RESUMO
Circular RNAs (circRNAs) are a member of non-coding RNAs with no ability in encoding proteins and their aberrant dysregulation is observed in cancers. Their closed-loop structure has increased their stability, and they are reliable biomarkers for cancer diagnosis. Urological cancers have been responsible for high mortality and morbidity worldwide, and developing new strategies in their treatment, especially based on gene therapy, is of importance since these malignant diseases do not respond to conventional therapies. In the current review, three important aims are followed. At the first step, the role of circRNAs in increasing or decreasing the progression of urological cancers is discussed, and the double-edged sword function of them is also highlighted. At the second step, the interaction of circRNAs with molecular targets responsible for urological cancer progression is discussed, and their impact on molecular processes such as apoptosis, autophagy, EMT, and MMPs is highlighted. Finally, the use of circRNAs as biomarkers in the diagnosis and prognosis of urological cancer patients is discussed to translate current findings in the clinic for better treatment of patients. Furthermore, since circRNAs can be transferred to tumor via exosomes and the interactions in tumor microenvironment provided by exosomes such as between macrophages and cancer cells is of importance in cancer progression, a separate section has been devoted to the role of exosomal circRNAs in urological tumors.
Assuntos
Biomarcadores Tumorais , Resistencia a Medicamentos Antineoplásicos , RNA Circular , Neoplasias Urológicas , Humanos , RNA Circular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/diagnóstico , Biomarcadores Tumorais/genética , Metástase Neoplásica , AnimaisRESUMO
Seed priming with nanomaterials is an emerging approach for improving plant stress tolerance. Here, we demonstrated a mechanism for enhancing salt tolerance in rice under salt stress via priming with nonstimulatory nanoparticles such as selenium nanoparticles (SeNPs), distinct from stimulatory nanomaterials. Due to the dynamic transformation ability of SeNPs, SeNP priming could enhance rice salt tolerance by mediating the glutathione cycle to eliminate excess reactive oxygen species (ROS). During priming, SeNPs penetrated rice seeds and transitioned into a soluble form (99.9%) within the embryo endosperm. Subsequently, the soluble selenium (Se) was transported to rice roots and metabolized into various Se-related derivatives, including selenomethionine (SeMet), Na2SeO3 (Se IV), selenocysteine (SeCys2), and methylselenocysteine (MeSeCys). These derivatives significantly enhanced the root activities of key enzymes such as glutathione peroxidase (GSH-PX), glutathione reductase (GR), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) by 24.97%, 47.98%, 16.23%, 16.81%, and 14.82%, respectively, thus reinforcing the glutathione cycle and ROS scavenging pathways. Moreover, these alterations induced transcriptional changes in rice seedlings, with genes involved in signal transduction, transcription factors (TFs), ROS scavenging, and protein folding being upregulated, activating signal perception and self-repair mechanisms. These findings offer valuable insights for the agricultural application of nanomaterials.
Assuntos
Nanopartículas , Oryza , Tolerância ao Sal , Sementes , Selênio , Oryza/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The peptidyl-prolyl cis/trans isomerase NIMA-interaction 1 (Pin1) catalyzes the transition of the proline ring from the cis to trans conformation, resulting in conformational and functional changes in proteins that are regulated by proline-guided serine/threonine phosphorylation. In recent years, Pin1 has emerged as a novel molecular target for the diagnosis and treatment of various malignant tumors. Notably, it has been found that Pin1 is highly expressed in pancreatic cancer. This article focuses on the mechanisms by which Pin1 orchestrates multiple oncogenic functions in the development of pancreatic cancer. By exploring the intricate interactions between Pin1 and the pancreatic tumor microenvironment, we provide an overview of Pin1's role in modifying glycolytic metabolism, redox balance, and the hypoxic microenvironment of pancreatic cancer. Furthermore, we summarize the potential anticancer effects of Pin1 inhibitors, aiming to elucidate Pin1's promise as a potential anticancer agent, particularly in the context of pancreatic cancer.
RESUMO
Buffaloes are vital contributors to the global dairy industry. Understanding the genetic basis of milk production traits in buffalo populations is essential for breeding programs and improving productivity. In this study, we conducted whole-genome resequencing on 387 buffalo genomes from 29 diverse Asian breeds, including 132 river buffaloes, 129 swamp buffaloes, and 126 crossbred buffaloes. We identified 36,548 copy number variants (CNV) spanning 133.29 Mb of the buffalo genome, resulting in 2,100 CNV regions (CNVR), with 1,993 shared CNVR being found within the studied buffalo types. Analyzing CNVR highlighted distinct genetic differentiation between river and swamp buffalo subspecies, verified by evolutionary tree and principal component analyses. Admixture analysis grouped buffaloes into river and swamp categories, with crossbred buffaloes displaying mixed ancestry. To identify candidate genes associated with milk production traits, we employed 3 approaches. First, we used Vst-based population differentiation, revealing 11 genes within CNVR that exhibited significant divergence between different buffalo breeds, including genes linked to milk production traits. Second, expression quantitative loci analysis revealed differentially expressed CNVR-derived genes (DECG) associated with milk production traits. Notably, known milk production-related genes were among these DECG, validating their relevance. Last, a GWAS identified 3 CNVR significantly linked to peak milk yield. Our study provides comprehensive genomic insights into buffalo populations and identifies candidate genes associated with milk production traits. These findings facilitate genetic breeding programs aimed at increasing milk yield and improving quality in this economically important livestock species.
Assuntos
Búfalos , Variações do Número de Cópias de DNA , Leite , Animais , Búfalos/genética , Leite/metabolismo , Feminino , Genoma , Cruzamento , Lactação/genéticaRESUMO
Covering: 2018 to 2022Meroterpenoids found in fungal species of the genus Ganoderma and known as Ganoderma meroterpenoids (GMs) are substances composed of a 1,2,4-trisubstituted benzene and a polyunsaturated side chain. These substances have attracted the attention of chemists and pharmacologists due to their diverse structures and significant bioactivity. In this review, we present the structures and possible biosynthesis of representative GMs newly found from 2018 to 2022, as well as chemical synthesis and biological activity of some interesting GMs. We propose for the first time a plausible biosynthetic pathway for GMs, which will certainly motivate further research on the biosynthetic pathway in Ganoderma species, as well as on chemical synthesis of GMs as important bioactive compounds for the purpose of drug development.
Assuntos
Ganoderma , Estrutura Molecular , Ganoderma/química , Terpenos/farmacologia , Terpenos/químicaRESUMO
The PI3K/AKT/mTOR signaling pathway is one of the most common abnormal activation pathways in tumor cells, and has associated with multiple functions such as tumor cell growth, proliferation, migration, invasion, and tumor angiogenesis. Here, a series of 3-amino-1H-indazole derivatives were synthesized, and their antiproliferative activities against HT-29, MCF-7, A-549, HepG2 and HGC-27 cells were evaluated. Among them, W24 exhibited the broad-spectrum antiproliferative activity against four cancer cells with IC50 values of 0.43-3.88 µM. Mechanism studies revealed that W24 inhibited proliferation by affecting the DNA synthesis, induced G2/M cell cycle arrest and apoptosis by regulating Cyclin B1, BAD and Bcl-xL, meanwhile induced the change of intracellular ROS and mitochondrial membrane potential in HGC-27 cells. Moreover, W24 inhibited the migration and invasion of HGC-27 cells by decreasing EMT pathway related proteins and reducing the mRNA expression levels of Snail, Slug and HIF-1α. Furthermore, W24 displayed low tissue toxicity profile and good pharmacokinetic properties in vivo. Therefore, 3-amino-1H-indazole derivatives might serve as a new scaffold for the development of PI3K/AKT/mTOR inhibitor and anti-gastric cancer reagent.
Assuntos
Indazóis , Neoplasias , Humanos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Indazóis/química , Indazóis/farmacologiaRESUMO
A supramolecular solvent-based dispersive liquid-liquid microextraction was proposed for the extraction and determination of lignans in Forsythiae Fructus combined with high-performance liquid chromatography. The supramolecular solvent, consisting of tetrabutylammonium bromide and n-hexanol, was mixed with the sample solution to extract the analytes by a vortex. After accomplishing the extraction, the extraction phase was separated by centrifugation and collected for high-performance liquid chromatography analysis. In this work, the important extraction variables such as the type and amount of extraction solvent, pH and salt amount in the sample phase, and extraction time were optimized. The synthesis of supramolecular solvent was studied and its microstructure was characterized by transmission electron microscopy. Under the optimal conditions, the analytes' enrichment factors were between 6 and 170 for the proposed procedure. Satisfactory linear ranges (r ≥ 0.99), detection limits (0.025-0.4 ng/ml), precisions (< 9.2%), and accuracies (recoveries: 96.5%-104.8%) were obtained. The method has been successfully applied to the preconcentration of lignans in Forsythiae Fructus with simple and rapid operation, low cost, and environmental friendliness.
Assuntos
Lignanas , Microextração em Fase Líquida , Solventes/química , Microextração em Fase Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cloreto de SódioRESUMO
A simple and rapid instantaneous nebulization dispersive liquid-phase microextraction method was developed, and combined with high-performance liquid chromatography for determination of the contents of seven analytes in traditional Chinese medicines. In this study, using the sprinkler device to achieve instantaneous synchronous dispersion and extraction, only one spray can rapidly achieve the concentration and enrichment of seven kinds of chalcone and isoflavones. The key factors affecting the extraction efficiency were optimized including the type and volume of extractant, the pH and salt concentration of the sample phase, and the number of dispersion. Under the optimal conditions, the enrichment factor of the target analytes ranged from 103.1 to 180.9, with good linearity and correlation coefficients above 0.9970. The limits of detection ranged from 0.02 to 0.15 ng/mL, with good accuracy (recoveries 91.1 to 108.9%) and precision (relative standard deviations 1.5-7.1%). This method has short extraction time (2 s), low organic solvent consumption and high enrichment effect, so it has a wide application prospects.
Assuntos
Chalcona , Chalconas , Isoflavonas , Microextração em Fase Líquida , Cromatografia Líquida de Alta Pressão , Medicina Tradicional Chinesa , Microextração em Fase Líquida/métodosRESUMO
OBJECTIVE: Anterior bone loss (ABL) was considered as a non-progressive process secondary only to motion-preserving implant and has been noticed recently in cervical disk replacement (CDR) let alone patients with anterior cervical diskectomy and fusion (ACDF). Our purpose is to reveal this unnoticed phenomenon in ACDF and further explore its clinical and radiological outcomes. METHODS: A total of 77 patients underwent ACDF with a minimum follow-up of at least one year were retrospectively reviewed. The average follow-up time was 22.51 ± 16.31 months. There were 50 patients in group A with ABL, while there were 27 patients in group B without ABL. ABL was measured and classified into four grades according to Kieser's methods. Clinical evaluation, radiological parameters and fusion rate were recorded. RESULTS: The incidence of bone ABL was 64.9% of Zero-P and 55.2% of endplates. The incidence of upper and lower endplates was 61% and 49%, respectively, and such difference was not significant. Mild ABL occurred in 22%, moderate ABL in 38% and severe ABL of 40% patients underwent ACDF with ABL. ABL would not affect both clinical outcomes and fusion rate. However, ABL would result in a higher incidence of subsidence. CONCLUSION: ABL should be considered as a common phenomenon that both CDR and ACDF owned a non-progressive process which confined in one year. ABL would result in a higher incidence of subsidence. Luckily, this phenomenon does not have an effect on postoperative clinical and fusion rate.
Assuntos
Vértebras Cervicais , Discotomia , Humanos , Seguimentos , Estudos Retrospectivos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Discotomia/métodos , Remodelação ÓsseaRESUMO
The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I (1-9), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the Rf values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A (1) featured an unusual 8,14-seco-pregnane skeleton. Compounds 1, 8, and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC50 values of 37.5, 38.8, and 42.8 µM (L-NMMA was used as a positive control, IC50 39.3 µM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.
Assuntos
Marsdenia , Plantas Medicinais , Humanos , Plantas Medicinais/química , Marsdenia/química , China , Pregnanos/química , Glicosídeos/químicaRESUMO
This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.
Assuntos
Farmacologia em Rede , Piroptose , Caspase 3/metabolismo , Gasderminas , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
Acylglycerophosphate acyltransferases (AGPATs) are the rate-limiting enzymes for the de novo pathway of triacylglycerols (TAG) synthesis. Although AGPATs have been extensively explored by evolution, expression and functional studies, little is known on functional characterization of how many members of the AGPAT family are involved in TAG synthesis and their impact on the cell proliferation and apoptosis. Here, 13 AGPAT genes in buffalo were identified, of which 12 AGPAT gene pairs were orthologous between buffalo and cattle. Comparative transcriptomic analysis and real-time quantitative reverse transcription PCR (qRT-PCR) further showed that both AGPAT1 and AGPAT6 were highly expressed in milk samples of buffalo and cattle during lactation. Knockdown of AGPAT1 or AGPAT6 significantly decreased the TAG content of buffalo mammary epithelial cells (BuMECs) and bovine mammary epithelial cells (BoMECs) by regulating lipogenic gene expression (p < 0.05). Knockdown of AGPAT1 or AGPAT6 inhibited proliferation and apoptosis of BuMECs through the expression of marker genes associated with the proliferation and apoptosis (p < 0.05). Our data confirmed that both AGPAT1 and AGPAT6 could regulate TAG synthesis and growth of mammary epithelial cells in buffalo. These findings will have important implications for understanding the role of the AGPAT gene in buffalo milk performance.
Assuntos
Aciltransferases , Búfalos , Animais , Bovinos , Feminino , Aciltransferases/genética , Aciltransferases/metabolismo , Búfalos/genética , Búfalos/metabolismo , Células Epiteliais/metabolismo , Lactação/genética , Glândulas Mamárias Animais/metabolismo , Leite/metabolismo , Triglicerídeos/metabolismoRESUMO
Objective: To investigate the dietary nutrient intake and the nutritional status of children with Duchenne muscular dystrophy (DMD), and to explore the correlation between them, so as to provide theoretical basis for the formulation of proper nutritional treatment for children with DMD. Methods: A total of 223 children aged 2 to 14 years who came to West China Second University Hospital, Sichuan University from July 2017 to April 2021, and who were diagnosed with DMD by genetic testing were enrolled as the subjects of the study. Dietary assessment was conducted with a 3-day 24-hour dietary recall, and serum vitamin D level was measured by chemiluminescence method. Results: Only 33.2% of the children with DMD were found to be of normal nutritional status. The incidences of stunted growth, underweight, overweight and obesity were 13.5%, 14.4%, 14.3% and 8.1%, respectively. Among the children with DMD, those with serum vitamin D deficiency and insufficiency accounted for 9.0% and 89.7%, respectively. According to the dietary recall of the children with MDM, the daily energy ratio of carbohydrate, protein and fat were (47.40±6.64)%, (14.46±2.22)%, and (38.17±5.30)%, respectively. The daily intake of dietary calcium and vitamin D were (433.32±164.39) mg per day and (155.73±89.30) IU per day, respectively. The ratio of daily protein intake to the estimated average requirement for protein ( P=0.003) and ratio of daily energy intake to the estimated energy requirement ( P=0.007) were lower in children with stunted growth than those of DMD children of normal nutritional status. Conclusion: The dietary structure of children with DMD is obviously not suited to their condition and nutritional deficiency coexists with overnutrition among them. Further research needs to be done for developing appropriate nutritional guidance programs and standardized nutritional management measures for children with DMD.
Assuntos
Distrofia Muscular de Duchenne , Estado Nutricional , Criança , Humanos , Estudos Transversais , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/epidemiologia , Ingestão de Energia , Ingestão de Alimentos , Transtornos do Crescimento , China/epidemiologia , Vitamina DRESUMO
A new series of N-(3,4,5-trimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amine derivatives as tubulin polymerization inhibitors were synthesized, and evaluated for the anti-proliferative activities. A structure-activity relationship study revealed that the free amino moiety of 1H-pyrazolo[3,4-b]pyridin-3-amine played an essential role in the anti-proliferative activities. Especially, compound 15c displayed the strongest anti-proliferation against MCF-7 cells with IC50 value of 0.067 ± 0.003 µM, and high selectivity over the normal human embryonic lung WI-38 cells with IC50 value of 23.41 ± 1.53 µM. Further mechanistic studies revealed that 15c showed strong anti-tubulin polymerization activity, changed the morphology of tubulin, and arrested the cell cycle at the G2/M transition in MCF-7 cells. Molecular docking analysis suggested that 15c well occupied the colchicine-binding pocket of tubulin. Additionally, 15c demonstrated anti-angiogenic activities with blocking the migration, invasion and tube formation, disrupting the newly formed tube, and regulating both MMP-9 and TIMP-1 in HUVEC cells. In summary, our results highlight that compound 15c is a potential antitumor compound that are worthy of further development.
Assuntos
Aminas/farmacologia , Antineoplásicos/farmacologia , Pirazóis/farmacologia , Piridinas/farmacologia , Moduladores de Tubulina/farmacologia , Tubulina (Proteína)/metabolismo , Aminas/síntese química , Aminas/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Polimerização/efeitos dos fármacos , Pirazóis/síntese química , Pirazóis/química , Piridinas/síntese química , Piridinas/química , Relação Estrutura-Atividade , Suínos , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/químicaRESUMO
Nine new pyrrole alkaloids, including two undescribed dimeric pyrrole 2carbaldehyde alkaloids, lepipyrrolins A-B (1-2), seven pyrrole-alkaloid derivatives, macapyrrolins D-J (3-9), along with three known ones (10-12) were isolated from the rhizomes of Lepidium meyenii. Their structures and absolute configurations were demonstrated by extensive spectroscopic data (1D, 2D NMR, HRESIMS), and calculated electronic circular dichroism (ECD) experiment. Compounds 1, 3-12 were tested for their nitric oxide inhibitory effects. Furthermore, compound 1 was evaluated for its cytotoxic activity against five human tumor cell lines (HL-60, SMMC-7221, A549, MCF-7, and SW480) in vitro, and displayed selective cytotoxicity against SMMC-7721 with IC50 value of 16.78 ± 0.49 µM.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Lepidium/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
Previously, we have demonstrated the antiadipogenic benefits of Ganoderma triterpenoids (GTs), which indicated GTs have potential therapeutic implications for obesity. In this study, the EtOAc extract of Ganoderma applanatum was further phytochemically investigated for searching new antiadipogenic agents, which led to the isolation of a total of 15 highly oxygenated lanostane triterpenoids, including 9 new compounds (1-9) and 6 known analogues (10-15). Structurally, ganodapplanoic acids A and B (1, 2) are two rearranged 6/6/5/6-fused lanostane-type triterpenoids with an unusual C-13/C-15 oxygen bridge moiety. In addition, the EtOAc extract (GAE) and isolates (1-4,6-15) were assayed for their antiadipogenic effects in 3T3-L1 adipocytes. The results revealed that compound 9 effectively repressed adipogenesis through down-regulating the expression of major proteins (PPARγ, CEBPß and FAS) involving differentiation and adipogenesis in 3T3-L1 adipocytes. Thus, the present study further demonstrated the antiadipogenic potential of GTs and provided a possible perspective for obesity treatment.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Ganoderma/química , Triterpenos/farmacologia , Células 3T3-L1 , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Lipídeos/análise , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Four pairs of novel meroterpenoid dimers, (±)-applandimeric acids A-D (1-4) with an unprecedented spiro[furo[3,2-b]benzofuran-3,2'-indene] core were isolated from the fruiting bodies of Ganoderma applanatum. Their planar structures were unambiguously determined via extensive spectroscopic analysis. Their relative and absolute configurations were confirmed through calculated internuclear distance, coupling constant, 13C NMR with DP4 + analysis and electronic circular dichroism (ECD). Furthermore, the molecular docking-based method was used to evaluate their interaction with formyl peptide receptor 2 (FPR2) associated with inflammation. Interestingly, (±)-applandimeric acid D (4) can bond with FPR2 by some key hydrogen bonds. Furthermore, an in vitro bioassay verified that 4 can inhibit the expression of FPR2 with IC50 value of 7.93 µM. In addition, compared to the positive control LiCl (20 mM), 4 showed comparable anti-lipogenesis activity at the concentration of 20 µM. Meanwhile, 4 can suppress the protein levels of peroxisome proliferators-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-ß (C/EBP-ß), adipocyte fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS) through activating AMP-activated protein kinase (AMPK) signaling pathway. Thus, our findings indicate that compound 4 could be a lead compound to treat obesity and obesity-related diseases by inhibiting lipid accumulation in adipocyte and alleviating inflammation.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ganoderma/química , Lipogênese/efeitos dos fármacos , Receptores de Formil Peptídeo/antagonistas & inibidores , Receptores de Lipoxinas/antagonistas & inibidores , Terpenos/farmacologia , Células 3T3-L1 , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Camundongos , Simulação de Dinâmica Molecular , Estrutura Molecular , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Receptores de Formil Peptídeo/genética , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/genética , Receptores de Lipoxinas/metabolismo , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
BACKGROUND: To investigate the relationship between intrapartum maternal fever and the duration and dosage of patient-controlled epidural analgesia (PCEA). METHODS: This observational study included 159 pregnant women who voluntarily accepted PCEA. During labor, patients with body temperature ≥ 38 °C were classified into the Fever group, (n = 42), and those with body temperature < 38 °C were classified into the No-fever group (n = 117). The outcome measures included the duration of PCEA, number of PCEA, and total PCEA amount. Body temperature and parturient variables, including interpartum fever status and the duration of any fever were monitored. RESULTS: The total PCEA duration and total PCEA amount in the Fever group were significantly higher than the corresponding values in the No-fever group (both, p < 0.05). The duration of fever was weakly correlated with the duration of PCEA (R2 = 0.08) and the total PCEA amount (R2 = 0.05) (both, p < 0.05). The total and effective PCEA were higher in the Fever group than in the No-fever group (both, p < 0.05). The total PCEA duration and total PCEA amount were positively correlated with the incidence of fever (both, p < 0.05). The diagnostic cutoff value for fever was 383 min, with a sensitivity of 78.6% and specificity of 57.3%. The mean temperature-time curves showed that parturients who developed fever had a steeper rise in temperature. CONCLUSIONS: This study showed that there were weak time- and dose-dependent correlations between PCEA and maternal fever during delivery. A total PCEA duration exceeding 6.3 h was associated with an increase in the duration of maternal intrapartum fever.
Assuntos
Analgesia Epidural/estatística & dados numéricos , Analgesia Obstétrica/estatística & dados numéricos , Analgesia Controlada pelo Paciente/estatística & dados numéricos , Febre/epidemiologia , Febre/fisiopatologia , Trabalho de Parto , Adulto , Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Analgesia Controlada pelo Paciente/métodos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Gravidez , Fatores de TempoRESUMO
Two new pyrrolizidine alkaloids, sclerwalins A and B (1 and 2), and one known 9-O-E-hydroxysenecioylretronecine (3) were first isolated from the seeds of Scleropyrum wallichianum. Their chemical structures were elucidated by extensive 1 D NMR and 2 D NMR (HSQC, HMBC, COSY, and ROESY), MS and IR spectra. Cytotoxicities of all isolates were evaluated against five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7 and SW480).[Formula: see text].
Assuntos
Alcaloides de Pirrolizidina , Linhagem Celular Tumoral , Células HL-60 , Humanos , Estrutura Molecular , SementesRESUMO
Nuclear magnetic resonance (NMR) spectroscopy was used for the qualitative and quantitative analysis of aqueous extracts of unroasted and roasted coffee silverskin (CS). Twenty compounds were identified from 1D and 2D NMR spectra, including caffeine, chlorogenic acid (CGA), trigonelline, fructose, glucose, sucrose, etc. For the first time, the presence of trigonelline was detected in CS. Results of the quantitative analysis showed that the total amount of the main components after roasting was reduced by 45.6% compared with values before roasting. Sugars in the water extracts were the main components in CS, and fructose was the most abundant sugar, its relative content accounting for 38.7% and 38.4% in unroasted and roasted CS, respectively. Moreover, 1D NMR combined with 2D NMR technology shows application prospects in the rapid, non-destructive detection of CS. In addition, it was observed by optical microscopy and scanning electron microscopy (SEM) that the morphology of CS changed obviously before and after roasting.