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2.
Eur J Med Res ; 29(1): 257, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689322

RESUMO

BACKGROUND: This study aimed to explore the expression, molecular mechanism and its biological function of potassium two pore domain channel subfamily K member 1 (KCNK1) in bladder cancer (BC). METHODS: We integrated large numbers of external samples (n = 1486) to assess KCNK1 mRNA expression levels and collected in-house samples (n = 245) for immunohistochemistry (IHC) experiments to validate at the KCNK1 protein level. Single-cell RNA sequencing (scRNA-seq) analysis was performed to further assess KCNK1 expression and cellular communication. The transcriptional regulatory mechanisms of KCNK1 expression were explored by ChIP-seq, ATAC-seq and ChIA-PET data. Highly expressed co-expressed genes (HECEGs) of KCNK1 were used to explore potential signalling pathways. Furthermore, the immunoassay, clinical significance and molecular docking of KCNK1 were calculated. RESULTS: KCNK1 mRNA was significantly overexpressed in BC (SMD = 0.58, 95% CI [0.05; 1.11]), validated at the protein level (p < 0.0001). Upregulated KCNK1 mRNA exhibited highly distinguishing ability between BC and control samples (AUC = 0.82 [0.78-0.85]). Further, scRNA-seq analysis revealed that KCNK1 expression was predominantly clustered in BC epithelial cells and tended to increase with cellular differentiation. BC epithelial cells were involved in cellular communication mainly through the MK signalling pathway. Secondly, the KCNK1 transcription start site (TSS) showed promoter-enhancer interactions in three-dimensional space, while being transcriptionally regulated by GRHL2 and FOXA1. Most of the KCNK1 HECEGs were enriched in cell cycle-related signalling pathways. KCNK1 was mainly involved in cellular metabolism-related pathways and regulated cell membrane potassium channel activity. KCNK1 expression was associated with the level of infiltration of various immune cells. Immunotherapy and chemotherapy (docetaxel, paclitaxel and vinblastine) were more effective in BC patients in the high KCNK1 expression group. KCNK1 expression correlated with age, pathology grade and pathologic_M in BC patients. CONCLUSIONS: KCNK1 was significantly overexpressed in BC. A complex and sophisticated three-dimensional spatial transcriptional regulatory network existed in the KCNK1 TSS and promoted the upregulated of KCNK1 expression. The high expression of KCNK1 might be involved in the cell cycle, cellular metabolism, and tumour microenvironment through the regulation of potassium channels, and ultimately contributed to the deterioration of BC.


Assuntos
Regulação Neoplásica da Expressão Gênica , Canais de Potássio de Domínios Poros em Tandem , Neoplasias da Bexiga Urinária , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Simulação de Acoplamento Molecular , Canais de Potássio de Domínios Poros em Tandem/genética , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Transdução de Sinais , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
3.
J Hazard Mater ; 465: 133156, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38061128

RESUMO

Ethephon (ETH) is a common pesticide, and its overuse has resulted in a variety of health problems for humans. However, the existing ETH detection methods are tedious and time-consuming, and real-time ETH identification remains a significant difficulty. To mitigate this concern, a dual-emission ratiometric fluorescent probe Ru@ZrMOF was rationally synthesized for the detection of ETH. In the presence of ETH, the emission peak at 435 nm gradually increased, while the peak at 600 nm remained constant, accompanied by the fluorescence color change from red, pink, blue-violet to blue. The fluorescence intensity ratio (F435/F600) demonstrated two linear relations with the ETH concentration ranges at 3 - 50 µM and 50 - 500 µM, with a lowest detection limit at 1 µM. This was attributed to the formation of Zr-O-P bonds which attenuated the ligand-metal charge transfer (LMCT) process, resulting in the recovery of blue fluorescence of the ligand 2-Aminoterephthalic acid (2-APDC). To validate the practical application of the developed platform, a YOLO v5x-based WeChat applet "96 Speckles" was developed, and a 96-well plate and smartphone-embedded 3D-printed portable toolbox was designed for the real-time intelligent detection of ETH. This smart platform allows for real-time and efficient ETH analysis in various real samples including apples, pears and tomatoes.

4.
Methods Mol Biol ; 2748: 279-288, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38070120

RESUMO

With the inherent antitumor function and unique "off-the-shelf" potential, genetically engineered human natural killer (NK) cells with chimeric antigen receptors (CARs) bear great promise for the treatment of multiple hematological malignancies and solid tumors. Current methods of producing large-scale CAR-NK cells mainly rely on mRNA transfection and viral vector transduction. However, mRNA CAR-NK cells were not stable in CAR expression while viral vector transduction mostly ended up with low efficiency. In this chapter, we described an optimized protocol to generate CAR-NK cells by using the piggyBac transposon system via electroporation and to further expand these engineered CAR-NK cells in a large scale together with artificial antigen-presenting feeder cells. This method can stably engineer human primary NK cells with high efficiency and supply sufficient scale of engineered CAR-NK cells for the future possible clinical applications.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Células Matadoras Naturais , Neoplasias/patologia , Vetores Genéticos/genética , RNA Mensageiro/metabolismo , Imunoterapia Adotiva/métodos
5.
ACS Appl Mater Interfaces ; 15(41): 48506-48518, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37796018

RESUMO

In this study, we designed and fabricated a spermine-responsive triple-emission ratiometric fluorescent probe using dual-emissive carbon nanoparticles and quantum dots, which improve the sensor's accuracy and reduce interfering environmental effects. The probe is advantageous for the proportionate detection of spermine because it has good emission resolution, and the maximum points of the two emission peaks differ by 95 nm. As a proof of concept, cuvettes and a 96-well plate were combined with a smartphone and YOLO series algorithms to accomplish real-time, visual, and high-throughput detection of seafood and meat freshness. In addition, the reaction mechanism was verified by density functional theory and fundamental characterizations. Upon exposure to different amounts of spermine, the intensity of the fluorescent probe changed linearly, and the fluorescent color shifted from yellow-green to red, with a limit of detection of 0.33 µM. To enable visual identification of food-originated spermine, a hydrogel-based visual sensing platform was successfully developed utilizing the triple-emission fluorescent probe. Consequently, spermine could be identified and quantified without complicated equipment.


Assuntos
Pontos Quânticos , Espermina , Corantes Fluorescentes , Carbono , Limite de Detecção
6.
Cell Signal ; 104: 110594, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36646297

RESUMO

Ferroptosis is a form of iron-dependent programmed cell death discovered in recent years that has been shown to be involved in diverse neurological disorders. Hydrogen sulfide (H2S) is an important signaling molecule with neuroprotective effects, including antioxidation. However, whether the protective mechanism of H2S is related to ferroptosis remains unknown. Therefore, in this study, we focused on the protective mechanisms of sodium hydrosulfide (NaHS, a donor of H2S) against ferroptosis caused by intracerebral hemorrhage (ICH) using a hemin-induced BV2 cell injury model in vitro. Our results indicated that NaHS enhanced cell viability and reduced hemin-induced lactate dehydrogenase (LDH) release. NaHS suppressed ferroptosis after hemin treatment, which was confirmed by attenuated reactive oxygen species (ROS) and lipid peroxidation, maintained iron homeostasis, recovery of the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7-member 11 (SLC7A11), and increased glutathione (GSH) production. Moreover, we demonstrated that inhibiting ferroptosis improved cell survival and prevented hemin-induced oxidative stress. In addition, NaHS was also able to block ferroptosis inducer RSL3-induced ferroptotic cell death. We also found that NaHS increased cystathionine-ß-synthase (CBS) expression and H2S levels after hemin treatment. Furthermore, NaHS-induced ferroptosis reduction was inhibited by the CBS inhibitor aminooxyacetic acid (AOAA) as well as by CBS small interference RNA (siCBS). In summary, these findings demonstrated that NaHS protects against hemin-induced ferroptosis by reducing lipid peroxidation, inhibiting iron overload, increasing GSH production, and improving GPX4 and SLC7A11 via the CBS/H2S system. The CBS/H2S system may be a promising target for preventing ferroptosis after ICH.


Assuntos
Ferroptose , Sulfeto de Hidrogênio , Cistationina beta-Sintase/metabolismo , Glutationa/metabolismo , Hemina/farmacologia , Hemina/metabolismo , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Ferro , Peroxidação de Lipídeos , Animais , Camundongos , Linhagem Celular
7.
Aesthetic Plast Surg ; 47(1): 365-377, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36097079

RESUMO

BACKGROUND: Botulinum toxin type A (BoNT/A) has been used in aesthetic applications worldwide, including glabellar lines. Currently, four BoNT/A preparations were approved for the improvement of moderate-to-severe glabellar lines: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and prabotulinumtoxinA. DaxibotulinumtoxinA is a new form of BoNT/A drug that is developed in clinical application. We performed this network meta-analysis (NMA) to assess the efficacy and safety of all these different BoNT/A formulations for treating glabellar lines. METHODS: The investigators searched randomized controlled trials (RCTs) using the Medical Subject Headings (MeSH) terms "botulinum toxin" and "glabellar lines." We searched the relevant studies in electronic databases as following: PubMed, Elsevier, EMBASE and the Cochrane Library. The end points included the percentage of subjects with a glabellar line severity (GLS) score of none (0) or mild (1), and the percentage of subjects achieving ≥ 1-point and 2-point improvement in glabellar line severity at maximum frown at approximately month 1 by the investigators' assessment. RESULTS: All formulations of BoNT/A were far superior to placebo in efficacy. DaxibotulinumtoxinA was the only treatment that significantly increased the proportion of subjects achieving ≥ 1 point improvement in GLS score compared with other BoNT/A formulations. Moreover, daxibotulinumtoxinA was ranked the highest for the proportion of subjects achieving ≥ 2-point improvement in GLS score. No significant differences were revealed for the incidence of any adverse events (AEs) that related to treatment or drug among all BoNT/A preparations. CONCLUSION: The overall results of this NMA suggested that daxibotulinumtoxinA is a new BoNT/A preparation that may be not only more effective but also well-tolerated for the treatment of glabellar lines. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Envelhecimento da Pele , Humanos , Metanálise em Rede , Testa , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Método Duplo-Cego
8.
J Mol Neurosci ; 71(8): 1636-1647, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33876384

RESUMO

The present study aimed to detect the effect of tenascin C (TNC) on cell function and chemosensitivity to paclitaxel and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling in glioma cells.Human glioma cells U87, LN-229, T98G and U251 and normal human astrocytes were obtained, in which TNC expression was detected. The U87 cells and U251 cells were chosen and infected with lentivirus of control overexpression, TNC overexpression, control knockdown, and TNC knockdown for functional experiments. Rescue experiments were then performed to evaluate the effect of PI3K/AKT activator 740 Y-P on cell function and chemosensitivity to paclitaxel in TNC knockdown U251 cells. TNC mRNA and protein expression was elevated in glioma cells, including U87, LN-229, U251 and T98G cells, compared to normal human astrocytes. In U87 and U251 cells, TNC promoted proliferation while inhibiting apoptosis. In addition, TNC upregulated PI3K and p-AKT protein expression in U87 and U251 cells. As for chemosensitivity, TNC increased relative viability in U251 cells treated with 400 ng/mL and 800 ng/mL paclitaxel. In terms of stemness, TNC increased the sphere number per 1000 cells, CD44+CD133+ cell percentage and 1/stem cell frequency (assessed by extreme limiting dilution analysis) in U251 cells. In rescue experiments, 740 Y-P reduced the effect of TNC on proliferation, apoptosis, chemosensitivity to paclitaxel, and stemness in U251 cells. TNC acts as an oncogenic factor by promoting cancer cell proliferation and stemness while inhibiting apoptosis and chemosensitivity to paclitaxel in glioma via modulation of PI3K/AKT signaling.


Assuntos
Neoplasias Encefálicas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Glioma/metabolismo , Tenascina/metabolismo , Antineoplásicos/toxicidade , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Paclitaxel/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Tenascina/genética
9.
Zhongguo Gu Shang ; 33(10): 965-9, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33107262

RESUMO

OBJECTIVE: To evaluate clinical effect of poking reduction cannulated screw based on Pingle orthopedic muscle-bone interoperability balance theory in treating Sanders Ⅱ calcaneal fracture. METHODS: From October 2014 to December 2017, 28 patients with Sanders Ⅱ calcaneal fracture were treated with poking reduction cannulated screw guided by Pingle orthopedic muscle-bone interoperability balance theory, including 20 males and 8 females, aged from 24 to 55 years old with an average of (37.2±3.9) years old. Calcaneal width, Bhler angle, and Gissane angle were measured before and after operation, and Maryland Score before and 6 months after operation were compared. RESULTS: All patients were followed up from 12 to 16 months with an average of (13.7±1.3) months. All fractures healed normally, and healing time ranged from 9 to 12 weeks with an average of (10.2±1.3) weeks. No postoperative wound infection, cortical necrosis, or osteomyelitis occurred. The width of the calcaneus decreased from (34.15±2.58) mm before surgery to (30.49±2.37) mm after surgery, Bhler angle increased from (14.16±3.27)° before operation to (31.95±3.07)°after operation, Gissane angle decreased from (128.45±9.04)° before operation to (120.83±8.15)° after operation. Maryland Score was 15.68±4.73 before operation, and was improved to 88.32±2.65 at 6 months after operation;19 patients got excellent result, 6 good, 2 fair and 1 poor. CONCLUSION: Poking reduction cannulated screw based on Pingle orthopedic muscle-bone interoperability balance theory in treating Sanders Ⅱ calcaneal fracture has certain clinical effects, high acceptation of patient, and without special demand for soft tissue around fracture. But it should avoid choosing severe comminuted Sanders Ⅲand Ⅳcalcaneal fracture.


Assuntos
Calcâneo , Fraturas Ósseas , Adulto , Parafusos Ósseos , Calcâneo/cirurgia , Feminino , Fixação Interna de Fraturas , Fraturas Ósseas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
10.
Adv Clin Exp Med ; 28(9): 1249-1255, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31430071

RESUMO

BACKGROUND: The single-nucleotide polymorphisms (SNPs) of apurinic/apyrimidinicendonuclease 1 (APE1), which has been implicated in cancers and the DNA base excision repair (BER) process, have not been thoroughly investigated in association with the risks of oxidative stress-related vitiligo. OBJECTIVES: The aim of this study is to investigate associations between APE1 single-nucleotide polymorphisms 141T >G and 1349T >G and risk and prognosis of vitiligo. MATERIAL AND METHODS: From June 2013 to June 2015, a total of 460 vitiligo patients were randomly recruited as a case group; 200 of these patients received narrow bound ultraviolet B (NB-UVB) treatment. Meanwhile, 460 healthy controls were included as a control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to explore the distribution frequencies of genotypes. RESULTS: Significant differences were detected between the case group and the control group in the frequencies of the 141T >G and 1349T >G genotypes. At 141T >G, compared with patients carrying the TG + GG genotype, male patients carrying the TT genotype aged more than 20 years with active non-segmental vitiligo, without a family history of vitiligo or other autoimmune diseases, exhibited an increased risk of vitiligo. Binary logistic regression analysis demonstrated that the TT genotype at 141T >G and the non-TT genotype at 1349T >G were independent risk factors for vitiligo development. At 1349T >G, compared with patients carrying the TT genotype, male patients carrying the TG + GG genotype aged more than 20 years with active non-segmental vitiligo, without a family history of vitiligo or other autoimmune diseases, exhibited an increased risk of vitiligo. Moreover, patients carrying 141TG + GG or 1349 TT genotypes had better photochromic effects, lower cumulative radiation doses, shorter treatment times, and earlier first photochromic times.


Assuntos
Povo Asiático/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Polimorfismo de Nucleotídeo Único , Vitiligo , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Prognóstico , Vitiligo/genética , Vitiligo/metabolismo , Adulto Jovem
11.
Cell Biol Int ; 43(2): 182-191, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30571843

RESUMO

Wound healing is a basic biological process including proliferation and migration of keratinocyte. The effects of microRNAs on skin wound healing remain largely unexplored. This study aimed to investigate the role of microRNA-126 (miR-126) in human skin wound healing. Relative expression of miR-126 after injury was evaluated by qRT-PCR. Cell viability, colony formation, cycle distribution, migration, and the alternation of PI3 K/AKT pathway after miR-126 knockdown or overexpression were detected, respectively. In addition, potential target gene of miR-126 was also explored by luciferase assay. Results showed that miR-126 was up-regulated during skin wound healing. Moreover, overexpression of miR-126 promoted cell proliferation and migration, whereas inhibition of miR-126 led to the opposite effects. Additionally, we discovered that PLK2, which inhibited cell viability, colony formation and migration of keratinocyte, was a target gene of miR-126. The expression of PLK2 was negatively correlated with the level of miR-126 during wound healing. Finally, we demonstrated that overexpression of miR-126 significantly increased the expression of p-AKT, p-ERK2, and PI3 K, indicating that overexpression of miR-126 activated PI3 K/AKT signaling pathway. In conclusion, our results demonstrated that miR-126 acted as a critical regulator for promoting proliferation and migration in keratinocyte during skin wound healing.


Assuntos
MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pele/metabolismo , Regiões 3' não Traduzidas , Antagomirs/metabolismo , Pontos de Checagem do Ciclo Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Pele/patologia , Regulação para Cima , Cicatrização/genética
12.
Int J Immunopathol Pharmacol ; 32: 394632017739531, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29359608

RESUMO

Melanoma is the most common skin cancer and malignant melanoma which can cause skin cancer-related deaths. Toll-like receptor 4 (TLR4) had been reported to play an important role in melanoma, and tea polyphenol (TP) is regarded as an anticancer substance. However, the relationship between TP and TLR4 in melanoma is not well explored. Therefore, our aim is to figure out how TP has an influence on melanoma. Melanoma cell lines (B16F10 and A375) were treated with TP and lipopolysaccharides (LPS). Western blot assay was used to examine TLR4 expression, and MTT assay was conducted to assess proliferation. Wound healing assay was conducted to evaluate the migration of melanoma cells, and transwell assay was used to examine the melanoma cells' invasiveness. Besides, in vivo experiments were practiced for TP function in mice with melanoma cells. TP inhibited the proliferation, migration and invasion ability of melanoma cells, which displayed a dosage and time dependence. TLR4 was highly expressed in melanoma cells compared with normal skin cells. TP could suppress TLR4 expression both in normal melanomas and in stimulated melanomas by TLR4 agonist LPS. Suppressing TLR4 in melanomas could inhibit cell function (proliferation, migration, and invasion), and blocking the expression of 67LR could abolish TP function on TLR4. TP can inhibit melanoma (B16F10) growth in vivo.


Assuntos
Proliferação de Células/fisiologia , Melanoma Experimental/metabolismo , Polifenóis/farmacologia , Neoplasias Cutâneas/metabolismo , Chá , Receptor 4 Toll-Like/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Humanos , Melanoma Experimental/patologia , Invasividade Neoplásica/patologia , Polifenóis/isolamento & purificação , Neoplasias Cutâneas/patologia , Receptor 4 Toll-Like/antagonistas & inibidores
13.
Mater Sci Eng C Mater Biol Appl ; 64: 243-248, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27127050

RESUMO

Three-dimensional flower-like Bi2WO6 microspheres (3D-Bi2WO6 MSs) have been synthesized through a simple hydrothermal method. The morphology and structure of 3D-Bi2WO6 MSs were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The 3D-Bi2WO6 MSs subsequently were used to immobilize horseradish peroxidase (HRP) and fabricate a mediator-free biosensor for the detection of H2O2. Spectroscopic and electrochemical results reveal that 3D-Bi2WO6 MSs constitute an excellent immobilization matrix with biocompatibility for enzymes. Meanwhile, due to unique morphology of the flower-like microspheres, the direct electron transfer of HRP is facilitated and the prepared biosensors display good performances for the detection of H2O2 with a wide linear range, including two linear sections: 0.5-100µM (R(2)=0.9983) and 100-250µM (R(2)=0.9981), as well as an extremely low method detection limit of 0.18µM.


Assuntos
Técnicas Biossensoriais/métodos , Bismuto/química , Técnicas Eletroquímicas/métodos , Peróxido de Hidrogênio/análise , Microesferas , Compostos de Tungstênio/química , Enzimas Imobilizadas/química , Peroxidase do Rábano Silvestre/química
14.
Yao Xue Xue Bao ; 51(6): 926-30, 2016 06.
Artigo em Chinês | MEDLINE | ID: mdl-29879346

RESUMO

This study was designed to investigate the inhibitory effects of Jiawei Foshou San (JWFSS) capsule in vitro on five major human liver microsomes CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, as well as on rat liver microsomes CYP1A2, CYP2C9, CYP2D2, CYP2E1, CYP3A1/2. The test groups included a negative control group, an inhibitor positive control group, an ferulic acid (FA) group, a ligustrazine (LZ) group, a tetrahydropalmatine (THP) group, and an JWFSS capsule group. After incubating the liver microsomes with a cocktail of probe drugs, the metabolites were quantitated with LC-MS/MS, and IC(50) values were calculated to assess the inhibitory effect of JWFSS capsule and its components on five rat/human CYP450 enzymes. All of the IC(50) values for the FA and the LZ for the five CYPs could not be determined. The IC(50) of the THP for rat CYP3A1/2 and for human CYP2D6 was 7.46 and 9.24 µmol·L(-1), respectively. The IC(50) of the JWFSS capsule for rat CYP2D2, CYP2E1 and CYP3A1/2 was 241.3, 369.8 and 293.0 mg·L(-1), for human CYP2D6, CYP2E1 and CYP3A4 was 123.9, 189.9 and 171.3 mg·L(-1) respectively. The results indicated there were little probability that FA and LZ inhibited the activity of rat and human liver five CYPs; THP was identified as moderate-intensity inhibitor of rat liver CYP3A1/2 and human liver CYP2D6; JWFSS capsule might have a inhibitory effect on the activity of rat and human liver CYP2D, CYP2E1 and CYP3A in vitro, showing that there was a strengthened efficacy and a prolonged effective time for drugs metabolized by CYP2D, CYP2E1, CYP3A and combined with JWFSS capsule.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Microssomos Hepáticos/efeitos dos fármacos , Animais , Alcaloides de Berberina/farmacologia , Ácidos Cumáricos/farmacologia , Citocromo P-450 CYP1A2 , Citocromo P-450 CYP2E1 , Citocromo P-450 CYP3A , Humanos , Fígado , Microssomos Hepáticos/enzimologia , Pirazinas/farmacologia , Ratos
15.
Zhongguo Zhong Yao Za Zhi ; 40(10): 2030-6, 2015 May.
Artigo em Chinês | MEDLINE | ID: mdl-26390668

RESUMO

To investigate the effect of Jiawei Foshou San and its various combined administration on hepatic P450 enzyme activity and hepatocyte morphology in rats. Rats were orally administered with drugs for four weeks and then sacrificed to prepare liver microsomes. The liver microsomes were incubated with the cocktail method; The metabolites were determined with the rapid liquid chromatography with tandem mass spectrometry (LC-MS/MS) to investigate the hepatocyte P450 enzyme activity. In addition, the hepatic pathological changes were observed by using the hematoxylin and eosin (HE) staining. Compared with the control group, the enzyme activity of CYP1A2 and CYP3A4 in the Jiawei Foshou san group showed a significant rise (P < 0.05); the enzyme activity of CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in the ferulic acid + ligustrazine group and the ligustrazine + tetrahydropalmatine group showed a significant rise (P < 0.05) ; the enzyme activity of CYP1A2, CYP2D6 and CYP2E1 in the ligustrazine group showed a significant rise (P < 0.05); the enzyme activity of CYP3A4 in the ferulic acid group showed a significant reduction (P < 0.05). After the administration with various drugs, the hepatocyte morphologies in the ferulic acid group and the ligustrazine group were normal. The pathological changes were observed in the tetrahydropalmatine group, such as unclear boundary of hepatic lobules, disordered hepatic cell arrangement, blurred edge, anisokaryosis and infiltration of inflammatory cells. The ferulic acid + tetrahydropalmatine group, the ligustrazine + tetrahydropalmatine group and the Jiawei Foshou San group also showed inflammatory infiltration, but with less pathological changes, particularly the Jiawei Foshou San group. The study result shows that Jiawei Foshou San can induce the enzyme activity of CYP1A2 and CYP3A4, and ligustrazine may be the effective substance for inducing CYP1A2. Its combination with ferulic acid and ligustrazine can significantly reduce the liver toxicity of tetrahydropalmatine.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Animais , Feminino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Ratos , Ratos Sprague-Dawley
16.
Mater Sci Eng C Mater Biol Appl ; 53: 43-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26042689

RESUMO

WO3 nanowires (WO3NWs) with high length-diameter ratio have been synthesized through a simple synthetic route without any additive and then used to immobilize hemoglobin (Hb) to fabricate a mediator-free biosensor. The morphology and structure of WO3NWs were characterized by scanning electron microscopy, transmission electronic microscopy and X-ray diffraction. Spectroscopic and electrochemical results revealed that WO3NWs are an excellent immobilization matrix with biocompatibility for redox protein, affording good protein bioactivity and stability. Meanwhile, due to unique morphology and property of the WO3 nanowires, the direct electron transfer of Hb is facilitated and the prepared biosensors displayed good performance for the detection of nitrite with a wide linear range of 1 to 4200 µM, as well as an extremely low detection limit of 0.28 µM. The WO3 nanowires with high length-diameter ratio could be a promising matrix for the fabrication of mediator-free biosensors, and may find wide potential applications in environmental analysis and biomedical detection.


Assuntos
Técnicas Biossensoriais/métodos , Hemoglobinas/química , Proteínas Imobilizadas/química , Nanofios/química , Nitritos/análise , Óxidos/química , Tungstênio/química , Técnicas Biossensoriais/instrumentação , Hemoglobinas/metabolismo , Proteínas Imobilizadas/metabolismo , Nanofios/ultraestrutura , Tamanho da Partícula , Reprodutibilidade dos Testes
17.
Zhongguo Zhong Yao Za Zhi ; 40(16): 3293-7, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26790310

RESUMO

To study the pharmacokinetic effect of different combined administration with monarch drug Ziziphi Spinosae Semen on its main components in rats. Sprague-Dawley (SD) rats were randomly divided into Ziziphi Spinosae Semen group, Ziziphi Spinosae Semen-Fructus Schisandrae Chinensis group, Ziziphi spinosae Semen-Salviae Miltiorrhize Radix et Rhizoma group and Zaoren Ansheng prescription group. After oral administration, HPLC was eluted with the mobile phase of acetonitrle-0.03% phosphate acid water in a gradient mode. The detection wavelength was 280 nm. The pharmacokinetic parameters of spinosin and ferulic acid were calculated by DAS 2. 0 software. Compared with Ziziphi Spinosae Semen group, Ziziphi Spinosae Semen-Fructus Schisandrae Chinensis group, Ziziphi Spinosae Semen-Salviae miltiorrhizae Radix et Rhizoma group showed a lower maximum plasma concentration (C(max)) and area under curve (AUC(0-t)) for spinosin and ferulic acid but higher clearance speed (CL/F); whereas the Zaoren Ansheng prescription group showed higher maximum plasma concentration (C(max)) and area under curve (AUC(0-t)) for spinosin and ferulic acid but lower clearance speed (CL/F). Compared with Ziziphi Spinosae Semen group, prescription group showed slower metabolism of spinosin and ferulic


Assuntos
Ácidos Cumáricos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/administração & dosagem , Ácidos Cumáricos/sangue , Interações Medicamentosas , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Feminino , Flavonoides/administração & dosagem , Flavonoides/sangue , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Ziziphus/química
19.
Med Mycol ; 47(6): 663-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19301174

RESUMO

A slowly enlarging arm ulcer appeared in a 61-year-old man with cutaneous T cell lymphoma. Skin biopsy revealed aseptate hyphae and nodular small/medium-sized pleomorphic CD4(+) T cell infiltration. Cultures yielded Absidia corymbifera which was identified by phenotypic and molecular methods. Since a thorough examination did not detect organ involvement, the patient was diagnosed as having primary cutaneous zygomycosis. This is the first case report of cutaneous zygomycosis caused by A. corymbifera in a patient with primary cutaneous CD4(+) small/medium-sized pleomorphic T-cell lymphoma. Other cases of primary cutaneous zygomycosis caused by A. corymbifera are also reviewed.


Assuntos
Absidia/isolamento & purificação , Linfoma Cutâneo de Células T/complicações , Zigomicose/complicações , Zigomicose/diagnóstico , Absidia/citologia , Absidia/genética , Braço/microbiologia , Braço/patologia , DNA Fúngico/análise , Humanos , Imuno-Histoquímica , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Úlcera/microbiologia , Úlcera/patologia , Zigomicose/microbiologia , Zigomicose/patologia
20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 30(5): 599-602, 2008 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-19024394

RESUMO

OBJECTIVE: To construct an animal model infected by Trichophyton rubrum. METHODS: Three different strains of Trichophyton rubrum were separated from clinical specimen for the infection of guinea pigs. Corticosteroids were given before and after the construction of animal model to facilitate the infection. Direct microscopy, culture, and histopathologic methods were adopted to verify the construction. RESULTS: Ten days after the inoculation of Trichophyton rubrum, with the intervention of corticosteroid, the guinea pigs were examined. Prominent scales and inflammation could be seen on the inoculation site of the Trichophyton rubrum infected guinea pig. Scales and hairs of Trichophyton rubrum infected guinea pig dealt with 10% potassium hydroxide, hypha out of the hair and microconidia or hypha in the hair shaft could be seen. Seven days after the inoculation of scales and hair on SDA plate, cultures of Trichophyton rubrum showed that the colonial morphology were identical to the original dermatophytes. PAS staining of infected guinea pig skin tissue showed that hypha and microconidia could be seen in the infundibula and hair root. CONCLUSION: With the intervention of corticosteroid, a stable guinea pig model infected by Trichophyton rubrum were successfully constructed.


Assuntos
Modelos Animais de Doenças , Cobaias , Tinha/microbiologia , Trichophyton/fisiologia , Animais , Feminino , Humanos , Masculino , Distribuição Aleatória , Tinha/imunologia , Trichophyton/patogenicidade
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