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1.
BMC Gastroenterol ; 24(1): 171, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760704

RESUMO

BACKGROUND: Numerous researches have indicated a correlation between the intake of dietary micronutrients and the occurrence of constipation. Nevertheless, the correlation between constipation and vitamin B1 remains uninvestigated. The main aim of this research was to examine the association between chronic constipation and the consumption of vitamin B1 in the diet among adult participants of the National Health and Nutrition Examination Survey (NHANES). METHODS: This study used data from the NHANES, a survey on health and nutrition conducted between 2005 and 2010. The respondents' dietary information was gathered by utilizing the 24-hour dietary records. Various statistical analyses, such as multiple logistic regression, subgroup analysis, and curve-fitting analysis, were employed to investigate the correlation between dietary intake of vitamin B1 and chronic constipation. RESULTS: In the trial, there were 10,371 participants, out of which 1,123 individuals (10.8%) were identified as having chronic constipation. Fully adjusted multiple logistic regression analyses showed that increasing dietary intake of vitamin B1 (OR = 0.87, 95% CI: 0.77-0.99) was significantly associated with a reduced risk of constipation. Following adjustment for multiple variables in Model 3, the odds ratio (OR) and 95% confidence interval (CI) for the third tertile, in comparison to the first tertile (reference group), was 0.80 (0.65, 0.99). In addition, subgroup analyses and interaction tests showed a significant inverse association between vitamin B1 intake and the prevalence of constipation, especially among men, non-hypertensive, and non-diabetic individuals (all P-values less than 0.05). CONCLUSION: This research uncovered an inverse correlation between the consumption of vitamin B1 in the diet and the occurrence of chronic constipation. One potential explanation for this phenomenon is that the consumption of vitamin B1 in one's diet is linked to the softening of stools and an augmented occurrence of colonic peristalsis. Additional extensive prospective research is required to thoroughly examine the significance of thiamine in long-term constipation.


Assuntos
Constipação Intestinal , Dieta , Inquéritos Nutricionais , Tiamina , Humanos , Constipação Intestinal/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Tiamina/administração & dosagem , Doença Crônica , Modelos Logísticos , Idoso , Complexo Vitamínico B/administração & dosagem
2.
Lipids Health Dis ; 23(1): 38, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326904

RESUMO

OBJECTIVES: While lipid metabolism disorder is widely acknowledged as a contributing factor to inflammation, the association between remnant cholesterol (RC), which indicates lipid metabolism, and rheumatoid arthritis (RA) has not been investigated. Accordingly, this study evaluated whether RC is associated with RA disease events. METHODS: Data were collected and specifically extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2008 database. The RC value was derived by subtracting the combined amount of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from the total cholesterol (TC). The association between RC and RA was evaluated using multivariate regression analysis and subgroup analysis. RESULTS: The study analyzed 7777 patients, of which 581 patients (7.47%) were diagnosed with RA. After accounting for different covariates, the multivariate logistic regression analysis revealed a notable correlation between increased RC levels and an increased likelihood of RA (odds ratio OR = 1.54; 95% confidence interval CI: 1.11-2.13; P = 0.0092). The interaction test did not yield statistically significant effects on this association. The linear correlation between RC and RA was observed within restricted cubic spline regression model limitations. CONCLUSION: The results suggest that higher RC levels are associated with increased odds of RA, indicating that RC can serve as a novel and convenient index for forecasting the likelihood of RA in the United States. Additionally, these findings offer insights into early intervention strategies for susceptible populations at risk of developing RA.


Assuntos
Artrite Reumatoide , Humanos , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Artrite Reumatoide/epidemiologia , Colesterol , LDL-Colesterol , HDL-Colesterol , Fatores de Risco
3.
Lipids Health Dis ; 22(1): 132, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608322

RESUMO

OBJECTIVES: Insulin resistance is a well-established contributor to inflammation; however, the specific association between the triglyceride glucose (TyG) index, a biomarker reflecting insulin resistance, and arthritis remains unexplored. As a result, the main aim of this study was to examine the correlation between the TyG index and arthritis. METHODS: This observational study used data from the National Health and Nutrition Examination Survey (NHANES), which was conducted between 2007 and 2018. To investigate the relationship between the TyG index and arthritis, various statistical analyses were employed, including weighted multivariable logistic regression analysis, subgroup analysis, curve fit analysis, and threshold effect analysis. RESULTS: In total, 14,817 patients were enrolled in the trial, with 4,191 individuals (28.29%) diagnosed with arthritis. An increased risk of arthritis was found to be significantly correlated with higher TyG index values (odds ratio OR = 1.15, 95% confidence interval CI: 1.07-1.23), according to the results of multivariable logistic regression analysis after full adjustment. Subgroup analysis and interaction tests further indicated that the TyG index exhibited an additive effect when combined with other established risk factors, including age (OR = 1.29; 95% CI: 1.17-1.41), body mass index (BMI) (OR = 1.43; 95% CI: 1.24-1.69), and diabetes (OR = 1.20; 95% CI: 1.11-1.31). Additionally, curve fit analysis and threshold effect analysis demonstrated a nonlinear relationship with a breakpoint identified at 8.08 µmol/L. CONCLUSION: The TyG index was positively correlated with arthritis in adults under 60 years of age in the United States who had normal weight and no diabetes. Further large-scale prospective studies are warranted for a comprehensive analysis of the role of the TyG index in arthritis.


Assuntos
Artrite , Resistência à Insulina , Adulto , Humanos , Inquéritos Nutricionais , Resistência à Insulina/genética , Glucose , Triglicerídeos
4.
Int J Mol Sci ; 24(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36835183

RESUMO

N-fused pyrrolidinyl spirooxindole belongs to a class of privileged heterocyclic scaffolds and is prevalent in natural alkaloids and synthetic pharmaceutical molecules. To realize the switchable synthesis of divergent N-fused pyrrolidinyl spirooxindoles for further biological activity evaluation via a substrate-controlled strategy, a chemically sustainable, catalysis-free, and dipolarophile-controlled three-component 1,3-dipolar cycloaddition of isatin-derived azomethine ylides with diverse dipolarophiles is described in this work. A total of 40 functionalized N-fused pyrrolidinyl spirooxindoles were synthesized in 76-95% yields with excellent diastereoselectivities (up to >99:1 dr). The scaffolds of these products can be well-controlled by employing different 1,4-enedione derivatives as dipolarophiles in EtOH at room temperature. This study provides an efficient strategy to afford a spectrum of natural-like and potentially bioactive N-fused pyrrolidinyl spirooxindoles.


Assuntos
Isatina , Reação de Cicloadição , Isatina/química
5.
Chin J Traumatol ; 26(6): 323-328, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37940448

RESUMO

PURPOSE: Previous studies have confirmed that Achilles tendon occurs Achilles thickening after repair surgery of the rupture. Although this mechanism has been elucidated in the laboratory, there are few reports on its impact on clinical function. We designed a retrospective study to investigate the Achilles thickening after Achilles tendon rupture repair and its correlation between the elasticity and postoperative function. METHODS: In this retrospective analysis, patients who underwent surgical treatment for acute Achilles tendon rupture from April 2016 to April 2020 were included. All the patients were regularly followed up at 3 months, 1 year, and 2 years after surgery. American Orthopaedic Foot Ankle Surgeon (AOFAS) scale and Leppilahti score were used to evaluate functional outcomes. Achilles elasticity was measured by ultrasound shear wave of elasticity. Achilles thickening was calculated as maximal transverse and longitudinal diameter in cross-sectional plane of magnetic resonance scan. Sample t-tests was used for different follow-up periods. Correlation between Achilles thickening and other factors were analyzed using Pearson's method. p < 0.05 indicates a statistically significant difference. RESULTS: AOFAS scale and Leppilahti score at 1 year were significantly higher than at 3 months postoperatively (both p < 0.001). These functional scales were also improved at 2-year follow-up significantly (both p < 0.001). The dorsiflexion difference showed gradually recovery in each follow-up period (t = -17.907, p < 0.001). The elasticity of the Achilles appeared to continuously decreases during the postoperative follow-up period in all position sets (p < 0.001). In thickening evaluation, the cross-sectional area of the thickest plane of Achilles was significantly higher at 1 year postoperatively (310.5 ± 25.2) mm2 than that at 3 months postoperatively ((278.0 ± 26.2) mm2, t = -8.219, p < 0.001) and became thinner in 2-year magnetic resonance scan ((256.1 ± 15.1) mm2, t = 16.769, p < 0.001). The correlations between Achilles thickening, elasticity, and functional outcome did not show statistical significance (p > 0.05) in every follow-up period. CONCLUSION: Achilles tendon thickens after surgery in the 1st year, but begins to gradually return to thinning about 2 years after surgery. There was no significant correlation between the increase and decrease of thickening and the patients' clinical function scores, Achilles elasticity, and bilateral ankle dorsiflexion difference.


Assuntos
Tendão do Calcâneo , Traumatismos dos Tendões , Humanos , Tendão do Calcâneo/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Elasticidade , Traumatismos dos Tendões/diagnóstico por imagem , Traumatismos dos Tendões/cirurgia , Ruptura/cirurgia
6.
Acc Chem Res ; 54(1): 207-220, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33289536

RESUMO

Photodynamic therapy (PDT) is a clinically approved therapeutic modality that has shown great potential for the treatment of cancers owing to its excellent spatiotemporal selectivity and inherently noninvasive nature. However, PDT has not reached its full potential, partly due to the lack of ideal photosensitizers. A common molecular design strategy for effective photosensitizers is to incorporate heavy atoms into photosensitizer structures, causing concerns about elevated dark toxicity, short triplet-state lifetimes, poor photostability, and the potentially high cost of heavy metals. To address these drawbacks, a significant advance has been devoted to developing advanced smart photosensitizers without the use of heavy atoms to better fit the clinical requirements of PDT. Over the past few years, heavy-atom-free nonporphyrinoid photosensitizers have emerged as an innovative alternative class of PSs due to their superior photophysical and photochemical properties and lower expense. Heavy-atom-free nonporphyrinoid photosensitizers have been widely explored for PDT purposes and have shown great potential for clinical oncologic applications. Although many review articles about heavy-atom-free photosensitizers based on porphyrinoid structure have been published, no specific review articles have yet focused on the heavy-atom-free nonporphyrinoid photosensitizers.In this account, the specific concept related to heavy-atom-free photosensitizers and the advantageous properties of heavy-atom-free photosensitizers for cancer theranostics will be briefly introduced. In addition, recent progress in the development of heavy-atom-free photosensitizers, ranging from molecular design approaches to recent innovative types of heavy-atom-free nonporphyrinoid photosensitizers, emphasizing our own research, will be presented. The main molecular design approaches to efficient heavy-atom-free PSs can be divided into six groups: (1) the approach based on traditional tetrapyrrole structures, (2) spin-orbit charge-transfer intersystem crossing (SOCT-ISC), (3) reducing the singlet-triplet energy gap (ΔEST), (4) the thionation of carbonyl groups of conventional fluorophores, (5) twisted π-conjugation system-induced intersystem crossing, and (6) radical-enhanced intersystem crossing. The innovative types of heavy-atom-free nonporphyrinoid photosensitizers and their applications in cancer diagnostics and therapeutics will be discussed in detail in the third section. Finally, the challenges that need to be addressed to develop optimal heavy-atom-free photosensitizers for oncologic photodynamic therapy and a perspective in this research field will be provided. We believe that this review will provide general guidance for the future design of innovative photosensitizers and spur preclinical and clinical studies for PDT-mediated cancer treatments.


Assuntos
Desenho de Fármacos , Fármacos Fotossensibilizantes/química , Boro/química , Compostos de Boro/química , Humanos , Luz , Naftalimidas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Pirróis/química , Teoria Quântica , Oxigênio Singlete/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 47(13): 3609-3618, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-35850815

RESUMO

This study aims to systematically elucidate the pharmacodynamics and network pharmacological mechanism of Mongolian medicinal plants Scabiosa comosa, explore their key targets and related pathways, and further clarify the mechanism of the plants in treating liver fibrosis. Wistar rats were assigned into the blank group, carbon tetrachloride-induced liver fibrosis model group, and low-, medium-, and high-dose S. comosa groups. HE staining and Masson staining were performed for the observation of liver tissue under a microscope. Further, Wistar rats were assigned into a control group and a S. comosa group for administration. Seven days later, blood was collected from the abdominal aorta, and different doses of drug-containing serum samples were used to treat hepatic stellate cell-T6(HSC-T6). Flow cytometry was adopted to detect the apoptosis of HSC-T6 cells. Ultra-high performance liquid chromatography-time of flight-mass spectrometry(UHPLC-TOF-MS) was employed to determine the components in Scabiosa comosa. The target of S. comosa and liver fibrosis were obtained from SwissTargetPrediction and GeneCards, respectively, and the common targets were selected as the anti-liver fibrosis targets. Protein-protein interaction was analyzed via STRING. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out via Metascape. Phosphatidylinosital 3-kinase(PI3 K), protein kinase B(AKT), p-AKT, p38, and p-p38 targets which are involved in the top-ranked PI3 K/AKT and mitogen activated kinase-like protein(MAPK) signaling pathways were selected for validation via Western blot. The HE and Masson staining results showed that Scabiosa alleviated the hyperplasia of connective tissue and the fibrosis. The serum containing Scabiosa significantly promoted the apoptosis of HSC-T6 in a concentration-dependent manner. A total of 76 chemical components were identified by UHPLC-TOF-MS, among which flavonoids, alkaloids, terpenoids, phenols, and fatty acids were the main components. According to the prediction, there were 63 anti-liver fibrosis targets in Scabiosa comosa, the annotated GO terms of which involved biological processes, cell components, and molecular functions. The KEGG pathway enrichment showed that the targets were mainly involved in PI3 K/AKT, epidermal growth factor receptor(EGFR), RAS-associated protein 1(Rap1), hypoxia-inducible factor 1(HIF-1), resistance to audiogenic seizures(Ras), and MAPK signaling pathways. Western blot results showed that compared with the model group, S. comosa down-regulated the protein levels of α-smooth muscle actin(α-SMA), collagen Ⅰ, PI3 K, AKT, p-AKT, p38, and p-p38 in liver tissue. Compared with the control group, the low-, medium-, and high-dose S. comosa significantly down-regulated the protein levels of α-SMA, collagen Ⅰ, PI3 K, AKT, p-AKT, p38, and p-p38 in HSC-T6. The evidence of pharmacodynamics, network pharmacology, and molecular biology indicated that the plants of S. comosa had significant activity against liver fibrosis, the mechanism of which may involve the regulation of the key targets PI3 K, AKT, and MAPK14 p38 in the PI3 K/AKT and MAPK signaling pathways.


Assuntos
Dipsacaceae , Medicamentos de Ervas Chinesas , Animais , Colágeno Tipo I/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Farmacologia em Rede , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar
8.
Angew Chem Int Ed Engl ; 61(33): e202203758, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35384206

RESUMO

We observed a long-lived charge transfer (CT) state in a novel orthogonal compact electron donor-acceptor dyads, with closed form of rhodamine (Rho) as electron donor and pyromellitimide (PI),or thionated PI, as electron acceptor. The two parts in the dyads are connected via a spiro quaternary carbon atom, thus the torsion between the donor and acceptor is completely inhibited, which is beneficial to reduce the reorganization energy and to exploit the Marcus inverted region effect to prolong the CT state lifetime. Femtosecond transient absorption spectra show that the charge separation is rather fast, while nanosecond transient absorption spectra confirmed the formation of long-lived CT state (2.6 µs). Time-resolved electron paramagnetic resonance (TREPR) spectra determined the spin multiplicity of the long living state and assigned it to a 3 CT state. Replacement of an oxygen atom in the PI part with a sulfur atom favoring classical intersystem crossing processes, causes a consistently shortening of the lifetime of the 3 CT state (0.29 µs).

9.
Biosci Biotechnol Biochem ; 85(4): 775-785, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33686395

RESUMO

This research aimed to evaluate the antihepatic fibrosis effect and explore the mechanism of Qiwei Qinggan Powder (QGS-7) in vivo and in vitro. Carbon tetrachloride (CCl4)-treated rats and hepatic stellate cells (HSCs) were used. QGS-7 treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. Meanwhile, the hydroxyproline of liver was significantly decreased. Histopathological results indicated that QGS-7 alleviated liver damage and reduced the formation of fibrosis septa. Moreover, QGS-7 significantly attenuated expressions of Alpha smooth muscle actin, Collagen I, Janus kinase 2 (JAK2), phosphorylation-JAK2, signal transducer and activator of transcription 3 (STAT3), phosphorylation-STAT3 in the rat hepatic fibrosis model. QGS-7 inhibited HSC proliferation and promoted it apoptosis. QGS-7 may affect hepatic fibrosis through JAK2/STAT3 signaling pathway so as to play an antihepatic fibrosis role.


Assuntos
Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Medicina Tradicional da Mongólia , Animais , Intoxicação por Tetracloreto de Carbono/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , Hidroxiprolina/metabolismo , Janus Quinase 2/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Testes de Função Hepática , Mongólia , Fosforilação , Pós , Ratos , Fator de Transcrição STAT3/metabolismo
10.
Korean J Chem Eng ; 38(11): 2235-2246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522057

RESUMO

Catalytic pyrolysis offers a sustainable route to convert plastic wastes into fuel. We investigated the catalytic performance of coal ash (fly and bottom ash) at blending ratio of 5 wt%, and 15 wt% during pyrolysis of linear low-density polyethylene (LLDPE). The influence on activation energy and oil was characterized via thermogravimetric analyzer (TGA) and gas chromatography-mass spectrometry (GC-MS). Results have shown that 15 wt% bottom ash exhibited higher catalytic activity. The activation energy estimated by Coats-Redfern method decreased from 458.7 kJ·mol-1 to 437.8 kJ·mol-1, while the alicyclic hydrocarbon yield increased from 5.97% to 32.09%. This implies that CaO, which is abundant in bottom ash, could promote the conversion of LLDPE. Furthermore, a cradle-to-factory gate life cycle assessment was performed to investigate three scenarios (non-catalytic pyrolysis, 15 wt% fly ash, and 15 wt% bottom ash) of LLDPE conversion strategies via a normalization and weighting approach. It was found that LLDPE pyrolysis with 15 wt% bottom ash also showed the lowest normalized score of 2.83, implying the lowest environmental impact. This work has demonstrated that the recycling of coal ash, particularly bottom ash, as catalysts for LLDPE pyrolysis is effective.

11.
Angew Chem Int Ed Engl ; 59(37): 16114-16121, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32449273

RESUMO

Intersystem crossing (ISC) of triplet photosensitizers is a vital process for fundamental photochemistry and photodynamic therapy (PDT). Herein, we report the co-existence of efficient ISC and long triplet excited lifetime in a heavy atom-free bodipy helicene molecule. Via theoretical computation and time-resolved EPR spectroscopy, we confirmed that the ISC of the bodipy results from its twisted molecular structure and reduced symmetry. The twisted bodipy shows intense long wavelength absorption (ϵ=1.76×105 m-1 cm-1 at 630 nm), satisfactory triplet quantum yield (ΦT =52 %), and long-lived triplet state (τT =492 µs), leading to unprecedented performance as a triplet photosensitizer for PDT. Moreover, nanoparticles constructed with such helical bodipy show efficient PDT-mediated antitumor immunity amplification with an ultra-low dose (0.25 µg kg-1 ), which is several hundred times lower than that of the existing PDT reagents.


Assuntos
Compostos de Boro/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Relação Dose-Resposta a Droga , Espectroscopia de Ressonância de Spin Eletrônica , Estrutura Molecular , Teoria Quântica
12.
Mol Plant Microbe Interact ; 32(9): 1148-1161, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30933666

RESUMO

The methylcitrate cycle metabolizes propionyl-CoA, a toxic metabolite, into pyruvate. Pyricularia oryzae (syn. Magnaporthe oryzae) is a phytopathogenic fungus that causes a destructive blast disease in rice and wheat. We characterized the essential roles of the methylcitrate cycle in the development and virulence of P. oryzae using functional genomics. In P. oryzae, the transcript levels of MCS1 and MCL1, which encode a 2-methylcitrate synthase and a 2-methylisocitrate lyase, respectively, were upregulated during appressorium formation and when grown on propionyl-CoA-producing carbon sources. We found that deletion of MCS1 and MCL1 inhibited fungal growth on media containing both glucose and propionate, and media using propionate or propionyl-CoA-producing amino acids (valine, isoleucine, methionine, and threonine) as the sole carbon or nitrogen sources. The Δmcs1 mutant formed sparse aerial hyphae and did not produce conidia on complete medium (CM), while the Δmcl1 mutant showed decreased conidiation. The aerial mycelium of Δmcs1 displayed a lowered NAD+/NADH ratio, reduced nitric oxide content, and downregulated transcription of hydrophobin genes. Δmcl1 showed reduced appressorium turgor, severely delayed plant penetration, and weakened virulence. Addition of acetate recovered the growth of the wild type and Δmcs1 on medium containing both glucose and propionate and recovered the conidiation of both Δmcs1 and Δmcl1 on CM by reducing propionyl-CoA formation. Deletion of MCL1 together with ICL1, an isocitrate lyase gene in the glyoxylate cycle, greatly reduced the mutant's virulence as compared with the single-gene deletion mutants (Δicl1 and Δmcl1). This experimental evidence provides important information about the role of the methylcitrate cycle in development and virulence of P. oryzae by detoxification of propionyl-CoA and 2-methylisocitrate.


Assuntos
Proteínas Fúngicas , Magnaporthe , Oryza , Doenças das Plantas , Virulência , Proteínas Fúngicas/genética , Hifas/genética , Isocitrato Liase/genética , Magnaporthe/crescimento & desenvolvimento , Magnaporthe/patogenicidade , Oryza/microbiologia , Doenças das Plantas/microbiologia , Esporos Fúngicos/genética , Virulência/genética
14.
Environ Microbiol ; 20(9): 3427-3441, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30126031

RESUMO

Pyricularia oryzae is a plant pathogen causing rice blast, a serious disease spreading in cultivated rice globally. Transcription factors play important regulatory roles in fungal development and pathogenicity. Here, we characterized the biological functions of Crf1, a basic helix-loop-helix (bHLH) transcription factor, in the development and pathogenicity of P. oryzae with functional genetics, molecular and biochemical approaches. We found that CRF1 is necessary for virulence and plays an indispensable role in the regulation of carbohydrate and lipid metabolism in P. oryzae. Deletion of CRF1 led to defects in utilization of lipids, ethanol, glycerol and L-arabinose, and down-regulation of many important genes in lipolysis, ß-oxidation, gluconeogenesis, as well as glycerol and arabinose metabolism. CRF1 is also essential for peroxisome and vacuole function, and conidial cell death during appressorium formation. The appressorium turgor, penetration ability and virulence in Δcrf1 were restored by supplementation of exogenous glucose. The virulence of Crf1 mutant was also recovered by adding exogenous D-xylose, but not by addition of ethanol, pyruvate, leucine or L-arabinose. These data showed that Crf1 plays an important role in the complex regulatory network of carbohydrate and lipid metabolism that governs fungal development and pathogenicity.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Metabolismo dos Carboidratos , Proteínas Fúngicas/metabolismo , Metabolismo dos Lipídeos , Magnaporthe/metabolismo , Magnaporthe/patogenicidade , Oryza/microbiologia , Doenças das Plantas/microbiologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Magnaporthe/genética , Magnaporthe/crescimento & desenvolvimento , Deleção de Sequência , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/metabolismo , Esporos Fúngicos/patogenicidade , Fatores de Transcrição/genética , Virulência
15.
New Phytol ; 211(3): 1035-51, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27041000

RESUMO

The Cys2 -His2 (C2H2) zinc finger protein family is the second-largest family of transcription factors (TFs) in Magnaporthe oryzae, the causal fungus responsible for the destructive rice blast disease. However, little is known about the roles of most C2H2 TFs in the development and pathogenicity of M. oryzae. The roles of 47 C2H2 genes in development and pathogenicity were investigated by gene deletion in M. oryzae. The TF-dependent genes in mycelia or appressoria were analyzed with RNA sequencing and quantitative PCR (qPCR). Forty-four C2H2 genes are involved in growth (20 genes), conidiation (28 genes), appressorium formation (four genes) and pathogenicity (22 genes) in M. oryzae. Of these, MGG_14931, named as VRF1, is required for pathogenicity, specifically controlling appressorium maturation by affecting the expression of genes related to appressorial structure and function, including melanin biosynthesis, chitin catabolism, lipid metabolism, proteolysis, transmembrane transport, and response to oxidative stress; MGG_01776, named as VRF2, is required for plant penetration and invasive growth; conidiation-related gene CON7 is required for conidial differentiation; and MoCREA, encoding a carbon catabolite repression protein, is a novel repressor of lipid catabolism when glucose obtainable in M. oryzae. This study provides many insights into the regulation of growth, asexual development, appressorium formation, and pathogenicity by C2H2 TFs in M. oryzae.


Assuntos
Proteínas Fúngicas/metabolismo , Magnaporthe/patogenicidade , Oryza/microbiologia , Doenças das Plantas/microbiologia , Dedos de Zinco , Vias Biossintéticas/genética , Regulação Fúngica da Expressão Gênica , Genes Fúngicos , Hordeum/microbiologia , Magnaporthe/genética , Magnaporthe/crescimento & desenvolvimento , Melaninas/biossíntese , Mutação/genética , Micélio/crescimento & desenvolvimento , Fenótipo , Folhas de Planta/microbiologia , Esporos Fúngicos/fisiologia , Virulência
16.
Chem Biodivers ; 12(7): 1040-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26172324

RESUMO

Four new limonoids, azadiraindins A-D (1-4, resp.), together with seven known analogs, were isolated from the MeOH extract of Azadirachta indica. The structures of 1-4 were elucidated by NMR and MS spectroscopic analyses, and the relative configuration of 1 was determined by single-crystal X-ray crystallography. The compounds isolated in comparatively large amount were evaluated for their antifeedant activities against Plutella xylostella; the antifeedant rate of 10 was 90.6% and the corrected mortality of 8 was 79.2%.


Assuntos
Azadirachta/química , Comportamento Alimentar/efeitos dos fármacos , Inseticidas/farmacologia , Lepidópteros/efeitos dos fármacos , Limoninas/farmacologia , Animais , Cristalografia por Raios X , Inseticidas/química , Inseticidas/isolamento & purificação , Larva/efeitos dos fármacos , Limoninas/química , Limoninas/isolamento & purificação , Modelos Moleculares , Conformação Molecular
17.
J Asian Nat Prod Res ; 17(1): 14-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25289883

RESUMO

Three new limonoids, azadiraindins E-G (1-3, respectively), together with six known analogs, were isolated from the fresh fruit coats of Azadirachta indica. The structures of these compounds were elucidated by spectroscopic methods (IR, MS, HR-ESI-MS, 1D NMR, and 2D NMR).


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Azadirachta/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Limoninas/isolamento & purificação , Antineoplásicos Fitogênicos/química , Medicamentos de Ervas Chinesas/química , Frutas/química , Limoninas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química
18.
Theranostics ; 14(5): 2075-2098, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505622

RESUMO

Obesity-related metabolic diseases, including obesity, diabetes, hyperlipidemia, and non-alcoholic fatty liver diseases pose a significant threat to health. However, comprehensive pathogenesis exploration and effective therapy development are impeded by the limited availability of human models. Notably, advances in organoid technology enable the generation of adipose organoids that recapitulate structures and functions of native human adipose tissues to investigate mechanisms and develop corresponding treatments for obesity-related metabolic diseases. Here, we review the general principles, sources, and three-dimensional techniques for engineering adipose organoids, along with strategies to promote maturation. We also outline the application of white adipose organoids, primarily for disease modeling and drug screening, and highlight the therapeutic potential of thermogenic beige and brown adipose organoids in promoting weight loss and glucose and lipid metabolic homeostasis. We also discuss the challenges and prospects in the establishment and bench-to-bedside of adipose organoids, as well as their potential applications.


Assuntos
Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Tecido Adiposo Marrom/metabolismo , Obesidade/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Doenças Metabólicas/metabolismo , Termogênese
19.
Sex Med ; 12(3): qfae028, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38827361

RESUMO

Background: The correlation between osteoarthritis (OA) and rheumatoid arthritis (RA), both significant components of arthritis, and erectile dysfunction (ED) has yet to be thoroughly investigated. Aim: In this study we aimed to assess the association of OA and RA with ED. Methods: In this observational study we used data from the National Health and Nutrition Examination Survey, which was conducted between 2001 and 2004. Various statistical analyses were employed to investigate the associations of OA and RA with ED, including multivariable logistic regression analysis and subgroup analysis. Outcomes: The primary outcome for this investigation was arthritis as assessed through self-reporting. Results: In this comprehensive nationally representative survey spanning 4 years, our findings revealed a notably elevated incidence of ED within both OA and RA populations in comparison to the general population. Additional research is imperative to provide a deeper understanding of these correlations and their potential implications for both pathogenesis and treatment strategies. Clinical Implications: The research outcomes reported here may serve as a valuable guide for clinicians to assist OA and RA patientsin staying vigilant in addressing their sexual health concerns. Strengths and Limitations: We explored the association of OA and RA with ED. However, this is only a cross-sectional study. Conclusion: In this comprehensive nationally representative survey spanning 4 years, our findings revealed a notably elevated incidence of ED within both OA and RA patient populations in comparison to the general population. Ongoing research is imperative to provide a deeper understanding of these correlations.

20.
Exp Ther Med ; 27(4): 174, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476900

RESUMO

The present study aimed to compare the diagnostic performance of three imaging tests: X-ray, computed tomography (CT) and magnetic resonance imaging (MRI), for subtle Lisfranc injuries and three anatomical subtype injuries. The non-weight-bearing X-ray, CT and MRI imaging results of patients with subtle Lisfranc injuries from September 2013 to March 2022 were retrospectively reviewed. Subtle Lisfranc injuries and three anatomical subtypes (first, second and cuneiform rays) were diagnosed based on the surgical reports. The diagnostic performance of X-ray, CT and MRI was compared. The sensitivity (Sn), specificity (Sp), positive predictive value, negative predictive value, area under the receiver operating characteristic curve (AUC) and κ coefficient were reported. A total of 31 patients were included in the study. The correct diagnosis was made in 48.4% (15/31), 87.1% (27/31) and 96.8% (30/31) of patients by X-ray, CT and MRI, respectively. A total of 54 different anatomical injuries were found intraoperatively in all patients, with MRI and CT having high agreement (Sn, 72.2 and 87.0%; κ, 0.69 and 0.78, respectively) and X-ray having a low agreement (Sn, 29.6%; κ, 0.26) with the surgical findings. Regarding the first-ray injuries, CT had the highest Sn (76.9%), Sp (100%) and AUC (0.885) in diagnosing subtle Lisfranc injuries. MRI showed the best Sn (88.5 and 93.3%, respectively) and AUC (0.942 and 0.904, respectively) in both second and cuneiform rays. In conclusion, non-weight-bearing X-rays had poor diagnostic accuracy for subtle Lisfranc injuries and their subtypes. CT was superior to X-rays and MRI in diagnosing first-ray injuries. Although not significantly different from CT in terms of overall diagnosis, MRI was superior to X-ray and CT in diagnosing second and cuneiform-ray injuries.

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