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1.
J Am Heart Assoc ; 13(10): e034145, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38761086

RESUMEN

BACKGROUND: This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. METHODS AND RESULTS: This is a longitudinal analysis of the population-based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility-weighted imaging. We assessed vertex-wise cortex maps and diffusion maps at both baseline and follow-up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex-wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow-up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (ß=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold-free cluster enhancement P<0.05, adjusted for age and sex). Of particular interest, we found a bidirectional trend association between DMVs number and change in brain volumes. Specifically, participants with mild DMVs disruption showed greater cortical enlargement, whereas those with severe disruption exhibited more significant brain atrophy, primarily involving clusters in the frontal and parietal lobes (multiple comparison corrected P<0.05, adjusted for age, sex, and total intracranial volume). CONCLUSIONS: Our findings posed the dynamic pattern of brain parenchymal lesions related to DMVs injury, shedding light on the interactions and chronological roles of various pathological mechanisms.


Asunto(s)
Venas Cerebrales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Venas Cerebrales/diagnóstico por imagen , Venas Cerebrales/patología , Estudios Longitudinales , China/epidemiología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adulto , Anciano
2.
Brain Imaging Behav ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713331

RESUMEN

While alterations in cortical thickness have been widely observed in individuals with alcohol dependence, knowledge about cortical thickness-based structural covariance networks is limited. This study aimed to explore the topological disorganization of structural covariance networks based on cortical thickness at the single-subject level among patients with alcohol dependence. Structural imaging data were obtained from 61 patients with alcohol dependence during early abstinence and 59 healthy controls. The single-subject structural covariance networks were constructed based on cortical thickness data from 68 brain regions and were analyzed using graph theory. The relationships between network architecture and clinical characteristics were further investigated using partial correlation analysis. In the structural covariance networks, both patients with alcohol dependence and healthy controls displayed small-world topology. However, compared to controls, alcohol-dependent individuals exhibited significantly altered global network properties characterized by greater normalized shortest path length, greater shortest path length, and lower global efficiency. Patients exhibited lower degree centrality and nodal efficiency, primarily in the right precuneus. Additionally, scores on the Alcohol Use Disorder Identification Test were negatively correlated with the degree centrality and nodal efficiency of the left middle temporal gyrus. The results of this correlation analysis did not survive after multiple comparisons in the exploratory analysis. Our findings may reveal alterations in the topological organization of gray matter networks in alcoholism patients, which may contribute to understanding the mechanisms of alcohol addiction from a network perspective.

3.
J Psychiatr Res ; 172: 402-410, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38458112

RESUMEN

We aimed to examine the hypotheses that glucolipid metabolism is linked to neurocognition and gray matter volume (GMV) and that GMV mediates the association of glucolipid metabolism with neurocognition in first-episode, drug-naïve (FEDN) patients with schizophrenia. Parameters of glucolipid metabolism, neurocognition, and magnetic resonance imaging were assessed in 63 patients and 31 controls. Compared to controls, patients exhibited higher levels of fasting glucose, triglyceride, and insulin resistance index, lower levels of cholesterol and high-density lipoprotein cholesterol, poorer neurocognitive functions, and decreased GMV in the bilateral insula, left middle occipital gyrus, and left postcentral gyrus. In the patient group, triglyceride levels and the insulin resistance index exhibited a negative correlation with Rapid Visual Information Processing (RVP) mean latency, a measure of attention within the Cambridge Neurocognitive Test Automated Battery (CANTAB), while showing a positive association with GMV in the right insula. The mediation model revealed that triglyceride and insulin resistance index had a significant positive indirect (mediated) influence on RVP mean latency through GMV in the right insula. Glucolipid metabolism was linked to both neurocognitive functions and GMV in FEDN patients with schizophrenia, with the effect pattern differing from that observed in chronic schizophrenia or schizophrenia comorbid with metabolic syndrome. Moreover, glucolipid metabolism might indirectly contribute to neurocognitive deficits through the mediating role of GMV in these patients.


Asunto(s)
Resistencia a la Insulina , Esquizofrenia , Humanos , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/patología , Imagen por Resonancia Magnética/métodos , Colesterol , Triglicéridos
4.
Artículo en Inglés | MEDLINE | ID: mdl-38403735

RESUMEN

There is inconsistent evidence for an association of obesity with white matter microstructural alterations. Such inconsistent findings may be related to the cumulative effects of obesity and alcohol dependence. This study aimed to investigate the possible interactions between alcohol dependence and overweight/obesity on white matter microstructure in the human brain. A total of 60 inpatients with alcohol dependence during early abstinence (44 normal weight and 16 overweight/obese) and 65 controls (42 normal weight and 23 overweight/obese) were included. The diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and radial diffusivity (RD)] of the white matter microstructure were compared between groups. We observed significant interactive effects between alcohol dependence and overweight/obesity on DTI measures in several tracts. The DTI measures were not significantly different between the overweight/obese and normal-weight groups (although widespread trends of increased FA and decreased RD were observed) among controls. However, among the alcohol-dependent patients, the overweight/obese group had widespread reductions in FA and widespread increases in RD, most of which significantly differed from the normal-weight group; among those with overweight/obesity, the alcohol-dependent group had widespread reductions in FA and widespread increases in RD, most of which were significantly different from the control group. This study found significant interactive effects between overweight/obesity and alcohol dependence on white matter microstructure, indicating that these two controllable factors may synergistically impact white matter microstructure and disrupt structural connectivity in the human brain.

5.
Phytomedicine ; 126: 155222, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38382279

RESUMEN

BACKGROUND: Diabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed. PURPOSE: This study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies. METHODS: Firstly, the content determination methods of QXLZY were established with calycosin-7-O-ß-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results. RESULTS: A method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine. CONCLUSION: This study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.


Asunto(s)
Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Ratones , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Farmacología en Red , Metabolómica/métodos , Medicina Tradicional China/métodos , Nefropatías Diabéticas/tratamiento farmacológico , Aminoácidos
6.
J Psychiatr Res ; 168: 13-21, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37871461

RESUMEN

Previous diffusion tensor imaging (DTI) studies have demonstrated widespread white matter microstructure damage in individuals with alcoholism. However, very little is known about the alterations in the topological architecture of white matter structural networks in alcohol dependence (AD). This study included 67 AD patients and 69 controls. The graph theoretical analysis method was applied to examine the topological organization of the white matter structural networks, and network-based statistics (NBS) were employed to detect structural connectivity alterations. Compared to controls, AD patients exhibited abnormal global network properties characterized by increased small-worldness, normalized clustering coefficient, clustering coefficient, and shortest path length; and decreased global efficiency and local efficiency. Further analyses revealed decreased nodal efficiency and degree centrality in AD patients mainly located in the default mode network (DMN), including the precuneus, anterior cingulate and paracingulate gyrus, median cingulate and paracingulate gyrus, posterior cingulate gyrus, and medial part of the superior frontal gyrus. Furthermore, based on NBS approaches, patients displayed weaker subnetwork connectivity mainly located in the region of the DMN. Additionally, altered network metrics were correlated with intelligence quotient (IQ) scores and global assessment function (GAF) scores. Our results may reveal the disruption of whole-brain white matter structural networks in AD individuals, which may contribute to our comprehension of the underlying pathophysiological mechanisms of alcohol addiction at the level of white matter structural networks.


Asunto(s)
Alcoholismo , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Alcoholismo/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Corteza Prefrontal
7.
Asian J Psychiatr ; 89: 103767, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37717506

RESUMEN

Identifying biomarkers to predict lapse of alcohol-dependence (AD) is essential for treatment and prevention strategies, but remains remarkably challenging. With an aim to identify neuroimaging features for predicting AD lapse, 66 male AD patients during early-abstinence (baseline) after hospitalized detoxification underwent resting-state functional magnetic resonance imaging and were then followed-up for 6 months. The relevance-vector-machine (RVM) analysis on baseline large-scale brain networks yielded an elegant model for differentiating relapsing patients (n = 38) from abstainers, with the area under the curve of 0.912 and the accuracy by leave-one-out cross-validation of 0.833. This model captured key information about neuro-connectome biomarkers for predicting AD lapse.


Asunto(s)
Alcoholismo , Humanos , Masculino , Alcoholismo/terapia , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Neuroimagen , Biomarcadores
8.
Neurology ; 101(20): e1979-e1991, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37775315

RESUMEN

BACKGROUND AND OBJECTIVES: Previous studies reported that carriers of rare NOTCH3 variants comprised more than 10% of the general population and are susceptible to a heavy overall burden of cerebral small vessel disease while the injury patterns remain uncovered. This study aimed to investigate the imaging features in relation to rare NOTCH3 variants and the interaction between cortical atrophy and white matter lesions from a longitudinal view, with respect to spatial and dynamic patterns. METHODS: As part of a community-based cohort, we included participants with complete whole-exome sequencing and brain MRI in the baseline analysis. All participants were invited for a 5-year follow-up MRI, and those who did not complete the follow-up were excluded from the longitudinal analysis. NOTCH3 variants with minor allele frequency <1% in all 4 public population databases were defined as rare variants. We used general linear models to compare the volume of white matter hyperintensity (WMH) volume and brain parenchymal fraction between rare NOTCH3 variant carriers and noncarriers. In addition, we compared the WMH probability map and vertex-wise cortex maps at a voxel/vertex-wise level. RESULTS: A total of 1,054 participants were included in baseline analysis (13.56% carried rare NOTCH3 variants), among whom 661 had a follow-up brain MRI (13.76% carried rare NOTCH3 variants). Rare NOTCH3 variant carriers had a heavier white matter hyperintensity burden (1.65 vs 0.85 mL, p = 0.025) and had more extensive WMH distributed in the periventricular areas. We also found that rare NOTCH3 variant carriers were susceptible to worse cortical atrophy (ß = -0.004, SE = 0.002, p = 0.057, adjusted for age and sex). Cortical atrophy of multiple regions in the frontal and parietal lobes was related to white matter hyperintensity progression. DISCUSSION: Individuals with rare NOTCH3 variants have a distinct pattern of brain parenchymal damage related to CSVD. Our findings uncover the important genetic predisposition in age-related cerebral small vessel disease in the general population.


Asunto(s)
Lesiones Encefálicas , Enfermedades de los Pequeños Vasos Cerebrales , Sustancia Blanca , Humanos , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/genética , Enfermedades de los Pequeños Vasos Cerebrales/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Neuroimagen , Lesiones Encefálicas/patología , Atrofia/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Receptor Notch3/genética
9.
Eur J Neurol ; 30(10): 3172-3181, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37452734

RESUMEN

BACKGROUND AND PURPOSE: The development of high-resolution magnetic resonance imaging (HR-MRI) has enabled submillimeter-level evaluation of intracranial artery plaque and luminal thrombus. We sought to investigate the value of HR-MRI in assessing the pathogenesis of acute intracranial artery thrombus. METHODS: We examined the presence of intracranial thrombus on three-dimensional T1-weighted HR-MRI in acute ischemic stroke patients with intracranial artery occlusion on magnetic resonance angiography. We defined two thrombus-related HR-MRI features (peri-thrombus plaque and distal residual flow beyond the thrombus) and analyzed their association with potential embolic sources. RESULTS: Luminal thrombus and a shrunken artery without luminal thrombus were detected in 162 (96.4%) and six (3.6%) of 168 patients with intracranial artery occlusion, respectively. Among 111 patients with culprit major artery thrombus, peri-thrombus plaques were observed in 46.8% and distal residual flow beyond the thrombus in 64.0%. Patients with peri-thrombus plaque had a higher prevalence of diabetes (44.2% vs. 25.4%; p = 0.037), a lower prevalence of potential sources of cardioembolism (0% vs. 16.9%; p = 0.002), and a nonsignificantly lower prevalence of potential embolic sources from extracranial arteries (9.6% vs. 20.3%; p = 0.186) than those without. Patients with distal residual flow beyond the thrombus had a lower prevalence of potential sources of cardioembolism (1.4% vs. 22.5%; p < 0.001) and smaller infarct volumes (5.0 [1.4-12.7] mL vs. 16.6 [2.4-94.6] mL; p = 0.012) than those without. CONCLUSIONS: Our study showed that HR-MRI helps clarify the pathogenesis of acute intracranial artery thrombus. The presence of peri-thrombus plaque and distal residual flow beyond the thrombus favor the stroke mechanism of atherosclerosis rather than cardioembolism.


Asunto(s)
Arteriosclerosis Intracraneal , Trombosis Intracraneal , Accidente Cerebrovascular Isquémico , Placa Aterosclerótica , Accidente Cerebrovascular , Trombosis , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Imagen por Resonancia Magnética/métodos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/complicaciones , Angiografía por Resonancia Magnética/efectos adversos , Angiografía por Resonancia Magnética/métodos , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/diagnóstico por imagen , Arterias/patología , Trombosis/diagnóstico por imagen , Trombosis Intracraneal/complicaciones , Trombosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis Intracraneal/diagnóstico por imagen
11.
Zhongguo Zhong Yao Za Zhi ; 48(5): 1280-1288, 2023 Mar.
Artículo en Chino | MEDLINE | ID: mdl-37005812

RESUMEN

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.


Asunto(s)
Bufanólidos , Pez Cebra , Animales , Bufanólidos/análisis , Bufonidae , Cromatografía Líquida de Alta Presión , Control de Calidad , Línea Celular Tumoral
12.
Front Mol Neurosci ; 16: 1136398, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36910261

RESUMEN

Astrocytes play an important role in the pathogenesis of Alzheimer's disease (AD). It is widely involved in energy metabolism in the brain by providing nutritional and metabolic support to neurons; however, the alteration in the metabolism of astrocytes in AD remains unknown. Through integrative analysis of single-nucleus sequencing datasets, we revealed metabolic changes in various cell types in the prefrontal cortex of patients with AD. We found the depletion of some important metabolites (acetyl-coenzyme A, aspartate, pyruvate, 2-oxoglutarate, glutamine, and others), as well as the inhibition of some metabolic fluxes (glycolysis and tricarbocylic acid cycle, glutamate metabolism) in astrocytes of AD. The abnormality of glutamate metabolism in astrocytes is unique and important. Downregulation of GLUL (GS) and GLUD1 (GDH) may be the cause of glutamate alterations in astrocytes in AD. These results provide a basis for understanding the characteristic changes in astrocytes in AD and provide ideas for the study of AD pathogenesis.

13.
Cerebrovasc Dis ; 52(4): 480-486, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36446342

RESUMEN

BACKGROUND AND PURPOSE: The circle of Willis (COW) is a circulatory anastomosis located at the base of the brain. Little is known about the association between covert vascular brain injury and COW configurations in the general population. We explored this relationship in a community-based Chinese sample. METHODS: A total of 1,055 patients (mean age, 54.8 ± 8.9 years; 36.0% men) without intracranial arterial stenosis were included in the analysis. Magnetic resonance imaging was performed to evaluate the presence of imaging markers of covert vascular brain injury, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy. Magnetic resonance angiography was used to classify the COW configurations according to the completeness, symmetry, and presence of the fetal posterior cerebral artery (FTP). The association between vascular lesions and variations in COW was analyzed. RESULTS: Among the 1,055 patients, 104 (9.9%) had a complete COW. Completeness correlated with age (p = 0.001). Incomplete COW was positively associated with WMH severity (OR = 2.071; 95% CI, 1.004-4.270) and CMB presence (OR = 1.542; 95% CI, 1.012-2.348), independent of age and sex. The presence of FTP was associated with lacunes (OR = 1.878; 95% CI, 1.069-3.298), more severe WMHs (OR = 1.739; 95% CI, 1.064-2.842), and less severe enlarged perivascular spaces (OR = 0.562; 95% CI, 0.346-0.915). CONCLUSIONS: COW configuration was significantly related to various covert vascular brain injuries.


Asunto(s)
Traumatismos Cerebrovasculares , Círculo Arterial Cerebral , Humanos , Círculo Arterial Cerebral/diagnóstico por imagen , Círculo Arterial Cerebral/patología , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Angiografía por Resonancia Magnética , Traumatismos Cerebrovasculares/patología
14.
Front Psychiatry ; 13: 955741, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36226110

RESUMEN

Background: Obesity is a multi-systemic disease with complex etiology. And consistent evidence indicated obesity or overweight subjects render brain structure changes. Increasing evidence indicates these subjects have shown widespread structural brain gray matter volume (GMV) changes. However, results from other neuroimaging studies have been inconsistent. Consequently, the question remains whether body mass index (BMI), a gold standard to define obesity/overweight, is associated with brain structural changes. Methods: This study will apply an updated meta-analysis of voxel-based GMV studies to compare GMV changes in overweight and obese subjects. Online databases were used to build on relevant studies published before May 2022. The updated Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) explores GMV changes in individuals with overweight and obesity and further examines the correlation between GMV and obesity-related variables, specifically body mass index (BMI). Results: This research included fourteen studies and provided a whole-brain analysis of GMV distribution in overweight and obese individuals. It revealed lower GMV in brain regions, including the left putamen and right precentral gyrus, in individuals with overweight and obesity compared to lean controls. Further, meta-regression analyses revealed GMV in the left middle occipital gyrus was negatively correlated with the BMI of the whole sample. Conclusion: GMV decreased was reported in reward circuit processing areas and sensorimotor processing areas of individuals with overweight and obesity diagnoses, suggesting an underlying structural basis for reward processing and sensorimotor processing dysregulation in overweight and obese subjects. Our results also suggest that GMV in occipital gyrus, a key region for food visual and gustatory encoding, is negatively associated with BMI. These results provide further evidence for the dysregulated reward circuit in individuals with overweight and obesity.

15.
Proc Natl Acad Sci U S A ; 119(40): e2123030119, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36161902

RESUMEN

Lorises are a group of globally threatened strepsirrhine primates that exhibit many unusual physiological and behavioral features, including a low metabolic rate, slow movement, and hibernation. Here, we assembled a chromosome-level genome sequence of the pygmy loris (Xanthonycticebus pygmaeus) and resequenced whole genomes from 50 pygmy lorises and 6 Bengal slow lorises (Nycticebus bengalensis). We found that many gene families involved in detoxification have been specifically expanded in the pygmy loris, including the GSTA gene family, with many newly derived copies functioning specifically in the liver. We detected many genes displaying evolutionary convergence between pygmy loris and koala, including PITRM1. Significant decreases in PITRM1 enzymatic activity in these two species may have contributed to their characteristic low rate of metabolism. We also detected many evolutionarily convergent genes and positively selected genes in the pygmy loris that are involved in muscle development. Functional assays demonstrated the decreased ability of one positively selected gene, MYOF, to up-regulate the fast-type muscle fiber, consistent with the lower proportion of fast-twitch muscle fibers in the pygmy loris. The protein product of another positively selected gene in the pygmy loris, PER2, exhibited weaker binding to the key circadian core protein CRY, a finding that may be related to this species' unusual circadian rhythm. Finally, population genomics analysis revealed that these two extant loris species, which coexist in the same habitat, have exhibited an inverse relationship in terms of their demography over the past 1 million years, implying strong interspecies competition after speciation.


Asunto(s)
Adaptación Biológica , Evolución Biológica , Lorisidae , Adaptación Biológica/genética , Animales , Demografía , Hibernación , Lorisidae/genética , Metagenómica , Metaloendopeptidasas/genética
16.
Aging Cell ; 21(11): e13723, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36165462

RESUMEN

The entorhinal cortex is of great importance in cognition and memory, its dysfunction causes a variety of neurological diseases, particularly Alzheimer's disease (AD). Yet so far, research on entorhinal cortex is still limited. Here, we provided the first single-nucleus transcriptomic map of primate entorhinal cortex aging. Our result revealed that synapse signaling, neurogenesis, cellular homeostasis, and inflammation-related genes and pathways changed in a cell-type-specific manner with age. Moreover, among the 7 identified cell types, we highlighted the neuronal lineage that was most affected by aging. By integrating multiple datasets, we found entorhinal cortex aging was closely related to multiple neurodegenerative diseases, particularly for AD. The expression levels of APP and MAPT, which generate ß-amyloid (Aß) and neurofibrillary tangles, respectively, were increased in most aged entorhinal cortex cell types. In addition, we found that neuronal lineage in the aged entorhinal cortex is more prone to AD and identified a subpopulation of excitatory neurons that are most highly associated with AD. Altogether, this study provides a comprehensive cellular and molecular atlas of the primate entorhinal cortex at single-cell resolution and provides new insights into potential therapeutic targets against age-related neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer , Corteza Entorrinal , Animales , Corteza Entorrinal/metabolismo , Enfermedad de Alzheimer/metabolismo , Transcriptoma/genética , Análisis de la Célula Individual , Envejecimiento/genética , Envejecimiento/metabolismo , Primates/genética
17.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4372-4376, 2022 Aug.
Artículo en Chino | MEDLINE | ID: mdl-36046864

RESUMEN

The present study established an RP-HPLC method for simultaneous determination of two active components in Qingfei Paidu Granules and investigated the transfer rates of neohesperidin and naringin in the preparation process to provide references for improving the quality control standard and production of Qingfei Paidu Granules.RP-HPLC was performed on a YMC Triart C_(18) column(4.6 mm×150 mm, 5 µm)with column temperature of 30 ℃, acetonitrile(A) and 0.2% phosphoric acid solution(B) as mobile phases for gradient elution at a flow rate of 1.0 mL·min~(-1) and detection wavelength of 284 nm.Good linearity was observed for naringin at 0.10-1.0 µg(R~2=0.999 9) and neohesperidin at 0.12-1.2 µg(R~2=0.999 9).The average recovery of naringin was 99.52% with an RSD of 1.2%, and that of neohesperidin was 100.8% with an RSD of 1.2%.The transfer rates of naringin and neohesperidin between medicinal materials, extracts, concentrates, and granules were measured by this method.The average transfer rate of naringin from medicinal materials to granules was 54.89%±4.38%, and that of neohesperidin was 57.63%±5.88%.The process from medicinal materials to extracts was presumedly the key link affecting the whole preparation process.The established method is simple and sensitive and can be adopted for the quality control of Qingfei Paidu Granules.Meanwhile, it can be used to investigate the transfer rate of neohesperidin and naringin in the preparation of Qingfei Paidu Granules, and further improve the quality control standard of Aurantii Fructus Immaturus in Qingfei Paidu Granules.


Asunto(s)
Medicamentos Herbarios Chinos , Flavanonas , Hesperidina , Cromatografía Líquida de Alta Presión/métodos , Hesperidina/análogos & derivados
18.
J Alzheimers Dis ; 89(2): 593-603, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35912739

RESUMEN

BACKGROUND: Cognitive impairment is common in the elderly population. Exploring patterns of white matter damage at the microstructural level would give important indications for the underlying mechanisms. OBJECTIVE: To investigate the spatial patterns of white matter microstructure and structural network alternations in relation to different cognition domainsMethods:Participants from the community-based Shunyi Study were included to investigate the association between white matter measurements and cognition cross-sectionally, via both global and local analysis. Cognitive functions were assessed using digit span, trail making test (TMT)-A/B, Fuld object Memory, and 12-Word Philadelphia Verbal Learning Test (PVLT). White matter measurements including fractional anisotropy (FA), mean diffusivity (MD), and structural network parameters were calculated based on diffusion tensor imaging. RESULTS: Of the 943 participants included, the mean (SD) age was 55.8 (9.1) years, and the mean (SD) education level was 6.7 (3.2) years. We found the whole set of cognitive measurements was related to diffused white matter microstructural integrity damage and lower global efficiency. Poor executive functions (TMTA/B complete time) were related to lower FA and higher MD predominantly on the anterior white matter skeleton, while verbal memory loss (PVLT test scores) was related to sub-network dysconnectivity in the midline and the right temporal lobe. CONCLUSION: The anterior brain is dominantly involved in executive dysfunction, while midline and right temporal brain disconnection are more prominent in verbal memory loss. Global and regional disruption of white matter integrity and network connectivity is the anatomical basis of the cognitive impairment in the aging population.


Asunto(s)
Sustancia Blanca , Anciano , Encéfalo/diagnóstico por imagen , Cognición , Imagen de Difusión Tensora/métodos , Humanos , Trastornos de la Memoria , Pruebas Neuropsicológicas , Sustancia Blanca/diagnóstico por imagen
19.
Atherosclerosis ; 352: 27-34, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35667161

RESUMEN

BACKGROUND AND AIMS: Evidence shows that artery geometries play a role in atherogenesis by influencing blood flow dynamics. However, whether upstream artery geometries influence downstream atherosclerosis remains unclear. We aimed to investigate whether carotid artery geometries were associated with middle cerebral artery (MCA) atherosclerosis. METHODS: We reviewed our institutional database of 3-dimensional head-neck combined high-resolution magnetic resonance imaging. The carotid artery geometries, carotid atherosclerosis, MCA configurations, and MCA atherosclerosis were examined. The associations between carotid artery geometry and MCA atherosclerosis were also analyzed. A final model integrating carotid artery geometries was established, and the incremental diagnostic value was evaluated and compared to a basic model that included only traditional risk factors. RESULTS: Among the 575 artery units of the ipsilateral carotid artery and MCA, the artery units with MCA plaques (n = 273) were associated with a larger bifurcation angle (odds ratio [OR], 1.138 per 10-degree increase; 95% confidential interval [CI], 1.023-1.264) and kinking-type extracranial internal carotid artery (ICA; OR, 2.193; 95%CI, 1.283-3.748) compared with those without MCA plaques (n = 302). These associations were independent of traditional risk factors, carotid atherosclerosis, and MCA configuration. A larger carotid bifurcation angle was also associated with tandem ICA and MCA atherosclerosis (OR, 1.211 per 10-degree increase; 95%CI, 1.110-1.321). The incremental diagnostic value of carotid artery geometry to traditional risk factors was revealed by comparing the area under the curves of the two diagnostic models (basic model, 0.673 vs. final model, 0.701; p = 0.016). CONCLUSIONS: Carotid artery geometries are independently associated with ipsilateral MCA atherosclerosis, providing new insights into the pathophysiology of intracranial atherosclerosis.


Asunto(s)
Aterosclerosis , Enfermedades de las Arterias Carótidas , Arteriosclerosis Intracraneal , Aterosclerosis/patología , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Interna/diagnóstico por imagen , Humanos , Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/patología , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/patología
20.
Zhongguo Zhong Yao Za Zhi ; 47(8): 1995-2007, 2022 Apr.
Artículo en Chino | MEDLINE | ID: mdl-35531714

RESUMEN

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of "higher quality, higher price, and priority for the high quality" for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the "experience-ingredients-activity-electronic sensing" evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.


Asunto(s)
Medicamentos Herbarios Chinos , China , Electrónica , Medicina Tradicional China , Restricción Física
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