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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 230-235, 2024 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-38557373

RESUMO

OBJECTIVES: To explore the risk factors associated with cow's milk protein allergy (CMPA) in infants. METHODS: This study was a multicenter prospective nested case-control study conducted in seven medical centers in Beijing, China. Infants aged 0-12 months were included, with 200 cases of CMPA infants and 799 control infants without CMPA. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for the occurrence of CMPA. RESULTS: Univariate logistic regression analysis showed that preterm birth, low birth weight, birth from the first pregnancy, firstborn, spring birth, summer birth, mixed/artificial feeding, and parental history of allergic diseases were associated with an increased risk of CMPA in infants (P<0.05). Multivariate logistic regression analysis revealed that firstborn (OR=1.89, 95%CI: 1.14-3.13), spring birth (OR=3.42, 95%CI: 1.70-6.58), summer birth (OR=2.29, 95%CI: 1.22-4.27), mixed/artificial feeding (OR=1.57, 95%CI: 1.10-2.26), parental history of allergies (OR=2.13, 95%CI: 1.51-3.02), and both parents having allergies (OR=3.15, 95%CI: 1.78-5.56) were risk factors for CMPA in infants (P<0.05). CONCLUSIONS: Firstborn, spring birth, summer birth, mixed/artificial feeding, and a family history of allergies are associated with an increased risk of CMPA in infants.


Assuntos
Hipersensibilidade a Leite , Nascimento Prematuro , Lactente , Gravidez , Feminino , Animais , Bovinos , Recém-Nascido , Humanos , Hipersensibilidade a Leite/etiologia , Estudos de Casos e Controles , Estudos Prospectivos , Nascimento Prematuro/induzido quimicamente , Fatores de Risco , Proteínas do Leite
2.
Chem Commun (Camb) ; 59(30): 4479-4482, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-36960888

RESUMO

A three-in-one self-assembled metallo-nanophotosensitizer system (NLCD) was constructed by cooperative coordination of amphiphilic L-arginine-modified photosensitizer NBS-L-Arg and DOX in the presence of Cu2+via the synergy of coordination, hydrophobic, and π-π stacking interactions. The resulting NLCD NPs possessed uniform size, well-defined nanosphere structure, and GSH-responsive ability. In vitro studies exhibited that NLCD NPs integrating photodynamic/chemodynamic/chemo multimodal therapy achieved an enhanced therapeutic effect.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Neoplasias/tratamento farmacológico
3.
Chem Commun (Camb) ; 59(23): 3455-3458, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36866731

RESUMO

An L-arginine-functionalized pillar[5]arene-based supramolecular photosensitizer LAP5⊃NBSPD was constructed by host-guest interactions, which could self-assemble into nano-micelles to achieve effective delivery and selective release of LAP5 and NBS in cancer cells. In vitro studies revealed that LAP5⊃NBSPD NPs exhibited excellent cancer cell membrane disruption and ROS generation properties, which provides a novel route for synergistically enhanced cancer therapeutic effectiveness.


Assuntos
Calixarenos , Neoplasias , Humanos , Calixarenos/farmacologia , Micelas , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Compostos de Amônio Quaternário , Arginina/química
4.
Chem Commun (Camb) ; 59(8): 989-1005, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36621829

RESUMO

Covalently bridged pillararene-based polymers (CBPPs) are a special class of macrocycle-based polymers in which multiple pillararene monomers are attached to the polymer structures by covalent bonds. Owing to the unique molecular structures including the connection components or the spatial structures, CBPPs have become increasingly popular in applications ranging from environmental science to biomedical science. In this review, CBPPs are divided into three types (linear polymers, grafted polymers, and cross-linked polymers) according to their structural characteristics and described from the perspective of synthesis methods comprehensively. In addition, the applications of CBPPs are presented, including selective adsorption and separation, fluorescence sensing and detection, construction of supramolecular gels, anticancer drug delivery, artificial light-harvesting, catalysis, and others. Finally, the current challenging issues and comprehensive prospects of CBPPs are discussed.


Assuntos
Sistemas de Liberação de Medicamentos , Polímeros , Polímeros/química , Géis/química
5.
Front Cell Infect Microbiol ; 13: 1351814, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38304460

RESUMO

Introduction: Respiratory viral infection (RVI) is of very concern after the outbreak of COVID-19, especially in pediatric departments. Learning pathogen spectrum of RVI in children previous the epidemic of COVID-19 could provide another perspective for understanding RVI under current situation and help to prepare for the post COVID-19 infection control. Methods: A nucleic acid sequence-based amplification (NASBA) assay, with 19 pairs of primers targeting various respiratory viruses, was used for multi-pathogen screening of viral infections in children presenting influenza-like illness (ILI) symptoms. Children with ILI at the outpatient department of Beijing Tsinghua Changgung Hospital during the influenza epidemic from 12/2018 to 01/2019 were included. Throat swabs were obtained for both the influenza rapid diagnostic test (IRDT) based on the colloidal gold immunochromatographic assay and the NASBA assay, targeting various respiratory viruses with an integrated chip technology. Results and discussion: Of 519 patients, 430 (82.9%) were positive in the NASBA assay. The predominant viral pathogens were influenza A H1N1 pdm1/2009 (pH1N1) (48.4%) and influenza A (H3N2) (18.1%), followed by human metapneumovirus (hMPV) (8.8%) and respiratory syncytial virus (RSV) (6.1%). Of the 320 cases identified with influenza A by NASBA, only 128 (40.0%) were positive in the IRDT. The IRDT missed pH1N1 significantly more frequently than A (H3N2) (P<0.01). Influenza A pH1N1 and A (H3N2) were the major pathogens in <6 years and 6-15 years old individuals respectively (P<0.05). In summary, influenza viruses were the major pathogens in children with ILI during the 2018-2019 winter influenza epidemic, while hMPV and RSV were non-negligible. The coexistence of multiple pathogen leading to respiratory infections is the normalcy in winter ILI cases.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Viroses , Criança , Humanos , Lactente , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Vírus da Influenza A Subtipo H3N2 , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia
6.
Chem Commun (Camb) ; 58(99): 13731-13734, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36444745

RESUMO

Real-time detection of glycosylation on label-free cancer cell surfaces is of significance for the diagnosis and treatment of cancer. In this work, we have successfully developed a novel dynamic reversible sensor based on pH-sensitive phenylboronic esters to determine in real-time the binding kinetics of protein-carbohydrate interactions on suspension cancer cell surfaces using a quartz crystal microbalance (QCM) technique.


Assuntos
Técnicas Biossensoriais , Neoplasias , Técnicas de Microbalança de Cristal de Quartzo/métodos , Ácidos Borônicos , Cinética , Carboidratos/química
7.
Front Surg ; 9: 899795, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795229

RESUMO

Purpose: To analyze the obstetric high-risk factors and serological characteristics of early-onset neonatal bacterial infections (EONBI). Methods: 119 neonates with early-onset bacterial infection who were admitted to the neonatal ward of our hospital from October 2020 to December 2021 were recorded as the study group, and 100 neonates without bacterial infection who were admitted during the same period were used as the reference group. Comparative analysis of obstetric high-risk factors and serological characteristics of EONBI. Results: There was no statistical difference between the two groups in terms of gender and age at admission (P > 0.05). The gestational age and birth weight of newborns in the study group were lower than those in the reference group (P < 0.001). Comparing the maternal factors of EONBI between the two groups, there was no statistical difference in age, number of obstetric inspections, whether to use antibiotics, and mode of delivery (P > 0.05). Univariate analysis showed that preterm birth, unexplained asphyxia, fecal contamination of amniotic fluid, maternal infection during pregnancy, and premature rupture of membranes ≥18 h were significantly associated with EONBI (P < 0.05); while there was no significant difference between the two groups in the comparison between diabetic mother and child and maternal fever at delivery (P > 0.05). Multifactorial analysis showed that preterm birth, fecal contamination of amniotic fluid, maternal infection during pregnancy, and premature rupture of membranes ≥18 h had a good multivariate dependence on EONBI (P < 0.05), while there was no significant association with unexplained asphyxia, diabetic mother and child, and maternal fever at delivery (P > 0.05). The incidence of neonatal temperature >37.9°C was higher in the study group than in the reference group (P < 0.05), and there were no statistical differences in the comparison of other clinical manifestations (P > 0.05). The CRP level of neonates in the study group (47.33 ± 4.14) mg/L was higher than that of the reference group (4.84 ± 1.03) mg/L (P < 0.001). The WBC level of neonates in the study group (5.64 ± 1.18) 109/L was higher than that of the reference group (0.28 ± 0.04) 109/L (P < 0.001). The PCT level of neonates in the study group (5.41 ± 0.85) µg/L was higher than that of the reference group (0.24 ± 0.07) µg/L (P < 0.001). Conclusion: EONBI is closely associated with several obstetric high-risk factors, including preterm birth, fecal contamination of amniotic fluid, maternal infection during pregnancy, and premature rupture of membranes ≥18 h; EONBI has no specific symptoms and signs, but serum CRP, WBC, and PCT levels are significantly higher than those of newborns without co-infection with bacteria.

8.
Taiwan J Obstet Gynecol ; 61(3): 453-458, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35595437

RESUMO

OBJECTIVE: To evaluate the obstetrical and oncological progression of twin pregnancies with hydatidiform mole coexisting fetus (HMCF). MATERIALS AND METHODS: Using a retrospective method based on patients from the Women's Hospital, Zhejiang University School of Medicine database between January 1990 and October 2020, 17 patients were histologically confirmed as having HMCF, and the patients' prenatal diagnosis, outcomes and development of gestational trophoblastic neoplasia (GTN) were reviewed. RESULTS: Among these 17 cases, 11 (64.71%) cases were complete hydatidiform mole coexisting fetus (CHMCF), and 6 (35.29%) cases were partial hydatidiform mole coexisting fetus (PHMCF). The gestational age at diagnosis of CHMCF was significantly earlier than that of PHMCF [9 (8-24) vs. 18 (11-32) weeks, respectively, P < 0.05]. The live birth rate of PHMCF was slightly higher than that of CHMCF (33.33%; 18.18%), but this difference was not statistically significant. The overall rate of GTN incidence of HMCF was 47.06% (8/17), and the GTN rates of PHMCF and CHMCF were 33.33% (2/6) and 54.55% (6/11), respectively. There was no significant difference in the GTN rate between patients who chose to continue pregnancy and those who terminated pregnancy before 24 weeks of gestation. The GTN rate of patients with term delivery was not significantly higher than that of preterm delivery. CONCLUSION: In HMCF cases, the incidence rate of CHMCF was higher than that of PHMCF, and PHMCF is more difficult to diagnose in the early stage. Continuing pregnancy does not increase the risk of GTN compared to terminating pregnancy. In cases of HMCF, when the fetal karyotype is normal and maternal complications are controlled, it is safe to continue the pregnancy and extend it to term.


Assuntos
Doença Trofoblástica Gestacional , Mola Hidatiforme , Neoplasias Uterinas , Feminino , Feto , Humanos , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/epidemiologia , Recém-Nascido , Gravidez , Gravidez de Gêmeos , Estudos Retrospectivos , Neoplasias Uterinas/diagnóstico
9.
Int J Nanomedicine ; 17: 1567-1575, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401000

RESUMO

Background: Multifunctional nanocarriers based on tumor targeting and intracellular monitoring have received much attention and been a subject of intensive study by researchers in recent years. In this study, we report multifunctional glyconanoparticles with activatable near-infrared probes for tumor imaging and targeted drug delivery. Methods: Disulfide-functionalized dicyanomethylene-4H-pyran (DCM-SS-NH2) and amino-functionalized lactose were modified and loaded onto the surfaces of polydopamine nanoparticles (NPs) by Michael addition or Schiff-base reaction as GSH stimulation-responsive fluorescent probes and tumor-targeting moieties, respectively. Doxorubicin (DOX), a model anticancer drug, was loaded onto polydopamine through π-π interactions directly to prepare multifunctional PLDD (PDA@Lac/DCM/DOX) NPs. Results: Experimental results showed that PLDD NPs had been successfully prepared. DCM, the fluorescence of which was quenched in PLDD NPs, was able to restore red fluorescence in a solution with a GSH concentration of 5 mM. The amount of DOX released from PLDD NPs was 44% over 72 hours in a weak-acid environment (pH 5). The results of CLSM and flow cytometry indicated that the PLDD NPs had good HepG2-targeting ability due to the special recognition between lactose derivative of NPs and overexpressed asialoglycoprotein receptors on HepG2 cell membrane. More importantly, the disulfide bond of DCM-SS-NH2 was broken by the high concentration of GSH inside cancer cells, activating the near-infrared fluorescence probe DCM for cancer-cell imaging. MTT assays indicated that PLDD NPs exhibited higher anticancer efficiency for HepG2 cells and had reduced side effects on normal cells compared with free DOX. Conclusion: The fluorescence of modified DCM loaded onto PLDD NPs is able to be restored in the high-concentration GSH environment within cancer cells, while improving the effectiveness of chemotherapy with reduced side effects. It provides a good example of integration of tumor imaging and targeted drug delivery.


Assuntos
Lactose , Nanopartículas , Dissulfetos , Doxorrubicina , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química
10.
Asia Pac J Clin Nutr ; 31(1): 147-155, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35357113

RESUMO

BACKGROUND AND OBJECTIVES: Cow's milk allergy (CMA) is the most common food allergy in young children. Previous studies have reported that single-nucleotide polymorphisms (SNPs) are associated with CMA. The extent to which SNPs contribute to the occurrence of CMA is unknown. The purpose of this study was to investigate the independent relevance of genetic predisposition to CMA in Chinese children. METHODS AND STUDY DESIGN: 200 infants with CMA and 799 healthy controls aged 0-12 months were included. Five previously identified genetic variants (rs17616434, rs2069772, rs1800896, rs855791 and rs20541) were genotyped. Logistic regression was used to analyze the genetic associations or their interactions with a family history of allergy on CMA. RESULTS: Among the five SNPs, only IL10 rs1800896 was significantly associated with CMA (odds ratio (OR) 1.60, p=0.042). Each 1-risk allele increase in the genetic risk score (GRS) was suggestively associated with an 11% higher risk of CMA (1.11: 0.99-1.27, p=0.069) and a 45% increased risk of CMA in the GRS high-risk group compared to the GRS low-risk group (1.45: 1.02-2.06, p=0.037). Furthermore, parental allergy also increased the risk of CMA among children (1.87: 1.46-2.39, p<0.001). Importantly, parental allergy exacerbated the genetic effect on the risk of CMA. CONCLUSIONS: The rs1800896 variant in the IL-10 gene is associated with CMA in Chinese children. In addition, the GRS had an interaction with parental history of allergy, implying that genetic risk for CMA was exacerbated among those with parental history of allergy.


Assuntos
Interleucina-10 , Hipersensibilidade a Leite , Animais , Bovinos , China , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Interleucina-10/genética , Hipersensibilidade a Leite/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco
11.
Eur J Surg Oncol ; 48(1): 142-149, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34452770

RESUMO

BACKGROUND: Microvascular invasion (MVI) adversely affects long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to examine the association between preoperative type 2 diabetes mellitus (T2DM) with incidences of MVI and prognosis in HBV-related HCC after liver resection (LR). MATERIAL AND METHODS: Data of HBV-related HCC patients who underwent LR as an initial therapy from four hospitals in China were retrospectively collected. Clinicopathological factors associated with the incidence of MVI were identified using univariate and multivariate logistic regression analysis. The recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of 1473 patients who were included, 219 (14.9%) patients had T2DM. Preoperative T2DM, HBV DNA load, antiviral treatment, AFP level, varices, and tumor encapsulation were identified to be independent predictors of the incidence of MVI. Patients with HBV-related HCC and T2DM had a higher incidence of MVI (65.8%) than those without T2DM (55.4%) (P = 0.004). The RFS and OS were significantly worse in patients with T2DM than those without T2DM (median RFS: 11.1 vs 16.7 months; OS: 26.4 vs 42.6 months, both P < 0.001). Equivalent results were obtained in HCC patients with MVI who had or did not have T2DM (median RFS: 10.0 vs 15.9 months; OS: 24.5 vs 37.9 months, both P < 0.001). CONCLUSIONS: Preoperative T2DM was an independent risk factor of incidence of MVI. Patients with HBV-related HCC and T2DM had worse prognosis than those without T2DM after LR.


Assuntos
Carcinoma Hepatocelular/patologia , Diabetes Mellitus Tipo 2/epidemiologia , Hepatite B Crônica/complicações , Neoplasias Hepáticas/patologia , Microvasos/patologia , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estudos Retrospectivos , Taxa de Sobrevida
12.
Chem Commun (Camb) ; 57(84): 10983-10997, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34604891

RESUMO

Covalently bridged pillararene-based oligomers (CBPOs) are formed by covalent bonding of pillararene monomers, and they play a critical role in expanding the multi-disciplinary application of pillararenes due to their excellent molecular complexing ability, specially designed geometry and multifunctional linking groups. This article provides a comprehensive review of the synthesis and applications of CBPOs. The design and synthetic strategies of a series of CBPOs (dimers, trimers, tetramers and others) are first introduced. Many CBPOs with multi-cavities and unique geometry are very attractive and efficient building blocks for constructing novel smart supramolecular polymers (SPs) with different topological structures through host-guest interactions. We describe the methods of constructing various SPs based on CBPOs in detail. Furthermore, the extensive applications of CBPOs and CBPO-based SPs in recognition and detection of ions and organic small molecules, selective adsorption and separation, artificial light-harvesting systems, catalysis, drug delivery systems, and others are systematically introduced. Finally, the future challenges and perspectives for CBPOs are also highlighted.

13.
Gastroenterol Rep (Oxf) ; 9(4): 313-322, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34567563

RESUMO

BACKGROUND: Chronic hepatitis B (CHB) patients have a high virological relapse rate after cessation of nucleos(t)ide analog (NA) treatment, but the clinical outcome remains unclear. This study aimed to investigate the 96-week clinical outcomes and the risk factors for relapse in CHB after cessation of NAs. METHODS: This study was a prospective trial; 74 eligible patients were enrolled. The patients underwent NA cessation and follow-up according to the 2012 Asian Pacific Association for the Study of the Liver Guideline. Symptoms, biochemical (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, urea nitrogen, creatinine), virological data (hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], hepatitis B e antibody [HBeAb], hepatitis B virus [HBV] DNA levels), and color Doppler ultrasound examination results were recorded and analysed. RESULTS: After NA cessation, 19 cases were HBsAg-negative without relapse during the 96-week follow-up. Of the 55 cases of HBsAg-positive after cessation, four types of clinical outcomes were observed. Twelve patients had no relapse during the 96-week follow-up (type A, 21.8%), 7 patients underwent virological relapses but spontaneously had a non-virological relapse (type B, 12.7%), 10 patients maintained virological relapse (type C, 18.2%), and 26 patients turned to clinical relapse, received NA retreatment, and achieved ALT normalization and negative conversion of HBV DNA within 12 months (type D, 47.3%). The 2-year overall cumulative rates of virological and clinical relapses were 58.1% and 24.3%, respectively. Independent factors associated with virological relapse were duration of negative HBV DNA, EOT (end of treatment) HBsAg, and original status of HBeAg. The EOT HBsAg was also an independent factor for clinical relapse. CONCLUSIONS: There are four types of clinical outcomes in patients with CHB after cessation of NA treatment. Further research is needed to explore the mechanism of different clinical outcomes. The EOT HBsAg level is an independent factor associated with both virological and clinical relapse.

14.
BMC Pregnancy Childbirth ; 21(1): 551, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384374

RESUMO

BACKGROUND: We encourage Hepatitis B virus-infected mothers to breastfeed postpartum, even when continuing pregnancy category B nucleos(t)ide analogs (NAs) treatment. However, a large proportion of the Hepatitis B virus-infected mothers were noncompliant with this breastfeeding recommendation. This study aimed to investigate the factors associated with noncompliance with breastfeeding recommendation in Hepatitis B virus-infected mothers who had received NAs treatment during pregnancy. METHODS: A total of 155 mothers with chronic hepatitis B receiving NAs treatment for preventing mother-to-child transmission during the late gestation period were included and divided into exclusive breastfeeding (n = 63), mixed feeding (n = 34), and artificial feeding (n = 58) groups according to the postpartum feeding methods. Independent variables associated with feeding methods were analyzed using logistic regression analysis. RESULTS: Compared to the breastfeeding and mixed feeding groups, the artificial feeding group had significantly more multiparity, later postpartum timing of stopping NAs treatment, and a lower proportion of having knowledge of NAs medications (all P < 0.05). In addition, multivariable logistic regression analysis confirmed that multiparity, later postpartum timing of stopping NAs treatment, and lacking knowledge of medication were independent factors associated with noncompliance with breastfeeding recommendation. CONCLUSIONS: Hepatitis B virus-infected mothers who stopped NAs treatment at late postpartum period or had less knowledge of medication were more likely to be noncompliant with breastfeeding recommendation. Strengthening health education for participants taking NAs may be an important method to improve compliance with breastfeeding recommendation.


Assuntos
Antivirais/uso terapêutico , Aleitamento Materno , Nucleosídeos/uso terapêutico , Cooperação do Paciente , Período Pós-Parto , Telbivudina/uso terapêutico , Tenofovir/uso terapêutico , Adulto , China/epidemiologia , Feminino , Hepatite B Crônica/prevenção & controle , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Retrospectivos , Fatores de Risco
15.
Chem Commun (Camb) ; 57(62): 7625-7628, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34235523

RESUMO

A galactose-targeting supramolecular photosensitizer system DOX@GP5⊃NBSPD was constructed based on a host-guest inclusion complex. The supramolecular system could achieve efficient delivery of DOX/NBS and selective release under GSH stimulation. In vitro studies revealed that this supramolecular DOX/NBS co-delivery system exhibited high ROS production and excellent cancer cell damage capability in a hypoxic environment. This strategy can therefore achieve enhanced hypoxic-tumor therapeutic effectiveness by chemo-photodynamic combination.


Assuntos
Calixarenos/química , Calixarenos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Hipóxia Tumoral/efeitos da radiação , Doxorrubicina/química , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Fotoquimioterapia
16.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34201944

RESUMO

Photodynamic therapy (PDT) as a safe, non-invasive modality for cancer therapy, in which the low oxygen and high glutathione in the tumor microenvironment reduces therapeutic efficiency. In order to overcome these problems, we prepared a supramolecular photosensitive system of O2-Cu/ZIF-8@ZIF-8@WP6-MB (OCZWM), which was loaded with oxygen to increase the oxygen concentration in the tumor microenvironment, and the Cu2+ in the system reacted with glutathione (GSH) to reduce the GSH concentration to generate Cu+. It is worth noting that the generated Cu+ can produce the Fenton reaction, thus realizing the combination therapy of PDT and chemodynamic therapy (CDT) to achieve the purpose of significantly improving the anti-cancer efficiency.


Assuntos
Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes , Microambiente Tumoral/efeitos dos fármacos , Células Hep G2 , Humanos , Azul de Metileno/química , Neoplasias/metabolismo , Neoplasias/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Compostos de Amônio Quaternário/química
17.
Int J Nanomedicine ; 15: 10417-10424, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376329

RESUMO

BACKGROUND: Conventional chemotherapy using small molecular antitumor drugs suffers from several limitations, for instance poor water solubility, high toxicity, and lack of specificity. However, prodrugs constructed by covalent modification of anticancer drugs can overcome these limitations, which are able to release its active form after entering the tumor tissues by specific stimulus response. METHODS: A GSH-responsive glyco-nanoprodrug system has been constructed by self-assembled of amphiphilic lactosemodified camptothecin prodrug molecular (Lac-SS-CPT) for targeting drug delivery and combination therapy. RESULTS: Using HL7702 cells as experimental models, the cytotoxic effects of Lac-SS-CPT were investigated to 10-30 µmol/L for 48 hours. Notably, the cell viability of Lac-SS-CPT to HL7702 cells was higher compared with free CPT which indicated that Lac-SS-CPT can reduce side-effects. Simultaneously, we have evaluated the anticancer efficiency of doxorubicin hydrochloride (DOX)-loaded Lac-SS-CPT glyco-nanoprodrug system (Lac-SS-CPT@DOX), where Lac-SS-CPT@DOX and free DOX incubated with HpeG2 cells and HL7702 cells for 24, 48, and 72 hours, respectively. It turned out that Lac-SS-CPT@DOX encapsulated anticancer drug (DOX) could decrease DOX side-effect on HL7702 cells and increase DOX anticancer efficiency. More importantly, the CPT and DOX were released from Lac-SS-CPT@DOX in HepG2 cells where a higher GSH concentration exists. Moreover, combination therapy efficiency was evaluated, where free DOX and Lac-SS-CPT@DOX incubated with DOX-resistance HepG2 cells (HepG2-ADR cells), respectively. CONCLUSION: The results revealed that the Lac-SS-CPT@DOX could enhance the cytotoxicity of DOX for HepG2-ADR cells and provided a new idea for designing an advanced nano-prodrug system toward combination therapy.


Assuntos
Camptotecina/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Lactose/química , Pró-Fármacos/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Camptotecina/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Combinação de Medicamentos , Liberação Controlada de Fármacos , Glutationa/metabolismo , Células Hep G2 , Humanos , Nanopartículas/administração & dosagem , Nanopartículas/química
18.
Chem Commun (Camb) ; 56(62): 8861-8864, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32638757

RESUMO

A supramolecular nanoprodrug based on the host-guest complexation of water-soluble pillar[5]arene (WP5) and a boronate ester linked curcumin (Cur) was constructed, which had dual-responsiveness towards pH and GSH, allowing the drug to be selectively released in hepatoma cells. In vitro studies revealed that the Dox-loaded WP5G-Cur nanoprodrug achieved co-delivery of Dox/Cur. The anti-cancer efficiency could be enhanced through synergistic chemotherapies of Dox/Cur.


Assuntos
Ácidos Borônicos/química , Calixarenos/química , Curcumina/química , Ésteres/química , Nanoestruturas/química , Pró-Fármacos/química , Água/química , Curcumina/metabolismo , Curcumina/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sinergismo Farmacológico , Glutationa/metabolismo , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Pró-Fármacos/metabolismo , Solubilidade
19.
J Med Virol ; 92(12): 3381-3389, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32410298

RESUMO

The efficacy of prenatal antiviral therapy (AVT) for preventing the vertical transmission of hepatitis B virus (HBV) is well demonstrated. However, data are limited regarding the safety of postpartum cessation of AVT, which may induce alanine aminotransferase (ALT) elevation. We aimed to investigate the necessity of prolonging maternal AVT after delivery. Chronic hepatitis B mothers at the immune-tolerant phase with HBV DNA levels >6 log10 IU/mL were prospectively enrolled and received AVT during the third trimester until delivery. Patients were offered to discontinue AVT either at delivery or postpartum week (PPW) 6. In addition, mothers who deferred AVT during pregnancy served as the control group. All mothers were followed until PPW 52 for clinical and virological parameters of hepatitis flares. Among 118 mothers recruited, 91 received AVT with 53 (group A) and 24 (group B) discontinue their treatment at delivery and PPW 6, respectively. Twenty-seven mothers who deferred AVT during pregnancy were followed as the control (group C). A total of 104 of 118 mothers who completed the study, 50% (52/104) had postpartum-elevated ALT levels, which were mild and moderate except 6 of 104 (5.77%) of patients had levels ≥5 times the upper limit of normal; 70% (36/52) of the ALT flares occurred within 12 weeks after delivery. In subgroup analyses, the frequency of ALT elevation was similar among the groups A vs B vs C (50.9% [27/53] vs 58.3% [14/24] vs 40.7% [11/27], respectively; P = .447), as well as the mean peak ALT level (108.4/74.1/126.7 U/L in groups A/B/C, respectively; P = .291). Although postpartum ALT flares were common for mothers with or without AVT during pregnancy, most cases of ALT elevation were mild to moderate. Our study observed that extending AVT to PPW 6 did not affect maternal outcomes and ATV should be discontinued at birth. Close monitoring is warranted as severe flares rarely occurred.

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