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Spider mites (Tetranychidae) are destructive agricultural pests which have evolved strategies to overcome plant defenses, such as the ability to puncture the leaves of their hosts to feed. The expression of many genes with unknown functions is altered during feeding, but little is known about the role of these genes in plant-mite interactions. Here, we identified 3 novel gene families through analysis of genomic and transcriptomic data from 3 spider mite species. These GARP family genes encode glycine and alanine-rich proteins; they are present in mites (Acariformes) but absent in ticks (Parasitiformes) in the subclass Acari, indicating that these genes have undergone a significant expansion in spider mites and thus play important adaptive roles. Transcriptomic analysis revealed that the expression of GARP genes is strongly correlated with feeding and the transfer to new hosts. We used RNA interference to silence GARP1d in the two-spotted spider mite Tetranychus urticae, which inhibited feeding and egg laying and significantly increased mortality when the mites were transferred to soybean shoots; a similar effect was observed after TuVATPase was silenced. However, no changes in mite mortality were observed after TuGARP1d-silenced mites were placed on an artificial diet, which was different from the effect of TuVATPase silencing. Our results indicate that GARP family members play important roles in mite-plant interactions. Additional studies are needed to clarify the mechanisms underlying these interactions.
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[This retracts the article DOI: 10.1016/j.jsps.2020.10.012.].
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RNA viruses are extremely diverse and rapidly evolving in various organisms. Our knowledge on viral evolution with interacted hosts in the manner of ecology is still limited. In the agricultural ecosystem, invasive insect species are posing a great threat to sustainable crop production. Among them, fruit flies (Diptera: Tephritidae Bactrocera and Zeugodacus) are destructive to fruits and vegetables, which are also closely related and often share similar ecological niches. Thus, they are ideal models for investigating RNA virome dynamics in host species. Using meta-transcriptomics, we found 39 viral sequences in samples from 12 fly species. These viral species represented the diversity of the viromes including Dicistroviridae, negev-like virus clades, Thika virus clades, Solemoviridae, Narnaviridae, Nodaviridae, Iflaviridae, Orthomyxoviridae, Bunyavirales, Partitiviridae, and Reoviridae. In particular, dicistrovirus, negev-like virus, orthomyxovirus, and orbivirus were common in over four of the fly species, which suggests a positive interaction between fly viromes that exist under the same ecological conditions. For most of the viruses, the virus-derived small RNAs displayed significantly high peaks in 21 nt and were symmetrically distributed throughout the viral genome. These results suggest that infection by these viruses can activate the host's RNAi immunity. Our study provides RNA virome diversity and evidence on their infection activity in ecologically associated invasive fruit fly species, which could help our understanding of interactions between complex species and viruses.
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Vírus de RNA , Tephritidae , Animais , Ecossistema , Quênia , Vírus de RNA/genética , TranscriptomaRESUMO
OBJECTIVE: To assess the prevalence and survival rate of newborns with a delayed diagnosis of critical congenital heart defects (CCHD) in Beijing. METHODS: This retrospective study analysed data from births between 2010 and 2017 from the Birth Defects Monitoring Network in Beijing. Newborns with CCHD were analysed according to seven categories. Statistical analyses were used to calculate the mortality rate within the first week (days 0-6) after live birth. Multivariate logistic regression analysis of survival was performed to analyse the potential risk factors for newborn mortality. RESULTS: A total of 1 773 935 perinatal newborns were screened in Beijing and 1851 newborns were diagnosed with CCHD, showing a prevalence of 10.43 per 10 000. Among the total 1851 CCHD patients, the majority (1692 of 1851; 91.41%) were identified through prenatal diagnosis, 104 of 1851 (5.62%) were diagnosed before obstetric discharge/transfer and 55 of 1851 (2.97%) were identified through delayed diagnosis. The prevalence of CCHD in newborns was 1.96 per 10 000 births. Multivariate logistic regression analysis of survival demonstrated that gestational age at delivery was the only risk factor for death within the first week after birth. CONCLUSIONS: Within the first week after birth, gestational age was the only risk factor for death in newborns with CCHD.
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Diagnóstico Tardio , Cardiopatias Congênitas , Pequim/epidemiologia , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/epidemiologia , Humanos , Recém-Nascido , Triagem Neonatal , Oximetria , Gravidez , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
In this study, we investigated the effect of latanoprost on the expression of TGF- ß1 and Wnt / ß - Catenin signal pathway in the choroid of form-deprivation myopia model rats. Forty rats were randomly divided into two groups: the control group and the FDM model group. Each group had 20 rats. The FDM model group was established by feeding latanoprost daily for 28 days. 15 rats in each group were used to measure the length of the ocular axis and the level of TGF-ß1 in choroidal tissue; the remaining 5 rats in each group were used for choroidal fibroblast culture. After modeling, the rats were killed, the length of the ocular axis was measured with a vernier caliper, and the level of TGF - ß1 protein and mRNA in the choroidal tissue of each group were measured with RT-PCR method. Results showed that compared with the control group, there was a significant difference in the axial length of the FDM model group (P< 0.05). There was a significant difference in the expression of TGF- ß1 protein and mRNA between the two groups (P<0.05). The cultured cells were identified as choroidal fibroblasts by immunocytochemistry. There was no significant difference (P>0.05) in the comparison of GSK3 ß protein in choroidal fibroblasts of rats in each group. TGF-ß 1 and APC protein in FDM group were significantly lower than those in the control group (P<0.05), while dcl3, p21-gsk3 ß and ß - Catenin proteins were significantly higher (P<0.05), and there was no significant difference (P>0.05) in the ratio of various indexes protein in FDM + ddk1 group and the comparison of TGF - ß1 and APC protein in FDM + ddk1 group and FDM group The expression of dcl3, p21-gsk3 ß and ß - Catenin decreased significantly (P<0.05). There was no significant difference in the expression of GSK3 ß mRNA in the choroidal fibroblasts of each group (P>0.05). The expression of TGF - ß 1 and APC mRNA in FDM group was significantly lower than that in the control group (P<0.05), while the expression of dcl3, p21-gsk3 ß and ß-catenin mRNA in FDM + ddk1 group was significantly higher than that in the control group (P<0.05) >In FDM + ddk1 group, TGF-ß 1 and APC mRNA were significantly lower than those in FDM group (P<0.05), while dcl3, p21-gsk3 ß and ß-Catenin mRNA were significantly higher (P<0.05).
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Corioide/efeitos dos fármacos , Latanoprosta/farmacologia , Miopia/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Células Cultivadas , Corioide/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Masculino , Miopia/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Pulmonary route of drug delivery has drawn significant attention due to the limitations associated with conventional routes and available treatment options. Drugs administered through pulmonary route has been an important research area that focuses on to developing effective therapeutic interventions for asthma, chronic obstructive pulmonary disease, tuberculosis, lung cancer etc. The intravenous route has been a natural route of delivery of proteins and peptides but associated with several issues including high cost, needle-phobia, pain, sterility issues etc. These issues might be addressed by the pulmonary administration of macromolecules to achieving an effective delivery and efficacious therapeutic impact. Efforts have been made to develop novel drug delivery systems (NDDS) such as nanoparticles, microparticles, liposomes and their engineered versions, polymerosomes, micelles etc to achieving targeted and sustained delivery of drug(s) through pulmonary route. Further, novel approaches such as polymer-drug conjugates, mucoadhesive particles and mucus penetrating particles have attracted significant attention due to their unique features for an effective delivery of drugs. Also, use of semi flourinated alkanes is in use for improvising the pulmonary delivery of lipophilic drugs. Present review focuses on to unravel the mechanism of pulmonary absorption of drugs for major pulmonary diseases. It summarizes the development of interventional approaches using various particulate and vesicular drug delivery systems. In essence, the orchestrated attempt presents an inflammatory narrative on the advancements in the field of pulmonary drug delivery.
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The isolation and modification of natural products play an important role in the synthesis of anti-tumor drugs for the treatment of cancer. The present study was designed to evaluate the effects of fangchinoline derivatives against cancer cells. In vitro cytotoxicity of all derivatives against five cancer cell lines (A549, Hela, HepG-2, MCF-7 and MDA-MB-231 cell lines) and HL-7702 normal cells was assessed using the CCK-8 assay, and the results showed that most of the synthesized compounds displayed better cytotoxic effects on all the tested cells compared to that of the parent fangchinoline. In particular, compound 3i had the strongest inhibitory effect on cell proliferation, with an IC50 value of 0.61⯵M against A549 cells. Compared with fangchinoline and HCPT (hydroxycamptothecine), the anti-proliferative activity of compound 3i was significantly increased. More interestingly, compound 3i had slight toxic side effects on normal cells, with an IC50 value of 27.53⯵M. Moreover, the cell viability and cell cycle assays revealed that compound 3i inhibited A549 cell proliferation and arrested A549 cells at the G2/M-phase. The apoptosis-inducing effects of compound 3i and the associated molecular mechanisms were assessed using flow cytometry, cell staining, reactive oxygen species assays, RT-qPCR and Western blot analysis. These results suggested that compound 3i induces apoptosis through a mitochondria-mediated intrinsic pathway. This study revealed that compound 3i is a promising candidate for future development as an anti-tumor drug.
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Antineoplásicos/farmacologia , Benzilisoquinolinas/farmacologia , Desenho de Fármacos , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Benzilisoquinolinas/síntese química , Benzilisoquinolinas/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Cynomolgus disease models that are similar to the preclinical stage of human type 2 diabetes mellitus (T2DM) were established by feeding middle-aged cynomolgus monkeys different high energy diets to study the differential expression of diabetes-related genes. METHODS: A total of 36 male monkeys were randomly divided into four groups and fed human diets with high sugar, high fat, double high sugar and fat, and a normal diet. The preclinical diabetes phase was determined by monitoring the metabolic characteristic indices and the results of oral glucose tolerance tests (OGTT). The mRNA expression of 45 diabetes-related genes in peripheral blood leukocytes was analyzed using real-time PCR. RESULTS: A total of 22, 25, and 21 genes were significantly up-regulated (P < 0.05) and 5, 7, and 5 genes were significantly down-regulated (P < 0.05) in the above three induced groups, respectively, compared with the control group. Of the 45 tested genes, the expression profiles of 21 genes were consistent. Most of the expression levels in the double high sugar-and-fat individuals were slightly lower than those in the high glucose and high fat groups, although the expression patterns of the three groups were essentially similar. CONCLUSION: The different high energy diets all induced diabetes and shared some phenotypic properties with human T2DM. Most of the expression patterns of the related genes were identical. The gene expression profiles could be used as references for the study of early diagnostic indicators and T2DM pathogenesis.
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OBJECTIVES: To evaluate regulation of the endoplasmic reticulum stress (ERS) response by acupuncture and to investigate its neuroprotective effect on brain injury caused by heroin addiction. METHODS: A total of 48 male Sprague-Dawley rats were randomly divided into a healthy control group (Control), an untreated heroin exposed group (Heroin) and a heroin exposed group receiving electroacupuncture (EA) treatment at GV14 and GV20 (Heroin+acupuncture) with n=16 rats per group. A rat model of heroin addiction was established by intramuscular injection of incremental doses of heroin for 8 consecutive days. A rat model of heroin relapse was established according to the exposure (addiction) â detoxification method. Apoptotic changes in nerve cells in the hippocampus and ventral tegmental area (VTA) were evaluated in each group of rats using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. PERK, eIF2a, CHOP, IRE1 and JNK gene expression and protein expression were measured using quantitative real-time PCR (RT-qPCR) assay and immunohistochemical assay, respectively. RESULTS: The total number of positive nerve cells in the hippocampus and VTA was significantly lower in the Heroin+acupuncture group than in the Heroin group (p<0.01). Compared with the Heroin group, mRNA and protein expression of PERK, eIF2a, CHOP, IRE1 and JNK in the hippocampus and VTA were significantly downregulated in the Heroin+acupuncture group (p<0.05). CONCLUSION: The acupuncture-regulated ERS response appears to mediate the neuroprotective effect of acupuncture in heroin-addicted rats with brain injury. Inhibition of CHOP and JNK upregulation and reduction of nerve cell apoptosis may be the main mechanisms underlying the effects of acupuncture on heroin addiction-induced brain injury.
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Lesões Encefálicas/etiologia , Encéfalo/patologia , Eletroacupuntura , Estresse do Retículo Endoplasmático , Dependência de Heroína/complicações , Heroína/efeitos adversos , Terapia por Acupuntura , Animais , Apoptose , Encéfalo/citologia , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Modelos Animais de Doenças , Dependência de Heroína/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Fármacos Neuroprotetores , Ratos Sprague-Dawley , Fator de Transcrição CHOP/metabolismoRESUMO
Twenty phenylpropenamide analogs with structural novelty were designed and synthesized upon pharmacophore-combination strategy. The structures of target compounds were elucidated by IR, 1H NMR, 13C NMR and MS, and all the target compounds were biologically evaluated for the inhibitory activities of platelet aggregation induced by adenosine diphoshateï¼ADPï¼ andï¼AAï¼ arachidonic acid via Bron method. As a result, compounds 6b, 9b, 9d and 9h demonstrated potent inhibitory activity against platelet aggregation induced by AA. Meanwhile, compounds 6b, 6d, 6j, 9b and 9g exhibited significant suppression of platelet aggregation induced by ADP.
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Amidas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Amidas/síntese química , Desenho de Fármacos , Humanos , Inibidores da Agregação Plaquetária/síntese químicaRESUMO
BACKGROUND: Mitochondrial diseases are a group of energy metabolic disorders with multisystem involvements. Variable clinical features present a major challenge in pediatric diagnoses. We summarized the clinical spectrum of m.3243A>G mutation in Chinese pediatric patients, to define the common clinical manifestations and study the correlation between heteroplasmic degree of the mutation and clinical severity of the disease. METHODS: Clinical data of one-hundred pediatric patients with symptomatic mitochondrial disease harboring m.3243A>G mutation from 2007 to 2013 were retrospectively reviewed. Detection of m.3243A>G mutation ratio was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Correlation between m.3243A>G mutation ratio and age was evaluated. The differences in clinical symptom frequency of patients with low, middle, and high levels of mutation ratio were analyzed by Chi-square test. RESULTS: Sixty-six patients (66%) had suffered a delayed diagnosis for an average of 2 years. The most frequent symptoms were seizures (76%), short stature (73%), elevated plasma lactate (70%), abnormal magnetic resonance imaging/computed tomography (MRI/CT) changes (68%), vomiting (55%), decreased vision (52%), headache (50%), and muscle weakness (48%). The mutation ratio was correlated negatively with onset age (r = -0.470, P < 0.001). Myopathy was more frequent in patients with a high level of mutation ratio. However, patients with a low or middle level of m.3243A>G mutation ratio were more likely to suffer hearing loss, decreased vision, and gastrointestinal disturbance than patients with a high level of mutation ratio. CONCLUSIONS: Our study showed that half of Chinese pediatric patients with m.3243A>G mutation presented seizures, short stature, abnormal MRI/CT changes, elevated plasma lactate, vomiting, and headache. Pediatric patients with these recurrent symptoms should be considered for screening m.3243A>G mutation. Clinical manifestations and laboratory abnormalities should be carefully monitored in patients with this point mutation.
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DNA Mitocondrial/genética , Doenças Mitocondriais/genética , Adolescente , Idade de Início , Povo Asiático , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Perda Auditiva/patologia , Perda Auditiva/fisiopatologia , Humanos , Lactente , Ácido Láctico/sangue , Imageamento por Ressonância Magnética , Masculino , Doenças Mitocondriais/sangue , Doenças Mitocondriais/patologia , Doenças Mitocondriais/fisiopatologia , Mutação , Mutação Puntual/genética , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Convulsões/patologia , Convulsões/fisiopatologiaRESUMO
Six novel ligustrazine chalcone aromatic oxygen alkyl acids compounds and two pyridine chalcone aromatic oxygen alkyl acids ester compounds were synthesized according to the traditional Chinese medicine theory removing blood stasis. The structures of target compounds were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid(AA) were measured by the liver microsomal incubation method in vitro. Hypolipidemic activities of compounds were tested in vivo for better inhibitory activities of platelet aggregation. Preliminary pharmacological results showed that compounds 7c, 8a and 11 a had potent inhibitory activity against platelet aggregation induced by AA, compounds 7c, 7d, 8a and 11 b showed significant inhibitory activity against platelet aggregation induced by ADP. Compounds 7c and 8a exhibited good hypolipidemic activities in high-fat-diet(HFD) induced hyperlipidemia C57/BL6 mice and worthy for further investigation.
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Chalconas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Pirazinas/farmacologia , Difosfato de Adenosina , Animais , Ácido Araquidônico , Chalconas/síntese química , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/síntese química , Hipolipemiantes/farmacologia , Camundongos Endogâmicos C57BL , Oxigênio , Agregação Plaquetária , Inibidores da Agregação Plaquetária/síntese química , Pirazinas/síntese químicaRESUMO
A series of valproic acid salicylanilide esters were designed and synthesized based on the principle of prodrug. The structures of the target compounds were confirmed by MS, 1H NMR and 13C NMR. Anti-tumor activities of these compounds against K562, A549, A431 cells in vitro were investigated by MTT assay and SRB assay. The results indicated that the compounds 6h-6j were found to have stronger cell growth inhibitory action than gefitinib, and comparable to niclosamide, which are worth to be intensively studied further.
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Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Pró-Fármacos/síntese química , Salicilanilidas/síntese química , Ácido Valproico/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ésteres , Humanos , Concentração Inibidora 50 , Células K562 , Estrutura Molecular , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Salicilanilidas/química , Salicilanilidas/farmacologia , Relação Estrutura-Atividade , Ácido Valproico/química , Ácido Valproico/farmacologiaRESUMO
Leaching of nitrate from agricultural land to groundwater and the resulting nitrate pollution are a major environmental problem worldwide. Its impact is often mitigated in aquifers hosting sufficiently reactive reductants that can promote autotrophic denitrification. In the case of pyrite acting as reductant, however, denitrification is associated with the release of sulfate and often also with the mobilization of trace metals (e.g., arsenic). In this study, reactive transport modeling was used to reconstruct, quantify and analyze the dynamics of the dominant biogeochemical processes in a nitrate-polluted pyrite-containing aquifer and its evolution over the last 50 years in response to changing agricultural practices. Model simulations were constrained by measured concentration depth profiles. Measured (3)H/(3)He profiles were used to support the calibration of flow and conservative transport processes, while the comparison of simulated and measured sulfur isotope signatures acted as additional calibration constraint for the reactive processes affecting sulfur cycling. The model illustrates that denitrification largely prevented an elevated discharge of nitrate to surface waters, while sulfate discharges were significantly increased, peaking around 15 years after the maximum nitrogen inputs.
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Água Subterrânea/química , Ferro/química , Modelos Teóricos , Nitratos/química , Sulfetos/química , Poluentes Químicos da Água/química , Desnitrificação , Oxirredução , Sulfatos/química , Isótopos de Enxofre , Movimentos da ÁguaRESUMO
A Gram-positive, non-motile, non-spore-forming, rod-shaped bacterium, strain 7087(T), was isolated from rhizosphere of maize in China. The strain grew at 4-50 °C and at pH 4-10, with optima of 37 °C and pH 7.0, respectively. Phylogenetic analysis based on the full-length 16S rRNA gene sequence revealed that strain 7087(T) was a member of the genus Microbacterium. High levels of 16S rRNA gene similarities were found between strain 7087(T) and Microbacterium binotii DSM 19164(T) (99.8 %). However, the DNA-DNA hybridization value between strain 7087(T) and Microbacterium binotii DSM 19164(T) was 24.2 %. The DNA G+C content of strain 7087(T) was 69.9 mol%. The major fatty acids were anteiso-C(17 : 0) (36.45 %), anteiso-C(15 : 0) (36.08 %) and iso-C(16 : 0) (16.11 %). The predominant menaquinones were MK-10 (28.1 %), MK-11 (54.8 %) and MK-12 (17.1 %). The diagnostic diamino acid in the cell-wall peptidoglycan was ornithine. The major polar lipids are diphosphatidylglycerol, unknown phospholipids, an unknown glycolipid and unknown amino lipids. On the basis of these results, strain 7087(T) is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium neimengense sp. nov. is proposed. The type strain is 7087(T) ( = ACCC 03008(T) = DSM 24985(T)).
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Actinomycetales/classificação , Filogenia , Rizosfera , Microbiologia do Solo , Zea mays/microbiologia , Actinomycetales/genética , Actinomycetales/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/análise , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Peptidoglicano/análise , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análiseRESUMO
Gibberellin (GA), a diterpene hormone, plays diverse roles in plant growth and development, including seed germination, stem elongation, and flowering time. Although it is known that GA accelerates flowering through degradation of transcription repressors, DELLAs, the underlying mechanism is poorly understood. We show here that DELLA directly binds to microRNA156 (miR156)-targeted SQUAMOSA PROMOTER BINDING-LIKE (SPL) transcription factors, which promote flowering by activating miR172 and MADS box genes. The interaction between DELLA and SPL interferes with SPL transcriptional activity and consequently delays floral transition through inactivating miR172 in leaves and MADS box genes at shoot apex under long-day conditions or through repressing MADS box genes at the shoot apex under short-day conditions. Our results elucidate the molecular mechanism by which GA controls flowering and provide the missing link between DELLA and MADS box genes.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Flores/fisiologia , Giberelinas/farmacologia , MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Ativação Transcricional , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Flores/efeitos dos fármacos , Flores/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Giberelinas/metabolismo , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , MicroRNAs/genética , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/fisiologia , Brotos de Planta , Regiões Promotoras Genéticas , Ligação Proteica , Mapeamento de Interação de Proteínas , Proteólise , Proteínas Repressoras/genética , Fatores de Tempo , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transformação Genética , Técnicas do Sistema de Duplo-HíbridoRESUMO
To explore pathological alteration of T2DM in cynomolgus monkeys, gene expression profiles of peripheral blood leukocytes from spontaneous and diet-induced T2DM models was analyzed using quantitative real-time PCR. Among 36 T2DM associated genes tested, 19 genes (including G6PC, CCR2B, CTLA4) displayed a similar expression pattern in both spontaneous and diet-induced T2DM models and were significantly up-regulated or down-regulated compared to controls. Interestingly, expression abundance of all up-regulated genes in the diet-induced T2DM was stronger, although not significantly, than spontaneous models, indicating diet-induced T2DM in monkeys should be a reliable research model for changes in gene expression. The characteristic gene expression pattern obtained here may be useful for the clinical diagnosis of T2DM.
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Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Modelos Animais de Doenças , Macaca fascicularis , Animais , Diabetes Mellitus Tipo 2/etiologia , Gorduras na Dieta/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Macaca fascicularis/genética , Macaca fascicularis/metabolismoRESUMO
CRYPTOCHROMES (CRYs) are photolyase-like ultraviolet-A/blue light photoreceptors that mediate various light responses in plants. The signaling mechanism of Arabidopsis CRYs (CRY1 and CRY2) involves direct CRY-COP1 interaction. Here, we report that CRY1(G380R), which carries a Gly-to-Arg substitution of the highly conserved G380 in the photolyase-related (PHR) domain of Arabidopsis CRY1, shows constitutive CRY1 photoreceptor activity in Arabidopsis. Transgenic plants overexpressing CRY1(G380R) display a constitutively photomorphogenic (COP) phenotype in darkness, as well as a dramatic early flowering phenotype under short-day light conditions (SD). We further demonstrate that CRY1(G380R) expression driven by the native CRY1 promoter also results in a COP phenotype in darkness. Moreover, overexpression of either the Arabidopsis homolog CRY2(G377R) or the rice ortholog OsCRY1b(G388R) of CRY1(G380R) in Arabidopsis results in a COP phenotype in darkness. Cellular localization studies indicate that CRY1(G380R) co-localizes with COP1 in the same nuclear bodies (NBs) in vivo and inhibits the nuclear accumulation of COP1 in darkness. These results suggest that the conserved G380 may play a critical role in regulating the photoreceptor activity of plant CRYs and that CRY1(G380R) might constitutively phenocopy the photo-activated CRY1 in darkness and thus constitutively mediate CRY1 signaling.
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Substituição de Aminoácidos , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/efeitos da radiação , Criptocromos/química , Criptocromos/metabolismo , Glicina/genética , Motivos de Aminoácidos , Arabidopsis/química , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Sequência Conservada , Criptocromos/genética , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Glicina/metabolismo , Luz , Estrutura Terciária de ProteínaRESUMO
A total of 138 middle and aged cynomolgus monkeys (Macaca fascicularis) (above 10 years) were classified into three groups based on fasting plasma glucose (FPG) values, specifically low FPG, normal FPG, and high FPG group. Total cholesterol (TCHO), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected in blood by automatic biochemical analyzer. The mRNA expressions of 37 diabetes-associated genes were analyzed with Real-time PCR in monocytes isolated from monkey peripheral blood. No significant correlation between the four serum lipid indictors HDL-C, LDL-C, TCHO, TG and FPG (P>0.05) were found. However, the expressions of ACE, ACLY, PRKCB1, SLC2A4, SNAP23, VAPA, IGF2BP2, and IFNG were significantly enhanced when FPG increased (P<0.05).
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Diabetes Mellitus Tipo 2/genética , Regulação da Expressão Gênica , Macaca fascicularis , Fatores Etários , Animais , Glicemia/análise , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Feminino , Humanos , Macaca fascicularis/genética , Macaca fascicularis/metabolismo , Masculino , Triglicerídeos/sangueRESUMO
To screen spontaneous diabetic mellitus and explore methods for its rapid identification, the basal and inferred levels of blood glucose of 440 overweight, middle- and old-aged cynomolgus monkeys were analyzed. Diagnostic diabetes was further validated by the oral glucose tolerance test (OGTT) and urine glucose. The average level of blood glucose of these cynomolgus monkeys was (3.88±0.98) mmol/L, which was lower than the level for suspected diabetes (5.0 mmol/L). Of them, 56 (12.72%) monkeys were identified with levels of blood glucose greater than 5.0 mmol/L and diagnosed as the diabetic subjects. This population showed impaired glucose tolerance using the OGTT and 39 of the 56 (69.23%) had glucose positive urine. The methods for screening diabetic mellitus used in this study were simple, quick, and limited the harm to animals. However, the incidence of diabetes was higher in these tested monkeys than in the regular human population in China (9.7%), suggesting that these methods are useful for screening diabetic disease in a large population but not suitable for all cynomolgus monkeys.