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1.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445135

RESUMO

Human pregnancy is a sequence of events finely tuned by several molecular interactions that come with a new birth. The precise interlocking of these events affecting the reproductive system guarantees safe embryo formation and fetal development. In this scenario, melatonin and myo-inositol seem to be pivotal not only in the physiology of the reproduction process, but also in the promotion of positive gestational outcomes. Evidence demonstrates that melatonin, beyond the role of circadian rhythm management, is a key controller of human reproductive functions. Similarly, as the most representative member of the inositol's family, myo-inositol is essential in ensuring correct advancing of reproductive cellular events. The molecular crosstalk mediated by these two species is directly regulated by their availability in the human body. To date, biological implications of unbalanced amounts of melatonin and myo-inositol in each pregnancy step are growing the idea that these molecules actively contribute to reduce negative outcomes and improve the fertilization rate. Clinical data suggest that melatonin and myo-inositol may constitute an optimal dietary supplementation to sustain safe human gestation and a new potential way to prevent pregnancy-associated pathologies.


Assuntos
Inositol/farmacologia , Melatonina/farmacologia , Oócitos/efeitos dos fármacos , Parto/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Animais , Feminino , Fertilização/efeitos dos fármacos , Humanos , Gravidez , Resultado da Gravidez
2.
Nutrients ; 13(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209137

RESUMO

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.


Assuntos
Hipotálamo/metabolismo , Inositol/análogos & derivados , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Administração Oral , Animais , Glicemia/metabolismo , Ativação Enzimática/efeitos dos fármacos , Glucagon/sangue , Homeostase , Hipotálamo/efeitos dos fármacos , Inositol/administração & dosagem , Inositol/sangue , Inositol/química , Inositol/farmacologia , Insulina/sangue , Insulina/metabolismo , Resistência à Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
3.
Clin Nutr ESPEN ; 44: 78-84, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34330516

RESUMO

BACKGROUND & AIMS: Potential effects of inositol supplementation on blood pressure (BP) have been examined in several interventional studies. Nevertheless, findings in this context are controversial. Therefore, the current systematic review and meta-analysis aimed to comprehensively assess the impact of inositol supplementation on BP. METHODS: Five online databases including Web of Science, Scopus, Embase, Cochrane, Google Scholar, and PubMed were systematically searched from inception to March 2020. We included all randomized clinical trials (RCTs) evaluating the effects of inositol supplementation on systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) in humans. RESULTS: The random-effects meta-analysis of 7 eligible RCTs demonstrated the significant decline in both SBP (WMD - 5.69 mmHg; 95% CI - 7.35 to - 4.02, P < 0.001) and DBP (WMD - 7.12 mmHg; 95% CI - 10.18 to - 4.05, P < 0.001) following supplementation with inositol. Subgroup analysis showed that studies performed in individuals with metabolic syndrome with a longer duration (>8 weeks) and a dose of 4000 mg resulted in a more effective reduction in SBP and DBP with acceptable homogeneity. CONCLUSIONS: The current meta-analysis, indicated that supplementation with inositol significantly decrease SBP and DBP. Further large-scale RCTs with better design are needed to confirm these findings.


Assuntos
Hipertensão , Inositol , Pressão Sanguínea , Suplementos Nutricionais , Humanos , Hipertensão/tratamento farmacológico , Inositol/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
J Food Biochem ; 45(7): e13771, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34028050

RESUMO

Hawthorn berry has been proved hypoglycemic effect due to the presence of some α-glucosidase inhibitors. Herein, screening and identifying of α-glucosidase inhibitors from hawthorn berry were conducted, and the results showed polyphenols mainly containing quercetin (74.58%) and hyperioside (9.58%) were responsible for its bioactivity. In order to enhance the hypoglycemic effect, the combined glucose-lowering complex (DEH) consisting of hawthorn polyphenols, D-chiro-inositol (DCI), and epigallocatechin gallate (EGCG) was prepared, where three ingredients exerted the synergistic hypoglycemic effect to enhance glucose consumption and glycogen levels and inhibit hepatic gluconeogenesis in IR-HepG2 cells. In STZ/HFD-induced mice, DEH effectively improved insulin resistance, reduced fasting blood glucose (FBG) and hepatic gluconeogenesis, and increased hepatic glycogen synthesis and storage via down-regulation of PI3K/Akt/FOXO1-mediated PEPCK and G6Pase and up-regulation of PI3K/Akt/GSK3-mediated GS activation in the liver. In summary, these findings indicate that DEH is a potential novel strategy for the treatment of type 2 diabetes. PRACTICAL APPLICATIONS: Glucose-lowering complex (DEH) with superior hypoglycemic effect, can effectively improve the insulin resistance, reduce the fasting blood glucose, hepatic gluconeogenesis and increase the hepatic glycogen synthesis and storage in mice, which represents a potential novel strategy for the treatment of type 2 diabetes.


Assuntos
Crataegus , Diabetes Mellitus Tipo 2 , Animais , Catequina/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quinase 3 da Glicogênio Sintase , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Inositol/farmacologia , Camundongos , Fosfatidilinositol 3-Quinases , Polifenóis/farmacologia
5.
Mol Plant Pathol ; 22(7): 769-785, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33934484

RESUMO

Deoxynivalenol (DON) is a vital virulence factor of Fusarium graminearum, which causes Fusarium head blight (FHB). We recently found that validamycin A (VMA), an aminoglycoside antibiotic, can be used to control FHB and inhibit DON contamination, but its molecular mechanism is still unclear. In this study, we found that both neutral and acid trehalase (FgNTH and FgATH) are the targets of VMA in F. graminearum, and the deficiency of FgNTH and FgATH reduces the sensitivity to VMA by 2.12- and 1.79-fold, respectively, indicating that FgNTH is the main target of VMA. We found FgNTH is responsible for vegetative growth, FgATH is critical to sexual reproduction, and both of them play an important role in conidiation and virulence in F. graminearum. We found that FgNTH resided in the cytoplasm, affected the localization of FgATH, and positively regulated DON biosynthesis; however, FgATH resided in vacuole and negatively regulated DON biosynthesis. FgNTH interacted with FgPK (pyruvate kinase), a key enzyme in glycolysis, and the interaction was reduced by VMA; the deficiency of FgNTH affected the localization of FgPK under DON induction condition. Strains with a deficiency of FgNTH were more sensitive to demethylation inhibitor (DMI) fungicides. FgNTH regulated the expression level of FgCYP51A and FgCYP51B by interacting with FgCYP51B. Taken together, VMA inhibits DON biosynthesis by targeting FgNTH and reducing the interaction between FgNTH and FgPK, and synergizes with DMI fungicides against F. graminearum by decreasing FgCYP51A and FgCYP51B expression.


Assuntos
Fungicidas Industriais/farmacologia , Fusarium/genética , Inositol/análogos & derivados , Doenças das Plantas/microbiologia , Trealase/antagonistas & inibidores , Tricotecenos/metabolismo , Triticum/microbiologia , Família 51 do Citocromo P450/genética , Família 51 do Citocromo P450/metabolismo , Sinergismo Farmacológico , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/metabolismo , Fusarium/efeitos dos fármacos , Fusarium/patogenicidade , Inositol/farmacologia , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , Trealase/genética , Trealase/metabolismo , Virulência
6.
Nat Commun ; 12(1): 2148, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846320

RESUMO

Deregulation of chromatin modifiers plays an essential role in the pathogenesis of medulloblastoma, the most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation of inositol metabolism in a proportion of medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically in medulloblastoma of the molecular subgroup G4 characterised by a BMI1High;CHD7Low signature and show this can be counteracted by IP6 treatment. Finally, we demonstrate that IP6 synergises with cisplatin to enhance its cytotoxicity in vitro and extends survival in a pre-clinical BMI1High;CHD7Low xenograft model.


Assuntos
Adaptação Fisiológica , Neoplasias Cerebelares/genética , Epigênese Genética , Inositol/farmacologia , Meduloblastoma/genética , Adaptação Fisiológica/efeitos dos fármacos , Animais , Contagem de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Proteínas de Ligação a DNA/metabolismo , Sinergismo Farmacológico , Epigênese Genética/efeitos dos fármacos , Humanos , Camundongos , Células-Tronco Neurais/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Fosfatidilinositóis/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Proteínas com Domínio T , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Biosci Biotechnol Biochem ; 85(3): 643-655, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33589894

RESUMO

The long-term imposition of pressure overload on the cardiac tissue causes left ventricular hypertrophy (LVH) and cardiac fibrosis. Pinitol has been reported to possess antioxidant potential. The aim was to evaluate the efficacy of pinitol against pressure overload-induced cardiac hypertrophy and fibrosis in the aortic stenosis (AS) rat model. Cardiac hypertrophy was produced in Sprague-Dawley rats by abdominal aortic constriction and treated with lisinopril (15 mg/kg) or pinitol (5, 10, and 20 mg/kg). Pressure overload-induced alterations in hemodynamic and left ventricular function tests, cardiac SOD, GSH, MDA, NO, Na-K-ATPase, and mitochondrial complex enzyme levels were significantly attenuated by pinitol. The upregulated mRNA expressions of cardiac ANP, BNP, cTn-I, TNF-α, IL-1ß, IL-6, Bax, Caspase-3, collagen-I, and cardiac apoptosis were markedly downregulated by pinitol. In conclusion, pinitol ameliorated pressure overload-induced LVH and fibrosis via its anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic potential in experimental AS.


Assuntos
Cardiomegalia/prevenção & controle , Inositol/análogos & derivados , Animais , Cardiomegalia/enzimologia , Cardiomegalia/etiologia , Cardiomegalia/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Testes de Função Cardíaca , Inositol/farmacologia , Inositol/uso terapêutico , Lisinopril/farmacologia , Lisinopril/uso terapêutico , Mitocôndrias Cardíacas/enzimologia , Mitocôndrias Cardíacas/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Regulação para Cima
8.
Food Funct ; 12(6): 2554-2568, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33625409

RESUMO

Ulcerative colitis is a recrudescent intestinal inflammation coupled with diarrhea, weight loss, pus, and blood stool, which seriously impacts the quality of patient life. d-Pinitol, which can be a food supplement isolated from the food plant-like soybeans, Ceratonia siliqua Linn and Bruguiera gymnorrhiza, has been proved to show anti-oxidative and anti-inflammatory effects. However, the potential mechanism of d-pinitol still remains ill-defined contemporarily. In the current study, the therapeutic effect and potential mechanisms of d-pinitol against colitis were investigated. Oxidative stress and inflammation of experimental colitis were caused by 3% DSS treatment once daily for 7 days. During DSS treatment, the mice of the positive drug group and three other groups were orally administered SASP or d-pinitol once daily. Clinical symptoms were analyzed, and macroscopic scores were calculated. The levels of oxidative and inflammatory cytokines were measured using assay kits and RT-PCR. Additionally, the protein expression of the Nrf2/ARE pathway and PPAR-γ was measured by Western blot. Results showed that d-pinitol enormously alleviated DSS-induced bodyweight loss, colon shortening, and histological injuries, achieving a therapeutic efficacy superior to SASP. Moreover, the oxidative stress and colonic inflammatory response were mitigated. d-pinitol not only significantly activated the Nrf2/ARE signaling pathway via facilitating the translocation of Nrf2 from sitoplazma to cytoblast, upregulating the protein expression levels of GCLC, GCLM, HO-1, and NQO1, but also improved the PPAR-γ level by binding to the active site of PPAR-γ, when suppressing NF-κB p65 and IκBα phosphorylation. In conclusion, d-pinitol exhibited a dramatic anti-colitis efficacy by activating the Nrf2/ARE pathway and PPAR-γ. Hence, d-pinitol may be a promising therapeutic drug against UC in the future.


Assuntos
Colite/metabolismo , Inositol/análogos & derivados , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Inositol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , PPAR gama/metabolismo
9.
Protein Pept Lett ; 28(7): 769-780, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33511923

RESUMO

BACKGROUND: Solanum lycocarpum is a medicinal plant used in Brazil with hypoglycemic activity by its fruits use. However, the fruits production is restricted in some periods of the year, differently of leaves. OBJECTIVE: To evaluate the effects of hydroalcoholic extracts of S. lycocarpum leaves in alloxan-induced diabetic mice. METHODS: Hydroalcoholic extract of S. lycocarpum was characterized by phytochemical and GCMS analysis. The Antidiabetic activity was assessed following treatment for 22 days with S. lycocarpum extract at 125, 250, and 500 mg/kg. Bodyweight, water, and food intake, glycemia, biochemical parameters, anatomy-histopathology of the pancreas, liver and kidney, and expression of target genes were analyzed. In addition, oral acute toxicity was evaluated. RESULTS: Animals treated showed a significant reduction (p < 0.05) in glycemia following a dose of 125 mg/kg. Food intake remained similar for all groups. Decreased polydipsia symptoms were observed after treatment with 250 (p < 0.001) and 500 mg/kg (p < 0.01) compared with diabetic control, although normal rates were observed when 125 mg/kg was administered. A protective effect was also observed in the pancreas, liver, and kidneys, through the regeneration of the islets. Hypoglycemic activity can be attributed to myo-inositol, which stimulates insulin secretion, associated with α-tocopherol, which prevents damage from oxidative stress and apoptosis of ß-pancreatic cells by an increased Catalase (CAT) and Glutathione peroxidase 4 (GPX4) mRNA expression. The toxicological test demonstrated safe oral use of the extract under the present conditions. CONCLUSION: Hydroalcoholic extract of S. lycocarpum promotes the regulation of diabetes in the case of moderate glycemic levels, by decreasing glycemia and exerting protective effects on the islets.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Solanum/química , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Aloxano/administração & dosagem , Animais , Aspartato Aminotransferases/metabolismo , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Hipoglicemiantes/química , Inositol/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , alfa-Tocoferol/farmacologia
10.
ACS Appl Mater Interfaces ; 13(2): 2165-2178, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33400482

RESUMO

Oxidative damage to cells from metabolites at a wound site is one of the trickiest factors inhibiting tissue regeneration, especially with bulk damage. In addition, an excessive inflammatory reaction by the body at the wound site can make it even worse. How to scavenge the reactive oxygen species (ROS) produced from metabolism and inflammatory reactions has become a critical issue in tissue engineering. Here, we utilize the natural bioactive small molecules l-arginine and l-phenylalanine and the growth factor inositol to synthesize a branched poly(ester amide) (BPEA) to fabricate BPEA nanocapsules for vitamin E delivery at wound sites. BPEA nanocapsules loaded with vitamin E (BPEA@VE NCs) could protect cells from both extracellular and intracellular damage by scavenging ROS. Simultaneously, the inflammatory reaction could also be downregulated, benefiting from the introduction of l-arginine. Furthermore, the biodegradation products of BPEA are natural metabolites of the body, such as amino acids and growth factors, guaranteeing the biocompatibility of the BPEA@VE NCs. The protective ability of the BPEA@VE NCs was also investigated in vivo for accelerated wound healing. All the results indicate that the BPEA@VE NCs have promising potential for the modulation of the local microenvironment in tissue engineering for excellent antioxidative and anti-inflammatory properties.


Assuntos
Aminoácidos/administração & dosagem , Antioxidantes/administração & dosagem , Inositol/administração & dosagem , Nanocápsulas/química , Vitamina E/administração & dosagem , Cicatrização/efeitos dos fármacos , Aminoácidos/farmacologia , Aminoácidos/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Arginina/administração & dosagem , Arginina/farmacologia , Arginina/uso terapêutico , Células Endoteliais da Veia Umbilical Humana , Humanos , Inositol/farmacologia , Inositol/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Masculino , Camundongos , Células NIH 3T3 , Fenilalanina/administração & dosagem , Fenilalanina/farmacologia , Fenilalanina/uso terapêutico , Poliésteres/química , Células RAW 264.7 , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Engenharia Tecidual , Vitamina E/farmacologia , Vitamina E/uso terapêutico
11.
J Biochem Mol Toxicol ; 35(1): e22622, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32926510

RESUMO

Pneumonia is a chronic disorder of the respiratory system associated with worsening quality of life and a significant economic burden. Pinitol, a plant cyclic polyol, has been documented for immune-inflammatory potential. The aim of present investigation was to evaluate the potential and possible mechanism of action of pinitol against lipopolysaccharide (LPS)-induced pneumonia in the experimental animal model. Pneumonia was induced in Sprague-Dawley rats by intratracheal administration of LPS (2 mg/kg). Animals were treated with either vehicle or dexamethasone or pinitol (5 or 10 or 20 mg/kg). Potential of pinitol against LPS-induced pulmonary insult was assessed based on behavioral, biochemical, molecular, and ultrastructural studies. Intratracheal instillation of LPS induced significant (P < .05) inflammatory infiltration in bronchoalveolar lavage fluid (BALF) and lung tissue reflected by elevated pleural effusion volume, lung edema, BALF polymorphonuclear leukocytes count and lung myeloperoxidase levels, which was attenuated by pinitol (10 and 20 mg/kg) administration. Pinitol also markedly (P < .05) inhibited LPS-induced alterations in electrocardiographic, hemodynamic changes, right ventricular, and lung function tests. The LPS-induced downregulated nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1), whereas upregulated transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), and inducible nitric oxide synthase (iNOs) lung messenger RNA expressions were significantly (P < .05) inhibited by pinitol. Western blot analysis suggested pinitol markedly (P < .05) decreased nuclear factor-κB (NF-κB), inhibitor of nuclear factor κB (IkBα), toll-like receptor 4 (TLR-4), and cyclooxygenase-II (COX-II) protein expressions in the lung. These findings were further supported by histological and ultrastructural analyses of lung tissue that show pinitol significantly (P < .05) ameliorates LPS-induced aberrations in lung tissue. In conclusion, pinitol attenuated LPS-induced pneumonia via inhibition of TLR-4 to downregulate the NF-κB/IκBα signaling cascade and thus ameliorated the production of proinflammatory cytokines (TNF-α, ILs, NLRP3, and TGF-ß), inflammatory mediators (COX-II and iNOs) and elevated oxidative stress (Nrf-2 and HO-1).


Assuntos
Inositol/análogos & derivados , Lipopolissacarídeos/toxicidade , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Pneumonia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Inositol/farmacologia , Masculino , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Pneumonia/patologia , Ratos , Ratos Sprague-Dawley
12.
Insect Sci ; 28(3): 718-734, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32428381

RESUMO

The Asian citrus psyllid, Diaphorina citri is the principal vector of huanglongbing, which transmits Candidatus Liberibacter asiaticus. Trehalase is a key enzyme involved in trehalose hydrolysis and plays an important role in insect growth and development. The specific functions of this enzyme in D. citri have not been determined. In this study, three trehalase genes (DcTre1-1, DcTre1-2, and DcTre2) were identified based on the D. citri genome database. Bioinformatic analysis showed that DcTre1-1 and DcTre1-2 are related to soluble trehalase, whereas DcTre2 is associated with membrane-bound trehalase. Spatiotemporal expression analysis indicated that DcTre1-1 and DcTre1-2 had the highest expression levels in the head and wing, respectively, and DcTre2 had high expression levels in the fat body. Furthermore, DcTre1-1 and DcTre1-2 expression levels were induced by 20-hydroxyecdysone and juvenile hormone Ⅲ, but DcTre2 was unaffected. The expression levels of DcTre1-1, DcTre1-2, and DcTre2 were significantly upregulated, which resulted in high mortality after treatment with validamycin. Trehalase activities and glucose contents were downregulated, but the trehalose content increased after treatment with validamycin. In addition, the expression levels of chitin metabolism-related genes significantly decreased at 24 and 48 h after treatment with validamycin. Furthermore, silencing of DcTre1-1, DcTre1-2, and DcTre2 reduced the expression levels of chitin metabolism-related genes and led to a malformed phenotype of D. citri. These results indicate that D. citri trehalase plays an essential role in regulating chitin metabolism and provides a new target for control of D. citri.


Assuntos
Hemípteros , Trealase , Animais , Quitina/metabolismo , Regulação da Expressão Gênica , Genes de Insetos , Hemípteros/genética , Hemípteros/metabolismo , Inositol/análogos & derivados , Inositol/farmacologia , Controle de Pragas , Interferência de RNA , Trealase/efeitos dos fármacos , Trealase/genética , Trealase/metabolismo , Trealose/metabolismo
13.
Molecules ; 26(1)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374769

RESUMO

Chronic inflammation is one of the most common and well-recognized risk factors for human cancer, including colon cancer. Inflammatory bowel disease (IBD) is defined as a longstanding idiopathic chronic active inflammatory process in the colon, including ulcerative colitis and Crohn's disease. Importantly, patients with IBD have a significantly increased risk for the development of colorectal carcinoma. Dietary inositol and its phosphates, as well as phospholipid derivatives, are well known to benefit human health in diverse pathologies including cancer prevention. Inositol phosphates including InsP3, InsP6, and other pyrophosphates, play important roles in cellular metabolic and signal transduction pathways involved in the control of cell proliferation, differentiation, RNA export, DNA repair, energy transduction, ATP regeneration, and numerous others. In the review, we highlight the biologic function and health effects of inositol and its phosphates including the nature and sources of these molecules, potential nutritional deficiencies, their biologic metabolism and function, and finally, their role in the prevention of colitis-induced carcinogenesis.


Assuntos
Colite/complicações , Neoplasias do Colo/prevenção & controle , Fosfatos de Inositol/farmacologia , Inositol/farmacologia , Animais , Neoplasias do Colo/etiologia , Neoplasias do Colo/patologia , Humanos
14.
Eur Rev Med Pharmacol Sci ; 24(16): 8529-8536, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32894558

RESUMO

OBJECTIVE: To evaluate the efficacy of a treatment with Myo-inositol (MI) plus melatonin and vitamin D3 in women underwent intra cytoplasmatic sperm injection (ICSI). PATIENTS AND METHODS: 100 women undergoing ICSI procedure were enrolled and randomly divided 1:1 in two groups. The study group was treated with 2 g MI, 50 mg Alpha-Lactalbumin (alpha-LA) and 200 µg folic acid in powder every morning for 6 months (3 months before oocyte pick up and 3 months after ICSI); the same patients underwent treatment with 600 mg MI, 1 mg melatonin plus 200 µg folic acid during the evening for 3 months before oocyte pick up; subsequently the pick up these patients were treated with 600 mg MI, 200 µg folic acid, 1 mg melatonin, 50 µg vitamin D3 as cholecalciferol until the 12th week of gestation. The control group was treated with 200 µg folic acid twice a day. Clinical pregnancy rate was evaluated as primary outcome, followed by blastocyst and oocyte quality, as well as gestational period as secondary outcomes. RESULTS: Treatment significantly improved blastocyst and oocyte quality in the study group, achieving the 42% of clinical pregnancies vs. 24% in the control group, even though the course of pregnancy did not significantly differ between the groups. However, the mean gestational period was shorter in the control group. CONCLUSIONS: The supplementation of MI in combination with melatonin in the first 3 months before oocyte pick up and with vitamin D3 in the further 3 months could represent an innovative support for all those women undergoing ICSI.


Assuntos
Colecalciferol/farmacologia , Fertilização In Vitro/efeitos dos fármacos , Inositol/farmacologia , Melatonina/farmacologia , Oócitos/efeitos dos fármacos , Injeções de Esperma Intracitoplásmicas , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Gravidez , Estudos Prospectivos
15.
Expert Opin Drug Metab Toxicol ; 16(12): 1187-1198, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32966143

RESUMO

INTRODUCTION: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). AREAS COVERED: In view of the recent knowledge, changes in nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplemenation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs. EXPERT OPINION: Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions.


Assuntos
Diabetes Gestacional/prevenção & controle , Inositol/administração & dosagem , Defeitos do Tubo Neural/prevenção & controle , Animais , Feminino , Humanos , Recém-Nascido , Inositol/farmacologia , Insulina/metabolismo , Gravidez
16.
Int J Mol Sci ; 21(17)2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32842637

RESUMO

Polycystic ovarian syndrome (PCOS) is the main cause of female infertility. It is a multifactorial disorder with varying clinical manifestations including metabolic/endocrine abnormalities, hyperandrogenism, and ovarian cysts, among other conditions. D-Chiro-inositol (DCI) is the main treatment available for PCOS in humans. To address some of the mechanisms of this complex disorder and its treatment, this study examines the effect of DCI on reproduction during the development of different PCOS-associated phenotypes in aged females and two mouse models of PCOS. Aged females (8 months old) were treated or not (control) with DCI for 2 months. PCOS models were generated by treatment with dihydrotestosterone (DHT) on Days 16, 17, and 18 of gestation, or by testosterone propionate (TP) treatment on the first day of life. At two months of age, PCOS mice were treated with DCI for 2 months and their reproductive parameters analyzed. No effects of DCI treatment were produced on body weight or ovary/body weight ratio. However, treatment reduced the number of follicles with an atretic cyst-like appearance and improved embryo development in the PCOS models, and also increased implantation rates in both aged and PCOS mice. DCI modified the expression of genes related to oocyte quality, oxidative stress, and luteal sufficiency in cumulus-oocyte complexes (COCs) obtained from the aged and PCOS models. Further, the phosphorylation of AKT, a main metabolic sensor activated by insulin in the liver, was enhanced only in the DHT group, which was the only PCOS model showing glucose intolerance and AKT dephosphorylation. The effect of DCI in the TP model seemed mediated by its influence on oxidative stress and follicle insufficiency. Our results indicate that DCI works in preclinical models of PCOS and offer insight into its mechanism of action when used to treat this infertility-associated syndrome.


Assuntos
Blastocisto/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Inositol/farmacologia , Oócitos/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Envelhecimento , Animais , Blastocisto/fisiologia , Células do Cúmulo/efeitos dos fármacos , Di-Hidrotestosterona/toxicidade , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Intolerância à Glucose/tratamento farmacológico , Infertilidade Feminina/etiologia , Infertilidade Feminina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos , Oócitos/fisiologia , Fosforilação/efeitos dos fármacos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Propionato de Testosterona/toxicidade
17.
J Agric Food Chem ; 68(34): 9052-9060, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32806117

RESUMO

The low utilization rate of pesticides causes serious problems such as food safety and environmental pollution. Stimulus-responsive release can effectively improve the utilization rate of pesticides. Reactive oxygen species (ROS) burst, as an early event of plant-pathogen interaction, can stimulate the release of pesticides. In this work, a polymeric micelle with ROS-responsive was prepared and then Validamycin (Vail) was loaded into polymeric micelle to prepare Vail-loaded polymeric micelle. The Vail-loaded polymeric micelle displayed excellent ROS-dependent release kinetics. In vitro and in vivo antifungal experiments confirmed that the Vail-loaded polymeric micelle could improve antifungal efficacy against Rhizoctonia solani than with the Vail reagent. Therefore, as a biostimulation and controlled release system, ROS-responsive polymeric micelles can improve the utilization rate of pesticides and alleviate the problem of food safety and environmental pollution.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Fungicidas Industriais/química , Inositol/análogos & derivados , Polímeros/química , Espécies Reativas de Oxigênio/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/instrumentação , Liberação Controlada de Fármacos , Fungicidas Industriais/farmacologia , Inositol/química , Inositol/farmacologia , Cinética , Micelas , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento
18.
Mol Plant Microbe Interact ; 33(12): 1424-1437, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32815479

RESUMO

Validamycin A (VMA) is an aminoglycoside antibiotic used to control rice sheath blight. Although it has been reported that VMA can induce the plant defense responses, the mechanism remains poorly understood. Here, we found that reactive oxygen species (ROS) bursts and callose deposition in Arabidopsis thaliana, rice (Oryza sativa L.), and wheat (Triticum aestivum L.) were induced by VMA and were most intense with 10 µg of VMA per milliliter at 24 h. Moreover, we showed that VMA induced resistance against Pseudomonas syringae, Botrytis cinerea, and Fusarium graminearum in Arabidopsis leaves, indicating that VMA induces broad-spectrum disease resistance in both dicots and monocots. In addition, VMA-mediated resistance against P. syringae was not induced in NahG transgenic plants, was partially decreased in npr1 mutants, and VMA-mediated resistance to B. cinerea was not induced in npr1, jar1, and ein2 mutants. These results strongly indicated that VMA triggers plant defense responses to both biotrophic and necrotrophic pathogens involved in salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) signaling pathways and is dependent on NPR1. In addition, transcriptome analysis further revealed that VMA regulated the expression of genes involved in SA, JA/ET, abscisic acid (ABA), and auxin signal pathways. Taken together, VMA induces systemic resistance involving in SA and JA/ET signaling pathways and also exerts a positive influence on ABA and auxin signaling pathways. Our study highlights the creative application of VMA in triggering plant defense responses against plant pathogens, providing a valuable insight into applying VMA to enhance plant resistance and reduce the use of chemical pesticides.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Arabidopsis , Ciclopentanos , Resistência à Doença , Inositol/análogos & derivados , Oxilipinas , Ácido Salicílico , Transdução de Sinais , Arabidopsis/efeitos dos fármacos , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Botrytis/fisiologia , Ciclopentanos/metabolismo , Resistência à Doença/efeitos dos fármacos , Etilenos/metabolismo , Fusarium/fisiologia , Inositol/farmacologia , Oxilipinas/metabolismo , Doenças das Plantas/microbiologia , Ácido Salicílico/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Food Chem Toxicol ; 144: 111577, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32679288

RESUMO

Arsenic is a well-known potent toxicant affecting people by causing various human diseases. Long-term exposure to arsenic has strong adverse health effects on liver and kidney disorders, and various forms of cancer. Contrarily, curcumin and D-pinitol are bioactive dietary compounds that have antioxidant properties. Both are used to treat a broad variety of human diseases. Thus, we hypothesized that both may have synergistic effects against arsenic-induced toxicity in PC12 cells. Cells were pretreated with curcumin (1, 2.5, 5 and 10 µM), D-pinitol (1, 2.5, 5 and 10 µM) alone or in combination, then exposed to sodium arsenite (10 µM). The final concentration of curcumin 2.5 µM and D-pinitol 5 µM was selected for combination treatment based on their highest protection at lowest concentration against arsenic toxicity. Results demonstrated that pretreatment of curcumin and D-pinitol and their combined treatment with arsenic rescued PC12 cells. Western blot analysis results showed that pretreatment of curcumin and D-pinitol and their combined treatment with arsenic significantly inhibited arsenic-induced cell death through up-regulation of pro-survival proteins and down-regulation of cell death-related proteins, although these protein expressions were negatively regulated by arsenic. Furthermore, the effect of combined treatment with curcumin and D-pinitol was stronger than individual treatment.


Assuntos
Arsênio/toxicidade , Curcumina/farmacologia , Inositol/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Citometria de Fluxo , Glutationa/metabolismo , Inositol/administração & dosagem , Inositol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos
20.
Fish Shellfish Immunol ; 106: 691-704, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32711153

RESUMO

Myo-inositol is an essential vitamin for most animals, and it can modulate multiple physiological functions. In this study, we performed transcriptome gene expression profiling of gill tissue from turbot Scophthalmus maximus fed different concentrations of myo-inositol (0, 300, 600, 900, 1200 mg/kg). Results of expression tendency analysis, Weighted Gene Co-Expression Network Analysis (WGCNA), integrated transcriptome analyses, and KEGG annotation analysis of all differentially expressed genes (DEGs) demonstrated that the cytokine-cytokine receptor interaction played a core role in effects of myo-inositol on turbot, which was followed by the Jak-STAT signaling pathway. The results of qRT-PCR also showed myo-inositol mediated the gene expression of the cytokine-cytokine receptor interaction and the Jak-STAT signaling pathway in turbot. The ELISA assay indicated that myo-inositol affected the concentration change of interleukins (IL-2 and IL-10). Consequently, the interleukins associated with immune functions in the cytokine-cytokine receptor interaction played a core role in the effects of myo-inositol on turbot, which was followed by the Jak-STAT signaling pathway. Additionally, 10 hub genes associated with myo-inositol-traits were identified via WGCNA.


Assuntos
Linguados/genética , Inositol/farmacologia , Transcriptoma/efeitos dos fármacos , Animais , Citocinas/genética , Perfilação da Expressão Gênica , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Janus Quinase 2/genética , Fatores de Transcrição STAT/genética
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