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1.
Chemphyschem ; 25(8): e202300657, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38311591

RESUMO

Transition metal oxides are investigated as electrochemically active anodes for several years due to the merits of high specific capacity, low cost, abundant resources and controllable synthesis. But the poor cycle performances have hindered their further wide application. Herein, porous La-doped FeOOH nanorods have been synthesized through a facile hydrothermal method, which could be transformed into porous La-doped Fe2O3 (Fe2O3-La) via a simple heating process. Compared with the undoped Fe2O3, the Fe2O3-La showed larger surface area, higher specific capacities and more stable cycle performances for lithium/sodium ion batteries. In addition, as an advanced sulfur host for lithium-sulfur batteries, the Fe2O3-La also displayed much more excellent cycle and rate performances than the undoped Fe2O3. The superior electrochemical performances of the Fe2O3-La may could be attributed to the doping of La, which could induce more porous morphology and offer more reactive sites. The positive effects of La-doping for electrochemical performances of porous Fe2O3 nanorods provide novel insights for further applications of rare earth metal doping.

2.
Neurochem Int ; 172: 105643, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38007071

RESUMO

Traumatic brain injury (TBI) is a potentially fatal health event that cannot be predicted in advance. After TBI occurs, it can have enduring consequences within both familial and social spheres. Yet, despite extensive efforts to improve medical interventions and tailor healthcare services, TBI still remains a major contributor to global disability and mortality rates. The prompt and accurate diagnosis of TBI in clinical contexts, coupled with the implementation of effective therapeutic strategies, remains an arduous challenge. However, a deeper understanding of changes in gene expression and the underlying molecular regulatory processes may alleviate this pressing issue. In recent years, the study of regulatory non-coding RNAs (ncRNAs), a diverse class of RNA molecules with regulatory functions, has been a potential game changer in TBI research. Notably, the identification of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs has revealed their potential as novel diagnostic biomarkers and therapeutic targets for TBI, owing to their ability to regulate the expression of numerous genes. In this review, we seek to provide a comprehensive overview of the functions of regulatory ncRNAs in TBI. We also summarize regulatory ncRNAs used for treatment in animal models, as well as miRNAs, lncRNAs, and circRNAs that served as biomarkers for TBI diagnosis and prognosis. Finally, we discuss future challenges and prospects in diagnosing and treating TBI patients in the clinical settings.


Assuntos
Lesões Encefálicas Traumáticas , MicroRNAs , RNA Longo não Codificante , Animais , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Circular , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , MicroRNAs/metabolismo , Biomarcadores , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/tratamento farmacológico
3.
Oncoimmunology ; 12(1): 2215096, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37261086

RESUMO

The expression of viral antigens in chronic hepatitis B virus (HBV) infection drives continuous liver inflammation, one of the main risk factors to develop liver cancer. HBV developed immune-suppressive functions to escape from the host immune system, but their link to liver tumor development is not well understood. Here, we analyzed if and how HBV surface antigen (HBs) expression in combined hepatocellular-cholangiocarcinoma (cHCC/iCCA) cells influences their antigenicity for CD8 T cells. We randomly isolated liver tumor tissues from AlfpCre+-Trp53fl/fl/Alb-HBs+ tg mice and established primary carcinoma cell lines (pCCL) that showed a bilineal (CK7+/HNF4α+) cHCC/iCCA phenotype. These pCCL uniformly expressed HBs (HBshi), and low levels of MHC-I (MHC-Ilo), and were transiently convertible to a high antigenicity (MHC-Ihi) phenotype by IFN-γ treatment. HBshi/pCCL induced HBs/(Kb/S190-197)-specific CD8 T cells and developed slow-growing tumors in subcutaneously transplanted C57Bl/6J (B6) mice. Interestingly, pCCL-ex cells, established from HBshi/pCCL-induced and re-explanted tumors in B6 but not those in immune-deficient Rag1-/- mice showed major alterations, like an MHC-Ihi phenotype, a prominent growth-biased gene expression signature, a significantly decreased HBs expression (HBslo) and a switch to fast-growing tumors in re-transplanted B6 or PD-1-/- hosts with an unlocked PD-1/PD-L1 control system. CD8 T cell-mediated elimination of HBshi/pCCL, together with the attenuation of the negative restraints of HBs in the tumor cells, like ER-stress, reveals a novel mechanism to unleash highly aggressive HBslo/pCCL-ex immune-escape variants. Under certain conditions, HBs-specific CD8 T-cell responses thus potentiate tumor growth, an aspect that should be considered for therapeutic vaccination strategies against chronic HBV infection and liver tumors.


Assuntos
Carcinoma , Hepatite B Crônica , Neoplasias Hepáticas , Camundongos , Animais , Hepatite B Crônica/genética , Vírus da Hepatite B/genética , Receptor de Morte Celular Programada 1 , Linfócitos T CD8-Positivos , Linhagem Celular , Neoplasias Hepáticas/genética
4.
Artigo em Inglês | MEDLINE | ID: mdl-36881562

RESUMO

A new porous organic polymer (CTF-CAR), which takes carbazole as the electron-rich center unit and thiophenes as the auxiliary group, has been synthesized through catalyst-free Schiff-base polymerization. At the same time, the structure, thermal stability, morphology, and other basic properties of the polymer were analyzed by IR, NMR, TGA, and SEM. Then, CTF-CAR was applied to iodine capture and rhodamine B adsorption. Due to its strong electron donor ability and abundant heteroatom binding sites, which have a positive effect on the interaction between the polymer network and adsorbates, CTF-CAR exhibits high uptake capacities for iodine vapor and rhodamine B as 2.86 g g-1 and 199.7 mg g-1, respectively. The recyclability test also confirmed that it has good reusability. We found that this low-cost and catalyst-free synthetic porous organic polymer has great potential for the treatment of polluted water and iodine capture.

5.
Materials (Basel) ; 15(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36431397

RESUMO

Li dendrite growth, which causes potential internal short circuit and reduces battery cycle life, is the main hazard to lithium metal batteries. Separators have the potential to suppress dendrite growth by regulating Li+ distribution without increasing battery weight significantly. However, the underlying mechanism is still not fully understood. In this paper, we apply an electrochemical phase-field model to investigate the influences of separator thickness and surface coating on dendrite growth. It is found that dendrite growth under thicker separators is relatively uniform and the average dendrite length is shorter since the ion concentration within thicker separators is more uniform. Moreover, compared to single layer separators, the electrodeposition morphology under particle-coated separators is smoother since the particles can effectively regulate Li ionic flux and homogenize Li deposition. This study provides significant guidance for designing separators that inhibit dendrites effectively.

6.
Front Endocrinol (Lausanne) ; 13: 1041761, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419769

RESUMO

Background: The primary objective of the study was to discuss the sex differences in insulin resistance-induced changes in metabolic and inflammatory markers in school-aged children with overweight and obesity. Methods: A cross-sectional study of 800 children aged seven and twelve years was performed. Questionnaires, anthropometric data and fasting blood samples were collected. Results: Children with overweight and obesity showed statistically significant differences in multiple metabolic and inflammatory markers compared with children with normal BMI. The correlation coefficient (r) between white blood cell count, absolute neutrophil count, fasting plasma insulin, HOMA-IR, HOMA-ß, triglyceride, HDL-C, triglyceride/HDL ratio, alanine transaminase, serum uric acid, systolic blood pressure and BMI were higher in all children, but the linear relationships between white blood cell count, absolute neutrophil count and BMI were stronger in girls with overweight and obesity than in boys with overweight and obesity. Subsequently, HOMA-IR was shown to be more strongly associated with increased white blood cell count and absolute neutrophil count in school-aged girls with overweight and obesity by partial correlation analysis and the multiple linear regression analysis. Conclusions: Elevated white blood cell count and absolute neutrophil count in children with overweight and obesity, especially girls, can serve as markers of insulin resistance.


Assuntos
Resistência à Insulina , Sobrepeso , Criança , Feminino , Humanos , Masculino , Neutrófilos , Estudos Transversais , Ácido Úrico , Obesidade , Contagem de Leucócitos , Triglicerídeos
7.
Cell Res ; 32(8): 761-772, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35739238

RESUMO

Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of Gi1-bound SSTR2 in the presence of the endogenous ligand SST-14, as well as two cryo-EM structures of Gi1-bound SSTR4 in complex with SST-14 and a small-molecule agonist J-2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. Together with computational and functional analyses, the key determinants responsible for ligand recognition and selectivity of different SSTR subtypes and multiform binding modes of peptide and non-peptide ligands were identified. Insights gained in this study will help uncover ligand selectivity of various SSTRs and accelerate the development of new molecules with better efficacy by targeting SSTRs.


Assuntos
Neoplasias , Receptores de Somatostatina , Microscopia Crioeletrônica , Humanos , Ligantes , Neoplasias/metabolismo , Receptores de Somatostatina/agonistas , Receptores de Somatostatina/metabolismo , Somatostatina/metabolismo , Somatostatina/farmacologia , Somatostatina/uso terapêutico
8.
Nature ; 604(7907): 779-785, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35418679

RESUMO

Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis1-7. An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs8,9, but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk-transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis-deficient ADGRF1, supporting a cleavage-independent manner of receptor activation. The stalk-induced activation is facilitated by a cascade of inter-helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. Furthermore, the intracellular region of ADGRF1 contains a specific lipid-binding site, which proves to be functionally important and may serve as the recognition site for the previously discovered endogenous ADGRF1 ligand synaptamide. These findings highlight the diversity and complexity of the signal transduction mechanisms of the aGPCRs.


Assuntos
Receptores Acoplados a Proteínas G , Transdução de Sinais , Humanos , Ligantes , Proteínas Oncogênicas/agonistas , Proteínas Oncogênicas/metabolismo , Ligação Proteica , Domínios Proteicos , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo
9.
Small ; 18(2): e2105308, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34741427

RESUMO

The ever-increasing development of flexible and wearable electronics has imposed unprecedented demand on flexible batteries of high energy density and excellent mechanical stability. Rechargeable lithium (Li) metal battery shows great advantages in terms of its high theoretical energy density. However, the use of Li metal anode for flexible batteries faces huge challenges in terms of its undesirable dendrite growth, poor mechanical flexibility, and slow fabrication speed. Here, a highly scalable Li-wicking strategy is reported that allows ultrafast fabrication of mechanically flexible and electrochemically stable Li metal anodes. Through the rational design of the interface and structure of the wicking host, the mean speed of Li-wicking reaches 10 m2 min-1 , which is 1000 to 100 000 fold faster than the reported electrochemical deposition or thermal infusion methods and meets the industrial fabrication speed. Importantly, the Li-wicking process results in a unique 3D Li metal structure, which not only offers remarkable flexibility but also suppresses the dendrite formation. Paring the Li metal anode with lithium-iron phosphate or sulfur cathode yields flexible full cells that possess a high charging rate (8.0 mA cm-2 ), high energy density (300-380 Wh kg-1 ), long cycling stability (over 550 cycles), and excellent mechanical robustness (500 bending cycles).


Assuntos
Eletrônica , Lítio , Ação Capilar , Eletrodos
10.
J Nanobiotechnology ; 19(1): 428, 2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34923976

RESUMO

Molybdenum oxide (MoOx) nanosheets have drawn increasing attention for minimally invasive cancer treatments but still face great challenges, including complex modifications and the lack of efficient accumulation in tumor. In this work, a novel multifunctional degradable FA-BSA-PEG/MoOx nanosheet was fabricated (LA-PEG and FA-BSA dual modified MoOx): the synergistic effect of PEG and BSA endows the nanosheet with excellent stability and compatibility; the FA, a targeting ligand, facilitates the accumulation of nanosheets in the tumor. In addition, DTX, a model drug for breast cancer treatment, was loaded (76.49%, 1.5 times the carrier weight) in the nanosheets for in vitro and in vivo antitumor evaluation. The results revealed that the FA-BSA-PEG/MoOx@DTX nanosheets combined photothermal and chemotherapy could not only inhibit the primary tumor growth but also suppress the distant tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%), which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, which co-contributes towards effective suppression of tumor and lung metastasis. Our experiments demonstrated that this novel multifunctional nanosheet is a promising platform for combined chemo-photothermal therapy.


Assuntos
Materiais Biocompatíveis/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Molibdênio/química , Nanoestruturas/uso terapêutico , Óxidos/química , Animais , Materiais Biocompatíveis/farmacocinética , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Ácido Fólico/química , Humanos , Hipertermia Induzida , Raios Infravermelhos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/química , Nanoestruturas/toxicidade , Polietilenoglicóis/química , Soroalbumina Bovina/química , Ácido Tióctico/química , Distribuição Tecidual
11.
Brain Inform ; 8(1): 23, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34725741

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative brain pathology formed due to piling up of amyloid proteins, development of plaques and disappearance of neurons. Another common subtype of dementia like AD, Parkinson's disease (PD) is determined by the disappearance of dopaminergic neurons in the region known as substantia nigra pars compacta located in the midbrain. Both AD and PD target aged population worldwide forming a major chunk of healthcare costs. Hence, there is a need for methods that help in the early diagnosis of these diseases. PD subjects especially those who have confirmed postmortem plaque are a strong candidate for a second AD diagnosis. Modalities such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) can be combined with deep learning methods to diagnose these two diseases for the benefit of clinicians. RESULT: In this work, we deployed a 3D Convolutional Neural Network (CNN) to extract features for multiclass classification of both AD and PD in the frequency and spatial domains using PET and SPECT neuroimaging modalities to differentiate between AD, PD and Normal Control (NC) classes. Discrete Cosine Transform has been deployed as a frequency domain learning method along with random weak Gaussian blurring and random zooming in/out augmentation methods in both frequency and spatial domains. To select the hyperparameters of the 3D-CNN model, we deployed both 5- and 10-fold cross-validation (CV) approaches. The best performing model was found to be AD/NC(SPECT)/PD classification with random weak Gaussian blurred augmentation in the spatial domain using fivefold CV approach while the worst performing model happens to be AD/NC(PET)/PD classification without augmentation in the frequency domain using tenfold CV approach. We also found that spatial domain methods tend to perform better than their frequency domain counterparts. CONCLUSION: The proposed model provides a good performance in discriminating AD and PD subjects due to minimal correlation between these two dementia types on the clinicopathological continuum between AD and PD subjects from a neuroimaging perspective.

12.
Front Pediatr ; 9: 674504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422716

RESUMO

Objective: The objective of this study is to further explore the difference between elevated blood pressure (EBP), elevated pulse pressure (EPP), and elevated mean arterial pressure (EMAP) and obesity in Chinese school-age children by sex. Methods: We performed a cross-sectional study of 935 children between 7 and 12 years old. Overweight and obesity were defined by body mass index and body composition. The multivariate logistic regression and the adjusted population attributable risk were used to assess the effects of obesity on pre-EBP/EBP, EPP, and EMAP. The interactions were used to identify the modification of obese on the relationship between related indicators of blood pressure and height or age. Results: The average age of the children included in the study was 10. Boys with overweight and obesity had higher pre-EBP/EBP, EPP, and EMAP (p < 0.05). The multivariate logistic regression analysis showed that overweight and obesity had a greater impact on BP and MAP than PP, especially in boys [odds ratio (OR) > 1]. Pre-EBP/EBP in 79% of boys and 76% of girls could be attributable to the visceral fat level. The interaction between BP, PP, MAP, and height or age was modestly increased in children with overweight and obesity, especially in boys. Conclusions: Independent of age and height, obesity not only increases blood pressure, it also increases mean arterial pressure and pulse pressure, and this effect is more pronounced in boys.

13.
ACS Nano ; 15(8): 12567-12603, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34339170

RESUMO

Immunotherapy that harnesses the human immune system to fight cancer has received widespread attention and become a mainstream strategy for cancer treatment. Cancer immunotherapy not only eliminates primary tumors but also treats metastasis and recurrence, representing a major advantage over traditional cancer treatments. Recently with the development of nanotechnology, there exists much work applying nanomaterials to cancer immunotherapy on the basis of their excellent physiochemical properties, such as efficient tissue-specific delivery function, huge specific surface area, and controllable surface chemistry. Consequently, nanotechnology holds significant potential in improving the efficacy of cancer immunotherapy. Nanotechnology-based immunotherapy mainly manifests its inhibitory effect on tumors via two different approaches: one is to produce an effective anti-tumor immune response during tumorigenesis, and the other is to enhance tumor immune defense ability by modulating the immune suppression mechanism in the tumor microenvironment. With the success of tumor immunotherapy, understanding the interaction between the immune system and smart nanomedicine has provided vigorous vitality for the development of cancer treatment. This review highlights the application, progress, and prospect of nanomedicine in the process of tumor immunoediting and also discusses several engineering methods to improve the efficiency of tumor treatment.


Assuntos
Imunoterapia , Neoplasias , Humanos , Imunoterapia/métodos , Nanomedicina/métodos , Neoplasias/patologia , Nanotecnologia , Microambiente Tumoral , Fatores Imunológicos
14.
J Nanobiotechnology ; 19(1): 251, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419071

RESUMO

BACKGROUND: Glioblastoma is a lethal neoplasm with few effective therapy options. As a mainstay in the current treatment of glioma at present, chemotherapeutic agents usually show inadequate therapeutic efficiency due to their low blood brain barrier traversal and brain targeting, together with tumor multidrug resistance. Novel treatment strategies are thus urgently needed to improve chemotherapy outcomes. RESULTS: Here, we report that nanomedicines developed by functionalizing the neurotropic rabies virus-derived polypeptide, RVG, and loading reduction-sensitive nanomicelles (polymer and doxorubicin) enable a highly specific and efficacious drug accumulation in the brain. Interestingly, curcumin serves as the hydrophobic core of the polymer, while suppressing the major efflux proteins in doxorubicin-resistant glioma cells. Studies on doxorubicin-resistant rat glioma cells demonstrate that the RVG-modified micelles exhibit superior cell entry and antitumor activity. In vivo research further showed that RVG modified nanomicelles significantly enhanced brain accumulation and tumor inhibition rate in mice, leading to a higher survival rate with negligible systemic toxicity. Moreover, effective suppression of recurrence and pulmonary metastatic nodules were also determined after the RVG-modified nanomicelles treatment. CONCLUSIONS: The potential of RVG-modified nanomicelles for glioma was demonstrated. Brain accumulation was markedly enhanced after intravenous administration. This unique drug delivery nanoplatform to the brain provides a novel and powerful therapeutic strategy for the treatment of central nervous system disorders including glioma.


Assuntos
Encéfalo/metabolismo , Doxorrubicina/administração & dosagem , Doxorrubicina/metabolismo , Micelas , Animais , Antineoplásicos , Materiais Biocompatíveis , Neoplasias Encefálicas/tratamento farmacológico , Sobrevivência Celular , Sistemas de Liberação de Medicamentos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Glioblastoma , Glioma/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Peptídeos/metabolismo , Ratos
15.
Carbohydr Res ; 506: 108358, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34111687

RESUMO

PFC-3 is a homogeneous polysaccharide extracted from the dried pulps of Fructus Corni with a molecular weight of 40.3 kDa. The crude polysaccharide was obtained and further purified by DEAE-Sephadex A-25 and Sephadex G-100 columns to investigate its structure and glycemic effect. The monosaccharides in the PFC-3, determined by high-performance liquid chromatography, consisted of glucose (Glc), xylose (Xyl), and galactose (Gal) with a mass molar ratio of 2.35:12.49:1.00. The methylation analysis combined with 1D (1H and 13C), and 2D NMR (1H-1H COSY, HSQC, and HMBC) further demonstrated that PFC-3 was mainly composed of 1,3-α-D-Xylp, 1,6-α-D-Galp, 1,2-α-D-Glcp, and T-α-D-Galp, and contained a backbone fragment of →6)-α-D-Galp-(1 â†’ 2)-α-D-Glcp-(1 â†’ 3)-α-D-Xylp-(1 â†’ . The hypoglycemic effect of PFC-3 in vitro was evaluated by glucose uptake and consumption assays, and the results showed that PFC-3 concentration-dependently enhanced glucose uptake and significantly improved glucose consumption in insulin-resistant HepG2 cells. Furthermore, PFC-3 significantly reduced fasting blood glucose level, glycosylated hemoglobin level, amylase activity, ameliorate lipid metabolism, and hepatic lesions in streptozotocin-induced diabetic rats. Our research provided insights into the hypoglycemic activities of PFC-3.


Assuntos
Cornus , Diabetes Mellitus Experimental , Animais , Hipoglicemiantes , Masculino , Ratos
16.
Int J Obes (Lond) ; 45(9): 2132-2136, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34091592

RESUMO

There may be sex differences in BMI and blood pressure levels in school-age children, especially in the face of lifestyle changes. This study aimed to explore sex differences in changes in BMI and blood pressure in Chinese school-aged children during the COVID-19 quarantine. The cohort study of 445 school-aged children examined the change of BMI and blood pressure during the five-month quarantine. Multivariable Cox regression models were created to identify potential predictors of overweight, obesity, and elevated blood pressure (EBP). During the COVID-19 quarantine, the proportion of boys with overweight and obesity increased (P = 0.036), and the proportion of both boys and girls with Pre-EBP and EBP increased (P = 0.004 in boys; P < 0.001 in girls). The multivariate Cox regression analysis demonstrated that the setting, eating chili, parents' perception of their child's size and family doting were associated with overweight, obesity, and EBP. The study showed that BMI was more likely to increase in boys, and blood pressure increased in both boys and girls during the COVID-19 quarantine.


Assuntos
Pressão Sanguínea , Índice de Massa Corporal , COVID-19 , Quarentena , Fatores Sexuais , Criança , China , Estudos de Coortes , Feminino , Humanos , Masculino , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia
17.
Drug Dev Ind Pharm ; 47(6): 839-856, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34033496

RESUMO

Despite a potential drug with multiple pharmacological activities, curcumin has disadvantages of the poor water solubility, rapid metabolism, low bioavailability, which considerably limit its clinical application. Currently, polymeric micelles (PMs) have gained widespread concern due to their advantageous physical and chemical properties, easy preparation, and biocompatibility. They can be used to improve drug solubility, prolong blood circulation time, and allow passive targeted drug delivery to tumor through enhanced penetration and retention effect. Moreover, studies focused on tumor microenvironment offer alternatives to design stimulus-responsive smart PMs based on low pH, high levels of glutathione, altered enzyme expression, increased reactive oxygen species production, and hypoxia. There are various external stimuli, such as light, ultrasound, and temperature. These endogenous/exogenous stimuli can be used for the research of intelligent micelles. Intelligent PMs can effectively load curcumin with improved solubility, and intelligently respond to release the drug at a controlled rate at targeted sites such as tumors to avoid early release, which markedly improves the bioavailability of curcumin. The present review is aimed to discuss and summarize recent developments in research of curcumin-loaded intelligent PMs based on endogenous and exogenous stimuli, and facilitates the development of novel delivery systems for future research.


Assuntos
Antineoplásicos , Curcumina , Neoplasias , Antineoplásicos/uso terapêutico , Curcumina/uso terapêutico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Micelas , Neoplasias/tratamento farmacológico , Polímeros , Microambiente Tumoral
18.
Biomater Sci ; 9(11): 3989-4004, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-33908449

RESUMO

Sonodynamic therapy (SDT) is a promising non-invasive approach for cancer therapy. However, tumor hypoxia, a pathological characteristic of most solid tumor types, poses a major challenge in the application of SDT. In this study, a novel CD44 receptor-targeted and redox/ultrasound-responsive oxygen-carrying nanoplatform was constructed using chondroitin sulfate (CS), reactive oxygen species (ROS)-generating sonosensitizer Rhein (Rh), and perfluorocarbon (PFC). Perfluoroalkyl groups introduced into the structures preserved the oxygen carrying ability of PFC, increasing the oxygen content in B16F10 melanoma cells and enhancing the efficiency of SDT. Controlled nanoparticles without PFC generated lower ROS levels and exerted inferior tumor inhibition effects, both in vitro and in vivo, under ultrasound-treatment. In addition, SDT promoted immunogenic cell death (ICD) by inducing exposure of calreticulin (CRT) after treatment with CS-Rh-PFC nanoparticles (NPs). The immune system was significantly activated by docetaxel (DTX)-loaded NPs after SDT treatment due to the enhanced secretion of IFN-γ, TNF-α, IL-2 and IL-6 cytokines and tumor-infiltrating CD4+ and CD8+ T cell contents. Our findings support the utility of CS-Rh-PFC as an effective anti-tumor nanoplatform that promotes general immunity and accommodates multiple hydrophobic drugs to enhance the beneficial effects of chemo-SDT therapy.


Assuntos
Autoimunidade , Nanopartículas , Linhagem Celular Tumoral , Docetaxel , Oxigênio , Espécies Reativas de Oxigênio
19.
Carbohydr Polym ; 254: 117459, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357918

RESUMO

As a major therapeutic approach for cancer treatment, the effectiveness of chemotherapy is challenged by multidrug resistance (MDR). Herein, we fabricated novel redox-responsive, chondroitin sulfate-based nanoparticles that could simultaneously deliver quercetin (chemosensitizer), chlorin e6 (photosensitizer) and paclitaxel (chemotherapeutic agent) to exert enhanced chemo-photodynamic therapy for overcoming MDR and lung metastasis of breast cancer. In vitro cell study showed that nanoparticles down-regulated the expression of P-glycolprotein (P-gp) on MCF-7/ADR cells and thereby improved the anticancer efficacy of PTX against MCF-7/ADR cells. Moreover, NIR laser irradiation could induce nanoparticles to generate cellular reactive oxygen species (ROS), leading to mitochondrial membrane potential loss, and meanwhile facilitating lysosomal escape of drugs. Importantly, the novel nanoplatform exhibited effective in vivo MDR inhibition and anti-metastasis efficacy through enhanced chemo-photodynamic therapy. Thus, the study suggested that the multifunctional nanoplatform had good application prospect for effective breast cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/terapia , Portadores de Fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Neoplasias Pulmonares/terapia , Fármacos Fotossensibilizantes/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Clorofilídeos , Sulfatos de Condroitina/química , Terapia Combinada , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Expressão Gênica , Humanos , Raios Infravermelhos/uso terapêutico , Lasers , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Células MCF-7 , Nanopartículas/administração & dosagem , Nanopartículas/química , Paclitaxel/farmacologia , Porfirinas/farmacologia , Quercetina/farmacologia , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Digit Imaging ; 33(5): 1073-1090, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32728983

RESUMO

Alzheimer's disease (AD) is an irreversible devastative neurodegenerative disorder associated with progressive impairment of memory and cognitive functions. Its early diagnosis is crucial for the development of possible future treatment option(s). Structural magnetic resonance images (sMRI) play an important role to help in understanding the anatomical changes related to AD especially in its early stages. Conventional methods require the expertise of domain experts and extract hand-picked features such as gray matter substructures and train a classifier to distinguish AD subjects from healthy subjects. Different from these methods, this paper proposes to construct multiple deep 2D convolutional neural networks (2D-CNNs) to learn the various features from local brain images which are combined to make the final classification for AD diagnosis. The whole brain image was passed through two transfer learning architectures; Inception version 3 and Xception, as well as a custom Convolutional Neural Network (CNN) built with the help of separable convolutional layers which can automatically learn the generic features from imaging data for classification. Our study is conducted using cross-sectional T1-weighted structural MRI brain images from Open Access Series of Imaging Studies (OASIS) database to maintain the size and contrast over different MRI scans. Experimental results show that the transfer learning approaches exceed the performance of non-transfer learning-based approaches demonstrating the effectiveness of these approaches for the binary AD classification task.


Assuntos
Doença de Alzheimer , Aprendizado Profundo , Doença de Alzheimer/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem
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