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Acta Trop ; : 105211, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31600522


Enterocytozoon bieneusi is a potentially important zoonotic pathogen. However, there is no information on E. bieneusi infection of captive long-tailed macaques (Macaca fascicularis) in Hainan Province, China. Here 193 fecal specimens of M. fascicularis were collected from a breeding base in Hainan Province, China, housing non-human primates for experimental use. E. bieneusi was identified and genotyped by nested PCR analysis of the internal transcribed spacer (ITS) region of the rRNA gene. A total of 59 (30.6%) specimens were PCR-positive for E. bieneusi and 16 ITS genotypes were identified including nine known genotypes: Type IV (n = 19), D (n = 11), CM1 (n = 8), PigEBITS7 (n = 4), Pongo2 (n = 4), Peru8 (n = 3), Peru11 (n = 1), WL21 (n = 1) and CM2 (n = 1) and seven novel genotypes HNM-I to HNM-VII (one each). Importantly, genotypes D, Type IV, Peru8, PigEBITS7, and Peru11, which were the predominant (38/59, 64.4%) genotypes identified among captive M. fascicularis in this study, are also well-known human-pathogenic genotypes. All the genotypes of E. bieneusi identified here, including the seven novel ones, belonged to zoonotic Group 1. This is the first report of the identification of E. bieneusi in M. fascicularis in Hainan Province, China. The finding that the numerous known human-pathogenic types and seven novel genotypes of E. bieneusi all belong to zoonotic Group 1 indicates the possibility of transmission of this important pathogenic parasite between M. fascicularis and humans.

J Nanobiotechnology ; 17(1): 78, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269964


BACKGROUND: The construction of a multifunctional drug delivery system with a variety of advantageous features, including targeted delivery, controlled release and combined therapy, is highly attractive but remains a challenge. RESULTS: In this study, we developed a MoS2-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving targeted delivery of camptothecin (CPT) and dual-stimuli-responsive drug release. HA was connected to MoS2 via a disulfide linkage, forming a sheddable HA shell on the surface of MoS2. This unique design not only effectively prevented the encapsulated CPT from randomly leaking during blood circulation but also significantly accelerated the drug release in response to tumor-associated glutathione (GSH). Moreover, the MoS2-based generated heat upon near-infrared (NIR) irradiation could further increase the drug release rate as well as induce photothermal ablation of cancer cells. The results of in vitro and in vivo experiments revealed that MoS2-SS-HA-CPT effectively suppressed cell proliferation and inhibited tumor growth in lung cancer cell-bearing mice under NIR irradiation via synergetic chemo-photothermal therapy. CONCLUSIONS: The as-prepared MoS2-SS-HA-CPT with high targeting ability, dual-stimuli-responsive drug release, and synergistic chemo-photothermal therapy may provide a new strategy for cancer therapy.

Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/administração & dosagem , Dissulfetos/química , Portadores de Fármacos/química , Molibdênio/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Liberação Controlada de Fármacos , Feminino , Corantes Fluorescentes/química , Humanos , Ácido Hialurônico/química , Hipertermia Induzida , Raios Infravermelhos , Camundongos Nus , Transplante de Neoplasias , Oxirredução , Fotoquimioterapia/métodos
ChemMedChem ; 14(15): 1378-1383, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31210412


The development of efficient phototherapeutic agents (PTA) through rational and specific principles exhibits great potential to the biomedical field. In this study, a facile and rational strategy was used to design PTA through perturbation theory. According to the theory, both the intersystem crossing rate for singlet oxygen generation and nonradiative transition for photothermal conversion efficiency can be simultaneously enhanced by the rational optimization of donor-acceptor groups, heavy atom number, and their functional positions, which can effectively decrease the energy gap between the singlet and triplet states and increase the spin-orbit coupling constant. Finally, efficient PTA were obtained that showed excellent performance in multimode-imaging-guided synergetic photodynamic/photothermal therapy. This study therefore expands the intrinsic mechanism of organic PTA and should help guide the rational design of future organic PTA via perturbation theory.

Free Radic Biol Med ; 129: 107-115, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30227269


S-nitrosocaptopril (CapNO) possesses dual capacities of both Captopril and an NO donor with enhanced efficacy and reduced side effects. CapNO crystals are difficult to make due to its unstable S-NO bond. Here, we report a novel stable S-nitrosocaptopril monohydrate (CapNO·H2O) that is stabilized by intermolecular five-membered structure, where one H of H2O forms a hydrogen bond with O- of the stable resonance zwitterion Cap-S+=N-O-, and the O in H2O forms the dipole-dipole interaction with S+ through two unpaired electrons. With the chelation and common ion effect, we synthesized and characterized CapNO·H2O that is stable at 4 °C for 180 days and thereafter without significant degradation. Compared to Captopril, CapNO showed direct vasorelaxation and beneficial effect on PAH rats, and could be self-assembled in rat stomach when Captopril and NaNO2 were given separately. This novel CapNO·H2O with low entropy paves an avenue for its clinical trials and commercialization.

Biochim Biophys Acta ; 1858(8): 1801-11, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27117641


The clathrin-mediated endocytosis is likely a major mechanism of liposomes' internalization. A kinetic approach was used to assess the internalization mechanism of doxorubicin (Dox) loaded cationic liposomes and to establish physiology-based cell membrane traffic mathematic models. Lipid rafts-mediated endocytosis, including dynamin-dependent or -independent endocytosis of noncaveolar structure, was a dominant process. The mathematic models divided Dox loaded liposomes binding lipid rafts (B) into saturable binding (SB) and nonsaturable binding (NSB) followed by energy-driven endocytosis. The intracellular trafficking demonstrated early endosome-late endosome-lysosome or early/late endosome-cytoplasm-nucleus pathways. The three properties of liposome structures, i.e., cationic lipid, fusogenic lipid, and pegylation, were investigated to compare their contributions to cell membrane and intracellular traffic. The results revealed great contribution of cationic lipid DOTAP and fusogenic lipid DOPE to cell membrane binding and internalization. The valid Dox in the nuclei of HepG2 and A375 cells treated with cationic liposomes containing 40mol% of DOPE were 1.2-fold and 1.5-fold higher than that in the nuclei of HepG2 and A375 cells treated with liposomes containing 20mol% of DOPE, respectively, suggesting the dependence of cell type. This tendency was proportional to the increase of cell-associated total liposomal Dox. The mathematic models would be useful to predict intracellular trafficking of liposomal Dox.

Doxorrubicina/análogos & derivados , Endocitose/fisiologia , Microdomínios da Membrana/fisiologia , Modelos Biológicos , Transporte Biológico , Cátions , Linhagem Celular , Doxorrubicina/administração & dosagem , Doxorrubicina/metabolismo , Ácidos Graxos Monoinsaturados/química , Células Hep G2 , Humanos , Lipossomos , Fusão de Membrana , Lipídeos de Membrana/química , Microscopia de Fluorescência , Fosfatidiletanolaminas/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Compostos de Amônio Quaternário/química
Tumour Biol ; 35(7): 7217-23, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24771263


Numerous attempts for detection of circulating tumor cells (CTC) have been made to develop reliable assays for early diagnosis of cancers. In this study, we validated the application of folate receptor α (FRα) as the tumor marker to detect CTC through tumor-specific ligand PCR (LT-PCR) and assessed its utility for diagnosis of bladder transitional cell carcinoma (TCC). Immunohistochemistry for FRα was performed on ten bladder TCC tissues. Enzyme-linked immunosorbent assay (ELISA) for FRα was performed on both urine and serum specimens from bladder TCC patients (n = 64 and n = 20, respectively) and healthy volunteers (n = 20 and n = 23, respectively). Western blot analysis and qRT-PCR were performed to confirm the expression of FRα in bladder TCC cells. CTC values in 3-mL peripheral blood were measured in 57 bladder TCC patients, 48 healthy volunteers, and 15 subjects with benign urologic pathologies by the folate receptor α ligand-targeted PCR. We found that FRα protein was overexpressed in both bladder TCC cells and tissues. The levels of FRα mRNA were also much higher in bladder cancer cell lines 5637 and SW780 than those of leukocyte. Values of FRα were higher in both serum and urine specimens of bladder TCC patients than those of control. CTC values were also higher in 3-mL peripheral blood of bladder TCC patients than those of control (median 26.5 Cu/3 mL vs 14.0 Cu/3 mL). Area under the receiver operating characteristic (ROC) curve for bladder TCC detection was 0.819, 95 % CI (0.738-0.883). At the cutoff value of 15.43 Cu/3 mL, the sensitivity and the specificity for detecting bladder cancer are 82.14 and 61.9 %, respectively. We concluded that quantitation of CTCs through FRα ligand-PCR could be a promising method for noninvasive diagnosis of bladder TCC.

Carcinoma de Células de Transição/sangue , Receptor 1 de Folato/sangue , Células Neoplásicas Circulantes , Neoplasias da Bexiga Urinária/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Receptor 1 de Folato/isolamento & purificação , Humanos , Ligantes , Masculino , RNA Mensageiro/biossíntese , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia