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1.
Plant Cell Rep ; 41(1): 95-118, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34546426

RESUMO

KEY MESSAGE: Herein, the inoculation with strain wp-6 promoted the growth of wheat seedlings by improving the energy production and conversion of wheat seedlings and alleviating salt stress. Soil salinization decreases crop productivity due to high toxicity of sodium ions to plants. Plant growth-promoting rhizobacteria (PGPR) have been demonstrated to alleviate salinity stress. However, the mechanism of PGPR in improving plant salt tolerance remains unclear. In this study, physiological analysis, proteomics, and metabolomics were applied to investigate the changes in wheat seedlings under salt stress (150 mM NaCl), both with and without plant root inoculation with wp-6 (Bacillus sp.). Under salt stress, root inoculation with strain wp-6 increased plant biomass (57%) and root length (25%). The Na+ content was reduced, while the K+ content and K+/Na+ ratio were increased. The content of malondialdehyde was decreased by 31.94% after inoculation of wp-6 under salt stress, while the content of proline, soluble sugar, and soluble protein were increased by 7.48%, 12.34%, and 4.12%, respectively. The peroxidase, catalase, and superoxide dismutase activities were increased after inoculation of wp-6 under salt stress. Galactose metabolism, phenylalanine metabolism, caffeine metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and glutathione metabolism might play an important role in promoting the growth of salt-stressed wheat seedlings after the inoculation with wp-6. Interaction analysis of differentially expressed proteins and metabolites found that energy production and transformation-related proteins and six metabolites (D-arginine, palmitoleic acid, chlorophyllide b, rutin, pheophorbide a, and vanillylamine) were mainly involved in the growth of wheat seedlings after the inoculation with wp-6 under salt stress. Furthermore, correlation analysis found that inoculation with wp-6 promotes the growth of salt-stressed wheat seedlings mainly through regulating amino acid metabolism and porphyrin and chlorophyll metabolism. This study provides an eco-friendly method to increase agricultural productivity and paves a way to sustainable agriculture.


Assuntos
Bacillus/fisiologia , Metaboloma/fisiologia , Proteínas de Plantas/fisiologia , Proteoma/fisiologia , Tolerância ao Sal/genética , Triticum/fisiologia , Triticum/genética , Triticum/microbiologia
2.
Plant Physiol Biochem ; 166: 605-620, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34186284

RESUMO

BACKGROUND: Soil salinization is a major constraint limiting agricultural development and affecting crop growth and productivity, especially in arid and semi-arid regions. Understanding the molecular mechanism of the adaptability of canola to salt stress is very important to improve the salt tolerance of canola and promote its cultivation in saline alkali soil. RESULTS: To identify the metabolomic and transcriptomic mechanisms of canola under alkaline salt stress, we collected roots of control (no salt treatment) and 72 h Na2CO3-stressed canola seedlings (hydroponics) for metabolic profiling of metabolites, supplemented with RNA-Seq analysis and real-time quantitative PCR validation. Metabolomic analysis showed that the metabolites of amino acids and fatty acids were higher accumulated under alkaline salt stress, including L-proline, L-glutamate, L-histidine, L-phenylalanine, L-citrulline, L-tyrosine, L-saccharopine, L-tryptophan, linoleic acid, dihomo gamma linolenic acid, alpha linolenic acid, Eric acid, oleic acid and neuronic acid, while the metabolism of carbohydrate (sucrase, alpha, alpha trehalose), polyol (ribitol), UDP-D-galactose, D-mannose, D-fructose and D-glucose 6-phosphate decreased. Transcriptomic and metabolomic pathway analysis indicated that carbohydrate metabolism may not play an important role in the resistance of canola to alkaline salt stress. Organic acid metabolism (fatty acid accumulation) and amino acid metabolism are important metabolic pathways in the root of canola under alkaline salt stress. CONCLUSIONS: These results suggest that the genes and metabolites involved in fatty acid metabolism and amino acids metabolism in roots of canola may regulate salt tolerance of canola seedlings under alkaline salt stress, which improves our understanding of the molecular mechanisms of salt tolerance in canola.


Assuntos
Brassica napus , Álcalis , Brassica napus/genética , Metabolômica , Raízes de Plantas , Transcriptoma
3.
Environ Sci Pollut Res Int ; 28(17): 21823-21834, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33415627

RESUMO

Solution chemistry is of great importance to the removal of arsenic by coagulation through influencing the speciation of arsenic, the in situ precipitation of metal salts coupled with the adsorption and coprecipitation behavior of arsenic during coagulation. While the researches on the influence of solution chemistry in As(III) removal by titanium salts, a promising candidate for drinking water treatment was still deficient. Batch tests were performed to evaluate the removal of As(III) by titanium salts coagulation under solution chemistry influences. The results indicated that As(III) removal by Ti(SO4)2 and TiCl4 increased first and then decreased with the rising of solution pH from 4 to 10. TiCl4 preformed better in As(III) removal than Ti(SO4)2 at pH 4-8, but the opposite trends were observed at pH 9-10. XPS analysis indicated that the involvement of surface hydroxyl groups was primarily responsible for As(III) adsorption on Ti(IV) precipitates. As(III) removal was inhibited in the presence of SO42- mainly by competitive adsorption, especially at elevated SO42- concentration under acidic and alkaline conditions. F- exerted a greater suppressive effect than SO42- via indirectly hindering Ti(IV) precipitate formation, and through direct competitive adsorption with H3AsO3, the inhibitive effect increased as F- concentration increased and depended highly on solution pH. As(III) removal was promoted by co-existing Fe(II) primarily through the facilitation of Ti(IV) precipitation, especially under neutral and alkaline conditions, while it was inhibited to a different extent by the presence of high-concentration Mn(II) possibly via competitive adsorption. The presence of Ca2+ and Mg2+ enhanced the removal of As(III), but the positive effect did not increase as ionic concentration elevated.


Assuntos
Arsênio , Poluentes Químicos da Água , Purificação da Água , Adsorção , Concentração de Íons de Hidrogênio , Sais , Titânio , Poluentes Químicos da Água/análise
4.
Eur J Endocrinol ; 183(3): 245-254, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32520725

RESUMO

OBJECTIVE: To identify CCDC141 variants in a large Chinese cohort with congenital hypogonadotropic hypogonadism (CHH) and to assess the contribution of CCDC141 to CHH. DESIGN: Detailed phenotyping was conducted in CHH patients with CCDC141 variants and co-segregation analysis was performed, when possible. METHODS: Whole-exome sequencing was performed in 177 CHH patients and 450 unrelated, ethnically matched controls from China. RESULTS: Seven novel CCDC141 rare sequencing variants (RSVs) were identified in 12 CHH pedigrees. Four of the variants were private mutations; however, p.Q409X, p.Q871X and p.G1488S were identified in more than one patient. Up to 75% (9/12) of patients had mutations in other CHH-associated genes, which is significantly higher than CHH patients without CCDC141 RSVs. The co-segregation analysis for eight CHH families showed that 75% (6/8) CCDC141 RSVs were inherited from their fertile parents. Over half (58.3%, 8/18) of the patients exhibited other clinical deformities in addition to hypogonadism. One patient harbouring a CCDC141 RSV showed a reversal of CHH after sex-steroid replacement. CONCLUSIONS: Our results broaden the genotypic spectrum of CCDC141 in CHH, as CCDC141 RSVs alone do not appear sufficient to cause CHH. The phenotypic spectrum in patients with CCDC141 RSVs is much wider than originally believed.


Assuntos
Hipogonadismo/genética , Hipogonadismo/patologia , Proteínas do Tecido Nervoso/genética , China , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Mutação/genética , Linhagem , Fenótipo , Sequenciamento Completo do Exoma/métodos
5.
Clin Genet ; 97(5): 696-703, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32060892

RESUMO

Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder characterized by impaired sexual development and infertility, caused by the deficiency of hypothalamic gonadotropin-releasing hormone neurons. IHH is named Kallmann's syndrome (KS) or normosmic IHH (nIHH) when associated with a defective or normal sense of smell. Variants in SEMA3A have been recently identified in patients with KS. In this study, we screened SEMA3A variants in a cohort of Chinese patients with IHH by whole exome sequencing. Three novel heterozygous SEMA3A variants (R197Q, R617Q and V458I) were identified in two nIHH and one KS patients, respectively. Functional studies indicated that R197Q and R617Q variants were ineffective in activating the phosphorylation of FAK (focal adhesion kinase) in GN11 cells, despite normal production and secretion in HEK293T cells. The V458I SEMA3A had defect in secretion as it was not detected in the conditioned medium from HEK293T cells. Compared with wild type SEMA3A protein, all three SEMA3A mutant proteins were ineffective in inducing the migration of GN11 cells. Our study further showed the contribution of SEMA3A loss-of-function variants to the pathogenesis of IHH.


Assuntos
Hipogonadismo/genética , Infertilidade/genética , Síndrome de Kallmann/genética , Semaforina-3A/genética , Adulto , Movimento Celular/genética , Feminino , Quinase 1 de Adesão Focal/genética , Hormônio Liberador de Gonadotropina/genética , Células HEK293 , Heterozigoto , Humanos , Hipogonadismo/patologia , Infertilidade/patologia , Síndrome de Kallmann/patologia , Masculino , Mutação/genética , Linhagem , Fenótipo , Sequenciamento Completo do Exoma
6.
Fertil Steril ; 113(1): 158-166, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748124

RESUMO

OBJECTIVE: To analyze the prevalence of FGFR1, FGF8, and FGF17 mutations in a Chinese cohort with idiopathic hypogonadotropic hypogonadism (IHH) and to characterize the clinical presentations and therapeutic outcomes of IHH patients with FGFR1, FGF8, and FGF17 mutations. DESIGN: Retrospective cohort. SETTING: University hospital. PATIENT(S): A total of 145 IHH probands (125 men and 20 women) were recruited for this study. INTERVENTIONS(S): Hormone assays. MAIN OUTCOME MEASURE(S): Whole-exome sequencing, polymerase chain reaction-Sanger sequencing, in silico functional prediction. RESULT(S): Six novel mutations (p.154_158del, p.E496Rfs*12, p.W190X, p.S134D, p.W10X, and c.1552 + 3insT) in FGFR1, two novel mutations (p.E176K and p.R184C) in FGF8, three novel mutations (p.48_52del, p.P120L, and p.K191R) in FGF17, and five reported mutations (p.W289X, p.G237S, p.V102I, p.R250Q, and p.T340M) in FGFR1 were identified in 18 IHH patients. The functional consequences of all mutations were analyzed in silico. In addition to hypogonadotropic hypogonadism, 44.4% (8/18) patients exhibited other clinical deformities, including dental agenesis (3/18, 16.7%), hearing loss (3/18, 16.7%), and hand malformation (2/18, 11.1%). hCG/hMG therapy was effective in promoting sexual development in IHH patients with FGFR1, FGF8, and FGF17 mutations. CONCLUSION(S): We extended the mutational spectrum of FGFR1, FGF8, and FGF17 in IHH patients. The prevalence of FGFR1, FGF8, and FGF17 mutations in IHH was 12.4%. hCG/hMG therapy was effective to acquire fertility for patients with FGFR1, FGF8, and FGF17 mutations but has a risk of transmitting the mutations and IHH to the next generation.


Assuntos
/genética , Fator 8 de Crescimento de Fibroblasto/genética , Fatores de Crescimento de Fibroblastos/genética , Hipogonadismo/genética , Mutação/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adolescente , Adulto , Estudos de Coortes , Feminino , Genótipo , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/terapia , Masculino , Linhagem , Fenótipo , Estudos Retrospectivos , Sequenciamento Completo do Exoma/métodos , Adulto Jovem
7.
J Clin Endocrinol Metab ; 105(5)2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31689711

RESUMO

PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) and CHARGE (C, coloboma; H, heart abnormalities; A, choanal atresia, R, retardation of growth and/or development; G, gonadal defects; E, ear deformities and deafness) syndrome are 2 distinct developmental disorders sharing features of hypogonadism and/or impaired olfaction. CHD7 variants contribute to >60% CHARGE syndrome and ~10% IHH patients. A variety of extended CHARGE-like features are frequently reported in CHARGE patients harboring CHD7 variants. In this study, we aimed to systematically analyze the diagnostic CHARGE features and the extended CHARGE-like features in patients with IHH with CHD7 variants. METHODS: Rare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 177 IHH probands. Detailed phenotyping was performed in the IHH patients harboring CHD7 variants and their available family members. RESULTS: CHD7 RSVs were identified in 10.2% (18/177) of the IHH probands. Two diagnostic CHARGE features, hearing loss and ear deformities, were significantly enriched in patients with CHD7 variants. Furthermore, CHD7 variants were significantly associated with a panel of extended CHARGE-like phenotypes, including mild ocular defects, dyspepsia/gastroesophageal reflux disease and skeletal defects. We also developed a predictive model for prioritizing CHD7 genetic testing in IHH patients. CONCLUSION: CHD7 variants rarely cause isolated IHH. Surveillance of symptoms in CHARGE syndrome-affected organs will facilitate the proper treatment for these patients. Certain clinical features can be useful for prioritizing CHD7 genetic screening.


Assuntos
DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Hipogonadismo/genética , Hipogonadismo/patologia , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , China , Estudos de Coortes , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Mutação de Sentido Incorreto , Fenótipo , Adulto Jovem
8.
Arch Microbiol ; 201(9): 1219-1232, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31190086

RESUMO

In recent years, understanding the impact of reclamation of abandoned salinized field on microbial community structure is of great importance for ecosystem restoration in arid regions. The aim of this work was to investigate the effects of reclamation years on soil properties, bacterial community composition and diversity based on field sampling and llumina MiSeq sequencing. The five reclamation years are: unreclaimed salinized and reclaimed (1, 5, 10, and 15 years) fields. The results showed soil properties are significantly altered by abandoned salinized field. In particular, reclamation significantly decreased soil electrical conductivity, Cl-, SO42-, Na+, and Ca2+, during 5 years of reclamation. In addition, reclamation increased the richness and diversity of the bacterial community, except for the 1-year field soils. There was a large difference in the abundant bacterial phyla in 1-year field soils compared with other field soils. Proteobacteria were the most abundant in all of the field soils. Principal coordinates analysis showed that the abandoned and 1-year field soils exhibited specific differences in bacterial community structures compared with other field soils. Statistical analyses showed that available phosphorus, SO42-, Mg2+, and Ca2+ were the main physicochemical properties affecting the soil bacterial communities. Overall, reclamation improved soil physicochemical properties and altered the structure and composition of soil bacterial communities compared with unreclaimed salinized soil.


Assuntos
Recuperação e Remediação Ambiental , Microbiota/genética , Proteobactérias/classificação , Proteobactérias/isolamento & purificação , Solo/química , Biodiversidade , China , Fazendas , Proteobactérias/genética , Águas Salinas , Microbiologia do Solo
9.
Gene ; 702: 99-106, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30914325

RESUMO

Kallmann syndrome (KS) is characterized by the association of anosmia and hypogonadotropic hypogonadism. The hypogonadotropic hypogonadism is due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH). Mutations in transcription factor SOX10 have been recently identified in patients with KS and hearing loss. In this study, we identified three novel SOX10 mutations in a cohort of Chinese KS patients by using exome sequencing. Two mutations (A44G and L80V) are in heterozygous state whereas the other one (G41V) is a homozygous mutation. The patient with a homozygous G41V mutation had impaired hearing in both ears, whereas the patient with a heterozygous L80V mutation showed subtle hearing impairment in the left ear. Functional studies indicated that all three SOX10 mutations showed reduced capacity to transactivate the MITF promoter alone or in synergy with PAX3, although they showed similar subcellular localization, and DNA binding ability. Our study further highlighted the significance of SOX10 haploinsufficiency as a genetic cause of KS with hearing problem.


Assuntos
Síndrome de Kallmann/genética , Mutação , Fatores de Transcrição SOXE/genética , Adulto , Animais , China , DNA/metabolismo , Células HEK293 , Audição/genética , Humanos , Síndrome de Kallmann/fisiopatologia , Masculino , Camundongos , Células NIH 3T3 , Fatores de Transcrição SOXE/metabolismo , Ativação Transcricional , Adulto Jovem
10.
Prog Mol Biol Transl Sci ; 161: 149-179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30711026

RESUMO

Prokineticins are two conserved small proteins (~8kDa), prokineticin 1 (PROK1; also called EG-VEGF) and prokineticin 2 (PROK2; also called Bv8), with an N-terminal AVITGA sequence and 10 cysteines forming 5 disulfide bridges. PROK1 and PROK2 bind to two highly related G protein-coupled receptors (GPCRs), prokineticin receptor 1 (PROKR1) and prokineticin receptor 2 (PROKR2). Prokineticins and their receptors are widely expressed. PROK1 is predominantly expressed in peripheral tissues, especially steroidogenic organs, whereas PROK2 is mainly expressed in the central nervous system and nonsteroidogenic cells of the testes. Prokineticins signaling has been implicated in several important physiological functions, including gastrointestinal smooth muscle contraction, circadian rhythm regulation, neurogenesis, angiogenesis, pain perception, mood regulation, and reproduction. Dysregulation of prokineticins signaling has been observed in a variety of diseases, such as cancer, ischemia, and neurodegeneration, in which prokineticins signaling seems to be a promising therapeutic target. Based on the phenotypes of knockout mice, PROKR2 and PROK2 have recently been identified as causative genes for idiopathic hypogonadotropic hypogonadism, a developmental disorder characterized by impaired development of gonadotropin-releasing hormone neurons and infertility. In vitro functional studies with these disease-associated PROKR2 mutations uncovered some novel features for this receptor, such as biased signaling, which may be used to understand GPCR signaling regulation in general.


Assuntos
Doença , Saúde , Receptores Acoplados a Proteínas G/metabolismo , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/metabolismo , Sequência de Aminoácidos , Animais , Humanos , Mutação/genética , Nociceptividade , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/genética , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/química , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/genética
11.
FASEB J ; 33(3): 4538-4546, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30576231

RESUMO

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare disorder caused by the deficient production, secretion, or action of gonadotropin-releasing hormone. Prokineticin (PROK) receptor 2 ( PROKR2), a causative gene for IHH, encodes a GPCR PROKR2. When PROKR2 binds to its ligands PROKs, it may activate several signaling pathways, including IP3/Ca2+, MAPK, and cAMP pathways. However, the mutational spectrum of PROKR2 in Chinese patients with IHH has not been established. In the present study, we found that up to 13.3% (18/135) of patients with IHH in China carried mutations in PROKR2. Most of the variants in this study were private; however, a PROKR2 (c.533G > C; p.W178S) mutation was identified in 10 independent patients, implying a possible founder mutation. Functional studies indicated that 6 novel PROKR2 mutations led to decreased signaling to various extents. Two IHH-associated mutations (L218P and R270H) disrupted Gαq-dependent signaling but maintained normal Gαs and ERK1/2 signaling. A glutathione S-transferase pull-down experiment demonstrated that R270H mutation disrupted the interaction of intracellular loop 3 of PROKR2 to Gαq protein but not Gαs protein. Our results indicated that selective disruption of the interaction with a specific Gα-protein might underlie the biased signaling for certain IHH-associated PROKR2 mutations.-Zhao, Y., Wu, J., Jia, H., Wang, X., Zheng, R., Jiang, F., Chen, D.-N., Chen, Z., Li, J.-D. PROKR2 mutations in idiopathic hypogonadotropic hypogonadism: selective disruption of the binding to a Gα-protein leads to biased signaling.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Hipogonadismo/genética , Mutação de Sentido Incorreto , Mutação Puntual , Receptores Acoplados a Proteínas G/genética , Receptores de Peptídeos/genética , /genética , AMP Cíclico/metabolismo , Feminino , Efeito Fundador , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Hipogonadismo/etnologia , Sistema de Sinalização das MAP Quinases , Masculino , Mapeamento de Interação de Proteínas , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Peptídeos/metabolismo , Proteínas Recombinantes/metabolismo , Frações Subcelulares/química , Sequenciamento Completo do Exoma
12.
Mol Med Rep ; 18(1): 261-267, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29749493

RESUMO

The combination of cerebellar degeneration, hypogonadotropic hypogonadism and chorioretinal dystrophy defines Boucher­Neuhäuser syndrome (BNS), which has been associated with autosomal­recessive mutations in the patatin­like phospholipase domain containing 6 (PNPLA6) gene. However, no BNS cases have been reported in mainland China. In the present study, to the best of the authors' knowledge, the first patient with BNS was identified in China. A 39­year­old male was first diagnosed with hypogonadotropic hypogonadism. The proband additionally exhibited retinal degeneration and cerebellar dystrophy. Whole exome sequencing identified a compound heterozygous mutation in PNPLA6 (c.3386G>T+ c.3534G>C). The mutant amino acids were highly conserved and the mutations were predicted to be deleterious. This result further confirmed the role of PNPLA6 in BNS and suggested that whole exome sequencing may be applied for the diagnosis of complex syndromes, including BNS, prior to the observation of obvious symptoms.


Assuntos
Heterozigoto , Hipogonadismo/genética , Mutação , Fosfolipases/genética , Distrofias Retinianas/genética , Ataxias Espinocerebelares/genética , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Biochem Biophys Res Commun ; 501(2): 593-597, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29753739

RESUMO

Cisplatin is a platinum-based chemotherapy drug that is widely used to treat various types of malignancies. Although the involvement of circadian clock in cisplatin metabolism and excretion has been reported, the effect of cisplatin on circadian rhythm remains unclear. In the present study, we investigated the effects of cisplatin on clock genes expression in mouse peripheral tissues. Cisplatin induced severe nephrotoxicity, as revealed by the significant increase of blood urea nitrogen and serum creatinine levels. Moreover, cisplatin circadian time-dependently induced p21 expression in the liver, heart and kidney, with the highest increase during the dark phase. In addition, cisplatin altered the clock genes expression in the liver, heart and kidney in a tissue- and gene-specific manner. Interesting, the expression of D site of the albumin promoter binding protein (Dbp), a gene involved in detoxification and drug metabolism, was consistently suppressed in the liver, heart and kidney after cisplatin treatment, implying a role of DBP in the toxicity of cisplatin.


Assuntos
Antineoplásicos/efeitos adversos , Proteínas CLOCK/genética , Cisplatino/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Rim/metabolismo , Fígado/metabolismo , Camundongos
14.
Biosci. j. (Online) ; 34(3): 778-789, mai/jun. 2018. graf
Artigo em Inglês | LILACS | ID: biblio-967000

RESUMO

Usually, weak inorganic acids have been used to disperse collagen as green solvents for fabricating kinds of biomaterials all the time. However, it is an open question how much the dissolving process preserves or alters the native structure of collagen till now. Herein, we have examined the effect of three different solvents (HAc, HCl, H3PO4) on the secondary structures of collagen, based on circular dichroism (CD) spectra of collagen from 185 to 260 nm together with CDNN programs. We have found that collagen almost completely preserved its triple helical structure in the three inorganic acids at pH=3.0 or so, which demonstrated that it was the concentration of free H+ in the above three solutions whose pH was fixed at 3.0 that can maintain an proper amount of surface charge on the collagen colloidal particles and appropriately loose the three-helix structure, which can not only lead to a better dispersion behavior, but also maximize the preservation of the integrity of the collagen structure. Although the fractions of kinds of secondary structures in collagen were different from all the three solvents based on CDNN data, which gave very similar results for each other. These results was tested for the first time in this work to estimate the secondary structures for collagen in the different common inorganic acids, which provides a new avenue for green collagen solvents to prepare collagen-based composite with well triple-helical structure for tissue engineering.


Habitualmente, os ácidos inorgânicos fracos têm sido usados para dispersar colágeno como solventes verdes para fabricar tipos de biomateriais o tempo todo. No entanto, é uma questão aberta quanto o processo de dissolução preserva ou altera a estrutura nativa do colágeno até agora. Aqui, examinamos o efeito de três solventes diferentes (HAc, HCl, H3PO4) nas estruturas secundárias de colágeno, com base em espectros de dicroísmo circular (CD) de colágeno de 185 a 260 nm em conjunto com programas CDNN. Descobrimos que o colágeno preservou quase completamente sua estrutura helicoidal tripla nos três ácidos inorgânicos a pH = 3,0 ou mais, o que demonstrou que foi a concentração de H+ livre nas três soluções acima cujo pH foi fixado em 3,0 que pode manter uma boa quantidade de carga superficial sobre as partículas coloidais de colágeno e destrói adequadamente a estrutura de três hélices, o que não só pode levar a um melhor comportamento de dispersão, mas também maximizar a preservação da integridade da estrutura de colágeno. Embora as frações de tipos de estruturas secundárias em colágeno fossem diferentes de todos os três solventes com base em dados CDNN, que deram resultados muito semelhantes entre si. Estes resultados foram testados pela primeira vez neste trabalho para estimar as estruturas secundárias para o colágeno nos diferentes ácidos inorgânicos comuns, o que fornece uma nova alternativa para solventes de colágeno verdes para preparar compósitos à base de colágeno com a estrutura helicoidal tripla para engenharia de tecidos.


Assuntos
Dicroísmo Circular , Colágeno Tipo I , Ácidos Inorgânicos , Solventes , Materiais Biocompatíveis
15.
Gene ; 621: 1-4, 2017 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-28411082

RESUMO

Kallmann syndrome (KS) is characterized by isolated hypogonadotropic hypogonadism (IHH) with anosmia. Fibroblast growth factor receptor 1 (FGFR1) is one of KS-associated genes, accounts for approximately 10% of total patients. FGFR1 mutations have also been identified in more severe craniosynostosis syndromes, and a subset of craniosynostosis syndromes-associated FGFR1 mutations show dominant negative effect. In this study, we identified a novel FGFR1 mutation (c.867G>A; p.W289X) in a KS patient. The p.W289X mutation leads premature termination, producing a truncated FGFR1 without the transmembrane and intracellular domains. Indeed, the W289X FGFR1 was secreted into culture medium. Further, W289X FGFR1 interfered with the function of wild type receptor to induce ERK1/2 phosphorylation. We therefore identified a dominant negative FGFR1 mutation in the KS patient, and this mutant FGFR1 may be used to decipher the physiological function of FGFR1.


Assuntos
Síndrome de Kallmann/genética , Mutação , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adulto , Feminino , Genes Dominantes , Células HEK293 , Humanos , Síndrome de Kallmann/patologia , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Transporte Proteico , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Terminação da Transcrição Genética
16.
Chem Commun (Camb) ; 52(81): 12092-12095, 2016 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-27711293

RESUMO

Photo responsive polyethyl vinyl ketone (PEVK) and various block copolymers were prepared through the visible light induced cobalt mediated radical polymerization (CMRP) process. The first order kinetics and linear increase in molecular weight with conversion demonstrated a well-behaved system. Chain extension experiments showed the retention of the living end of PEVK.

17.
Chem Sci ; 6(5): 2979-2988, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29308172

RESUMO

The control of the polymerization of a wide range of monomers under mild conditions by a single catalyst remains a major challenge in polymer science. We report a versatile, well-defined organocobalt salen complex to control living radical polymerization of different categories of monomers, including acrylates, acrylamides and vinyl acetate, under visible light irradiation at ambient temperature. Both household light and sunlight were effectively applied in the synthesis of polymers with controlled molecular weights and narrow polydispersities. Narrowly dispersed block copolymers (Mw/Mn < 1.2) were obtained under various conditions. The structures of the polymers were analyzed by 1H NMR, 2D NMR, 13C NMR, GPC, MALDI-TOF-MS and isotopic labeling experiments, which showed that the ω and α ends of the polymer chains were capped with (salen)Co and -CO2CH3 segments, respectively, from the photoinitiator (salen)Co-CO2CH3. The ω end was easily functionalized through oxygen insertion followed by hydrolysis from 18O2 to -18OH. This robust system can proceed without any additives, and offers a versatile and green way to produce well-defined homo and block copolymers.

18.
Org Biomol Chem ; 12(43): 8580-7, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25238612

RESUMO

Mediation of reversible deactivation radical polymerization (RDRP) by cobalt(II) complexes (CMRP) is the most highly developed subcategory of organometallic mediated RDRP (OMRP). Attention was paid to CMRP for its unusual high efficiency observed for the control of acrylate and vinyl acetate polymerization that produced homo- and block copolymers with narrow molecular weight distribution and a predictable molecular weight. The reactions of organic radicals with cobalt(II) metallo-radicals and organo-cobalt(III) complexes have a central role in the pathways that mediate this type of reversible deactivation radical polymerization. The reversible deactivation pathway dominates the polymerization when cobalt(II) complexes can reversibly deactivate the radicals to form organo-cobalt(III) complexes. Degenerative transfer becomes the major pathway when the cobalt(II) species fully convert to organo-cobalt(III) complexes and the radicals in solution rapidly exchange with radicals in organo-cobalt(III) complexes. This review describes the polymerization behavior and control mechanisms used by cobalt complexes in the mediation of reversible deactivation radical polymerization. The emerging developments for CMRP in the aqueous phase and with photo-initiation are also described, followed by the challenges and future applications of this method.

19.
Chem Commun (Camb) ; 49(45): 5186-8, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23629632

RESUMO

This article describes the photo-induced living radical polymerization of acrylamides mediated by organo-cobalt porphyrins through photo-cleavage of the Co-C bond to give organic radicals, which propagate polymerization, and cobalt(II), which is a persistent metal-centered radical. Photo stimulus controls the initiation steps and regulates chain growth by activating the Co-C bond.

20.
Chem Commun (Camb) ; 48(29): 3506-8, 2012 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-22388481

RESUMO

Living radical polymerization (LRP) of organic and water soluble acrylates and acrylamides was mediated by a versatile cobalt porphyrin complex (TMP-OH)Co. The capability of this cobalt complex to mediate LRP in both polar and non-polar media permits the direct synthesis of useful and previously difficult to prepare functional block copolymers.

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