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1.
J Oral Pathol Med ; 53(6): 386-392, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772727

RESUMO

BACKGROUND: Buccal mucosa squamous cell carcinoma (BMSCC) is an aggressive disease. This study investigated the clinicopathological significance of tumor budding (TB), depth of invasion (DOI), and mode of invasion (MOI) on occult cervical metastasis (CM) of BMSCC. METHODS: Seventy-one cT1-2N0 BMSCC patients were included in this retrospective study. TB, DOI, MOI, and other clinicopathological features were reviewed. Risk factors for occult CM, locoregional recurrence-free survival (LRRFS), and overall survival (OS) were analyzed using logistic regression and Cox's proportional hazard models, respectively. RESULTS: Multivariate analysis with the logistic regression model revealed that MOI, DOI, and TB were significantly associated with occult CM in early-stage BMSCC after adjusting for variates. However, multivariate analysis with the Cox's proportional hazard model found only TB to be a prognostic factor for LRRFS (hazard ratio 15.03, 95% confidence interval [CI] 1.94-116.66; p = 0.01; trend test p = 0.03). No significant association was found between MOI, DOI, or TB and OS. CONCLUSIONS: The optimal predictor of occult CM and prognosis of early-stage BMSCC is TB, which may assist clinicians in identifying patients at high risk of cervical metastasis.


Assuntos
Carcinoma de Células Escamosas , Mucosa Bucal , Invasividade Neoplásica , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/patologia , Idoso , Mucosa Bucal/patologia , Adulto , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais , Fatores de Risco , Modelos de Riscos Proporcionais , Prognóstico , Metástase Linfática/patologia
2.
J Med Virol ; 95(10): e29187, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37877809

RESUMO

Chronic infection of hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC). Notably, 90% of HBV-positive HCC cases exhibit detectable HBV integrations, hinting at the potential early entanglement of these viral integrations in tumorigenesis and their subsequent oncogenic implications. Nevertheless, the precise chronology of integration events during HCC tumorigenesis, alongside their sequential structural patterns, has remained elusive thus far. In this study, we applied whole-genome sequencing to multiple biopsies extracted from six HBV-positive HCC cases. Through this approach, we identified point mutations and viral integrations, offering a blueprint for the intricate tumor phylogeny of these samples. The emergent narrative paints a rich tapestry of diverse evolutionary trajectories characterizing the analyzed tumors. We uncovered oncogenic integration events in some samples that appear to happen before and during the initiation stage of tumor development based on their locations in reconstituted trajectories. Furthermore, we conducted additional long-read sequencing of selected samples and unveiled integration-bridged chromosome rearrangements and tandem repeats of the HBV sequence within integrations. In summary, this study revealed premalignant oncogenic and sequential complex integrations and highlighted the contributions of HBV integrations to HCC development and genome instability.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B/genética , Carcinogênese , Transformação Celular Neoplásica
3.
Methods ; 199: 67-79, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34971759

RESUMO

Disulfide bonds (S-S) are widely found in chemistry, biology, and materials science. Polymer nanomaterials containing disulfide bonds with a variety of excellent properties have great potential as drug and gene delivery carriers. The disulfide bond can exist stably in extracellular environment, but upon entering cancer cells, it will undergo a sulfhydryl-disulfide bond exchange reaction with glutathione (GSH) in the cytoplasm, causing the disulfide bond cleavage. Therefore, polymeric nanomaterials containing disulfide bonds are promising in cancer treatment due to the elevated GSH concentration inside cancer cells. This review highlights various synthetic approaches to prepare disulfide containing redox-responsive polymeric nanomedicine, including synthesis of disulfide bonds containing polymers, construction of polymeric nanoparticle with shell or core crosslinked disulfide bonds, preparation of polymer-drug conjugates via disulfide linkers, and disulfide linked responsive payloads.


Assuntos
Dissulfetos , Nanomedicina , Dissulfetos/química , Portadores de Fármacos/química , Micelas , Oxirredução , Polímeros/química
4.
J Clin Rheumatol ; 24(2): 65-69, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29232321

RESUMO

PURPOSES: The aim of this study was to investigate the serum levels and clinical significance of interleukin 1ß (IL-1ß) and IL-6 in children with hyperuricemia (HUA). METHODS: We included 71 children with HUA and 71 children with no HUA as control subjects. Children with HUA were divided into groups I and II according to whether they had a history of acute gout-like attacks (including sudden monoarthritis of rapid onset with intense pain and swelling). Group I was examined twice (A, in the acute phase; B, in the remission phase). Serum IL-1ß and IL-6 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum IL-1ß and IL-6 levels were increased in children with HUA and were overall statistically different from the control group (P < 0.05, respectively). Serum IL-1ß and IL-6 were significantly higher in group IA in comparison with group IB, group II, and control subjects (P < 0.05, respectively), as well as in groups IB and II compared with control subjects (P < 0.05, respectively). In group IB, the serum IL-1ß and IL-6 concentrations were higher than those in group II, but there were no statistical differences (P > 0.05). In addition, in children with HUA, serum IL-1ß and IL-6 levels were positively associated with white blood cell count, neutrophil count, monocyte count, uric acid levels, erythrocyte sedimentation rate, C-reactive protein, blood urea nitrogen, and serum creatinine levels (all P < 0.05), but were not associated with triglycerides, total cholesterol, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol levels (all P > 0.05). CONCLUSION: IL-1ß and IL-6 levels are increased in children with hyperuricemia, even if they have not had acute gout. Further studies are necessary to fully characterize the significance of IL-1ß and IL-6 found in HUA children, and whether they could be correlated with long-term prognosis.


Assuntos
Hiperuricemia/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Contagem de Leucócitos , Masculino
5.
J Am Chem Soc ; 139(11): 4009-4018, 2017 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-28286953

RESUMO

Peptides perform a diverse range of physiologically important functions. The formulation of nanoparticles directly from functional peptides would therefore offer a versatile and robust platform to produce highly functional therapeutics. Herein, we engineered proapoptotic peptide nanoparticles from mitochondria-disrupting KLAK peptides using a template-assisted approach. The nanoparticles were designed to disassemble into free native peptides via the traceless cleavage of disulfide-based cross-linkers. Furthermore, the cytotoxicity of the nanoparticles was tuned by controlling the kinetics of disulfide bond cleavage, and the rate of regeneration of the native peptide from the precursor species. In addition, a small molecule drug (i.e., doxorubicin hydrochloride) was loaded into the nanoparticles to confer synergistic cytotoxic activity, further highlighting the potential application of KLAK particles in therapeutic delivery.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Nanopartículas/química , Peptídeos/farmacologia , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dissulfetos/química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Cinética , Tamanho da Partícula , Peptídeos/síntese química , Peptídeos/química , Propriedades de Superfície
6.
J Clin Rheumatol ; 23(5): 258-261, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28700526

RESUMO

PURPOSES: The aims of this study were to investigate urinary macrophage migration inhibitory factor (MIF) levels and their clinical significance in Henoch-Schönlein purpura (HSP) children with or without nephritis (N) and to assess the influence of steroid treatment on the urine MIF levels of HSPN patients. METHODS: Group I comprised 35 children with HSPN who were examined twice (A before treatment and B after steroid treatment). Group II comprised 41 children with HSP. The control group included 32 healthy children. Urinary MIF levels were measured via enzyme linked immunosorbent assay. The levels of serum creatinine, blood urea nitrogen, urinary microalbumin (mAlb), and 24-hour proteinuria were performed to determine their associations with MIF levels. RESULTS: Urinary MIF levels were significantly higher in group I compared with group II and the control group (P < 0.01); however, no significant difference was found between group II and the control group (P > 0.05). Upon examination, albeit urinary MIF concentration was significantly lower in group IB compared with group IA (P < 0.05), these concentrations were statistically higher than that of group II (P < 0.05). In addition, in the HSPN patients, the urinary MIF was positively associated with urinary microalbumin and 24-hour proteinuria but no association with serum creatinine and blood urea nitrogen. CONCLUSIONS: Elevated urinary MIF levels were found to be correlated with proteinuria in pediatric HSPN. An obvious decrease in urinary MIF concentrations among the children with HSPN was associated with steroid treatment. Urinary MIF can be used as a noninvasive biomarker in pediatric HSPN.


Assuntos
Vasculite por IgA , Oxirredutases Intramoleculares/urina , Fatores Inibidores da Migração de Macrófagos/urina , Nefrite , Biomarcadores/urina , Criança , Pré-Escolar , Monitoramento de Medicamentos/métodos , Feminino , Glucocorticoides/administração & dosagem , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/diagnóstico , Testes de Função Renal/métodos , Masculino , Nefrite/diagnóstico , Nefrite/etiologia , Nefrite/urina , Estatística como Assunto
7.
Nanoscale ; 16(5): 2250-2264, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38213302

RESUMO

Messenger RNA (mRNA)-based therapeutic agents have demonstrated significant potential in recent times, particularly in the context of the COVID-19 pandemic outbreak. As a promising prophylactic and therapeutic strategy, polypeptide-based mRNA delivery systems attract significant interest because of their low cost, simple preparation, tuneable sizes and morphology, convenient large-scale production, biocompatibility, and biodegradability. In this review, we begin with a brief discussion of the synthesis of polypeptides, followed by a review of commonly used polypeptides in mRNA delivery, including classical polypeptides and cell-penetrating peptides. Then, the challenges against mRNA delivery, including extracellular, intracellular, and clinical barriers, are discussed in detail. Finally, we highlight a range of strategies for polypeptide-based mRNA delivery, offering valuable insights into the advancement of polypeptide-based mRNA carrier development.


Assuntos
Peptídeos Penetradores de Células , Pandemias , Humanos , RNA Mensageiro/genética
8.
J Mater Chem B ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899918

RESUMO

This paper outlines a novel drug delivery system for highly cytotoxic mertansine (DM1) by conjugating to an albumin-binding Evans blue (EB) moiety through a tuneable responsive disulfide linker, providing valuable insights for the development of effective drug delivery systems toward cancer therapy.

9.
ACS Appl Mater Interfaces ; 16(21): 27087-27101, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38752799

RESUMO

An ideal vehicle with a high transfection efficiency is crucial for gene delivery. In this study, a type of cationic carbon dot (CCD) known as APCDs were first prepared with arginine (Arg) and pentaethylenehexamine (PEHA) as precursors and conjugated with oleic acid (OA) for gene delivery. By tuning the mass ratio of APCDs to OA, APCDs-OA conjugates, namely, APCDs-0.5OA, APCDs-1.0OA, and APCDs-1.5OA were synthesized. All three amphiphilic APCDs-OA conjugates show high affinity to DNA through electrostatic interactions. APCDs-0.5OA exhibit strong binding with small interfering RNA (siRNA). After being internalized by Human Embryonic Kidney (HEK 293) and osteosarcoma (U2OS) cells, they could distribute in both the cytoplasm and the nucleus. With APCDs-OA conjugates as gene delivery vehicles, plasmid DNA (pDNA) that encodes the gene for the green fluorescence protein (GFP) can be successfully delivered in both HEK 293 and U2OS cells. The GFP expression levels mediated by APCDs-0.5OA and APCDs-1.0OA are ten times greater than that of PEI in HEK 293 cells. Furthermore, APCDs-0.5OA show prominent siRNA transfection efficiency, which is proven by the significantly downregulated expression of FANCA and FANCD2 proteins upon delivery of FANCA siRNA and FANCD2 siRNA into U2OS cells. In conclusion, our work demonstrates that conjugation of CCDs with a lipid structure such as OA significantly improves the gene transfection efficiency, providing a new idea about the designation of nonviral carriers in gene delivery systems.


Assuntos
Carbono , RNA Interferente Pequeno , Transfecção , Humanos , Células HEK293 , Carbono/química , Transfecção/métodos , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , Lipídeos/química , Cátions/química , DNA/química , Pontos Quânticos/química , Técnicas de Transferência de Genes , Ácido Oleico/química , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Fluorescência Verde/genética , Linhagem Celular Tumoral
10.
Free Radic Biol Med ; 212: 360-374, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38171407

RESUMO

Evidence recently showed that pleiotropic cytokine interferon-gamma (IFN-γ) in the tumor microenvironment (TME) plays a positive role in hepatocellular carcinoma (HCC) progression through the regulation of liver cancer stem cells (LCSCs) in HCC. The present study explored the role and potential mechanism of mitochondrial programmed cell death-ligand 1 (PD-L1) and its regulation of ferroptosis in modulating the cancer stemness of LCSCs. It was shown that mimicking TME IFN-γ exposure increased the LCSCs ratio and cancer stemness phenotypes in HCC cells. IFN-γ exposure inhibited sorafenib (Sora)-induced ferroptosis by enhancing glutathione peroxidase 4 (GPX4) expression as well reactive oxygen species (ROS) and lipid peroxidation (LPO) generation in LCSCs. Furthermore, IFN-γ exposure upregulated PD-L1 expression and its mitochondrial translocation, inducing dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and correlating with glycolytic metabolism reprogramming in LCSCs. The genetic intervention of PD-L1 promoted ferroptosis-dependent anti-tumor effects of Sora, reduced glycolytic metabolism reprogramming, and inhibited cancer stemness of HCC in vitro and in vivo. Our results revealed a novel mechanism that IFN-γ exposure-induced mitochondrial translocation of PD-L1 enhanced glycolytic reprogramming to mediate the GPX4-dependent ferroptosis resistance and cancer stemness in LCSCs. This study provided new insights into the role of mitochondrial PD-L1-Drp1-GPX4 signal axis in regulating IFN-γ exposure-associated cancer stemness in LCSCs and verified that PD-L1-targeted intervention in combination with Sora might achieve promising synergistic anti-HCC effects.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Ferroptose/genética , Linhagem Celular Tumoral , Microambiente Tumoral
11.
Acta Biomater ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38849023

RESUMO

Alzheimer's disease (AD) is the most common form of senile dementia, presenting a significant challenge for the development of effective treatments. AD is characterized by extracellular amyloid plaques and intraneuronal neurofibrillary tangles. Therefore, targeting both hallmarks through inhibition of amyloid beta (Aß) and tau aggregation presents a promising approach for drug development. Carbon dots (CD), with their high biocompatibility, minimal cytotoxicity, and blood-brain barrier (BBB) permeability, have emerged as promising drug nanocarriers. Congo red, an azo dye, has gathered significant attention for inhibiting amyloid-beta and tau aggregation. However, Congo red's inability to cross the BBB limits its potential to be used as a drug candidate for central nervous system (CNS) diseases. Furthermore, current studies only focus on using Congo red to target single disease hallmarks, without investigating dual inhibition capabilities. In this study, we synthesized Congo red-derived CD (CRCD) by using Congo red and citric acid as precursors, resulting in three variants, CRCD1, CRCD2 and CRCD3, based on different mass ratios of precursors. CRCD2 and CRCD3 exhibited sustained low cytotoxicity, and CRCD3 demonstrated the ability to traverse the BBB in a zebrafish model. Moreover, thioflavin T (ThT) aggregation assays and AFM imaging revealed CRCD as potent inhibitors against both tau and Aß aggregation. Notably, CRCD1 emerged as the most robust inhibitor, displaying IC50 values of 0.2 ± 0.1 and 2.1 ± 0.5 µg/mL against tau and Aß aggregation, respectively. Our findings underscore the dual inhibitory role of CRCD against tau and Aß aggregation, showcasing effective BBB penetration and positioning CRCD as potential nanodrugs and nanocarriers for the CNS. Hence, CRCD-based compounds represent a promising candidate in the realm of multi-functional AD therapeutics, offering an innovative formulation component for future developments in this area. STATEMENT OF SIGNIFICANCE: This article reports Congo red-derived carbon dots (CRCD) as dual inhibitors of tau and amyloid-beta (Aß) aggregation for the treatment of Alzheimer's disease (AD). The CRCD are biocompatible and show strong fluorescence, high stability, the ability to cross the blood-brain barrier, and the function of addressing two major pathological features of AD.

12.
Front Immunol ; 14: 1173796, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168852

RESUMO

Introduction: The Hippo signaling pathway is an evolutionarily conserved signaling cascade that plays a crucial role in regulating cell proliferation, differentiation, and apoptosis. It has been shown to be a key regulator of cell fate and cellular homeostasis in various immune processes. Despite its well-established functions in vertebrate immunity, its roles in marine invertebrate immunity remain poorly understood. Therefore, our present work provides fresh mechanistic insights into how the Hippo pathway orchestrates hemocytic functions in Crassostrea hongkongensis, with implications for studies on its major forms and modifications in animal evolution. Method: The complete set of Hippo pathway genes, including SAV1, MOB1, LATS, YAP/TAZ, TEAD, and MST, were identified from the C. hongkongensis genome. Quantitative PCR assays were conducted to examine the mRNA expression levels of these genes in different tissues and the levels of these genes in hemocytes before and after bacterial challenges. The study also examined the crosstalk between the Hippo pathway and other immune pathways, such as the AP-1 and p53-dependent p21 signaling cascades. RNA interference was used to knock down MST and TEAD, and MST is a core orchestrator of non-canonical Hippo signaling, to investigate its impact on phagocytosis and bacterial clearance in hemocytes. Result: The results demonstrated that members of the Hippo pathway were highly expressed in hemocytes, with their expression levels significantly increasing following bacterial challenges. Crosstalk between the Hippo pathway and other immune pathways triggered hemocytic apoptosis, which functioned similarly to the canonical Mst-Lats-Yap signaling pathway in Drosophila and mammals. Knocking down MST resulted in increased phagocytosis and boosted the efficiency of bacterial clearance in hemocytes, presumably due to mobilized antioxidant transcription by Nrf for maintaining immune homeostasis. Discussion: This study provides novel insights into the regulatory mechanisms underlying the Hippo pathway in immune responses of C. hongkongensis hemocytes. The study highlights the importance of the Hippo pathway in maintaining immune homeostasis and orchestrating hemocytic functions in oysters. Moreover, this study demonstrates the divergence of the Hippo pathway's roles in marine invertebrate immunity from mammalian observations, indicating the need for further comparative studies across species. These findings have significant implications for future research aimed at elucidating the evolutionary trajectory and functional diversity of the Hippo signaling pathway in animal evolution.


Assuntos
Crassostrea , Animais , Regulação da Expressão Gênica , Hemócitos , Transdução de Sinais/genética , Invertebrados , Homeostase , Mamíferos
13.
Genome Biol ; 23(1): 82, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313930

RESUMO

The increasing number of scRNA-seq data emphasizes the need for integrative analysis to interpret similarities and differences between single-cell samples. Although different batch effect removal methods have been developed, none are suitable for heterogeneous single-cell samples coming from multiple biological conditions. We propose a method, scINSIGHT, to learn coordinated gene expression patterns that are common among, or specific to, different biological conditions, and identify cellular identities and processes across single-cell samples. We compare scINSIGHT with state-of-the-art methods using simulated and real data, which demonstrate its improved performance. Our results show the applicability of scINSIGHT in diverse biomedical and clinical problems.


Assuntos
Algoritmos , Análise de Célula Única , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Sequenciamento do Exoma
14.
J Comput Biol ; 29(11): 1233-1236, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35920848

RESUMO

Data integration is a critical step in the analysis of multiple single-cell RNA sequencing samples to account for heterogeneity due to both biological and technical variability. scINSIGHT is a new integration method for single-cell gene expression data, and can effectively use the information of biological condition to improve the integration of multiple single-cell samples. scINSIGHT is based on a novel non-negative matrix factorization model that learns common and condition-specific gene modules in samples from different biological or experimental conditions. Using these gene modules, scINSIGHT can further identify cellular identities and active biological processes in different cell types or conditions. Here we introduce the installation and main functionality of the scINSIGHT R package, including how to preprocess the data, apply the scINSIGHT algorithm, and analyze the output.


Assuntos
Perfilação da Expressão Gênica , Análise de Célula Única , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , RNA-Seq , Perfilação da Expressão Gênica/métodos , Sequenciamento do Exoma , Algoritmos , Análise por Conglomerados
15.
Clin Breast Cancer ; 22(3): 252-260, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34535389

RESUMO

INTRODUCTION: To investigate ultrasonographic features and analyze causes of misdiagnosis of focal fibrocystic change (FC) of the breast. MATERIALS AND METHODS: The ultrasonographic features of 95 women (104 lesions) with postoperatively pathologically confirmed focal FC (Group 1) were retrospectively analyzed and compared with those of 105 women (107 lesions) with ductal carcinoma in situ (DCIS) (Group 2), and 164 women (177 lesions) with invasive ductal carcinoma (IDC) (Group 3). RESULTS: There were significant differences in 12 features among groups. The sizes and distributions of cystic changes among the groups were significantly different. In group 1, the incidence of cystic changes was 75%(78/104), and the main manifestation was scattered cystic changes (88.5%, 69/78) and microcapsules (81.8%, 63/78). Among focal FC lesions, 36.5% were preoperative BI-RADS classifications 4b-5 (30.8% 4b and 4c). Lesions misdiagnosed as malignant showed solid or cystic solid mixed echoes, and 70.2% of group 1 were irregularly shaped, and 63.5% had unclear edges. In group 1, 5 cases had "hyperechoic halo," 11.5% (12/104) appeared echo attenuation behind the mass, and 21 cases appeared punctate hyperechoic. CONCLUSION: FC frequently exhibits low heterogeneity, scattered microcapsules with posterior enhancement, "pit-like" or "grid-like" changes, posterior enhancement, rare hyperechoic halo, calcification, and lack of blood supply. Certain focal FC are irregularly shaped with unclear edges, with malignant signs such as crab feet and burr, hyperechoic halo, and calcification, which ultrasound BI-RADS classification may easily misdiagnose as malignant. Local magnification function should be considered, and the internal structure should be carefully observed to prevent misdiagnosis.


Assuntos
Neoplasias da Mama , Calcinose , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Cápsulas , Erros de Diagnóstico/prevenção & controle , Feminino , Humanos , Masculino , Estudos Retrospectivos , Ultrassonografia Mamária
16.
Adv Sci (Weinh) ; 9(23): e2201895, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35712773

RESUMO

Immune checkpoint blockade (ICB) has significantly advanced cancer immunotherapy, yet its patient response rates are generally low. Vaccines, including immunostimulant-adjuvanted peptide antigens, can improve ICB. The emerging neoantigens generated by cancer somatic mutations elicit cancer-specific immunity for personalized immunotherapy; the novel cyclic dinucleotide (CDN) adjuvants activate stimulator of interferon genes (STING) for antitumor type I interferon (IFN-I) responses. However, CDN/neoantigen vaccine development has been limited by the poor antigen/adjuvant codelivery. Here, pH-responsive CDN/neoantigen codelivering nanovaccines (NVs) for ICB combination tumor immunotherapy are reported. pH-responsive polymers are synthesized to be self-assembled into multivesicular nanoparticles (NPs) at physiological pH and disassembled at acidic conditions. NPs with high CDN/antigen coloading are selected as NVs for CDN/antigen codelivery to antigen presenting cells (APCs) in immunomodulatory lymph nodes (LNs). In the acidic endosome of APCs, pH-responsive NVs facilitate the vaccine release and escape into cytosol, where CDNs activate STING for IFN-I responses and antigens are presented by major histocompatibility complex (MHC) for T-cell priming. In mice, NVs elicit potent antigen-specific CD8+ T-cell responses with immune memory, and reduce multifaceted tumor immunosuppression. In syngeneic murine tumors, NVs show robust ICB combination therapeutic efficacy. Overall, these CDN/neoantigen-codelivering NVs hold the potential for ICB combination tumor immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Vacinas , Adjuvantes Imunológicos , Animais , Imunoterapia , Camundongos , Neoplasias/terapia , Polímeros
17.
Arch Med Sci ; 17(1): 100-105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33488861

RESUMO

INTRODUCTION: The incidence of hyperuricemia (HUA) at younger ages is increasing along the coastal regions of China. This study aimed to compare the frequency of dual energy CT (DECT) urate crystal deposition between symptomatic hyperuricemic children and asymptomatic hyperuricemic children. MATERIAL AND METHODS: Fifty-six hyperuricemic children were divided into a Joint Group (n = 33) and an Asymptomatic Group (n = 23) according to whether they had a history of arthritis symptoms, which includes rapid onset monoarthritis with intense pain and swelling. We analyzed DECT scans of their feet from the Joint Group and the Asymptomatic Group and compared their clinical features. RESULTS: DECT urate deposits were observed in 28/33 (84.8%) children with symptomatic HUA and 14/23 (60.9%) with asymptomatic HUA. We found 60 areas of urate deposition in the Joint Group; DECT urate crystal deposition was most frequently observed in the first metatarsophalangeal (MTP) joint (30.0%), ankle joint (15.0%), and calcaneus (13.3%). 39 urate deposits were found in the Asymptomatic Group; DECT urate crystal deposition was most frequently observed in the calcaneus (25.6%), the first MTP joint (17.9%), and the first phalanx (15.4%). CONCLUSIONS: Urate deposition can occur in children with HUA, and these deposits occur more frequently in hyperuricemic children with a history of arthritis symptoms. Also, the urate deposition in the first MTP joint and calcaneus was more prevalent than in other joints. It is important to give more attention to hyperuricemic children.

18.
Peptides ; 138: 170505, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33539872

RESUMO

Neuropeptide Y is known to stimulate food intake in fish. In this study, we investigated tilapia NPY (tNPY) both for its effects on the growth of tilapia (Oreochromis niloticus, GIFT) in low fish meal and for its thermal stability. Three diets were formulated containing 0, 3 and 10 % fish meal (NF, LF and HF). From these diets, six experimental diets were prepared by spraying either tNPY solution (0.3 µg/g feed) or distilled water (DW) onto the surface of formulated feeds (NF + DW, NF + tNPY, LF + DW, LF + tNPY, HF + DW and HF + tNPY). Tilapia were fed the six experimental diets for 8 weeks. Fish in the NF + tNPY, LF + tNPY and HF + tNPY groups showed increasing trends in the weight gain rate and specific growth rate compared to its corresponding control group. The feed coefficient of group HF + tNPY was significantly lower than that of the control group. The growth performance of the LF + tNPY approached that of the HF + DW group. The mRNA levels of npy in NF + tNPY were significantly higher than those in NF + DW. A field experiment in which tNPY was sprayed in feeds by the vacuum spray method with doses of 0, 0.2 and 0.4 µg/g feed was performed for three months, and the FBW of tilapia receiving tNPY at 0.2 and 0.4 µg/g feed was higher than that of the control group although not significantly. The bioactivity of tNPY was confirmed by its ability to reduce cAMP levels and activate the ERK1/2 pathway. These results demonstrated that tNPY could promote tilapia growth with oral administration low fish meal diets.


Assuntos
Ração Animal , Neuropeptídeo Y/genética , Tilápia/crescimento & desenvolvimento , Aumento de Peso/genética , Animais , Dieta , Neuropeptídeo Y/metabolismo , Tilápia/metabolismo
19.
Technol Cancer Res Treat ; 20: 15330338211034269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34396867

RESUMO

Whole-brain radiotherapy (WBRT) is the mainstay of therapy in treating cancer patients with brain metastases, but unfortunately, it might also lead to decline in neurocognitive function. This study aims to investigate the preservation of long-term neurocognitive function in patients after hippocampal avoidance whole-brain radiotherapy (HA-WBRT). Retrospectively, 47 patients diagnosed with brain metastases of non-small cell lung cancer (NSCLC) between 2015-01-01 and 2017-12-31 at the Department of Oncology, XXX Hospital were selected and divided into 2 groups. Group A (n = 27) received HA-WBRT, whereas group B (n = 20) received WBRT. Neurocognitive function was analyzed at baseline and at 3, 6, 9, 12 and 24 months after radiotherapy, using Mine-Mental State Examination (MMSE) scales and Montreal Cognitive Assessment (MoCA) scales. The OS, PFS and tumor recurrence sites were also analyzed. When evaluated at 12 and 24 months after radiotherapy, the cognitive function scores of the hippocampal avoidance group were significantly higher than those of the non-hippocampal avoidance group (P < 0.001). In terms of patient survival, there was no significant difference in OS (P = 0.2) and PFS (P = 0.18) between these 2 groups. Fourteen patients in group A and 12 patients in group B had brain tumor recurrence after radiation, only one patient in group A occurred within 5 mm from the edge of the hippocampus (P > 0.05). In conclusion, HA-WBRT might have a protective effect on long-term neurocognitive function and did not affect patient survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Irradiação Craniana/métodos , Hipocampo/efeitos da radiação , Neoplasias Pulmonares/radioterapia , Transtornos Neurocognitivos/prevenção & controle , Tratamentos com Preservação do Órgão/métodos , Lesões por Radiação/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/patologia , Prognóstico , Lesões por Radiação/patologia , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos
20.
Mitochondrial DNA B Resour ; 6(3): 835-836, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33763596

RESUMO

In this study, the whole mitochondrial genome of Silurus grahami was reported to be 16,518 bp in length, including 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and one control region. The phylogenetic analysis based on 13 protein-coding genes showed that S. grahami was sister to clade of S. meridionalis and S. lanzhouensis. A total of 81 bases differences were identified in COI barcoding region, which could be used for species identification in catfish.

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