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1.
Zhongguo Zhong Yao Za Zhi ; 47(4): 988-1000, 2022 Feb.
Artículo en Zh | MEDLINE | ID: mdl-35285199

RESUMEN

This study explored the mechanism of Shenling Baizhu Powder(SLBZP) in the prevention and treatment of type 2 diabetes from the perspective of flora disorder and chronic inflammation. Fifty rats were randomly divided into normal control group, model control group, low-dose SLBZP group, medium-dose SLBZP group, and high-dose SLBZP group, with 10 rats in each group. The rats of 5 weeks old were administrated by gavage with ultrapure water and different doses of SLBZP decoction. The basic indicators such as body weight and blood glucose were monitored every week, and stool and intestinal contents were collected from the rats of 9 weeks old for 16 S rRNA sequencing and metabolomic analysis. An automatic biochemical analyzer was used to measure the serum biochemical indicators, ELISA to measure serum insulin, and chipsets to measure leptin and inflammatory cytokines. The results showed that SLBZP reduced the body weight as well as blood glucose, glycosylated hemoglobin, and lipid levels. In the rats of 9 weeks, the relative abundance of Anaerostipes, Turicibacter, Bilophila, Ochrobactrum, Acinetobacter, and Prevotella decreased significantly in the model control group, which can be increased in the high-dose SLBZP group; the relative abundance of Psychrobacter, Lactobacillus, Roseburia and Staphylococcus significantly increased in the model control group, which can be down-regulated in the high-dose SLBZP group. The differential metabolites of intestinal flora included 4-hydroxyphenylpyruvic acid, phenylpyruvic acid, octanoic acid, 3-indolepropionic acid, oxoglutaric acid, malonic acid, 3-methyl-2-oxovaleric acid, and methylmalonic acid. Moreover, SLBZP significantly lowered the levels of free insulin, insulin resistance and leptin resistance in rats. The variations in the serum levels of interleukin 1ß(IL-1ß) and monocyte chemoattractant protein-1(MCP-1) showed that SLBZP could alleviate chronic inflammation in rats. In conclusion, SLBZP can regulate intestinal flora and metabolites and relieve chronic inflammation to control obesity and prevent type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Insulina , Polvos , Ratas
2.
Plant Physiol ; 184(2): 933-944, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32788299

RESUMEN

Root development is important for normal plant growth and nutrient absorption. Studies have revealed the involvement of various factors in this complex process, improving our understanding of the relevant regulatory mechanisms. Here, we functionally characterize the role of Arabidopsis (Arabidopsis thaliana) phosphatidylinositol 4-kinase γ2 (PI4Kγ2) in root elongation regulation, which functions to modulate stability of the RING-type E3 ligase MYB30-INTERACTING E3 LIGASE1 (MIEL1) and auxin metabolism. Mutant plants deficient in PI4Kγ2 (pi4kγ2) exhibited a shortened root length and elongation zone due to reduced auxin level. PI4Kγ2 was shown to interact with MIEL1, regulating its degradation and furthering the stability of transcription factor MYB30 (which suppresses auxin metabolism by directly binding to promoter regions of GH3 2 and GH3 6). Interestingly, pi4kγ2 plants presented altered hypersensitive response, indicating that PI4Kγ2 regulates synergetic growth and defense of plants through modulating auxin metabolism. These results reveal the importance of protein interaction in regulating ubiquitin-mediated protein degradation in eukaryotic cells, and illustrate a mechanism coordinating plant growth and biotic stress response.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Variación Genética , Genotipo , Organogénesis de las Plantas/genética , Organogénesis de las Plantas/fisiología , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
3.
Sens Actuators B Chem ; 327: 128899, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32952300

RESUMEN

The recent pandemic outbreak of COVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a threat to public health globally. Thus, developing a rapid, accurate, and easy-to-implement diagnostic system for SARS-CoV-2 is crucial for controlling infection sources and monitoring illness progression. Here, we reported an ultrasensitive electrochemical detection technology using calixarene functionalized graphene oxide for targeting RNA of SARS-CoV-2. Based on a supersandwich-type recognition strategy, the technology was confirmed to practicably detect the RNA of SARS-CoV-2 without nucleic acid amplification and reverse-transcription by using a portable electrochemical smartphone. The biosensor showed high specificity and selectivity during in silico analysis and actual testing. A total of 88 RNA extracts from 25 SARS-CoV-2-confirmed patients and eight recovery patients were detected using the biosensor. The detectable ratios (85.5 % and 46.2 %) were higher than those obtained using RT-qPCR (56.5 % and 7.7 %). The limit of detection (LOD) of the clinical specimen was 200 copies/mL, which is the lowest LOD among the published RNA measurement of SARS-CoV-2 to date. Additionally, only two copies (10 µL) of SARS-CoV-2 were required for per assay. Therefore, we developed an ultrasensitive, accurate, and convenient assay for SARS-CoV-2 detection, providing a potential method for point-of-care testing.

4.
Curr Microbiol ; 77(1): 123-128, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31664502

RESUMEN

Phage PA-YS35 is a novel lytic Pseudomonas aeruginosa phage belonging to the Myoviridae family and was isolated from the sewage of the First Hospital of Jilin University. The biological properties testing indicated that phage PA-YS35 is stable between - 20 and 60 °C and pH 4-9. The one-step growth curve shows that the latent period of PA-YS35 was 9 min, and the burst period was about 21 min by the size of approximately 380 progeny phages per host cell. The genome of phage PA-YS35 is linear double-stranded DNA with a size of 93,296 bp and a GC content of 49.35%. The results from RAST gene annotation analysis showed that the PA-YS35 genome contains 172 open reading frames (ORFs); the function of 41 ORFs can be predicted, whereas the product of remaining 131 ORFs are hypothetical proteins. According to phylogenetic tree of RNA ligase encoding sequence, phage PA-YS35 has a close evolutionary relationship with Pseudomonas phage PAK P1 because both of them are located on the same branch. The study of phage PA-YS35 genome will provide useful information for further research on the interaction between phages and their hosts.


Asunto(s)
Genoma Viral/genética , Fagos Pseudomonas/genética , Composición de Base/genética , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Transmisión , Sistemas de Lectura Abierta/genética , Filogenia
5.
PLoS Genet ; 12(8): e1006252, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27529511

RESUMEN

Normal leaf margin development is important for leaf morphogenesis and contributes to diverse leaf shapes in higher plants. We here show the crucial roles of an atypical type II phosphatidylinositol 4-kinase, PI4Kγ5, in Arabidopsis leaf margin development. PI4Kγ5 presents a dynamics expression pattern along with leaf development and a T-DNA mutant lacking PI4Kγ5, pi4kγ5-1, presents serrated leaves, which is resulted from the accelerated cell division and increased auxin concentration at serration tips. Studies revealed that PI4Kγ5 interacts with and phosphorylates a membrane-bound NAC transcription factor, ANAC078. Previous studies demonstrated that membrane-bound transcription factors regulate gene transcription by undergoing proteolytic process to translocate into nucleus, and ANAC078 undergoes proteolysis by cleaving off the transmembrane region and carboxyl terminal. Western blot analysis indeed showed that ANAC078 deleting of carboxyl terminal is significantly reduced in pi4kγ5-1, indicating that PI4Kγ5 is important for the cleavage of ANAC078. This is consistent with the subcellular localization observation showing that fluorescence by GFP-ANAC078 is detected at plasma membrane but not nucleus in pi4kγ5-1 mutant and that expression of ANAC078 deleting of carboxyl terminal, driven by PI4Kγ5 promoter, could rescue the leaf serration defects of pi4kγ5-1. Further analysis showed that ANAC078 suppresses the auxin synthesis by directly binding and regulating the expression of auxin synthesis-related genes. These results indicate that PI4Kγ5 interacts with ANAC078 to negatively regulate auxin synthesis and hence influences cell proliferation and leaf development, providing informative clues for the regulation of in situ auxin synthesis and cell division, as well as the cleavage and functional mechanism of membrane-bound transcription factors.


Asunto(s)
1-Fosfatidilinositol 4-Quinasa/genética , Proteínas de Arabidopsis/genética , Ácidos Indolacéticos/metabolismo , Desarrollo de la Planta/genética , Factores de Transcripción/genética , 1-Fosfatidilinositol 4-Quinasa/biosíntesis , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/biosíntesis , División Celular/genética , Proliferación Celular/genética , ADN Bacteriano/genética , Regulación de la Expresión Génica de las Plantas , Mutación , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Plantas Modificadas Genéticamente , Factores de Transcripción/biosíntesis
6.
Bioconjug Chem ; 29(9): 3104-3112, 2018 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-30105903

RESUMEN

Depending on increasing extracellular protein utilization and altering metabolic programs, cancer cells could proliferate and survive without restricion by ingesting human serum albumin (HSA) to serve as nutritional amino acids. Here, we hypothesize that the consumption of albumin by cancer cells could be utilized as an efficient approach to targeted drug delivery. Lidamycin (LDM), an antitumor antibiotic with extremely potent cytotoxicity to cultured cancer cells, consists of an apoprotein (LDP) and an active enediyne chromophore (AE). In the present study, a novel albumin-lidamycin conjugate was prepared by DNA recombination and molecular reconstitution. Results show that the IC50 values of albumin-lidamycin conjugate (HSA-LDP-AE) for a variety of tested cancer cells were at subnanomolar levels. At tolerated doses, the albumin-lidamycin conjugate significantly inhibited the growth of lung carcinoma PG-BE1 xenografts by 97.8%. The therapeutic efficacy of the albumin-lidamycin conjugate was much stronger than that of free lidamycin. Meanwhile, the images of albumin-lidamycin conjugate showed obvious and lasting tumor localization and fluorescence enrichment and there was no detectable signal in nontumor locations. Taken together, albumin-lidamycin conjugate, a new format of lidamycin, could be a promising antitumor therapeutic agent and albumin-integration might be a feasible approach to targeted antitumor drug delivery.


Asunto(s)
Albúminas/química , Aminoglicósidos/química , Aminoglicósidos/uso terapéutico , Antibióticos Antineoplásicos/uso terapéutico , Enediinos/química , Enediinos/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Antibióticos Antineoplásicos/química , Línea Celular Tumoral , Femenino , Humanos , Ratones , Imagen Óptica , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Environ Monit Assess ; 189(11): 533, 2017 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-28971264

RESUMEN

The salinity stress inhibits the growth of Populus euphratica (P. euphratica), and the extent of inhibition tends to increase with a rise of salt concentration while the net photosynthesis rate, stomatal conductance, transpiration rate, and internal CO2 concentration are seen to decline with increasing salt concentration. Compared with the control group, the percentage decline is found to be about 48.50, 15.72, 42.09, and 48.33%, respectively. Although all chlorophyll fluorescence of P. euphratica exhibits a typical O-J-I-P curve in differently concentrated salt solutions, salinity stress shows a significant influence on the value of J and I step (P < 0.05). However, salinity stress was seen to induce a decrease in variable fluorescence (Fv)/maximal fluorescence value by 2.32, 8.78, 12.80, 12.93, 16.46, and 19.63% treated by 50-, 100-, 150-, 200-, 250-, and 300-mM salt solution compared with the control group, respectively. Salinity stress appeared also to induce a decrease in Fv/minimal fluorescence values by a magnitude of 5.22, 16.02, 18.06, 22.95, 26.34, and 32.19% in P. euphratica treated by 50-, 100-, 150-, 200-, 250-, and 300-mM salt solution relative to the control group, respectively. An increase in the content of malondialdehyde amounted to 4.12, 25.59, 34.60, 68.11, 70.72, and 67.68% in P. euphratica treated by 50-, 100-, 150-, 200-, 250-, and 300-mM salt solution compared to the control group, respectively. In terms of the content of proline, the salinity stress induced an increase by 4.94, 29.49, 53.20, 77.65, 82.46, and 90.68% in P. euphratica treated by 50-, 100-, 150-, 200-, 250-, and 300-mM salt solution, respectively.


Asunto(s)
Populus/fisiología , Salinidad , Estrés Fisiológico/fisiología , Monitoreo del Ambiente , Malondialdehído , Fotosíntesis/efectos de los fármacos , Prolina/metabolismo , Cloruro de Sodio
8.
Anal Bioanal Chem ; 406(22): 5359-67, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24916075

RESUMEN

A thermoresponsive imprinted monolith with the ability of molecular recognition for ketoprofen was prepared for the first time. The smart monolith was synthesized in a stainless steel column using acrylamide (AAm) and 2-acrylamide-2-methyl propanesulfonic acid (AMPS) as functional monomers, which can form interpolymer complexation to restrict access of the analyte to the imprinted networks at low temperatures. To avoid a high back pressure of the column derived from neat dimethyl sulfoxide (DMSO) as a porogenic solvent that is needed to solve polar AMPS, an ionic liquid, [BMIM]BF4, was introduced into the pre-polymerization mixture. The molecular recognition ability towards ketoprofen of the resulting thermoresponsive molecularly imprinted polymer (MIP) monolith displayed significant dependence on temperature compared with a non-imprinted column (NIP), and the greatest imprinting factor was achieved at the transition temperature of 35 °C (above 10). Furthermore, the number of binding sites of the smart MIP monolith at 35 °C was about 76 times as large as that at 25 °C. In addition, Freundlich analyses indicated that the thermoresponsive MIP monolith had homogeneous affinity sites at both 25 and 35 °C with heterogeneity index 0.9251 and 0.9851, respectively.


Asunto(s)
Acrilamida/análisis , Líquidos Iónicos/química , Cetoprofeno/química , Impresión Molecular , Ácidos Sulfónicos/análisis , Acrilamida/química , Adsorción , Animales , Química Farmacéutica , Dimetilsulfóxido/química , Contaminación de Alimentos , Gases , Concentración de Iones de Hidrógeno , Mercurio , Leche/química , Polímeros/química , Porosidad , Presión , Solventes/química , Espectroscopía Infrarroja por Transformada de Fourier , Ácidos Sulfónicos/química , Temperatura
9.
Int J Nanomedicine ; 19: 3805-3825, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38708177

RESUMEN

Telomere is a protective structure located at the end of chromosomes of eukaryotes, involved in maintaining the integrity and stability of the genome. Telomeres play an essential role in cancer progression; accordingly, targeting telomere dynamics emerges as an effective approach for the development of cancer therapeutics. Targeting telomere dynamics may work through multifaceted molecular mechanisms; those include the activation of anti-telomerase immune responses, shortening of telomere lengths, induction of telomere dysfunction and constitution of telomerase-responsive drug release systems. In this review, we summarize a wide variety of telomere dynamics-targeted agents in preclinical studies and clinical trials, and reveal their promising therapeutic potential in cancer therapy. As shown, telomere dynamics-active agents are effective as anti-cancer chemotherapeutics and immunotherapeutics. Notably, these agents may display efficacy against cancer stem cells, reducing cancer stem levels. Furthermore, these agents can be integrated with the capability of tumor-specific drug delivery by the constitution of related nanoparticles, antibody drug conjugates and HSA-based drugs.


Asunto(s)
Antineoplásicos , Neoplasias , Telomerasa , Telómero , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Telómero/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Telomerasa/antagonistas & inhibidores , Animales , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Inmunoterapia/métodos , Células Madre Neoplásicas/efectos de los fármacos
10.
Front Oncol ; 14: 1340872, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38463235

RESUMEN

Objective: At present, the structure of knowledge in the field of childhood thyroid cancer is not clear enough, and scholars lack a sufficient understanding of the developing trends in this field, which has led to a shortage of forward-looking outputs. The purpose of this research is to help scholars construct a complete knowledge framework and identify current challenges, opportunities, and development trends. Methods: We searched the literature in the Web of Science Core Collection database on August 7, 2023 and extracted key information from the top 100 most cited articles, such as the countries, institutions, authors, themes, and keywords. We used bibliometric tools such as bibliometrix, VOSviewer, and CiteSpace for a visualization analysis and Excel for statistical descriptions. Results: The top 100 most cited articles fluctuated over time, and the research was concentrated in European countries, the United States, and Japan, among which scientific research institutions and scholars from the United States made outstanding contributions. Keyword analysis revealed that research has shifted from simple treatment methods for pediatric thyroid cancer (total thyroidectomy) and inducing factors (the Chernobyl power station accident) to the clinical applications of genetic mutations (such as the BRAF and RET genes) and larger-scale genetic changes (mutation studies of the DICER1 gene). The thematic strategy analysis showed an increasing trend towards the popularity of fusion oncogenes, while the popularity of research on traditional treatments and diagnostics has gradually declined. Conclusion: Extensive research has been conducted on the basic problems of pediatric thyroid cancer, and there has been significant outputs in the follow-up and cohort analysis of conventional diagnostic and treatment methods. However, these methods still have certain limitations. Therefore, scholars should focus on exploring fusion genes, the clinical applications of molecular targets, and novel treatment methods. This study provides a strong reference for scholars in this field.

11.
Bioorg Med Chem ; 21(5): 1248-56, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23369687

RESUMEN

Two series (14a-d and 21a-h) of novel spin-labeled combretastatin derivatives were synthesized and evaluated for cytotoxicity against four tumor cell lines (K562, SGC-7901, Hela and HepG-2). Simultaneously, a representative compound 21a was selected to investigate the antitumor mechanisms of these synthetic compounds. The results indicated that some of the compounds showed significant cytotoxicity against four tumor cell lines in vitro and were more active than etoposide, a clinically available anticancer drug. Among the newly synthesized compounds, 21a, 21b and 21c displayed the greatest cytotoxicity against three tested tumor cell lines (HEPG-2, BGC-832 and Hela), with IC(50) values ranging from 0.15 to 1.05 µM, compared with values of 0.014-0.403 µM for 3-amino-deoxycombretastatin A-4 (3). In addition, the mechanistic analysis revealed that compound 21a effectively interfered with tubulin dynamics to prevent mitosis in cancer cells, leading to cell cycle arrest and, eventually, dose dependent apoptosis.


Asunto(s)
Antineoplásicos/síntesis química , Bibencilos/química , Antineoplásicos/química , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Bibencilos/síntesis química , Bibencilos/toxicidad , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Células Hep G2 , Humanos , Células K562 , Mitosis/efectos de los fármacos , Marcadores de Spin , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química , Moduladores de Tubulina/toxicidad
12.
Yao Xue Xue Bao ; 48(10): 1563-9, 2013 Oct.
Artículo en Zh | MEDLINE | ID: mdl-24417083

RESUMEN

This study is to optimize the preparation process of fusion protein Fv-LDP which was expressed in the form of inclusion body and consisted of lidamycin apoprotein LDP and single-chain Fv antibody (scFv) directed against type IV collagenase. The preparation and the dissolution of inclusion body, the immobilized metal affinity chromatography of the target protein and the renaturization by stepwise dialysis were optimized by single-factor analysis or orthogonal design. In addition, the refolded fusion protein Fv-LDP was refined by Sephadex G-75 chromatography followed by fluorescence-activated cell sorter (FACS)-based saturation binding assay to measure its antigen-binding activity. After optimization of the process, the purity of fusion protein Fv-LDP existed in the inclusion body was 63.9% and the corresponding solubility was 95.7%; Under denaturing conditions, the purity of fusion protein Fv-LDP was more than 95% after the purification process. The percentage of monomeric fusion protein Fv-LDP was 60% after the refolding process, while it was further refined to 85% which was 5.6-fold higher than that of the initial refolding condition. The refined fusion protein Fv-LDP could bind to human lung adenocarcinoma PAa cells and human hepatoma BEL-7402 cells with the dissociation constants (Kd) of 0.176 micromol x L(-1) and 0.904 micromol x L(-1), respectively. The preparation process of fusion protein Fv-LDP has been successfully optimized, which provides the experimental basis for the production and future development of fusion protein Fv-LDP, and might serve as a relatively practical system for the preparation of other scFv-based proteins expressed in the form of inclusion body.


Asunto(s)
Aminoglicósidos , Apoproteínas , Enediinos , Proteínas Recombinantes de Fusión , Anticuerpos de Cadena Única , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Aminoglicósidos/química , Aminoglicósidos/metabolismo , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Apoproteínas/química , Apoproteínas/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Colagenasas/inmunología , Enediinos/química , Enediinos/metabolismo , Escherichia coli/química , Escherichia coli/metabolismo , Humanos , Cuerpos de Inclusión/química , Cuerpos de Inclusión/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Unión Proteica , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Anticuerpos de Cadena Única/química , Anticuerpos de Cadena Única/metabolismo
13.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(6): 859-63, 2013 Dec 18.
Artículo en Zh | MEDLINE | ID: mdl-24343062

RESUMEN

OBJECTIVE: To study the expression of PPARγ mRNA in granulosa cells of patients with polycystic ovary syndrome (PCOS) and the impact of testosterone, insulin and PPARγ agonist rosiglitazone on granulosa cells (GCs). METHODS: The expression of PPARγ mRNA in GCs of patients with PCOS and normal controls were analyzed by Real-time PCR. We assessed the level of PPARγ mRNA in GCs from normal controls after treatment with testosterone, insulin, and rosiglitazone. RESULTS: The expression of PPARγ mRNA was lower in the GCs of PCOS than that of the controls (P<0.05). When testosterone concentration was 1 nmol/L, the expression of PPARγ mRNA was lower in the GCs as compared with the blank control (P<0.05). When testosterone concentration was 10 nmol/L, PPARγ mRNA increased in the GCs as compared with the blank control, which was of no significance (P>0.05). When insulin concentration was 10 nmol/L, the expression of PPARγ mRNA was higher in the GCs as compared with the blank control (P<0.05). When insulin concentration was 100 nmol/L, the expression of PPARγ mRNA increased, but the difference was not statistically significant (P>0.05). When rosiglitazone concentration was 1 nmol/L, the expression of PPARγ mRNA in ovarian GCs significantly increased, as compared with the blank control (P<0.05). When rosiglitazone concentration was at 10 nmol/L, the PPARγ mRNA expression significantly increased, as compared with the concentration at 1 nmol/L (P<0.05). CONCLUSION: PPARγ mRNA expression is down-regulated by testosterone, and up-regulated by insulin and rosiglitazone with different dosages. Decreased PPARγ mRNA in the GCs of PCOS is related to the clinical characteristics of PCOS.


Asunto(s)
Células de la Granulosa/metabolismo , PPAR gamma/metabolismo , Síndrome del Ovario Poliquístico/patología , Adulto , Femenino , Humanos , Insulina/metabolismo , PPAR gamma/agonistas , PPAR gamma/genética , Síndrome del Ovario Poliquístico/metabolismo , ARN Mensajero/metabolismo , Rosiglitazona , Testosterona/metabolismo , Tiazolidinedionas/metabolismo
14.
Zhonghua Gan Zang Bing Za Zhi ; 21(3): 213-7, 2013 Mar.
Artículo en Zh | MEDLINE | ID: mdl-23967744

RESUMEN

OBJECTIVE: To construct a short hairpin (sh)RNA targeting the gene encoding the MDM2 oncoprotein in order to investigate its role in human hepatocellular carcinoma (HCC) and its potential for use as a gene therapy strategy to inhibit HCC growth in vivo. METHODS: Small interfering (si)RNAs were designed targeting the MDM2 gene (siMDM2-1 and siMDM2-2) and unrelated sequences (negative control) and cloned into the expression plasmid pGCSilencer-U6-neo-GFP. A HCC mouse model was established by subcutaneous inoculation of HepG2 cells (2 x 10(6) in 0.2 ml) into 20 nude mice. The inoculated mice were divided into four equal groups for tumor-localized injections of saline, negative control siRNA plasmid, siMDM2-1 plasmid, and siMDM2-2 plasmid. Tumor growth was observed daily (by caliper measurement) for one month, when mice were sacrificed by cervical dislocation. The tumor mass was resected for analysis of tumor inhibition rate (% = [(average tumor weight of control group - average tumor weight of treatment group) / average tumor weight of control group x 100]) and effects on MDM2 and p53 mRNA and protein expression (by reverse transcription- PCR and western blotting, both normalized to beta-actin). Significance of between-group differences was assessed by one-way ANOVA or LSD test; pairwise comparisons were made by the Chi-squared test. RESULTS: siMDM2-1 and siMDM2-2 suppressed the xenografted tumor growth remarkably (60.6% and 54.6% inhibition rates, respectively), significantly reduced the expression ofMDM2 gene (62.8% and 61.6%) and protein (60.7% and 59.5%), and significantly increased p53 gene (47.1% and 45.6%) and protein (45.9% and 44.3%) (all, P < 0.05). CONCLUSION: shRNA-mediated silencing of the MDM2 gene effectively inhibits HCC tumorigenesis of subcutaneously xenografted HepG2 cells in nude mice, and the mechanism may involve p53.


Asunto(s)
Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas Proto-Oncogénicas c-mdm2/genética , ARN Interferente Pequeño , Animales , Carcinoma Hepatocelular/genética , Proliferación Celular , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Masculino , Ratones , Ratones Desnudos , Plásmidos , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Interferencia de ARN , ARN Mensajero/genética , Transfección , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Int J Biol Macromol ; 226: 1088-1099, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36435475

RESUMEN

OBJECTIVE: To prepare a recombinant EGFR-targeted fusion protein drug conjugate acting on telomere and telomerase; and evaluate its antitumor efficacy. METHODS: We prepared a recombinant fusion protein Fv-LDP-D3 which consists of the Fv fragment of an anti-EGFR monoclonal antibody (MAb), the apoprotein of lidamycin (LDP), and the third domain (D3) of human serum albumin (HSA); then generated the conjugate Fv-LDP-D3∼AE by integrating the active enediyne chomophore (AE) of lidamycin. Accordingly, in vitro and in vivo experiments were performed. RESULTS: As shown, Fv-LDP-D3 specifically bound to EGFR highly-expressing cancer cells and intensely entered K-Ras mutant cells via enhanced macropinocytosis. By in vivo imaging, Fv-LDP-D3 displayed intense accumulation and persistent retention in tumor-site. Furthermore, the conjugate Fv-LDP-D3∼AE displayed highly potent cytotoxicity to cancer cells with IC50 at 0.1 nM level. The conjugate induced telomere shortening and downregulation of telomerase and EGFR pathway related proteins. Fv-LDP-D3∼AE exhibited prominent antitumor efficacy against human colorectal cancer xenograft accompanying with significant increase of serum IFN-ß in athymic mice. CONCLUSION: The recombinant fusion protein conjugate that exhibits the capability of tumor-targeting drug delivery can induce telomere shortening and telomerase downregulation. The investigation may lay the foundation for the development of MAb-HSA domain-based fusion protein drug conjugates.


Asunto(s)
Inmunoconjugados , Telomerasa , Animales , Ratones , Humanos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/metabolismo , Telomerasa/genética , Telomerasa/metabolismo , Receptores ErbB/metabolismo , Regulación hacia Abajo , Acortamiento del Telómero , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Inmunoconjugados/farmacología , Telómero/metabolismo
16.
World J Gastrointest Oncol ; 15(10): 1823-1828, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37969415

RESUMEN

BACKGROUND: Multiple primary colorectal carcinoma (MPCC) is a rare clinical disease, which is challenging to differentiate from metastatic disease using histopathological methods. Next-generation sequencing (NGS) has been employed to identify multiple primary cancers. CASE SUMMARY: This study a rare case of a 63-year-old male patient diagnosed with MPCC by targeted NGS, which was initially missed by radiological evaluation. The patient was found to have two tumors located on the surface of the colorectum which had distinct genomic alterations. Based on wild-type KRAS detected in the unresected tumor, the patient benefited from the epidermal growth factor receptor (EGFR) inhibitor cetuximab treatment, but developed novel mutations including KIF5B-RET fusion, which provides a possible resistance mechanism to anti-EGFR therapy. CONCLUSION: Our case highlights the necessity of using genetic testing for primary tumor diagnosis and the application of serial plasma circulating tumor DNA profiling for dynamic disease monitoring.

17.
Zhong Yao Cai ; 35(5): 749-56, 2012 May.
Artículo en Zh | MEDLINE | ID: mdl-23213739

RESUMEN

OBJECTIVE: To analyze the differentially expressed proteins of the synergy effect of Radix Hedysari polysaccharides (HPS)combined with chemotherapy (Cy) on S180 tumor cells. METHODS: The total proteins extracted from the HPS combined with Cy treated S180 cells in tumor-bearing mice were separated by two dimentional gel electrophoresis (2-DE)and compared with those from Cy treated S180 cells using PDQuest 8.0 software. Mass spectrometry was applied to identify the differentially expressed proteins. Western blot was used to determine the differential expression of one protein. RESULTS: Twenty-four differentially-expressed proteins in HPS group were discovered. The five differential expressed proteins among twenty-four proteins were later identified by mass spectrometry and Mascot software as heat-shock protein hsp84 (HSP90beta), apolipoprotein A, albumin, heat shock protein beta-1 (HSP27)and unnamed protein product, including one up regulated and four down regulated expressed proteins respectively. Results from Western blot manifested the same trend as from proteomics analysis. CONCLUSION: Proteomics technique can be used to discover target proteins associated with the synergy effect of HPS combined with Cy on S180 tumor cells, involving some important proteins related to energy metabolism, oxidative stress and apoptosis induction signal transduction.


Asunto(s)
Ciclofosfamida/farmacología , Fabaceae/química , Polisacáridos/farmacología , Proteínas/metabolismo , Proteómica , Sarcoma 180/metabolismo , Animales , Apoptosis , Western Blotting , Línea Celular Tumoral , Ciclofosfamida/administración & dosificación , Quimioterapia Combinada , Electroforesis en Gel Bidimensional , Femenino , Regulación Neoplásica de la Expresión Génica , Masculino , Ratones , Polisacáridos/administración & dosificación , Proteínas/análisis , Sarcoma 180/patología
18.
Front Plant Sci ; 13: 967849, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36275515

RESUMEN

As a desert shrub, Haloxylon ammodendron combines ecological, economic, and social benefits and plays an important role in the ecological conservation of arid desert areas. Understanding its physiological characteristics and its mechanism of light energy utilization is important for the conservation and utilization of H. ammodendron. Therefore, we selected five stands (5-, 11-, 22-, 34-, and 46-year-old) of H. ammodendron as research objects in the study and measured their photosynthetic light response curves by a portable open photosynthesis system (Li-6400) with a red-blue light source (6400-02B). Then, we measured the leaf chlorophyll parameters in the laboratory, calculated the photosynthetic characteristics by using Ye Zipiao's photosynthetic model, analyzed their variation patterns across stand ages, and explored the relationships between leaf chlorophyll parameters and photosynthetic characteristics. The results showed that leaf chlorophyll parameters and photosynthetic characteristics of H. ammodendron at different stand ages were significantly different. Chl content, P nmax, and LUEmax of H. ammodendron were V-shaped with the increase of stand age. The 5-year-old H. ammodendron was in the rapid growth period, synthesized more Chl a+b content (8.47 mg g-1) only by using a narrower range of light, and the Pnmax and LUEmax were the highest with values of 36.21 µmol m-2 s-1 and 0.0344, respectively. For the 22-year-old H. ammodendron, due to environmental stress, the values of Chl a+b content, P nmax, and LUEmax were the smallest and were 2.64 mg g-1, 25.73 µmol m-2 s-1, and 0.0264, respectively. For the older H. ammodendron, its Chl content, P nmax, and LUEmax were not significantly different and tended to stabilize but were slightly higher than those of the middle-aged H. ammodendron. On the other hand, the other photosynthetic parameters did not show significant variation patterns with stand age, such as R d, AQE, LSP, LCP, and I L-sat. In addition, we found that the relationships between Chl a+b content and P nmax and between Chl a+b content and LUEmax were highly correlated, except for the older H. ammodendron. Thus, using leaf chlorophyll content as a proxy for photosynthetic capacity and light use efficiency should be considered with caution. This work will provide a scientific reference for the sustainable management of desert ecosystems and vegetation restoration in sandy areas.

19.
Drug Dev Ind Pharm ; 37(7): 868-74, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21231900

RESUMEN

Particulate systems that could deliver drug specifically to duodenum have not yet been reported. The aim of this study was to develop a novel duodenum-specific drug delivery system based on thiolated chitosan and hydroxypropyl methylcellulose acetate maleate (HPMCAM) for the duodenal ulcer application. Berberine hydrochloride was used as model drug. Thiolated chitosan was synthesized and further used for the preparation of mucoadhesive microspheres. HPMCAM, which is insoluble below pH 3.0 was synthesized and used for the coating of thiolated chitosan microspheres (TCM). The resulting thiolated chitosan immobilized on chitosan was 268.21 ± 18 µmol/g. In vitro mucoadhesion study showed that the mucoadhesion property of TCM was better than that of chitosan microspheres. Morphological observation showed that the HPMCAM coating would maintain its integrity in simulated gastric fluid (SGF) for 2 h and dissolved quickly in simulated pathological duodenal fluid (SPDF; pH 3.3). In vitro drug release studies showed that only 4.75% of the drug was released in SGF for 2 h, while nearly 90% of the drug was released within 6 h after transferring into SPDF.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Duodeno/efectos de los fármacos , Adhesividad , Berberina/administración & dosificación , Quitosano , Úlcera Duodenal/tratamiento farmacológico , Duodeno/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Derivados de la Hipromelosa , Técnicas In Vitro , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Metilcelulosa/análogos & derivados , Microscopía Electrónica de Rastreo , Microesferas , Comprimidos Recubiertos
20.
Int J Ophthalmol ; 14(10): 1581-1588, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34667736

RESUMEN

AIM: To compare the clinical outcomes of wavefront guided femtosecond LASIK (WFG LASIK) and conventional femtosecond LASIK (NWFG LASIK) in eyes with myopia and myopia astigmatism. METHODS: This was a retrospective, nonrandomized, comparative investigation enrolling 236 eyes of 122 patients (18-50y) with low & moderate and high myopia. The WFG group including 97 eyes (50 patients) undergone WFG LASIK and the NWFG group including 139 eyes (72 patients) undergone conventional LASIK. Mean efficacy index, high order aberrations (HOAs), pupil size and the quality of visual questionnaire were evaluated 6mo postoperatively. RESULTS: There is no difference between WFG group (-0.054±0.049 in logMAR) and NWFG group (-0.040±0.056) in uncorrected distance visual acuity (UDVA) postoperatively. The myopia astigmatism is higher in WFG group than that in NWFG group (P<0.05). However, the mean efficacy index (MEI) in the WFG group (1.09±0.106) is better than that in the NWFG group (1.036±0.124; P<0.001). Increased HOAs were observed in NWFG group (0.30±0.196) than that in WFG group (0.146±0.188; P<0.001). The pupil size is larger in WFG group (5.15±0.76 mm) than that in NWFG group (4.32±0.52 mm). The patients are satisfied with the clinical surgery, yet WFG group showed better visual quality using the questionnaire survey. Meanwhile, high myopia would result in worse MEI, HOAs and visual quality than low & moderate myopia. CONCLUSION: WFG and NWFG FS-LASIK are both effective and safe procedures to correct low & moderate and high myopia, but WFG FS-LASIK gives a better postoperative MEI, aberrometric control and predictable outcome. Meanwhile, WFG FS-LASIK is better than NWFG FS-LASIK in correction of myopia astigmatism. Low & moderate myopia allow better clinical outcomes than high myopia using any surgical method.

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