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1.
ACS Nano ; 17(24): 25468-25482, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38096153

RESUMO

The complexity and progressive nature of diseases require the exploitation of multifunctional materials. However, introducing a function inevitably increases the complexity of materials, which complicates preparation and decreases reproducibility. Herein, we report a supramolecular integration of multifunctional nanomaterials based on mannose-modified azocalix[4]arene (ManAC4A) and ginsenoside Rb1 (Rb1), which showed advances of simplicity and reproducibility. ManAC4A possesses reactive oxygen species (ROS) scavenging capacity and hypoxia-responsiveness, together with macrophage-targeting and induction functionality. Collectively, the Rb1@ManAC4A assembly simply prepared by two components is integrated with multifunction, including triple targeting (ELVIS targeting, macrophage-targeting, and hypoxia-targeted release) and triple therapy (ROS scavenging, macrophage polarization, and the anti-inflammatory effect of Rb1). The spontaneous assembly and recognition of ManAC4A, with its precise structure and molecular weight, facilitated the simple and straightforward preparation of Rb1@ManAC4A, leading to excellent batch consistency. Progress in simplicity and reproducibility, as directed by this research, will catalyze the clinical translation of multifunctional materials.


Assuntos
Artrite Reumatoide , Nanoestruturas , Humanos , Espécies Reativas de Oxigênio , Manose , Reprodutibilidade dos Testes , Hipóxia
2.
Front Pharmacol ; 14: 1260599, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074142

RESUMO

Background: Ciprofol, a novel sedative-hypnotic drug, has been approved for its use in inducing and maintaining general anesthesia, as well as for providing sedation. Methods: In this phase I, single-center, parallel, controlled, open-label clinical trial, our objective was to analyze the pharmacokinetics (PK), pharmacodynamics (PD), and safety of ciprofol emulsion in 24 participants with mild and moderate renal impairment (n = 8 per group) and matched healthy participants (n = 8). An initial loading infusion of ciprofol was administered at 0.4 mg/kg for 1 min, followed by a maintenance infusion at a rate of 0.4 mg/kg/h for 30 min. We collected plasma and urine samples from the participants to assess the PK of ciprofol and its metabolite M4. The evaluation of PD involved using a modified observer's alertness/sedation scale (MOAA/S) in combination with bispectral index (BIS) monitoring. Safety assessments were conducted throughout the trial process. Results: The plasma concentration-time curve of ciprofol in participants with renal impairment was similar to that in participants with normal kidney function. The area under the curve (AUC) and maximum concentration (Cmax) of total and unbound ciprofol in plasma for participants with renal impairment were only slightly higher (0.7-1.2-fold) than those in participants with normal renal function. In contrast, for the metabolite M4, AUC values were 1.3- and 2.1-fold greater in participants with mild and moderate renal impairment, respectively, than in healthy controls. However, renal impairment had no significant impact on the PD parameters. The study found that ciprofol was well-tolerated, with all adverse events (AEs) reported being mild or moderate in severity. Conclusion: Based on these findings, we can conclude that no dosage adjustment of ciprofol is necessary for patients with mild-moderate renal impairment who receive the injection. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04142970.

3.
Front Oncol ; 13: 1247682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074651

RESUMO

Purpose: This bi-institutional study aimed to establish a robust model for predicting clinically significant prostate cancer (csPCa) (pathological grade group ≥ 2) in PI-RADS 3 lesions in the transition zone by comparing the performance of combination models. Materials and methods: This study included 243 consecutive men who underwent 3-Tesla magnetic resonance imaging (MRI) and ultrasound-guided transrectal biopsy from January 2020 and April 2022 which is divided into a training cohort of 170 patients and a separate testing cohort of 73 patients. T2WI and DWI images were manually segmented for PI-RADS 3 lesions for the mean ADC and radiomic analysis. Predictive clinical factors were identified using both univariate and multivariate logistic models. The least absolute shrinkage and selection operator (LASSO) regression models were deployed for feature selection and for constructing radiomic signatures. We developed nine models utilizing clinical factors, radiological features, and radiomics, leveraging logistic and XGboost methods. The performances of these models was subsequently compared using Receiver Operating Characteristic (ROC) analysis and the Delong test. Results: Out of the 243 participants with a median age of 70 years, 30 were diagnosed with csPCa, leaving 213 without a csPCa diagnosis. Prostate-specific antigen density (PSAD) stood out as the only significant clinical factor (odds ratio [OR], 1.068; 95% confidence interval [CI], 1.029-1.115), discovered through the univariate and multivariate logistic models. Seven radiomic features correlated with csPCa prediction. Notably, the XGboost model outperformed eight other models (AUC of the training cohort: 0.949, and validation cohort: 0.913). However, it did not surpass the PSAD+MADC model (P > 0.05) in the training and testing cohorts (AUC, 0.949 vs. 0.888 and 0.913 vs. 0.854, respectively). Conclusion: The machine learning XGboost model presented the best performance in predicting csPCa in PI-RADS 3 lesions within the transitional zone. However, the addition of radiomic classifiers did not display any significant enhancement over the compound model of clinical and radiological findings. The most exemplary and generalized option for quantitative prostate evaluation was Mean ADC+PSAD.

4.
J Affect Disord ; 340: 567-574, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37573890

RESUMO

OBJECTIVES: The study sought to examine the impact of longitudinal changes in depressive symptoms in middle-aged adults before and after their first stroke, and the impact of different ages. METHODS: The study monitored middle-aged patients with a first stroke in the China Family Panel Study (CFPS) survey from 2016 to 2020. This study examined longitudinal changes in depressive symptoms in middle-aged adults and their controls before and after stroke using multilevel models, and also explored factors influencing middle-aged adults at the time of their respective stroke and depressive symptoms using conditional regression models and stepwise regression models, respectively. A chi-square test was used to determine whether long-term changes in depressive symptoms in patients before and after stroke could be attributed to changes in a single depressive symptom. RESULTS: The study identified 582 first-time stroke patients and 5522 controls from a population of 17,588 participants. Middle-aged populations may have an increased risk of depressive symptoms after a first stroke compared to older populations. First-time stroke victims showed increased severity of depressive symptoms in both the two years before and the two years after stroke when depressive symptoms were assessed. Differences in the presentation of a single depressive symptom were most pronounced in sleep-related symptoms. CONCLUSIONS: The link between first stroke and changes in the trajectory of increased depressive symptoms is complex and bidirectional. Age is an important factor influencing changes in depressive symptoms, some attention should be paid to the middle-aged population. Special attention should also be paid to sleep-related symptoms in the long-term care of patients.


Assuntos
Depressão , Acidente Vascular Cerebral , Adulto , Pessoa de Meia-Idade , Humanos , Estudos Longitudinais , Depressão/epidemiologia , Depressão/diagnóstico , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , China/epidemiologia
5.
BMC Public Health ; 23(1): 1145, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316848

RESUMO

BACKGROUND: Depression is on the rise globally. Additionally, the United States has a high level of population mobility. The main aim of this study was to provide a reference for improving the mental health of internal migrants by investigating the relationship between internal migration experience and depressive symptoms. METHODS: We analysed data from the Panel Study of Income Dynamics (PSID). We included PSID data from the 2005 to 2019 waves in which all respondents were asked about their internal migration experience and depressive symptoms. This study included 15,023 participants. T tests, chi-square tests, multiple logistic regression methods were performed and fixed effects model. RESULTS: In the sample, the prevalence of depressive symptoms was 4.42%. The risk of depression in internal migrants was 1.259 times (OR = 1.259, 95% CI = (1.025-1.547, p < 0.05) that of nonmigrants. Internal migration experience was significantly positively associated with female depressive episodes (OR = 1.312, 95% CI = 1.010-1.704, p < 0.05) and increased risk of becoming depressed at a young age (OR = 1.304, 95% CI = 1.010-1.684, p < 0.05). The association between internal migration experience and depressive symptoms was more significant for participants who might move (OR = 1.459, 95% CI = 1.094-1.947, p < 0.05). In addition, different internal migratory causes are associated with depressive symptoms to varying degrees. CONCLUSIONS: Our findings highlight the need for greater policy attention to mental health inequalities between Internal migrants and those who never move away from their hometown in the United States. Our study provides a foundation for further research.


Assuntos
Depressão , Renda , Humanos , Feminino , Depressão/epidemiologia , Saúde Mental , Políticas
6.
Mater Horiz ; 10(5): 1689-1696, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-36825769

RESUMO

Host-guest drug delivery systems (HGDDSs) have been studied in an effort to modify the characteristics of therapeutic agents through noncovalent interactions, reduce toxic side effects and improve therapeutic effects. However, it is still an important task to continuously improve the targeting ability of HGDDSs, which is conducive to the development of precision medicine. Herein, we utilize the lactose-modified azocalix[4]arene (LacAC4A) as a triple targeting drug carrier customized for antitumor purposes. LacAC4A integrates three targeting features, passive targeting through the enhancing permeability and retention effect, active targeting by the interactions of lactose and the asialoglycoprotein receptors on the surface of tumor cells, and stimuli-responsive targeting via the reduction of the azo group under a hypoxia microenvironment. After loading doxorubicin (DOX) in LacAC4A, the supramolecular nanoformulation DOX@LacAC4A clearly showed the effective suppression of tumor growth through in vivo experiments. LacAC4A can achieve effective targeting, rapid release, and improve drug bioavailability. This design principle will provide a new material for drug delivery systems.


Assuntos
Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Neoplasias , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Lactose , Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Humanos
7.
Br J Clin Pharmacol ; 89(3): 1139-1151, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36217805

RESUMO

AIMS: The aim of this study was to develop a population pharmacokinetic (PK) model to simultaneously describe both total and unbound concentrations of ciprofol and its major glucuronide metabolite, M4, and to link it to the population pharmacodynamics (PD) model in subjects with various renal functions. METHODS: A total of 401 and 459 pairs of total and unbound plasma concentrations of ciprofol and M4, respectively, as well as 2190 bispectral index (BIS) data from 24 Chinese subjects with various renal functions were available. Covariates that may potentially contribute to the PK and PD variability of ciprofol were screened using a stepwise procedure. The optimal ciprofol induction dosing regimen was determined by model-based simulations. RESULTS: The PK of unbound ciprofol could best be described by a three-compartment model, while a two-compartment model could adequately describe unbound M4 PK. The concentrations of total and unbound ciprofol and M4 were linked using a linear protein binding model. The relationship between plasma concentrations of ciprofol and BIS data was best described by an inhibitory sigmoidal Emax model with a two-compartment biophase distribution compartment. Hemoglobin was the identified covariate determining the central compartment clearance of ciprofol; uric acid was a covariate affecting the central compartment clearance of M4 and protein binding rate, kB . The included covariates had no effect on the PD of ciprofol. Simulation results indicated that the label-recommended dose regimen was adequate for anaesthesia induction. CONCLUSIONS: The developed model fully characterized the population PK and PD profiles of ciprofol. No dose adjustment is required in patients with mild and moderate renal impairment.


Assuntos
Rim , Modelos Biológicos , Humanos , Relação Dose-Resposta a Droga , Rim/fisiologia
8.
Nat Prod Res ; 37(12): 1961-1968, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35975763

RESUMO

The phytochemical study on the stems and leaves of Morinda citrifolia L. resulted in the isolation of a new naturally occurring bisabolane-type sesquiterpenoid, morincitrinoid A (1), together with five known analogues (2-6). The chemical structure of 1 was elucidated by comprehensive spectral analyses. The known compounds 2-6 were identified by comparing their spectral data with those reported in the literature, which were isolated from M. citrifolia for the first time. In addition, the anti-inflammatory and anti-HIV activities of compounds 1-6 were evaluated in vitro. Compounds 1-6 displayed significant inhibitory activities on NO (nitric oxide) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells with IC50 values ranging from 0.98 ± 0.07 to 6.32 ± 0.11 µM, which was comparable to hydrocortisone. Meanwhile, compounds 1-6 showed remarkable anti-HIV-1 reverse transcriptase (RT) effects with the EC50 values ranging from 0.16 to 6.29 µM.


Assuntos
Sesquiterpenos Monocíclicos , Animais , Camundongos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Óxido Nítrico/química , Morinda/química , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/farmacologia , Estrutura Molecular
9.
Nat Prod Res ; 37(9): 1456-1462, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-34894893

RESUMO

The phytochemical investigation on the fruits of Morinda citrifolia led to the isolation and characterization of a new anthraquinone, moricitrifone (1), along with seven known anthraquinones (2-8). The chemical structure of 1 was elucidated by extensive spectral analyses. The known compounds (2-8) were identified by comparing their spectral data with those reported in the literature. The antiproliferative activities of all isolated anthraquinones (1-8) against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 were evaluated in vitro. Compounds 1-8 exhibited remarkable antiproliferative activities with IC50 values ranging from 0.26 ± 0.05 to 16.58 ± 0.18 µM, which were comparable to those of doxorubicin.


Assuntos
Morinda , Humanos , Morinda/química , Estrutura Molecular , Frutas/química , Extratos Vegetais/química , Antraquinonas/química
10.
J Ethnopharmacol ; 300: 115691, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36087844

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Erigeron breviscapus (Vant.) Hand.-Mazz.,a Chinese herbal medicine with multiple pharmacological effects and clinical applications, has been traditionally used in the treatment of paralysis caused by stroke and joint pain from rheumatism by the Yi minority people of Southwest China for generations.However, its mechanism involves many factors and has not been fully clarified. AIM OF THE STUDY: Taking intestinal flora as the target, the protective effect of extract(breviscapine) of E. breviscapus on cerebral ischemia and its possible mechanism were discussed from the perspective of brain inflammatory pathway and intestinal CYP3A4, which depends on intestinal flora. MATERIALS AND METHODS: In this study, we first verified the binding ability between major active ingredient of Erigeron breviscapus and the core target TLR4 protein by molecular docking using Vina software.We established a rat model of cerebral ischemia-reperfusion injury in vivo.The neurological function of rats was scored by Bederson score table, the cerebral infarction volume was detected by TTC staining, and the serum NSE level was detected by ELASA. 16S rRNA sequencing was used to detect the intestinal flora of rats in each group.The expression levels of cerebral TLR4/MyD88/NF-κB and CYP3A4 mRNA and protein in different intestinal segments were detected by qRT-PCR and Western blot. RESULTS: Compared with the model group, the neurological injury score, infarct volume and serum NSE concentration of breviscapine low, medium and high dose groups and nimodipine groups decreased significantly. Meanwhile, breviscapine could significantly reduce the expression level of the TLR4/MyD88/NF-κB in brain tissue and CYP3A4 in different intestinal segments of rats with cerebral ischemia-reperfusion injury. In addition, breviscapine also significantly ameliorated intestinal flora dysbiosis of rats with cerebral ischemia-reperfusion injury. CONCLUSIONS: Breviscapine can protect rats from cerebral ischemia-reperfusion injury by regulating intestinal flora, inhibiting brain TLR4/MyD88/NF-κB inflammatory pathway and intestinal CYP3A4 expression.


Assuntos
Isquemia Encefálica , Medicamentos de Ervas Chinesas , Erigeron , Microbioma Gastrointestinal , Traumatismo por Reperfusão , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Erigeron/genética , Erigeron/metabolismo , Flavonoides , Simulação de Acoplamento Molecular , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Nimodipina/farmacologia , RNA Mensageiro/metabolismo , RNA Ribossômico 16S , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
11.
Cardiol J ; 30(3): 353-360, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36200544

RESUMO

BACKGROUND: Previous studies have established that moderately to severely calcified lesions (MSCL) are associated with high rates of major adverse cardiovascular events, even when drug-eluting stents are implanted after rotational atherectomy (RA). Yet, the changes in coronary function indexes during follow-ups have never been investigated. The quantitative flow ratio (QFR), a novel coronary function index, has been increasingly adopted in daily practice in recent years. METHODS: A total of 111 MSCL patients were retrospectively enrolled in this study. The vessel QFR (QFRv) loss was defined as post-percutaneous coronary intervention QFRv minus follow-up QFRv. The study subjects were divided into high QFRv loss (n = 51) and low QFRv loss (n = 60) groups according to the binary method. The obtained predictors of QFRv loss were then analyzed. RESULTS: The results showed that the final burr-to-vessel ratio (B to V ratio) in the high QFRv loss group decreased significantly compared to the low QFRv loss group (p < 0.01). The univariate and multivariate regression analyses indicated that the final B to V ratio was an excellent predictor of QFRv loss. The cut-off value of the final B to V ratio for QFRv loss prediction was 0.50 (sensitivity: 50.98%, specificity: 68.33%, and area under the curve: 0.627 [95% confidence interval: 0.530-0.717], p < 0.05). Additionally, the target vessel failure incidence in the high QFRv loss group was higher than in the low QFRv loss group (p < 0.01). CONCLUSIONS: An increased burr-to-vessel ratio can prevent QFRv loss in patients with MSCLs after RA, an effect that might be closely associated with a low target vessel failure incidence.


Assuntos
Aterectomia Coronária , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Calcificação Vascular , Humanos , Aterectomia Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Intervenção Coronária Percutânea/efeitos adversos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/cirurgia , Angiografia Coronária
12.
Zhonghua Nan Ke Xue ; 29(9): 810-814, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-38639593

RESUMO

OBJECTIVE: To evaluate the therapeutic effects of Xuanju compound capsule combined with urofollitropin (uFSH) in the treatment of idiopathic oligoasthenozoospermia. METHODS: From June 2022 to June 2023, patients with idiopathic oligoastheospermia were enrolled in this study, and divided into trail group (Xuanju compound capsule combined with urofollitropin tablets, n=53) and control group (urofollitropin tablets, n=61) according to the difference in treatment. Treatment methods: Xuanju compound capsule, 3 pills, three times a day; Urofollitropin, 75IU, one times three day. The curses of treatments for control group and trail group is 12 weeks. In order to evaluate the therapeutic effects of control group and trial group, semen volume, sperm concentration, progressive sperm ratio (PR), peripheral serum sex hormone, liver functions were analyzed before and after treatment for two times. RESULTS: Compared with the baseline, the semen volume and liver function were not significantly changed after the treatment in control group and trial group. However, sperm concentration, PR, testosterone (T) levels, follicle stimulating hormone (FSH) levels, and luteinizing hormone (LH) levels were significantly unregulated after the treatment in control group and trial group. More importantly, compared to control group, sperm concentration, PR, T leves, FSH levels, LH levels, and T/E2 ratio of trial group were further enhanced after the treatment, which were statistically significant (P < 0.05). CONCLUSIONS: Xuanju compound capsule combined with urofollitropin tablets could significantly improve the semen quality, up-regulate the testosterone levels and T/E2 ratio in patients with idiopathic oligoasthenozoospermia.


Assuntos
Urofolitropina , Humanos , Masculino , Hormônio Foliculoestimulante , Sêmen , Análise do Sêmen , Contagem de Espermatozoides , Testosterona , Resultado do Tratamento , Urofolitropina/uso terapêutico
13.
Front Oncol ; 12: 990247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338724

RESUMO

It has been established that long-chain coding RNA (lncRNA) SLC25A25-AS1 is associated with cancer progression. However, the roles and mechanisms of SLC25A25-AS1 in prostate cancer (PC) have not been reported in the literature. The present study explored the relationship between SLC25A25-AS1 expression and PC progression via comprehensive analysis. The pan-cancer expression of SLC25A25-AS1 was identified using data from The Cancer Genome Atlas (TCGA) database and tissue specimens from our hospital. The expression levels of SLC25A25-AS1 in various subgroups based on the clinical features were identified. The prognostic value of SLC25A25-AS1 and SLC25A25-AS1 co-expressed lncRNAs in PC patients was assessed by survival analysis and ROC analysis, and prognosis-related risk models of SLC25A25-AS1 were constructed. The relationship between SLC25A25-AS1 and the PC immune microenvironment was investigated using correlation analysis. SLC25A25-AS1 expression in PC was significantly increased and correlated with the T stage, clinical stage, Gleason score (GS), and dismal prognosis. SLC25A25-AS1 overexpression exhibited good performance in evaluating the prognosis of PC patients. The area under the curves (AUCs) of the 1-, 3-, and 5-year overall survival (OS) for SLC25A25-AS1 was 1, 0.876, and 0.749. Moreover, the AUCs for the 1-, 3-, and 5-year progress free interval (PFI) for SLC25A25-AS1 were 0.731, 0.701, and 0.718. SLC25A25-AS1 overexpression correlated with the infiltration of CD8 T cells, interstitial dendritic cells (IDC), macrophages and other cells. AC020558.2, ZNF32-AS2, AP4B1-AS1, AL355488.1, AC109460.3, SNHG1, C3orf35, LMNTD2-AS1, and AL365330.1 were significantly associated with SLC25A25-AS1 expression, and short OS and PFI in PC patients. The risk models of the SLC25A25-AS1-related lncRNAs were associated with a dismal prognosis in PC. Overall, SLC25A25-AS1 expression was increased in PC and related to the prognosis and PC immune microenvironment. The risk model of SLC25A25-AS1 have huge prospect for application as prognostic tools in PC.

14.
Ann Clin Transl Neurol ; 9(12): 1974-1984, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36314483

RESUMO

OBJECTIVE: Brain magnetic resonance imaging (MRI) findings in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are nonspecific and rarely have obvious associations with clinical characteristics and outcomes. This study aimed to comprehensively describe the MRI features of patients with NMDAR encephalitis, examine their associations with clinical characteristics, and evaluate their predictive power for disease recurrence and prognosis. METHODS: We retrospectively extracted the clinical data and brain MRI findings of 144 patients with NMDAR encephalitis. Patients underwent a 2-year follow-up to assess disease outcomes. We evaluated the associations of brain MRI findings at the onset with clinical characteristics, recurrence, and prognosis. RESULTS: Initial MRI showed typical abnormalities in 65 patients (45.1%); of these, 34 (29.3%) developed recurrence and 10 (9.4%) had poor prognosis (mRS ≥3). Binary logistic regression analyses revealed that insula abnormalities were associated with acute seizure (odds ratio [OR] = 3.048, 95% confidence interval [CI]: 1.026-9.060) and white matter lesions were associated with cognitive impairment (OR = 2.730, 95% CI: 1.096-6.799). Risk factors for a poor 2-year prognosis included a higher number of brain MRI abnormalities (OR = 1.573, 95% CI: 1.129-2.192) and intensive care unit (ICU) admissions (OR = 15.312, 95% CI: 1.684-139.198). The risk factors for 2-year recurrence included abnormalities of the thalamus (HR = 3.780, 95% CI: 1.642-8.699). INTERPRETATIONS: Brain MRI features of patients with NMDAR encephalitis were associated with clinical manifestations, prognosis, and recurrence. Higher numbers of MRI abnormalities and ICU admissions were predictive of poor prognosis. Abnormalities of the thalamus constituted a recurrence-related risk factor.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Encefalopatias , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico por imagem , Estudos Retrospectivos , Recidiva Local de Neoplasia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Receptores de N-Metil-D-Aspartato
15.
Ann Diagn Pathol ; 60: 152021, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35939880

RESUMO

BACKGROUND: Molecular markers for the detection of lymph node micrometastases of malignant tumors have been extensively investigated. However, epigenetic signatures have rarely been reported for identification of metastatic lymph nodes and disease relapse. Septin 9 is the most frequently reported hypermethylated gene in colorectal cancer (CRC). This study aimed to assess the clinical relevance of Septin 9 methylation in regional lymph nodes in recurrence/metastases of CRC. METHODS: We analyzed Septin 9 methylation of DNA from resected lymph nodes in 75 CRC patients with or without tumor recurrence using quantitative methylation-sensitive PCR (qMS-PCR). RESULTS: Of the 30 histologically negative lymph node CRC patients without recurrence (group 1), methylated Septin 9 was detected in 3 (10 %) cases. The positivity rate of methylated Septin 9 in group 2 containing 30 histologically node-negative CRC patients with recurrence was 30 % (9/30). For group 3, lymphatic invasion as well as tumor recurrence, 11 (73 %) out of 15 subjects had Septin 9 methylation-positive lymph nodes. Moreover, patients in group 3 had a higher level of methylated Septin 9 compared to subjects in group 1 and group 2 (p < 0.05). In addition, CRC patients with Septin 9 methylation in lymph nodes had significantly reduced survival (Log-rank P < 0.0001). CONCLUSION: Our data support the predictive role of Septin 9 methylation analysis of lymph node micrometastases for tumor relapse after surgery.


Assuntos
Neoplasias Colorretais , Micrometástase de Neoplasia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Metilação , Micrometástase de Neoplasia/diagnóstico , Micrometástase de Neoplasia/patologia , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias , Prognóstico , Septinas/genética , Septinas/metabolismo
16.
Cancer Lett ; 545: 215827, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35842018

RESUMO

The endothelium is the critical barrier that controls transendothelial communications. Blood vessels in cancer tissue are poorly developed and highly permeable. However, it is poorly understood how circulating cancer cells released through these "leaky" vessels break the intact vasculature of remote organs to metastasize. We investigated the roles of cancer cell-derived extracellular vesicles (CEVs) in regulating cancer metastasis by analyzing samples from gastric cancer patients, performing in vitro experiments, and studying mouse models. We made several novel observations. First, the rate of metastasis was closely associated with plasma levels of CEVs in patients with gastric cancer. Second, cultured endothelial cells endocytosed CEVs, resulting in cytoskeletal rearrangement, low expression of the junction proteins cadherin and CD31, and forming large intercellular gaps to allow the transendothelial migration of cancer cells. The dynamin inhibitor Dynasore prevented these CEV-induced changes of endothelial cells by blocking CEVs endocytosis. Third, CEVs disrupted the endothelial barrier of cancer-bearing mice to promote cancer metastasis. Finally, lactadherin promoted the clearance of circulating CEVs to reduce metastasis. These results demonstrate the essential role of CEVs in promoting the metastasis of gastric cancer.


Assuntos
Vesículas Extracelulares , Neoplasias Gástricas , Animais , Caderinas/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Vesículas Extracelulares/metabolismo , Camundongos , Neoplasias Gástricas/patologia
17.
Asia Pac J Clin Nutr ; 31(2): 305-311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35766566

RESUMO

BACKGROUND AND OBJECTIVES: This study evaluated the relationship between dietary inflammatory index (DII) and metabolic health in the Chinese elderly. METHODS AND STUDY DESIGN: A total of 6,730 participants from the "Community-based Cardiovascular and Health Promotion Study" (CoCHPS) cohort were included in this study. The DII scores were acquired using a validated 125-item food-frequency questionnaire (FFQ) (ranged -5.84 to 3.90). The correlation of DII with metabolic health indexes was evaluated with logistic regression and multivariable cox regression using SPSS and R software. RESULTS: Compared with low DII scores, subjects in the highest DII score quartiles had higher odds of metabolic dysfunction (OR=1.36, 95% CI: 1.07-1.68, p trend=0.023). In the subgroup analyses, the effect of a pro-inflammatory diet on metabolic dysfunction was particularly evident among people with hyperglycaemia (HR=1.58, 95% CI: 1.35-2.14), hypertension (HR=1.48, 95% CI: 1.07-2.09), dyslipidemia (HR=1.45, 95% CI: 1.24-1.87), abdominal obesity (HR=2.16, 95% CI: 1.57-2.96), and ≥60 years old (HR=1.32, 95% CI: 1.04-1.56) or who were women (HR=1.35, 95% CI: 1.08-1.67). CONCLUSIONS: DII score was associated with metabolic health. Further studies are needed to deepen our understanding of dietary parameters and different populations.


Assuntos
Dieta , Inflamação , Idoso , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Inflamação/complicações , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
18.
ACS Macro Lett ; 11(5): 615-621, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35570815

RESUMO

Renal-clearable nanomedicines are considered the next generation of nanomedicines, and show potential application for future clinical translations. However, it is important to determine whether self-assembly can form large aggregates that accrue in tumors and then tailor the size of these assemblies to be excreted renally. In this paper, a renal-clearable nanomedicine based on quanterrylene bisimide-mannose conjugates (QDI-Man) was developed. QDI-Man showed a high renal clearance efficiency of 80.31 ± 2.85% in mice. We confirmed that the self-assembly of QDI-Man exhibited a dynamic adjustment process through the renal filtration thresholds, that is, "aggregation → self-regulating the aggregate size through the renal filtration thresholds → reaggregating into aggregates". Benefiting from the modification of mannose-based glycoclusters, QDI-Man showed selective photothermal therapy because of the mannose receptors overexpressed in breast cancer cells, and showed good photothermal therapy in mice. This paper developed a dynamic adjustment theory for effective renal clearance based on organic self-assembly.


Assuntos
Neoplasias , Terapia Fototérmica , Animais , Humanos , Rim , Manose/uso terapêutico , Camundongos , Nanomedicina , Neoplasias/tratamento farmacológico
19.
Artigo em Inglês | MEDLINE | ID: mdl-35482508

RESUMO

A Gram-negative, rod-shaped aerobic bacterium designated as strain 2R12T was isolated from the rhizosphere soil of Hosta plantaginea. Phylogenetic analyses based on the 16S rRNA gene revealed that strain 2R12T should be assigned to the genus Chitinophaga with the highest sequence similarity to Chitinophaga arvensicola DSM 3695T (99.1 %) and Chitinophaga ginsengisegetis DSM 18108T (98.6 %). The major fatty acids of strain 2R12T (>10 %) were iso-C15 : 0, C16 :1 ω5c and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and five unidentified lipids. The predominant respiratory quinone was MK-7. The genomic DNA G+C content was 46.1 mol%. The average nucleotide identity values of strain 2R12T with C. arvensicola DSM 3695T and C. ginsengisegetis DSM 18108T were 77.9 and 78.8 %, respectively, while in silico DNA-DNA hybridization values for strain 2R12T with these strains were 22.8 and 23.3 %, respectively. Based on comparative analysis of phylogenetic, phylogenomic, phenotypic and chemotaxonomic characteristics, strain 2R12T represents a novel species in the genus Chitinophaga, for which the name Chitinophaga hostae sp. nov. is proposed. The type strain is 2R12T (=ACCC 61757T=JCM 34719T).


Assuntos
Gammaproteobacteria , Hosta , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Gammaproteobacteria/genética , Hosta/genética , Filogenia , RNA Ribossômico 16S/genética , Rizosfera , Análise de Sequência de DNA , Solo , Microbiologia do Solo , Vitamina K 2
20.
Acta Neurol Scand ; 145(4): 434-441, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34927233

RESUMO

BACKGROUND: The factors associated with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis relapse are yet to be elucidated. AIMS OF THE STUDY: To investigate the factors associated with relapse and prognosis of anti-NMDA receptor encephalitis. METHODS: This retrospective study included patients diagnosed with anti-NMDA receptor encephalitis admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to October 2019. The clinical features, auxiliary examinations, treatment regimens, and follow-up were recorded. The outcomes were relapse and 2-year disease prognosis. RESULTS: A total of 160 patients were included. Consequently, 6 (5%) deaths, 34 (25.4%) relapses, and 19 (15.2%) patients had a poor prognosis (modified Rankin score (mRS) ≥3) were recorded. The multivariable analyses showed that age (p = .011), abnormal magnetic resonance imaging (MRI) (p = .019), glucocorticoid pulse (p = .009), and intracranial pressure (p = .023) were independently associated with the relapse, while age (p = .030) and central hypoventilation (p = .020) were independently associated with a poor prognosis at 2 years. CONCLUSION: Glucocorticoid pulse therapy reduces the relapse of anti-NMDA receptor encephalitis. Age, abnormal MRI, and intracranial pressure are risk factors for relapse, while age and central hypoventilation are independently associated with poor prognosis.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico por imagem , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/complicações , Receptores de N-Metil-D-Aspartato , Estudos Retrospectivos
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