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1.
World J Surg Oncol ; 22(1): 42, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310233

RESUMO

AIMS: To present a case series of 11 rare uterine tumors resembling ovarian sex cord tumors (UTROSCTs), and review the literature on this topic to offer up-to-date treatment management for UTROSCTs. METHOD: Eight cases from Fujian Cancer Hospital between January 2017 and May 2023 and three patients from Fujian Union Hospital between October 2012 and October 2020 were retrospectively reviewed. All cases were pathologically confirmed as UTROSCTs by two senior and experienced pathologists. Clinical behaviors, medical data, histopathological features, therapy approaches, and survival outcomes were discussed. RESULTS: The median age at initial diagnosis was 53 years (29-70 years). 3 (27.3%) patients were under 40. Seven cases presented with abnormal vaginal bleeding, one with menstrual disorder, one with abnormal vaginal secretion, and two patients were accidentally found by physical examination without any symptoms. Three patients were initially misdiagnosed with endometrial cancer by MRI. Curettage was performed in all cases. Nine of them were well diagnosed by routine curettage, except for two samples, which were identified after surgery. Immunohistochemical biomarkers, such as CD99, Desmin, WT-1, CK, Vimentin, SMA, α-Inhibin, Ki67, CD56, ER, PR, and CR, tend to be positive in UTRO SCs patients. Six patients underwent hysterectomy with bilateral salpingo-oophorectomy. Two cases received a radical hysterectomy with bilateral salpingo-oophorectomy, retroperitoneal lymph node dissection, and omentum dissection. Three UTROSCTs were under observation after mass resection. The median PFS was 24 months (range 1-125 months). CONCLUSION: UTROSCT is a rare mesenchymal tumor with low malignant potential. Treatment modalities should be carefully considered to balance the therapy outcomes and patient needs. Surgery conservative management might be suitable for young women with fertility desires.


Assuntos
Neoplasias do Endométrio , Neoplasias Ovarianas , Neoplasias Uterinas , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia , Neoplasias do Endométrio/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Histerectomia
2.
Int Microbiol ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37987892

RESUMO

We determined whether there exists a complementary pathway of cordycepin biosynthesis in wild-type Cordyceps militaris, high-cordycepin-producing strain C. militaris GYS60, and low-cordycepin-producing strain C. militaris GYS80. Differentially expressed genes were identified from the transcriptomes of the three strains. Compared with C. militaris, in GYS60 and GYS80, we identified 145 and 470 upregulated and 96 and 594 downregulated genes. Compared with GYS80, in GYS60, we identified 306 upregulated and 207 downregulated genes. Gene Ontology analysis revealed that upregulated genes were mostly involved in detoxification, antioxidant, and molecular transducer in GYS60. By Clusters of Orthologous Groups of Proteins and Kyoto Encyclopedia of Genes and Genomes analyses, eight genes were significantly upregulated: five genes related to purine metabolism, one to ATP production, one to secondary metabolite transport, and one to RNA degradation. In GYS60, cordycepin was significantly increased by upregulation of ATP production, which promoted 3',5'-cyclic AMP production. Cyclic AMP accelerated 3'-AMP accumulation, and cordycepin continued to be synthesized and exported. We verified the novel complementary pathway by adding the precursor adenosine and analyzing the expression of four key genes involved in the main pathway of cordycepin biosynthesis. Adenosine addition increased cordycepin production by 51.2% and 10.1%, respectively, in C. militaris and GYS60. Four genes in the main pathway in GYS60 were not upregulated.

3.
Cancer Med ; 12(24): 21798-21806, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37994611

RESUMO

OBJECT: This study aimed to establish an effective risk nomogram to predict the early distant metastasis (EDM) probability of cervical cancer (CC) patients treated with radical radiotherapy to aid individualized clinical decision-making. METHODS: A total of 489 patients with biopsy-confirmed CC between December 2018 and January 2021 were enrolled. Logistic regression with the stepwise backward method was used to identify independent risk factors. The nomogram efficacy was evaluated by using the area under the receiver operating characteristic curve (AUC), C-index by 1000 bootstrap replications, etc. Finally, patients were divided into high- and low-risk groups of EDM based on the cut-off value of nomogram points. RESULTS: 36 (7.36%) CC patients had EDM, and 20 (55.6%) EDM had more than one metastatic site involved. Age below 51 (OR = 2.298, p < 0.001), tumor size larger than 4.5 cm (OR = 3.817, p < 0.001) and radiotherapy (OR = 3.319, p < 0.001) were independent risk factors of EDM. For the nomogram model, C-index was 0.701 (95% CI = 0.604-0.798), and 0.675 (95% CI = 0.578-0.760) after 1000 bootstrap resampling validations. The Hosmer-Lemeshow test demonstrated no overfitting (p = 0.924). According to the Kaplan-Meier curve of risk score, patients with high risk were more prone to get EDM (p < 0.001). CONCLUSION: This is the first research to focus on EDM in CC patients. We have developed a robust scoring system to predict the risk of EDM in CC patients to screen out appropriate cases for consolidation therapy and more intensive follow-up.


Assuntos
Nomogramas , Neoplasias do Colo do Útero , Feminino , Humanos , Prognóstico , Neoplasias do Colo do Útero/radioterapia , Estudos Retrospectivos , Medição de Risco
4.
J Cancer Res Clin Oncol ; 149(14): 13201-13210, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37479758

RESUMO

PURPOSE: Cervical cancer (CC) patients are more likely to develop second primary malignancies (SPMs) than general population. With the advancement in cancer therapy, CC patients are achieving long-term survival, leading SPMs to our attention. Our study aims to establish diagnostic and prognostic nomograms for CC patients with second primary malignancies (CCSPMs) to help make personalized follow-up plans and treatments. METHODS: Data of CCSPMs between 2000 and 2019 was extracted from SEER. The proportions and the median interval time of CCSPM onset were calculated. 11 related clinical characteristics, including age, race, marital status, grade, FIGO stage, radiotherapy, chemotherapy, and surgery, were further explore. Logistic and Cox regressions were employed to predict risk factors for CCSPMs diagnosis. Finally, two nomograms were developed to predict the probability occurrence and prognosis of CCSPMs, respectively. RESULTS: For diagnostic nomogram construction, 59,178 CC patients were randomly divided into training (n = 41,426) and validation cohorts (n = 17,752). For prognostic nomogram construction, 3527 CCSPMs patients were randomly divided into training (n = 2469) and validation cohorts (n = 1058). The diagnostic nomogram consisting of above 11 independent risk factors (all P < 0.05), had high accuracy (AUCtraining = 0.851 and AUCvalidating = 0.845). The prognostic nomogram integrated with eight independent prognostic factors such as treatments, FIGO stage and TNM stage performed well in predicting 5-year OS (AUCtraining = 0.835 and AUCvalidating = 0.837). CONCLUSION: Our diagnostic and prognostic nomograms could facilitate clinicians to quantify individual SPMs risk and survival probabilities and optimize the surveillance recommendations and personalized clinical decision-making.

5.
BMC Cancer ; 22(1): 1160, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357839

RESUMO

BACKGROUND: In recent years, it has been proved that necroptosis plays an important role in the occurrence, development, invasion, metastasis and drug resistance of malignant tumors. Hence, further evaluation and targeting of necroptosis may be of clinical benefit for gynecologic cancers (GCs). METHODS: To compare consistency and difference, we explored the expression pattern and prognostic value of necroptosis-related genes (NRGs) in pan-GC analysis through Linear regression and Empirical Bayesian, Univariate Cox analysis, and public databases from TCGA and Genotype-Tissue Expression (GTEx), including CESC, OV, UCEC, and UCS. We explored the copy number variation (CNV), methylation level and enrichment pathways of NRGs in the four GCs. Based on LASSO Cox regression analysis or principal component analysis, we established the prognostic NRG-signature or necroptosis-score for the four GCs. In addition, we predicted and compared functional pathways, tumor mutational burden (TMB), somatic mutation features, immunity status, immunotherapy, chemotherapeutic drug sensitivity of the NRG-signature based on NRGs. We also examined the expression level of several NRGs in OV samples that we collected using Quantitative Real-time PCR. RESULTS: We confirmed the presence of NRGs in expression, prognosis, CNV, and methylation for four GCs, thus comparing the consistency and difference among the four GCs. The prognosis and independent prognostic value of the risk signatures based on NRGs were determined. Through the results of subclass mapping, we found that GC patients with lower risk score may be more sensitive to PDL1 response and more sensitive to immune checkpoint blockade therapy. Drug susceptibility analysis showed that, 51, 45, 64, and 29 drugs with differences between risk groups were yielded in CESC, OV, UCEC, and UCS respectively. For OV, the expression differences of several NRGs in the tissues we collected were similar to that in TCGA. CONCLUSION: Our comprehensive analysis of NRGs and NRG-signature demonstrated their similarity and difference, as well as their potential roles in prognosis and could guide therapeutic strategies, thus improving the outcome of GC patients.


Assuntos
Neoplasias dos Genitais Femininos , Necroptose , Humanos , Feminino , Necroptose/genética , Variações do Número de Cópias de DNA , Teorema de Bayes , Prognóstico , Neoplasias dos Genitais Femininos/genética
6.
Molecules ; 27(12)2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35745031

RESUMO

Metal organic frameworks (MOFs) are formed by self-assembly of metal ions and organic ligands. A special type of MOF called ZIF-8, which is formed by self-assembly of zinc ions and 2-methylimidazole, shows excellent stability in aqueous solutions and disintegrates under acidic conditions. These properties make ZIF-8 a suitable carrier material for pH-stimulated drug delivery systems. Glabridin is an isoflavane compound that is widely present in the roots of licorice. Because of its outstanding skin whitening properties, glabridin is widely used as a whitener in the cosmetics industry. In this study, ZIF-8 was employed to encapsulate glabridin. Glabridin-loaded ZIF-8 was successfully prepared with a drug encapsulation efficiency of 98.67%. The prepared sample showed a fusiform or cruciate flower-like structure, and its size was about 3 µm. ZIF-8 enabled pH-controlled release of glabridin. Moreover, ZIF-8 encapsulation significantly enhanced the intracellular anti-oxidant activity and melanogenesis inhibitory activity of glabridin. This study provides a new approach that shows great potential to improve the biological application of glabridin.


Assuntos
Estruturas Metalorgânicas , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Isoflavonas , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Fenóis/farmacologia
7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(2): 146-152, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35356883

RESUMO

Objective To investigate the role of circular RNA cleavage and polyadenylation specificity factor 6 (circRNA CPSF6) in the apoptosis of trophoblast cells induced by homocysteine (Hcy) and its mechanism. Methods HTR-8/SVneo human chorionic trophoblast cells were cultured in vitro and divided into control group (0 mmol/L Hcy treatment) and 1 mmol/L Hcy treatment group. Immunofluorescence cytochemical staining was used to detect the expression of caspase-3 in trophoblasts, and Western blot analysis was used to detect the caspase-3 protein level. The mRNA expression level of circRNA CPSF6 was detected by real-time quantitative PCR. Small interfering RNA (siRNA) was used to knock down the expression of circRNA CPSF6 in trophoblast cells. The expressions of caspase-3, caspase-9, Bcl2, and BAX were detected by Western blot analysis. Real-time quantitative PCR was used to detect the expression level of circRNA CPSF6 in the cytoplasm/nucleus of trophoblast cells before and after Hcy treatment. Results Compared with those in the control group, the expressions of caspase-3 and circRNA CPSF6 mRNA in the Hcy treatment group significantly increased. After knocking down circRNA CPSF6, the expression of caspase-3 decreased, and the mitochondrial apoptosis pathway was inhibited. In normal cultured trophoblast cells, circRNA CPSF6 was expressed in large amounts in the cytoplasm, and after Hcy treatment, circRNA CPSF6 was mainly expressed in the nucleus. Conclusion The mitochondrial apoptotic pathway is activated by circRNA CPSF6 nuclear translocation to promote trophoblast apoptosis induced by Hcy.


Assuntos
RNA Circular , Trofoblastos , Apoptose/genética , Homocisteína/metabolismo , Homocisteína/farmacologia , Humanos , Mitocôndrias/metabolismo , Trofoblastos/metabolismo
8.
Plant Biotechnol J ; 20(6): 1054-1068, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35114063

RESUMO

The pollen wall exine provides a protective layer for the male gametophyte and is largely composed of sporopollenin, which comprises fatty acid derivatives and phenolics. However, the biochemical nature of the external exine is poorly understood. Here, we show that the male sterile line 1355A of cotton mutated in NO SPINE POLLEN (GhNSP) leads to defective exine formation. The GhNSP locus was identified through map-based cloning and confirmed by genetic analysis (co-segregation test and allele prediction using the CRISPR/Cas9 system). In situ hybridization showed that GhNSP is highly expressed in tapetum. GhNSP encodes a polygalacturonase protein homologous to AtQRT3, which suggests a function for polygalacturonase in pollen exine formation. These results indicate that GhNSP is functionally different from AtQRT3, the latter has the function of microspore separation. Biochemical analysis showed that the percentage of de-esterified pectin was significantly increased in the 1355A anthers at developmental stage 8. Furthermore, immunofluorescence studies using antibodies to the de-esterified and esterified homogalacturonan (JIM5 and JIM7) showed that the Ghnsp mutant exhibits abundant of de-esterified homogalacturonan in the tapetum and exine, coupled with defective exine formation. The characterization of GhNSP provides new understanding of the role of polygalacturonase and de-esterified homogalacturonan in pollen exine formation.


Assuntos
Regulação da Expressão Gênica de Plantas , Poligalacturonase , Fertilidade , Pectinas/metabolismo , Pólen/genética , Pólen/metabolismo , Poligalacturonase/genética , Poligalacturonase/metabolismo
9.
Mater Horiz ; 8(4): 1199-1206, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821912

RESUMO

Synaptic vesicle-inspired nanoparticles (RT-PPB NPs) as a "nanoguard" were designed for clearing the toxic α-synuclein aggregates in diseased neurons and preventing the culprits from escaping to affect other normal cells. The NPs could overcome a series of tissue and cellular barriers and controllably release drugs in the diseased neurons, which ensured the optimization of synergistic treatment. This study indicates that the synaptic vesicle-inspired NPs may have the potential to open up a new avenue for the treatment of synucleinopathies, as well as other neurodegenerative diseases.


Assuntos
Nanopartículas , Sinucleinopatias , Preparações de Ação Retardada , Humanos , Neurônios , Vesículas Sinápticas , alfa-Sinucleína
10.
Front Psychiatry ; 12: 707326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658951

RESUMO

Ketamine is a glutamate N-methyl D-aspartate receptor antagonist and an anaesthetic agent that has been effectively used to treat depression. However, ketamine has also been increasingly used for recreational purposes. The dissociative side-effects of ketamine use, such as hallucinations, are the reason for abuse. Additionally, long-term ketamine abuse has been highly associated with liver-gallbladder and urinary symptoms. The present study reports the case of a 28-year-old young male adult with an 8-year history of daily inhalation of ketamine. We investigated the association between ketamine abuse and the mechanism of its adverse effects, particularly encephalatrophy, and attempted to find a link between these disorders. These results would help us to better understand ketamine usage, ketamine abuse effects and the addictive mechanism. To the best of our knowledge, the present case is the first report of severe brain atrophy related to ketamine abuse. Details of the patient are presented and the mechanism of the encephalatropy-associated ketamine abuse is discussed. Furthermore, organ dysfunction following chronic ketamine abuse may indicate that the side effects are the result of comprehensive action on multiple regions in the brain.

11.
Sci Adv ; 6(50)2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33310840

RESUMO

The most critical problem in the treatment of neurodegenerative diseases is brain neuronal protection, which can be overcome by clearing pathological substances and regulating the immune environment. In the above treatment strategies, the traditional poor drug delivery problem is inevitable. Here, we show an engineering core-shell hybrid system named rabies virus glycoprotein (RVG) peptide-modified exosome (EXO) curcumin/phenylboronic acid-poly(2-(dimethylamino)ethyl acrylate) nanoparticle/small interfering RNA targeting SNCA (REXO-C/ANP/S). It is a nanoscavenger for clearing α-synuclein aggregates and reducing their cytotoxicity in Parkinson's disease neurons. The motor behavior of Parkinson's disease mice is substantially improved after REXO-C/ANP/S treatment. In particular, we demonstrate that REXO-C/ANP/S is also a nanoscavenger for clearing immune activation due to its natural immature dendritic cell EXO coating. Our findings show that REXO-C/ANP/S may serve as a platform for neurodegenerative diseases treatment.


Assuntos
Exossomos , Doenças Neurodegenerativas , Doença de Parkinson , Animais , Fator Natriurético Atrial , Exossomos/genética , Camundongos , Doença de Parkinson/genética , Doença de Parkinson/patologia , alfa-Sinucleína/genética
12.
J Biomed Nanotechnol ; 16(6): 931-940, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33187588

RESUMO

Amino acids are significant for human life and therefore considered as the crucial nutrients for human body with high biosafety. Due to their high biocompatibilities and various physicochemical properties, their polymers can be applied to construct drug delivery systems for various diseases' treatments. Among them, glioblastoma multiforme received special attention and numerous efforts regarding to nanotechnology were developed to treat such tumor. However, the biosafety of the delivering materials in those efforts arises as a critical issue in consideration of the weak patients. Therefore, a ROSresponsive nanoparticle (DOX@PLSPL) with poly(amino acids) encapsulating doxorubicin was developed for glioblastoma multiforme treatment. DOX@PLSPL was constructed by poly-lysine and poly-leucine with high biocompatibility. The high doxorubicin encapsulation efficiency and the controlled release manner of DOX@PLSPL ensured its high anti-tumor effect. Totally, this DOX@PLSPL can be used as a promising drug delivery system for glioblastoma multiforme treatments.


Assuntos
Glioblastoma , Nanopartículas , Aminoácidos , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Humanos , Concentração de Íons de Hidrogênio , Espécies Reativas de Oxigênio
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1143-1145, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924121

RESUMO

OBJECTIVE: To explore the genetic basis for a fetus with autosomal recessive polycystic kidney disease (ARPKD). METHODS: Fetal tissue and peripheral blood samples were respectively obtained from the abortus and the couple. Following extraction of genomic DNA, genetic testing was carried out. RESULTS: The fetus was found to carry compound heterozygous variants of the PKHD1 gene, namely c.5336A>T (p.N1779I) and c.9455delA (p.N3152Tfs*10), which were respectively inherited from the husband and wife. CONCLUSION: The c.5336A>T and c.9455delA variants of the PKHD1 gene probably account for the ARPKD in the fetus. Above results have enabled genetic counseling and prenatal diagnosis for the couple.


Assuntos
Rim Policístico Autossômico Recessivo , Receptores de Superfície Celular/genética , Feminino , Feto , Testes Genéticos , Humanos , Mutação , Rim Policístico Autossômico Recessivo/genética , Gravidez
14.
Adv Sci (Weinh) ; 7(2): 1901555, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31993283

RESUMO

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive and memory loss. The vicious circle between dysfunctional microglia and amyloid-ß (Aß) is a crucial pathological event and accelerates the progression of AD. Herein, a zwitterionic poly(carboxybetaine) (PCB)-based nanoparticle (MCPZFS NP) with normalizing the dysfunctional microglia and Aß recruitment is established for the treatment of AD. Compared with the neural polyethylene glycol (PEG)-based nanoparticles (MEPZFS NPs), the MCPZFS NPs significantly alleviate the priming of microglia by decreasing the level of proinflammatory mediators and promoting the secretion of BDNF. Most importantly, quite different from PEG, the PCB-based NPs exhibit the behavior to recruit Aß into microglia, which significantly enhances the Aß phagocytosis. Moreover, the Aß degradation is changed from the conventional lysosomal/autophagy to the proteasomal pathway in the presence of MCPZFS NPs. After the treatment with MCPZFS NPs, the Aß burden, neuron damages, memory deficits, and neuroinflammation of APPswe/PS1dE9 mice are significantly attenuated in the brain. Therefore, the PCB-based MCPZFS NPs have great potential to serve as an "Aß cleaner" and provide a new insight into the therapeutic strategy for AD therapy.

15.
Clin Cancer Res ; 26(3): 738-745, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31653641

RESUMO

PURPOSE: Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2+ breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is unclear.Experimental Design: Hematoxylin and eosin-stained slides (n = 59) were used to score stromal (s-)TILs from pretreatment biopsies of patients enrolled in the neoadjuvant TBCRC006 trial of 12-week lapatinib plus trastuzumab therapy (plus endocrine therapy for ER+ tumors). A 60% threshold was used to define lymphocyte-predominant breast cancer (LPBC). Multiplexed immunofluorescence (m-IF) staining (CD4, CD8, CD20, CD68, and FoxP3) and multispectral imaging were performed to characterize immune infiltrates in single formalin-fixed paraffin-embedded slides (n = 33). RESULTS: The pathologic complete response (pCR) rate was numerically higher in patients with LPBC compared with patients with non-LPBC (50% vs. 19%, P = 0.057). Unsupervised hierarchical clustering of the five immune markers identified two patient clusters with different responses to lapatinib plus trastuzumab treatment (pCR = 7% vs. 50%, for cluster 1 vs. 2 respectively; P = 0.01). In multivariable analysis, cluster 2, characterized by high CD4+, CD8+, CD20+ s-TILs, and high CD20+ intratumoral TILs, was independently associated with a higher pCR rate (P = 0.03). Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by s-CD4, intratumoral (i-) CD4, and i-CD20+ TILs. CONCLUSIONS: LPBC was marginally associated with higher pCR rate than non-LPBC in patients with lapatinib plus trastuzumab treated HER2+ breast cancer. Quantitative assessment of the immune infiltrate by m-IF is feasible and may help correlate individual immune cell subpopulations and immune cell profiles with treatment response.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos/imunologia , Terapia Neoadjuvante/métodos , Receptor ErbB-2/imunologia , Receptor ErbB-2/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Lapatinib/administração & dosagem , Linfócitos/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Pessoa de Meia-Idade , Prognóstico , Trastuzumab/administração & dosagem
16.
Chem Commun (Camb) ; 55(5): 596-599, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30480678

RESUMO

Fluorescent nanoarchitectures, such as hydrophobic micelles and hydrophilic vesicles decorated with fluorescent carbon nanoparticles, were fabricated from one fatty acid by means of photo-triggering. The biomimetic nanostructures, like cell membrane structures, have applications in fluorescence imaging in both the cell cytoplasm and nucleus. Besides, hydrophobic micelles can be used as very stable fluorescent inks.


Assuntos
Materiais Biomiméticos/química , Ácidos Graxos/química , Corantes Fluorescentes/química , Nanopartículas/química , Células A549 , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/efeitos da radiação , Materiais Biomiméticos/toxicidade , Carbono/química , Carbono/efeitos da radiação , Carbono/toxicidade , Ácidos Graxos/efeitos da radiação , Ácidos Graxos/toxicidade , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Humanos , Interações Hidrofóbicas e Hidrofílicas , Tinta , Membranas Artificiais , Micelas , Microscopia Confocal , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Raios Ultravioleta , Água/química
17.
Theranostics ; 8(19): 5469-5481, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555558

RESUMO

α-synclein (αS) aggregation is a representative molecular feature of the pathogenesis of Parkinson's disease (PD). Epigallocatechin gallate (EGCG) can prevent αS aggregation in vitro. However, the in vivo effects of PD treatment are poor due to the obstacles of EGCG accumulation in dopaminergic neurons, such as the blood brain barrier and high binding affinities between EGCG and membrane proteins. Therefore, the key to PD treatment lies in visual examination of EGCG accumulation in dopaminergic neurons. Methods: DSPE-PEG-B6, DSPE-PEG-MA, DSPE-PEG-phenylboronic acid, and superparamagnetic iron oxide nanocubes were self-assembled into tracing nanoparticles (NPs). EGCG was then conjugated on the surface of the NPs through the formation of boronate ester bonds to form a "cell-addictive" dual-target traceable nanodrug (B6ME-NPs). B6ME-NPs were then used for PD treatment via intravenous injection. Results: After treatment with B6ME-NPs, the PD-like characteristics was alleviated significantly. First, the amount of EGCG accumulation in PD lesions was markedly enhanced and traced via magnetic resonance imaging. Further, αS aggregation was greatly inhibited. Finally, the dopaminergic neurons were considerably increased. Conclusion: Due to their low price, simple preparation, safety, and excellent therapeutic effect on PD, B6ME-NPs are expected to have potential application in PD treatment.


Assuntos
Catequina/análogos & derivados , Neurônios Dopaminérgicos/metabolismo , Proteínas de Membrana/metabolismo , Terapia de Alvo Molecular/métodos , Nanopartículas/administração & dosagem , Fármacos Neuroprotetores/farmacocinética , Doença de Parkinson/tratamento farmacológico , Animais , Animais Geneticamente Modificados , Catequina/administração & dosagem , Catequina/farmacocinética , Linhagem Celular , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Humanos , Camundongos , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson/patologia , Agregação Patológica de Proteínas , Resultado do Tratamento , alfa-Sinucleína/análise
18.
J Am Chem Soc ; 140(11): 4164-4171, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29486118

RESUMO

Due to the vast differences in chemical properties among small molecule drugs, nucleotide drugs, and superparamagnetic iron oxide nanocubes (SPIONs), such as charge and hydrophobicity, entrapment of these within a single carrier for traceable synergistic therapy has been proven difficult. Herein, we synthesize positively charged polyprodrug amphiphiles. The hydrophobic polyprodrug unit of the amphiphiles is positively charged, which can simultaneously load hydrophobic SPIONs and absorb negative let-7b antisense oligonucleotide to construct traceable co-delivery nanoparticles (NPs). This characteristic avoids the use of inert materials and enhances drug loading of the traceable NPs. The traceable NPs can achieve controlled release of drugs to reduce the differentiation of exogenous neural stem cells (NSCs) and enhance their secretion of brain-derived neurotrophic factor (BDNF) synergistically. Exogenous NSCs treated with the NPs significantly rescue the memory deficits in 2xTg-AD mice. In addition, the transplantation site and migration of exogenous NSCs can be traced using the SPIONs with high r2 value for magnetic resonance imaging. Therefore, traceable NPs self-assembled from the positively charged polyprodrug amphiphiles may have the potential to open up a new avenue for treatment of Alzheimer's disease (AD), as well as other neurodegenerative disorders.


Assuntos
Nanopartículas de Magnetita/química , Doenças Neurodegenerativas/tratamento farmacológico , Polímeros/farmacologia , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tensoativos/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Estrutura Molecular , Células-Tronco Neurais/efeitos dos fármacos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Polímeros/química , Pró-Fármacos/química , Tensoativos/química
19.
Curr Med Chem ; 25(25): 2987-3000, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28393688

RESUMO

Nanomedicine is widely developed in recent years. In nanomedicine system, nanoscale and nanostructured functional materials are used to manipulate the human biology systems at the molecular level for cancer imaging and therapy. New nanostructure based functional materials consist of nanoscale liposomes, spheres, micelles, capsules, emulsion, suspension and phamacosomes. Several functional nanoparticles such as lipidbased and polymer-based materials are demonstrated to be drug delivery vehicles and imaging agents. These materials are biodegradable, biocompatible and have better biodistribution, lower side effect and lower toxicity. In addition, hybrids with these materials coating provide uniquely electrical, optical and magnetic properties. This review discusses the research on the applications of functional materials, especially nanoparticles as imaging contrast agents, cancer therapeutic agents and multi-functional agents and this review focused on the theranostic integration treatments on liver cancer and brain cancer.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Meios de Contraste/análise , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Nanoestruturas/uso terapêutico , Nanomedicina Teranóstica , Materiais Biocompatíveis/química , Meios de Contraste/química , Humanos , Nanoestruturas/química
20.
BMC Neurol ; 17(1): 105, 2017 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-28577542

RESUMO

BACKGROUND: The effectiveness of creatine in treating Parkinson's disease (PD) has not been conclusively determined. Therefore, we performed a meta-analysis to address this issue. METHODS: The Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, and other databases were searched, and outcomes measured by the Total Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab & England Scale were analyzed. RESULTS: Five randomized controlled trials (RCTs) were selected, and 1339 participants were included in the analysis. There were no significant differences between the control and treatment groups in the total, mental, activities of daily living (ADL), or motor UPDRS scores, but an improvement in Schwab & England Scale scores was observed. CONCLUSIONS: Creatine has no observed benefit in PD patients, although more correlated studies are still needed.


Assuntos
Creatina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Atividades Cotidianas , Humanos , Resultado do Tratamento
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