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1.
Sci Rep ; 14(1): 22467, 2024 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-39341957

RESUMO

The study aims to investigate the potential of training efficient deep learning models by using 2.5D (2.5-Dimension) masks of sICH. Furthermore, it intends to evaluate and compare the predictive performance of a joint model incorporating four types of features with standalone 2.5D deep learning, radiomics, radiology, and clinical models for early expansion in sICH. A total of 254 sICH patients were enrolled retrospectively and divided into two groups according to whether the hematoma was enlarged or not. The 2.5D mask of sICH is constructed with the maximum axial, coronal and sagittal planes of the hematoma, which is used to train the deep learning model and extract deep learning features. Predictive models were built on clinic, radiology, radiomics and deep learning features separately and four type features jointly. The diagnostic performance of each model was measured using the receiver operating characteristic curve (AUC), Accuracy, Recall, F1 and decision curve analysis (DCA). The AUCs of the clinic model, radiology model, radiomics model, deep learning model, joint model, and nomogram model on the train set (training and Cross-validation) were 0.639, 0.682, 0.859, 0.807, 0.939, and 0.942, respectively, while the AUCs on the test set (external validation) were 0.680, 0.758, 0.802, 0.857, 0.929, and 0.926. Decision curve analysis showed that the joint model was superior to the other models and demonstrated good consistency between the predicted probability of early hematoma expansion and the actual occurrence probability. Our study demonstrates that the joint model is a more efficient and robust prediction model, as verified by multicenter data. This finding highlights the potential clinical utility of a multifactorial prediction model that integrates various data sources for prognostication in patients with intracerebral hemorrhage. The Critical Relevance Statement: Combining 2.5D deep learning features with clinic features, radiology markers, and radiomics signatures to establish a joint model enabling physicians to conduct better-individualized assessments the risk of early expansion of sICH.


Assuntos
Aprendizado Profundo , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Curva ROC , Idoso , Diagnóstico Precoce
2.
Artigo em Inglês | MEDLINE | ID: mdl-39186424

RESUMO

Dopaminergic treatment has proved effective to Parkinson's disease (PD), but the conventional treatment assessment is human-administered and prone to intra- and inter-assessor variability. In this paper, we propose a knowledge-driven framework and discover that brain ACtivation-Transition-Spectrum (ACTS) features achieve effective quantified assessments of dopaminergic therapy in PD. Firstly, brain activities of fifty-one PD patients during clinical walking tests under the OFF and ON states (without and with dopaminergic medication) were measured with functional near-infrared spectroscopy (fNIRS). Then, brain ACTS features were formulated based on the medication-induced variations in temporal features of brain regional activation, transition features of brain hemodynamic states, and graph spectrum of brain functional connectivity. Afterwards, a prior selection algorithm was constructed based on recursive feature elimination and graph spectrum analysis for the selection of principal discriminative features. Further, linear discriminant analysis was conducted to predict the treatment-induced improvements. The results demonstrated that the proposed method decreased the misclassification probability from 42% to 16% in the evaluations of dopaminergic treatment and outperformed existing fNIRS-based methods. Therefore, the proposed method promises a quantified and objective approach for dopaminergic treatment assessment, and our brain ACTS features may serve as promising functional biomarkers for treatment evaluation.


Assuntos
Algoritmos , Encéfalo , Doença de Parkinson , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/metabolismo , Análise Discriminante , Dopaminérgicos/uso terapêutico , Caminhada/fisiologia , Hemodinâmica
3.
J Neuroinflammation ; 21(1): 214, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217343

RESUMO

BACKGROUND: Leukocyte immunoglobulin-like receptor B4 (LILRB4) plays a significant role in regulating immune responses. LILRB4 in microglia might influence the infiltration of peripheral T cells. However, whether and how LILRB4 expression aggravates brain damage after acute ischemic stroke remains unclear. This study investigates the role of LILRB4 in modulating the immune response and its potential protective effects against ischemic brain injury in mice. METHODS AND RESULTS: Microglia-specific LILRB4 conditional knockout (LILRB4-KO) and overexpression transgenic (LILRB4-TG) mice were constructed by a Cre-loxP system. Then, they were used to investigate the role of LILRB4 after ischemic stroke using a transient middle cerebral artery occlusion (tMCAO) mouse model. Spatial transcriptomics analysis revealed increased LILRB4 expression in the ischemic hemisphere. Single-cell RNA sequencing (scRNA-seq) identified microglia-cluster3, an ischemia-associated microglia subcluster with elevated LILRB4 expression in the ischemic brain. Flow cytometry and immunofluorescence staining showed increased CD8+ T cell infiltration into the brain in LILRB4-KO-tMCAO mice. Behavioral tests, cortical perfusion maps, and infarct size measurements indicated that LILRB4-KO-tMCAO mice had more severe functional deficits and larger infarct sizes compared to Control-tMCAO and LILRB4-TG-tMCAO mice. T cell migration assays demonstrated that LILRB4-KD microglia promoted CD8+ T cell recruitment and activation in vitro, which was mitigated by CCL2 inhibition and recombinant arginase-1 addition. The scRNA-seq and spatial transcriptomics identified CCL2 was predominantly secreted from activated microglia/macrophage and increased CCL2 expression in LILRB4-KD microglia, suggesting a chemokine-mediated mechanism of LILRB4. CONCLUSION: LILRB4 in microglia plays a crucial role in modulating the post-stroke immune response by regulating CD8+ T cell infiltration and activation. Knockout of LILRB4 exacerbates ischemic brain injury by promoting CD8+ T cell recruitment. Overexpression of LILRB4, conversely, offers neuroprotection. These findings highlight the therapeutic potential of targeting LILRB4 and its downstream pathways to mitigate immune-mediated damage in ischemic stroke.


Assuntos
Linfócitos T CD8-Positivos , AVC Isquêmico , Microglia , Receptores Imunológicos , Regulação para Cima , Animais , Camundongos , Microglia/metabolismo , Microglia/patologia , Linfócitos T CD8-Positivos/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , AVC Isquêmico/imunologia , AVC Isquêmico/genética , Camundongos Knockout , Camundongos Transgênicos , Camundongos Endogâmicos C57BL , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/metabolismo , Lesões Encefálicas/patologia , Lesões Encefálicas/metabolismo , Masculino
4.
Front Neurol ; 15: 1346522, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144709

RESUMO

Introduction: This study aims to examine brain activity during different swallowing actions in patients with dysphagia caused by medullary infarction (MI) before and after treatment using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Methods: Fifteen patients were enrolled in this study. Brain activation during saliva swallowing and effortful saliva swallowing was observed using BOLD imaging in the acute phase of stroke and after 4 weeks of rehabilitation training. Differences in the activation of brain regions during saliva swallowing before and after treatment, during effortful saliva swallowing before and after treatment, and between the two swallowing actions before and after treatment were compared. Results: In the acute phase of stroke, only the bilateral precentral and left lingual gyrus were partially activated during saliva swallowing, and there was no obvious activation in the insula. Effortful saliva swallowing activated more brain regions than saliva swallowing before treatment, including the bilateral supplementary motor area (SMA), postcentral gyrus, and right insular cortex. The number of brain regions activated during saliva swallowing increased after treatment, including the bilateral precentral gyrus, postcentral gyrus, insula, thalamus, and SMA. Discussion: Cortical activation increases after recovery from dysphagia, and the increased activation of the postcentral gyrus might play a functional compensatory role. Effortful saliva swallowing is a more effective rehabilitation training method for patients with dysphagia caused by MI.

5.
Arch Esp Urol ; 77(5): 598-604, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38982790

RESUMO

OBJECTIVE: This study aimed to analyse the characteristics of biochemical recurrence after radical prostatectomy via bi-parametric magnetic resonance imaging. METHODS: A total of 200 patients with radical prostatectomy admitted to our hospital from January 2016 to January 2021 were retrospectively enrolled as observation objects. According to whether there was biochemical recurrence after surgery, the patients were divided into the abnormal group (n = 62) and normal group (n = 138). Clinical data, encapsulation infiltration, seminal vesicle infiltration and prostate imaging report and data system (PI-RADS) were collected and compared between the two groups. Propensity score matching (PSM) was used to balance the baseline data of the two groups. Student's t-test and Chi-square test were used to analyse the data. RESULTS: PSM was performed in a 1:1 ratio, and a total of 72 patients were included in the abnormal and normal groups. The baseline data of the patients in each group were not statistically significant. The incidence of extraperitoneal invasion and seminal vesicle invasion was higher in the abnormal group than in the normal group, and we observed a significant difference in PI-RADS scores between the two groups (p < 0.05). Extracapsular invasion, seminal vesicle invasion, PI-RADS score and biochemical recurrence were significantly correlated (p < 0.05). The PI-RADS score has a high value for predicting biochemical recurrence, with an area under the curve value of 0.824, sensitivity of 0.667, specificity of 0.861 and Youden index of 0.528. CONCLUSIONS: Bi-parametric magnetic resonance imaging has a high predictive value in biochemical recurrence after radical prostatectomy, which can provide reference for early intervention measures.


Assuntos
Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Imageamento por Ressonância Magnética , Antígeno Prostático Específico/sangue , Imageamento por Ressonância Magnética Multiparamétrica
6.
Artigo em Inglês | MEDLINE | ID: mdl-38867482

RESUMO

CONTEXT: Patients with Cushing's syndrome (CS) have higher risk of obesity and diabetes, which are important risk factors of cancers. However, if patients with CS have a higher incidence of cancer remains unknown. OBJECTIVE: To investigate if endogenous CS is associated with increased cancer incidence. DESIGN: A nationwide cohort study. SETTING: Analysis of the data retrieved from Taiwan's National Health Insurance program in 2006-2017. PARTICIPANTS: Between 2006-2017, 1278 patients with newly diagnosed endogenous CS were identified. Among them, 1246 patients without a history of malignancy were enrolled in this study. EXPOSURES: Endogenous CS. MAIN OUTCOMES MEASURES: The age- and sex-standardized incidence rate of all-cause cancer and age-sex-calendar year standardized incidence ratio (SIR) of cancer in association with endogenous CS. RESULTS: The age- and sex-standardized incidences of CS decreased from 4.84 to 3.77 per million person-years between 2006-2017. The age at diagnosis of CS was 45.3 ± 14.8 years, and 80.0% of the patients were female. Cushing's disease and adrenal CS accounted for 35.4% and 64.6% of patients with CS, respectively. The incidence rate of cancer in patients with CS was 7.77 (95% Confidence Interval [CI] = 5.84-10.14) per 1000 person-years, with an SIR of 2.08 (95% CI = 1.54-2.75). The three most common cancer types were liver (27.7%), kidney (16.7%), and lung (13.0%). CONCLUSIONS: Patients with endogenous CS have a higher incidence of cancer.

7.
Arch Pharm Res ; 47(6): 505-537, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38850495

RESUMO

The oceans are rich in diverse microorganisms, animals, and plants. This vast biological complexity is a major source of unique secondary metabolites. In particular, marine fungi are a promising source of compounds with unique structures and potent antibacterial properties. Over the last decade, substantial progress has been made to identify these valuable antibacterial agents. This review summarizes the chemical structures and antibacterial activities of 223 compounds identified between 2012 and 2023. These compounds, effective against various bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus, exhibit strong potential as antibacterial therapeutics. The review also highlights the relevant challenges in transitioning from drug discovery to product commercialization. Emerging technologies such as metagenomics and synthetic biology are proposed as viable solutions. This paper sets the stage for further research on antibacterial compounds derived from marine fungi and advocates a multidisciplinary approach to combat drug-resistant bacteria.


Assuntos
Antibacterianos , Produtos Biológicos , Fungos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/química , Fungos/efeitos dos fármacos , Organismos Aquáticos/química , Animais , Humanos , Bactérias/efeitos dos fármacos , Descoberta de Drogas , Testes de Sensibilidade Microbiana
8.
Ann Fam Med ; 22(4): 309-316, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914437

RESUMO

PURPOSE: We undertook a study to investigate the relationship between duration of medication use and prevalence of impaired awareness of hypoglycemia (IAH) among patients with insulin-treated or sulfonylurea-treated type 2 diabetes in Taiwan. METHODS: A total of 898 patients (41.0% insulin users, 65.1% sulfonylurea users; mean [SD] age = 59.9 [12.3] years, 50.7% female) were enrolled in pharmacies, clinics, and health bureaus of Tainan City, Taiwan. Presence of IAH was determined with Chinese versions of the Gold questionnaire (Gold-TW) and Clarke questionnaire (Clarke-TW). Sociodemographics, disease and treatment histories, diabetes-related medical care, and health status were collected. We used multiple logistic regression models to assess the relationship between duration of medication use and IAH. RESULTS: Overall IAH prevalence was 41.0% (Gold-TW) and 28.2% (Clarke-TW) among insulin users, and 65.3% (Gold-TW) and 51.3% (Clarke-TW) among sulfonylurea users. Prevalence increased with the duration of sulfonylurea use, whereas it decreased with the duration of insulin use. After controlling for potential confounders, 5 or more years of sulfonylurea use was significantly associated with 3.50-fold (95% CI, 2.39-5.13) and 3.06-fold (95% CI, 2.11-4.44) increases in the odds of IAH based on the Gold-TW and Clarke-TW criteria, respectively. On the other hand, regular blood glucose testing and retinal examinations were associated with reduced odds in both insulin users and sulfonylurea users. CONCLUSIONS: The prevalence of IAH was high among patients using sulfonylureas long term, but the odds of this complication were attenuated for those who received regular diabetes-related medical care. Our study suggests that long-term sulfonylurea use and irregular follow-up increase risk for IAH. Further prospective studies are needed to confirm the observed associations.Annals Early Access article.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Hipoglicemiantes , Insulina , Compostos de Sulfonilureia , Humanos , Compostos de Sulfonilureia/uso terapêutico , Compostos de Sulfonilureia/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Idoso , Insulina/uso terapêutico , Prevalência , Modelos Logísticos , Inquéritos e Questionários , Fatores de Tempo , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais
9.
Heliyon ; 10(9): e30718, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38765065

RESUMO

Although serum albumin and neuroticism have revealed a strong association with suicidal ideation in individuals with depression, the causal relationship between them is uncertain. This study analyzed the causal association of serum albumin, neuroticism and suicidal ideation using large-scale GWAS data and Univariable Mendelian Randomization (UVMR) methods. The Multivariable MR (MVMR) analysis was used to explore the causal pathways. UVMR analysis revealed that genetically determined serum albumin is causally associated with neuroticism (ß = -0.006 S.D.; 95 % CI: 0.009, -0.002; p = 0.003) and suicidal ideation (ß = 0.009 S.D.; 95 % CI: 0.001, 0.016; p = 0.037); and that neuroticism mediates 100 % of the causal association between serum albumin and suicidal ideation in individuals with depression. These findings suggest genetic evidence for the causal effect of serum albumin on suicidal ideation in depressed patients and the significant mediation effect of neuroticism on this causal association. This study proves the protective role of serum albumin for neuroticism and the riskiness of personality traits for suicidal ideation in individuals with depression.

10.
Ecol Evol ; 14(5): e11355, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38694754

RESUMO

The mitochondrial genome (mitogenome) has been extensively used as molecular markers in determining the insect phylogenetic relationships. In order to resolve the relationships among tribes and subtribes of Satyrinae at the mitochondrial genomic level, we obtained the complete mitogenome of Aulocera merlina (Oberthür, 1890) (Lepidoptera: Nymphalidae: Satyrinae) with a size of 15,259 bp. The mitogenome consisted of 37 typical genes, including 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and an A + T-rich region. The gene organization and arrangement were similar to those of all other known Satyrinae mitogenomes. All PCGs were initiated with the canonical codon pattern ATN, except for the cox1 gene, which used an atypical CGA codon. Nine PCGs used the complete stop codon TAA, while the remaining PCGs (cox1, cox2, nad4, and nad5) were terminated with a single T nucleotide. The canonical cloverleaf secondary structures were found in all tRNAs, except for trnS1 which lacked a dihydrouridine arm. The 448 bp A + T-rich region was located between rrnS and trnM, and it included the motif ATAGA followed by a 19-bp poly-T stretch and a microsatellite-like (TA)6 element preceded by the ATTTA motif. The phylogenetic tree, inferred using Bayesian inference and maximum likelihood methods, generated similar tree topologies, revealing well-supported monophyletic groups at the tribe level and recovering the relationship ((Satyrini + Melanitini) + ((Amathusiini + Elymniini) + Zetherini)). The close relationship between Satyrina and Melanargiina within the Satyrini was widely accepted. Additionally, Lethina, Parargina, and Mycalesina were closely related and collectively formed a sister group to Coenonymphina. Moreover, A. merlina was closely related to Oeneis buddha within the Satyrina. These findings will provide valuable information for future studies aiming to elucidate the phylogenetic relationships of Satyrinae.

11.
Am J Gastroenterol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38775310

RESUMO

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

12.
Nanomaterials (Basel) ; 14(10)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38786841

RESUMO

Two-dimensional transition metal dichalcogenides (2D-TMDs) possess appropriate bandgaps and interact via van der Waals (vdW) forces between layers, effectively overcoming lattice compatibility challenges inherent in traditional heterojunctions. This property facilitates the creation of heterojunctions with customizable bandgap alignments. However, the prevailing method for creating heterojunctions with 2D-TMDs relies on the low-efficiency technique of mechanical exfoliation. Sb2Te3, recognized as a notable p-type semiconductor, emerges as a versatile component for constructing diverse vertical p-n heterostructures with 2D-TMDs. This study presents the successful large-scale deposition of 2D Sb2Te3 onto inert mica substrates, providing valuable insights into the integration of Sb2Te3 with 2D-TMDs to form heterostructures. Building upon this initial advancement, a precise epitaxial growth method for Sb2Te3 on pre-existing WS2 surfaces on SiO2/Si substrates is achieved through a two-step chemical vapor deposition process, resulting in the formation of Sb2Te3/WS2 heterojunctions. Finally, the development of 2D Sb2Te3/WS2 optoelectronic devices is accomplished, showing rapid response times, with a rise/decay time of 305 µs/503 µs, respectively.

13.
Animals (Basel) ; 14(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38791685

RESUMO

Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.

14.
Adv Sci (Weinh) ; 11(24): e2309517, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38647405

RESUMO

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the primary treatment for ischemic stroke. However, rtPA treatment can substantially increase blood-brain barrier (BBB) permeability and susceptibility to hemorrhagic transformation. Herein, the mechanism underlying the side effects of rtPA treatment is investigated and demonstrated that ferroptosis plays an important role. The ferroptosis inhibitor, liproxstatin-1 (Lip) is proposed to alleviate the side effects. A well-designed macrocyclic carrier, glucose-modified azocalix[4]arene (GluAC4A), is prepared to deliver Lip to the ischemic site. GluAC4A bound tightly to Lip and markedly improved its solubility. Glucose, modified at the upper rim of GluAC4A, imparts BBB targeting to the drug delivery system owing to the presence of glucose transporter 1 on the BBB surface. The responsiveness of GluAC4A to hypoxia due to the presence of azo groups enabled the targeted release of Lip at the ischemic site. GluAC4A successfully improved drug accumulation in the brain, and Lip@GluAC4A significantly reduced ferroptosis, BBB leakage, and neurological deficits induced by rtPA in vivo. These findings deepen the understanding of the side effects of rtPA treatment and provide a novel strategy for their effective mitigation, which is of great significance for the treatment and prognosis of patients with ischemic stroke.


Assuntos
Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Ferroptose , AVC Isquêmico , Ativador de Plasminogênio Tecidual , Animais , Ferroptose/efeitos dos fármacos , Camundongos , AVC Isquêmico/tratamento farmacológico , Ativador de Plasminogênio Tecidual/farmacologia , Ativador de Plasminogênio Tecidual/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Masculino , Quinoxalinas , Compostos de Espiro
16.
Mol Ther ; 32(9): 2992-3011, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582962

RESUMO

Cellular senescence associates with pathological aging and tissue dysfunctions. Studies utilizing mouse models for cell lineage tracings have emphasized the importance of senescence heterogeneity in different organs and cell types. Here, we constructed a p21- (Akaluc - tdTomato - Diphtheria Toxin Receptor [DTR]) (ATD) mouse model to specifically study the undefined mechanism for p21-expressing senescent cells in the aged and liver injury animals. The successful expressions of these genes enabled in vitro flow cytometric sorting, in vivo tracing, and elimination of p21-expressing senescent cells. During the natural aging process, p21-expressing cells were found in various tissues of p21-ATD mice. Eliminating p21-expressing cells in the aged p21-ATD mice recovered their multiple biological functions. p21-ATD/Fah-/- mice, bred from p21-ATD mice and fumarylacetoacetate hydrolase (Fah)-/- mice of liver injury, showed that the majority of their senescent hepatocytes were the phenotype of p21+ rather than p16+. Furthermore, eliminating the p21-expressing hepatocytes significantly promoted the engraftment of grafted hepatocytes and facilitated liver repopulation, resulting in significant recovery from liver injury. Our p21-ATD mouse model serves as an optimal model for studying the pattern and function of p21-expressing senescent cells under the physical and pathological conditions during aging.


Assuntos
Senescência Celular , Inibidor de Quinase Dependente de Ciclina p21 , Modelos Animais de Doenças , Hepatócitos , Regeneração Hepática , Animais , Camundongos , Senescência Celular/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Hepatócitos/metabolismo , Fígado/metabolismo , Fígado/patologia , Hidrolases/genética , Hidrolases/metabolismo , Camundongos Transgênicos , Camundongos Knockout
17.
Parkinsonism Relat Disord ; 123: 106949, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38564831

RESUMO

INTRODUCTION: Gait initiation (GI) includes automatic and voluntary movements. However, research on their impact on the first step in patients with Parkinson's disease (PD) and their relationship to freezing of gait (FOG) is lacking. We examined the effects of automatic movements (anticipatory postural adjustments [APAs]) and voluntary movements (limits of stability [LOS]) on the first step (first-step duration and first-step range of motion), along with their early recognition and prediction of slight FOG. METHODS: Twenty-three patients with PD and slight freezing (PD + FOG) and 25 non-freezing patients with PD (PD-FOG) were tested while off medications and compared with 24 healthy controls (HC). All participants completed a 7-m Stand and Walk Test (7 m SAW) and wore inertial sensors to quantify the APAs and first step. LOS was quantified by dynamic posturography in different directions using a pressure platform. We compared differences among all three groups, analysed correlations, and evaluated their predictive value for slight FOG. RESULTS: In PD + FOG, APAs and LOS were worse than those in the PD-FOG and HC groups (p < 0.001), and the first step was worse than that in HC (p < 0.001). APAs were correlated mainly with the first-step duration. APAs and LOS were correlated with the first-step range of motion. APAs have been recognized as independent predictors of FOG, and their combination with LOS enhances predictive sensitivity. CONCLUSION: APAs and LOS in patients with PD directly affect the first step during GI. In addition, the combination of APAs and LOS helped predict slight FOG.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Equilíbrio Postural , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Masculino , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/diagnóstico , Idoso , Equilíbrio Postural/fisiologia , Pessoa de Meia-Idade
18.
Int J Rheum Dis ; 27(4): e15145, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38661314

RESUMO

OBJECTIVES: To determine the alteration of peripheral T and B cell subsets in patients with systemic sclerosis (SSc) and to evaluate their correlation with the progression of SSc. METHODS: We recruited 47 SSc patients and 45 healthy controls (HCs) in this study. Demographic and clinical data were then collected. Flow cytometry was used to detect the proportions of 44 different T and B cell subsets in circulating blood. RESULTS: The proportion of total B cells (p = .043) decreased in SSc patients, together with similar frequencies of total T cells, CD4+ T cells, and CD8+ T cells in both groups. Several subsets of T and B cells differed significantly between these two groups. Follicular helper T cells-1 (Tfh1) (p < .001), helper T cells-1 (Th1) (p = .001), regulatory T cells (Treg) (p = .004), effector memory CD8+ T cells (p = .041), and cytotoxic T cells-17 (Tc17) (p = .01) were decreased in SSc patients. Follicular helper T cells-2 (Tfh2) (p = .001) and, helper T cells-2 (Th2) (p = .001) levels increased in the SSc group. Regulatory B cells (Breg) (p = .015) were lower in the SSc group, together with marginal zone (MZ) B cells (p < .001), memory B cells (p = .001), and non-switched B cells (p = .005). The modified Rodnan skin score (mRSS) correlated with helper T cells-17 (Th17) (r = -.410, p = .004), Tfh1 (r = -.321, p = .028), peripheral helper T cells (Tph) (r = -.364, p = .012) and plasma cells (r = -.312, p = .033). CONCLUSIONS: The alterations in T and B cells implied immune dysfunction, which may play an essential role in systemic sclerosis.


Assuntos
Subpopulações de Linfócitos B , Escleroderma Sistêmico , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos de Casos e Controles , Subpopulações de Linfócitos B/imunologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico , Subpopulações de Linfócitos T/imunologia , Citometria de Fluxo , Fenótipo , Progressão da Doença , Imunofenotipagem , Idoso
19.
Arch Esp Urol ; 77(2): 217-223, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38583015

RESUMO

OBJECTIVE: We aimed to investigate the value of magnetic resonance imaging (MRI) radiomics combined with serum prostate-specific antigen (PSA) in predicting the extracapsular extension (ECE) of prostate cancer. METHODS: In total, 213 patients with prostate cancer admitted to our hospital from May 2021 to April 2023 were retrospectively enrolled as observation subjects. Based on the presence or absence of extracapsular extension, the patients were divided into occurrence (n = 70) and non-occurrence (n = 143) groups. The clinical data, PSA levels, Prostate Imaging Reporting and Data System (PI-RADS®), and MRI-ECE scores of the two groups were compared. RESULTS: In total, 80 patients were included in the occurrence (n = 40) and non-occurrence groups (n = 40), and no statistical significance was observed in the baseline data of the two groups. Preoperative PSA levels were significantly higher in the occurrence group than in the non-occurrence group, and the PI-RADS and MRI-ECE scores of each group differed significantly (p < 0.05). The area under the curve (AUC) for the combined determination of PSA levels and PI-RADS and MRI-ECE scores was 0.900, which was significantly higher than the AUC for the individual determination of the mentioned indicators (p < 0.05). CONCLUSIONS: The combination of MRI radiomics and PSA can accurately predict the extracapsular extension of prostate cancer; Thus, it is a favorable reference for subsequent precise diagnosis and treatment.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/cirurgia , Imageamento por Ressonância Magnética/métodos , Antígeno Prostático Específico , Estudos Retrospectivos , Radiômica , Extensão Extranodal
20.
Parkinsonism Relat Disord ; 123: 106102, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38507892

RESUMO

BACKGROUND: Peripheral inflammation plays a significant role in Parkinson's disease (PD). Conflicting studies on whether inflammatory indicators in blood could serve as biomarkers to distinguish PD. OBJECTIVE: Include a wider range of biomarkers and control confounding factors to comprehensively evaluate the value of peripheral inflammation-related indicators. METHODS: A total of 80 PD patients were recruited and 80 one-to-one matched healthy controls (HCs). The levels of B-cell, T-cell, and natural killer (NK)-cell in blood were measured using flow cytometry. The levels of neurodegeneration-related proteins in serum were detected and clinical blood test results were collected. Multivariable logistic regression analysis was conducted to explore the role of significant variables in PD. Receiver operating characteristic curve analysis was performed to assess the potential value of these variables. RESULTS: Compared to HCs, PD patients showed lower levels of lymphocyte, B-cell, T-cell, high-density lipoprotein cholesterol (HDL-C) and lymphocyte-to-monocyte ratio, while the levels of neutrophil, NK-cell, ß-amyloid40, neurofilament light chain, neutrophil-to-lymphocyte ratio, and neutrophil-to-HDL-C ratio (NHR) were increased. A higher B-cell count was associated with a lower risk of PD, while higher levels of NK-cell and NHR were associated with a higher risk of PD. B-cell, NK-cell and NHR have potential value in distinguishing PD from non-PD. B-cell and NHR levels were significantly correlated with PD dyskinesia scores. CONCLUSIONS: B-cell, NK-cell, and NHR may potentially contribute to distinguishing PD patients from HCs. There could be a correlation between the number of B-cell, the level of NHR, and the severity of PD dyskinesia.


Assuntos
Biomarcadores , Células Matadoras Naturais , Doença de Parkinson , Humanos , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Idoso , Inflamação/sangue , Inflamação/diagnóstico , Linfócitos B , Linfócitos T , Neutrófilos
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