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1.
Eur Spine J ; 32(4): 1326-1333, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36829066

RESUMEN

PURPOSE: Clinical outcome of spinal cavernous malformation (SCM) varies because of its unclear natural history, and reliable prognostic prediction model for SCM patients is limited. The aim of the present study was to investigate potential factors that predict one-year neurological status in postoperative patients with SCM. METHODS: This was a multicenter prospective observational study in consecutive patients with SCMs. SCMs treated microsurgically between January 2015 and January 2021 were included. Outcome was defined as the American Spinal Injury Association Impairment Scale (AIS) grade at one year after operation. Multivariable analyses were used to construct the best predictive model for patient outcomes. RESULTS: We identified 268 eligible SCM patients. Neurological outcome had worsened from preoperative baseline in 51 patients (19.0%) at one year. In the multivariable logistic regression, the best predictive model for unfavorable outcome included symptom duration ≥ 26 months (95% CI 2.80-16.96, P < 0.001), size ≤ 5 mm (95% CI 1.43-13.50, P = 0.010), complete intramedullary (95% CI 1.69-8.14, P = 0.001), subarachnoid hemorrhage (95% CI 2.92-12.57, P < 0.001), AIS B (95% CI 1.91-40.93, P = 0.005) and AIS C (95% CI 1.12-14.54, P = 0.033). CONCLUSIONS: Admission size of the lesion, morphology, symptom duration, AIS grade and the presence of subarachnoid hemorrhage were strong outcome predictors regarding prognostication of neurological outcome in postoperative patients with SCMs. A decision to surgically remove a symptomatic SCM should be justified by systematic analysis of all factors potentially affecting outcome.


Asunto(s)
Anomalías Musculoesqueléticas , Hemorragia Subaracnoidea , Humanos , Estudios Prospectivos , Procedimientos Neuroquirúrgicos , Pronóstico , Resultado del Tratamiento , Estudios Retrospectivos
2.
J Environ Manage ; 347: 119091, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37793288

RESUMEN

Canopy interception loss affects the local water budget by removing a non-negligible proportion of rainfall from the terrestrial surface. Thus, quantifying interception loss is essential for thoroughly understanding the role of vegetation in the local hydrological cycle, especially in dryland ecosystems. However, sparse shrubs in dryland ecosystems have not been sufficiently studied, owing to time- and labor-intensive field experiments and challenging model parameterization. In this work, 4-year growing season field experiments on rainfall partitioning were conducted for three dominant shrub species (Haloxylon ammodendron, Nitraria sphaerocarpa, and Calligonum mongolicum) in an oasis-desert ecotone in northwestern China. The revised Gash analytical model was well parameterized, which reliably simulated the cumulative interception loss for sparse shrubs, and the validated model performed better for H. ammodendron, followed by C. mongolicum and N. sphaerocarpa, with relative errors of 8.4%, 15.4%, and 23.9%, respectively. The mean individual interception loss percentage for H. ammodendron (28.4%) was significantly higher than that for C. mongolicum (11.0%) and N. sphaerocarpa (10.9%) (p < 0.05), which could be ascribed to the higher canopy storage capacity and wet-canopy evaporation rate of H. ammodendron. For all shrub species, the majority proportion of interception loss occurred during canopy saturation and drying-out periods, accounting for approximately 79-85% of the cumulative interception loss. Overall, the mean local interception loss of three dominant shrub species in the ecotone removed nearly 17% of the corresponding cumulative rainfall during the growing season. These results not only provide methodological references for estimating the interception loss of sparse vegetation in dryland ecosystems, but also provide scientific insights for water resource management and ecosystem restoration in water-limited regions similar to the experimental site.


Asunto(s)
Chenopodiaceae , Fabaceae , Ecosistema , Lluvia , Movimientos del Agua , Agua
3.
J Viral Hepat ; 29(6): 455-464, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35080256

RESUMEN

Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. Our previous studies indicated that alfosbuvir monotherapy was well-tolerated and druggable in healthy subjects and HCV-infected patients. Here, we evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV genotype 1, 2, 3 or 6. In this open-label study, patients with chronic HCV infection were randomly assigned with a 1:1:1 ratio to receive 12 weeks of daclatasvir 60 mg plus alfosbuvir at a dose of 400, 600 or 800 mg (Cohort A, B or C) daily. Randomization was stratified by HCV genotype and the presence or absence of cirrhosis at screening. The primary endpoint was a sustained virologic response 12 weeks after the end of treatment (SVR12). A total of 124 patients were enrolled in the study, all of whom were available for post-treatment week 12 assessments. SVR12 was achieved in 92.7% (38/41), 95.2% (40/42) and 100% (41/41) of patients in Cohort A, B and C respectively. The most common adverse events were hepatic steatosis, upper respiratory tract infection, hypercholesterolaemia, hypertriglyceridaemia, blood bilirubin increased, and total bile acids increased. There were no discontinuations due to adverse events, and no treatment-related serious adverse events were reported. Once-daily oral administration of alfosbuvir plus daclatasvir were highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3 or 6, suggesting this regimen could be a promising drug candidate for HCV treatment irrespective of genotype. (ClinicalTrials.gov number, NCT04070235).


Asunto(s)
Hepacivirus , Hepatitis C Crónica , Antivirales/efectos adversos , Carbamatos , China , Quimioterapia Combinada , Genotipo , Hepacivirus/genética , Humanos , Imidazoles , Pirrolidinas , Ribavirina/uso terapéutico , Resultado del Tratamiento , Valina/análogos & derivados
4.
Bioorg Med Chem Lett ; 61: 128552, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35051574

RESUMEN

The transforming growth factor type ß receptor I (TGF-ß R1, also known as activin-like kinase 5 or ALK5) plays a significant role in the pathogenesis of multiple diseases such as malignant tumors and tissue fibrosis. Specific inhibition of ALK5 provides a novel method for controlling the development of cancers and fibrotic diseases. Herein, a novel series of 4-(pyridine-4-oxy)-3-(tetrahydro-2H-pyran-4-yl)-pyrazole derivatives was synthesized and identified as ALK5 inhibitors. Among them, compound 8h inhibited ALK5 autophosphorylation and NIH3T3 cell activity with IC50 values of 25 nM and 74.6 nM, respectively. Compound 8h also showed favorable pharmacokinetic profile and ameliorated hERG inhibition. More importantly, 30 mg/kg oral administration of 8h could significantly induce tumour growth inhibition in CT26 xenograft model without obvious toxicity.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Pirazoles/farmacología , Piridinas/farmacología , Receptor Tipo I de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Estructura Molecular , Células 3T3 NIH , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Pirazoles/síntesis química , Pirazoles/química , Piridinas/síntesis química , Piridinas/química , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Relación Estructura-Actividad
5.
Future Oncol ; 17(24): 3203-3216, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33947216

RESUMEN

Aim: We aimed at investigating the mechanism of RAB1A proliferation and invasion in gliomas. Materials & methods: Genome-wide expression profile data and immunohistochemistry were analyzed to assess RAB1A expression in gliomas. The Transwell assay, wound healing assay, brain slice coculture model, cellular fluorescence and intracranial xenograft model of nude mice were used to determine the proliferation and invasion of glioma cells. Results & conclusion: RAB1A was highly expressed in gliomas compared with normal brain tissue. The overall survival time of glioma patients with high RAB1A expression was significantly shortened. RAB1A regulated the activity of RAC1 by inhibiting the mTOR signaling pathway, affecting actin polymerization, cell morphology and cell polarity. RAB1A downregulation inhibited the epithelial-mesenchymal transition, proliferation and invasion of glioma cells.


Asunto(s)
Neoplasias Encefálicas/patología , Transición Epitelial-Mesenquimal/fisiología , Glioma/patología , Serina-Treonina Quinasas TOR/metabolismo , Proteínas de Unión al GTP rab1/metabolismo , Animales , Proliferación Celular/fisiología , Xenoinjertos , Humanos , Ratones , Ratones Desnudos , Invasividad Neoplásica/patología , Transducción de Señal/fisiología
6.
J Clin Lab Anal ; 35(2): e23599, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33247622

RESUMEN

The diagnosis of renal cell carcinoma (RCC) is often made late since there is no early symptom, which thus results in dismal patient prognosis. As a result, new biomarkers are urgently needed and efforts should be made to identify their functions in predicting RCC prognosis. microRNAs (miRNAs) are a class of small noncoding RNAs that are about 20-22 nucleotides in length, and they have been demonstrated to function as prognostic markers in numerous tumors. This study aimed to assess the role of miR-30b-5p in predicting the prognosis of RCC postoperatively. In this study, RNA was extracted from 284 formalin-fixed and paraffin-embedded kidney cancer tissue samples. After cDNA synthesis, real-time quantitative PCR (RT-qPCR) was adopted for detecting the relative miR-30b-5p level. Then, the Kaplan-Meier method, Cox regression analysis, and the receiver operating characteristic curve analysis were applied in analyzing the miR-30b-5p effect on the prognosis for patients. Our findings indicated that, following adjustment for age, gender, tumor stage, and tumor size, patients with low miR-30b-5p expression had remarkably longer overall survival. Thus, the miR-30b-5p level might be related to RCC prognosis.


Asunto(s)
Carcinoma de Células Renales/genética , Carcinoma de Células Renales/mortalidad , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , MicroARNs/genética , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Regulación hacia Arriba
7.
Molecules ; 26(11)2021 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-34070610

RESUMEN

As a significant co-activator involved in cell cycle and cell growth, differentiation and development, p300/CBP has shown extraordinary potential target in cancer therapy. Herein we designed new compounds from the lead compound A-485 based on molecular dynamic simulations. A series of new spirocyclic chroman derivatives was prepared, characterized and proven to be a potential treatment of prostate cancer. The most potent compound B16 inhibited the proliferation of enzalutamide-resistant 22Rv1 cells with an IC50 value of 96 nM. Furthermore, compounds B16-P2 displayed favorable overall pharmacokinetic profiles, and better tumor growth inhibition than A-485 in an in vivo xenograft model.


Asunto(s)
Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Cromanos/química , Neoplasias de la Próstata/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Cromanos/farmacología , Xenoinjertos , Humanos , Concentración 50 Inhibidora , Masculino , Simulación del Acoplamiento Molecular , Neoplasias de la Próstata/patología , Análisis Espectral/métodos , Relación Estructura-Actividad
8.
AAPS PharmSciTech ; 22(1): 46, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33442785

RESUMEN

Combination therapy is one of the most common clinical practices in the treatment of malignancies. Synergistic effects, however, are produced only when optimal ratios of combined drugs were delivered to tumor cells. Thus, carriers co-encapsulating of multiple drugs are widely utilized for coordinated delivery. Herein, co-encapsulated pegylated liposomal formulation of mitoxantrone (MIT) and berberine (BER) at an optimal ratio has been developed (MBL) with high encapsulation efficiency (EE) and drug loading in order to achieve the purpose of ratiometric loading and delivery. MBL can not only extend blood circulation but also enhance tumor accumulation for both MIT and BER. More importantly, MBL can maintain the originally desired drug ratio in tumors within 48 h of intravenous injection for synergistic therapy. Compared with the liposomal formulation of MIT-treated group (ML), the progression of tumor growth was inhibited significantly in murine 4T1 breast tumor model after the treatment of MBL, as well as a lower cardiac toxicity. In addition, MBL evidently prolonged the survival of mice with L1210 ascitic tumor model. In summary, such a strategy of co-encapsulated liposomes could improve the clinical applications against multiple cancers.


Asunto(s)
Antineoplásicos/administración & dosificación , Berberina/administración & dosificación , Cardiotoxicidad/prevención & control , Corazón/efectos de los fármacos , Liposomas , Mitoxantrona/administración & dosificación , Animales , Antineoplásicos/toxicidad , Berberina/farmacología , Línea Celular Tumoral , Femenino , Humanos , Ratones , Mitoxantrona/toxicidad
9.
Bioorg Med Chem Lett ; 30(16): 127339, 2020 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-32631540

RESUMEN

TGF-ß type I receptor (also known as activin-like kinase 5 or ALK5) plays a critical role in the progression of fibrotic diseases and tumor invasiveness and metastasis, as well. The development of small inhibitors targeting ALK5 has been validated as a potential therapeutic strategy for fibrotic diseases and cancer. Here, we developed various 4-((1-cyclopropyl-3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl) oxy) pyridine-2-yl) amino derivatives as ALK5 inhibitors. The optimization led to identification of potent and selective ALK5 inhibitors 12r. The compound 12r exhibited strong inhibitory activity both in vitro and in vivo, and pharmacokinetics study showed an oral bioavailability of 57.6%. Thus, compound 12r may provide as new therapeutic option as ALK5 TGF-ßR1 inhibitor.


Asunto(s)
Diseño de Fármacos , Inhibidores de Proteínas Quinasas/farmacología , Receptor Tipo I de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , Ratones , Estructura Molecular , Células 3T3 NIH , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Piridinas , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Relación Estructura-Actividad
10.
Int J Med Sci ; 17(15): 2269-2275, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32922191

RESUMEN

Cancer vasculature is immature, disorganized and hyperpermeable and can serve as a target for anti-cancer therapies. Vascular disrupting agents (VDAs) are tubulin protein binding and depolymerizing agents that induce rapid tumoral vascular shutdown and subsequent cancer necrosis. However, two clinical problems exist with all VDAs, i.e. 1) incomplete anticancer effect and 2) dose-dependent toxicity. To tackle these problems, in our ongoing research, a novel VDA C118P is applied by transarterial administration of half the intravenous dose in rabbits with implanted VX2 liver tumor to assess its therapeutic efficacy. Nearly complete tumor necrosis was achieved by only a single arterial dose of C118P at 5 mg/kg, which was documented in a representative case by in vivo digital subtraction arteriogram (DSA) and magnetic resonance imaging (MRI), and further confirmed by ex vivo microangiogram and histopathology. This convincing and promising preliminary outcome would warrant further comprehensive studies to explore the potentials of VDAs by transarterial administration either in mono-drug or in combination for management of solid cancers.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Imidazoles/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Éteres Fenílicos/administración & dosificación , Angiografía de Substracción Digital , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Ensayos de Selección de Medicamentos Antitumorales , Arteria Hepática/diagnóstico por imagen , Humanos , Inyecciones Intraarteriales , Hígado/diagnóstico por imagen , Hígado/efectos de los fármacos , Hígado/patología , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Neovascularización Patológica/diagnóstico , Neovascularización Patológica/patología , Conejos
11.
J Clin Lab Anal ; 34(12): e23517, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32761678

RESUMEN

OBJECTIVE: Previous research has shown that the miR-130 family is closely related to the occurrence and development of bladder cancer. We hope to use the miR-130 family members as new, non-invasive, and easily detectable biomarkers for bladder cancer. METHODS: We analyzed 428 cases in The Cancer Genome Atlas-Bladder Urothelial Carcinoma database and verified that the miR-130 family members were significantly overexpressed in bladder cancer. A total of 74 bladder cancer patients and 90 controls were enrolled. The relative expression of the miR-130 family in serum was detected using quantitative reverse transcription-polymerase chain reaction. The diagnostic efficacy of the miR-130 family members was determined using the receiver operating characteristic method (ROC), and a diagnostic panel was built using logistic regression. The results of the study were further confirmed in an external validation set of 492 samples from the Gene Expression Omnibus database. RESULTS: The expression of the miR-130 family members (except for miR-301b-3p) in the serum of bladder cancer patients was higher than that in the controls. The diagnostic capabilities for bladder cancer were 0.847 (miR-130a-3p), 0.762 (miR-130b-3p), and 0.892 (miR-301a-3p). We established a three-miRNA panel with an area under the ROC curve as high as 0.961, indicating that it is a promising clinical diagnostic biomarker of bladder cancer with high sensitivity and specificity. CONCLUSION: The expression levels of miR-130 family members in serum can effectively distinguish the bladder cancer patients from healthy controls. This finding will facilitate the clinical diagnosis of bladder cancer.


Asunto(s)
Biomarcadores de Tumor/sangre , MicroARNs/sangre , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo
12.
J Plant Res ; 129(5): 841-851, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27262588

RESUMEN

A better understanding of the sap flow characteristics of maize plants is critical for improving irrigation water-use efficiency, especially for regions facing water resource shortages. In this study, sap flow rates, related soil-physics and plant-growth parameters, and meteorological factors, were simultaneously monitored in a maize field in two consecutive years, 2011 and 2012, and the sap flow rates of the maize plants were extensively analyzed based on the monitored data. Seasonal and daily variational characteristics were identified at different growth stages and under different weather conditions, respectively. The analyses on the relationships between sap flow rate and reference evapotranspiration (ET0), as well as several plant-growth parameters, indicate that the irrigation schedule can exert an influence on sap flow, and can consequently affect crop yield. The ranking of the main meteorological factors affecting the sap flow rate was: net radiation > air temperature > vapor pressure deficit > wind speed. For a quick estimation of sap flow rates, an empirical formula based on the two top influencing factors was put forward and verified to be reliable. The sap flow rate appeared to show little response to irrigation when the water content was relatively high, implying that some of the irrigation in recent years may have been wasted. These results may help to reveal the bio-physical processes of maize plants related to plant transpiration, which could be beneficial for establishing an efficient irrigation management system in this region and also for providing a reference for other maize-planting regions.


Asunto(s)
Exudados de Plantas/fisiología , Ríos , Zea mays/fisiología , Riego Agrícola , China , Clima , Luz , Hojas de la Planta/anatomía & histología , Tallos de la Planta/anatomía & histología , Transpiración de Plantas/fisiología , Estaciones del Año , Suelo/química , Temperatura , Agua , Zea mays/anatomía & histología , Zea mays/crecimiento & desarrollo
13.
Mol Med Rep ; 29(4)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38362959

RESUMEN

Following the publication of the above article and a corrigendum in 2018 that corrected details of the correspondence information for authors, errors made in Fig. 5 and the funding details (doi: 10.3892/mmr.2018.9117), an interested reader drew to the authors' attention that, in Fig. 6 on p. 8515 showing the results of cell migration and invasion assay experiments, a pair of data panels were overlapping, such that data which were intended to show the results from differently performed experiments appeared to have been derived from the same original source. After having consulted their original data, the authors have realized that Fig. 6 was assembled incorrectly, The revised version of Fig. 6, now showing the correct data for the 'ACHN/migratory/NC' experiment, is shown on the next page. Note that all the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. The authors regret their oversight in allowing this error to be included in the paper, and also apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 8510­8517, 2018; DOI: 10.3892/mmr.2018.8899].

14.
Int J Mol Med ; 53(6)2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38666527

RESUMEN

Following the publication of the above article, an interested reader drew to the attention of the Editorial Office that, in Fig. 3A on p. 530, two pairs of data panels were overlapping, such that certain of the panels appeared to have been derived from the same original sources where the results from differently performed experiments were intended to have been portrayed. The authors have examined their original data, and realize that errors associated with data handling/labelling during the preparation of the representative images in Fig. 3A had occurred. The revised version of Fig. 3, showing the correct data for the 'NC/ACHN/Invasion and Migration' data panels, the 'Inhibitor NC/786­O' panel and the 'Inhibitor NC/ACHN/Invasion' panel, is shown on the next page. The authors can confirm that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for giving them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 43: 525­534, 2019; DOI: 10.3892/ijmm.2018.3931].

15.
Neurologist ; 28(6): 419-421, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37247422

RESUMEN

INTRODUCTION: We report a patient with extraordinary pontine infarction-induced contralateral central facial palsy and weakened limb strength. CASE REPORT: This is a 66-year-old man with left arm movement difficulty for 10 days and worsening over the last 1 day. His left nasolabial fold flattening and left arm strength and sensory were decreased. He could not complete the finger-nose test well with his right hand. Magnetic resonance and magnetic resonance angiography tests confirmed his right pontine acute infarction but without large vessel stenosis or occlusion. CONCLUSION: "Uncrossed paralysis" patients may present with contralateral face and body weakness with pontine infarcts, if the infarct occurs above the level of the facial nucleus head, and may be simmilar with the higher level pontine lesions or cerebrum semisphere infarction, which need particular attention during clinical practice.


Asunto(s)
Infartos del Tronco Encefálico , Parálisis Facial , Masculino , Humanos , Anciano , Parálisis Facial/complicaciones , Parálisis Facial/diagnóstico por imagen , Infarto Cerebral/complicaciones , Infarto Cerebral/diagnóstico por imagen , Puente/diagnóstico por imagen , Puente/patología , Imagen por Resonancia Magnética , Infartos del Tronco Encefálico/complicaciones , Infartos del Tronco Encefálico/diagnóstico por imagen , Infartos del Tronco Encefálico/patología , Parálisis
16.
Eur J Med Res ; 28(1): 377, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37752534

RESUMEN

BACKGROUND: Although dietary intake is believed to be associated with constipation, there is currently a lack of research exploring the relationship between niacin intake and constipation. Therefore, the aim of this study is to investigate the association between niacin intake in adults and constipation using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This study included 5170 participants (aged ≥ 20 years) from the NHANES survey conducted between 2009 and 2010. Participants who reported experiencing constipation "always", "most of the time", or "sometimes" in the past 12 months were defined as constipation cases. The daily niacin intake was obtained from dietary recall and dietary supplement recalls of the patients. Weighted multivariate logistic regression analysis, restricted cubic spline regression, subgroup analysis, and interaction analysis were used to assess the correlation between niacin intake and constipation. RESULTS: After adjustment for covariates, the multivariate logistic regression model showed that low niacin intake was associated with a higher risk of constipation (Model 1: OR: 0.917, 95% CI 0.854-0.985, P = 0.023; Model 2: OR: 0.871, 95% CI 0.794-0.955, P = 0.01). After dividing niacin intake into four groups, a daily intake of 0-18 mg niacin was associated with a higher risk of constipation (Model 1: OR: 1.059, 95% CI 1.012-1.106, P = 0.019; Model 2: OR: 1.073, 95% CI 1.025-1.123, P = 0.013). The restricted cubic spline regression analysis also showed a non-linear relationship between niacin intake and the risk of constipation. CONCLUSION: The findings of this study suggested that daily intake of 0-18 mg of niacin was associated with a higher risk of constipation compared to a daily intake of 18-27 mg of niacin.


Asunto(s)
Niacina , Humanos , Adulto , Niacina/efectos adversos , Encuestas Nutricionales , Estreñimiento/inducido químicamente , Estreñimiento/epidemiología , Suplementos Dietéticos/efectos adversos , Modelos Logísticos
17.
Oncol Rep ; 50(5)2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37800638

RESUMEN

Cancer is one of the greatest dangers to human wellbeing and survival. A key barrier to effective cancer therapy is development of resistance to anti­cancer medications. In cancer cells, the AAA+ ATPase family member thyroid hormone receptor interactor 13 (TRIP13) is key in promoting treatment resistance. Nonetheless, knowledge of the molecular processes underlying TRIP13­based resistance to anticancer therapies is lacking. The present study evaluated the function of TRIP13 expression in anticancer drug resistance and potential methods to overcome this resistance. Additionally, the underlying mechanisms by which TRIP13 promotes resistance to anticancer drugs were explored, including induction of mitotic checkpoint complex surveillance system malfunction, promotion of DNA repair, the enhancement of autophagy and the prevention of immunological clearance. The effects of combination treatment, which include a TRIP13 inhibitor in addition to other inhibitors, were discussed. The present study evaluated the literature on TRIP13 as a possible target and its association with anticancer drug resistance, which may facilitate improvements in current anticancer therapeutic options.


Asunto(s)
Antineoplásicos , Proteínas de Ciclo Celular , Humanos , Proteínas de Ciclo Celular/genética , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo
18.
Front Neurosci ; 17: 1083928, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36777638

RESUMEN

Background: Parkinson's disease (PD) is Pengfei Zhang Liwen Zhao Pengfei Zhang Liwen Zhao a common neurological disorder involving a complex relationship with immune infiltration. Therefore, we aimed to explore PD immune infiltration patterns and identify novel immune-related diagnostic biomarkers. Materials and methods: Three substantia nigra expression microarray datasets were integrated with elimination of batch effects. Differentially expressed genes (DEGs) were screened using the "limma" package, and functional enrichment was analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to explore the key module most significantly associated with PD; the intersection of DEGs and the key module in WGCNA were considered common genes (CGs). The CG protein-protein interaction (PPI) network was constructed to identify candidate hub genes by cytoscape. Candidate hub genes were verified by another two datasets. Receiver operating characteristic curve analysis was used to evaluate the hub gene diagnostic ability, with further gene set enrichment analysis (GSEA). The immune infiltration level was evaluated by ssGSEA and CIBERSORT methods. Spearman correlation analysis was used to evaluate the hub genes association with immune cells. Finally, a nomogram model and microRNA-TF-mRNA network were constructed based on immune-related biomarkers. Results: A total of 263 CGs were identified by the intersection of 319 DEGs and 1539 genes in the key turquoise module. Eleven candidate hub genes were screened by the R package "UpSet." We verified the candidate hub genes based on two validation sets and identified six (SYT1, NEFM, NEFL, SNAP25, GAP43, and GRIA1) that distinguish the PD group from healthy controls. Both CIBERSORT and ssGSEA revealed a significantly increased proportion of neutrophils in the PD group. Correlation between immune cells and hub genes showed SYT1, NEFM, GAP43, and GRIA1 to be significantly related to immune cells. Moreover, the microRNA-TFs-mRNA network revealed that the microRNA-92a family targets all four immune-related genes in PD pathogenesis. Finally, a nomogram exhibited a reliable capability of predicting PD based on the four immune-related genes (AUC = 0.905). Conclusion: By affecting immune infiltration, SYT1, NEFM, GAP43, and GRIA1, which are regulated by the microRNA-92a family, were identified as diagnostic biomarkers of PD. The correlation of these four genes with neutrophils and the microRNA-92a family in PD needs further investigation.

19.
Clin Case Rep ; 11(2): e6916, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36789325

RESUMEN

We present a 60-year-old man suffering from delayed arterial hemorrhage post liver biopsy. Contrast-enhanced ultrasound was used to detect the bleeding point and to evaluate the efficacy of microwave ablation (MWA). The hemorrhage was controlled by MWA at the bedside. This is the first application of MWA for delayed hemorrhage.

20.
Mol Immunol ; 162: 125-132, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37677989

RESUMEN

Hepatocellular carcinoma (HCC) remains one of the most common and highly fatal malignancies in humans worldwide with increasing prevalence and limited therapeutic options. For many decades, many researchers have attempted to find effective curative methods for HCC and great strides have been made. GPC3 is overexpressed in HCC, but not in normal liver, making it a rational immunotherapeutic target for HCC. GC33, a humanized mAb directed against GPC3, is a safe and well-tolerated therapy choice for patients with HCC, which tested in a phase I trial in advanced HCC patients. Phase II trials of GC33 to evaluate its efficacy and safety in advanced or metastatic HCC, showed no significant differences in overall survival and progression-free survival compared with the placebo. Retrospective analysis indicates that high drug exposure and high CD16 expression may contribute to the clinical efficacy of GC33. Chugai Pharmaceutical has restarted its Phase I trial of GC33, continuing to explore its clinical value targeting GPC3 in solid tumors. To enhance the antitumor potency of GC33, we designed a GPC3/CD16A bispecific antibody (QDEB). In this study, we obtained QDEB at high purity and assessed its effectiveness in the therapy of HCC compared with GC33. In vitro cytotoxicity assays and in vivo experiments demonstrated that QDEB could enhance anti-tumor efficacy compared with GC33. CD16A activation and increased cytokines release were associated with higher anti-tumor activity. In conclusion, this bispecific antibody may possibly help develop new therapeutic strategies for HCC and develop new treatment options in the future.


Asunto(s)
Anticuerpos Biespecíficos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Hepáticas/tratamiento farmacológico , Factores Inmunológicos , Anticuerpos Biespecíficos/uso terapéutico , Inmunoterapia , Glipicanos
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