Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.045
Filtrar
1.
Clin Rheumatol ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358619

RESUMO

This study aims to investigate the clinical manifestations, imaging features, and treatment considerations in the rare occurrence of pneumatosis cystoides intestinalis (PCI) within the context of granulomatosis with polyangiitis (GPA). We present the case of a 71-year-old Chinese woman diagnosed with GPA, who, despite exhibiting fatigue, knee pain, and nasosinusitis, remained asymptomatic for PCI. Regular follow-up revealed laboratory and imaging evidence indicative of clinical relapse. The patient received GPA treatment but was not specifically managed for PCI. Serial abdominal CT scans were performed to monitor the progression of PCI. Radiological diagnosis confirmed the presence of gas within the colon wall, indicating pneumatosis cystoides intestinalis. Notably, the patient remained asymptomatic for abdominal complaints. Despite ongoing GPA treatment, a follow-up CT scan 2 months later revealed persistent gas within the colon wall, suggesting a persistent state of PCI. Patient consent was obtained for the publication of this case report, and ethical approval was not obtained as this study constitutes a retrospective review. This case underscores the importance of recognizing pneumatosis cystoides intestinalis as a potential complication in GPA patients, even in the absence of typical abdominal symptoms. Further research is warranted to elucidate the underlying mechanisms and optimal management strategies for this rare association. Key points • Rare association: This case report sheds light on the uncommon occurrence of pneumatosis cystoides intestinalis (PCI) within the context of granulomatosis with polyangiitis (GPA), adding to the understanding of the spectrum of manifestations of GPA. • Clinical manifestations: Despite being diagnosed with GPA and experiencing symptoms such as fatigue, knee pain, and nasosinusitis, the patient remained asymptomatic for PCI, emphasizing the importance of vigilant clinical monitoring in GPA patients. • Imaging features: Radiological imaging, including serial abdominal CT scans, played a crucial role in diagnosing and monitoring the progression of PCI in the absence of typical abdominal complaints, highlighting the utility of imaging modalities in detecting silent manifestations of gastrointestinal complications in GPA. • Treatment considerations: The case highlights the challenge of managing PCI in GPA patients, especially when asymptomatic, and raises questions about the optimal management strategies for such rare associations, underscoring the need for further research in this area.

2.
Anal Chem ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269432

RESUMO

The chimeric antigen receptor (CAR) T cells targeting CD4 expressed cells in acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) could reduce the risk of off target effects in normal tissues. However, the efficacy of adoptive cell therapy is predominantly attributed to CD8+ T cells, necessitating their purification before lentivirus transfection to enhance the production of CD4-CAR-T cells. In this study, we developed a microfluidic chip functionalized with an optimized CD8 aptamer, A3t-MU, to facilitate the enrichment and purification of CD8+ T cells. The presented chip showed efficient capture and seamless release of CD8+ T cells from cultured T cells and peripheral blood mononuclear cells (PBMCs). The purity of the released CD8+ T cells reached 98.1%, representing a 13% improvement over the conventional magnetic bead separation method. CD4-CAR was efficiently transduced into the purified CD8+ T cells to construct CAR-T cells. We evaluated the antitumor capability of the CD4-CAR transduced CD8+ T cells (anti-CD4 CD8-CAR T cells) both in vitro and in vivo. The anti-CD4 CD8-CAR T cells exhibited significant cancer-cell-killing capacity across multiple tumor cell lines, including CEM, Jurkat, and MV4-11. Meanwhile, anti-CD4 CD8-CAR T cells significantly inhibited tumor growth in vivo. In conclusion, the presented microfluidic chip offers a cost-effective and high-purity approach for CD8+ T cell separation, enhancing CD4-CAR transduction and achieving efficient antitumor capability both in vitro and in vivo.

3.
Phys Rev Lett ; 133(9): 096901, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39270179

RESUMO

We propose a scheme for producing and manipulating quantized exciton-polariton vortices in the higher-order topological corner modes of a two-dimensional array of micropillars. By nonresonantly exciting p-orbital condensates with different orientations at two input corners, polariton vortices carrying the required topological charges can be controllably created at output corners away from the pumping spots. Besides, polariton vortices formed at input corners can be copied to the output corners through the topological edge states. Our scheme provides topological double insurance for intrinsic binary information memory and holds potential applications in remote information processing.

4.
Ecotoxicol Environ Saf ; 285: 117094, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39317071

RESUMO

The problem of paddy Cadmium (Cd) contamination is currently the focus of global research. Earlier researches have confirmed that utilization of organic fertilizers regulates Cd chemical fraction distribution by increases organic bound Cd. However, environmental behaviours of organic fertilizers in paddy are still lack exploration. Here, we critical reviewed previous publications and proposed a novel research concept to help us better understand it. Three potential impact pathways of utilization of organic fertilizers on the bioavailability of Cd are presented: (i) use of organic fertilizers changes soil physicochemical properties, which directly affects Cd bioavailability by changing chemical form of Cd(II); (ii) use of organic fertilizers increases soil nutrient content, which indirectly regulates Cd supply and bioaccumulation through ion adsorption and competition for ion-transport channels between nutrients and Cd; and (iii) use of organic fertilizers increases activity of microorganisms and efflux of rice root exudates, which indirectly affects Cd bioavailability of through complexation and sequestration of these organic materials with Cd. Meanwhile, dissolved organic matter (DOM) in the rhizosphere of rice is believed to be the key to revealing the effects of organic fertilizers on Cd. DOM is capable of adsorption and complexation-chelation reactions with Cd and the fractionation of Cd(II) is regulated by DOM. Molecular mass, chemical composition, major functional groups and reaction sequence of DOM determine the formation and solubilization of DOM-Cd complexes.

5.
Chemosphere ; 364: 143239, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39236928

RESUMO

Combined Cd (cadmium) and As (arsenic) pollution in cultivated land affects the safety of crops production and endangers human health. Rice (Oryza sativa L.) is a crop that uptakes Si (silicon), and Si can effectively promote rice growth and mitigate heavy metal toxicity. This study examined the effect and mechanism of Si-rich amendment (HA) prepared by aerobic combustion of rice husk on Cd and As accumulation in iron plaque and rice seedlings via hydroponic experiments. HA enhanced the vitality of rice growth because of its Si content and increased the amount of amorphous fraction iron plaques, furthermore, Cd content was decreased while the As was increased in both amorphous fraction and crystalline fraction iron plaques, resulting in the contents of Cd and As decreases by 10.0%-38.3% and 9.6%-42.8% for the shoots, and by 13.4%-45.2% and 9.9%-20.0% for the roots, respectively. In addition, X-ray diffraction and X-ray photoelectron spectroscopy illustrated significantly more Fe2O, MnO2 and MnO in the iron plaque after HA supply and the simultaneous existence of Mn-As and Mn-Si compounds. This result revealed less Cd from iron plaque and more As retention with HA supply, reducing the amount of Cd and As up taking and accumulation by rice seedlings. HA is beneficial to rice growth and reduce the absorption of heavy metals in plants. At the same time, HA is environmentally friendly, it can be used for the remediation of paddy fields contaminated by Cd and As.


Assuntos
Arsênio , Cádmio , Ferro , Oryza , Plântula , Silício , Poluentes do Solo , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Cádmio/metabolismo , Arsênio/metabolismo , Ferro/metabolismo , Plântula/metabolismo , Plântula/crescimento & desenvolvimento , Silício/metabolismo , Poluentes do Solo/metabolismo , Raízes de Plantas/metabolismo , Solo/química
6.
Mol Cytogenet ; 17(1): 22, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334424

RESUMO

BACKGROUND: Right aortic arch (RAA) is a common congenital aortic arch abnormality. Fetuses with RAA frequently have good outcomes after birth. However, chromosomal abnormalities and genetic syndromes suggest poor prognosis for these patients. So far the underlying genetic etiology is still not identified in most RAA patients based on traditional genetic techniques and a problem is still debated whether fetuses with isolated RAA should be referred for CMA. Our study aims to investigate the genetic etiology of fetuses with right aortic arch (RAA) by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) and evaluate the efficacy of CMA in fetal isolated RAA. RESULTS: Among these 153 fetuses, 99 (64.7%) with isolated RAA and 54 (35.3%) with non-isolated RAA; 25.5% (39/153) with additional intracardiac anomalies (ICA), and 19.0% (29/153) with extracardiac anomalies (ECA). Tetralogy of Fallot (n = 10) and persistent left superior vena cava (n = 11) are the most common ICA and ECA, respectively. CMA detected 15 clinically significant copy number variations (CNVs) in 14 cases (9.2%); microdeletion of 22q11.21 was the most common pathogenic CNVs (7.8%). The chromosomal abnormalities rate was higher in non-isolated RAA and RAA with ICA groups than in isolated RAA group (16.7% vs. 5.1%; 20% vs. 5.1%, both p < 0.05). From five cases further undergoing WES, a diagnostic variant in MTOR gene (c.7255G > A, de novo) was first reported in prenatal, extending the prenatal manifestation of Smith-Kingsmore syndrome (OMIM: 616638); a clinically relevant variant c.3407A > T in STAG2 was identified, being inherited from the healthy mother. Moreover, the premature birth and termination rates were higher in non-isolated RAA group than in isolated RAA group (11.1% vs. 1.0%; 37.0% vs. 2.0%, both p < 0.01). CONCLUSIONS: We demonstrate that CMA and WES are useful diagnostic tools for fetal RAA, particularly non-isolated RAA, and all fetuses with RAA should be referred for CMA. The data probably aids in prenatal diagnosis and prenatal counseling of fetal RAA.

8.
Chin Clin Oncol ; 13(Suppl 1): AB091, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39295409

RESUMO

BACKGROUND: Traditional preclinical experiments on brainstem gliomas mainly rely on patient-derived primary cell lines, but there are problems such as low success rate in establishment and inability to preserve tumor heterogeneity, which limit the clinical transformation. As a new type of in vitro tumor model, organoids have similar structure and function to the original tumor, requiring less tissue for cultivation, with short cycle and high success rate, which is particularly suitable for brainstem glioma biopsy. There is currently no precedent for the successful construction of brainstem glioma organoid models. This new established organoid provides us a more robust preclinical tool for comprehending the pathogenesis and conducting drug screening for this kind of disease. METHODS: Cultivate patient-derived brainstem glioma organoids in vitro, verify the genetic fidelity and consistency of the organoids through morphological experiments as well as sequencing technology. Then explore the evolutionary direction of multiple types of brainstem gliomas through pseudo-time series analysis. Complete drug screening, natural killer (NK) cell co-culture, oncolytic virus therapy, and other treatments based on organoids in vitro, and evaluate the efficacy. Complete co-culture of organoids and Institute of Cancer Research (ICR) mouse brain slices in vitro. Establish patient-derived organoid xenograft (PDOX) mouse models derived from organoids in vivo. RESULTS: The establishment of organoids of all types of brainstem gliomas was completed for the first time in the world, with a total of 41/48 organoid models derived from patients, with a success rate of 85.4%, covering all segments and pathological types. The results of morphological experiments and sequencing showed that the genetic characteristics of organoids were highly consistent with those of tumor tissues. Drug screening tests for temozolomide and panobinostat were completed in vitro, and NK cell co-culture and oncolytic virus therapy testing were achieved. Co-culture of brainstem glioma organoids and mouse brain slices was achieved in vitro. Furthermore, a PDOX model of brainstem glioma was established. CONCLUSIONS: Brainstem glioma organoids can be established maturely, stably, and reliably, and can be used for preclinical drug testing for patients. Animal models derived from brainstem glioma organoids have broad preclinical experimental value.


Assuntos
Neoplasias do Tronco Encefálico , Glioma , Organoides , Glioma/patologia , Humanos , Camundongos , Animais , Neoplasias do Tronco Encefálico/patologia , Feminino , Masculino
9.
Front Surg ; 11: 1387351, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39345660

RESUMO

Objectives: Magnetic resonance imaging (MRI) is increasingly used to detect knee osteoarthritis (KOA). In this study, we aimed to systematically examine the global research status on the application of medical knee MRI in the treatment of KOA, analyze research hotspots, explore future trends, and present results in the form of a knowledge graph. Methods: The Web of Science core database was searched for studies on medical knee MRI scans in patients with KOA between 2004 and 2023. CiteSpace, SCImago Graphica, and VOSviewer were used for the country, institution, journal, author, reference, and keyword analyses. Results: A total of 2,904 articles were included. The United States and Europe are leading countries. Boston University is the main institution. Osteoarthritis and cartilage is the main magazine. The most frequently cocited article was "Radiological assessment of osteoarthrosis". Guermazi A was the author with the highest number of publications and total references. The keywords most closely linked to MRI and KOA were "cartilage", "pain", and "injury". Conclusions: The application of medical knee MRI in KOA can be divided into the following parts: (1). MRI was used to assess the relationship between the characteristics of local tissue damage and pathological changes and clinical symptoms. (2).The risk factors of KOA were analyzed by MRI to determine the early diagnosis of KOA. (3). MRI was used to evaluate the efficacy of multiple interventions for KOA tissue damage (e.g., cartilage defects, bone marrow edema, bone marrow microfracture, and subchondral bone remodeling). Artificial intelligence, particularly deep learning, has become the focus of research on MRI applications for KOA.

10.
J Hazard Mater ; 480: 135950, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39326145

RESUMO

Polyvinyl chloride (PVC) microplastics present in sewage were trapped in sludge, thereby hindering anaerobic digestion performance of waste active sludge (WAS). Phages regulate virocell metabolism by encoding auxiliary metabolic genes (AMGs) related to energy acquisition and material degradation, supporting hosts survive in harsh environments and play a crucial role in biogeochemical cycles. This study investigated the potential effects of phages on the recovery of WAS anaerobic digestion under PVC stress. We observed a significant alteration in the phage community induced by PVC microplastics. Phages encoded AMGs related to anaerobic digestion and cell growth probably alleviate PVC microplastics inhibition on WAS anaerobic digestion, and 54.2 % of hydrolysis-related GHs and 40.8 % of acidification-related AMGs were actively transcribed in the PVC-exposed group. Additionally, the degradation of chitin and peptidoglycan during hydrolysis and the conversion of glucose to pyruvate during acidification were more susceptible to phages. Prediction of phage-host relationship indicated that the phyla Pseudomonadota were predominantly targeted hosts by hydrolysis-related and acidification-related phages, and PVC toxicity had minimal impact on phage-host interaction. Our findings highlight the importance of phages in anaerobic digestion and provide a novel strategy for using phages in the functional recovery of microplastic-exposed sludge.

11.
Int Ophthalmol ; 44(1): 387, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39312014

RESUMO

OBJECTIVES: To investigate the clinical and image characteristics of primary systemic vasculitis-associated optic neuritis patients. METHODS: This is a retrospective study. The patients clinically diagnosed with primary system vasculitis-induced optic neuritis were recruited from March 2013 to December 2023. All cases received orbital magnetic resonance imaging scans were analyzed. The ocular findings, systemic manifestations, laboratory data and prognosis were reviewed retrospectively. In addition, the related literature was reviewed. RESULTS: Fourteen patients (21 eyes), including 10 men and 4 women, were enrolled in this study. The ages ranged from 30 to 86 years in this cohort. Orbits MRI detects the enlargement and/or enhancement of the optic nerve. Cases 1-5 reported a confirmed diagnosis of Takayasu's arteritis, and cases 6-8 had giant cell arteritis. Cases 9-13 were antineutrophil cytoplasmic antibody-associated vasculitis. Case 14 was Cogan's syndrome. Mult organs and tissues, such as the kidneys, heart, paranasal sinuses, meninges, and respiratory system, were involved. In all of the 14 involved patients, the disease onset was either during the fall or winter season. There were no or only slight improvements in visual activity after conventional therapies. CONCLUSIONS: The autoantibodies' attack on the optic nerve, ischemic damage, or destruction of the blood-brain barrier may be the potential pathogenesis of vasculitis-associated optic neuritis. Even with prompt and aggressive clinical interventions, the prognosis remains unsatisfactory.


Assuntos
Imageamento por Ressonância Magnética , Neurite Óptica , Humanos , Neurite Óptica/diagnóstico , Neurite Óptica/etiologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Sistêmica/diagnóstico , Vasculite Sistêmica/complicações , Nervo Óptico/patologia , Nervo Óptico/diagnóstico por imagem , Acuidade Visual , Seguimentos
12.
Updates Surg ; 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39342519

RESUMO

Performing a pulmonary segmentectomy is a complex process, with precise localization of pulmonary nodules and recognition of intraoperative anatomical variations posing significant challenges. This study aims to assess the advantages of preoperative three-dimensional reconstruction (3D-RE) in thoracoscopic segmentectomy. The study, at Fujian Medical University Cancer Hospital, analyzed data from segmentectomy patients from January 2016 to February 2022. It compared 3D-RE and two-dimensional computed tomography (2D-CT) preoperative scans, focusing on perioperative complications within30 days to identify any differences. This investigation encompassed a total of 265 instances, with 148 belonging to the 3D-RE group and 117 aligned with the 2D-CT group. The 3D-RE group showed reduced intraoperative blood loss and shorter postoperative hospital stays (P < 0.001). They also had higher rates of lymph node sampling and combined subsegmentectomy and segmentectomy procedures (P < 0.01). Postoperative complications, particularly pneumonia and lung fistula, were lower in the 3D-RE group (P = 0.041). The rates of minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) were significantly higher in the 3D-RE group, while adenocarcinoma in situ (AIS) and benign cases were less common (P = 0.006). Surgical duration, chest tube duration, chest drainage volume, surgery complexity, and pathological diagnoses showed no significant differences between the groups. Utilization of preoperative 3D-RE holds potential to minimize both intraoperative and postoperative complications, thereby enhancing the safety and feasibility of undertaking segmentectomy procedures.

13.
Front Plant Sci ; 15: 1416936, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39290739

RESUMO

Soil salinity pollution is increasing worldwide, seriously affecting plant growth and crop production. Existing reports on how potassium indole-3-butyric acid (IBAK) regulates rice salt stress adaptation by affecting rice carbon metabolism, transcription factor (TF) genes expression, and biosynthesis of secondary metabolites still have limitations. In this study, an IBAK solution at 40 mg L-1 was sprayed on rice leaves at the seedling stage. The results showed that the IBAK application could promote shoot and root growth, decrease sucrose and fructose content, increase starch content, and enhance acid invertase (AI) and neutral invertase (NI) activity under salt stress, indicating altered carbon allocation. Furthermore, the expression of TF genes belonging to the ethylene responsive factor (ERF), WRKY, and basic helix-loop-helix (bHLH) families was influenced by IBAK. Many key genes (OsSSIIc, OsSHM1, and OsPPDKB) and metabolites (2-oxoglutaric acid, fumaric acid, and succinic acid) were upregulated in the carbon metabolism pathway. In addition, this study highlighted the role of IBAK in regulating the biosynthesis of secondary metabolites pathway, potentially contributing to rice stress adaptability. The results of this study can provide new sustainable development solutions for agricultural production.

14.
Angew Chem Int Ed Engl ; : e202415540, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39233328

RESUMO

Using combinatory electrolyte blends represents an imperative avenue to achieve good magnesium (Mg)-metal anode compatibility and commercial feasibility in fields of promising rechargeable Mg batteries. However, fundamental challenges of how to manipulate component modifier reactivity on molecule level still remain to be solved. Here, molecular structure design concepts towards seeking bromophenyl complex-based component modifiers has been proposed according to implications of electron-donating and/or electron-withdrawing substituents on Br-C bond dissociation reactivity. Exceptional Mg electro-plating/stripping properties (a stable cycle life of 250 days in Mg//Cu asymmetric cells) have been firstly achieved in a simple salt electrolyte with 1-(3-bromophenyl)-N,N-dimethylmethanamine (BPDMA) as optimal component modifier. Comprehensive analyses disclose the unique electrochemically-active Br-containing ion-pairs formation, such as [(Mg2+)2(TFSI-)Br-]2+ and [(Mg2+)2(TFSI-)(Br-)(G2)2]2+, which results in the much thinner Br- containing and organic-inorganic mixed interphases on Mg-metal anodes. Furthermore, conventional MgSO4-based electrolytes and even calcium (Ca)-ion electrolytes can also be revived by similar strategy, demonstrating its generality and superiority.

15.
Heliyon ; 10(17): e36558, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39286125

RESUMO

Purpose: 17q12 copy number variants (CNVs) have variable presentations and incomplete penetrance, challenging prenatal counseling and management. This study aims to investigate the intrauterine phenotype. Methods: We included 48 fetuses diagnosed with 17q12 microdeletion or microduplication by chromosomal microarray analysis. Results: For 17q12 deletion, renal anomalies were found in 35 fetuses (35/37, 94.6 %), with hyperechogenic kidneys (HEK, 28/37, 75.7 %) and multicystic dysplastic kidneys (17/37, 45.9 %) being the most common findings. Duodenal obstruction (DO) was most frequently combined in 17q12 duplication fetuses. In addition, cardiac abnormalities were the first reported prenatal phenotype in 17q12 duplication fetuses. Conclusion: Our study shows that HEK and DO are the most predominant presentations of 17q12 deletion and duplication, respectively, and cardiac structural abnormalities may be associated with the latter. Although 17q12 CNVs have incomplete penetrance and variable expressivity and may be mainly involved in neurodevelopmental disorders, their short-term prognosis appears positive.

16.
Virol J ; 21(1): 206, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223668

RESUMO

BACKGROUND: Human parainfluenza virus-1 (HPIV-1) is a notable pathogen instigating acute respiratory tract infections in children. The article is to elucidate the epidemiological and genetic characteristics of HPIV-1 circulating in Hangzhou during the period of 2021-2022. METHODS: A cohort of 2360 nasopharyngeal swabs were amassed and subsequently examined via RT-PCR, with HPIV-1 positive samples undergoing P gene sequencing. RESULTS: The highest HPIV-1 infection rates were found in children aged between 3 and 6 years. A pronounced positive rate persisted through the latter half of 2021, with a notable decline observed in the initial half of 2022. All HPIV-1 strains could be clustered into 2 groups: Cluster 1, with strains similar to those found in Japan (LC764865, LC764864), and Cluster 2, with strains similar to the Beijing strain (MW575643). CONCLUSION: In conclusion, our study contributes to the comprehensive data on the epidemiological and genetic characteristics of HPIV-1 in pediatric patients from Hangzhou, post the COVID-19 peak.


Assuntos
Vírus da Parainfluenza 1 Humana , Filogenia , Humanos , China/epidemiologia , Pré-Escolar , Criança , Vírus da Parainfluenza 1 Humana/genética , Vírus da Parainfluenza 1 Humana/isolamento & purificação , Masculino , Feminino , Lactente , Adolescente , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Nasofaringe/virologia , Infecções por Respirovirus/epidemiologia , Infecções por Respirovirus/virologia , Recém-Nascido
17.
Int J Nanomedicine ; 19: 8987-9007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246427

RESUMO

Intracerebral hemorrhage (ICH) is a primary, non-traumatic cerebral event associated with substantial mortality and disability. Despite advancements in understanding its etiology and refining diagnostic techniques, a validated treatment to significantly improve ICH prognosis remains elusive. Exosomes, a subtype of extracellular vesicles, encapsulate bioactive components, predominantly microRNAs (miRNAs), facilitating and regulating intercellular communication. Currently, exosomes have garnered considerable interests in clinical transformation for their nanostructure, minimal immunogenicity, low toxicity, inherent stability, and the ability to traverse the blood-brain barrier. A wealth of studies has demonstrated that exosomes can improve the prognosis of ICH through anti-apoptosis, neurogenesis, angiogenesis, anti-inflammation, immunomodulation, and autophagy, primarily via the transportation or overexpression of selected miRNAs. More importantly, exosomes can be easily customized with specific miRNAs or bioactive compounds to establish delivery systems, broadening their potential applications. This review focuses on the therapeutic potential of exosomes in ICH, reviewing the mechanisms of molecular biology mediated by certain miRNAs, discussing the benefits, challenges, and future prospects in ICH treatment. We hope comprehensive understanding of exosomes based on miRNAs will provide new insights into the treatment of ICH and guide the translation of exosome's research from laboratory to clinical practice.


Assuntos
Hemorragia Cerebral , Exossomos , MicroRNAs , Exossomos/metabolismo , Humanos , Hemorragia Cerebral/terapia , Animais , Barreira Hematoencefálica/metabolismo
18.
J Mol Recognit ; : e3101, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39221493

RESUMO

The SARS-CoV-2 main protease (Mpro) is an essential enzyme that promotes viral transcription and replication. Mpro conserved nature in different variants and its nonoverlapping nature with human proteases make it an attractive target for therapeutic intervention against SARS-CoV-2. In this work, the interaction mechanism between Mpro and diindolylmethane derivatives was investigated by molecular docking, enzymatic inhibition assay, UV-vis, fluorescence spectroscopy, and circular dichroism spectroscopy. Results of IC50 values show that 1p (9.87 µM) was the strongest inhibitor for Mpro in this work, which significantly inhibited the activity of Mpro. The binding constant (4.07 × 105 Lmol-1), the quenching constant (5.41 × 105 Lmol-1), and thermodynamic parameters indicated that the quenching mode of 1p was static quenching, and the main driving forces between 1p and Mpro are hydrogen bond and van der Waals force. The influence of molecular structure on the binding is investigated. Chlorine atoms and methoxy groups are favorable for the diindolylmethane derivative inhibitors of Mpro. This work confirms the changes in the microenvironment of Mpro by 1p, and provides clues for the design of potential inhibitors.

19.
Artigo em Inglês | MEDLINE | ID: mdl-39317823

RESUMO

Transesophageal echocardiography (TEE) is the standard method for diagnosing left atrial appendage (LAA) hypercoagulability in patients with atrial fibrillation (AF), which means LAA thrombus/sludge, dense spontaneous echo contrast and slow LAA blood flow velocity (< 0.25 m/s). Based on machine learning algorithms, cardiac computed tomography angiography (CCTA) radiomics features were adopted to construct prediction models and explore a suitable approach for diagnosing LAA hypercoagulability and adjusting anticoagulation. This study included 652 patients with non-valvular AF. The univariate analysis were used to select meaningful clinical characteristics to predict LAA hypercoagulability. Then 3D Slicer software was adopted to extract radiomics features from CCTA imaging. The radiomics score was calculated using the least absolute shrinkage and selection operator logistic regression analysis to predict LAA hypercoagulability. We then combined clinical characteristics and radiomics scores to construct a nomogram model. Finally, we got prediction models based on machine learning algorithms and logistic regression separately. The area under the receiver operating characteristic curve of radiomics score was 0.8449 in the training set and 0.7998 in the validation set. The nomogram model had a concordance index of 0.838. The final machine-learning based prediction models had good performances (best f1 score = 0.85). Radiomics features of long maximum diameter and high uniformity of Hounsfield unit in left atrial were significant predictors of the hypercoagulable state in LAA, with better predictive efficacy than clinical characteristics. Our combined models based on machine learning were reliable for hypercoagulable state screening and anticoagulation adjustment.

20.
J Adv Res ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142439

RESUMO

INTRODUCTION: Intracerebral haemorrhage (ICH) is a devastating disease that leads to severe neurological deficits. Microglia are the first line of defence in the brain and play a crucial role in neurological recovery after ICH, whose activities are primarily driven by glucose metabolism. However, little is known regarding the status of glucose metabolism in microglia and its interactions with inflammatory responses after ICH. OBJECTIVES: This study investigated microglial glycolysis and its mechanistic effects on microglial inflammation after ICH. METHODS: We explored the status of glucose metabolism in the ipsilateral region and in fluorescence-activated-cell-sorting-isolated (FACS-isolated) microglia via 2-deoxy-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) analyses and gamma emission, respectively. Energy-related targeted metabolomics, along with 13C-glucose isotope tracing, was utilised to analyse glycolytic products in microglia. Mitochondrial membrane potential and mitochondrial reactive oxygen species (MitoROS) accumulation was assessed by flow cytometry. Behavioural, western blotting, gene regulation, and enzymatic activity analyses were conducted with a focus on microglia. RESULTS: Neurological dysfunction was strongly correlated with decreased FDG-PET signals in the perihaematomal region, where microglial uptake of FDG was reduced. The decreased quantity of glucose-6-phosphate (G-6-P) in microglia was attributed to the downregulation of glucose transporter 1 (GLUT1) and hexokinase 2 (HK2). Enhanced inflammatory responses were driven by HK2 suppression via decreased mitochondrial membrane potential, which could be rescued by MitoROS scavengers. HK inhibitors aggravated neurological injury by suppressing FDG uptake and enhancing microglial inflammation in ICH mice. CONCLUSION: These findings indicate an unexpected metabolic status in pro-inflammatory microglia after ICH, consisting of glycolysis impairment caused by the downregulation of GLUT1 and HK2. Additionally, HK2 suppression promotes inflammatory responses by disrupting mitochondrial function, providing insight into the mechanisms by which inflammation may be facilitated after ICH and indicating that metabolic enzymes as potential targets for ICH treatment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA