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The abiotic synthesis of peptides, widely regarded as one of the key chemical reactions on the prebiotic Earth, is thermodynamically constrained in solution. Herein, a simulation of the lightning phenomenon on the sea surface using bubble bursting and arc plasma under ambient conditions enables dipeptide formation of six amino acids with conversion ratios ranging from 2.6 % to 25.5 %. Additionally, we observed the formation of biologically active tripeptides and investigated the stereoselectivity of the dipeptide formation reaction. By utilizing a mixture of 20 amino acids in the reaction, 102 possible dipeptides were generated. These results establish experimental constructions to mimic achievable prebiotic conditions and provide a credible pathway for endogenous biopolymer synthesis on prebiotic Earth.
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Dipeptídeos , Peptídeos , Peptídeos/química , Dipeptídeos/química , Aminoácidos/química , Termodinâmica , Estereoisomerismo , Gases em Plasma/química , Prebióticos , Origem da VidaRESUMO
Ammopiptanthus nanus as a Kirgiz medicine is widely used for the treatment of frostbite and chronic rheumatoid arthritis. However, due to a lack of systematic research on the chemical components of A. nanus and their metabolites, the bioactive components in it remain unclear. Herein, a reliable strategy based on UHPLC-Q-TOF-MS/MS was established to comprehensively analyze the chemical components and their metabolites in vivo. In total, 59 compounds were identified from A. nanus stem extract, among which 14 isoflavones, 10 isoprenylated isoflavones, 4 polyhydroxy flavonoids, 9 alkaloids and 1 polyol were characterized for the first time. After oral administration of A. nanus stem extract, 30 prototype constituents and 28 metabolites (12 phase I and 16 phase II metabolites) were speculated on and identified in rat serum, urine and feces. Furthermore, the metabolic pathways of the chemical components were systematically analyzed and proposed. In conclusion, the chemical components from A. nanus stem and their metabolites in vivo were first studied, which may provide useful chemical information for further study on the effective material basis and pharmacological mechanism of A. nanus.
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Alcaloides , Medicamentos de Ervas Chinesas , Isoflavonas , Ratos , Animais , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Administração OralRESUMO
BACKGROUND: Aerobic exercise therapy can improve brain function and promote positive emotions in patients with depression. This study aims to improve the efficacy of aerobic exercise therapy in depression by investigating the influencing factors therein. METHODS: This study conducted a single-centre cross-sectional analysis of clinical data from 211 depression patients who received aerobic exercise therapy at Heze Mudan People's Hospital from May 2021 to May 2023. After excluding 10 patients who did not meet the inclusion criteria, the final cohort included 201 patients. The clinical data of patients with effective treatment and patients with ineffective treatment were collected, such as socio-demographic characteristics, disease status, depression degree, treatment compliance, and social support. Binary Logistic regression was used to analyze the factors affecting the clinical efficacy of aerobic exercise therapy in patients. RESULTS: Among the 201 patients, the effective and ineffective rates of aerobic exercise therapy were 80.10% (161/201) and 19.90% (40/201), respectively. When analysed as groups, no significant differences were observed between the effective group (EG) and ineffective group (IG) regarding gender, body mass index, course of depression, age of first onset, mental symptoms, years of education, personal income, or marital status (p > 0.05). However, the EG exhibited a reduced probability of family history of mental illness, smoking history, and severity of depression (p < 0.05), along with higher treatment compliance and Social Support Rating Scale (SSRS) scores compared to the IG (p < 0.05). Binary logistic regression analysis revealed that smoking history, family history of mental illness, treatment compliance, depression, and SSRS score were the primary influencing factors on the efficacy of aerobic exercise therapy (p < 0.05). CONCLUSION: Smoking history, family history of mental illness, treatment compliance, severity of depression, and social support are the primary influencing factors on the efficacy of aerobic exercise therapy in patients with depression. These factors should be emphasized during follow-up treatment to optimize the clinical treatment effect.
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Depressão , Exercício Físico , Humanos , Estudos Transversais , Depressão/terapia , Cooperação do Paciente/psicologia , Resultado do TratamentoRESUMO
De novo sequencing of oligonucleotides remains challenging, especially for oligonucleotides with post-transcriptional or synthetic modifications. Mass spectrometry (MS) sequencing can reliably detect and locate all of the modification sites in oligonucleotides via m/z variance. However, current MS-based sequencing methods exhibit complex spectra and low ion abundance and usually require coupled instrumentation. Herein, we demonstrate a method of oligonucleotide sequencing using TiO2/ZnAl-layered double oxide (LDO)-assisted laser desorption/ionization (LDI)-MS based on radical-induced dissociation (RID). ·CH2OH radicals can be produced on the surface of a TiO2/ZnAl-LDO matrix via ultraviolet light, inducing an attack on the active site of the oligonucleotide phosphate skeleton to create typical "a-, a-B-, c·-, d-, w-, and y"-type fragments. Compared with the spectra obtained via collision-based methods, such as collision-induced dissociation and higher-energy collisional dissociation, the LDI-MS spectra based on RID exhibit single-charged signals, fewer types of fragments, and a lower proportion of unknown noise peaks. We demonstrate full sequence coverage for a 6-mer 2'-O-methyl-modified oligonucleotide and a 21-mer small interfering RNA and show that RID can sequence oligonucleotides with modifications. Importantly, the mechanism responsible for the RID of the oligonucleotide phosphate skeleton was investigated through offline experiments, demonstrating consistent results with density functional theory calculations.
Assuntos
Oligonucleotídeos , Óxidos , Oligonucleotídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , FosfatosRESUMO
PURPOSE: To develop two deep learning-based systems for diagnosing and localizing pneumothorax on portable supine chest X-rays (SCXRs). METHODS: For this retrospective study, images meeting the following inclusion criteria were included: (1) patient age ≥ 20 years; (2) portable SCXR; (3) imaging obtained in the emergency department or intensive care unit. Included images were temporally split into training (1571 images, between January 2015 and December 2019) and testing (1071 images, between January 2020 to December 2020) datasets. All images were annotated using pixel-level labels. Object detection and image segmentation were adopted to develop separate systems. For the detection-based system, EfficientNet-B2, DneseNet-121, and Inception-v3 were the architecture for the classification model; Deformable DETR, TOOD, and VFNet were the architecture for the localization model. Both classification and localization models of the segmentation-based system shared the UNet architecture. RESULTS: In diagnosing pneumothorax, performance was excellent for both detection-based (Area under receiver operating characteristics curve [AUC]: 0.940, 95% confidence interval [CI]: 0.907-0.967) and segmentation-based (AUC: 0.979, 95% CI: 0.963-0.991) systems. For images with both predicted and ground-truth pneumothorax, lesion localization was highly accurate (detection-based Dice coefficient: 0.758, 95% CI: 0.707-0.806; segmentation-based Dice coefficient: 0.681, 95% CI: 0.642-0.721). The performance of the two deep learning-based systems declined as pneumothorax size diminished. Nonetheless, both systems were similar or better than human readers in diagnosis or localization performance across all sizes of pneumothorax. CONCLUSIONS: Both deep learning-based systems excelled when tested in a temporally different dataset with differing patient or image characteristics, showing favourable potential for external generalizability.
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Aprendizado Profundo , Medicina de Emergência , Pneumotórax , Humanos , Adulto Jovem , Adulto , Estudos Retrospectivos , Pneumotórax/diagnóstico por imagem , Raios XRESUMO
Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1 day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.
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Bibenzilas/farmacologia , Neoplasias Pulmonares , Fenol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Dendrobium , Humanos , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TORRESUMO
Different responsive abilities of different types of eels (cultured, cultured feminized, and wild silver eels) during artificial maturation are recognized, and maturity status at the beginning of artificial maturation might be important. Maturity may represented by the distribution pattern of oocyte diameters. Androgens have been demonstrated to stimulate ovarian development in eels. To determine the initial status, operations were performed on eels to identify sex and to sample ovarian tissue. The recovered eels were then treated with 17α-methyltestosterone (17MT), and the responses of individual eels to 17MT were determined by the fold change in the mean oocyte diameter before and after treatment. Sampled ovarian tissues were fixed in Bouin's solution, oocytes were isolated, and the diameter of isolated oocytes was measured. The ovarian status, determined by kernel density estimation (KDE), was presented by the probability density of measured oocyte diameters; compared with histograms, a description method, KDE, provided more subtle information on the investigated ovary. Our data indicated a correlation between the initial ovarian status (density pattern) and the consequence of treatment (change of ovary); we also argued the semelparity of the Japanese eel. Our results supported the hypothesis that the initial ovarian status is an important factor affecting artificial maturation and that androgens could ameliorate the initial status of the eel ovary.
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Androgênios/farmacologia , Metiltestosterona/farmacologia , Ovário/efeitos dos fármacos , Anguilla , Animais , Preparações de Ação Retardada/farmacologia , Feminino , Oócitos/citologia , Oócitos/efeitos dos fármacos , Ovário/crescimento & desenvolvimentoAssuntos
Ansiedade , Depressão , Qualidade de Vida , Sobreviventes , Humanos , Ansiedade/psicologia , Depressão/psicologia , Terapia por Exercício/métodos , Qualidade de Vida/psicologia , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral/métodos , Reabilitação do Acidente Vascular Cerebral/psicologia , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricosRESUMO
Silvering is a prepubertal metamorphosis preparing the eel to the oceanic reproductive migration. A moderate gonad development occurs during this metamorphosis from the sedentary yellow stage to the migratory silver stage. The aim of this study was to elucidate the molecular aspects of various endocrine parameters of BPG axis at different ovarian developmental stages in wild yellow and silver female Japanese eels. The GSI of the sampled female eels ranged between 0.18 and 2.3%, corresponding to yellow, pre-silver and silver stages. Gonad histology showed changes from previtellogenic oocytes in yellow eels to early vitellogenic oocytes in silver eels. Both serum E2 and T concentrations significantly increased with ovarian development indicating a significant activation of steroidogenesis during silvering. In agreement with previous studies, significant increases in pituitary gonadotropin beta subunits FSH-ß and LH-ß transcripts were also measured by qPCR, supporting that the activation of pituitary gonadotropin expression is likely responsible for the significant ovarian development observed during silvering. We investigated for the first time the possible brain neuroendocrine mechanisms involved in the activation of the pituitary gonadotropic function during silvering. By analyzing the expression of genes representative of the stimulatory GnRH control and the inhibitory dopaminergic control. The transcript levels of mGnRH and the three GnRH receptors did not change in the brain and pituitary between yellow and silver stages, suggesting that gene expression of the GnRH system is not significantly activated during silvering. The brain transcript levels of tyrosine hydroxylase, limiting enzyme of DA synthesis did not change during silvering, indicating that the DA synthesis activity was maintained. In contrast, a significant decrease in DA-D2B receptor expression in the forebrain and pituitary was observed, with no changes in DA-D2A receptor. The decrease in the pituitary expression of DA-D2BR during silvering would allow a reduced inhibitory effect of DA. We may raise the hypothesis that this regulation of D2BR gene expression is one of the neuroendocrine mechanisms involved in the slight activation of the pituitary gonadotropin and gonadal activity that occur at silvering.
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Dopamina/metabolismo , Enguias/crescimento & desenvolvimento , Hormônio Liberador de Gonadotropina/metabolismo , Metamorfose Biológica/fisiologia , Sistemas Neurossecretores/fisiologia , Receptores de Dopamina D2/metabolismo , Pigmentação da Pele/fisiologia , Animais , Células Cultivadas , Enguias/metabolismo , Feminino , Subunidade beta do Hormônio Folículoestimulante/metabolismo , Regulação da Expressão Gênica , Immunoblotting , Técnicas Imunoenzimáticas , Hormônio Luteinizante Subunidade beta/metabolismo , Oócitos/citologia , Oócitos/metabolismo , Ovário/citologia , Ovário/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reprodução/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Maturidade SexualRESUMO
To investigate the chemical constituents of the whole plants of Bidens bipinnata, the separation and purification of constituents were performed by chromatography on macroporous resin, silica gel, MCI and Sephadex LH-20. Their structures were elucidated by spectroscopic data as quercetin (1), quercetin-3-0-alpha-L-rhamnoside (2), keampferol-3-O-beta-D-glucopyranoside (3), keampferol-3-O-alpha-L-rhamnoside (4), 3', 5-dyhydroxy-3, 6, 4'-trimethoxyl -7-O-beta-D-glucopyranoside flavonoid (5), 7, 8, 3', 4'-tetraflavanone(6), (2S)- and (2R)-isookanin-7-O-beta-D- glucopyranoside (7a/7b), (2S)- and (2R)-3'-methoxy-isookanin-8-O-beta-D-glucopyranoside (8a/8b), 6, 7, 3', 4'-tetrahydroxyaurone(9), maritimetin (10), esculetin (11), 3-O-caffeoyl-2-methyl-d-erythrono-1, 4-lactone (12), (7S, 8R) balanophonin-4-O-beta-D-glucopyranoside (13), eugenyl-O-beta-apiofuranosyl-( 1"-6') -O-beta-glucopyranoside (14), and (+)-syringaresinol-4'-O-beta-D-glucopyranoside (15). Compounds 8, 13, 14, and 15 were isolated from this genus for the first time. Compounds 1 and 6 were potent inhibitors against HSC-T6 cells in vitro and compounds 1, 2, 6, and 7 were capable of decreasing the inflammatory cytokine production of macrophage cells in vitro.
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Bidens/química , Medicamentos de Ervas Chinesas/química , Estrutura Molecular , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
C-H bond ortho-substitution reaction has always been a significant and challenging topic in organic chemistry. We proposed a synthesis method based on microwave plasma torches. High-resolution mass spectrometry was used to monitor rapid reaction products. 2-Alkylbenzimidazole can be formed through the reaction of phenylnitrenium ion and nitriles on a millisecond scale. This reaction can achieve the one-step formation of benzimidazoles from benzene ring single-substituted compounds without the addition of external oxidants or catalysts. A similar C-H bond activation reaction can be accomplished with ketones. Meanwhile, the microwave plasma reactor was modified, and the resulting 2-methylbenzimidazole was successfully collected, indicating the device has good application potential in organic reactions such as C-H bond activation reaction.
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BACKGROUND AND OBJECTIVE: Proteome microarrays are one of the popular high-throughput screening methods for large-scale investigation of protein interactions in cells. These interactions can be measured on protein chips when coupled with fluorescence-labeled probes, helping indicate potential biomarkers or discover drugs. Several computational tools were developed to help analyze the protein chip results. However, existing tools fail to provide a user-friendly interface for biologists and present only one or two data analysis methods suitable for limited experimental designs, restricting the use cases. METHODS: In order to facilitate the biomarker examination using protein chips, we implemented a user-friendly and comprehensive web tool called BAPCP (Biomarker Analysis tool for Protein Chip Platforms) in this research to deal with diverse chip data distributions. RESULTS: BAPCP is well integrated with standard chip result files and includes 7 data normalization methods and 7 custom-designed quality control/differential analysis filters for biomarker extraction among experiment groups. Moreover, it can handle cost-efficient chip designs that repeat several blocks/samples within one single slide. Using experiments of the human coronavirus (HCoV) protein microarray and the E. coli proteome chip that helps study the immune response of Kawasaki disease as examples, we demonstrated that BAPCP can accelerate the time-consuming week-long manual biomarker identification process to merely 3 min. CONCLUSIONS: The developed BAPCP tool provides substantial analysis support for protein interaction studies and conforms to the necessity of expanding computer usage and exchanging information in bioscience and medicine. The web service of BAPCP is available at https://cosbi.ee.ncku.edu.tw/BAPCP/.
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Biomarcadores , Análise Serial de Proteínas , Software , Biomarcadores/metabolismo , Humanos , Internet , Proteoma , Interface Usuário-Computador , Escherichia coli , Proteômica/métodos , Biologia ComputacionalRESUMO
Irritable bowel syndrome (IBS) is a common refractory disease. Chinese medicine (CM) has remarkable efficacy and advantages on the treatment of IBS. This review summarized the articles focusing on the treatment of IBS with CM to sum up the latest treatment methods for IBS and the underlying mechanisms. Literature analysis showed that prescriptions, acupuncture, and moxibustion are the primary methods of CM treatment for IBS. The potential mechanism centers on the regulation of the enteric nervous system, the alleviation of visceral hypersensitivity, the stability of intestinal flora, and the regulation of the immune system.
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Terapia por Acupuntura , Síndrome do Intestino Irritável , Moxibustão , Humanos , Síndrome do Intestino Irritável/terapia , Medicina Tradicional Chinesa , Terapia por Acupuntura/métodosRESUMO
Objective: Previous studies indicated that maternal thyroid dysfunction increase the offspring's risk for attention deficit/hyperactivity disorder (ADHD). However, the relationship between thyroid function and symptoms in children with ADHD remains unclear. Methods: A total of 49 children with ADHD were enrolled. The Conners 3 scale was used to estimate the symptoms associated with ADHD. Correlation between thyroid hormones and the scores of the Conners 3 scale was evaluated by Pearson correlation analysis. Then, ADHD children were divided into two groups according to the hyperactivity index (HI) of the Conners 3 scale: ADHD children with hyperactivity behaviors (HB) (HI > 1.5) and ADHD children without HB (HI < 1.5). The demographic characteristics, thyroid hormones, and routine laboratory parameters between the two groups were collected. To distinguish HI-related factors, a univariate analysis and a binary logistic regression predictive model were used. The discriminative ability of thyroid stimulating hormone (TSH) in predicting ADHD children with HB from ADHD children without HB was investigated using the receiver operating characteristic (ROC) curve method. Results: The levels of TSH were positively correlated to the scores of the Conners 3 scale (r = 0.338, P = 0.033) and HI (r = 0.371, P = 0.019). Moreover, the levels of TSH, serum ferritin, and lactic acid were significantly increased in ADHD children with HB compared to ADHD children without HB (all P < 0.05). Furthermore, the results of binary logistic regression found that TSH (OR 2.243 (CL 1.052-4.783)) and lactic acid (OR 1.018 (CI 1.003-1.032)) were independently associated with HI. Additionally, ROC analysis indicated the potential diagnostic value of TSH in discriminating ADHD children with HB from ADHD children without HB with an AUC of 0.684. Conclusion: These results suggested that the serum TSH levels may be related to the HB in children with ADHD.
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Chronic Obstructive Pulmonary Disease (COPD) is a chronic respiratory disease characterized by a slow progression and caused by the inhalation of harmful particulate matter. Cigarette smoke and air pollutants are the primary contributing factors. Currently, the pathogenesis of COPD remains incompletely understood. The PI3K/Akt signaling pathway has recently emerged as a critical regulator of inflammation and oxidative stress response in COPD, playing a pivotal role in the disease's progression and treatment. This paper reviews the association between the PI3K/Akt pathway and COPD, examines effective PI3K/Akt inhibitors and novel anti-COPD agents, aiming to identify new therapeutic targets for clinical intervention in this disease.
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OBJECTIVES: The present study was designed to obverse the protection of patchouli alcohol (PA) ameliorates hypertensive nephropathy in spontaneously hypertensive rats (SHR) and reveals potential mechanism. METHODS: Briefly, the adult spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats (half male and half female) were intragastric gavaged or not with PA (80, 40 and 20 mg/kg) for 8 weeks. Body weight, blood pressure (BP), renal weight, renal function and renal morphology were measured. Further, western blotting and immunohistochemical analysis were used to study the underlying mechanism. KEY FINDINGS: Compared with the WKY group, plasmatic levels of renin, angiotensin II (Ang-II), transforming growth factor beta 1(TGF-ß1), plasminogen activator inhibitor-1(PAI-1), creatinine (Cr), blood urea nitrogen (BUN), renal index, mRNA levels of ERK1/2 and α-SMA were significantly increased in SHR. Histology results showed that renal tubular injury and tubulointerstitial fibrosis occurred in SHR. After administration, SBP of captopril group decreased at each week after administration, especially at 3, 5, 6 7 and 8 weeks (P < 0.05 or P < 0.01). There is no significant effect was assessed in the olive oil group. Decreased plasma Cr, Renin, Ang-II, TGF-ß1, PAI-1, SCFAs and Renin, TGF-ß1, PAI-1 in renal tissues were observed significantly in captopril (P <0.05 or P < 0.01). Plasma BUN, Ang-II, TGF-ß1 and PAI-1 in renal tissues decreased in the olive oil group significantly (P <0.05 or P < 0.01). PA (80, 40 and 20 mg/kg) lowered BP and plasmatic levels of Renin, Ang-II, TGF-ß1 and PAI-1. Treatment with PA (40, 20 mg/kg) decreased levels of Cr, BUN and suppressed of activation of pro-fibrosis cytokines including TGF-ß1 in kidney. There is no ameliorative change in the olive oil group and the captopril group (P > 0.05) while PA treatment alleviated renal tubular injury and produced dramatic collagen fibre area reductions in mesangial membrane, basement membrane, and renal interstitium obviously (P < 0.05 or P < 0.01). Treatment of SHR with PA-inhibited MFB activation and downregulated mRNA of α-SMA. Treatment with PA suppressed excessive production of the extracellular matrix (ECM) via decreasing Col I, III and FN, downregulating mRNA of tissue inhibitor of TIMP-1 along with upregulating mRNA of MMP-9. The expression of Col III and MMP-9 mRNA-reduced in the captopril group (P < 0.05). In addition, the expression of ERK1/2 and pERK1/2 also reduced in the captopril group significantly (P < 0.05 or P < 0.01). Treatment with PA (20 mg/kg) downregulated proteins expression of Raf-1, ERK1/2 and pERK1/2 and mRNA expression of Ras, Raf-1 and ERK1/2. CONCLUSIONS: Overall, PA restored normal BP, alleviated renal dysfunction and renal fibrosis, possibly by suppressing Ang II and TGF-ß1-mediated Ras/Raf-1/ERK1/2 signalling pathway.
Assuntos
Hipertensão Renal , Hipertensão , Ratos , Animais , Masculino , Feminino , Ratos Endogâmicos SHR , Fator de Crescimento Transformador beta1/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Captopril , Ratos Endogâmicos WKY , Renina/metabolismo , Sistema de Sinalização das MAP Quinases , Azeite de Oliva , RNA Mensageiro/metabolismo , FibroseRESUMO
This study aimed at investigating the role of sexual steroids in the regulation of the expression of the single aromatase gene and steroid receptor subtypes in the brain-pituitary-ovarian axis of the Japanese eel. Unlike other teleosts, which possess duplicated genes for aromatase, cyp19a1a and cyp19a1b, expressed in the gonads and in the brain, respectively, eel species possess a single cyp19a1. Phylogenetic analysis indicated that eel brain/gonadal cyp19a1 branches at the basis of both teleost gonadal cyp19a1a and brain cyp19a1b clades. Female eels treated with catfish pituitary homogenate (CPH) to induce sexual maturation showed an increase in the expression of cyp19a1 and aromatase enzymatic activity in the brain and in the ovaries. Treatments with sex steroids (estradiol-17ß, E(2) or testosterone, T) revealed that the increase in cyp19a1 expression in the brain may result from E(2)-specific induction. In contrast, the increase in cyp19a1 expression in the ovaries of CPH-treated eels is a result of steroid-independent control, probably from a direct effect of gonadotropins contained in the pituitary extract. Analysis of the expression of estrogen and androgen receptor subtypes, esr-α, esr-ß, ar-α and ar-ß, in eels treated with CPH or sex steroids revealed differential regulations. In CPH-treated eels, the expression of esr-α and ar-α was significantly increased in the brain, while the expression of ar-α and ar-ß was increased in the ovaries. No change was observed in esr-ß in any organ. Steroid treatments induced an upregulation by E(2) of esr-α, but not esr-ß expression, in the brain, pituitary and ovaries, while no autoregulation by T of its own receptors could be observed. These results reveal both steroid-dependent and -independent mechanisms in the regulation of cyp19a1 and steroid receptor subtype expression in the eel.
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Aromatase/metabolismo , Encéfalo/metabolismo , Enguias/metabolismo , Ovário/metabolismo , Hipófise/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Animais , Estrogênios/farmacologia , Feminino , Receptores Androgênicos/efeitos dos fármacos , Receptores de Estrogênio/efeitos dos fármacos , Transdução de Sinais/fisiologia , Testosterona/farmacologia , Regulação para CimaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear. AIM OF THE STUDY: This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment. MATERIALS AND METHODS: The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting. RESULTS: The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01). CONCLUSION: The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.
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Citrus/química , Óleos de Plantas/farmacologia , Pogostemon/química , Úlcera Gástrica/tratamento farmacológico , Animais , Dinoprostona/sangue , Dinoprostona/genética , Dinoprostona/metabolismo , Gastrinas/sangue , Gastrinas/genética , Gastrinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Pepsinogênio C/sangue , Pepsinogênio C/genética , Pepsinogênio C/metabolismo , Óleos de Plantas/química , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Restrição Física/efeitos adversos , Serotonina/sangue , Serotonina/genética , Serotonina/metabolismo , Úlcera Gástrica/etiologiaRESUMO
A Lewis-acid-catalyzed selective reaction between anilines and glyoxylates was developed for synthesis of diarylmethanes or oxoimidazolidines. Under the catalysis of AgOTf, a series of anilines-based diarylmethanes, including primary, secondary, and tertiary anilines, were obtained in moderate to good yields. Moreover, stereoselective oxoimidazolidines were performed with the catalysis of Cu(OAc)2·H2O.
Assuntos
Glioxilatos , Ácidos de Lewis , Compostos de Anilina , Catálise , Estrutura MolecularRESUMO
Kawasaki disease (KD) is a form of acute systemic vasculitis that primarily affects children and has become the most common cause of acquired heart disease. While the etiopathogenesis of KD remains unknown, the diagnostic criteria of KD have been well established. Nevertheless, the diagnosis of KD is currently based on subjective clinical symptoms, and no molecular biomarker is yet available. We have previously performed and combined methylation array (Illumina HumanMethylation450 BeadChip) and transcriptome array (Affymetrix GeneChip Human Transcriptome Array 2.0) to identify genes that are differentially methylated/expressed in KD patients compared with control subjects. We have found that decreased methylation levels combined with elevated gene expression can indicate genes (e.g., toll-like receptors and CD177) involved in the disease mechanisms of KD. In this study, we constructed a database called KDmarkers to allow researchers to access these valuable potential KD biomarkers identified via methylation array and transcriptome array. KDmarkers provides three search modes. First, users can search genes differentially methylated and/or differentially expressed in KD patients compared with control subjects. Second, users can check the KD patient groups in which a given gene is differentially methylated and/or differentially expressed. Third, users can explore the DNA methylation levels and gene expression levels in all samples (KD patients and controls) for a particular gene of interest. We further demonstrated that the results in KDmarkers are strongly associated with KD immune responses. All analysis results can be downloaded for downstream experimental designs. KDmarkers is available online at https://cosbi.ee.ncku.edu.tw/KDmarkers/.