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1.
Biomed Pharmacother ; 169: 115914, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38000360

RESUMO

Sepsis is a life-threatening systemic inflammatory response syndrome caused by the host imbalanced response to infection. Lung injury is the most common complication of sepsis and one of the leading causes of patient death. Pyroptosis is a specific programmed cell death characterized by the release of inflammatory cytokines. Appropriate pyroptosis can reduce tissue damage and exert a protective effect against infection during sepsis. However, overactivated pyroptosis results in massive cell death, leading to septic shock, multiple organ dysfunction syndrome, and even an increased risk of secondary infection. Recent studies suggest that pyroptosis can interact with and cross-regulate other types of cell death programs to establish a complex network of cell death, which participates in the occurrence and development of septic lung injury. This review will focus on the interactions between pyroptosis and other types of cell death, including apoptosis, necroptosis, PANoptosis, NETosis, autophagy, and ferroptosis, to summarize the role of pyroptosis in sepsis-induced lung injury, and will discuss the potential therapeutic strategies of targeting pyroptosis during sepsis treatment.


Assuntos
Lesão Pulmonar , Sepse , Humanos , Piroptose , Lesão Pulmonar/complicações , Morte Celular , Apoptose , Sepse/complicações , Sepse/metabolismo
2.
Int Immunopharmacol ; 124(Pt B): 110958, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37741129

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, erythema, and skin barrier dysfunction. Gasdermin D (GSDMD) is the key executioner of an inflammatory cell death mechanism known as pyroptosis. However, the role of GSDMD in the pathogenesis of AD remains unclear. Through the analysis of publicly available Gene Expression Omnibus (GEO) datasets, we observed an upregulation of Gsdmd mRNA in the skin tissue of AD patients. Moreover, we delved into the impact of GSDMD deletion and inhibition on AD-like skin lesions using a mouse model induced by the topical application of oxazolone (Oxa). We found that mice lacking GSDMD exhibited relieved AD signs and symptoms in terms of reduced skin thickness, scarring and scratching behavior compared to wild-type mice after induction of AD-like skin lesions. This was associated with decreased infiltration of inflammatory cells, reduced epidermal thickness, and decreased serum levels of IgE and IL-4. Western blot analysis further revealed decreased GSDMD cleavage in the skin of GSDMD knockout mice, and reduced expression of IL-1ß and IL-18. Inhibition of GSDMD using the pharmacological agent disulfiram or the herbal compound matrine significantly attenuated the symptoms of AD-like skin lesions in wild-type mice, GSDMD cleavage and pro-inflammatory cytokines were reduced as well. Our results suggest that GSDMD-mediated pyroptosis plays a critical role in the development of AD-like skin lesions, and targeting GSDMD may be a promising therapeutic strategy for AD.


Assuntos
Dermatite Atópica , Animais , Humanos , Camundongos , Citocinas/metabolismo , Dermatite Atópica/metabolismo , Epiderme/patologia , Gasderminas , Proteínas de Ligação a Fosfato/genética , Proteínas de Ligação a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Pele/patologia
3.
Int J Mol Sci ; 24(3)2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36768464

RESUMO

Maize seedlings contain high amounts of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and the effect of DIMBOA is directly associated with multiple insect-resistance against insect pests such as Asian corn borer and corn leaf aphids. Although numerous genetic loci for multiple insect-resistant traits have been identified, little is known about genetic controls regarding DIMBOA content. In this study, the best linear unbiased prediction (BLUP) values of DIMBOA content in two ecological environments across 310 maize inbred lines were calculated; and their phenotypic data and BLUP values were used for marker-trait association analysis. We identified nine SSRs that were significantly associated with DIMBOA content, which explained 4.30-20.04% of the phenotypic variation. Combined with 47 original genetic loci from previous studies, we detected 19 hot loci and approximately 11 hot loci (in Bin 1.04, Bin 2.00-2.01, Bin 2.03-2.04, Bin 4.00-4.03, Bin 5.03, Bin 5.05-5.07, Bin 8.01-8.03, Bin 8.04-8.05, Bin 8.06, Bin 9.01, and Bin 10.04 regions) supported pleiotropy for their association with two or more insect-resistant traits. Within the 19 hot loci, we identified 49 candidate genes, including 12 controlling DIMBOA biosynthesis, 6 involved in sugar metabolism/homeostasis, 2 regulating peroxidases activity, 21 associated with growth and development [(auxin-upregulated RNAs (SAUR) family member and v-myb avian myeloblastosis viral oncogene homolog (MYB)], and 7 involved in several key enzyme activities (lipoxygenase, cysteine protease, restriction endonuclease, and ubiquitin-conjugating enzyme). The synergy and antagonism interactions among these genes formed the complex defense mechanisms induced by multiple insect pests. Moreover, sufficient genetic variation was reported for DIMBOA performance and SSR markers in the 310 tested maize inbred lines, and 3 highly (DIMBOA content was 402.74-528.88 µg g-1 FW) and 15 moderate (DIMBOA content was 312.92-426.56 µg g-1 FW) insect-resistant genotypes were major enriched in the Reid group. These insect-resistant inbred lines can be used as parents in maize breeding programs to develop new varieties.


Assuntos
Melhoramento Vegetal , Zea mays , Animais , Zea mays/genética , Insetos/genética , Variação Genética , Estudos de Associação Genética
4.
Comput Methods Programs Biomed ; 229: 107255, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36462426

RESUMO

BACKGROUND AND OBJECTIVE: Glioma is the most common primary craniocerebral tumor caused by the cancelation of glial cells in the brain and spinal cord, with a high incidence and cure rate. Magnetic resonance imaging (MRI) is a common technique for detecting and analyzing brain tumors. Due to improper hardware and operation, the obtained brain MRI images are low-resolution, making it difficult to detect and grade gliomas accurately. However, super-resolution reconstruction technology can improve the clarity of MRI images and help experts accurately detect and grade glioma. METHODS: We propose a glioma magnetic resonance image super-resolution reconstruction method based on channel attention generative adversarial network (CGAN). First, we replace the base block of SRGAN with a residual dense block based on the channel attention mechanism. Second, we adopt a relative average discriminator to replace the discriminator in standard GAN. Finally, we add the mean squared error loss to the training, consisting of the mean squared error loss, the L1 norm loss, and the generator's adversarial loss to form the generator loss function. RESULTS: On the Set5, Set14, Urban100, and glioma datasets, compared with the state-of-the-art algorithms, our proposed CGAN method has improved peak signal-to-noise ratio and structural similarity, and the reconstructed glioma images are more precise than other algorithms. CONCLUSION: The experimental results show that our CGAN method has apparent improvements in objective evaluation indicators and subjective visual effects, indicating its effectiveness and superiority.


Assuntos
Glioma , Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Imageamento por Ressonância Magnética/métodos , Encéfalo , Glioma/diagnóstico por imagem
5.
Arch Orthop Trauma Surg ; 143(7): 4099-4109, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36183274

RESUMO

INTRODUCTION: Posterolateral approach has been advocated for the treatment of ankle fractures involving the posterior malleolus and satisfactory results were demonstrated in several studies. The Bartonicek classification based on 3-dimensional CT scanning was commonly used for treatment recommendation of posterior malleolar fracture (PMF). The aim of this retrospective study was to evaluate the clinical effect of the posterolateral approach for the treatment of PMF and present outcomes of patients with different types of Bartonicek classification. METHOD: We retrospectively reviewed the clinical outcomes of 72 patients with ankle fractures involving posterior malleolus (PM) from January 2016 to December 2018. Posterior malleolus fractures (PMFs) were all directly reduced and fixed by a posterolateral approach using lag screws and/or buttress plates. AOFAS score and VAS pain score were used as the primary functional outcome measures. The radiographic evaluation included the quality of the reduction and Kellgren-Lawrence (KL) osteoarthritis classification. According to the CT-based Bartonicek classification, all patients were classified into three groups: 42 type II, 18 type III and 12 type IV. Bartonicek type II patients were further divided into subtype IIa 19 cases, subtype IIb 16 cases and subtype IIc 7 cases. The radiological and functional outcomes were analyzed among different types and subtypes of Bartonicek classification. RESULTS: Sixty-eight patients (94.5%) achieved good or excellent reduction of PMF after surgery. The mean AOFAS score was 81.35 ± 6.15 at 6 months and 90.56 ± 4.98 at the final follow-up, respectively. The VAS score was 6.62 ± 1.03 one week after surgery, and 1.20 ± 0.92 at the final follow-up. Radiological evaluation at the final follow-up showed that primary bone union was achieved in all patients and 65 patients (88.9%) got no (KL grade 0) or just doubtable (KL grade 1) post-traumatic osteoarthritis. AOFAS scores decreased significantly with the severity of Bartonicek classification at 6 month (p < 0.001) and final follow-up (p < 0.05), while there was no statistical difference of VAS pain score among different types of Bartonicek classification. Reduction quality and the presence of osteoarthritis was not correlated to Bartonicek classification either. Besides, AOFAS scores at the final follow-up were statistically different among three subtypes of Bartonicek type II fractures (p < 0.05), and Bartonicek subtype IIa fractures had the highest AOFAS scores as 93 ± 4.99. Presence and severity of osteoarthritis was lower in patients with subtype IIa PMF compared to other subtype groups, this finding was statistically significant (p < 0.05). CONCLUSION: The posterolateral approach could achieve good clinical outcomes in the treatment of posterior malleolus fracture. Patients with a Bartonicek type II fracture had a better functional outcome measured by the AOFAS score compared to other types. Bartonicek type IIa fractures got a higher AOFAS score and a lower incidence of osteoarthritis at the final follow-up than the other two subtypes. Classification of PMFs according to the Bartonicek classification was reliable.


Assuntos
Fraturas do Tornozelo , Osteoartrite , Humanos , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Articulação do Tornozelo/cirurgia , Dor , Resultado do Tratamento
6.
IET Nanobiotechnol ; 15(8): 674-679, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34694722

RESUMO

Neutral nanoparticles (NPs) of copper (Cu), iron (Fe) and zinc (Zn) are widely used in agriculture. Polymer seed coating with different metal NPs may supply important nutrients during plant growth and consequently enhances yields. In this research, three kinds of metal NPs were conducted to optimize the optimal concentration through seed coating for improving plant growth and productivity of tomato. Seeds of Venice tomato cultivars were coated by polymer-based mixture with different concentrations of Cu, Fe and Zn NPs, respectively. At harvest, seed germination, internode length, average weight of single fruit, yield and fruit shape index were measured. When compared with control, the internode length increased by 7.3% and 6.8% with low concentration of Fe NPs and Zn NPs, respectively. The average weight per fruit improved over control by 10.2% and 7.5% with low concentration of Cu NPs and Fe NPs, respectively. The yield with low concentration of Cu NPs and Fe NPs increased the yield by 10.7% and 6.5% compared with control. These results indicated that polymer seed coating with low concentration of metal NPs may promote the uptake of some nutrient and thus improve the productivity of tomato.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Solanum lycopersicum , Cobre , Ferro , Sementes , Zinco
7.
Molecules ; 26(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34500788

RESUMO

The biological activities of the primary metabolites and secondary metabolites of 69 green cabbage varieties were tested. The LC-MS detection method was used to determine the content of 19 free amino acids (lysine, tryptophan, phenylalanine, methionine, threonine, isoleucine, leucine, valine, arginine, asparagine, glycine, proline, tyrosine, glutamine, alanine, aspartic acid, serine, and glutamate). The content of 10 polyphenols (chlorogenic acid, gallic acid, 4-coumaric acid, ferulic acid, gentisic acid, cymarin, erucic acid, benzoic acid, rutin, and kaempferol) was determined by the HPLC detection method. Considering the complexity of the data obtained, variance analysis, diversity analysis, correlation analysis, hierarchical cluster analysis (HCA), and principal component analysis (PCA) were used to process and correlate amino acid or polyphenol data, respectively. The results showed that there were significant differences between the different amino acids and polyphenols of the 69 cabbage varieties. The most abundant amino acids and polyphenols were Glu and rutin, respectively. Both amino acids and polyphenols had a high genetic diversity, and multiple groups of significant or extremely significant correlations. The 69 cabbage varieties were divided into two groups, according to 19 amino acid indexes, by PCA. Among them, seven varieties with high amino acid content all fell into the fourth quadrant. The HCA of amino acids also supports this view. Based on 10 polyphenols, the 69 cabbage varieties were divided into two groups by HCA. Based on 29 indexes of amino acids and polyphenols, 69 cabbage varieties were evaluated and ranked by PCA. Therefore, in this study, cabbage varieties were classified in accordance with the level of amino acids and polyphenols, which provided a theoretical basis for the genetic improvement of nutritional quality in cabbage.


Assuntos
Aminoácidos/análise , Brassica/química , Polifenóis/análise , Análise Multivariada
8.
Genomics ; 113(6): 3565-3581, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34455034

RESUMO

Deep-seeding is an important way to improve maize drought resistance, mesocotyl elongation can significantly enhance its seedling germination. To improve our understanding of transcription-mediated maize mesocotyl elongation under deep-seeding stress. RNA-sequencing was used to identify differentially expressed genes (DEGs) in both deep-seeding tolerant W64A and intolerant K12 mesocotyls following culture for 10 days after 2.0 mg·L-1 24-epibrassinolide (EBR) induced stress at the depths of 3 and 20 cm. Phenotypically, the mesocotyl length of both maize significantly increased under 20 cm stress and in the presence of EBR. Microstructure observations revealed that the mesocotyls underwent programmed cell death under deep-seeding stress, which was alleviated by EBR. This was found to be regulated by multiple DEGs encoding cysteine protease/senescence-specific cysteine protease, aspartic protease family protein, phospholipase D, etc. and transcription factors (TFs; MYB, NAC). Additionally, some DEGs associated with cell wall components, i.e., cellulose synthase/cellulose synthase like protein (CESA/CSL), fasciclin-like arabinogalactan (APG), leucine-rich repeat protein (LRR) and lignin biosynthesis enzymes including phenylalanine ammonia-lyase, S-adenosyl-L-methionine-dependent methyltransferases, 4-coumarate-CoA ligase, cinnamoyl CoA reductase, cinnamyl alcohol dehydrogenase, catalase, peroxiredoxin/peroxidase were found to control cell wall sclerosis. Moreover, in auxin, ethylene, brassinosteriod, cytokinin, zeatin, abscisic acid, gibberellin, jasmonic acid, and salicylic acid signaling transduction pathways, the corresponding DEGs were activated/inhibited by TFs (ARF, BZR1/2, B-ARR, A-ARR, MYC2, ABF, TGA) and synthesis of phytohormones-related metabolites. These findings provide information on the molecular mechanisms controlling maize deep-seeding tolerance and will aid in the breeding of deep-seeding maize varieties.


Assuntos
Brassinosteroides , Zea mays , Brassinosteroides/metabolismo , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , RNA/metabolismo , Análise de Sequência de RNA , Estresse Fisiológico/genética , Zea mays/genética , Zea mays/metabolismo
9.
J Clin Lab Anal ; 35(2): e23638, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33314392

RESUMO

BACKGROUND: Although hematologic review criteria for general hospitals have been established, they may be insufficient for cancer hospitals. This study aimed to establish the appropriate review criteria for hematology analyzers in cancer hospitals. METHODS: A total of 1003 samples from our hospital were randomly selected for blood smear preparation and microscopic review. The review criteria of the International Consensus Group for Hematology Review (ICGH) and Chinese consensus group were used to obtain the review, true-negative (TN), true-positive (TP), false-negative (FN), and false-positive (FP) rates, as well as the triggered rules. Our review criteria were established by comparing flag or numeric value information of TP and FP samples, adjusting rules to obtain better efficiency, a low slide review rate, and an acceptable FN rate. RESULTS: Overall, 197 (19.64%) samples showed positive smear findings. Compared to the ICGH criteria, the slide review rate of the newly established criteria declined from 51.25% to 39.28%, and the TP and TN rates increased from 17.85% and 46.06% to 23.13% and 55.83%, respectively. The FN rate of the newly established criteria was 3.69%. Another set of samples used to validate the newly established criteria yielded the review, FN, and FP rates as 33.49%, 1.86%, and 25.58%, respectively. CONCLUSION: The newly established review criteria for hematology analyzers enabled the prompt identification, smear, and further verification of doubtful specimens, without a significant increase in the workload, thus improving the efficiency of the review process. This study provided data support for other cancer hospitals to establish review criteria.


Assuntos
Institutos de Câncer , Testes Hematológicos/instrumentação , Testes Hematológicos/normas , Laboratórios Hospitalares , Eritrócitos/patologia , Reações Falso-Negativas , Reações Falso-Positivas , Testes Hematológicos/métodos , Humanos , Leucócitos/patologia , Linfócitos/patologia
10.
Molecules ; 24(6)2019 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-30909541

RESUMO

Twenty eight 7-substitued fangchinoline analogues, of which twenty two were novel, were synthesized and evaluated for their effect to inhibit lipopolysaccharide/nigericin (LPS/NIG)-induced IL-1ß release at both cell and protein levels at the concentration of 5 µM. Among them, compound 6 exhibited promising inhibitory potency against IL-ß activation with an IC50 value of 3.7 µM. Preliminary mechanism study revealed that 6 might target NLRP3 protein, and then block ASC pyroptosome formation with-NLRP3, rather than acting on the activation of the NLRP3 inflammasome (NF-κB and MAPK pathways) or caspase-1 protein. Our current study supported the potential role of compound 6 against IL-ß activation, and provided powerful information for developing fangchinoline derivatives into a novel class of anti-inflammatory agents.


Assuntos
Anti-Inflamatórios/farmacologia , Benzilisoquinolinas/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Anti-Inflamatórios/síntese química , Benzilisoquinolinas/síntese química , Caspase 1/genética , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamassomos/genética , Inflamação/induzido quimicamente , Inflamação/genética , Interleucina-1beta/genética , Lipopolissacarídeos/toxicidade , NF-kappa B/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Nigericina/toxicidade , Fator de Transcrição RelA/genética
11.
J Craniofac Surg ; 28(6): 1531-1533, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28692516

RESUMO

OBJECTIVE: The aim of this study was to present a new immediate reconstructive option for oral tissue defects with a pedicled buccal fat pad flap in oral surgery. MATERIALS AND METHODS: Fifteen cases (10 males, 5 females; mean age: 50 years) suffering from oral tumor and attending the Affiliated Stomatology Hospital of Kunming Medical University were included in this study. All patients underwent immediate repair surgery involving a pedicled buccal fat pad graft in oral surgery, from July 2013 to August 2016. RESULTS: All cases underwent uneventful healing with a surviving graft flap. The buccal fat pad healed in about 9 to 10 weeks and its uncovered surface became epithelialized with similar feature to the normal mucosa. At a follow-up of 3 months to 3 years, a good outcome was obtained with minimal malfunction and face deformity. CONCLUSIONS: The pedicled buccal fat pad is ideal material for repair, and it is a viable option for immediate reconstruction of oral tissue defects in oral surgery.


Assuntos
Tecido Adiposo , Bochecha/cirurgia , Neoplasias Bucais/cirurgia , Procedimentos Cirúrgicos Bucais/métodos , Retalhos Cirúrgicos/cirurgia , Tecido Adiposo/cirurgia , Tecido Adiposo/transplante , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
J Craniofac Surg ; 28(3): e222-e225, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28468195

RESUMO

OBJECTIVE: To investigate the clinical application of a pedicled forearm flap in the reconstruction of soft tissue defects after oral cancer resection. METHODS: A retrospective analysis was performed on 31 patients with oral cancer in the Affiliated Stomatology Hospital of Kunming Medical University. The patients underwent repair of soft tissue defects, resulting from oral cancer resection, using a pedicled forearm flap. Patients were followed up for 3 months to 3 years to observe the survival rate of the pedicled forearm flap and the recovery of the patient's appearance and oral function. RESULTS: The pedicled forearm flap survived in 30 patients (96.77%), and 3 patients showed flap vascular crisis (9.67%; 2 patients were successfully rescued). The articulation, chewing, and swallowing function of the patients were improved after surgery. CONCLUSION: The pedicled forearm flap has advantages in terms of color and texture, its moderate thickness, long vascular pedicle, good blood supply, and strong infection resistance. It has a high survival rate and is an excellent skin-muscle flap suited to the repair of soft tissue defects after oral cancer resection.


Assuntos
Carcinoma/cirurgia , Neoplasias Bucais/cirurgia , Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Adulto , Idoso , Feminino , Antebraço , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Comb Chem High Throughput Screen ; 20(4): 346-353, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28215144

RESUMO

BACKGROUND: Chemical toxicity is an important reason for late-stage failure in drug R&D. However, it is time-consuming and expensive to identify the multiple toxicities of compounds using the traditional experiments. Thus, it is attractive to build an accurate prediction model for the toxicity profile of compounds. MATERIALS AND METHODS: In this study, we carried out a research on six types of toxicities: (I) Acute Toxicity; (II) Mutagenicity; (III) Tumorigenicity; (IV) Skin and Eye Irritation; (V) Reproductive Effects; (VI) Multiple Dose Effects, using local lazy learning (LLL) method for multi-label learning. 17,120 compounds were split into the training set and the test set as a ratio of 4:1 by using the Kennard-Stone algorithm. Four types of properties, including molecular fingerprints (ECFP_4 and FCFP_4), descriptors, and chemical-chemical-interactions, were adopted for model building. RESULTS: The model 'ECFP_4+LLL' yielded the best performance for the test set, while balanced accuracy (BACC) reached 0.692, 0.691, 0.666, 0.680, 0.631, 0.599 for six types of toxicities, respectively. Furthermore, some essential toxicophores for six types of toxicities were identified by using the Laplacian-modified Bayesian model. CONCLUSION: The accurate prediction model and the chemical toxicophores can provide some guidance for designing drugs with low toxicity.


Assuntos
Carcinógenos/toxicidade , Simulação por Computador , Descoberta de Drogas/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Modelos Biológicos , Mutagênicos/toxicidade , Preparações Farmacêuticas , Algoritmos , Animais , Carcinógenos/química , Bases de Dados de Produtos Farmacêuticos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Olho/efeitos dos fármacos , Humanos , Aprendizado de Máquina , Mutagênicos/química , Preparações Farmacêuticas/química , Relação Quantitativa Estrutura-Atividade , Reprodução/efeitos dos fármacos , Pele/efeitos dos fármacos , Testes de Toxicidade
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(3): 702-6, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27342494

RESUMO

OBJECTIVE: To investigate the clinical efficacy of regimen consisting of lenalidomide combined with chemotherapy for acute leukemia and its impact on vascular endothilial growth factor (vEGF) and basic fibroblast growth factor (bFGF), and to analyze the relationship lenalidomide with therapeutic efficacy of leukemia. METHODS: The patients with newly diagnosed acute myeloid leukemia (except M3) from October 2013 to October 2014 in our hospital were randomly divided into 2 groups: chemotherapy+placebo (CP) group and lenalidomide+chemotherapy (LC) group. In addition, healthy persons were used as healthy controls (HC). The expression of VEGF and bFGF was detected by ELISA, and the therapeutic efficacy for AML patients was analyzed. RESULTS: The therapeutic efficacy in LC group and CP group was 87.9% and 77.2% respectively. Before treatment, the VEGF level in LC and CP groups was obviously higher than that in HC group; after treatment, the VEGF level significanthy decreased, and the decreased degree in LC group was larger than that in CP group. Before treatment, the bFGF level in LC and CP groups was higher than that in HC group; after treatment, the bFGF level decreased, and decreased degree in LC group was larger than that in CP group. CONCLUSION: The lenalidomide combined with chemotherapy can significantly decrease the expression level of VEGF and bFGF, and enhance the remission rate of patients with AML.


Assuntos
Antineoplásicos/administração & dosagem , Fator 2 de Crescimento de Fibroblastos/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Talidomida/análogos & derivados , Fator A de Crescimento do Endotélio Vascular/metabolismo , Doença Aguda , Antineoplásicos/uso terapêutico , Quimioterapia Combinada , Humanos , Lenalidomida , Talidomida/administração & dosagem , Talidomida/uso terapêutico
15.
Tumour Biol ; 37(8): 10393-402, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26846104

RESUMO

We aimed to investigate the association between dihydropyrimidine dehydrogenase (DPYD) gene polymorphisms and the risk of pediatric acute lymphoblastic leukemia (ALL) and its prognosis after chemotherapy. A total of 147 pediatric ALL patients diagnosed by our hospital between January 2011 and December 2014 were included in the case group, and 102 healthy people who received a physical examination during the same time frame in our hospital were included in the control group. DNA sequencing was applied for site determination and genotyping of the DPYD 85T > C, 2194G > A, 1156G > T, and IVS14 + 1G > A polymorphisms. The genotype and allele frequencies of the two groups were compared. A significant difference was found in the comparison of the mutant gene and allele frequencies of the 85T > C polymorphism between the case and control groups (P < 0.05). The CT and CC genotypes in the 85T > C polymorphism were associated with the risk of the disease (OR = 1.592, 95 % CI = 1.010-2.509), suggesting that the recessive gene (85C) was more likely to lead to the occurrence of ALL compared with the dominant gene (85T) (P < 0.05). Patients carrying the C allele of the 85T > C polymorphism presented higher damage of their liver functions and higher infection rates compared with patients carrying the non-C allele (P < 0.05). A higher proportion of liver function damage and a higher infection rate were found in patients with the GA genotype in the IVS14 + 1G > A polymorphism compared with the GG genotype (P < 0.05). The complete remission (CR) rate in patients with the GG genotype in the IVS14 + 1G > A polymorphism was higher than in patients with the GA genotype (P = 0.020). After 5-fluorouracil/calcium folinate (5-FU/CF)-based chemotherapy, the event-free survival (EFS) rate of patients with the TT genotype was higher than patients with the CT and CC genotypes (P < 0.05). Our results revealed that the C allele of the 85T > C polymorphism might be associated with susceptibility to pediatric ALL. Patients carrying the C allele may have an increased risk of ALL. Thus, the 85T > C polymorphism may be a predictor of CR for pediatric ALL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Di-Hidrouracila Desidrogenase (NADP)/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Frequência do Gene , Genótipo , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Fatores de Risco
16.
Biochem Biophys Res Commun ; 455(3-4): 256-61, 2014 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-25449280

RESUMO

Osteoblasts regulate bone formation and remodeling, and are main target cells of oxidative stress in the progression of osteonecrosis. The stem cell factor (SCF)-c-Kit pathway plays important roles in the proliferation, differentiation and survival in a range of cell types, but little is known about its functions in osteoblasts. In this study, we found that c-Kit is functionally expressed in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Its ligand SCF exerted significant cyto-protective effects against hydrogen peroxide (H2O2). SCF activated its receptor c-Kit in osteoblasts, which was required for its cyto-protective effects against H2O2. Pharmacological inhibition (by Imatinib and Dasatinib) or shRNA-mediated knockdown of c-Kit thus inhibited SCF-mediated osteoblast protection. Further investigations showed that protection by SCF against H2O2 was mediated via activation of c-Kit-dependent Akt pathway. Inhibition of Akt activation, through pharmacological or genetic means, suppressed SCF-mediated anti-H2O2 activity in osteoblasts. In summary, we have identified a new SCF-c-Kit-Akt physiologic pathway that protects osteoblasts from H2O2-induced damages, and might minimize the risk of osteonecrosis caused by oxidative stress.


Assuntos
Osteoblastos/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Fator de Células-Tronco/metabolismo , Células 3T3 , Animais , Apoptose , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular , Ensaio de Imunoadsorção Enzimática , Peróxido de Hidrogênio/química , L-Lactato Desidrogenase/metabolismo , Ligantes , Camundongos , Necrose/patologia , Osteoblastos/citologia
17.
PLoS One ; 8(9): e74678, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24040315

RESUMO

Heavy nitrogen (N) application to gain higher yield of wheat (Triticum aestivum L.) resulted in increased production cost and environment pollution. How to diminish the N supply without losing yield and/or quality remains a challenge. To meet the challenge, we integrated and expressed a tobacco nitrate reductase gene (NR) in transgenic wheat. The 35S-NR gene was transferred into two winter cultivars, "Nongda146" and "Jimai6358", by Agrobacterium-mediation. Over-expression of the transgene remarkably enhanced T1 foliar NR activity and significantly augmented T2 seed protein content and 1000-grain weight in 63.8% and 68.1% of T1 offspring (total 67 individuals analyzed), respectively. Our results suggest that constitutive expression of foreign nitrate reductase gene(s) in wheat might improve nitrogen use efficiency and thus make it possible to increase seed protein content and weight without augmenting N supplying.


Assuntos
Nicotiana/enzimologia , Nitrato Redutase/biossíntese , Nitrogênio/química , Proteínas de Plantas/biossíntese , Sementes/enzimologia , Triticum/metabolismo , Agrobacterium tumefaciens/metabolismo , Biomassa , Técnicas de Cocultura , Canamicina/química , Nitrato Redutase/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/enzimologia , Nicotiana/genética , Triticum/genética
18.
Bull Math Biol ; 75(3): 543-63, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23381930

RESUMO

This paper is devoted to the investigation of the effects of periodic drug treatment on a standard within-host virus model. We first introduce the basic reproduction ratio for the model, and then show that the infection free equilibrium is globally asymptotically stable, and the disease eventually disappears if R0<1, while there exists at least one positive periodic state and the disease persists when R0>1. We also consider an optimization problem by shifting the phase of these drug efficacy functions. It turns out that shifting the phase can certainly affect the stability of the infection free steady state. A numerical study is performed to illustrate our analytic results.


Assuntos
Número Básico de Reprodução , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , HIV/isolamento & purificação , Modelos Biológicos , Inibidores da Transcriptase Reversa/administração & dosagem , Simulação por Computador , Infecções por HIV/imunologia , Inibidores da Protease de HIV/farmacocinética , Inibidores da Transcriptase Reversa/farmacocinética
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(5): 1086-9, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23114124

RESUMO

This study was aimed to investigate the influence and significance of celecoxib (specific inhibitor of cyclooxygenase-2) on mRNA expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), transforming growth factor ß (TGF-ß) in acute leukemia cells. The expressions of VEGF, b-FGF, TGF-ß mRNA were measured by RT-PCR in acute leukemia cells treated with celecoxib (80 µmol/L, for 48 h) or with PBS. The results showed that the obvious expressions of VEGF, b-FGF, TGF-ß mRNA were observed in acute leukemia cells. By using Pearson correlation analysis, there was positive correlation between VEGF mRNA and b-FGF mRNA expressions (r = 0.559, P = 0.001), and negative correlation between VEGF and TGF-ß mRNA expressions (r = -0.4, P = 0.029). Expression levels of VEGF, b-FGF, TGF-ß mRNA in experimental group were lower than that in control group (P < 0.01). It is concluded that COX-2 inhibitor celecoxib can inhabit vascular endothelial growth through down-regulating the mRNA expression of VEGF, b-FGF and TGF-ß in acute leukemia cells. COX-2 inhibitor may offer supplemental effect for treating acute leukemia.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Leucemia/metabolismo , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Adulto , Celecoxib , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Leucemia/tratamento farmacológico , Masculino , RNA Mensageiro/genética , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(4): 926-9, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21867616

RESUMO

The aim of this study was to investigate the expression of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in acute leukemia (AL) and its significance in the angiogenesis and progress of AL. Serum levels of OPN and VEGF in 25 de novo patients, 19 complete remitted (CR) patients, 14 unremitted patients, and 11 relapsed patients with AL were measured by enzyme-linked immunosorbent assay (ELISA), and compared with those in normal controls. The results showed that the serum levels of OPN and VEGF in de novo, unremitted, relapsed patients were significantly higher than those in normal controls and CR patients (p < 0.01). Compared with de novo AL patients group, the serum levels of OPN and VEGF in CR patients decreased significantly, but showed no significant difference from those in normal controls (p > 0.05). The expression of OPN and VEGF in acute leukemia was positively correlated with occurrence and development of AL. It is concluded that the expressions of OPN and VEGF are closely related with AL occurrence and development, the OPN may regulate VEGF expression and promote angiogenesis in acute leukemia. Preventing expressions of OPN may seem as targets for leukemia therapy in the future.


Assuntos
Leucemia/sangue , Leucemia/patologia , Neovascularização Patológica/patologia , Osteopontina/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Doença Aguda , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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