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1.
Small ; 18(47): e2203431, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36180405

RESUMO

Mesenchymal stem cell (MSC) therapy via intravenous transplantation exhibits great potential for brain tissue regeneration, but still faces thorny clinical translation challenges as the unknown dynamic fate leads to the contentious therapeutic mechanism and the poor MSC viability in harsh lesions limits therapeutic efficiency. Here, a vitality-enhanced dual-modal tracking system is designed to improve engraftment efficiency and is utilized to noninvasively explore the fate of intravenous transplanted human umbilical cord-derived MSCs during long-term treatment of ischemic stroke. Such a system is obtained by bioorthogonally conjugating magnetic resonance imaging (MRI) contrast and near-infrared fluorescence (NIRF) imaging nanoparticles to metabolic glycoengineered MSCs with a lipoic acid-containing extracellular antioxidative protective layer. The dynamic fates of MSCs in multi-dimensional space-time evolution are digitally detailed for up to 28 days using MRI and NIRF imaging equipment, and the protective layer greatly shields MSCs from reactive oxygen spices (ROS) degradation, enhances MSC survival, and engraftment efficiency. Additionally, it is observed that the bioengineered MSCs exhibit dynamic intelligent responses corresponding to microenvironment remodeling and exert enhanced therapeutic effects. This dual-modal tracking system enables long-term tracking of MSCs while improving their viability at the lesion sites, which may serve as a valuable tool for expediting the clinical translation of MSC therapy.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Acidente Vascular Cerebral , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical , Imageamento por Ressonância Magnética/métodos , Meios de Contraste/metabolismo , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia
2.
J Nanobiotechnology ; 20(1): 394, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045429

RESUMO

Epithelial-mesenchymal transition (EMT), a differentiation process with aberrant changes of tumor cells, is identified as an initial and vital procedure for metastatic processes. Inflammation is a significant inducer of EMT and provides an indispensable target for blocking EMT, however, an anti-inflammatory therapeutic with highlighted safety and efficacy is deficient. Metformin is a promising anti-inflammatory agent with low side effects, but tumor monotherapy with an anti-inflammation drug could generate therapy resistance, cell adaptation or even promote tumor development. Combination therapies with various anti-inflammatory mechanisms can be favorable options improving therapeutic effects of metformin, here we develop a tumor targeting hybrid micelle based on metformin and a histone deacetylase inhibitor propofol-docosahexaenoic acid for efficient therapeutic efficacies of anti-inflammatory drugs. Triptolide is further encapsulated in hybrid micelles for orthotopic tumor therapies. The final multifunctional nanoplatforms (HAOPTs) with hyaluronic acid (HA) modification can target tumor efficiently, inhibit tumor cell EMT processes, repress metastasis establishment and suppress metastatic tumor development in a synergistic manner. Collectively, the results afford proof of concept that the tumor targeting anti-inflammatory nanoplatform can provide a potent, safe and clinical translational approach for EMT inhibition and metastatic tumor therapy.


Assuntos
Metformina , Neoplasias , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Metformina/farmacologia , Metformina/uso terapêutico
3.
J Formos Med Assoc ; 121(9): 1739-1747, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35094913

RESUMO

BACKGROUND/PURPOSE: Youths with autism spectrum disorder (ASD) are at a high risk of involvement in school bully. The study investigated whether comorbid psychopathologies mediated the link between ASD and bullying involvement. METHODS: We assessed 353 youths (mean age, 11.8 ± 3.1 years), including 121 youths with ASD and 232 typically developing (TD) controls, using semi-structured diagnostic interviews on ASD and other psychiatric conditions. Follow-up assessments took place 2-5 years (37.6 ± 15 months) later. Meanwhile, their parents reported on the Social Adjustment Inventory for Children and Adolescents about bullying involvement statuses. We identified significant mediators by simple mediation models, followed by multiple mediation models to scrutinize the mediation effects of selected mediators. RESULTS: The results showed a sevenfold increased risk of bullying involvement among youths with ASD compared with TD controls at follow-up. In general, psychopathologies mediated the link between ASD and bullying involvement, even independent of age and sex. Specifically, we found mediating effects of social problems on victimization-only and aggressive behaviors on victimization-perpetration. CONCLUSION: Our findings strongly suggest the link between ASD and later bullying involvement is mediated by pre-existing comorbid psychiatric conditions, besides the direct effect of ASD on bullying victimization. Hence, early identification and intervention of these psychopathologies are highly suggested.


Assuntos
Transtorno do Espectro Autista , Bullying , Vítimas de Crime , Adolescente , Criança , Seguimentos , Humanos , Psicopatologia
4.
J Am Chem Soc ; 138(50): 16388-16397, 2016 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-27998090

RESUMO

We report herein the design, synthesis, and characterization of a two-segment fluorogenic analogue of vitamin K, B-VKQ, prepared by coupling vitamin K3, also known as menadione (a quinone redox center), to a boron-dipyrromethene (BODIPY) fluorophore (a lipophilic reporter segment). Oxidation-reduction reactions, spectroelectrochemical studies, and enzymatic assays conducted in the presence of DT-diaphorase illustrate that the new probe shows reversible redox behavior on par with that of vitamin K, provides a high-sensitivity fluorescence signal, and is compatible with biological conditions, opening the door to monitor remotely (i.e., via imaging) redox processes in real time. In its oxidized form, B-VKQ is non-emissive, while upon reduction to the hydroquinone form, B-VKQH2, BODIPY fluorescence is restored, with emission quantum yield values of ca. 0.54 in toluene. Density functional theory studies validate a photoinduced electron transfer intramolecular switching mechanism, active in the non-emissive quinone form and deactivated upon reduction to the emissive dihydroquinone form. Our results highlight the potential of B-VKQ as a fluorogenic probe to study electron transfer and transport in model systems and biological structures with optimal sensitivity and desirable chemical specificity. Use of such a probe may enable a better understanding of the role that vitamin K plays in biological redox reactions ubiquitous in key cellular processes, and help elucidate the mechanism and pathological significance of these reactions in biological systems.


Assuntos
Corantes Fluorescentes/química , Vitamina K/química , Eletroquímica , Transporte de Elétrons , Corantes Fluorescentes/metabolismo , Modelos Moleculares , NAD(P)H Desidrogenase (Quinona)/química , NAD(P)H Desidrogenase (Quinona)/metabolismo , Conformação Proteica , Vitamina K/metabolismo
5.
Cell Tissue Res ; 358(2): 453-64, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25064029

RESUMO

Tissue engineering provides new potential treatments for the repair of bone defects. Bone-marrow-derived mesenchymal stem cells (BMSCs) represent an attractive cell source for therapeutic applications involving tissue engineering, although disadvantages, such as pain of harvest and low proliferation efficiency, are major limitations to the application of BMSCs in the clinic. Adipose-derived stem cells (ASCs) with their multilineage potential and satisfactory proliferation potential can be induced into the osteogenic lineage in vitro and can be anchored onto suitable scaffolds as seed cells to repair bone defects successfully in an autologous setting. Previous studies have indicated that both undifferentiated BMSCs and ASCs exhibit immunosuppression and immunoprivilege properties. We compare the immuno-function of undifferentiated and osteo-differentiated ASCs in vitro and explore the feasibility of applying allogeneic ASCs to the repair of ulnar bone defects in the rabbit model. Our study demonstrates that allogeneic osteogenic differentiated ASCs maintain low immunogenicity and negative immunomodulation. The allogeneic osteogenic differentiated ASCs combined with demineralized bone matrix successfully regenerate ulnar bone defects in rabbits without immunosuppressive therapies.


Assuntos
Tecido Adiposo/citologia , Regeneração Óssea , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco/imunologia , Ulna/patologia , Ulna/fisiopatologia , Animais , Antozoários , Antígenos de Superfície/metabolismo , Diferenciação Celular , Linhagem da Célula , Proliferação de Células , Forma Celular , Células Cultivadas , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Imageamento Tridimensional , Terapia de Imunossupressão , Teste de Cultura Mista de Linfócitos , Osteogênese , Coelhos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Transplante Homólogo , Ulna/diagnóstico por imagem
6.
Inorg Chem ; 53(15): 7916-25, 2014 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-25054275

RESUMO

The kinetics and products for solvolysis of N-p-nitrophenyl-N',N'-bis(pyridin-2-ylmethyl) urea (7a), N-methyl-N-p-nitrophenyl-N',N'-bis(pyridin-2-yl methyl) urea (7b), and N-phenyl-N',N'-bis(pyridin-2-yl-methyl) urea (DPPU) (7c) promoted by Cu(II) ion in methanol and ethanol were studied under (s)(s)pH-controlled conditions at 25 °C. Methanolysis and ethanolysis of these substrates proceeds rapidly at a 1:1 ratio of substrate:metal ion, the half-times for decomposition of the Cu(II):7a complexes being ~150 min in methanol and 15 min in ethanol. In all cases, the reaction products are the Cu(II) complex of bis(2-picolyl)amine and the O-methyl or O-ethyl carbamate of the parent aniline, signifying that the point of cleavage is the bis(2-picolyl)-N-C=O bond. Reactions of the Cu(II):7b complexes in each solvent proceed about 3-5 times slower than their respective Cu(II):7a complexes, excluding an elimination mechanism that proceeds through an isocyanate which subsequently adds alcohol to give the observed products. The reactions also proceed in other solvents, with the order of reactivity ethanol > methanol >1-propanol >2-propanol > acetonitrile (with 0.2% methanol) > water spanning a range of 150-fold. The mechanism of the reactions is discussed, and the reactivity and mode of cleavage are compared with that of the M(II)-promoted ethanolytic cleavage of a mono-2-picolyl derivative, N-p-nitrophenyl-N'-(pyridin-2-yl-methyl) urea (4a), which had previously been shown to cleave at the aniline N-C=O bond. The large estimated acceleration of the rate of attack of ethoxide on 7b of at least 2 × 10¹6 provided by associating Cu(II) with the departing group in this urea is discussed in terms of a trifunctional role for the metal ion involving Lewis acid activation of the substrate, intramolecular delivery of a Cu(II)-coordinated ethoxide, and metal-ion-assisted leaving group departure.


Assuntos
Álcoois/química , Aminas/química , Cobre/química , Ureia/análogos & derivados , Catálise , Hidrólise , Solventes , Ureia/química
7.
Mol Biol Rep ; 40(10): 5987-92, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24057180

RESUMO

The association between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of head and neck cancer (HNC) were investigated in many published studies; however, the currently available results are inconclusive. Therefore, we conducted this meta-analysis for deriving a more precise estimation of association between VEGF polymorphisms and the risk of HNC. Finally, we yield eight case-control studies involving six polymorphisms contain 2,444 individuals from PubMed, Embase, and CNKI up to January 30, 2013 (last updated on May 4, 2013). The results of meta-analysis showed that all the six polymorphisms of VEGF were not associated with risk of HNC [OR 1.25, 95 % CI (0.60-1.58) for TT vs. CC for 936 C/T; OR 1.41, 95 % CI (0.79-2.52) for GG vs. AA for -1,154 A/G; OR 0.97, 95 % CI (0.38-2.50) for CC vs. GG for 405 G/C; OR 1.44, 95 % CI (0.80-2.61) for AA vs. CC for 2,578 C/A; OR 1.27, 95 % CI (0.77-3.72) for TT vs. CC for -460 C/T; and OR 0.87, 95 % CI (0.37-2.06) for GG vs. CC for -634 G/C]. When performed subgroup analysis according to ethnicity for VEGF 936 C/T, the results suggested that it was not associated with the risk of HNC for either Asians [OR 0.84, 95 % CI (0.27-2.56) for TT vs. CC] or Caucasians [OR 2.10, 95 % CI (0.82-5.37) for TT vs. CC]. However, due to the limitations of this meta-analysis, more well designed, larger sample size, and adjusted risk factors studies are suggested to further assess the findings.


Assuntos
Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo de Nucleotídeo Único/genética , Fator A de Crescimento do Endotélio Vascular/genética , Humanos , Razão de Chances , Viés de Publicação , Fatores de Risco
8.
Nat Commun ; 14(1): 435, 2023 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702831

RESUMO

The limited benefits of immunotherapy against glioblastoma (GBM) is closely related to the paucity of T cells in brain tumor bed. Both systemic and local immunosuppression contribute to the deficiency of tumor-infiltrating T cells. However, the current studies focus heavily on the local immunosuppressive tumor microenvironment but not on the co-existence of systemic immunosuppression. Here, we develop a nanostructure named Nano-reshaper to co-encapsulate lymphopenia alleviating agent cannabidiol and lymphocyte recruiting cytokine LIGHT. The results show that Nano-reshaper increases the number of systemic T cells and improves local T-cell recruitment condition, thus greatly increasing T-cell infiltration. When combined with immune checkpoint inhibitor, this therapeutic modality achieves 83.3% long-term survivors without recurrence in GBM models in male mice. Collectively, this work unveils that simultaneous reprogramming of systemic and local immune function is critical for T-cell based immunotherapy and provides a clinically translatable option for combating brain tumors.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Masculino , Camundongos , Animais , Glioblastoma/patologia , Imunoterapia/métodos , Neoplasias Encefálicas/patologia , Terapia de Imunossupressão , Imunidade , Microambiente Tumoral
9.
ACS Nano ; 17(14): 14014-14031, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37428140

RESUMO

Metabolic therapy targeting the metabolic addictions driven by gain-of-function mutations in KRAS is promising in fighting cancer through selective killing of malignant cells without hurting healthy cells. However, metabolic compensation and heterogeneity make current metabolic therapies ineffective. Here, we proposed a biomimetic "Nutri-hijacker" with "Trojan horse" design to induce synthetic lethality in KRAS-mutated (mtKRAS) malignant cells by hitchhiking and reprogramming the metabolic addictions. Nutri-hijacker consisted of the biguanide-modified nanoparticulate albumin that impaired glycolysis and a flavonoid that restrained glutaminolysis after the macropinocytosis of Nutri-hijacker by mtKRAS malignant cells. Nutri-hijacker suppressed the proliferation and spread of mtKRAS malignant cells while lowering tumor fibrosis and immunosuppression. Nutri-hijacker significantly extended the lifespan of pancreatic ductal adenocarcinoma (PDAC)-bearing mice when combined with the hydroxychloroquine-based therapies that failed in clinical trials. Collectively, our findings demonstrated that Nutri-hijacker is a strong KRAS mutation-customized inhibitor and the synthetic lethality based on mtKRAS-driven metabolic addictions might be a promising strategy against PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Camundongos , Proteínas Proto-Oncogênicas p21(ras)/genética , Biomimética , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/metabolismo , Mutação , Neoplasias Pancreáticas
10.
Clin Microbiol Infect ; 29(7): 933-939, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37059224

RESUMO

OBJECTIVES: To evaluate the impact of virtual care in preventing unnecessary healthcare visits for patients with SARS-CoV-2. METHODS: We conducted a retrospective matched cohort study, evaluating the COVID-19 Expansion to Outpatients (COVIDEO) programme involving virtual assessments for all positive patients in the Sunnybrook assessment centre from January 2020 to June 2021, followed by risk-stratified routine follow-up, couriering of oxygen saturation devices, and 24 hour/day direct-to-physician pager for urgent questions. We linked COVIDEO data to province-wide datasets, matching each eligible COVIDEO patient to ≤10 other Ontario SARS-CoV-2 patients on age, sex, neighbourhood, and date. The primary outcome was emergency department (ED) visit, hospitalization or death within 30 days. Multivariable regression accounted for comorbidities, vaccination, and pre-pandemic healthcare utilization. RESULTS: Among 6508 eligible COVIDEO patients, 4763 (73.1%) were matched to ≥1 non-COVIDEO patient. COVIDEO care was protective against the primary composite outcome (adjusted odds ratio [aOR] 0.91, 95% CI, 0.82-1.02), with a reduction in ED visits (7.8% vs. 9.6%; aOR 0.79, 95% CI, 0.70-0.89), but increase in hospitalizations (3.8% vs. 2.7%, aOR 1.37, 95% CI, 1.14-1.63) reflecting more direct-to-ward admissions (1.3% vs. 0.2%, p < 0.0001). Results were similar when matched comparators were limited to patients who had not received virtual care elsewhere with a decrease in ED visits (7.8 vs. 8.6%, aOR 0.86, 95% CI, 0.75-0.99) and an increase in hospitalizations (3.7 vs. 2.4%, aOR 1.45, 95% CI, 1.17-1.80). DISCUSSION: An intensive remote care programme can prevent unnecessary ED visits and facilitate direct-to-ward hospitalizations and thereby mitigate the impact of COVID-19 on the healthcare system.


Assuntos
COVID-19 , Humanos , Estudos de Coortes , COVID-19/epidemiologia , COVID-19/terapia , Estudos Retrospectivos , SARS-CoV-2 , Hospitalização , Assistência Ambulatorial , Serviço Hospitalar de Emergência
11.
Clin Immunol ; 143(2): 180-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22406048

RESUMO

Total glucosides of paeony (TGP), an active compound extracted from Paeony root, has been used in therapy for autoimmune diseases. However the molecular mechanism of TGP in the prevention of autoimmune response remains unclear. In this study, we found that TGP treatment significantly increased the percentage and number of Treg cells in lupus CD4(+) T cells. Further investigation revealed that treatment with TGP increased the expression of Foxp3 in lupus CD4(+) T cells by down-regulating Foxp3 promoter methylation levels. However, we couldn't observe similar results in healthy control CD4(+) T cells treated by TGP. Moreover, our results also showed that IFN-γ and IL-2 expression was enhanced in TGP-treated lupus CD4(+) T cells. These findings indicate that TGP inhibits autoimmunity in SLE patients possibly by inducing Treg cell differentiation, which may in turn be due to its ability to regulate the methylation status of the Foxp3 promoter and activate IFN-γ and IL-2 signaling.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Fatores de Transcrição Forkhead/imunologia , Glucosídeos/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Paeonia , Adulto , Linfócitos T CD4-Positivos/imunologia , Citocinas/genética , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , RNA Mensageiro/imunologia , Adulto Jovem
12.
ACS Appl Mater Interfaces ; 14(24): 27743-27761, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35695238

RESUMO

High level of detrimental factors including reactive oxygen species (ROS) and inflammatory cytokines accumulated in the infarct core and their erosion to salvageable penumbra are key pathological cascades of ischemia-reperfusion injury in stroke. Few neuroprotectants can remodel the hostile microenvironment of the infarct core for the failure to interfere with dead or biofunctionally inactive dying cells. Even ischemia-reperfusion injury is temporarily attenuated in the penumbra by medications; insults of detrimental factors from the core still erode the penumbra continuously along with drug metabolism and clearance. Herein, a strategy named "nanobuffer" is proposed to neutralize detrimental factors and buffer destructive erosion to the penumbra. Inspired by neutrophils' tropism to the infarct core and affinity to inflammatory cytokines, poly(lactic-co-glycolic acid) (PLGA) nanoparticles are coated with neutrophil membrane to target the infarct core and absorb inflammatory cytokines; α-lipoic acid is decorated on the surface and cannabidiol is loaded for ROS scavenging and neuroprotection, respectively, to construct the basic unit of the nanobuffer. Such a nanobuffer exerts a comprehensive effect on the infarct area via detrimental factor neutralization and cannabidiol-induced neuroprotection. Besides, the nanobuffer can possibly be enhanced by dynamic ROP (ring-opening-polymerization)-induced membrane cross-fusion among closely adjacent units in vivo. Systematic evaluations show significant decrease of detrimental factors in the core and the penumbra, reduced infarct volume, and improved neurological recovery compared to the untreated group of stroke rats.


Assuntos
Isquemia Encefálica , Canabidiol , AVC Isquêmico , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Biomimética , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Canabidiol/uso terapêutico , Citocinas , Infarto , Neurônios/metabolismo , Neutrófilos/metabolismo , Ratos , Espécies Reativas de Oxigênio , Acidente Vascular Cerebral/tratamento farmacológico
13.
Front Psychiatry ; 13: 904380, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117658

RESUMO

The World Health Organization (WHO) developed the Caregiver Skills Training for Families of Children with Developmental Delays and Disabilities (CST) with support from Autism Speaks to address the resource gaps and worldwide needs for interventions for children with developmental disorders or delays, especially those with autism spectrum disorder (ASD), and their families. Evidence has indicated that parent-mediated interventions benefit both caregivers and children by strengthening caregivers' knowledge and confidence and children's social communication skills and behavioral regulation. The CST-Taiwan team began the prepilot field trial in 2017 and developed the project to serve families in various locations. This study (1) delineated the adaptations and promotion of CST-Taiwan; (2) determined the program's effectiveness in the promotional stage, in terms of caregiver and child outcomes, and (3) examined the maintenance of its effects. The materials, delivery, and facilitator training procedure of the original CST were adapted to Taiwan. The quantitative data indicated that CST-Taiwan is a promising program, it positively affected caregiver knowledge and confidence and reduced the severity of the children's autistic symptoms. The 3-month follow-up results suggested that the effects persisted. Thus, CST-Taiwan, and its promotional strategies are feasible and effective.

14.
Yao Xue Xue Bao ; 46(11): 1408-12, 2011 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-22260038

RESUMO

To identify the original plant of Daturae Flos from its adulterants by DNA barcoding, the sequences of ITS2, psbA-trnH, matK, rbcL of four species including Datura metel, Darura innoxia, Darura stramonium and Brugmansia arborea were compared and analyzed. The PCR and sequencing success rate of the four regions (ITS2, psbA-trnH, matK, rbcL) was 100%, 90%, 100% and 85%, respectively. Sequences were assembled with CodonCode Aligner. K2P distances were calculated and NJ tree was performed by MEGA 4.1. Thirty SNPs were found among ITS2 sequences, and 33 insert/deletes were found among psbA-trnH intergenic regions. The interspecific K2P distance of ITS2 and psbA-trnH was obviously higher than that of the intraspecific one. As to matK and rbcL, there was no "Barcoding Gap" existing between inter- and intra-specific distances. The NJ trees of the four regions/combinations were built separately. Samples of Brugmansia arborea were clustered into one clade, and the other species of Datura L. formed another clade. The results showed that either ITS2 or psbA-trnH was useful to identify Daturae Flos from its adulterants.


Assuntos
Código de Barras de DNA Taxonômico/métodos , Datura metel/genética , Datura/genética , Contaminação de Medicamentos , Plantas Medicinais/genética , Sequência de Bases , DNA Intergênico/genética , DNA de Plantas/genética , Datura/classificação , Datura stramonium/genética , Flores/genética , Filogenia , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Solanaceae/genética , Especificidade da Espécie
15.
Nat Commun ; 12(1): 3187, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34045459

RESUMO

Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form "micro-thrombi" with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of "micro-thrombi", and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Portadores de Fármacos/química , Neoplasias Mamárias Experimentais/terapia , Metástase Neoplásica/terapia , Nanomedicina Teranóstica/métodos , Animais , Anti-Inflamatórios/administração & dosagem , Anticoagulantes/administração & dosagem , Linhagem Celular Tumoral/transplante , Quimioterapia Adjuvante/métodos , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Heparina de Baixo Peso Molecular/administração & dosagem , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Glândulas Mamárias Animais/patologia , Glândulas Mamárias Animais/cirurgia , Neoplasias Mamárias Experimentais/patologia , Camundongos , Nanopartículas/química , Células Neoplásicas Circulantes/efeitos dos fármacos , Paclitaxel/administração & dosagem , Estudo de Prova de Conceito , Ratos , Estilbenos/administração & dosagem
16.
Zhonghua Zhong Liu Za Zhi ; 32(8): 590-4, 2010 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21122410

RESUMO

OBJECTIVE: To investigate the expression and clinical significance of mismatch repair genes hMLH1 and hMSH2 in sporadic colorectal carcinoma tissues. METHODS: The expression of hMLH1 and hMSH2 proteins was detected in the 63 sporadic colorectal carcinoma samples by immunohistochemical staining, including tumor tissue, adjacent tissue at 3 cm from the carcinoma, and normal tissue at 10 cm away from the tumor. RESULTS: The positive rate of hMLH1 protein expression in the 63 normal colorectal tissues, adjacent tissues and sporadic colorectal carcinoma tissues was 95.2%, 85.7% and 81.0%, respectively. The positive rate of hMLH1 protein expression was significantly lower in the tumor than in normal colorectal tissues (P < 0.05). The positive rate of hMSH2 protein in the 63 normal colorectal tissues, adjacent tissues and sporadic colorectal carcinoma tissues were 76.2%, 66.7% and 52.4%, respectively. The positive rate of hMSH2 protein expression was significantly lower in the tumor than in normal colorectal tissues (P < 0.01). The positive rate of hMLH1 protein expression was significantly higher in the tumor tissue of patients aged younger than 60 years (100%) than that in patients ≥ 60 years (75.0%, P < 0.05). The positive rate of hMLH1 protein expression in the tumor tissue accompanied by lymphatic metastasis was 50.0%, significantly lower than that (93.3%) in tumors without lymphatic metastasis (P < 0.05). The positive rate of hMSH2 protein expression in the tumor tissue of patients aged younger than 60 years was 80.0%, significantly higher than that (43.8%) in the cases ≥ 60 years (P < 0.05). The positive rate of hMSH2 protein expression in the tumor tissues with invasion reaching to the intestinal serosa (61.5%) was significantly higher than that (37.5%) in the tumors invading to submucosa or muscular layer (P < 0.05). There was a positive correlation between the expressions of hMLH1 and hMSH2 proteins in the sporadic colorectal carcinomas. CONCLUSION: There is a certain loss of expression of hMLH1 and hMSH2 proteins in sporadic colorectal carcinoma, and is correlated with the age of patients, lymphatic metastasis and different depth of cancer invasion. HMLH1 and hMSH2 may be used as a useful laboratory marker in clinical judgement of occurrence and development of sporadic colorectal carcinoma.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Neoplasias do Colo/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Retais/metabolismo , Adenocarcinoma/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Invasividade Neoplásica , Neoplasias Retais/patologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-32503092

RESUMO

OBJECTIVE: Disease-modifying drugs (DMDs) may alter the immune status and thus increase the susceptibility to coronavirus disease 2019 (COVID-19) in patients with MS or neuromyelitis optica spectrum disorders (NMOSD). However, evidence supporting this notion is currently lacking. In this study, we conducted a survey on the risk of COVID-19 in patients with MS and NMOSD. METHODS: The survey was conducted through the Chinese Medical Network for Neuroinflammation. Patients in 10 MS centers from 8 cities including Wuhan were included. Information about MS and NMOSD disease duration and the usage of DMDs were collected. Data of suspected cases of COVID-19 were obtained from hospital visits, questionnaires, and patient self-reporting. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was confirmed through clinical evaluation by a panel of experts in conjunction with chest CT and viral RNA detection. RESULTS: Eight hundred eighty-two of 1,804 (48.89%) patients with MS and 2,129 of 3,060 (69.58%) patients with NMOSD were receiving DMDs. There were no alterations in the patients' DMD regimen during January 15, 2020, to March 15, 2020, the 3-month period. None of the patients with MS treated with DMDs had COVID-19. However, 2 patients with relapsing NMOSD were diagnosed with COVID-19-related pneumonia. After treatment, both patients recovered from pneumonia and neither patient experienced new attacks due to predisposing SARS-CoV-2 infection in the following 2 months. CONCLUSIONS: No increased risk of COVID-19 infection was observed in patients with MS or NMOSD, irrespective of whether these patients received DMDs. A battery of stringent preventive measures adopted by neurologists to reduce COVID-19 infection in these patients may have contributed to low risk of COVID-19 infection.


Assuntos
Infecções por Coronavirus/epidemiologia , Imunossupressores/uso terapêutico , Esclerose Múltipla/epidemiologia , Neuromielite Óptica/epidemiologia , Pneumonia Viral/epidemiologia , COVID-19 , China/epidemiologia , Suscetibilidade a Doenças , Humanos , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Neuromielite Óptica/tratamento farmacológico , Pandemias , Risco
18.
Chin Med J (Engl) ; 131(23): 2776-2784, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30511679

RESUMO

BACKGROUND: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. METHODS: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). RESULTS: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. CONCLUSIONS: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.


Assuntos
Crotonatos/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Toluidinas/uso terapêutico , China , Crotonatos/administração & dosagem , Crotonatos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Humanos , Hidroxibutiratos , Imunossupressores/administração & dosagem , Estudos Multicêntricos como Assunto , Esclerose Múltipla/metabolismo , Nitrilas , Modelos de Riscos Proporcionais , Toluidinas/administração & dosagem , Toluidinas/efeitos adversos
19.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 19(7): 390-3, 2007 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-17631702

RESUMO

OBJECTIVE: To evaluate influence of recombinant human growth hormone (rhGH) on nutritional status and immune function in early postoperative stage of liver transplantation including hepatic function, acute rejection and infection rate, in order to assess its safety in clinical use. METHODS: Sixty patients with non-malignant diseases of the liver in terminal stages were randomly divided into two groups: treatment group (rhGH treatment n=30) and control group (n=30). All the patients received the same nutritional support and immunodepressant treatment regimes. The patients in treatment group received rhGH 10 U hypodermically daily for 10 days 24 hours after liver transplantation. The following parameters including siderophilin, prealbumin, albumin, urea nitrogen, CD4/CD8, immunoglobulin G (IgG), IgM, IgA, growth hormone (GH), insulin-like growth factor-1 (IGF-1), aspartate aminotransferase (AST), alanine aminotransferase (ALT), dosage of insulin to control blood sugar (8-10 mmol/L) were determined on 1st, 4th, 8th, 14th days after the operation, and acute rejection rate after 28 days of operation (confirmed by liver acupuncture biopsy), and infection rate were also assessed. RESULTS: Compared with control group, levels of siderophilin, prealbumin, CD4/CD8, GH, IGF-1 within 14 days in treatment group were increased significantly 14 days after the operation (all P<0.05), and level of urea nitrogen was decreased significantly (P<0.05). The level of albumin in treatment group was lower than that in control group 14 days after operation (P<0.05), while dosages of exogenous insulin were higher on 4th and 8th days after operation than that in control group (both P<0.05). There were no significant differences in levels of AST, ALT within 14 days, or acute rejection rate and infection rate within 28 days between two groups (all P>0.05). CONCLUSION: rhGH can accelerate recovery of nutritional status in the early liver transplantation period. It does not show superiority in improving immune function and influence on recovery of hepatic function, acute rejection or infection rate. The safety has been challenged by inducing high blood sugar as a side effect.


Assuntos
Hormônio do Crescimento Humano/uso terapêutico , Imunidade/efeitos dos fármacos , Transplante de Fígado , Estado Nutricional/efeitos dos fármacos , Adolescente , Adulto , Idoso , Glicemia , Criança , Feminino , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Apoio Nutricional , Período Pós-Operatório , Estudos Prospectivos , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-16321580

RESUMO

A new, simple and rapid high-performance liquid chromatography (HPLC) method with UV detection has been developed for the determination of apovincaminic acid in human plasma. Apovincaminic acid and internal standard were isolated from plasma samples by solid-phase extraction with OASIS HLB cartridges. The chromatographic separation was accomplished on a reversed-phase C(18) column and UV detection was set at 311 nm. The calibration curves were linear in the concentration range of 2.4-240.0 ng/ml, and the limits of quantification was 2.4 ng/ml. The precision and accuracy ranged from 0.84 to 8.54% and 91.5 to 108.3%, respectively. The developed method was subsequently applied to study the pharmacokinetics of apovincaminic acid in a group of 20 human subjects at a single oral dose of 10mg of vinpocetine tablet.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Alcaloides de Vinca/sangue , Calibragem , Humanos , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta/métodos , Alcaloides de Vinca/isolamento & purificação
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