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Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.
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Vacina BCG , Tuberculose , Humanos , Ácido Linoleico , Imunidade Treinada , Multiômica , Adjuvantes Imunológicos/farmacologiaRESUMO
Diabetic kidney disease is one of the complications of diabetes mellitus, which can eventually progress to end-stage kidney disease. The increasing prevalence of diabetic kidney disease has brought huge economic burden to society and seriously jeopardized public health. Ferroptosis is an iron-dependent, non-apoptosis-regulated form of cell death. The regulation of ferroptosis involves different molecular mechanisms and multiple cellular metabolic pathways. In recent years, ferroptosis has been proved to be closely related to the occurrence and development of diabetic kidney disease, and can interact with pathological changes such as fibrosis, inflammation, oxidative stress, and disorders of glucose and lipid metabolism, destroying the structure, form and function of the inherent cells of the kidney, and promoting the progression of the disease. Traditional Chinese medicine has a long history of treating diabetic kidney disease with remarkable curative effect. Current scholars have shown that the oral administration of traditional Chinese medicine and the external treatment of Chinese medicine can regulate GPX4, Nrf2, ACSL4, PTGS2, TFR1 and other key signaling molecules, curb ferroptosis, and prevent the progressive deterioration of diabetic kidney disease. In this paper, the mechanism of ferroptosis and diabetic kidney disease and the prevention and treatment of traditional Chinese medicine are analyzed and summarized, in order to provide new ideas and new plans for the treatment of diabetic kidney disease.
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Diabetes Mellitus , Nefropatias Diabéticas , Ferroptose , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Medicina Tradicional Chinesa , Rim , Administração OralRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic kidney disease (DKD) poses a severe threat to human health. Compound Xiancao Granule (CXCG), a classic Zhuang medicinal formula, is reported as highly effective in treating DKD. However, the mechanisms underlying the action of CXCG in DKD remain unclear. AIM OF THE STUDY: This study aimed to investigate the mechanisms of action of CXCG against DKD using multi-omics analysis, including 16s rRNA sequencing, metabolomics, and transcriptomics. MATERIALS AND METHODS: The chemical compounds of CXCG were identified using ultra-high- performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry analysis. A rat model of DKD was established by combining nephrectomy of the left kidney, high-fat diet, and streptozotocin. The therapeutic effects of CXCG on DKD were assessed based on body weight, blood glucose level, renal function, inflammatory cytokine levels, and histological staining. Subsequently, 16s rRNA sequencing, liquid chromatography-tandem mass spectrometry untargeted metabolomic profiling, and RNA sequencing analysis were used to investigate the mechanisms of action of CXCG in DKD. Spearman's correlation analysis was performed to elucidate the correlations between efficacy indicators, gut microbiota, metabolites, and inflammation-related genes. RESULTS: A total of 118 compounds were identified in CXCG. CXCG significantly ameliorated glucose metabolism disorders, improved renal function, attenuated inflammation, and delayed renal pathological changes in DKD rats. CXCG modulated gut microbiota dysbiosis, including Alloprevotella, Oscillibacter, Anaeroplasma, Anaerotruncus, and Faecalibacterium. In addition, metabolic disruption in DKD rats was regulated by CXCG, which is involved in the metabolism of carbohydrates and amino acids. Transcriptome analysis showed that CXCG affected DKD mainly by regulating inflammation-related genes and pathways, such as the PI3K/Akt and MAPK signaling pathways. Furthermore, there were significant correlations between efficacy indicators, gut microbiota, metabolites, and genes. CONCLUSION: This multi-omics association study provides novel insights into the effects of CXCG on DKD by remodeling the gut microbiota structure and restoring the metabolic homeostasis through the regulation of carbohydrate metabolism, amino acid metabolism, and inflammation-related pathways, highlighting a potential therapeutic strategy for DKD.
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Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Animais , Ratos , Nefropatias Diabéticas/tratamento farmacológico , RNA Ribossômico 16S , Multiômica , Fosfatidilinositol 3-Quinases , InflamaçãoRESUMO
Panax notoginseng (P. notoginseng) is an invaluable perennial medicinal herb. However, the roots of P. notoginseng are frequently subjected to severe damage caused by root-knot nematode (RKN) infestation. Although we have observed that P. notoginseng possessed adult-plant resistance (APR) against RKN disease, the defense response mechanisms against RKN disease in different age groups of P. notoginseng remain unexplored. We aimed to elucidate the response mechanisms of P. notoginseng at different stages of development to RKN infection by employing transcriptome, metabolome, and histochemistry analyses. Our findings indicated that distinct age groups of P. notoginseng may activate the phenylpropanoid and flavonoid biosynthesis pathways in varying ways, leading to the synthesis of phenolics, flavonoids, lignin, and anthocyanin pigments as both the response and defense mechanism against RKN attacks. Specifically, one-year-old P. notoginseng exhibited resistance to RKN through the upregulation of 5-O-p-coumaroylquinic acid and key genes involved in monolignol biosynthesis, such as PAL, CCR, CYP73A, CYP98A, POD, and CAD. Moreover, two-year-old P. notoginseng enhanced the resistance by depleting chlorogenic acid and downregulating most genes associated with monolignol biosynthesis, while concurrently increasing cyanidin and ANR in flavonoid biosynthesis. Three-year-old P. notoginseng reinforced its resistance by significantly increasing five phenolic acids related to monolignol biosynthesis, namely p-coumaric acid, chlorogenic acid, 1-O-sinapoyl-D-glucose, coniferyl alcohol, and ferulic acid. Notably, P. notoginseng can establish a lignin barrier that restricted RKN to the infection site. In summary, P. notoginseng exhibited a potential ability to impede the further propagation of RKN through the accumulation or depletion of the compounds relevant to resistance within the phenylpropanoid and flavonoid pathways, as well as the induction of lignification in tissue cells.
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Keystone species of microbial communities play a very important role in community structure and ecosystem function; however, the effect of long-term nitrogen (N) and phosphorus (P) fertilizers on key taxa and the mechanisms of community construction of rhizosphere microbial communities remain unclear. In this study, the effect of nine fertilization treatments (N0P0, N0P1, N0P2, N1P0, N1P1, N1P2, N2P0, N2P1, and N2P2) on soil microbial community diversity, keystone species, and construction methods in the crop rhizosphere were studied in a loess hilly area after 26 years of fertilization. The results showed that fertilization significantly increased the nutrient contents of the rhizospheric soil and root system and significantly affected microbial community composition (based on the Bray-Curtis distance) and community construction process (ß-nearest taxon index: ßNTI). The decrease in the abundance of oligotrophic bacteria (from phyla Acidobacteriota and Chloroflexi) in the keystone species of bacterial communities shifted the community construction process from homogenizing dispersal to variable selection process and was significantly regulated by soil factors (total P and carbon-N ratio). However, the decrease in the abundance of keystone species (from phylum Basidiomycota) in the fungal communities did not have a significant effect on community construction, which was mainly affected by root characteristics (root N content and soluble sugar). This study found that long-term N and P fertilization changed the keystone species composition of bacterial communities by affecting the nutrient content of the rhizospheric soil, such as total P, so that the construction mode of communities changed from a stochastic to a deterministic process, and the N2 fertilization, especially the N1P2 treatment was better for increasing network stability (modularity and clustering coefficient).
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Microbiota , Rizosfera , Fertilizantes/análise , Nitrogênio/análise , Fósforo/química , Microbiologia do Solo , Solo/química , BactériasRESUMO
Non-conventional seed oils are being considered novelty foods due to the unique properties of their chemical constituents. Numerous such seed oils serve as nutritional and functional supplements, making them a point of interest for scholars. Bitter gourd (Momordica charantia L.) seed oil (BGSO) has been widely used in folk medicine worldwide for the treatment of different pathologies, such as diabetes, cancer, and several inflammatory diseases. Therefore, its nutritional and medicinal value has been extensively studied. Considering the potential use of BGSO, it is imperative to have a comprehensive understanding of this product to develop and use its biologically active ingredients in innovative food and pharmaceutical products. An extensive understanding of BGSO would also help improve the economic feasibility of the bitter gourd seed processing industry and help prevent environmental pollution associated with the raw waste produced during the processing of bitter gourd seeds. This review addresses the potential uses of BGSO in terms of food and pharmaceuticals industry perspectives and comprehensively summarizes the oil extraction process, chemical composition, biological activity, and the application prospects of BGSO in clinical medicine.
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Momordica charantia , Neoplasias , Humanos , Momordica charantia/química , Sementes , Suplementos Nutricionais , Óleos de PlantasRESUMO
Exosomes are small extracellular vesicles and play an essential role in the mediation of intercellular communication both in health and disease. Traditional Chinese medicine (TCM) has historically been used to maintain human health and treat various diseases up till today. The interplay between exosomes and TCM has attracted researchers' growing attention. By integrating the available evidence, TCM formulas and compounds isolated from TCM as exosome modulators have beneficial effects on multiple disorders, such as tumors, kidney diseases, and hepatic disease, which may associate with inhibiting cells proliferation, anti-inflammation, anti-oxidation, and attenuating fibrosis. Exosomes, a natural delivery system, are essential in delivering compounds isolated from TCM to target cells or tissues. Moreover, exosomes may be the potential biomarkers for TCM syndromes, providing strategies for TCM treatment. These findings may provide a novel insight into TCM from exosomes and serve as evidence for better understanding and development of TCM.
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Acute alcoholic liver injury (AALI) is a threat to human health. Dendrobium officinale polysaccharide (DOP) has the potential to protect the liver by enhancing the anti-oxidative system to maintain the relative balance of ROS (active oxygen species) and antioxidants in AALI mice. However, the dynamic improvement effect of DOP on AALI is still not clear and accurate medication guidance is not available, which limits the clinical application of DOP. Because of the advantages of high sensitivity, noninvasiveness, and visualization, near-infrared (NIR) fluorescence imaging has been widely studied in biochemistry and biomedicine. As the glutathione (GSH) level in the liver is closely related to the progression of AALI, herein, an NIR fluorescent probe for GSH, HCG was used to dynamically evaluate the effect of DOP on AALI mice. In this study, DOP was proven to maintain the relative balance of GSH content in the liver to protect it from damage. To the best of our knowledge, it is the first time to assess the effect of DOP on AALI mice through a NIR fluorescence imaging technique. This study may also provide a potential NIR imaging agent for the clinical research to improve the management of liver injury-related diseases.
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Dendrobium/química , Hepatite Alcoólica/prevenção & controle , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Espectrometria de Fluorescência/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Doença Aguda , Animais , Glutationa/metabolismo , Hepatite Alcoólica/metabolismo , Fígado/metabolismo , CamundongosRESUMO
Diets of overloaded purine-rich foods for a long time are one of the important reasons to cause renal lesions. Eucommia ulmoides is one of the traditional Chinese medicine herbs, which has been used to recover functions of the kidney. However, its mechanism remains unclear. The aim of this study was to explore the effects and protective mechanism of Eucommia ulmoides extract on renal injury caused by long-term high purine diets in rats. SD rats underwent an intragastric adenine (200 mg kg-1 d-1) administration for 9 weeks and were treated for 15 weeks. The results demonstrated that Eucommia ulmoides extract significantly reduced serum Cre and BUN levels in rats. H&E and Masson's trichrome stains showed notable lowering of the infiltration of inflammatory cells, the formation of fibrous tissues and collagen fibers, and improvement in the pathological morphology of kidneys. It also suppressed the protein and mRNA expressions of TGF-ß1 and α-SMA and enhanced E-cadherin expression. Meanwhile, Eucommia ulmoides extract prominently inhibited the mRNA expression of Col I, Col III, Col IV, TIMP-1, and TIMP-2 and promoted expressions of MMP-1, MMP-2 and MMP-9. Through our study, it is the first time to prove that Eucommia ulmoides extract could ameliorate renal interstitial fibrosis and may involve in the regulation of the extracellular matrix (ECM) degradation enzyme (MMPs/TIMPs) system, promotion of the expression of E-cadherin, and suppression of expressions of TGF-ß1 and α-SMA. The results provide a significant implication for the utilization of Eunomia Ulmoides extract as functional foods to enhance renal functions and improve renal injury caused by high purine diets.
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Eucommiaceae/química , Rim/efeitos dos fármacos , Rim/lesões , Extratos Vegetais/farmacologia , Purinas/administração & dosagem , Animais , Caderinas/metabolismo , Medicamentos de Ervas Chinesas , Rim Fundido/metabolismo , Rim Fundido/patologia , Rim/patologia , Masculino , Medicina Tradicional Chinesa , Ratos , Ratos Sprague-Dawley , Insuficiência Renal , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: Women report a higher incidence of sleep problems than men. Few studies addressing the effect of gender on the efficacy of administering auricular acupressure (AA) at shenmen points (heart meridian 7 [HT7]) on sleep quality have been published. PURPOSE: The primary aim of this study was to investigate the effects of a 4-week AA intervention applied at the HT7 points on sleep quality, perceived physical health, and perceived mental health in community-dwelling individuals with poor self-reported sleep quality. Additional analyses were used to evaluate the gender-specific effects of this intervention. METHODS: A cluster randomized controlled trial with repeated-measures design was used. One hundred seventy-nine eligible participants were randomly assigned to either the AA group (n = 88; 47 women, 41 men) or the sleep hygiene instruction (SHI) group (n = 91; 52 women, 39 men). The AA group self-administered acupressure at HT7 on both ears for a 4-week period, whereas the SHI group received an SHI information sheet. Outcome measures included the Pittsburgh Sleep Quality Index (PSQI) and the Short-Form Health Survey-12 Version 2, with data collected at baseline and at 2, 4, and 8 weeks posttest. RESULTS: Linear mixed-model analysis revealed that the participants in the AA group experienced significantly greater reductions in mean PSQI global score and the three indices of sleep latency, subjective sleep quality, and daytime dysfunction than the SHI group at 2 and 4 weeks posttest. The improvements in subjective sleep quality and daytime dysfunction remained at 4 weeks posttest in the AA group, but not in the SHI group. The PSQI global score decreased significantly more in men than women in the AA group between baseline and 4 weeks posttest. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Four weeks of self-administered acupressure at HT7 on both ears is an effective intervention for community-dwelling poor sleepers who are over 45 years old. Moreover, the improvements in subjective sleep quality and daytime dysfunction persist for up to 4 weeks after the end of the intervention. This self-administered acupressure intervention is more effective in men than in women in terms of improving sleep quality. Gender bias is known to influence research results and may lead to inappropriate generalizations. Thus, future studies that are performed to build basic scientific evidence should include considerations of the effects of gender in the study design.
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Acupressão , Distúrbios do Início e da Manutenção do Sono , Feminino , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Autorrelato , Sexismo , Sono , Distúrbios do Início e da Manutenção do Sono/terapiaRESUMO
Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting (GV24) and Baihui (GV20) acupoints, with a dilatational wave (1-20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3K/Akt signaling pathway-related factors Beclin-1, mammalian target of rapamycin (mTOR), and PI3K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting (GV24) and Baihui (GV20) acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China (approval No. 8150150901) on March 10, 2016.
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Schizophrenia has prominent functional dysconnectivity, especially in the prefrontal cortex (PFC). However, it is unclear whether in the same group of patients with schizophrenia, PFC functional dysconnectivity appears in an organized manner or is stochastically located in different subregions. By investigating the resting-state functional connectivity (rsFC) of each PFC subregion from the Brainnetome atlas in 40 schizophrenia patients and 40 healthy subjects, we found 24 altered connections in schizophrenia, and the connections were divided into four categories by a clustering analysis: increased connections within the PFC, increased connections between the inferior PFC and the thalamus/striatum, reduced connections between the PFC and the motor control areas, and reduced connections between the orbital PFC and the emotional perception regions. In addition, the four categories of rsFC showed distinct cognitive engagement patterns. Our findings suggest that PFC subregions have specific functional dysconnectivity patterns in schizophrenia and may reflect heterogeneous symptoms and cognitive deficits in schizophrenia.
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Transtornos Cognitivos , Esquizofrenia , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , TálamoRESUMO
The ventral tegmental area (VTA) has dopamine, GABA, and glutamate neurons, which have been implicated in reward and aversion. Here, we determined whether VTA-glutamate or -GABA neurons play a role in innate defensive behavior. By VTA cell-type-specific genetic ablation, we found that ablation of glutamate, but not GABA, neurons abolishes escape behavior in response to threatening stimuli. We found that escape behavior is also decreased by chemogenetic inhibition of VTA-glutamate neurons and detected increases in activity in VTA-glutamate neurons in response to the threatening stimuli. By ultrastructural and electrophysiological analysis, we established that VTA-glutamate neurons receive a major monosynaptic glutamatergic input from the lateral hypothalamic area (LHA) and found that photoinhibition of this input decreases escape responses to threatening stimuli. These findings indicate that VTA-glutamate neurons are activated by and required for innate defensive responses and that information on threatening stimuli to VTA-glutamate neurons is relayed by LHA-glutamate neurons.
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Agressão/fisiologia , Ácido Glutâmico/fisiologia , Neurônios/fisiologia , Área Tegmentar Ventral/citologia , Área Tegmentar Ventral/fisiologia , Animais , Reação de Fuga , Humanos , Região Hipotalâmica Lateral/citologia , Região Hipotalâmica Lateral/fisiologia , Hipotálamo/citologia , Hipotálamo/fisiologia , Camundongos , Neurônios/ultraestrutura , Optogenética , Estimulação Luminosa , Reflexo Monosináptico/fisiologia , Área Tegmentar Ventral/ultraestrutura , Ácido gama-Aminobutírico/fisiologiaRESUMO
BACKGROUND: Osteoporosis is a chronic bone metabolism disorder affecting millions of the world population. The RANKL/RANK/OPG signaling pathway has been confirmed to be the main regulator of osteoporosis. It is of great interest to identify appropriate therapeutic agents that can regulate the RANKL/RANK/OPG pathway. Baicalin (BA) is a well-known traditional Chinese medicine formula against various inflammatory diseases with a proven role of the RANKL/RANK/OPG pathway regulation. However, the potential effect of BA on osteoporosis and the mechanisms underlying this remain unclear. In the present study, we aimed to evaluate the efficacy of BA in the prevention of dexamethasone (DEX)-induced osteoporosis in zebrafish. METHODS: In this study, growth and development changes of zebrafish and calcein staining were assessed with a micrograph. The expression levels of RANKL and OPG and transcription factors in response to DEX induction and BA administration were evaluated by Western blotting and qRT-PCR. In addition, the intermolecular interactions of BA and RANKL were investigated by molecular docking. RESULTS: Results show that BA enhances the growth and development of dexamethasone (DEX)-induced osteoporosis in zebrafish larvae. Calcein staining and calcium and phosphorus determination revealed that BA ameliorates mineralization of DEX-induced osteoporosis zebrafish larvae. BA also regulates the expression of RANKL and OPG and hampers the changes in gene expression related to bone formation and resorption under the induction of DEX in zebrafish. It can be inferred by molecular docking that BA may interact directly with the extracellular domain of RANKL. CONCLUSION: The findings, herein, reveal that BA ameliorates DEX-induced osteoporosis by regulation of the RANK/RANKL/OPG signaling pathway.
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Dexametasona/antagonistas & inibidores , Flavonoides/farmacologia , Osteoporose/tratamento farmacológico , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Larva/efeitos dos fármacos , Larva/metabolismo , Simulação de Acoplamento Molecular , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoporose/induzido quimicamente , Osteoprotegerina/genética , Ligante RANK/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/genética , Peixe-ZebraRESUMO
The disruption of salience network (SN) has been consistently found in patients with schizophrenia and thought to give rise to specific symptoms. However, the functional dysconnectivity pattern of SN remains unclear in first-episode schizophrenia (FES). Sixty-five patients with FES and sixty-six health controls (HC) were enrolled in this study and underwent resting-state functional magnetic resonance imaging (rs-fMRI). The eleven regions of interest (ROIs) within SN were derived from the peaks of the group independent component analysis (gICA). Seed-based whole-brain functional connectivity (FC) analyses were performed with all SN ROIs as the seeds. Both hyper- and hypo-connectivity of SN were found in the FES. Specifically, the increased FC mainly existed between the SN and cortico-cerebellar sub-circuit and prefrontal cortex, while the reduced FC mainly existed within cortico-striatal-thalamic-cortical (CSTC) sub-circuit. Our findings suggest that FES is associated with pronounced dysregulation of SN, characterized prominently by hyperconnectivity of SN-prefrontal cortex and cerebellum, as well as hypoconnectivity of CSTC sub-circuit of the SN.
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Esquizofrenia , Mapeamento Encefálico , Córtex Cerebral , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , TálamoRESUMO
A high-fat diet (HFD) is the main cause of metabolic diseases. However, HFD in previous studies consists of much lard, which contains a large amount of omega-6 (ω-6) polyunsaturated fatty acid (PUFA) and little omega-3 (ω-3) PUFA. The role of ω-6/ω-3 ratio of HFD in the development of metabolic diseases remains incompletely discussed. In this study, rats were fed with either a low or a high ω-6/ω-3 ratio HFD singly or combined with inulin. Metabolism state was valued and metabolomics of cecal content were detected. Results show that HFD with low ω-6/ω-3 ratio promotes the glucose utilization in rats. However, inulin had different effects on metabolism with different diets. Xanthosine and kynurenic acid in cecum were positively related to epididymal white adipose tissues (eWAT) mass. The present study indicates the beneficial effects of low ω-6/ω-3 ratio HFD (LRD) on the metabolic state of rats. Moreover, xanthosine and kynurenic acid were closely related to the development of metabolic diseases.
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Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Mucosa Intestinal/metabolismo , Inulina/metabolismo , Doenças Metabólicas/dietoterapia , Purinas/metabolismo , Triptofano/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Dieta Hiperlipídica , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-6/análise , Glucose/metabolismo , Humanos , Masculino , Doenças Metabólicas/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
CONTEXT: Eucommia ulmoides Oliver (Eucommiaceae) has various medicinal properties. Our previous studies revealed that Eucommia ulmoides has a protective effect on hyperuricaemia. OBJECTIVE: This study investigates the effect of Eucommia ulmoides cortex ethanol extract (EU) on hyperuricaemia and explores the underlying mechanism in Kunming mice and Sprague-Dawley rats. MATERIAL AND METHODS: Sixty mice and sixty rats were divided into normal control, hyperuricaemia, allopurinol (10 mg/kg) and three EU groups. The EU groups received intragastric EU at 80, 160, 320 mg/kg in mice and 100, 200, 400 mg/kg in rats for 7 days. Serum uric acid (SUA) was measured using a kit. mRNA and proteins were quantified by RT-qPCR and immunohistochemical assays (IHC), respectively. RESULTS: The Maximal Tolerable Dose (MTD) of EU administered intragastrically was 18 g/kg in mice. The intermediate (160 mg/kg) and high (320 mg/kg) EU treatment significantly reduced (p < 0.05) SUA levels to 130.16 µmol/L and 109.29 µmol/L, respectively, and markedly elevated the mRNA expression of organic anion transporters 1 (OAT1) and organic anion transporters 3 (OAT3), while significantly deceasing the mRNA levels of glucose transporter 9 (GLUT9) and uric acid transporter 1 (URAT1) in the mouse kidney (p < 0.05). In hyperuricemic rats, high EU (400 mg/kg) significantly reduced SUA levels to 253.85 µmol/L, and increased OAT1 and OAT3 levels, but decreased URAT1 and GLUT9, compared to the hyperuricaemia group (p < 0.05). DISCUSSION AND CONCLUSIONS: This study demonstrated the potential hyperuricaemia ameliorating effect of EU. Specific active ingredients in EU should be evaluated. These results are valuable for the development of antihyperuritic agents from EU.
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Eucommiaceae/química , Hiperuricemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Etanol/química , Feminino , Masculino , Dose Máxima Tolerável , Proteínas de Membrana Transportadoras/genética , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Ácido Úrico/sangueRESUMO
To date, many safety assessments of genetically modified (GM) food have been done, but there was still considerable skepticism about the safety of genetic modified foods because no study could be designed to discover all of the potential effects. Since behavioral endpoints could provide one of the most sensitive strategies to reveal subtle functional deficits. In the present study, behavioral profiles in mice fed with milk derived from human lactoferrin gene-modified cows were investigated to enrich the toxicological data of GM food. Conventional milk and GM milk were added to diets at a proportion of 7.5%, 15% and 30%(w/w). After the mice consuming different diets for 30 days, a battery of behavioral tests were conducted to evaluate motor, sensory and cognitive functions. No significant differences were observed in spontaneous activity, grip strength and nociception between the treatment groups. And animals of different groups exhibited similar performance in rotarod, dark box, step-down and MORRIS water maze task. The study suggested that mice fed with conventional milk or human lactoferrin gene-modified milk had similar motor, sensory and cognitive functions.