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1.
PLoS One ; 19(10): e0312545, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39475973

RESUMO

OBJECTIVE: This study focused on the gastrointestinal (GI) symptoms in the omicron variant infection and the related factors based on digestive health. METHODS: A cross-sectional study was conducted on individuals infected with the omicron variant. A structured questionnaire was developed to gather their demographic characteristics, preexisting digestive problems (diseases & symptoms), and clinical manifestations during the infection. RESULTS: 11,484 questionnaires were received from online platforms. 7,929 infected participants were selected based on inclusion and exclusion criteria. Among them, 4,225 (53.3%) were females, and the mean age was 36.0±8.8 years old. In general, the proportion of GI symptoms in the omicron variant infection was 31.4% (62.6% and 25.0% in participants with pre-existing digestive problems and those without, respectively). The participants with pre-existing digestive problems exhibited more severe clinical manifestations during infection compared to those without. Notably, participants with gastrointestinal symptoms during the infection had more severe clinical manifestations, regardless of basic digestive health. Upper, rather than lower GI symptoms were more closely associated with the severity of the clinical manifestations. NSAIDs may increase the occurrence of GI symptoms in participants with a healthy digestive system but not in those with preexisting digestive problems. CONCLUSION: Patients infected with the omicron variant may experience more severe clinical symptoms if they have gastrointestinal issues. Digestive health strongly influences the occurrence of gastrointestinal symptoms and the severity of clinical manifestations.


Assuntos
COVID-19 , Gastroenteropatias , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/virologia , COVID-19/epidemiologia , Feminino , Masculino , Adulto , SARS-CoV-2/isolamento & purificação , Estudos Transversais , Gastroenteropatias/virologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Doenças do Sistema Digestório/virologia , Doenças do Sistema Digestório/complicações
2.
Front Microbiol ; 15: 1412991, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974029

RESUMO

Age and gender have been recognized as two pivotal covariates affecting the composition of the gut microbiota. However, their mediated variations in microbiota seem to be inconsistent across different countries and races. In this study, 613 individuals, whom we referred to as the "healthy" population, were selected from 1,018 volunteers through rigorous selection using 16S rRNA sequencing. Three enterotypes were identified, namely, Escherichia-Shigella, mixture (Bacteroides and Faecalibacterium), and Prevotella. Moreover, 11 covariates that explain the differences in microbiota were determined, with age being the predominant factor. Furthermore, age-related differences in alpha diversity, beta diversity, and core genera were observed in our cohort. Remarkably, after adjusting for 10 covariates other than age, abundant genera that differed between age groups were demonstrated. In contrast, minimal differences in alpha diversity, beta diversity, and differentially abundant genera were observed between male and female individuals. Furthermore, we also demonstrated the age trajectories of several well-known beneficial genera, lipopolysaccharide (LPS)-producing genera, and short-chain fatty acids (SCFAs)-producing genera. Overall, our study further elucidated the effects mediated by age and gender on microbiota differences, which are of significant importance for a comprehensive understanding of the gut microbiome spectrum in healthy individuals.

3.
JGH Open ; 8(3): e13045, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38544955

RESUMO

Background and Aim: Both intestinal symptoms and comorbidities exist in irritable bowel syndrome (IBS) patients and influence their quality of life (QOL). More research is needed to determine how these variables impact the QOL of IBS patients. This study aimed to determine which specific factors had a higher influence on QOL and to further compare the effects of intestinal symptoms and comorbidities on QOL. Methods: IBS patients were recruited from six tertiary hospitals in different regions of China. QOL, gastrointestinal symptoms, and comorbidities were assessed by different scales. Correlation analysis, multiple linear regression, and mediation model were used for statistics. Results: Four hundred fifty-three IBS patients (39.7% women, mean age 45 years) were included and no significant differences in QOL were found across demographic characteristics. Abnormal defecation (r = -0.398), fatigue (r = -0.266), and weakness (r = -0.286) were found to show higher correlation with QOL. More than 40% of IBS patients were found to suffer from varying degrees of anxiety or depression, and anxiety (r = -0.564) and depression (r = -0.411) were significantly negatively correlated with QOL (P < 0.001). Psychological factors showed the strongest impact (ß' = -0.451) and play a strong mediating role in the impact of physiological symptoms on QOL. Anxiety was found to be the strongest factor (ß' = -0.421). Conclusion: Compared with other symptoms, psychological symptoms, particularly anxiety, are more common and have a more negative influence on QOL. The QOL of IBS patients is also significantly impacted by abnormal defecation, abdominal distension, and systemic extraintestinal somatic symptoms. In the treatment of IBS patients with unhealthy mental status, psychotherapy might be prioritized.

4.
Chem Commun (Camb) ; 60(28): 3794-3797, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38482848

RESUMO

A palladium catalysed construction of fluoroalkyl indoles and isoquinolones through aryl/monofluoroalkylation of allenamides has been developed. Monofluoromethyl-substituted heterocycles could be accessed under mild conditions with broad functional group tolerance. In addition, indole-oxindole bisheterocyclic scaffolds bearing a fluorine atom were successfully synthesized with 3-fluoro-oxindole as the nucleophile by applying this method.

5.
Org Lett ; 26(9): 1834-1839, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38388381

RESUMO

Efficient access to multiple functionalized allenes via a three component 1,4-alkylcyanation of enynes with cyclic alcohol derivatives in the presence of trimethylsilyl cyanide (TMSCN) under copper/photoredox dual catalysis has been developed. Both easily transformable aldehyde and cyano groups were introduced to tetra-substituted allenes through light-induced C-C bond cleavage of cyclic butanol and pentanol derivatives. The reactions proceeded smoothly under mild conditions with broad functional groups tolerance.

6.
BMC Pediatr ; 23(1): 503, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37803383

RESUMO

BACKGROUND: Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS. METHODS: We searched the WangFang and China National Knowledge Infrastructure databases with the keywords "Shwachman-Diamond syndrome," "SDS," "SBDS gene" and "inherited bone marrow failure" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using "Shwachman-diamond syndrome" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included. RESULTS: The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years. CONCLUSIONS: Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.


Assuntos
Doenças da Medula Óssea , Insuficiência Pancreática Exócrina , Feminino , Humanos , Lactente , Masculino , Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/epidemiologia , Doenças da Medula Óssea/genética , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/epidemiologia , Insuficiência Pancreática Exócrina/terapia , Mutação , Fenótipo , Síndrome de Shwachman-Diamond , Partícula de Reconhecimento de Sinal/genética
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(8): 939-946, 2023 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-37532492

RESUMO

OBJECTIVE: To explore the characteristics of Shwachman-Diamond syndrome (SDS) in Chinese children in order to provide a reference for early diagnosis. METHODS: With Shwachman-Diamond syndrome, SDS, SBDS gene and inherited bone marrow failure as the keywords, the search period was set from January 2002 to October 2022. Relevant literature was retrieved from the Wanfang Database and China National Knowledge Infrastructure (CNKI) database. In addition, by using Shwachman-diamond syndrome as a keyword, the search period was also retrieved from the Web of Science, PubMed, and MEDLINE databases from January 2002 to October 2022. A child with SDS treated at the Tongji Hospital was also included. A total of 44 cases with complete clinical data were analyzed with reference to the International Standard for SDS Diagnosis. Chi-square test and t test were used for statistical analysis. Evidence-based research was carried out in the form of systematic review. The epidemiology, clinical characteristics and key points of early diagnosis of the Chinese SDS children were summarized and compared with the international data. RESULTS: The main characteristics of SDS in Chinese children were summarized as follows: The ratio of males to females was about 1.3 : 1, the median age of onset was 3 months, and the median age of diagnosis was 14 months. The first symptoms were often exocrine pancreatic insufficiency (31.8%) and granulocytopenia with infection (31.8%). According to the international consensus, the incidence rates of the three major diseases of SDS were hemocytopenia (95.4%), pancreatic disease (72.7%), and bone abnormality (40.9%). The common factors underlying SDS disease were variants of the SBDS gene (c.258+2T>C and c.183_184TA>CT), albeit there was no significant correlation between genotype and phenotype (P > 0.05). Compared with international reports, the clinical manifestations and genotypes of Chinese SDS children are different (P < 0.05). CONCLUSION: The SDS children have an early age of onset and significant individual difference. It is necessary to analyze the case-related data to facilitate early recognition, diagnosis and clinical intervention.


Assuntos
Síndrome de Shwachman-Diamond , Feminino , Humanos , Masculino , Doenças da Medula Óssea/diagnóstico , Doenças da Medula Óssea/genética , Doenças da Medula Óssea/terapia , China , População do Leste Asiático , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/genética , Insuficiência Pancreática Exócrina/terapia , Síndrome de Shwachman-Diamond/diagnóstico , Síndrome de Shwachman-Diamond/genética , Síndrome de Shwachman-Diamond/terapia
8.
Int J Mol Sci ; 24(16)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37629134

RESUMO

Piezo1, a non-selective cation channel directly activated by mechanical forces, is widely expressed in the digestive system and participates in biological functions physiologically and pathologically. In this review, we summarized the latest insights on Piezo1's cellular effect across the entire digestive system, and discussed the role of Piezo1 in various aspects including ingestion and digestion, material metabolism, enteric nervous system, intestinal barrier, and inflammatory response within digestive system. The goal of this comprehensive review is to provide a solid foundation for future research about Piezo1 in digestive system physiologically and pathologically.


Assuntos
Sistema Digestório , Sistema Nervoso Entérico , Canais Iônicos , Humanos , Canais Iônicos/metabolismo , Sistema Digestório/metabolismo , Mecanotransdução Celular , Animais
9.
J Pediatr Hematol Oncol ; 42(8): e702-e706, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32969848

RESUMO

BACKGROUND: The efficacy, safety, and outcome of rabbit antihuman thymocyte globulin (rATG) as initial therapy for children aplastic anemia (AA) were evaluated. PATIENTS AND METHODS: Sixty-one children with AA were retrospectively analyzed, including 43 patients with severe AA and 18 patients with transfusion-dependent nonsevere AA. All patients received rATG in combination with cyclosporine A between September 2005 and January 2015. RESULTS: The overall response rates were 55.7%, 68.9%, and 68.9% at 6, 12, and 18 months, respectively. Surprisingly, the overall complete response rate kept increasing from 9.8% at 12 months to 39.3% at 18 months, indicating a delayed response for rATG. Overall survival at 5 and 10 years was 72.1% and 67.2%, respectively. The overall survival of patients who responded between 3 and 12 months was significantly higher than that of nonresponders (71.4% vs. 47.4%).Antithymocyte globulin-related adverse reactions were significantly higher in severe AA (83.7%) than in nonsevere AA (55.6%) and these reactions were controllable and not life threatening with comprehensive measures. CONCLUSIONS: This retrospective study shows an encouraging response and survival results in children with AA treated with rATG. Prolonged assessments were needed to evaluate the delayed responses to rATG. rATG could be used as an alternative in the first-line treatment of childhood AA.


Assuntos
Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(5): 505-511, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32434649

RESUMO

In order to clearly define the features of Shwachman-Diamond syndrome (SDS) in Chinese children, this article analyzes and summarizes the epidemiology, clinical features, and key points in the diagnosis and treatment of SDS in Chinese children with review of the clinical data of 27 children with SDS from related articles published previously. A comparative analysis was made between the Chinese and international data related to childhood SDS. The results showed a male/female ratio of about 2:1 in the Chinese children with SDS, with an age of onset of <1 month to 5 years (median 1 month) and an age of 3 months to 12 years (median 12 months) at the time of confirmed diagnosis. Reductions in peripheral blood cells due to myelopoiesis inhibition were observed in all 27 children with SDS, among whom 93% had neutropenia. Chronic diarrhea (85%), liver damage (78%), and short stature (83%) were the three main clinical features of SDS. Supplementation of pancreatin and component blood transfusion may temporarily alleviate the disease, while allogeneic hematopoietic stem cell transplantation is still an effective radical treatment. The comparative analysis of the Chinese and oversea data showed that compared with those in the European and American countries, the children with SDS in China had significantly higher incidence rates of chronic diarrhea, reductions in peripheral blood cells (three lineages), and liver damage, and there were also differences in the type of mutant genes.


Assuntos
Síndrome de Shwachman-Diamond , Criança , China , Insuficiência Pancreática Exócrina , Feminino , Humanos , Masculino , Neutropenia , Resultado do Tratamento
11.
Colloids Surf B Biointerfaces ; 185: 110585, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683203

RESUMO

Synergistic tumor treatment has recently attracted more and more attention due to its remarkable therapeutic effect. Herein, a multifunctional drug delivery system based on hyaluronic acid (HA) targeted dual stimulation responsive MoS2 nanosheets (HA-PEI-LA-MoS2-PEG, HPMP) for active interaction with CD44 receptor positive MCF-7 cells is reported. Melanin (Mel), a new type of photothermal agent and doxorubicin (DOX) are both loaded onto the HPMP nanocomposite and can be released by mild acid or hyperthermia. The prepared HPMP nanocomposite has a uniform hydrodynamic diameter (104 nm), a high drug loading (944.3 mg.g-1 HPMP), a remarkable photothermal effect (photothermal conversion efficiency: 55.3%) and excellent biocompatibility. The DOX release from HPMP@(DOX/Mel) can be precisely controlled by the dual stimuli of utilizing the acidic environment in the tumor cells and external laser irradiation. Meanwhile, loading of Mel onto the surface can enhance the photothermal effect of the MoS2 nanosheets. In vitro experiments showed that the HPMP@(DOX/Mel) nanoplatform could efficiently deliver DOX into MCF-7 cells and demonstrated enhanced cytotoxicity compared to that of the non-targeted nanoplatform. In vivo experiments in a breast cancer model of nude mice further confirmed that the HPMP@(DOX/Mel) significantly inhibited tumor growth under near infrared (NIR) laser irradiation, which is superior to any single therapy. In summary, this flexible nanoplatform, based on multi-faceted loaded MoS2 nanosheets, exhibits considerable potential for efficient pH/NIR-responsive targeted drug delivery and chemo-photothermal synergistic tumor therapy.


Assuntos
Neoplasias da Mama/terapia , Dissulfetos/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Hipertermia Induzida , Molibdênio/química , Nanocompostos/química , Fototerapia , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/patologia , Proliferação de Células , Doxorrubicina/química , Liberação Controlada de Fármacos , Feminino , Humanos , Raios Infravermelhos , Camundongos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
ACS Appl Bio Mater ; 3(4): 2350-2359, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35025285

RESUMO

Herein, we developed curcumin (Cur)-loaded porous poly(lactic-co-glycolic acid) (pPLGA) nanoparticles (NPs) by the nanoprecipitation method. Dopamine (DA) was then self-polymerized to form a polydopamine (PDA) layer on the surface of the NPs, yielding Cur@pPLGA/PDA NPs that are able to act as both chemotherapeutic and photothermal agents. These NPs were further camouflaged with the red blood cell membrane (RBCM) to construct RBCM-Cur@pPLGA/PDA NPs. The RBCM-pPLGA/PDA NPs were around 200 nm in size and demonstrated photothermal performance in the near-infrared (NIR) region, with a potent conversion efficiency (35.2%). The blank carrier has favorable cytocompatibility, but when drug loaded the NPs can efficiently induce the death of cancer cells (particularly when combined with NIR laser treatment). Cellular uptake results revealed greater in vitro uptake of RBCM-Cur@pPLGA/PDA NPs than bare Cur@pPLGA/PDA NPs in the case of cancer cells but reduced macrophage phagocytosis. In vivo studies in mice showed that the RBCM-Cur@pPLGA/PDA NPs exhibited prolonged blood circulation times and excellent photothermal properties, allowing tumor-specific chemo-photothermal therapy. The RBCM-Cur@pPLGA/PDA NP platform presents great potential for targeted synergistic cancer treatments.

13.
Hematology ; 24(1): 282-289, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31793407

RESUMO

BACKGROUND: Immunosuppressive therapy (IST) composed of antithymocyte globulin (ATG) and cyclosporine A (CSA) is one of the standard therapies in pediatric patients with acquired aplastic anemia (AA), but predictors of IST are lack of consensus. PROCEDURES: Ninety-four patients from two pediatric medical centers in China were included between January 2005 and March 2018. Clinical factors associated with the efficacy were analyzed according to multivariate logistic regression model previously established. RESULTS: We discovered that overall responsiveness was 77.66%. Five out of 35 factors were statistically significant in univariate analysis. Based on the cutoff point chosen by receiver operating characteristic (ROC) curve, 5 continuous variables were made categorical, among which 3 variables with significance were employed to establish the logistic regression equation. Based on these 3 variables, we found that starting IST within 126 days of the first appearance of symptoms (X1, p = .003), absolute neutrophil count (ANC) higher than 0.435×109/L (X2, p = .012), and rate of decreased actual lymphocyte count (ALC) higher than 59.2% within the 1st week after IST (X3, p = .001) were three independent risk factors for response to IST. The rate of decreased ALC higher than 59.2% after IST was the most significant variable (OR = 9.355, Log (P) = -2.161 + 2.149X1 + 1.662X2 + 2.236X3). The accuracy, sensitivity, and specificity of the model were 86.2%, 94.5% and 57.1%, respectively. CONCLUSION: Duration of AA, ANC and decreased ALC rate after IST might predict the response to IST, among which the rate of decreased ALC after IST is the most important predictive factor.


Assuntos
Anemia Aplástica/terapia , Imunossupressores/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunossupressores/farmacologia , Masculino , Estudos Retrospectivos
14.
Pharmaceutics ; 11(9)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450749

RESUMO

In this study, curcumin-loaded porous poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were prepared and surface modified with red blood cell membranes (RBCM) to yield biomimetic RBCM-p-PLGA@Cur NPs. The NPs displayed a visible cell-membrane structure at their exterior and had a uniform size of 162 ± 3 nm. In vitro studies showed that drug release from non-porous PLGA NPs was slow and that much of the drug remained trapped in the NPs. In contrast, release was accelerated from the porous PLGA NPs, and after the RBCM coating, a sustained release over 48 h was obtained. Confocal microscopy and flow cytometry results revealed that the RBCM-p-PLGA NPs led to a greater cellular uptake by H22 hepatocarcinoma cells than the uncoated analogue NPs, but could avoid phagocytosis by macrophages. The drug-free formulations were highly biocompatible, while the drug-loaded systems were effective in killing cancer cells. RBCM-p-PLGA@Cur NPs possess potent anti-tumor activity in a murine H22 xenograft cancer model (in terms of reduced tumor volume and mass, as well as inducing apoptosis of tumor cells), and have no observable systemic toxicity. Overall, our study demonstrates that the use of the RBCM to cloak nanoscale drug delivery systems holds great promise for targeted cancer treatment, and can ameliorate the severe side effects currently associated with chemotherapy.

15.
J Nanobiotechnology ; 17(1): 60, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31084622

RESUMO

BACKGROUND: Nanoscale drug-delivery systems (DDSs) have great promise in tumor diagnosis and treatment. Platelet membrane (PLTM) biomimetic DDSs are expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends "don't eat me" signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated on the surface of cancer cells. RESULTS: In this study, porous nanoparticles loaded with the anti-cancer drug bufalin (Bu) were prepared from a chitosan oligosaccharide (CS)-poly(lactic-co-glycolic acid) (PLGA) copolymer. These were subsequently coated with platelet membrane (PLTM) to form PLTM-CS-pPLGA/Bu NPs. The PLTM-CS-pPLGA/Bu NPs bear a particle size of ~ 192 nm, and present the same surface proteins as the PLTM. Confocal microscopy and flow cytometry results revealed a greater uptake of PLTM-CS-pPLGA/Bu NPs than uncoated CS-pPLGA/Bu NPs, as a result of the targeted binding of P-selectin on the surface of the PLTM to the CD44 receptors of H22 hepatoma cells. In vivo biodistribution studies in H22-tumor carrying mice revealed that the PLTM-CS-pPLGA NPs accumulated in the tumor, because of a combination of active targeting effect and the EPR effect. The PLTM-CS-pPLGA/Bu NPs led to more effective tumor growth inhibition over other bufalin formulations. CONCLUSIONS: Platelet membrane biomimetic nanoparticles played a promising targeted treatment of cancer with low side effect.


Assuntos
Antineoplásicos/química , Materiais Biomiméticos/química , Bufanolídeos/química , Portadores de Fármacos/química , Nanopartículas/química , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Transporte Biológico , Plaquetas/metabolismo , Bufanolídeos/efeitos adversos , Bufanolídeos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Oligossacarídeos/química , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Distribuição Tecidual
16.
Int J Pharm ; 559: 289-298, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30707933

RESUMO

In this study, we developed novel thermal and redox-responsive micelles based on the Pluronic F127 tri-block copolymer and employed these for redox-responsive intratumor release of bufalin, an anti-cancer drug. Pluronic F127 was first functionalized with carboxylate groups, and then assembled into micelles. The HOOC-F127-COOH micelles are 20 ±â€¯4 nm in size at 37 °C, but expand to 281 ±â€¯5 nm when cooled to 4 °C. This allows for the free diffusion of bufalin into the micellar cores at low temperatures, while at 37 °C the micelles are much more compact and the drug molecules can be effectively held in their interiors. A high encapsulation efficiency and loading content were obtained via drug incorporation at 4 °C. The drug-loaded micelles were cross-linked with cystamine, which contains a disulfide bond responsive to the local cancer microenvironment. In vitro studies showed that drug release from the cross-linked micelles was low under normal physiological conditions, but markedly accelerated upon exposure to conditions representative of the intracellular tumor environment. Confocal microscopy revealed that the cross-linked micelles gave high levels of drug release inside the cells. In vivo studies in mice showed the drug-loaded cross-linked micelles have potent anti-tumor activity, leading to high levels of apoptosis of tumor cells and significant reductions in tumor volume. The drug-loaded cross-linked micelles did not significantly influence body weight, and there was no evidence for detrimental off-target effects. These results indicate that the Pluronic-based micelles developed in this work are promising drug delivery systems for the targeted treatment of cancer.


Assuntos
Bufanolídeos/química , Poloxâmero/química , Animais , Apoptose/efeitos dos fármacos , Bufanolídeos/administração & dosagem , Linhagem Celular , Linhagem Celular Tumoral , Cistamina/química , Dissulfetos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Camundongos , Camundongos Endogâmicos ICR , Micelas , Tamanho da Partícula , Polímeros/química , Microambiente Tumoral/efeitos dos fármacos
17.
Int J Hematol ; 109(3): 328-335, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30604317

RESUMO

Dyskeratosis congenita (DC) is a rare-inherited bone marrow failure syndrome associated with multi-system disorder. To summarize the clinical features, epidemiology, and treatment of DC in mainland China, we retrospectively reviewed the medical records of two patients diagnosed with DC at our hospital and published reports on other DC patients in mainland China. The clinical features of 82 DC patients were summarized. The median age of onset was 5 years, but the median age at diagnosis was 16 years. Bone marrow failure occurred at a high rate of 44% and early, with a median onset age of 6 years (range 1-40 years). Only DKC1, TINF2, and TERT mutations were reported, which is a relatively simple signature. Aplastic anemia was treated mainly with low-dose androgens, glucocorticoids, or allogeneic hematopoietic stem cell transplantation, with an efficacy of 39% (14/36). In China, DC is relatively common in infants, with early age of onset but delayed diagnosis. Bone marrow failure occurred at a high rate and early. Improvement in the knowledge and awareness of DC combined with gene mutation tests will facilitate diagnosis and therapy in its early stages.


Assuntos
Androgênios/uso terapêutico , Anemia Aplástica , Disceratose Congênita , Glucocorticoides/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mutação , Idade de Início , Aloenxertos , Anemia Aplástica/diagnóstico , Anemia Aplástica/epidemiologia , Anemia Aplástica/genética , Anemia Aplástica/terapia , Proteínas de Ciclo Celular/genética , Criança , Pré-Escolar , China , Disceratose Congênita/diagnóstico , Disceratose Congênita/epidemiologia , Disceratose Congênita/genética , Disceratose Congênita/terapia , Feminino , Humanos , Masculino , Proteínas Nucleares/genética , Telomerase/genética , Proteínas de Ligação a Telômeros/genética
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(11): 964-967, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30477632

RESUMO

Iron deficiency (ID) is the most common trace element deficiency in childhood. Recent studies have shown that late fetus period, neonatal period, and infancy are important periods for brain development, and ID during these periods may cause irreversible damage to brain development, including abnormal emotion and behavior, cognitive decline, and attention deficit, which may still be present in adulthood. Therefore, it should be taken seriously. This article summarizes the research advances in major mechanisms involved in brain developmental disorder due to ID in the early stage of life and related intervention measures.


Assuntos
Anemia Ferropriva , Encefalopatias , Encéfalo , Criança , Deficiências do Desenvolvimento , Humanos , Ferro
19.
J Pediatr Hematol Oncol ; 39(8): 614-617, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29068868

RESUMO

BACKGROUND: Immunosuppressive therapy (IST) is the standard treatment for aplastic anemia (AA) children who lack a sibling donor, but the clinical response rate to IST varies. Predictors of response to IST are valuable for stratifying AA patients and making clinical decisions. METHODS: The serum interleukin (IL)-6 levels of 41 AA patients were measured at the time of diagnosis and the response rate of the patients to IST was evaluated at 3, 6, and 12 months after IST. Receiver-operator characteristic (ROC) analysis was used to calculate the predictive value of initial IL-6 levels in determining response at 6 months after IST. RESULTS: The initial IL-6 levels were significant higher in responders than nonresponders at 6 months after IST (211.89 vs. 18.09 pg/mL; P=0.005), using 36.8 pg/mL as a threshold, there were 80% sensitivity and 81% specificity for discriminating responders and nonresponders to IST. Patients with initial high IL-6 level (>36.8 pg/mL) have favorable response rates than those with initial low IL-6 level (<36.8 pg/mL) at 3, 6, and 12 months after IST (P<0.01). CONCLUSION: High levels of IL-6 at the time of diagnosis predict a favorable response to IST in children with AA and this may be helpful for patient's stratification and clinical decisions.


Assuntos
Anemia Aplástica/sangue , Anemia Aplástica/tratamento farmacológico , Imunossupressores/uso terapêutico , Interleucina-6/sangue , Adolescente , Anemia Aplástica/diagnóstico , Biomarcadores , Contagem de Células Sanguíneas , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Masculino , Curva ROC , Fatores de Tempo , Resultado do Tratamento
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(8): 899-903, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28774365

RESUMO

OBJECTIVE: To investigate the neurocognitive function of children with acute lymphoblastic leukemia (ALL) and long-term disease-free survival and related influencing factors. METHODS: A total of 40 ALL children with long-term disease-free survival were enrolled as study group, and 40 healthy children were enrolled as control group. The Chinese Wechsler Intelligence Scale for Children (C-WISC), continuous performance test (CPT), and Stroop test software were used for the evaluation of all children. Neurocognitive function was compared between groups and influencing factors were analyzed. RESULTS: Compared with the control group, the study group had significantly lower full intelligence quotient, verbal intelligence quotient, and performance intelligence quotient in C-WICS (P<0.05) and significantly higher numbers of mistakes and misses in CPT (P<0.05). There were no significant differences in the numbers of correct answers, mistakes, and misses of word-color consistency between the study group and the control group (P>0.05), while the study group had significantly higher numbers of mistakes and misses of word-color contradiction and irrelevance (P<0.05). The total dose of high-dose methotrexate and ALL risk classification were associated with the reduction in intelligence quotient, and children's younger age at diagnosis of ALL was associated with the higher numbers of misses and mistakes. Girls tended to have a significantly lower performance intelligence quotient than boys (P<0.05). CONCLUSIONS: ALL children with long-term disease-free survival have neurocognitive impairment, which may be associated with the dose of chemotherapeutic drugs, age at diagnosis, and sex.


Assuntos
Cognição , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Adolescente , Criança , Pré-Escolar , Cognição/efeitos dos fármacos , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Testes de Inteligência , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade
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