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1.
Microorganisms ; 12(4)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38674740

RESUMO

In practical applications, the effectiveness of biological control agents such as Bacillus is often unstable due to different soil environments. Herein, we aimed to explore the control effect and intrinsic mechanism of Bacillus in black soil and red soil in combination with tomato Verticillium wilt. Bacillus application effectively controlled the occurrence of Verticillium wilt in red soil, reducing the incidence by 19.83%, but played a limited role in black soil. Bacillus colonized red soil more efficiently. The Verticillium pathogen decreased by 71.13% and 76.09% after the application of Bacillus combinations in the rhizosphere and bulk of the red soil, respectively, while there was no significant difference in the black soil. Additionally, Bacillus application to red soil significantly promoted phosphorus absorption. Furthermore, it significantly altered the bacterial community in red soil and enriched genes related to pathogen antagonism and phosphorus activation, which jointly participated in soil nutrient activation and disease prevention, promoting tomato plant growth in red soil. This study revealed that the shaping of the bacterial community by native soil may be the key factor affecting the colonization and function of exogenous Bacillus.

2.
Microbiol Res ; 283: 127688, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479233

RESUMO

Plant secondary metabolites possess a wide range of pharmacological activities and play crucial biological roles. They serve as both a defense response during pathogen attack and a valuable drug resource. The role of microorganisms in the regulation of plant secondary metabolism has been widely recognized. The addition of specific microorganisms can increase the synthesis of secondary metabolites, and their beneficial effects depend on environmental factors and plant-related microorganisms. This article summarizes the impact and regulatory mechanisms of different microorganisms on the main secondary metabolic products of plants. We emphasize the mechanisms by which microorganisms regulate hormone levels, nutrient absorption, the supply of precursor substances, and enzyme and gene expression to promote the accumulation of plant secondary metabolites. In addition, the possible negative feedback regulation of microorganisms is discussed. The identification of additional unknown microbes and other driving factors affecting plant secondary metabolism is essential. The prospects for further analysis of medicinal plant genomes and the establishment of a genetic operation system for plant secondary metabolism research are proposed. This study provides new ideas for the use of microbial resources for biological synthesis research and the improvement of crop anti-inverse traits for the use of microbial resources.


Assuntos
Plantas Medicinais , Metabolismo Secundário
3.
Cell Cycle ; 23(3): 328-337, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38512812

RESUMO

OBJECTIVE: The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). METHODS: We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What's more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. RESULTS: Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. CONCLUSION: Our results suggest that NINJ2 polymorphisms are associated with CHD risk.


Assuntos
Moléculas de Adesão Celular Neuronais , Doença das Coronárias , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Masculino , Polimorfismo de Nucleotídeo Único/genética , Moléculas de Adesão Celular Neuronais/genética , Predisposição Genética para Doença/genética , Pessoa de Meia-Idade , Doença das Coronárias/genética , Estudos de Casos e Controles , Idoso , Fatores de Risco , Genótipo
4.
J Exp Clin Cancer Res ; 42(1): 253, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37770937

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR)-T immunotherapy fails to treat solid tumors due in part to immunosuppressive microenvironment. Excess lactate produced by tumor glycolysis increases CAR-T immunosuppression. The mechanism of lactate inducing the formation of immunosuppressive microenvironment remains to be further explored. METHODS: Immunocyte subpopulations and molecular characteristics were analyzed in the orthotopic xenografts of nude mice using flow cytometry assay and immunohistochemical staining after oxamate, a lactate dehydrogenase A (LDHA) inhibitor, and control T or CAR-T cells injection alone or in combination. RT-qPCR, western blot, flow cytometry, immunofluorescence, luciferase reporter assay, chromatin immunoprecipitation and ELISA were performed to measure the effect of lactate on the regulation of CD39, CD73 and CCR8 in cultured glioma stem cells, CD4 + T cells or macrophages. RESULTS: Oxamate promoted immune activation of tumor-infiltrating CAR-T cells through altering the phenotypes of immune molecules and increasing regulatory T (Treg) cells infiltration in a glioblastoma mouse model. Lactate accumulation within cells upregulated CD39, CD73 and CCR8 expressions in both lactate-treated cells and glioma stem cells-co-cultured CD4 + T cells and macrophages, and intracellular lactate directly elevated the activities of these gene promotors through histone H3K18 lactylation. CONCLUSIONS: Utilizing lactate generation inhibitor not only reprogramed glucose metabolism of cancer stem cells, but also alleviated immunosuppression of tumor microenvironment and reduced tumor-infiltrating CAR-Treg cells, which may be a potential strategy to enhance CAR-T function in glioblastoma therapy.


Assuntos
Glioblastoma , Glioma , Receptores de Antígenos Quiméricos , Camundongos , Animais , Humanos , Glioblastoma/genética , Receptores de Antígenos Quiméricos/genética , Camundongos Nus , Linhagem Celular Tumoral , Lactatos , Microambiente Tumoral , Receptores CCR8
5.
Int J Radiat Biol ; 99(12): 1890-1907, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37406172

RESUMO

PURPOSE: After irradiation, double-stranded DNA leaked into the cytoplasm activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, leading to the production of type I interferon (IFNI). In this study, we sought to probe the effect of ionizing radiation on activity of cGAS-STING-IFNI pathway in normoxic or hypoxic glioma cells and explore a more effective method to activate the signaling pathway, thereby activating the anti-tumor immune response and improving the therapeutic effect of radiotherapy for glioma. MATERIALS AND METHODS: Human glioma cells U251 and T98G cultured in normoxia or hypoxia (1% O2) were irradiated with different doses of X-ray. The relative expressions of cGAS, IFN-I stimulated genes (ISGs), and three-prime repair exonuclease 1 (TREX1) were detected by qPCR. The expression levels of interferon regulatory factor 3 (IRF3) and p-IRF3 proteins were detected by Western blot. The production of cGAMP and IFN-ß in the supernatant was detected by ELISA assay. U251 and T98G cell lines with stable knockdown of TREX1 were established after transfection with lentivirus vectors. EdU cell proliferation assay was used to screen suitable metal ions concentrations. The phagocytosis of DCs was observed by immunofluorescence microscope. The phenotype of DCs was detected by flow cytometry. The migration ability of DCs was detected by a transwell experiment. RESULTS: We found that cytosolic dsDNA, 2'3'-cGAMP, cGAS and ISGs expression, and IFN-ß in cell supernatant were all increased with the doses of X-ray in the range of 0-16 Gy in normoxic glioma cells. Nevertheless, hypoxia significantly inhibited the radiation-induced dose-dependent activation of cGAS-STING-IFNI pathway. Furthermore, manganese (II) ion (Mn2+) significantly improved cGAS-STING-IFNI pathway activation induced by X-ray in both normoxic and hypoxic glioma cells, thereby promoting the maturation and migration of DCs. CONCLUSIONS: The responses of cGAS-STING-IFNI pathway to ionizing radiation were mainly investigated under normoxic condition, but the experiments described here indicated that hypoxia could hinder the pathway activation. However, Mn2+ showed radiosensitizing effects on the pathway under either normoxic or hypoxic conditions demonstrating its potential as a radiosensitizer for glioma through activating an anti-tumor immune response.


Assuntos
Glioma , Manganês , Humanos , Manganês/farmacologia , Marrocos , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , DNA , Glioma/radioterapia , Radiação Ionizante , Hipóxia
6.
Mol Genet Genomics ; 298(6): 1353-1364, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37518364

RESUMO

The study was designed to detect the expression and clinical significance of the HEATR3 gene in bladder cancer (BCa) and to preliminarily explore whether this gene can affect the occurrence and development of BCa through the AKT/ERK signaling pathway. The expression and prognostic value of HEATR3 were explored based on The Cancer Genome Atlas (TCGA) and Genotypic Tissue Expression (GTEx) databases. Microarray immunohistochemical analysis was performed in 30 BCa cases to investigate the level of HEATR3 protein and to explore the relationship between HEATR3 and the clinicopathological features of BCa. Western Blot and qRT-PCR were used to detect HEATR3 protein and mRNA in BCa cell lines (5637, TCCSUP, SW780) and fallopian tube epithelial cell (SV-HUC-1). CCK8 method was employed to study the proliferation of BCa cells after heat treatment. Transwell assay was conducted to analyze the effect of HEATR3 on cell migration and invasion. And cell cycle and apoptosis were detected by flow cytometry. Furthermore, Western Blot assay was used to probe the effects of down-regulation of HEATR3 expression on the expression and phosphorylation levels of AKT and ERK proteins in BCa cells. Bioinformatics analysis showed that HEATR3 was significantly up-regulated in BCa, and high HEATR3 expression was associated with poor prognosis of BCa patients. In vitro experiments demonstrated that HEATR3 expression was up-regulated in BCa tissues compared with that in adjacent tissues. HEATR3 protein was also up-regulated in malignant cell lines. HEATR3 knockdown in BCa cells could inhibit cell proliferation, invasion and migration, block cell cycle and promote cell apoptosis. At the same time, HEATR3 knockdowns reduced the expression levels of p-AKT and p-ERK proteins. HEATR3 knockdown inhibits the development of BCa cells through the AKT/ERK signaling pathway. and it may become one of the most promising molecular targets for BCa treatment.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Neoplasias da Bexiga Urinária , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Ciclo Celular/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
7.
Int J Radiat Biol ; 99(12): 1908-1924, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37463506

RESUMO

PURPOSE: Ferroptosis is a type of regulatory cell death, caused by excessive lipid peroxidation This study aimed to explore whether ionizing radiation could induce ferroptosis in glioma cells and whether carbonic anhydrase 9 (CA9) knockdown could enhance the killing effect of ionizing radiation on hypoxic glioma cells through ferroptosis. MATERIALS AND METHODS: The protein levels of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) were detected by Western blot in glioma cells irradiated by different doses of X-ray. The relative mRNA levels of ferroptosis markers and intracellular iron-associated proteins were detected by Real-time qPCR. Lipid peroxidation of glioma cells was detected by oxidation-sensitive probe C11-BODIPY581/591 staining. CCK-8 Assay was used to detect cell viability after X-ray irradiation. Cloning formation assay was used to assess the radiosensitivity of glioma cells. The exposure of cell surface calreticulin was measured by immunofluorescence staining. RESULTS: X-ray induced lipid peroxidation and ferroptosis markers expression in U251 and GL261 glioma cells. Knockdown of CA9 in hypoxic glioma cells significantly altered the expression of iron regulation-related proteins and enhanced X-ray-induced ferroptosis and radiosensitivity. The ferroptosis inhibitor significantly improved the survival of cells irradiated by X-ray, while ferroptosis inducers (FINs) enhanced the lethal effect of X-ray on cells. Enhancing ferroptosis in glioma cells promoted the exposure and release of damage-associated molecular patterns (DAMPs). CONCLUSIONS: Ionizing radiation can induce ferroptosis in glioma cells. CA9 knockdown can enhance the radiosensitivity of hypoxic glioma cells and overcome the resistance of ferroptosis under hypoxia. Enhancing ferroptosis will become a new idea to improve the efficacy of radiotherapy for glioma.


Assuntos
Anidrase Carbônica IX , Ferroptose , Glioma , Tolerância a Radiação , Hipóxia Tumoral , Glioma/genética , Glioma/radioterapia , Radiação Ionizante , Anidrase Carbônica IX/genética , Técnicas de Silenciamento de Genes , Linhagem Celular Tumoral , Humanos , Animais , Camundongos , Alarminas/metabolismo , Peroxidação de Lipídeos
8.
Front Public Health ; 11: 1150310, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275480

RESUMO

Background: Loneliness is an important problem afflicting the health of older adults, and has been proven to be associated with social capital. Previous research in China rarely investigated the differences of social capital and loneliness between older adults living in community dwellings and nursing homes. This study aims to examine the status of social capital and loneliness among older adults living in community dwellings and nursing homes, and analyze the relationship between them. Methods: A total of 1,278 older adults were recruited for the study from the cities of Hangzhou, Huzhou, and Lishui in Zhejiang Province of China from July to October 2021 by using multi-stage stratified random sampling. Questionnaires were used to collect data on the participants' sociodemographic characteristics, social capital, and loneliness. Hierarchical multiple regression was used to examine the relationship between social capital and loneliness. The interaction of social capital and institutionalization on loneliness was also explored. Results: Compared with community-dwelling older adults, institutionalized older adults had higher levels of loneliness and lower degrees of social support, social connection, trust, cohesion, and reciprocity. A further analysis of the social capital showed that low levels of social support, trust, and cohesion were related to high levels of loneliness among adults in both community dwellings and nursing homes. Social connection was negatively correlated with loneliness among older adults living in community dwellings. Institutionalization itself demonstrated a strong effect on loneliness. Conclusion: Health-related policies should help older adults gain more social support, trust and cohesion to alleviate their loneliness. This is particularly crucial for older adults living in nursing homes, as they have higher levels of loneliness and lower levels of social capital than noninstitutionalized older adults.


Assuntos
Vida Independente , Capital Social , Humanos , Idoso , Solidão , Casas de Saúde , China/epidemiologia
9.
Life Sci ; 325: 121772, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37178864

RESUMO

AIMS: Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast in liver fibrosis remains unknown. In this study, we examined whether the pharmacological inhibition of CysLTR1 could protect mice against hepatic fibrosis. MATERIALS AND METHODS: Carbon tetrachloride (CCl4) and methionine-choline deficient (MCD) diet models were used in this study. The expression of CysLTR1 in liver were detected by RT-qPCR and Western blot analysis. Liver hydroxyproline levels, fibrotic genes expression, serum biochemical indexes and inflammatory factors were used to evaluate the effect of montelukast on liver fibrosis, injury, and inflammation. In vitro, we used the RT-qPCR and Western blot analysis to assess CysLTR1 in mouse primary hepatic stellate cell (HSC) and human LX-2 cell line. The role of montelukast on HSC activation and the underlying mechaisms were determined using RT-qPCR analysis, Western blot and immunostaining assays. KEY FINDINGS: Chronic stimulation from CCl4 and MCD diet upregulated the mRNA and protein levels of CysLTR1 in the liver. Pharmacological inhibition of CysLTR1 by montelukast ameliorated liver inflammation and fibrosis in both models. Mechanistically, montelukast suppressed HSC activation by targeting the TGFß/Smad pathway in vitro. The hepatoprotective effect of montelukast was also associated with reduced liver injury and inflammation. SIGNIFICANCE: Montelukast suppressed CCl4- and MCD-induced chronic hepatic inflammation and liver fibrosis. CysLTR1 might be a therapeutic target for treating liver fibrosis.


Assuntos
Tetracloreto de Carbono , Metionina , Camundongos , Humanos , Animais , Tetracloreto de Carbono/toxicidade , Metionina/metabolismo , Células Estreladas do Fígado/metabolismo , Transdução de Sinais , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Fígado/metabolismo , Fibrose , Racemetionina/metabolismo , Racemetionina/farmacologia , Inflamação/patologia , Dieta , Fator de Crescimento Transformador beta1/metabolismo
10.
Funct Integr Genomics ; 23(2): 85, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36930384

RESUMO

Pharmacogenomics has been widely used to study the very important pharmacogenetic (VIP) variants among different populations. However, there is little pharmacogenomic information about the Chinese Hui population. Our research aimed to reveal the outstandingly different loci in the Hui population, and provide a theoretical foundation for personalized drug use in the Hui population, so as to facilitate more effective treatment of diseases. This study genotyped 53 VIP variants of 26 genes in 200 independent Hui individuals based on the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB). Remarkable differences in the genotype and allele frequencies between the Hui and 26 other populations from the 1000 Genomes Project were assessed using the χ2 test. The genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in PTGS2 (rs20417), NAT2 (rs1801280), NAT2 (rs1208), ACE (rs4291), and CYP2D6 (rs1065852) were considerably different in the Hui population compared with those in the other 26 populations. Besides, using the PharmGKB database, we identified several VIP variants that may alter the drug metabolism of ibuprofen, rofecoxib (PTGS2), captopril (ACE), citalopram, and escitalopram (CYP2D6). We also discovered other variants associated with adverse reactions to cisplatin and cyclophosphamide (NAT2). Our study indicated that the loci of PTGS2 (rs20417), NAT2 (rs1801280 and rs1208), ACE (rs4291), and CYP2D6 (rs1065852) in the Hui population were obviously different from those in the other 26 populations, which provides reliable information for predicting drug efficacy. Besides, it supplements the pharmacogenomic knowledge of the Hui population and lays the foundation for the individualized treatment for the Hui population.


Assuntos
Arilamina N-Acetiltransferase , Farmacogenética , Humanos , Citocromo P-450 CYP2D6/genética , Ciclo-Oxigenase 2/genética , Etnicidade/genética , Polimorfismo de Nucleotídeo Único , Genótipo , China , Arilamina N-Acetiltransferase/genética
11.
Am J Chin Med ; 51(3): 575-594, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36823097

RESUMO

Breast cancer is a malignant disease with an increasing incidence. Chemotherapy is still an important means for breast cancer treatment, but multidrug resistance (MDR) greatly limits its clinical application. Therefore, the high-efficiency MDR reversal agents are urgently needed. Traditional Chinese medicine (TCM) monomers have unique advantages in reversing chemotherapeutic MDR because of its low toxicity, high efficiency, and ability to impact multiple targets. This review firstly summarizes the major mechanisms of MDR in breast cancer, including the reduced accumulation of intracellular chemotherapeutic drugs, the promoted inactivation of intracellular chemotherapeutic drugs, and the enhanced damage repair ability of DNA, etc., and secondly highlights the research progress of 15 kinds of TCM monomers, including curcumin, resveratrol, emodin, apigenin, tetrandrine, gambogic acid, matrine, paeonol, schisandrin B, [Formula: see text]-elemene, astragaloside IV, berberine, puerarin, tanshinone IIA, and quercetin, in reversing MDR of breast cancer. This review also provides the suggestion for the future research of MDR reversal agents in breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Medicina Tradicional Chinesa , Resistencia a Medicamentos Antineoplásicos , Resistência a Múltiplos Medicamentos
12.
BMC Cancer ; 22(1): 1181, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384536

RESUMO

BACKGROUND: Repair pathway genes play an important role in the development of lung cancer. The study aimed to assess the correlation between single nucleotide polymorphisms (SNPs) in DNA repair gene (GTF2H1 and RAD54L2) and the risk of lung cancer. METHODS: Five SNPs in GTF2H1 and four SNPs in RAD54L2 in 506 patients with lung cancer and 510 age-and gender-matched healthy controls were genotyped via the Agena MassARRAY platform. The influence of GTF2H1 and RAD54L2 polymorphisms on lung cancer susceptibility was assessed using logistic regression analysis by calculating odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: RAD54L2 rs9864693 GC genotype increased the risk of lung cancer (OR = 1.33, 95%CI: 1.01-1.77, p = 0.045). Stratified analysis found that associations of RAD54L2 rs11720298, RAD54L2 rs4687592, RAD54L2 rs9864693 and GTF2H1 rs4150667 with lung cancer risk were found in subjects aged ≤ 59 years. Precisely, a protective effect of RAD54L2 rs11720298 on the occurrence of lung cancer was observed in non-smokers and drinkers. GTF2H1 rs4150667 was associated with a decreased risk of lung cancer in subjects with BMI ≤ 24 kg/m2. RAD54L2 rs4687592 was associated with an increased risk of lung cancer in drinkers. In addition, GTF2H1 rs3802967 was associated with a reduced risk of lung squamous cell carcinoma. CONCLUSION: Our study first revealed that RAD54L2 rs9864693 was associated with an increased risk of lung cancer in the Chinese Han population. This study may increase the understanding of the effect of RAD54L2 and GTF2H1 polymorphisms on lung cancer occurrence.


Assuntos
DNA Helicases , Predisposição Genética para Doença , Neoplasias Pulmonares , Fator de Transcrição TFIIH , Humanos , Povo Asiático/genética , China/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Fator de Transcrição TFIIH/genética , DNA Helicases/genética
13.
Oxid Med Cell Longev ; 2022: 5424411, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238646

RESUMO

Objective: Local radiotherapy may cause distant tumor regression via inducing immunogenic cell death (ICD). Here, we investigated the effect of curcumin on ionizing radiation-induced immunogenic cell death in normoxic or hypoxic glioma cells and its mechanism in vitro and vivo. Methods: Hypoxic or normoxic glioma cell apoptosis and the cell surface exposure of calreticulin (CRT) were detected by flow cytometry. Extracellular ATP and HSP70 were measured by chemiluminescence assay and ELISA, respectively. Endoplasmic reticulum (ER) stress protein levels were detected by western blot. Moreover, the induction of bona fide ICD was detected by vaccination assays in mice bearing glioma model. Spleen lymphocytes and tumor-infiltrating lymphocyte subsets were analyzed by flow cytometry and immunohistochemistry. Results: Curcumin incubation before X-ray irradiation significantly increased radiation-induced apoptosis rate in normoxic or hypoxic glioma cells. Curcumin enhanced radiation-induced CRT exposure, release of HSP70 and ATP, and ER stress signaling activity. After treatment with ER stress pathway inhibitors, cell apoptosis and CRT exposure induced by the combination treatment of curcumin and X-ray were reduced. In vaccination experiments, glioma cells irradiated by X-ray produced a strong immunogenic response rejecting tumor formation in 70% mice. In comparison, cells treated by curcumin and X-ray produced a stronger immune response rejecting tumor formation in 90% mice. The combination treatment increased the percentage of tumor-infiltrating CD4+, CD8+ T lymphocytes, and CD11c+ dendritic cells compared to X-ray irradiation alone. Conclusion: Ionizing radiation-induced normoxic or hypoxic glioma immunogenic cell death could be further enhanced by curcumin through activating the ER stress PERK-eIF2α and IRE1α-XBP1 signaling pathways.


Assuntos
Curcumina , Glioma , Trifosfato de Adenosina/farmacologia , Animais , Apoptose , Calreticulina , Linhagem Celular Tumoral , Curcumina/farmacologia , Curcumina/uso terapêutico , Estresse do Retículo Endoplasmático , Endorribonucleases , Proteínas de Choque Térmico , Morte Celular Imunogênica , Camundongos , Proteínas Serina-Treonina Quinases , Radiação Ionizante , Transdução de Sinais
14.
Gene ; 844: 146825, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-35995116

RESUMO

BACKGROUND: Pharmacogenomics has been widely used to study the very important pharmacogenetic (VIP) variants among populations, but information on pharmacogenomics in the Lahu population is limited. The purpose of this study was to determine the differences in the distribution of VIP variants between the Lahu and the other 26 populations. METHODS: We genotyped 55 VIP variants of 27 genes in the Lahu population from the PharmGKB database. χ2 test was used to compare the genotype and allele frequencies between the Lahu and the other 26 populations from the 1000 Genomes Project. RESULTS: The genotype and allele frequencies of single nucleotide polymorphisms (SNPs) on rs20417 (PTGS2), rs776746 (CYP3A5), rs2115819 (ALOX5), and rs3093105 (CYP4F2) were considerably different in the Lahu population compared with those in the other 26 populations. Besides, based on the PharmGKB database, we identified several VIP variants that may alter the drug metabolism of aspirin (PTGS2), tacrolimus (CYP3A5), montelukast (ALOX5), and vitamin E (CYP4F2). CONCLUSION: The results show that there are significant differences in the genotype frequency distribution between the Lahu and the other 26 populations. Our study supplements the pharmacogenomics information of the Lahu population and provides a theoretical basis for individualized medicine in Lahu.


Assuntos
Citocromo P-450 CYP3A , Farmacogenética , China , Ciclo-Oxigenase 2/genética , Citocromo P-450 CYP3A/genética , Frequência do Gene , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
15.
Per Med ; 19(5): 403-410, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35801384

RESUMO

Aim: Our study aimed to screen the genotype frequencies of very important pharmacogenomic (VIP) mutations and identify their differences between Bai and other populations. Materials & methods: We selected 66 VIP variants from PharmGKB (www.pharmgkb.org/) for genotyping. χ2 test was used to identify differences in loci between these populations and FST values of Bai and the other 26 populations were analyzed. Results: Our study showed that the frequencies of SNPs of CYP3A5, ACE, PTGS2 and NAT2 differed significantly from those of the other 26 populations. At the same time, we found that some VIP variants may affect the metabolism of drugs and the genetic relationship between the Bai population and East Asian populations was found to be the closest. Conclusion: By comparing the genotype frequencies of different populations, the loci with significant differences were identified and discussed, providing a theoretical basis for individualized drug use in the Bai ethnic population.


Assuntos
Arilamina N-Acetiltransferase , Variantes Farmacogenômicos , Enzima de Conversão de Angiotensina 2/metabolismo , Arilamina N-Acetiltransferase/genética , China , Ciclo-Oxigenase 2/genética , Citocromo P-450 CYP3A/genética , Frequência do Gene/genética , Humanos , Peptidil Dipeptidase A/metabolismo , Farmacogenética
16.
Mol Genet Genomics ; 297(2): 407-417, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35146537

RESUMO

Previous studies have shown that the frequency of very important pharmacogenomic (VIP) genes varies in different populations which leads to the diversities in drug efficacy, safety, and the risk associated with adverse drug reactions (ADRs). The purpose of this study was to identify the distribution differences of VIP variants between the Li population and the other 13 populations. Based on the Pharmacogenomics Knowledgebase database (PhamGKB), we successfully genotyped 52 VIP variants within 27 genes in 200 unrelated Li population. χ2 test was used to evaluate the significant differences of genotype and allele frequencies between the Li and the other 13 populations from 1000 Genomes Project. Our study showed that the genotype frequencies of single nucleotide polymorphisms (SNPs) on KCNH2, ACE, CYP4F2, and CYP2E1 were considerably different between Li and the other 13 populations, especially in rs1805123 (KCNH2), rs4291 (ACE), rs3093105 (CYP4F2), and rs6413432 (CYP2E1) loci. Meanwhile, we found several VIP variants that might alter the drug metabolism of cisplatin-cyclophosphamide (CYP2E1), vitamin E (CYP4F2), asthma amlodipine, chlorthalidone, and lisinopril (ACE) through PharmGKB. We also identified other variants which were associated with adverse effects in isoniazid and rifampicin (CYP2E1; hepatotoxicity). The four loci rs1805123 (KCNH2), rs4291 (ACE), rs3093105 (CYP4F2), and rs6413432 (CYP2E1) provided a reliable basis for the prediction of the efficacy of certain drugs. The study complemented the existed pharmacogenomics information, which could provide theoretical basis for predicting the efficacy of certain drugs in the Li population.


Assuntos
Farmacogenética , Variantes Farmacogenômicos , Povo Asiático/genética , China , Etnicidade , Frequência do Gene , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
17.
Langmuir ; 37(12): 3620-3627, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33721491

RESUMO

The chief aim is to explore the wetting state on a microhole surface and to optimize the shape parameters of a microhole surface. A two-dimensional pseudopotential model was established, and the effects of shapes on the wetting behavior were explored. The shape parameters were optimized via the response surface methodology. The results reveal that the microhole surface can achieve a superhydrophobic state. When the diameter varies from 25 to 200 µm, the droplet is gradually lifted. However, when the diameter of the microhole is too large, the contact angle decreases rapidly. When the microhole diameter increases, relative radii of the x- and y-directions exhibit increasing trends. With the increase of the spacing, the gaps between the microholes are gradually filled with the droplet. When spacing increases, relative radii of x- and y-directions exhibit decreasing trends. The largest contact angle of 171.246° at the diameter of 76 µm and the spacing of 48 µm is observed.

18.
Biochem Genet ; 59(3): 697-713, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33507447

RESUMO

The expression of IL-2RA and IL-2RB was correlated with breast cancer (BC) progression. However, there is no literature investigating the association of IL-2RA and IL-2RB polymorphisms with BC predisposition among Chinese Han Women. Seven SNPs in IL-2RA and IL-2RB were genotyped by Agena MassARRAY platform among 553 BC patients and 550 healthy controls. Odds ratios (OR) and 95% confidence interval (CI) adjusted for age were calculated for the effect of IL-2RA and IL-2RB variants on BC susceptibility. IL-2RA rs12722498 was a protective factor for BC occurrence (OR = 0.70, p = 0.019), especially in subjects with age ≤ 52 years (OR = 0.55, p = 0.004). IL-2RA rs12569923 (OR = 9.07, p = 0.033), IL-2RB rs2281089 (OR = 0.67, p = 0.043) and rs9607418 (OR = 0.59, p = 0.012) were related to the incidence of estrogen receptor positive (ER +) BC. IL-2RB rs3218264 (OR = 1.38, p = 0.010) and rs9607418 (OR = 0.56, p = 0.009) were associated with the risk of developing progesterone receptor positive (PR +) BC. Rs2281089 (OR = 1.54, p = 0.012) and rs1573673 (OR = 0.72, p = 0.035) were correlated to Ki-67 level. Moreover, IL-2RB rs2281089 (OR = 0.72, p = 0.022) showed a reduced risk of BC metastasis, and IL-2RA rs12722498 (OR = 0.54, p = 0.030) had a lower frequency in BC patients with tumor size > 2 cm. Our study identified the potential effect of genetic variations in IL-2RA and IL-2RB on BC susceptibility and/or BC clinicopathologic indicators among Chinese Han Women.


Assuntos
Neoplasias da Mama/genética , Etnicidade/genética , Predisposição Genética para Doença , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade beta de Receptor de Interleucina-2/genética , Adulto , Idoso , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , China , Feminino , Humanos , Pessoa de Meia-Idade , Mutação
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 225: 117598, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605939

RESUMO

Silver nanoarrays were fabricated by inkjet printing silver nanoparticles ink on the gratings of compact disc recordable (CD-R). Rhodamine 6G (R6G) was chosen as a probe molecule to evaluate their surface-enhanced Raman scattering (SERS) performance. The finite-difference time domain (FDTD) solution was used to simulate local electric field distribution of silver nanoparticles on the grating surface and flat surface, respectively. It was found that the Ag/grating substrate possessed higher enhancement ability than the Ag/flat due to the high-density hot spots of periodic structure of the grating. The silver nanoarrays substrate exhibited high stability and the characteristic peaks of R6G can be still well observed after eight months. The substrate also exhibited a good spot-to-spot reproducibility with an RSD of 10.21% by eight points. SERS mappings of R6G adsorbed on silver nanoarrays were tested under the ultra-fast Raman imaging mode, and the relative standard deviation (RSD) values of uniformity were calculated to be 8.35% and 11.53% at 610 cm-1 band measured by 2500 and 6480 points, respectively. In addition, the as-prepared silver nanoarrays was successfully applied to the detection of melamine in adult milk powder solution directly. A good linear relationship with the correlation coefficient of 0.9968 between peak intensity and concentration was obtained from 1.2 to 100 mg/L.

20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 31(3): 241-4, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-20510044

RESUMO

OBJECTIVE: To investigate the impact of age on patients with metabolic syndrome (MS) and normal persons. METHODS: Data was gathered from 8280 persons including 4873 males and 3407 females who were randomly selected. All subjects were divided into normal group and MS group. According to the interval of ten years, the subjects were divided into seven age groups, to calculate the difference of impaired fasting glycaemia (IFG) between patients with diabetes mellitus (DM) and normal people, as well as the related portions. RESULTS: (1) The risk of IFG and DM appeared to be different among age groups among the target subjects as well as in the normal and the MS groups (P < 0.05). (2) Among the whole subjects, the overall prevalence of IFG was increasing with age. The prevalence of DM had an increasing trend with age augment in 20 - 79 years group, whereas a decreasing trend appeared in people over 80 years of age. (3) For normal persons, the prevalence of IFG and DM were all increasing with age augment in 20 - 79 years group, and then decreasing with age augment in the over-80-years group. (4) For MS patients, the prevalence of IFG had an increasing trend with age augment in 20 - 69 years group, whereas a decreasing trend appeared in people over 70 years of age. There was no tendency of variation with age augment in DM. CONCLUSIONS: (1) For normal persons, high prevalence rates of IFG and DM were correlated to age augment, especially in senior persons. (2) For MS patients, high prevalence of IFG was also correlated to age augment, but no association between prevalence of DM and age augment was seen. (3) Age from 70 to 79 years appeared to be in high risk with MS.


Assuntos
Diabetes Mellitus/epidemiologia , Síndrome Metabólica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
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