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1.
J Mater Chem B ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34842264

RESUMO

The non-invasive treatment of glioblastoma (GBM) is of great significance and can greatly reduce the complications of craniotomy. Sonodynamic therapy (SDT) is an emerging tumor therapeutic strategy that overcomes some fatal flaws of photodynamic therapy (PDT). Different from PDT, SDT has deep tissue penetration and can be applied in the non-invasive treatment of deep-seated tumors. However, effective sonosensitizers that can be used for SDT of GBM are still very rare. Herein, we have prepared a suitable assembly based on a hypocrellin derivative (CTHB) with good biocompatibility. Excitedly, the hypocrellin-based assembly (CTHB NPs) can effectively produce reactive oxygen species under ultrasound stimulation. The inherent fluorescence and photoacoustic imaging characteristics of the CTHB NPs are conducive to the precise positioning of the tumors. It has been proved both in subcutaneous and in intracranial tumor models that CTHB NPs can be used as an effective sonosensitizer to inhibit tumor growth under ultrasound irradiation. This hypocrellin-based assembly has a good clinical prospect in the non-invasive treatment of GBM.

2.
Adv Sci (Weinh) ; 8(22): e2102741, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34623034

RESUMO

Supramolecular self-assemblies of dendritic peptides with well-organized nanostructures have great potential as multifunctional biomaterials, yet the complex self-assembly mechanism hampers their wide exploration. Herein, a self-stabilized supramolecular assembly (SSA) constructed from a PEGylated dendritic peptide conjugate (PEG-dendritic peptide-pyropheophorbide a, PDPP), for augmenting tumor retention and therapy, is reported. The supramolecular self-assembly process of PDPP is concentration-dependent with multiple morphologies. By tailoring the concentration of PDPP, the supramolecular self-assembly is driven by noncovalent interactions to form a variety of SSAs (unimolecular micelles, oligomeric aggregates, and multi-aggregates) with different sizes from nanometer to micrometer. SSAs at 100 nm with a spherical shape possess extremely high stability to prolong blood circulation about 4.8-fold higher than pyropheophorbide a (Ppa), and enhance tumor retention about eight-fold higher than Ppa on day 5 after injection, which leads to greatly boosting the in vivo photodynamic therapeutic efficiency. RNA-seq demonstrates that these effects of SSAs are related to the inhibition of MET-PI3K-Akt pathway. Overall, the supramolecular self-assembly mechanism for the synthetic PEGylated dendritic peptide conjugate sheds new light on the development of supramolecular assemblies for tumor therapy.

3.
ACS Omega ; 6(40): 26575-26582, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34661012

RESUMO

The design and synthesis of single-molecule amphiphilic and multifunctional phototherapeutic agents are important to cancer diagnosis and therapy. In this work, we developed three amphiphilic diketopyrrolopyrrole derivatives (TPADPP, DTPADPP, and TPADDPP) with different donor-acceptor structures and poly(ethylene glycol) side chains. The corresponding nanoparticles (NPs) were obtained via a self-assembly from three amphiphilic DPP derivatives and used as smart phototherapeutic agents for tumor diagnosis and treatment. The three amphiphilic DPP NPs exhibited near-infrared (NIR) emissions and good biocompatibility. Thus, they could be used as fluorescence (FL) imaging agents for guided therapy. DTPADPP NPs and TPADDPP NPs also displayed excellent photothermal performance and high accumulation in the tumor. Owing to these beneficial features, the DTPADPP NPs and TPADDPP NPs synthesized herein are suitable for NIR FL imaging and effective photothermal therapy against the tumor in vivo.

4.
Ann Palliat Med ; 10(7): 7619-7626, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353049

RESUMO

BACKGROUND: The aim of this study is to evaluate the association between platelet parameters and soluble vascular endothelial growth factor receptor-1 (sFlt-1)/placenta growth factor (PlGF) in preeclampsia (PE) and establish a prediction model by analyzing commonly used biochemical markers. METHODS: A nested case-control study involving 270 pregnant women in their second trimester from the Beijing Jishuitan Hospital was conducted. They were divided into PE group and control group. The levels of PlGF, sFlt-1, sFlt-1/PlGF, and platelet parameters were recorded and compared at 20-24 gestational weeks. The correlation between platelet parameters and PlGF, sFlt-1, and sFlt-1/PLGF was then analyzed. A receiver operating characteristic (ROC) curve was used to calculate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of various biomarkers in predicting PE. RESULTS: In PE group, the levels of mean platelet volume (MPV), platelet distribution width (PDW), sFlt-1, and sFlt-1/PLGF were higher than in the control group, while the levels of platelet count (PC), PC/MPV, and PLGF in PE group were lower. Spearman correlation analysis showed that PC and PC/MPV were negatively correlated with sFlt-1 and sFlt-1/PLGF, and positively correlated with PLGF, while further analysis found that PC/MPV had the largest area under the ROC curve with sensitivity of 83.7% and specificity of 86.2%. The area under curve (AUC) of sFlt-1, PLGF, and sFlt-1/PLGF for predicting PE were 0.731, 0.772, and 0.825, respectively. Their AUCs could be improved to 0.820, 0.838, and 0.873 when combined with PC/MPV. CONCLUSIONS: The accuracy of sFlt-1/PlGF in predicting the risk of PE in the second trimester is significantly improved when combined with PC/MPV, which is expected to be an ideal tool for PE prediction.


Assuntos
Plaquetas , Fator de Crescimento Placentário/metabolismo , Pré-Eclâmpsia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Gravidez
5.
World J Clin Cases ; 9(11): 2562-2568, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33889621

RESUMO

BACKGROUND: Primary esophageal small cell carcinoma (PESCC) is a highly aggressive malignancy, and its detailed clinical behaviors have remained virtually unknown. Because of the rapid tumor progression, the diagnosis of esophageal small cell carcinoma at early stage is extremely difficult in clinical practice. Currently, only a handful of PESCC cases have been reported. CASE SUMMARY: Case 1: A 62-year-old man was diagnosed with an esophageal submucosal tumor by endoscopy. Endoscopic ultrasonography showed a 0.8 cm low echo nodule in the muscularis mucosa. As the patient refused to undergo endoscopic resection, neoplasia was detected by endoscopy 1 year later. Case 2: A 68-year-old woman was diagnosed as having an esophageal submucosal tumor by endoscopy at a local hospital. About 2 wk later, we performed endoscopic ultrasonography and found a 1 cm low echo nodule in the muscularis mucosa; the submucosal was thinner than normal but still continuous; mucosal hyperemia and erosion were found on the surface of the tumor. Endoscopic submucosal dissection (ESD) was performed and the histopathological finding showed a small cell carcinoma invading the submucosal layer. CONCLUSION: Early esophageal small cell carcinoma shows submucosal infiltrating growth with a hypoechoic mass in the muscularis mucosa as diagnosed by endoscopic ultrasonography. It is easily misdiagnosed as submucosal masses. Endoscopic manifestations should be identified and pathological biopsies should be employed. ESD may be performed to provide an opportunity for early treatment of PESCC.

6.
Chem Commun (Camb) ; 57(40): 4902-4905, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33870972

RESUMO

A bromine-substituted thermally activated delayed fluorescent (TADF) molecule AQCzBr2 is designed with both small singlet-triplet splitting (ΔEST) and increased spin-orbit coupling (SOC) to boost intersystem crossing (ISC) for singlet oxygen generation. AQCzBr2 nanoparticles (NPs) demonstrate high productivity of singlet oxygen generation (ΦΔ = 0.91) which allows highly efficient photodynamic therapy toward cancer cells.

7.
Chem Asian J ; 16(10): 1221-1224, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33881805

RESUMO

Peroxalate CL as an energy source to excite photosensitizers has attracted tremendous attention in photodynamic therapy (PDT). In this work, peroxyoxalate CPPO and hypocrellin B (HB)-based nanoparticles (CBNPs) for ultrasound (US)-enhanced self-exciting PDT were designed and prepared. CBNPs showed an excellent therapeutic effect against cancer cells with the assistance of US. This US-enhanced-chemiluminescence system avoids the dependence on external light and provides an example for inspiring more effective and precise strategies for cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Estruturas Metalorgânicas/farmacologia , Perileno/análogos & derivados , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Quinonas/farmacologia , Ondas Ultrassônicas , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Modelos Moleculares , Tamanho da Partícula , Perileno/química , Perileno/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Quinonas/química
8.
Acta Pharm Sin B ; 11(2): 544-559, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33643830

RESUMO

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.

9.
Carbohydr Polym ; 255: 117490, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33436250

RESUMO

To deliver photosensitizers with PEGylated heparin (HP) into tumor cells for photodynamic therapy, we prepared two polyethylene glycol (PEG)-functionalized HP-based polymers conjugated with pyropheophorbide-a (Ppa): a non-GSH-responsive nanoagent (HP-Ppa-mPEG) with the mPEG moiety chemically attached to HP directly; and a GSH-responsive nanoagent (HP-Ppa-SS-mPEG) with the mPEG moiety conjugated to HP via a disulfide linkage. The Ppa-functionalized HP without PEGylation (HP-Ppa) was designed as another control. These amphiphilic polymers could aggregate into nanoparticles. Cellular uptake of three nanoparticles by 4T1 cells led to abundant production of reactive oxygen species after irradiation by a 660 nm laser, inducing cell apoptosis. HP-Ppa-SS-mPEG was found to achieve the highest tumor accumulation, the longest retention time and the best penetration into tumor tissues, resulting in the highest in vivo anticancer efficacy with 94.3 % tumor growth inhibition rate, suggesting that tumor microenvironment-responsive PEGylated HP-based nanomedicines may act as efficient anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Clorofila/análogos & derivados , Heparina/química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofila/química , Feminino , Lasers , Luz , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanoconjugados/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
10.
Chem Asian J ; 15(21): 3462-3468, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-32909355

RESUMO

Hypocrellin B (HB) derived from naturally produced hypocrellins has attracted considerable attention in photodynamic therapy (PDT) because of its excellent photosensitive properties. However, the weak absorption within a "phototherapy window" (600-900 nm) and poor water solubility of HB have limited its clinical application. In this study, two HB derivatives (i. e., HE and HF) were designed and synthesized for the first time by introducing two different substituent groups into the HB structure. The obtained derivatives showed a broad absorption band covering the near-infrared (NIR) region, NIR emission (peaked at 805 nm), and singlet oxygen quantum yields of 0.27/0.31. HE-PEG-NPs were also prepared using 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) to achieve excellent dispersion in water and further explored their practical applications. HE-PEG-NPs not only retained their 1 O2 -generating ability, but also exhibited a photothermal conversion efficiency of 25.9%. In vitro and in vivo therapeutic results revealed that the synergetic effect of HE-PEG-NPs on PDT and photothermal therapy (PTT) could achieve a good performance. Therefore, HE-PEG-NPs could be regarded as a promising phototheranostic agent.


Assuntos
Antineoplásicos/farmacologia , Perileno/análogos & derivados , Fenol/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Terapia Fototérmica , Quinonas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Raios Infravermelhos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Camundongos , Imagem Óptica , Perileno/síntese química , Perileno/química , Perileno/farmacologia , Fenol/síntese química , Fenol/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Quinonas/síntese química , Quinonas/química , Nanomedicina Teranóstica
11.
Chem Commun (Camb) ; 56(74): 10902-10905, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32808621

RESUMO

A GGT-activated two-photon fluorescent probe (4F-2CN-GSH) was developed based on a cascade reaction. 4F-2CN-GSH could selectivily detect GGT with low detection limit and distinguish ovarian cancer cells from normal cells using both one-photon and two-photon fluorescence imaging.


Assuntos
Corantes Fluorescentes/química , Imagem Óptica , Fótons , gama-Glutamiltransferase/análise , Linhagem Celular Tumoral , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Estrutura Molecular , Espectrometria de Fluorescência , gama-Glutamiltransferase/metabolismo
12.
Adv Sci (Weinh) ; 7(14): 2000467, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32714757

RESUMO

Herein, two water-soluble PROXYL-based magnetic resonance imaging (MRI) macromolecular organic contrast agents (mORCAs) are designed and synthesized: linear and cross-linked PCE-mPEG-Ppa-PROXYL. They are prepared by conjugating linear and cross-linked poly(carboxylate ester) (PCE) with poly(ethylene glycol) (mPEG2000)-modified nitroxides (PROXYL), respectively. Both mORCAs form self-assembled aggregates in an aqueous phase and PROXYL is protected inside a hydrophobic core to achieve great resistance to reduction in the physiological environment, and they have low toxicity. Since cross-linked PCE-mPEG-Ppa-PROXYL possess a branched architecture, its self-assembled aggregate is more stable and compact with a greater particle size. Cross-linked PCE-mPEG-Ppa-PROXYL outperform the linear one in the following aspects: 1) its longitudinal relaxivity (r 1 = 0.79 mm -1 s-1) is higher than that of the linear one (r 1 = 0.64 mm -1 s-1) and both excel the best mORCA reported so far (r 1 = 0.42 mm -1 s-1); 2) its blood retention time (≈48 h) is longer than that of its linear counterpart (≈10 h); 3) cross-linked PCE-mPEG-Ppa-PROXYL provided better MR imaging contrast resolution in normal organs (liver and kidney) and tumor of mice than the linear one. Overall, cross-linked PCE-mPEG-Ppa-PROXYL may have great potential to be a novel metal-free macromolecular contrast agent for MR imaging.

13.
Mol Med Rep ; 21(4): 1897-1909, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32319609

RESUMO

The mechanism underlying the potential risk associated with in vitro fertilization and embryo transfer (IVF­ET) has been previously investigated but remains to be fully elucidated. As the placenta is a critical organ that sustains and protects the fetus, this is an important area of research. The aim of the present study was to determine the difference in trophoblast cell function in the first trimester between naturally conceived pregnancies and pregnancies achieved via IVF­ET therapy. A total of 20 placental villi in first trimester samples were obtained through fetal bud aspiration from patients undergoing IVF­ET due to oviductal factors between January 2016 and August 2018. In addition, a further 20 placental villi were obtained from those who naturally conceived and had normal pregnancies but were undergoing artificial abortion; these patients were recruited as the controls. Reverse transcription­quantitative (RT­q)PCR and semi­quantitative immunohistochemical methods were used to detect the mRNA and protein expression of α­fetoprotein (AFP), vascular endothelial growth factor (VEGF), transferrin (TF), tubulin ß1 class VI (TUBB1), metallothionein 1G (MT1G), BCL2, glial cells missing transcription factor 1 (GCM1), epidermal growth factor (EGF) receptor (EGFR), PTEN and leukocyte associated immunoglobulin like receptor 2 (LAIR2) in villi from both groups. Differentially expressed genes were analyzed using Search Tool for the Retrieval of Interacting Genes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted. The RT­qPCR data revealed that the mRNA expression levels of AFP, VEGF and TF were significantly higher in the IVF­ET group than in the control group (P<0.05), and those of TUBB1, MT1G, BCL2, GCM1, EGFR, PTEN and LAIR2 were significantly lower (P<0.05). These gene products were expressed in the placental villus tissues, either in the cytoplasm, or in the membrane of syncytiotrophoblast and cytotrophoblast cells. The immunohistochemistry results were in line with those observed using RT­qPCR. KEGG pathway analysis indicated that the trophoblast cell function of the IVF­ET group in the first trimester was different from naturally conceived pregnancies with regard to proliferation, invasion, apoptosis and vascular development. The IVF­ET process may trigger adaptive placental responses, and these compensatory mechanisms could be a risk for certain diseases later in life.


Assuntos
Transferência Embrionária , Fertilização In Vitro , Placenta/metabolismo , Trofoblastos/metabolismo , Adulto , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Humanos , Gravidez , Adulto Jovem
14.
Adv Sci (Weinh) ; 7(6): 1903243, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195104

RESUMO

A stimuli-responsive polymeric prodrug-based nanotheranostic system with imaging agents (cyanine5.5 and gadolinium-chelates) and a therapeutic agent paclitaxel (PTX) is prepared via polymerization and conjugating chemistry. The branched polymeric PTX-Gd-based nanoparticles (BP-PTX-Gd NPs) demonstrate excellent biocompatibility, and high stability under physiological conditions, but they stimuli-responsively degrade and release PTX rapidly in a tumor microenvironment. The in vitro behavior of NPs labeled with fluorescent dyes is effectively monitored, and the NPs display high cytotoxicity to 4T1 cells similar to free PTX by impairing the function of microtubules, downregulating anti-apoptotic protein Bcl-2, and upregulating the expression of Bax, cleaved caspase-3, cleaved caspase-9, cleaved-PARP, and p53 proteins. Great improvement in magnetic resonance imaging (MRI) is demonstrated by these NPs, and MRI accurately maps the temporal change profile of the tumor volume after injection of NPs and the tumor treatment process is also closely correlated with the T 1 values measured from MRI, demonstrating the capability of providing real-time feedback to the chemotherapeutic treatment effectiveness. The imaging-guided chemotherapy to the 4T1 tumor in the mice model achieves an excellent anti-tumor effect. This stimuli-responsive polymeric nano-agent opens a new door for efficient breast cancer treatment under the guidance of fluorescence/MRI.

15.
Adv Mater ; 32(14): e1907490, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32083784

RESUMO

Metabolic demand of cancer is quite unique compared to normal tissues and this is an emerging hallmark of cancer, which brings a potential opportunity to discover drugs that target cancer cell metabolism. Herein, the development of a dendronized pyropheophorbide a (Ppa)-conjugated polymer (DPP) is reported, and a linear Ppa-conjugated polymer (LPP) is reported as a control. DPP is found to disturb cellular metabolism including increased energy depletion, dysfunctional H+ regulation, and decreased antioxidation, resulting in deficiency in protecting cells from stresses. These vulnerable cells are subjected to photodynamic therapy (PDT) treatment in the presence of DPP, resulting in attenuated cancer cell growth and eventually cell death. The in vivo anticancer efficacy is also ascribed to significantly prolonged blood circulation and enhanced tumor accumulation of DPP due to its unique molecular structure. This study presents a new platform using dendronized polymers for tumor suppression by targeting cancer cell metabolism.


Assuntos
Clorofila/análogos & derivados , Fármacos Fotossensibilizantes/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofila/química , Clorofila/metabolismo , Clorofila/farmacologia , Clorofila/uso terapêutico , Humanos , Lasers , Camundongos , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
16.
ChemMedChem ; 15(2): 177-181, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31755659

RESUMO

Dopamine modified hypocrellin B (DAHB) derivative-loaded calcium phosphate nanorods (DAHB@CaP NRs) were prepared as a novel phototheranostic agent for effective tumor imaging and therapy. DAHB@CaP NRs were obtained through microwave treatment using DAHB, CaCl2 , NH3 ⋅H2 O, and H3 PO4 as precursors. The DAHB@CaP NRs possessed the following advantages: 1) efficient absorption in the near-infrared (NIR) region from 650 nm to 800 nm; 2) maximum NIR emission at approximately 735 nm; 3) enhanced cellular uptake efficiency in vitro and in vivo; and 4) efficient inhibition of tumor growth and low biotoxicity. These properties indicate the high capability of DAHB@CaP NRs for NIR fluorescence (FL) imaging-guided photodynamic therapy of cancer, thus offering promising new prospects for clinical applications.


Assuntos
Antineoplásicos/farmacologia , Fosfatos de Cálcio/farmacologia , Neoplasias Mamárias Experimentais/metabolismo , Nanotubos/química , Perileno/análogos & derivados , Fármacos Fotossensibilizantes/farmacologia , Quinonas/farmacologia , Nanomedicina Teranóstica , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Fosfatos de Cálcio/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dopamina/química , Dopamina/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Raios Infravermelhos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Camundongos , Estrutura Molecular , Imagem Óptica , Perileno/síntese química , Perileno/química , Perileno/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Quinonas/síntese química , Quinonas/química , Relação Estrutura-Atividade
17.
Medicine (Baltimore) ; 98(51): e18458, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861022

RESUMO

BACKGROUND: Chronic viral hepatitis b and its related complications have caused serious harm to human health and become a worldwide public health problem. Hepatitis b cirrhosis is one of the most common complications in Asia. Traditional Chinese medicine combined with antiviral therapy has become the first choice for clinical treatment of hepatitis b Cirrhosis. Biejia Pill is an effective prescription of traditional Chinese medicine in treating Compensatory period of cirrhosis, and there are more and more clinical reports about its validity in treating Compensatory period of cirrhosis. Therefore, we designed this study protocol to evaluate the adjuvant role of Biejia Pill in the treatment of Compensatory period of cirrhosis. METHOD: Electronic Databases, PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc, (CBM), will be systematically searched from inception to July 2019. Randomized controlled trials (RCTs) on Biejiajian Pill combined with Entecavir and Entecavir alone against Compensatory period of hepatitis b cirrhosis will be included; inclusion and exclusion criteria will be used to screen the trials. liver fibrosis biomarkers including ECM or its metabolites (serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), and type IV collagen (IV-C)) will be measured as primary outcomes. Liver function, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms will be measured as secondary outcomes. RevMan5 software will be used for literature quality evaluation and data synthesis and analysis. RESULT: To evaluate the efficacy and safety of Biejiajian Pill in combination therapy by observing the outcomes of serum liver fibrosis markers, adverse reactions and liver function. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of Biejia Pill in combination with entecavir in the treatment of Compensatory period of hepatitis b cirrhosis, as well as the adjuvant treatment of Biejia Pill in combination.PROSPERO registration number: CRD42019135402.


Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Guanina/análogos & derivados , Hepatite B/complicações , Cirrose Hepática/tratamento farmacológico , Biomarcadores/sangue , Quimioterapia Combinada , Guanina/uso terapêutico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Revisões Sistemáticas como Assunto
18.
Medicine (Baltimore) ; 98(44): e17031, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689742

RESUMO

The mechanisms underlying the potential risks of in vitro fertilization and embryo transfer (IVF-ET) have not been fully elucidated. The aim of this study was to explore changes in the complement and coagulation pathways in placentae subjected to IVF-ET in the first trimester compared to placentae from normal pregnancies. Four placenta samples in the first trimester were obtained from patients undergoing IVF-ET owing to oviductal factors only. An additional 4 control placentae were obtained from volunteers with normal pregnancies. A GeneChip Affymetrix HG-U133 Plus 2.0 Array was utilized to analyze the changes in gene expression between the normal and IVF-ET placentae. Differentially expressed genes (DEGs) were analyzed using the Database for Annotation and Visualization and Integrated Discovery bioinformatics resource, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Using real-time PCR, we confirmed the obtained microarray data in 10 dysregulated genes. Five of the gene products were further analyzed by immunohistochemistry (IHC) to determine their protein expression and localization. A total of fifty DEGs were identified in the complement and coagulation pathways in the IVF-ET treated placentae: 38 upregulated and 12 down-regulated. KEGG pathway analysis indicated that IVF-ET manipulation substantially over-activated the coagulation and complement pathways, while urokinase plasminogen activator- and urokinase plasminogen activator receptor-mediated trophoblastic invasion and tissue remodeling were inhibited. Furthermore, the 5 proteins analyzed by IHC were found to be localized specifically to the placenta. This is the first study to compare DEGs relating to the placental complement and coagulation pathways from patients undergoing IVF-ET treatment compared to those undergoing normal pregnancy. These findings identified valuable biomarkers and potential novel therapeutic targets to combat the unfavorable effects of IVF-ET.


Assuntos
Coagulação Sanguínea/genética , Proteínas do Sistema Complemento/genética , Transferência Embrionária , Fertilização In Vitro , Placenta/metabolismo , Primeiro Trimestre da Gravidez/metabolismo , Adulto , Regulação para Baixo , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
19.
ACS Appl Mater Interfaces ; 11(48): 44989-44998, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31755268

RESUMO

Tumor hypoxia severely limits the therapeutic efficacy of solid tumors in photodynamic therapy. One strategy is to develop photosensitizers with simultaneously high efficiency in photodynamic (PDT) and photothermal therapies (PTT) in a single natural-origin phototheranostic agent to overcome this problem. However, less attention has been paid to the natural-origin phototheranostic agent with high PDT and PTT efficiencies even though they have negligible side effects and are environmentally sustainable in comparison with many reported phototheranostic agents. In addition, almost all clinical applied photosensitizers are of natural origin so far. Herein, we synthesized a natural product-based hypocrellin derivative (AETHB), with a high singlet oxygen quantum yield of 0.64 as an efficient photosensitizer different from commercially available porphyrin-based photosensitizers. AETHB is further assembled with human serum albumin to construct nanoparticles (HSA-AETHB NPs) with a high photothermal conversion efficiency (more than 50%). As-prepared HSA-AETHB NPs have shown good water solubility and biocompatibility, pH and light stability, wide absorption (400-750 nm), and NIR emission centered at 710 nm. More importantly, HSA-AETHB NPs can be applied for fluorescent/photoacoustic dual-mode imaging and simultaneously highly efficient PDT/PTT in hypoxic solid tumors. Therefore, this natural-origin multifunctional phototheranostic agent is showing very promising for effective, precise, and safe cancer therapy in clinical applications.


Assuntos
Hipertermia Induzida , Neoplasias/terapia , Perileno/análogos & derivados , Fotoquimioterapia , Quinonas/química , Albumina Sérica/química , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Raios Infravermelhos , Camundongos , Camundongos Nus , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Perileno/administração & dosagem , Perileno/química , Fenol , Quinonas/administração & dosagem , Nanomedicina Teranóstica
20.
Medicine (Baltimore) ; 98(35): e17053, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464965

RESUMO

BACKGROUND: Bronchial asthma is one of the most common chronic diseases in the world and has become a serious public health problem. Combination therapy has become the first choice for clinical treatment of bronchial asthma. In addition to the combined use of routine medication, traditional Chinese medicine as an adjuvant therapy is also considered. Xiaoqinglong Decoction (XQLD) is an effective prescription of traditional Chinese medicine in treating asthma, and there are more and more clinical reports about its combination with western medicine in treating asthma. Therefore, we designed this study protocol to evaluate the adjuvant role of XQLD in the treatment of bronchial asthma. METHOD: The following electronic databases will be systematically searched from inception to April 2019: PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP), and China Biology Medicine disc, (CBM). And the following primary outcomes will be tested, including effective rate (ER), pulmonary function (FEV1, PEF, FEV1/FVC), adverse reactions (AR). RevMan5 software will be used for literature quality evaluation and stata14.0 software will be used for data synthesis and analysis. RESULT: To evaluate the efficacy and safety of Xiaoqinglong decoction in combination therapy by observing the outcomes of efficacy, adverse reactions and pulmonary function. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of XQLD in combination with conventional drugs in the treatment of bronchial asthma, as well as the adjuvant role of XQLD in combination. PROSPERO REGISTRATION NUMBER: CRD42019133549.


Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Testes de Função Respiratória
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