasing the ratio of ILC3 and NCR+ILC3. UHPLC-QE-MS analysis identified 443 components of PD, and network pharmacology suggested that PD could target the aryl hydrocarbon receptor (AHR) signaling pathway, which was confirmed by MNK-3 cells and in vitro fermentation experiments. Furthermore, MNK-3-conditioned medium (CM) increased the expression of ZO-1 and Occludin in NCM460 cells. In addition, 16S rDNA results indicated that PD promoted the abundance of Lactobacillales, thus contributing to mucosal damage repair by activating the AHR signal in ILC3s. CONCLUSION: In summary, our study demonstrates that PD repairs intestinal mucosal damage in chronic colitis by regulating the interaction of gut flora with ILC3, and the specific mechanism is related to the activation of AHR signaling pathway.
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Sulfato de Dextran , Microbioma Gastrointestinal , Interleucina-22 , Mucosa Intestinal , Ratones Endogámicos C57BL , Paeonia , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Ratones , Masculino , Paeonia/química , Linfocitos/efectos de los fármacos , Proteína de la Zonula Occludens-1/metabolismo , Interleucinas/metabolismo , Modelos Animales de Enfermedad , Interleucina-1beta/metabolismo , Ocludina/metabolismo , Interleucina-6/metabolismo , Colon/efectos de los fármacos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Medicamentos Herbarios Chinos/farmacología , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Mucina 2RESUMEN
Background: Rujin Jiedu decoction (RJJDD) is a classical prescription of Traditional Chinese Medicine that has long been applied to treat pneumonia caused by external infection, but whether and how it benefits influenza virus therapy remains largely unclear. The aim of this study was to investigate the anti-inflammatory effect of RJJDD on the mouse model of influenza and to explore its potential mechanism. Methods: The mice were mock-infected with PBS or infected with PR8 virus followed by treatment with RJJDD or antiviral oseltamivir. The weight loss and morbidity of mice were monitored daily. Network pharmacology is used to explore the potential pathways that RJJDD may modulate. qRT-PCR and ELISA were performed to assess the expression of inflammatory cytokines in the lung tissue and macrophages. The intestinal feces were collected for 16S rDNA sequencing to assess the changes in gut microbiota. Results: We demonstrate that RJJDD protects against IAV-induced pneumonia. Comprehensive network pharmacology analyses of the Mass Spec-identified components of RJJDD suggest that RJJDD may act through down-regulating key signaling pathways producing inflammatory cytokines, which was experimentally confirmed by cytokine expression analysis in IAV-infected mouse lung tissues and IAV single-strand RNA mimic R837-induced macrophages. Furthermore, gut microbiota analysis indicates that RJJDD prevented IAV-induced dysbiosis of host intestinal flora, thereby offering a mechanistic explanation for RJJDD's efficacy in influenza pneumonia. Conclusion: This study defines a previously uncharacterized role for RJJDD in protecting against influenza likely by maintaining homeostasis of gut microbiota, and provides a new therapeutic option for severe influenza.
RESUMEN
Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is derived from the conversion of adenosine triphosphate catalysed by adenylyl cyclase (AC). Protein kinase A (PKA), the main effector of cAMP, is a dimeric protein kinase consisting of two catalytic subunits and two regulatory subunits. When cAMP binds to the regulatory subunits of PKA, it leads to the dissociation and activation of PKA, which allows the catalytic subunit of PKA to phosphorylate target proteins, thereby regulating various physiological functions and metabolic processes in cellular function. Recent researches also implicate the involvement of cAMP-PKA signaling in the pathologenesis of anxiety disorder. However, there are still debates on the prevention and treatment of anxiety disorders from this signaling pathway. To review the function of cAMP-PKA signaling in anxiety disorder, we searched the publications with the keywords including "cAMP", "PKA" and "Anxiety" from Pubmed, Embase, Web of Science and CNKI databases. The results showed that the number of publications on cAMP-PKA pathway in anxiety disorder tended to increase. Bioinformatics results displayed a close association between the cAMP-PKA pathway and the occurrence of anxiety. Mechanistically, cAMP-PKA signaling could influence brain-derived neurotrophic factor and neuropeptide Y and participate in the regulation of anxiety. cAMP-PKA signaling could also oppose the dysfunctions of gamma-aminobutyric acid (GABA), intestinal flora, hypothalamic-pituitary-adrenal axis, neuroinflammation, and signaling proteins (MAPK and AMPK) in anxiety. In addition, chemical agents with the ability to activate cAMP-PKA signaling demonstrated therapy potential against anxiety disorders. This review emphasizes the central roles of cAMP-PKA signaling in anxiety and the targets of the cAMP-PKA pathway would be potential candidates for treatment of anxiety. Nevertheless, more laboratory investigations to improve the therapeutic effect and reduce the adverse effect, and continuous clinical research will warrant the drug development.
Asunto(s)
Ansiedad , Proteínas Quinasas Dependientes de AMP Cíclico , AMP Cíclico , Transducción de Señal , Humanos , AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Animales , Ansiedad/metabolismoRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common and complex endocrine disease in women, with a prevalence of 5% to 18% worldwide. HeQi San (HQS) is a Chinese medicine compound prescription, which has been applied to treat various endocrine and metabolic diseases. OBJECTIVE: The study was intended to investigate the effect of HQS on PCOS, and clarify the potential mechanism via in vivo and in vitro experiments. METHODS: The PCOS mouse model was established by injecting the dehydroepiandrosterone (DHEA) subcutaneously and fading high-fat diet for 3 weeks. After making model, PCOS mice were treated with HQS (8.75 g/kg and 17.5 g/kg, ig.) for 4 weeks. Firstly, we assessed the histopathological changes in ovary tissues and detected the hormone level. Subsequently, the study evaluated the capability of anti-inflammatory and regulating macrophage polarization of HQS in vivo and in vitro. The secretion of inflammation indicators was measured with Elisa kits, and the expression level of phosphorylated nuclear factor kappa-B (P-NFκB) and B-lymphocyte activation antigen B7 (CD80) was measured by immunofluorescence and Western blot. Meanwhile, the apoptosis of ovarian granulosa cells was detected via tunel staining and Western blot. The co-culture model in vitro was utilized to assess the effect between macrophage polarization and human ovarian granulosa cells (KGN cells) apoptosis. Furthermore, 16S rDNA sequencing was utilized to elevate gut microbiota change in PCOS mice. RESULTS: HQS reversed the abnormal hormone increase, ameliorated insulin resistance, and improved histopathological changes of the ovary tissue to exert the therapeutic effect. HQS inhibited the expression of P-NF-κB and decreased the production of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) to further prohibit the macrophage M1 polarization in ovary tissues and macrophages. The apoptosis-positive cells, Bcl-2 Assaciated X protein (BAX), and cleaved-caspase 3 expression were also decreased in the treatment group. The B-cell lymphoma-2 (Bcl2) expression was enhanced after HQS treatment in vivo. The co-culture experiments also verified that HQS could prevent the apoptosis of KGN cells. Furthermore, HQS mediated the abundance of gut flora. The abundance of bifldobacterium and parasutterella was increased and the abundance of lachnoclostridium was decreased. CONCLUSION: The study verified that HQS has the effect of anti-inflammation and inhibits macrophage M1 polarization. Besides, HQS could mediate the abundance of gut microbiota in mice with PCOS. Thus, this study would provide more reasonable basis of HQS for clinical use. In conclusion, HQS might be a potential candidate for PCOS treatment.