RESUMO
Planarians, which have a large population of stem cells called neoblasts, are molecularly tractable model systems used in the study of regeneration. However, planarians have strong resistance to hunger and have developed growth arrest strategies. For example, they can change their size and undergo growth regression during starvation periods. The results of the current study show that the microRNA, miR-71b, and the insulin/IGF-1 signaling pathway have important functions in the development of starvation-induced planarians. We demonstrate tissue-specific expression of miR-71b using in situ hybridization. By employing real-time polymerase chain reaction, we provide evidence that miR-71b is upregulated in starvation-induced planarians. Furthermore, we validate and verify the target genes of miR-71b.
Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Insulina/metabolismo , MicroRNAs/genética , Inanição/metabolismo , Animais , Planárias , Transdução de Sinais , Inanição/genética , Regulação para CimaRESUMO
Available phosphate (Pi) is a major limiting factor for plant growth, development, and productivity. Phosphate starvation response 1 (PHR1) is a binding dimer that binds to an imperfect palindromic sequence. PHR1-binding sequences (GnATATnC) exist in the promoter of Pi starvation-responsive structural genes, indicating an effect occurring downstream in the Pi starvation signaling pathway. These sequences are referred to as PHR1-binding site (P1BS) structures. In this study, the sequences of GmPHR1 and GmSPX1 from Glycine max (L.) Merr. soybean were determined and analyzed. We found that GmPHR1 is an MYB-related transcription factor. In addition, GmSPX1 contained a P1BS structure, which is an important cis-regulatory motif in the phosphate signaling pathway. We found that GmPHR1 can physically interact with GmSPX1 through the cis-element, which may be a major pathway for the GmPHR1-mediated Pi starvation stress response. Thus, the P1BS structure in the Pi starvation signaling pathway is an important cis-regulatory motif that improves the tolerance to low phosphorus conditions in soybean.
Assuntos
Sítios de Ligação , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Glycine max/genética , Glycine max/metabolismo , Motivos de Nucleotídeos , Fosfatos/metabolismo , Estresse Fisiológico , Sequência de Aminoácidos , Clonagem Molecular , Proteínas de Ligação a DNA/química , Dados de Sequência Molecular , Ligação Proteica , Sequências Reguladoras de Ácido Nucleico , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
BACKGROUNDS: The present study aimed to evaluate benefit of hepatic arterial infusion chemotherapy (HAI) combined with systemic chemotherapy (SCT) for patients with colorectal liver metastases (CLMs) in a palliative setting. METHODS: This was a retrospective single-center study including 43 consecutive patients with CLM after failure of standard SCT. Among them, 20 (47 %) patients underwent HAI combined with SCT (Group A) and 23 historical control patients who had received SCT with or without targeted agent treatment (Group B). RESULTS: The two groups had similar characteristics. Compared with SCT alone, HAI combined with SCT prolonged survival (median 19.8 vs. 9.0 months; P = 0.045). Median hepatic progression-free survival was significantly longer for HAI combined with SCT vs. SCT alone (median 8.1 vs. 4.7 months; P = 0.027), as were response rates (25 and 0 %; P = 0.038) and progression-free survival (median 5.7 vs. 3.0 months; P = 0.02). Three patients (15 %) achieved conversion to potentially curative surgery. Grade 3/4 toxicities for Group A and Group B were neutropenia (5 and 8.7 %, respectively), anemia (5 and 0 %, respectively), and hyperbilirubinemia (0 and 4.3 %, respectively). Other complications were mostly grade 1 or 2. CONCLUSIONS: HAI combined with SCT treatment can improve overall survival compared with SCT alone in highly advanced CLM refractory to intravenous chemotherapy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Terapia de Salvação/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Tissue engineering encapsulated cells such as chondrocytes in the carrier matrix have been widely used to repair cartilage defects. However, chondrocyte phenotype is easily lost when chondrocytes are expanded in vitro by a process defined as “dedifferentiation”. To ensure successful therapy, an effective pro-chondrogenic agent is necessary to overcome the obstacle of limited cell numbers in the restoration process, and dedifferentiation is a prerequisite. Gallic acid (GA) has been used in the treatment of arthritis, but its biocompatibility is inferior to that of other compounds. In this study, we modified GA by incorporating sulfamonomethoxine sodium and synthesized a sulfonamido-based gallate, JJYMD-C, and evaluated its effect on chondrocyte metabolism. Our results showed that JJYMD-C could effectively increase the levels of the collagen II, Sox9, and aggrecan genes, promote chondrocyte growth, and enhance secretion and synthesis of cartilage extracellular matrix. On the other hand, expression of the collagen I gene was effectively down-regulated, demonstrating inhibition of chondrocyte dedifferentiation by JJYMD-C. Hypertrophy, as a characteristic of chondrocyte ossification, was undetectable in the JJYMD-C groups. We used JJYMD-C at doses of 0.125, 0.25, and 0.5 µg/mL, and the strongest response was observed with 0.25 µg/mL. This study provides a basis for further studies on a novel agent in the treatment of articular cartilage defects.
Assuntos
Animais , Coelhos , Benzamidas/síntese química , Desdiferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Fenótipo , Pirimidinas/síntese química , Agrecanas/genética , Agrecanas/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Benzamidas/farmacologia , Sobrevivência Celular , Desdiferenciação Celular/imunologia , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Glicosaminoglicanos/análise , Imuno-Histoquímica , Citometria de Varredura a Laser , Cultura Primária de Células , Pirimidinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Engenharia TecidualRESUMO
Tissue engineering encapsulated cells such as chondrocytes in the carrier matrix have been widely used to repair cartilage defects. However, chondrocyte phenotype is easily lost when chondrocytes are expanded in vitro by a process defined as "dedifferentiation". To ensure successful therapy, an effective pro-chondrogenic agent is necessary to overcome the obstacle of limited cell numbers in the restoration process, and dedifferentiation is a prerequisite. Gallic acid (GA) has been used in the treatment of arthritis, but its biocompatibility is inferior to that of other compounds. In this study, we modified GA by incorporating sulfamonomethoxine sodium and synthesized a sulfonamido-based gallate, JJYMD-C, and evaluated its effect on chondrocyte metabolism. Our results showed that JJYMD-C could effectively increase the levels of the collagen II, Sox9, and aggrecan genes, promote chondrocyte growth, and enhance secretion and synthesis of cartilage extracellular matrix. On the other hand, expression of the collagen I gene was effectively down-regulated, demonstrating inhibition of chondrocyte dedifferentiation by JJYMD-C. Hypertrophy, as a characteristic of chondrocyte ossification, was undetectable in the JJYMD-C groups. We used JJYMD-C at doses of 0.125, 0.25, and 0.5 µg/mL, and the strongest response was observed with 0.25 µg/mL. This study provides a basis for further studies on a novel agent in the treatment of articular cartilage defects.
Assuntos
Benzamidas/síntese química , Desdiferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Fenótipo , Pirimidinas/síntese química , Agrecanas/genética , Agrecanas/metabolismo , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Benzamidas/farmacologia , Desdiferenciação Celular/imunologia , Sobrevivência Celular , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Glicosaminoglicanos/análise , Imuno-Histoquímica , Citometria de Varredura a Laser , Cultura Primária de Células , Pirimidinas/farmacologia , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Engenharia TecidualRESUMO
Here, we aimed to clone and identify the GmIMT1 gene related to the salt stress response in soybean. The full-length cDNA sequence of the GmIMT1 gene was amplified in soybean using degenerate primers of Mesembrythmum crystallium. To understand the stress response, the GmIMT1 gene was cloned and sequenced. Then, the expression vectors of the gene were constructed, and introduced into the model plant Arabidopsis thaliana through Agrobacterium mediated transformation, and the salt tolerance was analyzed in the transgenic plants. In addition, the expression patterns of GmIMT1 gene in soybean were analyzed. The expression was examined in different organs (roots, leaves, flower seeds, and stem) and under different stress conditions (drought, high salt, low temperature, salicylic acid, ethane, abscisic acid, and methyl jasmonate) by real-time fluorescent quantitative polymerase chain reaction analysis. The results showed that the root, leaves, and stems exhibited high level of GmIMT1 gene expression, whereas there was no expression in the seeds. In addition, the GmIMT1 gene expression was upregulated under all stress conditions. Overall, the results clearly indicate that GmIMT1 might be involved in multiple plant response pathways to the different environmental conditions. Furthermore transgenic plants exhibited higher salt-tolerance compared to wild type plants.