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1.
Neuroimage ; 297: 120688, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878916

RESUMO

The human brain is organized as a complex, hierarchical network. However, the structural covariance patterns among brain regions and the underlying biological substrates of such covariance networks remain to be clarified. The present study proposed a novel individualized structural covariance network termed voxel-based texture similarity networks (vTSNs) based on 76 refined voxel-based textural features derived from structural magnetic resonance images. Validated in three independent longitudinal healthy cohorts (40, 23, and 60 healthy participants, respectively) with two common brain atlases, we found that the vTSN could robustly resolve inter-subject variability with high test-retest reliability. In contrast to the regional-based texture similarity networks (rTSNs) that calculate radiomic features based on region-of-interest information, vTSNs had higher inter- and intra-subject variability ratios and test-retest reliability in connectivity strength and network topological properties. Moreover, the Spearman correlation indicated a stronger association of the gene expression similarity network (GESN) with vTSNs than with rTSNs (vTSN: r = 0.600, rTSN: r = 0.433, z = 39.784, P < 0.001). Hierarchical clustering identified 3 vTSN subnets with differential association patterns with 13 coexpression modules, 16 neurotransmitters, 7 electrophysiology, 4 metabolism, and 2 large-scale structural and 4 functional organization maps. Moreover, these subnets had unique biological hierarchical organization from the subcortex-limbic system to the ventral neocortex and then to the dorsal neocortex. Based on 424 unrelated, qualified healthy subjects from the Human Connectome Project, we found that vTSNs could sensitively represent sex differences, especially for connections in the subcortex-limbic system and between the subcortex-limbic system and the ventral neocortex. Moreover, a multivariate variance component model revealed that vTSNs could explain a significant proportion of inter-subject behavioral variance in cognition (80.0 %) and motor functions (63.4 %). Finally, using 494 healthy adults (aged 19-80 years old) from the Southwest University Adult Lifespan Dataset, the Spearman correlation identified a significant association between aging and vTSN strength, especially within the subcortex-limbic system and between the subcortex-limbic system and the dorsal neocortex. In summary, our proposed vTSN is robust in uncovering individual variability and neurobiological brain processes, which can serve as biologically plausible measures for linking biological processes and human behavior.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Adulto Jovem , Ontologias Biológicas , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Rede Nervosa/anatomia & histologia , Pessoa de Meia-Idade , Conectoma/métodos , Reprodutibilidade dos Testes , Idoso
2.
Small ; 20(25): e2311228, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38225708

RESUMO

Sonodynamic therapy (SDT) as a promising non-invasive anti-tumor means features the preferable penetration depth, which nevertheless, usually can't work without sonosensitizers. Sonosensitizers produce reactive oxygen species (ROS) in the presence of ultrasound to directly kill tumor cells, and concurrently activate anti-tumor immunity especially after integration with tumor microenvironment (TME)-engineered nanobiotechnologies and combined therapy. Current sonosensitizers are classified into organic and inorganic ones, and current most reviews only cover organic sonosensitizers and highlighted their anti-tumor applications. However, there have few specific reviews that focus on inorganic sonosensitizers including their design principles, microenvironment regulation, etc. In this review, inorganic sonosensitizers are first classified according to their design rationales rather than composition, and the action rationales and underlying chemistry features are highlighted. Afterward, what and how TME is regulated based on the inorganic sonosensitizers-based SDT nanoplatform with an emphasis on the TME targets-engineered nanobiotechnologies are elucidated. Additionally, the combined therapy and their applications in non-cancer diseases are also outlined. Finally, the setbacks and challenges, and proposed the potential solutions and future directions is pointed out. This review provides a comprehensive and detailed horizon on inorganic sonosensitizers, and will arouse more attentions on SDT.


Assuntos
Microambiente Tumoral , Humanos , Animais , Terapia por Ultrassom/métodos , Neoplasias/terapia , Compostos Inorgânicos/química , Espécies Reativas de Oxigênio/metabolismo
3.
Am J Pathol ; 193(9): 1208-1222, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37328100

RESUMO

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.


Assuntos
Fibrose Oral Submucosa , Humanos , Ratos , Animais , Fibrose Oral Submucosa/metabolismo , Fibrose Oral Submucosa/patologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Transição Epitelial-Mesenquimal , Miofibroblastos/metabolismo , Células Epiteliais/metabolismo
4.
Plant Physiol ; 191(1): 463-478, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36342216

RESUMO

Integuments form important protective cell layers surrounding the developing ovules in gymno- and angiosperms. Although several genes have been shown to influence the development of integuments, the transcriptional regulatory mechanism is still poorly understood. In this work, we report that the Class II KNOTTED1-LIKE HOMEOBOX (KNOX II) transcription factors KNOTTED1-LIKE HOMEBOX GENE 3 (KNAT3) and KNAT4 regulate integument development in Arabidopsis (Arabidopsis thaliana). KNAT3 and KNAT4 were co-expressed in inflorescences and especially in young developing ovules. The loss-of-function double mutant knat3 knat4 showed an infertility phenotype, in which both inner and outer integuments of the ovule are arrested at an early stage and form an amorphous structure as in the bell1 (bel1) mutant. The expression of chimeric KNAT3- and KNAT4-EAR motif repression domain (SRDX repressors) resulted in severe seed abortion. Protein-protein interaction assays demonstrated that KNAT3 and KNAT4 interact with each other and also with INNER NO OUTER (INO), a key transcription factor required for the outer integument formation. Transcriptome analysis showed that the expression of genes related with integument development is influenced in the knat3 knat4 mutant. The knat3 knat4 mutant also had a lower indole-3-acetic acid (IAA) content, and some auxin signaling pathway genes were downregulated. Moreover, transactivation analysis indicated that KNAT3/4 and INO activate the auxin signaling gene IAA INDUCIBLE 14 (IAA14). Taken together, our study identified KNAT3 and KNAT4 as key factors in integument development in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Óvulo Vegetal , Ácidos Indolacéticos/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas Nucleares/metabolismo
5.
Cancer Cell Int ; 24(1): 71, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347631

RESUMO

OBJECTIVE: Gastric cancer (GC) stands as a prevalent and deadly global malignancy. Despite its role as a preoperative neoadjuvant therapy, Apatinib's effectiveness is curtailed among GC patients exhibiting elevated YY1 expression. YY1's connection to adverse prognosis, drug resistance, and GC metastasis is established, yet the precise underlying mechanisms remain elusive. This study aims to unravel potential pathogenic pathways attributed to YY1. DESIGN: Utilizing bioinformatics analysis, we conducted differentially expressed genes, functional annotation, and pathway enrichment analyses, and further validation through cellular and animal experiments. RESULTS: Higher YY1 expression correlated with diminished postoperative progression-free survival (PFS) and disease-specific survival (DSS) rates in TCGA analysis, identifying YY1 as an independent DSS indicator in gastric cancer (GC) patients. Notably, YY1 exhibited significantly elevated expression in tumor tissues compared to adjacent normal tissues. Bioinformatics analysis revealed noteworthy differentially expressed genes (DEGs), transcriptional targets, factors, and co-expressed genes associated with YY1. LASSO Cox analysis unveiled Transferrin as a prospective pivotal protein regulated by YY1, with heightened expression linked to adverse DSS and PFS outcomes. YY1's role in governing the p53 signaling pathway and ferroptosis in GC cells was further elucidated. Moreover, YY1 overexpression dampened immune cell infiltration within GC tumors. Additionally, YY1 overexpression hindered GC cell ferroptosis and mediated Apatinib resistance via the p53 pathway. Remarkably, IFN-a demonstrated efficacy in reversing Apatinib resistance and immune suppression in GC tissues. CONCLUSIONS: Our findings underscore the pivotal role of YY1 in driving GC progression and influencing prognosis, thus pinpointing it as a promising therapeutic target to enhance patient outcomes.

6.
Mol Psychiatry ; 28(1): 17-27, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35790874

RESUMO

Individual differences in human brain structure, function, and behavior can be attributed to genetic variations, environmental exposures, and their interactions. Although genome-wide association studies have identified many genetic variants associated with brain imaging phenotypes, environmental exposures associated with these phenotypes remain largely unknown. Here, we propose that environmental neuroscience should pay more attention on exploring the associations between lifetime environmental exposures (exposome) and brain imaging phenotypes and identifying both cumulative environmental effects and their vulnerable age windows during the life course. Exposome-neuroimaging association studies face several challenges including the accurate measurement of the totality of environmental exposures varied in space and time, the highly correlated structure of the exposome, and the lack of standardized approaches for exposome-wide association studies. By agnostically scanning the effects of environmental exposures on brain imaging phenotypes and their interactions with genomic variations, exposome-neuroimaging association analyses will improve our understanding of causal factors associated with individual differences in brain structure and function as well as their relations with cognitive abilities and neuropsychiatric disorders.


Assuntos
Expossoma , Humanos , Estudo de Associação Genômica Ampla , Exposição Ambiental/efeitos adversos , Encéfalo , Cognição
7.
Mol Psychiatry ; 28(11): 4853-4866, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37737484

RESUMO

Exposure to preadult environmental exposures may have long-lasting effects on mental health by affecting the maturation of the brain and personality, two traits that interact throughout the developmental process. However, environment-brain-personality covariation patterns and their mediation relationships remain unclear. In 4297 healthy participants (aged 18-30 years), we combined sparse multiple canonical correlation analysis with independent component analysis to identify the three-way covariation patterns of 59 preadult environmental exposures, 760 adult brain imaging phenotypes, and five personality traits, and found two robust environment-brain-personality covariation models with sex specificity. One model linked greater stress and less support to weaker functional connectivity and activity in the default mode network, stronger activity in subcortical nuclei, greater thickness and volume in the occipital, parietal and temporal cortices, and lower agreeableness, consciousness and extraversion as well as higher neuroticism. The other model linked higher urbanicity and better socioeconomic status to stronger functional connectivity and activity in the sensorimotor network, smaller volume and surface area and weaker functional connectivity and activity in the medial prefrontal cortex, lower white matter integrity, and higher openness to experience. We also conducted mediation analyses to explore the potential bidirectional mediation relationships between adult brain imaging phenotypes and personality traits with the influence of preadult environmental exposures and found both environment-brain-personality and environment-personality-brain pathways. We finally performed moderated mediation analyses to test the potential interactions between macro- and microenvironmental exposures and found that one category of exposure moderated the mediation pathways of another category of exposure. These results improve our understanding of the effects of preadult environmental exposures on the adult brain and personality traits and may facilitate the design of targeted interventions to improve mental health by reducing the impact of adverse environmental exposures.


Assuntos
Encéfalo , Personalidade , Adulto , Humanos , Neuroticismo , Mapeamento Encefálico , Exposição Ambiental
8.
J Org Chem ; 89(7): 4395-4405, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38501298

RESUMO

A visible-light-induced chemodivergent synthesis of tetracyclic quinazolinones and 3-iminoisoindoliones has been developed. This chemodivergent reaction afforded two kinds of different products by substrate control. A detailed investigation of the reaction mechanism revealed that this consecutive photoinduced electron transfer (ConPET) cascade cyclization involved a radical process, and the aryl radical was the crucial intermediate. This method employed 4-DPAIPN as a photocatalyst and i-Pr2NEt as a sacrificial electron donor leading to metal-free conditions.

9.
Inorg Chem ; 63(36): 16740-16749, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39177239

RESUMO

The extremely low stability of lanthanide clusters with precise structures and nanometer dimensions in aqueous solutions limits their application in the field of photodynamic sterilization. In this study, an hourglass-shaped nine-nucleated Dy9 cluster (1) with excellent light-driven reactive oxygen species (ROS) generation ability and photodynamic sterilization property was constructed using acylhydrazone multidentate chelating ligands obtained via an in situ reaction. The eight chelating ligands were distributed outside cluster 1, tightly wrapping the cluster core, thus preventing solvent molecules from attacking the cluster nucleus and ensuring the stability of cluster 1 in solution, which was demonstrated via X-ray diffraction and high-resolution electrospray ionization mass spectrometry (HRESI-MS). Time-dependent HRESI-MS monitoring of the self-assembly process of cluster 1 allowed two possible self-assembly mechanisms. The heavy atom effect of multiple Dy(III) ions in the Dy9 cluster enhanced the ISC pathway through spin-orbit coupling, promoting energy transfer from the excited singlet state (S1) to the triplet state (T1), which was stabilized, inducing the generation of more ROS. Cluster 1 showed a remarkable sterilization effect due to the generation of abundant ROS under light irradiation conditions. To our knowledge, this is a rare instance of lanthanide clusters with photodynamic sterilization, providing new horizons for the construction of fast and efficient sterilizers.

10.
Org Biomol Chem ; 22(15): 2968-2973, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38529682

RESUMO

An Fe-catalyzed visible-light induced condensation of alkylbenzenes with anthranilamides has been developed. Upon irradiation, the trivalent iron complex could generate chlorine radicals, which successfully abstracted the hydrogen of benzylic C-H bonds to form benzyl radicals. And these benzyl radicals were converted into oxygenated products under air conditions, which subsequently reacted with anthranilamides for the synthesis of quinazolinones.

11.
J Gastroenterol Hepatol ; 39(3): 527-534, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37974384

RESUMO

BACKGROUND: Endoscopic resection (ER) for jejunoileal lesions (JILs) has been technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and safety of ER for JILs. METHOD: We retrospectively investigated 52 patients with JILs who underwent ER from January 2012 to February 2022. We collected and analyzed clinicopathological characteristics, procedure-related parameters, outcomes, and follow-up data. RESULTS: The mean age was 49.4 years. Of the 52 JILs, 33 ileal tumors within 20 cm from the ileocecal valve were resected with colonoscopy, while 19 tumors in the jejunum or the ileum over 20 cm from the ileocecal valve received enteroscopy resection. The mean procedure duration was 49.0 min. The en bloc resection and en bloc with R0 resection rates were 86.5% and 84.6%, respectively. Adverse events (AEs) included one (1.9%) major AE (delayed bleeding) and five (9.6%) minor AEs. During a median follow-up of 36.5 months, two patients had local recurrence (3.8%), while none had metastases. The 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) were 92.9% and 94.1%, respectively. Compared with the enteroscopy group, overall AEs were significantly lower in the colonoscopy group (P < 0.05), but no statistical differences were observed in RFS (P = 0.412) and DSS (P = 0.579). There were no significant differences in AEs, RFS, and DSS between the endoscopic submucosal dissection (ESD) and the endoscopic mucosal resection (EMR) group. CONCLUSIONS: ER of JILs has favorable short-term and long-term outcomes. Both ESD and EMR can safely and effectively resect JILs in appropriately selected cases.


Assuntos
Colonoscopia , Ressecção Endoscópica de Mucosa , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Viabilidade , Colonoscopia/efeitos adversos , Endoscopia Gastrointestinal , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Resultado do Tratamento , Recidiva Local de Neoplasia/patologia , Mucosa Intestinal/patologia
12.
Bioorg Chem ; 151: 107618, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39003940

RESUMO

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).


Assuntos
Catequina , Proliferação de Células , Triptofano , Catequina/química , Catequina/farmacologia , Catequina/isolamento & purificação , Triptofano/química , Triptofano/farmacologia , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Antifibróticos/farmacologia , Antifibróticos/química , Antifibróticos/isolamento & purificação , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Relação Dose-Resposta a Droga , Movimento Celular/efeitos dos fármacos , Animais , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Humanos , Raízes de Plantas/química
13.
Bioorg Chem ; 143: 107079, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38185011

RESUMO

Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia.


Assuntos
Benzofuranos , Glicosídeos , Raízes de Plantas , Glicosídeos/farmacologia , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Raízes de Plantas/química , Benzofuranos/química , Benzofuranos/farmacologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-39073445

RESUMO

BACKGROUND: Childhood trauma experiences and inflammation are pivotal factors in the onset and perpetuation of major depressive disorder (MDD). However, research on brain mechanisms linking childhood trauma experiences and inflammation to depression remains insufficient and inconclusive. METHODS: Resting-state fMRI scans were performed on fifty-six first-episode, drug-naive MDD patients and sixty healthy controls (HCs). A whole-brain functional network was constructed by thresholding 246 brain regions, and connectivity and network properties were calculated. Plasma interleukin-6 (IL-6) levels were assessed using enzyme-linked immunosorbent assays in MDD patients, and childhood trauma experiences were evaluated through the Childhood Trauma Questionnaire (CTQ). RESULTS: Negative correlations were observed between CTQ total (r = -0.28, p = 0.047), emotional neglect (r = -0.286, p = 0.042) scores, as well as plasma IL-6 levels (r = -0.294, p = 0.036), with mean decreased functional connectivity (FC) in MDD patients. Additionally, physical abuse exhibited a positive correlation with the nodal clustering coefficient of the left thalamus in patients (r = 0.306, p = 0.029). Exploratory analysis indicated negative correlations between CTQ total and emotional neglect scores and mean decreased FC in MDD patients with lower plasma IL-6 levels (n = 28), while these correlations were nonsignificant in MDD patients with higher plasma IL-6 levels (n = 28). CONCLUSIONS: This finding enhances our understanding of the correlation between childhood trauma experiences, inflammation, and brain activity in MDD, suggesting potential variations in their underlying pathophysiological mechanisms.

15.
Cereb Cortex ; 33(12): 8035-8045, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-36935097

RESUMO

Evidence highlights that dopamine (DA) system dysregulation and prefrontal cortex (PFC) dysfunction may underlie the pathophysiology of schizophrenia. However, the associations among DA genes, PFC morphometry, and schizophrenia have not yet been fully clarified. Based on the brain gene expression dataset from Allen Human Brain Atlas and structural magnetic resonance imaging data (NDIS = 1727, NREP = 408), we first identified 10 out of 22 PFC subregions whose gray matter volume (GMV) covariance profiles were reliably associated with their DA genes coexpression profiles, then four out of the identified 10 PFC subregions demonstrated abnormally increased GMV covariance with the hippocampus, insula, and medial frontal areas in schizophrenia patients (NCASE = 100; NCONTROL = 102). Moreover, based on a schizophrenia postmortem expression dataset, we found that the DA genes coexpression of schizophrenia was significantly reduced between the middle frontal gyrus and hippocampus, in which 21 DA genes showed significantly unsynchronized expression changes, and the 21 genes' brain expression were enriched in brain activity invoked by working memory, reward, speech production, and episodic memory. Our findings indicate the DA genes selectively regulate the structural covariance of PFC subregions by their coexpression profiles, which may underlie the disrupted GMV covariance and impaired cognitive functions in schizophrenia.


Assuntos
Dopamina , Regulação da Expressão Gênica , Substância Cinzenta , Córtex Pré-Frontal , Esquizofrenia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Esquizofrenia/metabolismo , Dopamina/metabolismo , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/metabolismo , Memória de Curto Prazo , Memória Episódica , Recompensa , Fala , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Conjuntos de Dados como Assunto , Imageamento por Ressonância Magnética
16.
Cereb Cortex ; 33(4): 1310-1327, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35368064

RESUMO

Alzheimer's disease (AD) patients suffer progressive cerebral atrophy before dementia onset. However, the region-specific atrophic processes and the influences of age and apolipoprotein E (APOE) on atrophic trajectory are still unclear. By mapping the region-specific nonlinear atrophic trajectory of whole cerebrum from amnestic mild cognitive impairment (aMCI) to AD based on longitudinal structural magnetic resonance imaging data from Alzheimer's disease Neuroimaging Initiative (ADNI) database, we unraveled a quadratic accelerated atrophic trajectory of 68 cerebral regions from aMCI to AD, especially in the superior temporal pole, caudate, and hippocampus. Besides, interaction analyses demonstrated that APOE ε4 carriers had faster atrophic rates than noncarriers in 8 regions, including the caudate, hippocampus, insula, etc.; younger patients progressed faster than older patients in 32 regions, especially for the superior temporal pole, hippocampus, and superior temporal gyrus; and 15 regions demonstrated complex interaction among age, APOE, and disease progression, including the caudate, hippocampus, etc. (P < 0.05/68, Bonferroni correction). Finally, Cox proportional hazards regression model based on the identified region-specific biomarkers could effectively predict the time to AD conversion within 10 years. In summary, cerebral atrophic trajectory mapping could help a comprehensive understanding of AD development and offer potential biomarkers for predicting AD conversion.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Imageamento por Ressonância Magnética/métodos , Apolipoproteínas E/genética , Atrofia , Biomarcadores , Progressão da Doença
17.
Environ Res ; 241: 117606, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37951378

RESUMO

The formation of stable and mature biofilms affects the efficient and stable removal of ammonium by biological activated carbon (BAC). In this study, the new granular activated carbon (GAC) was preloaded with the carbon source (glucose and sucrose) and nano manganese dioxide (nMnO2) before using. Then tests were performed to determine whether substrate preloading promoted ammonium removal. The ammonium removal treated by nMnO2 coupled with sucrose-loaded BAC reached 49.1 ± 2.5%, which was 1.7 times higher than that by the nonloaded BAC 28.2 ± 1.9%). The biomass on the substrate-loaded BAC reached 5.83 × 106-1.22 × 107 cells/g DW GAC on Day 7, which was 4.6-9.5 times higher than the value of the nonloaded BAC (1.28 × 106 cells/g DW GAC). The amount of extracellular polymer (i.e., protein) on nMnO2 coupled to sucrose-loaded BAC was promoted significantly. Flavobacterium (0.7%-11%), Burkholderiaceae (13%-20%) and Aquabacterium (30%-67%) were the dominant functional bacteria on the substrate-loaded BAC, which were conducive to the nitrification or denitrification process. The results indicated that loading nMnO2 and/or a carbon source accelerated the formation of biofilms on BAC and ammonium removal. Additionally, the ammonium removal treated by nMnO2 coupled with sucrose-loaded BAC was contributed by microbial degradation (56.0 ± 2.5%), biofilm adsorption (38.7 ± 2.1%) and GAC adsorption (5.3 ± 0.3%), suggesting a major role of microbial degradation.


Assuntos
Compostos de Amônio , Purificação da Água , Carvão Vegetal , Nitrificação , Biofilmes , Sacarose , Purificação da Água/métodos
18.
PLoS Genet ; 17(2): e1009363, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33630843

RESUMO

Genome-wide association studies (GWASs) have identified multiple susceptibility loci for Alzheimer's disease (AD), which is characterized by early and progressive damage to the hippocampus. However, the association of hippocampal gene expression with AD and the underlying neurobiological pathways remain largely unknown. Based on the genomic and transcriptomic data of 111 hippocampal samples and the summary data of two large-scale meta-analyses of GWASs, a transcriptome-wide association study (TWAS) was performed to identify genes with significant associations between hippocampal expression and AD. We identified 54 significantly associated genes using an AD-GWAS meta-analysis of 455,258 individuals; 36 of the genes were confirmed in another AD-GWAS meta-analysis of 63,926 individuals. Fine-mapping models further prioritized 24 AD-related genes whose effects on AD were mediated by hippocampal expression, including APOE and two novel genes (PTPN9 and PCDHA4). These genes are functionally related to amyloid-beta formation, phosphorylation/dephosphorylation, neuronal apoptosis, neurogenesis and telomerase-related processes. By integrating the predicted hippocampal expression and neuroimaging data, we found that the hippocampal expression of QPCTL and ERCC2 showed significant difference between AD patients and cognitively normal elderly individuals as well as correlated with hippocampal volume. Mediation analysis further demonstrated that hippocampal volume mediated the effect of hippocampal gene expression (QPCTL and ERCC2) on AD. This study identifies two novel genes associated with AD by integrating hippocampal gene expression and genome-wide association data and reveals candidate hippocampus-mediated neurobiological pathways from gene expression to AD.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Hipocampo/metabolismo , Polimorfismo de Nucleotídeo Único , Transcriptoma/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Feminino , Redes Reguladoras de Genes/genética , Genômica/métodos , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Sequenciamento Completo do Genoma/métodos
19.
Molecules ; 29(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38675536

RESUMO

Traditional Chinese medicine (TCM) possesses the potential of providing good curative effects with no side effects for the effective management of slow transit constipation (STC), an intestinal disease characterized by colonic dyskinesia. Mulberry leaves (Morus alba L.) and black sesame (Sesamum indicum L.), referred to as SH, are processed and conditioned as per standardized protocols. SH has applications as food and medicine. Accordingly, we investigated the therapeutic potential of SH in alleviating STC. The analysis of SH composition identified a total of 504 compounds. The intervention with SH significantly improved intestinal motility, reduced the time for the first black stool, increased antioxidant activity, and enhanced water content, thereby effectively alleviating colon damage caused by STC. Transcriptome analysis revealed the SH in the treatment of STC related to SOD1, MUC2, and AQP1. The analysis of 16S rRNA gene sequences indicated notable differences in the abundance of 10 bacteria between the SH and model. Metabolomic analysis further revealed that SH supplementation increased the levels of nine metabolites associated with STC. Integrative analysis revealed that SH modulated amino acid metabolism, balanced intestinal flora, and targeted key genes (i.e., SOD1, MUC2, AQP1) to exert its effects. SH also inhibited the AQP1 expression and promoted SOD1 and MUC2 expression.


Assuntos
Constipação Intestinal , Morus , Folhas de Planta , Sesamum , Morus/química , Constipação Intestinal/tratamento farmacológico , Folhas de Planta/química , Sesamum/química , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolômica/métodos , Masculino , Motilidade Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Perfilação da Expressão Gênica , Modelos Animais de Doenças , Multiômica
20.
J Sci Food Agric ; 104(3): 1539-1552, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37807825

RESUMO

BACKGROUND: Nanoemulsions (NEs) have been considered an effective carrier to protect environmentally labile bioactive compounds from degradation during food processing. Among the numerous types of NEs, biopolymer-stabilized NEs have gained much attention to achieve this function because of the extensive sources, biocompatibility, and tunability. Therefore, the antioxidant activities, environmental stability, and in vitro digestibility of astaxanthin (AST)-loaded soybean protein isolate (SPI)-alginate (SA) complexes-stabilized NEs (AST-SPI-SA-NEs) were investigated in this study. RESULTS: The AST-SPI-SA-NEs exhibited an encapsulation efficiency of 88.30 ± 1.67%, which is greater than that of the AST-loaded SPI-stabilized NEs (AST-SPI-NEs) (77.31 ± 0.83%). Both AST-SPI-SA-NEs and AST-SPI-NEs exhibited significantly stronger hydroxyl or diphenylpicryl-hydrazyl radical-scavenging activities than the free AST. The formation of SPI-SA complexes strengthened the thermal, light, and storage stability of AST-SPI-SA-NEs with no apparently increasing mean diameter (around 200 nm). AST-SPI-SA-NEs also exhibited a better freeze-thaw dispersibility behavior than AST-SPI-NEs. AST-SPI-SA-NEs were more stable than AST-SPI-NEs were under in vitro gastrointestinal digestion conditions and exhibited a greater bioaccessibility (47.92 ± 0.42%) than both AST-SPI-NEs (12.97 ± 1.33%) and free AST (7.87 ± 0.37%). Hydrogen bonding was confirmed to participate in the formation of AST-SPI-SA-NEs and AST-SPI-NEs based on the molecular docking results. CONCLUSIONS: The construction of SPI-SA-NEs is conducive to the encapsulation, protection, and absorption of AST, providing a promising method for broadening the application of AST in processed foods or developing novel ingredients of functional foods. © 2023 Society of Chemical Industry.


Assuntos
Alginatos , Proteínas de Soja , Alginatos/química , Proteínas de Soja/química , Antioxidantes , Simulação de Acoplamento Molecular , Emulsões/química
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