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Rationale: Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson's disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated. Methods: We generated an RNA binding motif protein 24 (Rbm24) knockout model to investigate its impact on adult neurogenesis in the SVZ, employing immunofluorescence, immunoblot, electrophysiology, RNA-sequencing, and in vitro experiments. Further investigations utilized a PD mouse model, along with genetic and pharmacological manipulations, to elucidate Rbm24 involvement in PD pathology. Results: Rbm24, a multifaceted post-transcriptional regulator of cellular homeostasis, exhibited broad expression in the SVZ from development to aging. Deletion of Rbm24 significantly impaired NSPC proliferation in the adult SVZ, ultimately resulting in collapsed neurogenesis in the olfactory bulb. Notably, Rbm24 played a specific role in maintaining Notch1 mRNA stability in adult NSPCs. The Rbm24/Notch1 signaling axis was significantly downregulated in the SVZ of PD mice. Remarkably, overexpression of Rbm24 rescued disruption of adult neurogenesis and olfactory dysfunction in PD mice, and these effects were hindered by DAPT, a potent inhibitor of Notch1. Conclusions: Our findings highlight the critical role of the Rbm24/Notch1 signaling axis in regulating adult SVZ neurogenesis under physiological and pathological circumstances. This provides valuable insights into the dynamic regulation of NSPC homeostasis and offers a potential targeted intervention for PD and related neurological disorders.
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Ventrículos Laterales , Ratones Noqueados , Células-Madre Neurales , Neurogénesis , Enfermedad de Parkinson , Proteínas de Unión al ARN , Receptor Notch1 , Transducción de Señal , Animales , Masculino , Ratones , Proliferación Celular , Modelos Animales de Enfermedad , Ventrículos Laterales/metabolismo , Ratones Endogámicos C57BL , Células-Madre Neurales/metabolismo , Trastornos del Olfato/metabolismo , Trastornos del Olfato/genética , Trastornos del Olfato/fisiopatología , Bulbo Olfatorio/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Receptor Notch1/metabolismo , Receptor Notch1/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genéticaRESUMEN
Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.
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The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica- and Ascophyllum nodosum-derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica-derived fucoidans than those of A. nodosum-derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum- and L. japonica-derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica-derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.
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Apolipoproteínas E , Ascophyllum , Hipolipemiantes , Laminaria , Polisacáridos , Animales , Laminaria/química , Ascophyllum/química , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Hipolipemiantes/farmacología , Apolipoproteínas E/genética , Masculino , Ratones Endogámicos C57BL , Triglicéridos/sangre , Triglicéridos/metabolismo , Colesterol/sangre , Colesterol/metabolismo , Ratones Noqueados , PPAR alfa/metabolismo , PPAR alfa/genética , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Hígado/metabolismo , Hígado/efectos de los fármacos , Humanos , Algas ComestiblesRESUMEN
BACKGROUND: Ulcerative colitis (UC) and systemic lupus erythematosus (SLE) are both systemic immunoreactive diseases, and their pathogenesis depends on the interaction between genes and environmental factors. There are no reports of UC with SLE in China, but six cases of SLE with UC have been reported in China. The combination of these two diseases has distinct effects on the pathogenesis of both diseases. CASE SUMMARY: A female patient (30 years old) came to our hospital due to dull umbilical pain, diarrhea and mucous bloody stool in August 2018 and was diagnosed with UC. The symptoms were relieved after oral administration of mesalazine (1 g po tid) or folic acid (5 mg po qd), and the patient were fed a control diet. On June 24, 2019, the patient was admitted for treatment due to anemia and tinnitus. During hospitalization, the patient had repeated low-grade fever and a progressively decreased Hb level. Blood tests revealed positive antinuclear antibody test, positive anti-dsDNA antibody, 0.24 g/L C3 (0.9-1.8 g/L), 0.04 g/L C4 (0.1-0.4 g/L), 32.37 g/L immunoglobulin (8-17 g/L), and 31568.1 mg/24 h total 24-h urine protein (0-150 mg/24 h). The patient was diagnosed with SLE involving the joints, kidneys and blood system. Previously reported cases of SLE were retrieved from PubMed to characterize clinicopathological features and identify prognostic factors for SLE. CONCLUSION: The patient was discharged in remission after a series of treatments, such as intravenous methylprednisolone sodium succinate, intravenous human immunoglobulin, cyclophosphamide injection, and plasma exchange. After discharge, the patient took oral prednisone acetate tablets, cyclosporine capsules, hydroxychloroquine sulfate tablets and other treatments for symptoms and was followed up regularly for 1 month, after which the patient's condition continued to improve and stabilize.
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BACKGROUND: Prior research underscores the significant impact of remnant cholesterol (RC) on stroke occurrence due to its proatherogenic and proinflammatory traits. This study aims to explore diverse risks of new-onset stroke associated with RC, considering distinct inflammation levels in the middle-aged and senior population in China. METHODS: We analyzed 6509 participants from the China Health and Retirement Longitudinal Study (CHARLS) across four waves (2011-2018). We employed a multivariable Cox proportional hazards regression model, incorporated restricted cubic spline techniques, and conducted sensitivity analyses to evaluate the association among RC, high-sensitivity C-reactive protein (hsCRP), and the risk of new-onset stroke. RESULTS: Over 7 years, 540 new-onset strokes occurred. Individuals in the highest quartile of RC levels exhibited a heightened risk of new-onset stroke, with a multivariable-adjusted hazard ratio (HR) peaking at 1.50 (95% confidence interval 1.12-2.00, P for trend = 0.021), showing a non-linear correlation (P nonlinearity = 0.049). High hsCRP alone had an adjusted HR of 1.10 (95% CI 0.87-1.39), compared to 1.40 (95% CI 1.00-1.96) for high RC alone. Additionally, concurrent high RC and hsCRP showed an adjusted HR of 1.43 (95% CI 1.05-1.96). Consistency persisted across various hsCRP thresholds, after adjusting for additional parameters, or excluding chronic diseases in the primary model, reinforcing result robustness. CONCLUSION: Our findings reveal a substantial and non-linear association between higher baseline RC levels and an elevated risk of new-onset stroke. Moreover, elevated levels of both RC and hsCRP jointly pose the highest risk for new-onset stroke, surpassing the risk associated with each factor individually.
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Colesterol , Inflamación , Accidente Cerebrovascular , Humanos , Masculino , Femenino , China/epidemiología , Estudios Longitudinales , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/sangre , Inflamación/sangre , Inflamación/epidemiología , Colesterol/sangre , Jubilación , Factores de Riesgo , Biomarcadores/sangre , Estudios de SeguimientoRESUMEN
The prognosis of patients with nonvalvular atrial fibrillation (NVAF) with a low CHA2DS2-VASc score (0-1) following a stroke is not well studied. In this investigation, stroke risk factors and prognostic markers in low-risk NVAF patients who are nonetheless at risk for stroke were examined.From January 2012 to January 2022, we retrospectively assessed atrial fibrillation (AF) patients at Xiamen University's Zhongshan Hospital for ischemic stroke. Along with a control group of patients with CHA2DS2-VASc scores of 0-1 who weren't suffering from a stroke, patients with CHA2DS2-VASc scores of 0-1 at the time of stroke were included in the study. Using multivariate logistic regression, independent risk factors were identified. To assess the cumulative occurrences of in-hospital mortality in patients with NVAF-related stroke, the Kaplan-Meier method was used.The study included 156 out of 3.237 inpatients with AF-related stroke who had CHA2DS2-VASc ratings of 0-1. Left atrial diameter (LAD) (odds ratio [OR]: 1.858, 95% confidence interval (CI) 1.136-3.036, P = 0.013), D-dimer (OR: 2.569, 95% CI 1.274-5.179, P = 0.008), and NT-proBNP (OR: 4.558, 95% CI 2.060-10.087, P = 0.000) were found to be independent risk factors for stroke in NVAF patients with a low CHA2DS2-VASc score. During hospitalization, nine patients with NVAF-related stroke died. In patients with NVAF-related stroke, NT-proBNP (hazard ratio: 3.504, 95% CI 1.079-11.379, P = 0.037) was an indicator of mortality risk.Patients with NVAF and CHA2DS2-VASc scores of 0-1 had independent risk factors for stroke in the form of LAD, D-dimer, and NT-proBNP. Notably, in low-risk NVAF patients with stroke, NT-proBNP was discovered to be a potent predictor of in-hospital death.
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Fibrilación Atrial , Accidente Cerebrovascular , Humanos , Pronóstico , Estudios Retrospectivos , Mortalidad Hospitalaria , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Medición de RiesgoRESUMEN
OBJECTIVE: Estrogen (E2) is the main contributor to the progression of endometrial cancer (EC). The long noncoding RNA HOX antisense intergenic RNA (HOTAIR) is emerging as a new regulator in several cancer types. This study aimed to investigate the role of HOTAIR in EC development and identify the underlying molecular mechanisms. METHODS: HOTAIR expression levels in human EC tissues and the corresponding adjacent tissues and human EC Ishikawa cells were determined by quantitative PCR. Ishikawa cells were treated with E2 or estrogen receptor (ER) inhibitor ICI182780, transfected with siHOTAIR oligo, or infected with lentivirus expressing shHOTAIR/shNC, alone or in combinations. The protein expression of polycomb repressive complex 2 (PRC2) was evaluated by western blotting, and cell migration was measured by transwell assays. A xenograft tumorigenic model was established by inoculating control or stable shHOTAIR-infected Ishikawa cells into nude mice and implanting 17ß-estradiol release pellets. RESULTS: HOTAIR expression was significantly elevated in human EC tissues. E2 exposure markedly increased HOTAIR levels in Ishikawa cells. Notably, E2 increased the protein expression of PRC2 and promoted EC cell migration, which were dependent on HOTAIR expression, as HOTAIR knockdown abolished these effects of E2. Similarly, E2 promoted the in vivo proliferation of grafted Ishikawa cells via upregulated HOTAIR expression in nude mice. CONCLUSIONS: Human EC tissues highly express HOTAIR, and E2-induced EC progression depends on HOTAIR expression. This work suggests that the E2-HOTAIR axis is a potential therapeutic target in EC therapy.
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Neoplasias Endometriales , ARN Largo no Codificante , Animales , Femenino , Humanos , Ratones , Apoptosis , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Estrógenos/farmacología , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , ARN Largo no Codificante/genéticaRESUMEN
Singapore grouper iridovirus (SGIV) is a new ranavirus species in the Iridoviridae family, whose high lethality and rapid spread have resulted in enormous economic losses for the aquaculture industry. Curcumin, a polyphenolic compound, has been proven to possess multiple biological activities, including antibacterial, antioxidant, and antiviral properties. This study was conducted to determine whether curcumin protected orange-spotted grouper (Epinephelus coioides) from SGIV-induced intestinal damage by affecting the inflammatory response, cell apoptosis, oxidative stress, and intestinal microbiota. Random distribution of healthy orange-spotted groupers (8.0 ± 1.0 cm and 9.0 ± 1.0 g) into six experimental groups (each group with 90 groupers): Control, DMSO, curcumin, SGIV, DMSO + SGIV, and curcumin + SGIV. The fish administered gavage received DMSO dilution solution or 640 mg/L curcumin every day for 15 days and then were injected intraperitoneally with SGIV 24 h after the last gavage. When more than half of the groupers in the SGIV group perished, samples from each group were collected for intestinal health evaluation. Our results showed that curcumin significantly alleviated intestine damage and repaired intestinal barrier dysfunction, which was identified by decreased intestine permeability and serum diamine oxidase (DAO) activity and increased expressions of tight junction proteins during SGIV infection. Moreover, curcumin treatment suppressed intestinal cells apoptosis and inflammatory response caused by SGIV and protected intestinal cells from oxidative injury by enhancing the activity of antioxidant enzymes, which was related to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Moreover, we found that curcumin treatment restored the disruption of the intestinal microbiota caused by SGIV infection. Our study provided a theoretical basis for the functional development of curcumin in aquaculture by highlighting the protective effect of curcumin against SGIV-induced intestinal injury.
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Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg-1·d-1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 µM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aß generation by inhibiting the ß-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aß plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aß generation in early AD, which is a potential therapeutic intervention for early AD treatment.
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Enfermedad de Alzheimer , Neuroblastoma , Enfermedades Neurodegenerativas , Ratones , Humanos , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Ácido Aspártico Endopeptidasas/metabolismo , Ratones Transgénicos , Retina/metabolismo , Modelos Animales de Enfermedad , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismoRESUMEN
BACKGROUND: Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson's disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. RESULTS: We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. CONCLUSIONS: Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.
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BACKGROUND: Jasminoidin (JA) and ursodeoxycholic acid (UA) were shown to act synergistically against ischemic stroke (IS) in our previous studies. PURPOSE: To investigate the holistic synergistic mechanism of JA and UA on cerebral ischemia. METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) mice were used to evaluate the efficacy of JA, UA, and JA combined with UA (JU) using neurological function testing and infarct volume examination. High-throughput RNA-seq combined with computational prediction and function-integrated analysis was conducted to gain insight into the comprehensive mechanism of synergy. The core mechanism was validated using western blotting. RESULTS: JA and UA synergistically reduced cerebral infarct volume and alleviated neurological deficits and pathological changes in MCAO/R mice. A total of 1437, 396, 1080, and 987 differentially expressed genes were identified in the vehicle, JA, UA, and JU groups, respectively. A strong synergistic effect between JA and UA was predicted using chemical similarity analysis, target profile comparison, and semantic similarity analysis. As the 'long-tail' drugs, the top 20 gene ontology (GO) biological processes of JA, UA, and JU groups primarily reflected inflammatory response and regulation of cytokine production, with specific GO terms of JU revealing enhanced regulation on immune response and tumor necrosis factor superfamily cytokine production. Comparably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling of common targets of JA, UA, and JU focused on extracellular matrix organization and signaling by interleukins, immune system, phagosomes, and lysosomes, which interlock and interweave to produce the synergistic effects of JU. The characteristic signaling pathway identified for JU highlighted the crosstalk between autophagy activation and inflammatory pathways, especially the Dectin-1-induced NF-κB activation pathway, which was validated by in vivo experiments. CONCLUSIONS: JA and UA can synergistically protect cerebral ischemia-reperfusion injury by attenuating Dectin-1-induced NF-κB activation. The strategy integrating high throughput data with computational models enables ever-finer mapping of 'long-tail' drugs to dynamic variations in condition-specific omics to clarify synergistic mechanisms.
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Isquemia Encefálica , Daño por Reperfusión , Ratones , Animales , FN-kappa B/metabolismo , Ácido Ursodesoxicólico/farmacología , Transducción de Señal , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Daño por Reperfusión/metabolismo , CitocinasRESUMEN
Great progress has been made in understanding the neural mechanisms associated with alcohol-dependent (AD) patients. However, the interactions within the reward circuits of the patients need further exploration. Glutamatergic projections from the prefrontal cortex to some brain regions are present in the reward circuit. However, little is known about the potential implications of glutamate levels in the prefrontal cortex on abnormal interactions within reward circuits in AD patients. To determine the potential roles of reward circuits in drinking, we investigated differences in resting-state functional connectivity (RSFC) and multivariate Granger causality analysis between 20 AD patients and 20 healthy controls (HC). The neuroimaging findings were then correlated with clinical variables (alcohol use disorder identification test). The ventromedial prefrontal cortex (VmPFC) is believed to play a critical role in addiction disorders, and glutamatergic projections from the prefrontal cortex to several regions of the brain are present in reward circuits. Proton magnetic resonance spectroscopy was also performed to assess the difference in glutamate levels in VmPFC between AD patients and HC. The results showed that the strength of functional connectivity in the reward circuit was generally attenuated in AD patients, and the reciprocal enhancement of activity between the right insula, left thalamus and VmPFC was found to be significantly greater in AD patients. It is worth noting that although glutamate levels in the VmPFC did not show significant differences between the two groups, the level of glutamate in the VmPFC was significantly correlated with RSFC. We hope that the current findings will help us to develop new intervention models based on the important role of the VmPFC in AD.
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Alcoholismo , Ácido Glutámico , Humanos , Alcoholismo/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Encéfalo , Etanol , Recompensa , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Ischemic stroke (IS) is a leading cause of death and severe long-term disability worldwide. Over the past few decades, considerable progress has been made in anti-ischemic therapies. However, IS remains a tremendous challenge, with favourable clinical outcomes being generally difficult to achieve from candidate drugs in preclinical phase testing. Traditional herbal medicine (THM) has been used to treat stroke for over 2,000 years in China. In modern times, THM as an alternative and complementary therapy have been prescribed in other Asian countries and have gained increasing attention for their therapeutic effects. These millennia of clinical experience allow THM to be a promising avenue for improving clinical efficacy and accelerating drug discovery. PURPOSE: To summarise the clinical evidence and potential mechanisms of THMs in IS. METHODS: A comprehensive literature search was conducted in seven electronic databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database, from inception to 17 June 2022 to examine the efficacy and safety of THM for IS, and to investigate experimental studies regarding potential mechanisms. RESULTS: THM is widely prescribed for IS alone or as adjuvant therapy. In clinical trials, THM is generally administered within 72 h of stroke onset and are continuously prescribed for over 3 months. Compared with Western medicine (WM), THM combined with routine WM can significantly improve neurological function defect scores, promote clinical total effective rate, and accelerate the recovery time of stroke with fewer adverse effects (AEs). These effects can be attributed to multiple mechanisms, mainly anti-inflammation, antioxidative stress, anti-apoptosis, brain blood barrier (BBB) modulation, inhibition of platelet activation and thrombus formation, and promotion of neurogenesis and angiogenesis. CONCLUSIONS: THM may be a promising candidate for IS management to guide clinical applications and as a reference for drug development.
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Terapias Complementarias , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Medicamentos Herbarios Chinos/efectos adversos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Medicina Tradicional , Accidente Cerebrovascular/tratamiento farmacológico , Medicina Tradicional ChinaRESUMEN
Gastric cancer (GC) is a common gastrointestinal tumor. Gastric precancerous lesions (GPL) are the last pathological stage before normal gastric mucosa transforms into GC. However, preventing the transformation from GPL to GC remains a challenge. Traditional Chinese medicine (TCM) has been used to treat gastric disease for millennia. A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL. This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC, especially focusing on anti-inflammatory, anti-angiogenesis, proliferation, and apoptosis. This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.
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Methicillin-resistant Staphylococcus aureus (MRSA) can induce multiple inflammations. The biofilm formed by MRSA is resistant to a variety of antibiotics and is extremely difficult to cure, which seriously threatens human health. Herein, a nanoparticle encapsulating berberine with polypyrrole core and pH-sensitive shell to provide chemo-photothermal dual therapy for MRSA infection is reported. By integrating photothermal agent polypyrrole, berberine, acid-degradable crosslinker, and acid-induced charge reversal polymer, the nanoparticle exhibited highly efficient MRSA infection treatment. In normal uninfected areas and bloodstream, nanoparticles showed negatively charged, demonstrating high biocompatibility and excellent hemocompatibility. However, once arriving at the MRSA infection site, the nanoparticle can penetrate and accumulate in the biofilm within 2 h. Simultaneously, berberine can be released into biofilm rapidly. Under the combined effect of photothermal response and berberine inhibition, 88.7% of the biofilm is removed at 1000 µg mL-1 . Moreover, the nanoparticles have an excellent inhibitory effect on biofilm formation, the biofilm inhibition capacity can reach up to 90.3%. Taken together, this pH-tunable nanoparticle can be employed as a new generation treatment strategy to fight against the fast-growing MRSA infection.
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Berberina , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Polímeros/farmacología , Polímeros/uso terapéutico , Berberina/farmacología , Berberina/uso terapéutico , Pirroles/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Biopelículas , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) transport and transmit intercellular information and play an essential role in physiological and pathological processes. MSC-EVs, MSC-EVs-microRNA, and genetically modified MSC-EVs are involved in the onset and progression of different liver diseases and play a role in reducing liver cell damage, promoting liver cell regeneration, inhibiting liver fibrosis, regulating liver immunity, alleviating liver oxidative stress, inhibiting liver cancer occurrence, and others. Hence, it will replace MSCs as a research hotspot for cell-free therapy. This article reviews the research progress of MSC-EVs in liver diseases and provides a new basis for cell-free therapy of clinical liver diseases.
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Humanos , Vesículas Extracelulares , MicroARNs/genética , Neoplasias Hepáticas , Células Madre MesenquimatosasRESUMEN
Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) is a common severe clinical syndrome in intensive care unit, may lead to a life-threatening form of respiratory failure, resulting in high mortality up to 30-40% in most studies. Nanotechnology-mediated anti-inflammatory therapy is an emerging novel strategy for the treatment of ALI, has been demonstrated with unique advantages in solving the dilemma of ALI drug therapy. Artesunate (ART), a derivative of artemisinin, has been reported to have anti-inflammatory effects. Therefore, in the present study, we designed and synthesized PEGylated ART prodrugs and assessed whether ART prodrugs could attenuate lipopolysaccharide (LPS) induced ALI in vitro and in vivo. All treatment groups were conditioned with ART prodrugs 1 h before challenge with LPS. Significant increased inflammatory cytokines production and decreased GSH levels were observed in the LPS stimulated mouse macrophage cell line RAW264.7. Lung histopathological changes, lung W/D ratio, MPO activity and total neutrophil counts were increased in the LPS-induced murine model of ALI via nasal administration. However, these results can be reversed to some extent by treatment of ART prodrugs. The effectiveness of mPEG2k-SS-ART in inhibition of ALI induced by LPS was confirmed. In conclusion, our results demonstrated that the ART prodrugs could attenuate LPS-induced ALI effectively, and mPEG2k-SS-ART may serve as a novel strategy for treatment of inflammation induced lung injury.
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BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a frequent cause of acute coronary syndrome in young to middle-aged women with few or no traditional cardiovascular risk factors. Chest pain is the most frequently described presenting symptom, but syncope is extremely rare. Herein, we report on a 16-year-old girl who presented with an episode of syncope occurring during a race. Despite significantly elevated troponin level, the diagnosis of the left main coronary artery SCAD with cardiogenic shock was delayed. CASE SUMMARY: A 16-year-old girl presented with an episode of syncope. Myocardial injury markers were positive. Echocardiography showed a mildly reduced left ventricular ejection fraction (50%). Although initially stable, she later experienced recurrent chest pain accompanying precordial ST segment elevation with dynamic changes and developed cardiogenic shock, necessitating emergent revascularization. Coronary angiography demonstrated almost total occlusion at the ostium and proximal segment of the left main trunk coronary artery (LMT). Intravascular ultrasound confirmed a false lumen with prominent dissection in the LMT. Percutaneous coronary intervention assisted by intra-aortic balloon pump was conducted in the LMT. A 3.5 mm × 24 mm everolimus-eluting stent was deployed to the focal lesions of the LMT. A postprocedural electrocardiogram showed alleviation of the precordial ST-segment elevation. The diagnosis of SCAD was confirmed. Transthoracic echocardiography showed an improved left ventricular ejection fraction (57%). The patient was asymptomatic during the 24-mo. follow-up period. CONCLUSION: SCAD should always be considered in the differential diagnosis of acute coronary syndrome presentations in low-risk patients, regardless of age.
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Background: The role of soluble interleukin-1 receptor type 2 (sIL-1R2) in acute myocardial infarction (AMI) remains undocumented. In the present study, we aimed to evaluate the possible associations of sIL-1R2 with left ventricular (LV) function, remodeling and future clinical events in the setting of AMI. Methods: Circulating sIL-1R2 levels were quantified after percutaneous coronary intervention (PCI) on day 1 of hospital admission for 204 AMI patients, and upon enrollment of 204 healthy controls. Echocardiography was conducted in the acute phase and at 12-month follow-up. Adverse clinical events were registered after 12 months. Results: Circulating sIL-1R2 levels were significantly higher in AMI patients than in healthy controls (medians respectively 6652.81 pg/mL, 3799.13 pg/mL, p < 0.0001). AMI patients with sIL-1R2 levels less than the median had a larger proportion of worsened LV ejection fraction [a decrease in LV ejection fraction (LVEF) of more than 10% units] and reduced LVEF (a final LVEF < 50%). After multivariate adjustment, sIL-1R2 levels less than the median were associated with an increased risk of worsened LVEF [odds ratio (OR): 3.7, 95% confidence interval (CI): 1.6-8.5, p = 0.002] and reduced LVEF at 12 months (OR: 2.1, 95% CI: 1.1-4.3, p = 0.035). Moreover, low sIL-1R2 levels were associated with an increased risk of having an adverse clinical event during the first 12 months after AMI [hazard ratio (HR): 2.5, 95% CI: 1.0-6.1, p = 0.039]. Conclusions: Low levels of circulating sIL-1R2 were associated with impaired recovery of LV function and adverse clinical outcomes in AMI patients. These findings might contribute to understanding the important role of sIL-1R2 in postinfarction inflammation.