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5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake.
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Background Pancreatic adenocarcinoma (PAAD) is a highly aggressive and malignant cancer type with the highest mortality rate of all major cancers. However, the molecular and tumor immune escape mechanism underlying pancreatic cancer remains largely unclear. α-enolase (ENO1) is a glycolytic enzyme reported to overexpress in a variety of cancer types. This study was undertaken to investigate the functional role and therapeutic potential of ENO1 in pancreatic cancer. Methods We examined the expression levels of ENO1 across a broad spectrum of cancer types from the TCGA database. ENO1-knockout (ENO1-KO) through CRISPR/CAS9 technology in a mouse pancreatic cancer cell line (PAN02) was used to analyze the role of ENO1 on proliferation and colony formation. Flow cytometry and RT-PCR were also applied to analyze T lymphocytes and relevant cytokines. Results In the present study, we identified that ENO1 promoted pancreatic cancer cell proliferation. Our bioinformatics data indicated that ENO1 was significantly overexpressed in pancreatic cancer cell lines and tissues. Survival analyses revealed that ENO1 overexpression implicated poor survival of PAAD patients. Knockout of ENO1 expression repressed the ability of proliferation and colony formation in PAN02. In addition, ENO1-KO significantly decreased tumor growth in mouse models. Further flow cytometry and RT-PCR analysis revealed that ENO1-KO modulates the tumor microenvironment (TME), especially in suppressed Treg cells and inducing anti-tumor cytokine responses. Conclusions Taken together, our data showed that ENO1 was an oncogenic biomarker and might serve as a promising target for immunotherapy of pancreatic cancer (AU)
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Humanos , Animais , Masculino , Feminino , Neoplasias Pancreáticas/patologia , Adenocarcinoma/patologia , Terapia de Imunossupressão , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Camundongos Knockout , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Microambiente TumoralRESUMO
Analyzing neuronal activities is essential to deciphering the function of neural circuits. In anesthetized rodents, simultaneous multisite recording of extracellular electrophysiological activity with defined electrical stimulation is a powerful tool to dissect reciprocal relationships between brain structures. Here, we present a protocol to simultaneously record from the subthalamic nucleus and substantia nigra pars reticulata while stimulating the pedunculopontine tegmental nucleus in anesthetized rats. This protocol describes the preparation of recording and stimulating electrodes, surgery setup, and detailed recording techniques. Basic post-recording data analysis methods are included as well. This protocol can be adapted to other brain areas of interest following the outlined procedures. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Assembly of recording and stimulating electrodes Basic Protocol 2: Implantation of recording and stimulating electrodes in an anesthetized rat Basic Protocol 3: Simultaneous recording from the STN and SNr with PPTg stimulation Basic Protocol 4: Histological verification of recording sites Basic Protocol 5: Analysis of electrophysiological data.
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Núcleo Tegmental Pedunculopontino , Núcleo Subtalâmico , Ratos , Animais , Substância Negra/fisiologia , Estimulação Elétrica , Núcleo Subtalâmico/fisiologia , Neurônios/fisiologiaRESUMO
Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aß aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila ß-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aß burden largely, but not exclusively, via dSir2.
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Doença de Alzheimer , Proteínas de Drosophila , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Drosophila/fisiologia , Proteínas de Drosophila/metabolismo , Resveratrol/farmacologia , Sirtuína 1 , SonoRESUMO
Loss of fragile X messenger ribonucleoprotein (FMRP) causes fragile X syndrome (FXS), the most prevalent form of inherited intellectual disability. Here, we show that FMRP interacts with the voltage-dependent anion channel (VDAC) to regulate the formation and function of endoplasmic reticulum (ER)-mitochondria contact sites (ERMCSs), structures that are critical for mitochondrial calcium (mito-Ca2+) homeostasis. FMRP-deficient cells feature excessive ERMCS formation and ER-to-mitochondria Ca2+ transfer. Genetic and pharmacological inhibition of VDAC or other ERMCS components restored synaptic structure, function, and plasticity and rescued locomotion and cognitive deficits of the Drosophila dFmr1 mutant. Expressing FMRP C-terminal domain (FMRP-C), which confers FMRP-VDAC interaction, rescued the ERMCS formation and mito-Ca2+ homeostasis defects in FXS patient iPSC-derived neurons and locomotion and cognitive deficits in Fmr1 knockout mice. These results identify altered ERMCS formation and mito-Ca2+ homeostasis as contributors to FXS and offer potential therapeutic targets.
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Proteínas de Drosophila , Síndrome do Cromossomo X Frágil , Animais , Camundongos , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/metabolismo , Cálcio/metabolismo , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Drosophila/metabolismo , Camundongos Knockout , Homeostase , Mitocôndrias/metabolismo , Retículo Endoplasmático/metabolismo , Canais de Ânion Dependentes de Voltagem/metabolismo , Proteínas de Drosophila/metabolismoRESUMO
Background: Hepatic portal vein collateral circulation plays an important role in maintaining the perfusion of hepatic portal vein. However, at present, there is little research on collateral circulation of hepatic portal vein. Our study aims to analysis the imaging types and clinical value of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) invading and completely blocking different branches of portal vein, secondary to hepatic portal vein collateral circulation. Methods: This study retrospectively analyzed Hepatocellular carcinoma (HCC) with PVTT diagnosed with enhanced CT examination of the upper abdomen in our hospital from May 2020 to October 2021.The inclusion criteria for patients were the following: (I) ultimately diagnosed with HCC, (II) accompanied by complete obstruction of the main portal vein or left/right branches, and (III) with collateral circulation of the hepatic portal vein established. All images were postprocessed by multiplanar reconstruction (MPR), maximum intensity projection (MIP), and other reconstruction techniques to obtain images of the abnormal portal vein system and the collateral vessels running toward the hepatic portal veins. Three physicians jointly judged the imaging anatomical classification of each collateral vessel. The qualitative variables were compared by chi-squared test. Results: A total of 125 hepatic portal vein collateral vessels were observed in MPR and MIP reconstruction images of 71 patients with portal vein cancer thrombosis with established hepatic portal vein collateral circulation. Common hepatic collateral branches in patients with PVTT mainly include the biliary collateral branch, gastric collateral branch, mesenteric collateral branch, accessory portal vein system and the splenic branch. The incidence rate was respectively 77.5%, 36.6%, 32.4%, 28.2%, 1.41%. Conclusions: The correct understanding of the imaging anatomical classification of the collateral vessels of the hepatic portal vein can provide clinicians with more information for diagnosis and treatment planning.
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BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a highly aggressive and malignant cancer type with the highest mortality rate of all major cancers. However, the molecular and tumor immune escape mechanism underlying pancreatic cancer remains largely unclear. α-enolase (ENO1) is a glycolytic enzyme reported to overexpress in a variety of cancer types. This study was undertaken to investigate the functional role and therapeutic potential of ENO1 in pancreatic cancer. METHODS: We examined the expression levels of ENO1 across a broad spectrum of cancer types from the TCGA database. ENO1-knockout (ENO1-KO) through CRISPR/CAS9 technology in a mouse pancreatic cancer cell line (PAN02) was used to analyze the role of ENO1 on proliferation and colony formation. Flow cytometry and RT-PCR were also applied to analyze T lymphocytes and relevant cytokines. RESULTS: In the present study, we identified that ENO1 promoted pancreatic cancer cell proliferation. Our bioinformatics data indicated that ENO1 was significantly overexpressed in pancreatic cancer cell lines and tissues. Survival analyses revealed that ENO1 overexpression implicated poor survival of PAAD patients. Knockout of ENO1 expression repressed the ability of proliferation and colony formation in PAN02. In addition, ENO1-KO significantly decreased tumor growth in mouse models. Further flow cytometry and RT-PCR analysis revealed that ENO1-KO modulates the tumor microenvironment (TME), especially in suppressed Treg cells and inducing anti-tumor cytokine responses. CONCLUSIONS: Taken together, our data showed that ENO1 was an oncogenic biomarker and might serve as a promising target for immunotherapy of pancreatic cancer.
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Adenocarcinoma , Neoplasias Pancreáticas , Animais , Camundongos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Terapia de Imunossupressão , Camundongos Knockout , Neoplasias Pancreáticas/patologia , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
BACKGROUND: Intracranial atherosclerotic stenosis is a major cause of ischemic stroke, accounting for 30% of ischemic strokes in Asian populations. PURPOSE: To investigate the relationship between the degree of arterial stenosis and enhancement grade of intracranial atherosclerotic disease (ICAD), the plaque characteristics in different remodeling patterns, and its potential impact. MATERIAL AND METHODS: A total of 210 patients diagnosed with ICAD were enrolled in this retrospective study. Patients were divided into the middle cerebral artery (MCA) group (101 cases), posterior cerebral artery (PCA) group (14 cases), basilar artery (BA) group (71 cases), and intracranial segment of vertebral artery (VA) group (90 cases) according to the difference of diseased vessels. Data on presence or absence of ischemic infarction, intracranial vascular position of lesions, plaque characteristics, ICAD enhancement grade, remodeling index, and degree of arterial stenosis were collected for analysis. RESULTS: The incidence of ischemic infarction in enhancement grade 2 was significantly higher than that in enhancement grade 1 in MCA group (P = 0.019). Enhancement grade 2 of ICAD was an independent risk factor for the development of ischemic infarction (odds ratio = 4.60; 95% confidence interval: 1.91-11.03; P = 0.001). There was no significant statistical difference in infarct rate between different remodeling modalities (P>0.05). CONCLUSION: Enhancement grade of ICAD is significantly associated with the degree of stenosis and the occurrence of ischemic stroke, which varies in different intracranial vessels. The pattern of vascular remodeling varies among different intracranial vessels, and the pattern of vascular remodeling has a significant impact on plaque characteristics.
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Aterosclerose , Arteriosclerose Intracraniana , AVC Isquêmico , Placa Aterosclerótica , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Constrição Patológica , Remodelação Vascular , Imageamento por Ressonância Magnética/efeitos adversos , Angiografia por Ressonância Magnética , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Aterosclerose/complicações , Infarto/complicações , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: The persistent trigeminal artery (PTA) is the most common remnant of primitive circulation, communicating the developing carotid and vertebrobasilar junction. PURPOSE: This study aimed to evaluate the implementation of magnetic resonance angiography for the detection of PTA and to reclassify the variations based on Weon typing. Moreover, the correlation of various Weon types with the posterior cerebral artery (PCA), Willis ring, basilar artery (BA) dysplasia, and the relationship between PTA and arteriosclerosis were analyzed. METHODS: From November 2017 to October 2019, a total of 48,184 patients underwent magnetic resonance angiography examination in our hospital, and 79 patients were diagnosed with PTA. Of these, 70 patients with complete radiological and clinical information were included in this study. RESULTS: Among the 70 patients with complete data, 27 were classified as Weon type I (38.6%), 7 as type II (10%), 14 as type III (20%), 8 as type IV (11.4%), and 3 as type V (4.3%: type Va, 1 case; type Vb, 2 cases). The remaining 11 cases were PCA with mixed blood supply, so the new type VI was divided into 3 subtypes: type VIa, type VIb, and type VIc, and each subtype of type V was further refined into 4 subtypes. There were 32 cases of PTA with BA dysplasia, including 14 with type I (51.9%), 5 with type II (71.4%), 2 with type III (14.3%), 5 with type IV (62.5%), and 6 with type VI (54.5%). Cerebral infarction was found in 55 cases (78.6%) of PTA, among which 11 had a cerebral infarction in the posterior circulation blood supply area. There were 46 cases (65.7%) accompanied by intracranial arteriosclerosis, and in 6 cases, arteriosclerosis mainly occurred in the posterior circulation. CONCLUSIONS: We redefined the classification of PTA based on Weon typing for a better understanding of clinical symptoms and surgical risks. Moreover, PTA was correlated with the fetal origin of PCA, BA dysplasia, and posterior circulation arteriosclerosis. These factors may increase the incidence of cerebral infarction in the posterior circulation blood supply area.
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Artéria Basilar , Angiografia por Ressonância Magnética , Artéria Basilar/diagnóstico por imagem , Infarto Cerebral , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância MagnéticaRESUMO
OBJECTIVE: To investigate the etiology of intracranial artery stenosis and the distribution characteristics of intracranial artery atherosclerotic stenosis using high-resolution magnetic resonance imaging (HR-MRI). METHODS: A total of 262 patients with intracranial artery stenosis that underwent HR-MRI from November 2019 to December 2020 were retrospectively enrolled. The etiology of intracranial anterior and posterior circulation artery stenosis was analyzed, and the relationship between the location of plaques and the distribution characteristics of plaques and the occurrence of ischemic stroke was summarized. RESULTS: A total of 276 plaques were identified with HR-MRI. There were 101 cases (36.59%) in the middle cerebral artery (MCA), 14 cases (5.07%) in the posterior cerebral artery (PCA), 90 cases (32.62%) in vertebral artery (VA), and 71 cases (25.72%) in the basilar artery (BA). The infarct rate of ventral and superior wall MCA plaques was higher than that of dorsal and inferior wall (63.33% vs 31.25% P = 0.021) (100.00% vs 50% P = 0.022). MCA with plaques throughout the course had the greatest degree of stenosis (P < 0.001). Sphenoid segment (M1) of MCA was most susceptible (85 cases, 84.16%), MCA plaques were most common in the proximal M1 segment (35 cases, 34.65%), and most BA plaques were found in the distal segment (28 cases, 39.44%). PCA plaques were most frequently involved in traffic anterior segment (P1) (7 cases, 50.00%). CONCLUSION: HR-MRI could provide accurate imaging reference for clinical evaluation of intracranial arterial stenosis and formulation of treatment plans. The intracranial arterial plates mostly appeared in the middle cerebral artery and vertebral artery. Middle cerebral arteries with atherosclerotic plaques are more likely to narrow.
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Arteriosclerose Intracraniana , Placa Aterosclerótica , Constrição Patológica/diagnóstico por imagem , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/patologia , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Estudos RetrospectivosRESUMO
α-Enolase (ENO1), also known as 2-phospho-D-glycerate hydrolase, is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid during glycolysis. It is a multifunctional oncoprotein that is present both in cell surface and cytoplasm, contributing to hit seven out of ten "hallmarks of cancer." ENO1's glycolytic function deregulates cellular energetic, sustains tumor proliferation, and inhibits cancer cell apoptosis. Moreover, ENO1 evades growth suppressors and helps tumors to avoid immune destruction. Besides, ENO1 "moonlights" on the cell surface and acts as a plasminogen receptor, promoting cancer invasion and metastasis by inducing angiogenesis. Overexpression of ENO1 on a myriad of cancer types together with its localization on the tumor surface makes it a great prognostic and diagnostic cancer biomarker as well as an accessible oncotherapeutic target. This review summarizes the up-to-date knowledge about the relationship between ENO1 and cancer, examines ENO1's potential as a cancer biomarker, and discusses ENO1's role in novel onco-immunotherapeutic strategies.
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Evidence suggests that impaired synaptic and firing homeostasis represents a driving force of early Alzheimer's disease (AD) progression. Here, we examine synaptic and sleep homeostasis in a Drosophila model by overexpressing human amyloid precursor protein (APP), whose duplication and mutations cause familial early-onset AD. We find that APP overexpression induces synaptic hyperexcitability. RNA-seq data indicate exaggerated expression of Ca2+-related signaling genes in APP mutants, including genes encoding Dmca1D, calcineurin (CaN) complex, and IP3R. We further demonstrate that increased CaN activity triggers transcriptional activation of Itpr (IP3R) through activating nuclear factor of activated T cells (NFAT). Strikingly, APP overexpression causes defects in synaptic downscaling and sleep deprivation-induced sleep rebound, and both defects could be restored by inhibiting IP3R. Our findings uncover IP3R as a shared signaling molecule in synaptic downscaling and sleep homeostasis, and its dysregulation may lead to synaptic hyperexcitability and AD progression at early stage.
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Precursor de Proteína beta-Amiloide , Sono , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Homeostase , Humanos , Receptores de Inositol 1,4,5-Trifosfato , Ativação Transcricional , Regulação para Cima/genéticaRESUMO
OBJECTIVE: To evaluate the utility of multidetector computed tomography MDCT quantitative measurements in identifying sarcopenia. MATERIALS AND METHODS: The clinical data and MDCT images of 64 patients of sarcopenia and 184 non-sarcopenic participants between October 2020 and January 2021were retrospectively analyzed. Propensity score matching was used to match the sarcopenic patients with the non-sarcopenic participants. Two radiologists independently measured the cross-sectional area (CSA) of skeletal muscle and intramuscular fat tissue and CT density of skeletal muscle at the middle L3 vertebral level on CT images of all participants. Intra-observer agreement was evaluated via intraclass correlation coefficients (ICC). A receiver operating characteristic (ROC) curve was built for each variable. Correlations between CT parameters and clinical data were assessed via Pearson or Spearman correlation coefficient. RESULTS: A total of 74 participants (mean age 72 ± 4 years, range 66-85 years; 38 men and 36 women) were included, comprising 37 sarcopenic patients and 37 non-sarcopenic participants. There were no significant intergroup differences regarding age, sex ratio, and body mass index (BMI) (P < 0.05). The CSA and density of skeletal muscle measured by two radiologists were reliable (ICC ≥ 0.75, P < 0.001). Compared with the sarcopenic group, the non-sarcopenic group had a significantly greater CSA and CT density of the total skeletal muscle (TSM) and paraspinal skeletal muscle (PSM) and skeletal muscle index at L3 level (L3 SMI) (P < 0.05). The fat infiltration ratio (FIR) of TSM, PSM, and psoas muscle was significantly higher in the sarcopenic group than that in non-sarcopenic participants (P < 0.05). ROC curve analysis showed the PSM FIR + PSM CT density (PSM D) had the best predictive value for sarcopenia (AUC = 0.836). The PSM FIR and age were moderately positively correlated (r = 0.410, P < 0.001). CONCLUSION: Fat infiltration of skeletal muscle had better predictive value than L3 SMI in the diagnosis of sarcopenic. The PSM FIR + PSMD had the best predictive value for sarcopenia, which was moderately positively correlated with age.
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Sarcopenia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Tomografia Computadorizada Multidetectores , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Pontuação de Propensão , Músculos Psoas/diagnóstico por imagem , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: The association between the cardiometabolic index (CMI) and hyperuricemia was investigated to provide theoretical support for the management of hyperuricemia in an asymptomatic population with normal body mass index (BMI). METHODS: A cross-sectional study was carried out among 374 asymptomatic adults with normal BMI. Traditional anthropometric indices and CMI were calculated. Anthropometric indices were divided into four quartiles and multivariate logistic analysis was used to analyze the association between these indices and hyperuricemia. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate the power of the indices to predict hyperuricemia values. The DeLong test was used to compare the AUC of different anthropometric indices. RESULTS: After adjusting for confounding variables, the CMI exhibited a stronger association with hyperuricemia than other anthropometric indices. The odds ratio (OR) for hyperuricemia in the highest quartile of the CMI was 16.674 (confidence interval [CI]=4.424-62.846). The AUC of the CMI was 0.777 (95% CI=0.719-0.835, p<0.001), which was higher than the values for other anthropometric indices. The differences in AUC between the CMI and other indices were statistically significant; the optimal cutoff value of the CMI was 0.655, with sensitivity of 57.1% and specificity of 84.2%. CONCLUSION: The CMI, which combines waist circumference, height and blood lipid parameters, was more strongly associated with hyperuricemia than other anthropometric indices in asymptomatic population with normal BMI. The CMI may serve as a potential monitoring indicator for hyperuricemia management in asymptomatic populations with normal BMI.
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TENM4, encoding a member of the teneurin protein family, is a risk gene shared by many types of mental diseases and is implicated in neuronal plasticity and signaling. However, the role and the mechanisms of TENM4 in schizophrenia (SCZ) remain unclear. We identified possible pathogenic mutations in the TENM4 gene through target sequencing of TENM4 in 68 SCZ families. We further demonstrated that aberrant expression of Ten-m leads to lower learning ability, sleep reduction, and increased aggressiveness in animal models. RNA sequencing showed that aberrant expression of Ten-m was related to stimulus perception and metabolic process, and Gene Ontology enrichment terms were neurogenesis and ATPase activity. This study provides strong evidence that TENM4 contributes to SCZ, and its functional mutations might be responsible for the impaired neural circuits and behaviors observed in SCZ.
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ABSTRATCIn recent years, emerging studies have observed gut microbiota (GM) alterations in Alzheimer's disease (AD), even in individuals with mild cognitive impairment (MCI). Further, impaired sleep and circadian patterns are common symptoms of AD, while sleep and circadian rhythm disruption (SCRD) is associated with greater ß-amyloid (Aß) burden and AD risk, sometimes years before the clinical onset of AD. Moreover, reports have demonstrated that GM and its metabolites exhibit diurnal rhythmicity and the role of SCRD in dampening the GM rhythmicity and eubiosis. This review will provide an evaluation of clinical and animal studies describing GM alterations in distinct conditions, including AD, sleep and circadian disruption. It aims to identify the overlapping and distinctive GM alterations in these conditions and their contributions to pathophysiology. Although most studies are observational and use different methodologies, data indicate partial commonalities in GM alterations and unanimity at functional level. Finally, we discuss the possible interactions between SCRD and GM in AD pathogenesis, as well as several methodological improvements that are necessary for future research.
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Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Ritmo Circadiano/fisiologia , Microbioma Gastrointestinal/fisiologia , Sono/fisiologia , Animais , Modelos Animais de Doenças , HumanosRESUMO
AIM OF THE STUDY: To explore the high-resolution magnetic resonance imaging (HR-MRI) characteristics of central nervous system (CNS) vasculitis and to explore the value of HR-MRI in the treatment effect and prognosis evaluation of CNS vasculitis. MATERIAL AND METHODS: During the follow-up of 24 patients diagnosed as CNS vasculitis by the Second Hospital of Hebei Medical University, 3.0T HR-MRI was used for imaging examination and HR-MRI characteristics were analysed. RESULTS: The affected vessel wall of 24 patients showed diffuse uniform centripetal thickening. The HR-MRI examination showed varying degrees of lumen stenosis, including 5 cases (20.8%) involving a single arterial segment, and 19 cases (79.2%) involving multiple arterial segments. And most cases (92.9%) showed grade 2 enhancement of the involved vessel wall. Except for one case involving the basilar artery at the same time, the remaining 23 cases involved only the anterior circulation vessels. We analysed and compared the affected vessels between the relapsed group and the non-relapsed group, and found that the average number of involved vascular segments was 6.5 ±3.4 (3-11) in the relapsed group and 3.5 ±2.1 (1-8) in the non-relapsed group, with a significant difference between the two groups (p = 0.039). CONCLUSIONS: The CNS vasculitis was more likely to involve the anterior circulation vessels. The number of affected vascular segments in the relapsed group of CNS vasculitis was higher than in the non-relapsed group, suggesting that the more vascular segments involved, the more prone to recurrence.
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Vasculite do Sistema Nervoso Central , Artéria Basilar , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Prognóstico , Vasculite do Sistema Nervoso Central/diagnósticoRESUMO
OBJECTIVES: To identify the prevalence of anaemia among older adults in China by sociodemographic and geographical regions, and cross-sectionally examine the associations between anaemia and several geriatric outcomes. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Participants were 6656 older adults aged at least 60 years with haemoglobin data from the 2015 to 2016 wave of the China Health and Retirement Longitudinal Study. METHODS: We examined the prevalence of anaemia by sociodemographics (age, sex, residence, education, marital status) and geographical regions, adjusting for age. We investigated the associations between anaemia and geriatric conditions. RESULTS: The prevalence of anaemia was 20.6% among adults ≥60 years and was higher at advanced ages, among those who were females, living in rural areas, and those who were unmarried. The southern region of China had a higher burden of anaemia than the north. Anaemic adults had a higher age-adjusted prevalence of falls, activities of daily living (ADL) disability, instrumental ADL disability, lower extremely functional limitation, upper extremely functional limitation, low gait speed, low grip strength and low self-reported memory. CONCLUSIONS: Anaemia affected approximately one in five older adults in China, particularly in those with disadvantaged sociodemographics, and anaemia was associated with a higher burden of geriatric conditions. Huge geographical disparities of anaemia prevalence between northern and southern regions reflected the dietary variations in different regions. Efforts on preventing anaemia and reducing regional disparities of anaemia were needed to improve older adults' health in China.
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Anemia , Vida Independente , Aposentadoria , Atividades Cotidianas , Idoso , Anemia/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Avaliação Geriátrica , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
PURPOSE: High-resolution magnetic resonance imaging (HR-MRI) has high spatial resolution and can simultaneously perform wall and lumen imaging. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can evaluate the integrity of the blood-brain barrier. In this paper, the result of 3.0T HR-MRI and 3.0T DCE-MRI has been evaluated to explore the application value of unilateral middle cerebral artery inflammatory stenosis and changes in vascular permeability parameters of stroke events. METHODS: Thirty-six cases of neurological suspicion of central nervous system vasculitis of our hospital were selected from 20 January 2018 to 1 January 2019, who were diagnosed as unilateral middle cerebral artery M1 stenosis/occlusion by 3D TOF MRA. 3.0T HR-MRI and 3.0T DCE-MRI has been applied. RESULTS: Among the 36 patients who met the inclusion criteria, 23 patients with central nervous system vasculitis were diagnosed. The 23 patients with HR-MRI showed diffuse thickening and enhanced stenosis. The Ktrans value of 10/23 patients with acute-subacute cerebral infarction and 3/23 patients in chronic phase were significantly higher than that of the mirror side, and the Ktrans value of these patients remeasured in the same region of interest is lower than before after 6 months treatment. The Ktrans value in the target area of 10 patients without cerebrovascular events was not statistically significant compared with the mirror side. The Ktrans value of patients with acute-subacute cerebral infarction was significantly higher than that without cerebrovascular events (0.098 ± 0.038 vs. 0.007 ± 0.001, p = .000), and there was no significant difference between Ktrans in the chronic infarction group and the other two groups (0.098 ± 0.038 vs. 0.044 ± 0.012, p = .058; 0.044 ± 0.012 vs. 0.007 ± 0.001, p = .057). CONCLUSION: HR-MRI is an accurate direct imaging method and has a high value for the etiological diagnosis of central nervous system vasculitis. DCE-MRI could be an effective way to evaluate and monitor blood-brain barrier to prevent clinical ischemic stroke.