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1.
J Cell Mol Med ; 28(17): e70018, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39223962

RESUMO

Ferroptosis, an iron-dependent form of cell death, plays a crucial role in the progression of liver injury in Wilson's disease (WD). Gandouling (GDL) has emerged as a potential therapeutic agent for preventing and treating liver injury in WD. However, the precise mechanisms by which GDL mitigates ferroptosis in WD liver injury remain unclear. In this study, we discovered that treating Toxic Milk (TX) mice with GDL effectively decreased liver copper content, corrected iron homeostasis imbalances, and lowered lipid peroxidation levels, thereby preventing ferroptosis and improving liver injury. Bioinformatics analysis and machine learning algorithms identified Hspb1 as a pivotal regulator of ferroptosis. GDL treatment significantly upregulated the expression of HSPB1 and its upstream regulatory factor HSF1, thereby activating the HSF1/HSPB1 pathway. Importantly, inhibition of this pathway by NXP800 reversed the protective effects of GDL on ferroptosis in the liver of TX mice. In conclusion, GDL shows promise in alleviating liver injury in WD by inhibiting ferroptosis through modulation of the HSF1/HSPB1 pathway, suggesting its potential as a novel therapeutic agent for treating liver ferroptosis in WD.


Assuntos
Ferroptose , Fatores de Transcrição de Choque Térmico , Degeneração Hepatolenticular , Fígado , Chaperonas Moleculares , Transdução de Sinais , Ferroptose/efeitos dos fármacos , Animais , Fatores de Transcrição de Choque Térmico/metabolismo , Fatores de Transcrição de Choque Térmico/genética , Camundongos , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/metabolismo , Degeneração Hepatolenticular/patologia , Chaperonas Moleculares/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Transdução de Sinais/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Modelos Animais de Doenças , Masculino , Ferro/metabolismo , Cobre/metabolismo , Camundongos Endogâmicos C57BL , Humanos
2.
Langmuir ; 40(39): 20550-20558, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39288013

RESUMO

Obtaining reliable and informative DNA data from soil samples is challenging due to the presence of interfering substances and typically low DNA yields. In this work, we prepared poly(ethylene glycol)-modified magnetic particles (PEG@Fe3O4) for DNA purification. The particles leverage the facilitative effect of calcium ions (Ca2+), which act as bridges between DNA and PEG@Fe3O4 by coordinating with the phosphate groups of DNA and the hydroxyl groups on the particles. The addition of 2-propanol further enhances this Ca2+-mediated DNA adsorption by inducing a conformational change from the B-form to the more compact A-form of DNA. PEG@Fe3O4 demonstrates a DNA adsorption capacity of 144.6 mg g-1. When applied to the extraction of genomic DNA from soil samples, PEG@Fe3O4 outperforms commercial kits and traditional phenol-chloroform extraction methods in terms of DNA yield and purity. Furthermore, we developed a 16-channel automated DNA extraction device to streamline the process and reduce the extraction time. The successful amplification of target bacterial and fungal amplicons underscores the potential of this automated, device-assisted method for studying soil microbial diversity.


Assuntos
2-Propanol , Cálcio , Polietilenoglicóis , Polietilenoglicóis/química , 2-Propanol/química , Cálcio/química , Microbiologia do Solo , DNA/química , DNA/isolamento & purificação , Solo/química , Adsorção , DNA Bacteriano/química , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/genética
3.
Chin Clin Oncol ; 13(Suppl 1): AB044, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39295362

RESUMO

BACKGROUND: Esthesioneuroblastomas (ENBs) represent a rare subset of malignancies originating within the upper aerodigestive tract, characterized by a propensity for local metastasis to the intracranial compartment through the cribriform plate. These neoplasms are frequently associated with a high incidence of local recurrence subsequent to therapeutic intervention. In this report, we review the literature and present a case of a patient with extensive meningeal and leptomeningeal dissemination of ENB, with a survival period of 2 years. METHODS: A systematic review of literature was conducted in accordance with the PRISMA guidelines. Additionally, the presentation, surgical management, chemotherapy, and outcomes of a 60-year-old female presenting with extensive meningeal metastasis at onset. RESULTS: Following the literature review, 43 distinct works were identified, extracted variables from the remaining seven papers that met our inclusion criteria included demographic data, presenting symptoms, recurrence status, primary tumor location, location of Leptomeningeal metastasis of ENB, interval from initial treatment to recurrence, initial treatment approach, treatment-related complications, survival outcomes, and post-treatment status of patients. The average age at diagnosis was 52.6 years (range, 31-76 years), with females comprising 63.6% of the sample. The majority underwent gross-total resection and received adjuvant radiotherapy as initial therapy. The median time to intracranial metastasis was 57 months post-primary tumor diagnosis. The median overall survival for ENB with intracranial metastasis was 14 months. CONCLUSIONS: ENB exhibits a marked propensity for recurrence and can metastasize to the intracranial space years post-remission, which correlates with reduced survival. Therefore, perpetual radiographic surveillance is warranted for all ENB patients to detect late recurrences and intracranial spread promptly.


Assuntos
Estesioneuroblastoma Olfatório , Neoplasias Meníngeas , Humanos , Estesioneuroblastoma Olfatório/terapia , Feminino , Pessoa de Meia-Idade , Neoplasias Meníngeas/terapia , Neoplasias Meníngeas/secundário , Adulto , Idoso , Neoplasias Nasais/terapia , Cavidade Nasal/patologia
4.
J Inflamm Res ; 17: 5599-5618, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39193124

RESUMO

Purpose: Neuroinflammation is a main cause of neurological damage in Wilson's disease (WD). Ferroptosis is present in the WD pathological process, which is also closely related to the neuroinflammation. LCN2, a ferroptosis-related gene in WD, is linked with the activation of NLRP3 inflammasome. Our group has previously demonstrated that Gandouling (GDL) can effectively improve neuroinflammation in WD. This study aims to investigate the protective effect of GDL on neuroinflammation in animal and cell models of WD, and whether the pharmacological mechanism is related to the LCN2/NLRP3 signaling pathway. Methods: Toxic milk (TX) mice and HT22 cells stimulated by copper ions were selected as models. The pathology of hippocampal tissues in TX mice were observed by HE staining and transmission electron microscopy. High-throughput sequencing analysis was conducted to screen ferroptosis-related genes in WD. The expression of LCN2 and GPX4 in hippocampus of TX mice were detected by immunohistochemical. The expression of LCN2, NLRP3, GPX4, and SLC7A11 was determined in TX mice and HT22 cells by Western blotting and RT-qPCR. The levels of Fe2+, inflammatory factor indicators TNF-α, IL-1ß and IL-6 and oxidative stress indicators 4-HNE, MAD, SOD, GSH and ROS were detected in each group by ELISA. Results: The results showed that GDL ameliorated pathological and mitochondrial damages in hippocampus of TX mice. The analysis of bioinformatics showed that LCN2 was a differential gene associated with ferroptosis in WD. The results of Western blotting and RT-qPCR indicated that GDL reduced the expression of LCN2 and NLRP3, and enhanced the expression of GPX4 and SLC711 in TX mice and HT22 cells. The ELISA results showed that GDL decreased the expression of Fe2+ and inflammatory factors TNF-α, IL-1ß and IL-6 in TX mice with ferroptosis inducer intervention and copper ion-loaded HT22 cells. GDL decreased the expression of oxidative stress indicators ROS, 4-HNE and MDA, and increased the expression of oxidative stress indicators GSH and SOD in TX mice and copper ion-loaded HT22 cells. Conclusion: GDL has anti-inflammatory and antioxidant effects. LCN2 is a differential gene associated with ferroptosis in WD. GDL may alleviate ferroptosis by inhibiting the LCN2/NLPR3 signaling pathway, thereby improving neuroinflammatory responses and exerting neuroprotective effects in WD.

5.
Front Nutr ; 11: 1408620, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135555

RESUMO

Polyphenols are a group of naturally occurring compounds that possess a range of biological properties capable of potentially mitigating or preventing the progression of age-related cognitive decline and Alzheimer's disease (AD). AD is a chronic neurodegenerative disease known as one of the fast-growing diseases, especially in the elderly population. Moreover, as the primary etiology of dementia, it poses challenges for both familial and societal structures, while also imposing a significant economic strain. There is currently no pharmacological intervention that has demonstrated efficacy in treating AD. While polyphenols have exhibited potential in inhibiting the pathological hallmarks of AD, their limited bioavailability poses a significant challenge in their therapeutic application. Furthermore, in order to address the therapeutic constraints, several polymer nanoparticles are being explored as improved therapeutic delivery systems to optimize the pharmacokinetic characteristics of polyphenols. Polymer nanoparticles have demonstrated advantageous characteristics in facilitating the delivery of polyphenols across the blood-brain barrier, resulting in their efficient distribution within the brain. This review focuses on amyloid-related diseases and the role of polyphenols in them, in addition to discussing the anti-amyloid effects and applications of polyphenol-based polymer nanoparticles.

6.
Sci Rep ; 14(1): 17443, 2024 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075190

RESUMO

Gliomas are the most common malignant tumors of the central nervous system, accounting for approximately 80% of all malignant brain tumors. Accumulating evidence suggest that pyroptosis plays an essential role in the progression of cancer. Unfortunately, the effect of the pyroptosis-related factor caspase-4 (CASP4) on immunotherapy and drug therapy for tumors has not been comprehensively investigated. In this study, we systematically screened six hub genes by pooling differential pyroptosis-related genes in The Cancer Genome Atlas (TCGA) glioma data and the degree of centrality of index-related genes in the protein-protein interaction network. We performed functional and pathway enrichment analyses of the six hub genes to explore their biological functions and potential molecular mechanisms. We then investigated the importance of CASP4 using Kaplan-Meier survival analysis of glioma patients. TCGA and the Chinese Glioma Genome Atlas (CGGA) databases showed that reduced CASP4 expression leads to the potent clinical deterioration of glioma patients. Computational analysis of the effect of CASP4 on the infiltration level and recruitment of glioma immune cells revealed that CASP4 expression was closely associated with a series of tumor-suppressive immune checkpoint molecules, chemokines, and chemokine receptors. We also found that aberrant CASP4 expression correlated with chemotherapeutic drug sensitivity. Finally, analysis at the cellular and tissue levels indicated an increase in CASP4 expression in glioma, and that CASP4 inhibition significantly inhibited the proliferation of glioma cells. Thus, CASP4 is implicated as a new prognostic biomarker for gliomas with the potential to further guide immunotherapy and chemotherapy strategies for glioma patients.


Assuntos
Neoplasias Encefálicas , Caspases Iniciadoras , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma , Humanos , Glioma/genética , Glioma/patologia , Glioma/imunologia , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Caspases Iniciadoras/metabolismo , Caspases Iniciadoras/genética , Piroptose/genética , Mapas de Interação de Proteínas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estimativa de Kaplan-Meier , Linhagem Celular Tumoral
7.
J Chromatogr A ; 1731: 465199, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39053252

RESUMO

The success of polymerase chain reaction (PCR) depends on the quality of deoxyribonucleic acid (DNA) templates. This study developed a cost-effective and eco-friendly DNA extraction system utilizing poly(3,4-dihydroxyphenylalanine)-modified cellulose paper (polyDOPA@paper). PolyDOPA@paper was prepared by oxidatively self-polymerizing DOPA under weak alkaline conditions and utilizing the adhesive property of polyDOPA on different materials. Compared to the uncoated cellulose paper, polyDOPA coating significantly enhances DNA adsorption owing to its abundant amino, carboxyl, and hydroxyl moieties. The DNA extraction mechanism using polyDOPA@paper was discussed. The maximum adsorption capacity of polyDOPA@paper for DNA was 20.7 µg cm-2. Moreover, an automated extraction system was designed and fabricated using 3D printing technology. The device simplifies the operation and ensures the reproducibility and consistency of the results. More importantly, it eliminates the need for specialized training of operators. The feasibility of the polyDOPA@paper-based automated extraction system was evaluated by quantitatively detecting Escherichia coli in spiked milk samples via a real-time PCR. The detection limit was 102 cfu mL-1. The results suggest that the system would have significant potential in detecting pathogens.


Assuntos
Celulose , Di-Hidroxifenilalanina , Limite de Detecção , Leite , Papel , Polímeros , Celulose/química , Celulose/análogos & derivados , Adsorção , Di-Hidroxifenilalanina/química , Di-Hidroxifenilalanina/isolamento & purificação , Di-Hidroxifenilalanina/análogos & derivados , Polímeros/química , Leite/química , Escherichia coli , Animais , Reprodutibilidade dos Testes , DNA/isolamento & purificação , DNA/química , Impressão Tridimensional , Reação em Cadeia da Polimerase em Tempo Real , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/análise
8.
J Cancer Res Clin Oncol ; 150(7): 346, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981916

RESUMO

PURPOSE: To develop a deep learning (DL) model for differentiating between benign and malignant ovarian tumors of Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US) Category 4 lesions, and validate its diagnostic performance. METHODS: A retrospective analysis of 1619 US images obtained from three centers from December 2014 to March 2023. DeepLabV3 and YOLOv8 were jointly used to segment, classify, and detect ovarian tumors. Precision and recall and area under the receiver operating characteristic curve (AUC) were employed to assess the model performance. RESULTS: A total of 519 patients (including 269 benign and 250 malignant masses) were enrolled in the study. The number of women included in the training, validation, and test cohorts was 426, 46, and 47, respectively. The detection models exhibited an average precision of 98.68% (95% CI: 0.95-0.99) for benign masses and 96.23% (95% CI: 0.92-0.98) for malignant masses. Moreover, in the training set, the AUC was 0.96 (95% CI: 0.94-0.97), whereas in the validation set, the AUC was 0.93(95% CI: 0.89-0.94) and 0.95 (95% CI: 0.91-0.96) in the test set. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive values for the training set were 0.943,0.957,0.951,0.966, and 0.936, respectively, whereas those for the validation set were 0.905,0.935, 0.935,0.919, and 0.931, respectively. In addition, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the test set were 0.925, 0.955, 0.941, 0.956, and 0.927, respectively. CONCLUSION: The constructed DL model exhibited high diagnostic performance in distinguishing benign and malignant ovarian tumors in O-RADS US category 4 lesions.


Assuntos
Aprendizado Profundo , Neoplasias Ovarianas , Ultrassonografia , Humanos , Feminino , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Ultrassonografia/métodos , Adulto , Idoso , Adulto Jovem
9.
Transl Neurodegener ; 13(1): 34, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39044270

RESUMO

BACKGROUND: Depressive symptoms often occur in patients with Alzheimer's disease (AD) and exacerbate the pathogenesis of AD. However, the neural circuit mechanisms underlying the AD-associated depression remain unclear. The serotonergic system plays crucial roles in both AD and depression. METHODS: We used a combination of in vivo trans-synaptic circuit-dissecting anatomical approaches, chemogenetic manipulations, optogenetic manipulations, pharmacological methods, behavioral testing, and electrophysiological recording to investigate dorsal raphe nucleus serotonergic circuit in AD-associated depression in AD mouse model. RESULTS: We found that the activity of dorsal raphe nucleus serotonin neurons (DRN5-HT) and their projections to the dorsal hippocampal CA1 (dCA1) terminals (DRN5-HT-dCA1CaMKII) both decreased in brains of early 5×FAD mice. Chemogenetic or optogenetic activation of the DRN5-HT-dCA1CaMKII neural circuit attenuated the depressive symptoms and cognitive impairments in 5×FAD mice through serotonin receptor 1B (5-HT1BR) and 4 (5-HT4R). Pharmacological activation of 5-HT1BR or 5-HT4R attenuated the depressive symptoms and cognitive impairments in 5×FAD mice by regulating the DRN5-HT-dCA1CaMKII neural circuit to improve synaptic plasticity. CONCLUSIONS: These findings provide a new mechanistic connection between depression and AD and provide potential pharmaceutical prevention targets for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Depressão , Modelos Animais de Doenças , Núcleo Dorsal da Rafe , Camundongos Transgênicos , Neurônios Serotoninérgicos , Animais , Núcleo Dorsal da Rafe/metabolismo , Masculino , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/fisiopatologia , Camundongos , Neurônios Serotoninérgicos/metabolismo , Neurônios Serotoninérgicos/fisiologia , Depressão/metabolismo , Depressão/genética , Depressão/psicologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Hipocampo/metabolismo , Serotonina/metabolismo , Optogenética , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia
10.
Sci Adv ; 10(26): eado1855, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941459

RESUMO

Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer's disease (AD). We found that deoxycholic acid (DCA) increased in brains of AD mice at an early stage. The enhanced production of DCA induces the up-regulation of the bile acid receptor Takeda G protein-coupled receptor (TGR5), which is also specifically increased in neurons of AD mouse brains at an early stage. The accumulation of exogenous DCA impairs cognitive function in wild-type mice, but not in TGR5 knockout mice. This suggests that TGR5 is the primary receptor mediating these effects of DCA. Furthermore, excitatory neuron-specific knockout of TGR5 ameliorates Aß pathology and cognition impairments in AD mice. The underlying mechanism linking TGR5 and AD pathology relies on the downstream effectors of TGR5 and the APP production, which is succinctly concluded as a "p-STAT3-APH1-γ-secretase" signaling pathway. Our studies identified the critical role of TGR5 in the pathological development of AD.


Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Neurônios , Receptores Acoplados a Proteínas G , Animais , Humanos , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Encéfalo/metabolismo , Encéfalo/patologia , Ácido Desoxicólico/farmacologia , Modelos Animais de Doenças , Camundongos Knockout , Neurônios/metabolismo , Neurônios/patologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais
11.
Geriatr Nurs ; 58: 266-273, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843755

RESUMO

Chronic constipation is a prevalent problem that significantly impacts older adults' well-being. This study aimed to explore how older adults describe constipation symptoms and impacts and understand the perceived taboo surrounding discussions on related issues. Twenty older adults with constipation were interviewed using a semi-structured format in Taiwan. The Interpretive Phenomenology Analysis approach was utilized for data analysis. Five techniques recommended by Lincoln and Guba (1985) were implemented to ensure the study's trustworthiness. The primary themes encompassed comprehensive portrayals of fecal characteristics, the discomfort symphony of constipation, emotional turbulence in the struggle against constipation, daily activities shadowed by constipation, and underlying factors contributing to communication taboos. Most participants considered the discussion of constipation taboo due to its association with an embarrassing secret, an unacceptable social norm and stigma, and apprehensions of potential gossip. Geriatric caregivers need to consider individual perspectives, communication taboos, and sociocultural contexts when addressing older adults' constipation.


Assuntos
Constipação Intestinal , Pesquisa Qualitativa , Tabu , Humanos , Constipação Intestinal/psicologia , Feminino , Masculino , Idoso , Taiwan , Comunicação , Idoso de 80 Anos ou mais , Atividades Cotidianas/psicologia , Entrevistas como Assunto
12.
iScience ; 27(5): 109778, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38746665

RESUMO

Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early emotional dysfunction, especially depressive symptoms in AD, remains elusive. Anterior cingulate cortex (ACC) is closely related to depression and vulnerable in AD. By quantitative whole-brain mapping and electrophysiological recording, we found that the decreased axonal calcium activity in neurons of ACC and the glutamatergic projection from ACC to the ventral hippocampal CA1 (vCA1) is significantly impaired in 3-month-old 5×FAD mice, which exhibit depressive-like phenotype before cognition defects in early stage. The activation of ACC-vCA1 circuit by chemogenetic manipulation efficiently ameliorated the early depressive-like behaviors in 5×FAD mice. We further identified the upregulated neuregulin-1 (Nrg1) in ACC impaired the excitatory synaptic transmission from the ACC to vCA1 in AD. Our work reveals the role of ACC-vCA1 circuit in regulating AD associated depression symptom in a mouse model of AD.

14.
Adv Sci (Weinh) ; 11(24): e2307953, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582517

RESUMO

FOXG1 syndrome is a developmental encephalopathy caused by FOXG1 (Forkhead box G1) mutations, resulting in high phenotypic variability. However, the upstream transcriptional regulation of Foxg1 expression remains unclear. This report demonstrates that both deficiency and overexpression of Men1 (protein: menin, a pathogenic gene of MEN1 syndrome known as multiple endocrine neoplasia type 1) lead to autism-like behaviors, such as social defects, increased repetitive behaviors, and cognitive impairments. Multifaceted transcriptome analyses revealed that Foxg1 signaling is predominantly altered in Men1 deficiency mice, through its regulation of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (Atrx) factor. Atrx recruits menin to bind to the transcriptional start region of Foxg1 and mediates the regulation of Foxg1 expression by H3K4me3 (Trimethylation of histone H3 lysine 4) modification. The deficits observed in menin deficient mice are rescued by the over-expression of Foxg1, leading to normalized spine growth and restoration of hippocampal synaptic plasticity. These findings suggest that menin may have a putative role in the maintenance of Foxg1 expression, highlighting menin signaling as a potential therapeutic target for Foxg1-related encephalopathy.


Assuntos
Modelos Animais de Doenças , Fatores de Transcrição Forkhead , Proteínas do Tecido Nervoso , Proteínas Proto-Oncogênicas , Animais , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Encefalopatias/genética , Encefalopatias/metabolismo , Comportamento Animal , Masculino
15.
Talanta ; 275: 126115, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38663068

RESUMO

High-quality DNA is an important guarantee to start downstream experiments in many biological and medical research areas. Magnetic particle-based DNA extraction methods from blood mainly depend on electrostatic adsorption in a low-pH environment. However, the strong acidic environment can influence the DNA stability. Herein, a polydopamine-functionalized magnetic particle (PDA@Fe3O4)-based protocol was developed for DNA extraction from whole blood samples. In the protocol, Mg2+ and Ca2+ were utilized to bridge the adsorption of DNA by PDA@Fe3O4 via the metal-mediated coordination. Isopropanol was found to efficiently promote DNA adsorption by triggering the change of the conformation of DNA from B-form to more compact A-form. In 50 % isopropanol solution, the DNA adsorption efficiency was nearly 100 % in the presence of 0.5 mM Ca2+ or 1.5 mM Mg2+. The role of metal ions and isopropanol in DNA adsorption was explored. The protocol averts the strong acidic environment and PCR inhibitors, such as high concentrations of salt or polyethylene glycol. It demonstrates superiority in DNA yield (59.13 ± 3.63 ng µL-1) over the commercial kit (27.33 ± 4.98 ng µL-1) and phenol-chloroform methods (37.90 ± 0.47 ng µL-1). In addition, to simplify the operastion, an automated nucleic acid extraction device was designed and fabricated to extract whole genomic DNA from blood. The feasibility of the device was verified by extracting DNA from cattle and pig blood samples. The extracted DNA was successfully applied to discriminate the beef authenticity by a duplex PCR system. The results demonstrate that the DNA extraction protocol and the automated device have great potential in blood samples.


Assuntos
2-Propanol , DNA , Indóis , Polímeros , Polímeros/química , 2-Propanol/química , DNA/química , DNA/isolamento & purificação , DNA/sangue , Indóis/química , Adsorção , Magnésio/química , Animais , Cálcio/química , Cálcio/sangue , Bovinos , Nanopartículas de Magnetita/química
17.
J Photochem Photobiol B ; 250: 112828, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101122

RESUMO

Rheumatoid arthritis (RA) is caused by inflammatory response of joints with cartilage and damage of synovium and bone erosion. In our previous studies, it has showed that irradiation of 630 nm LED reduce inflammation of synovial fibroblasts and cartilage and bone destruction in RA. However, the key genes and mechanism in ameliorating RA by irradiation of 630 nm LED remains unknown. In this study, human fibroblast-like synoviocytes (FLS) cell line MH7A and primary human RA-FLSs were treated with TNF-α and 630 nm LED irradiation with the different energy density. The mRNA sequencing was performed to screen the differentially expressed genes (DEGs). In all datasets, 10 DEGs were identified through screening. The protein interaction network analysis showed that 8 out of the 10 DEGs interacted with each other including IL-6, CXCL2, CXCL3, MAF, PGF, IL-1RL1, RRAD and BMP4. This study focused on BMP4, which is identified as important morphogens in regulating the development and homeostasis. CCK-8 assay results showed that 630 nm LED irradiation did not affect the cell viability. The qPCR and ELISA results showed that TNF-α stimulation inhibited BMP4 mRNA and protein level and irradiation of 630 nm LED increased the BMP4 mRNA and protein level in MH7A cells. In CIA and transgenic hTNF-α mice models, H&E staining showed that irradiation of 630 nm LED decreased the histological scores assessed from inflammation and bone erosion, while BMP4 expression level was up-regulated after 630 nm LED irradiation. Pearson correlation analysis shown that BMP4 protein expression was negatively correlated with the histological score of CIA mice and transgenic hTNF-α mice. These results indicated that BMP4 increased by irradiation of 630 nm LED was associated with the amelioration of RA, which suggested that BMP4 may be a potential targeting gene for photobiomodulation.


Assuntos
Artrite Experimental , Artrite Reumatoide , Proteína Morfogenética Óssea 4 , Luz , Animais , Humanos , Camundongos , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Artrite Reumatoide/terapia , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Proteína Morfogenética Óssea 4/fisiologia , Proliferação de Células , Células Cultivadas , Fibroblastos/metabolismo , Inflamação/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
18.
Med Mycol Case Rep ; 41: 16-19, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37706051

RESUMO

Adult tinea capitis is often neglected and misdiagnosed, especially in men. We herein reported an older man with seborrheic dermatitis-like tinea capitis caused by Trichophyton rubrum to raise awareness of the disease. Scale and alopecia were the critical diagnostic clues in this patient. Given the previous presence of tinea pedis and onychomycosis, relevant mycological examinations were promptly performed, and antifungal therapy, as well as patient education, were effectively administered.

19.
J Craniofac Surg ; 34(8): 2302-2307, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37427957

RESUMO

Computational fluid dynamics (CFD) was introduced into the study of palate growth and development to explain the mechanisms by which mouth breathing affects palate descent from an aerodynamic perspective. Cone beam computed tomography (CBCT) data were used to reconstruct a 3-dimensional model during natural mouth breathing of a volunteer. The model was imported into CFX 19.0 for numerical simulation of nasal breathing, mouth-nasal breathing, and mouth breathing. The pressure in the oronasal cavity was analyzed, and the pressure difference between the oral and nasal surfaces of hard palate under different breathing patterns was calculated. CFD can be used to simulate the stress on the oral and nasal surfaces of the palate under different breathing patterns. The pressure differences and resultant force between the oral and nasal surfaces of the hard palate during nasal inspiration, nasal expiration, mouth-nasal inspiration, mouth-nasal expiration, mouth inspiration, and mouth expiration were 0 Pa, 4 Pa (upward), 9 Pa (upward), 3 Pa (downward), 474 Pa (upward), 263 Pa (downward), respectively, and 87.99 N (upward), 88.03 N (upward), 88.01 N (upward), 88.01 N (upward), 88.05 N (upward), 87.94 N (upward), respectively. Therefore, CFD can be used to investigate the growth and development of the palate. When the volunteer opened his mouth, the pressure difference between the oral and nasal surfaces of the hard palate was about 88 N upward regardless of whether there was airflow in the mouth. The reversal of the direction of the force on the hard palate may be one of the factors affecting its descent of it.


Assuntos
Fissura Palatina , Respiração Bucal , Humanos , Hidrodinâmica , Respiração , Nariz , Palato Duro
20.
Crit Care ; 27(1): 275, 2023 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-37424026

RESUMO

BACKGROUND: The oXiris is a novel filter for continuous renal replacement therapy (CRRT) featuring an adsorption coating to adsorb endotoxins and remove inflammatory mediators. Given that no consensus has been reached on its potential benefits in treating sepsis, a meta-analysis was conducted to assess its impact on the clinical outcomes of this patient population. METHODS: Eleven databases were retrieved to find relevant observational studies and randomized controlled trials. The Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool were used to assess the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was employed to assess the certainty of evidence. The 28-day mortality was the primary outcome. Secondary outcomes were 7-, 14-, and 90-day mortality, length of intensive care unit (ICU) and hospital stay, ICU and hospital mortality, norepinephrine (NE) dose, interleukin-6 (IL-6) and lactate levels, and Sequential Organ Failure Assessment (SOFA) score. RESULTS: The meta-analysis, pooling data from 14 studies, involving 695 patients, showed significant reductions in 28-day mortality [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.36-0.77, p = 0.001] and length of ICU stay [weighted mean difference (WMD) - 1.91; 95% CI - 2.56 to - 1.26, p < 0.001)] in patients with sepsis using the oXiris filter compared to other filters. Besides, the SOFA score, NE dose, IL-6 and lactate levels, and 7- and 14-day mortalities were lower in the oXiris group. However, the 90-day mortality, ICU and hospital mortality, and length of hospital stay were comparable. The quality assessment of the ten observational studies indicated intermediate to high quality (average Newcastle-Ottawa score: 7.8). However, all four randomized controlled trials (RCTs) had an unclear risk of bias. The evidence for all outcomes had a low or very low level of certainty because the original study design was mainly observational studies and the RCTs included had an unclear risk of bias and a small sample size. CONCLUSION: The treatment with the oXiris filter during CRRT in sepsis patients may be associated with lower 28-, 7-, and 14-day mortalities, lactate levels, SOFA score, NE dose, and shorter length of ICU stay. However, due to the low or very low quality of evidence, the effectiveness of oXiris filters was still uncertain. Besides, no significant difference was observed for the 90-day mortality, ICU and hospital mortality, and length of hospital stay.


Assuntos
Terapia de Substituição Renal Contínua , Sepse , Humanos , Interleucina-6 , Adsorção , Lactatos/uso terapêutico
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