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1.
BMC Plant Biol ; 24(1): 173, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38443808

RESUMO

Polygonatum cyrtonema Hua is a traditional Chinese medicinal plant acclaimed for its therapeutic potential in diabetes and various chronic diseases. Its rhizomes are the main functional parts rich in secondary metabolites, such as flavonoids and saponins. But their quality varies by region, posing challenges for industrial and medicinal application of P. cyrtonema. In this study, 482 metabolites were identified in P. cyrtonema rhizome from Qingyuan and Xiushui counties. Cluster analysis showed that samples between these two regions had distinct secondary metabolite profiles. Machine learning methods, specifically support vector machine-recursive feature elimination and random forest, were utilized to further identify metabolite markers including flavonoids, phenolic acids, and lignans. Comparative transcriptomics and weighted gene co-expression analysis were performed to uncover potential candidate genes including CHI, UGT1, and PcOMT10/11/12/13 associated with these compounds. Functional assays using tobacco transient expression system revealed that PcOMT10/11/12/13 indeed impacted metabolic fluxes of the phenylpropanoid pathway and phenylpropanoid-related metabolites such as chrysoeriol-6,8-di-C-glucoside, syringaresinol-4'-O-glucopyranosid, and 1-O-Sinapoyl-D-glucose. These findings identified metabolite markers between these two regions and provided valuable genetic insights for engineering the biosynthesis of these compounds.


Assuntos
Polygonatum , Polygonatum/genética , Análise por Conglomerados , Flavonoides , Perfilação da Expressão Gênica , Aprendizado de Máquina
2.
Acta Pharmacol Sin ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902502

RESUMO

The vasopressin V2 receptor (V2R) is a validated therapeutic target for autosomal dominant polycystic kidney disease (ADPKD), with tolvaptan being the first FDA-approved antagonist. Herein, we used Gaussian accelerated molecular dynamics simulations to investigate the spontaneous binding of tolvaptan to both active and inactive V2R conformations at the atomic-level. Overall, the binding process consists of two stages. Tolvaptan binds initially to extracellular loops 2 and 3 (ECL2/3) before overcoming an energy barrier to enter the pocket. Our simulations result highlighted key residues (e.g., R181, Y205, F287, F178) involved in this process, which were experimentally confirmed by site-directed mutagenesis. This work provides structural insights into tolvaptan-V2R interactions, potentially aiding the design of novel antagonists for V2R and other G protein-coupled receptors.

3.
BMC Musculoskelet Disord ; 25(1): 61, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38216881

RESUMO

BACKGROUND: Traditional Scarf osteotomy (TSO) is an effective procedure with a good record in moderate to severe hallux valgus (MSHV) surgery. In order to overcome shortcomings of TSO, Modified Rotary Scarf osteotomy (MRSO) was introduced in this study, which aimed to compare the clinical and radiological outcome in the patients treated with MRSO or TSO. METHODS: Of 175 patients (247 feet) with MSHV, 100 patients (138 feet) treated with MRSO and 75 patients (109 feet) treated with TSO were evaluated according to relevant indicators in twenty-four months follow-up. Pre-surgical and post-surgical HVA, IMA, DMAA, MTP-1 ROM, sesamoid grade and AOFAS (American Orthopaedic Foot and Ankle Society) scores and postsurgical complications were evaluated. RESULTS: Both groups manifested similar baseline characters. The mean follow-up was of 25.9 (range, 22-37) months. Significantly lower IMA, lower Sesamoid grade and higher DMAA at six months, twelve months and twenty-four months post-surgically had been showed in MRSO group compared to TSO group. There was no significant difference in HVA, MTP-1 ROM and AOFAS data at each follow-up time point post-surgically between the two groups. No major complications occurred in either group. CONCLUSION: MRSO showed comparable results to TSO, and improved IMA and sesamoid grade to a greater extent, with a lower probability of throughing effect. Although DMAA could be increased by MRSO, MRSO could still be a reproducible, non-dangerous and efficacious alternative procedure for treating HV patients which do not have severe DMAA.


Assuntos
Joanete , Hallux Valgus , Ossos do Metatarso , Humanos , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Osteotomia/efeitos adversos , Osteotomia/métodos , Ossos do Metatarso/cirurgia
4.
Pharmacol Res ; 187: 106587, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36460279

RESUMO

Cucurbitacin B (CuB, C32H46O8), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely distributed in a variety of plants and mainly isolated from plants in the Cucurbitaceae family. CuB is mostly obtained from the pedicel of Cucumis melo L. Modern pharmacological studies have confirmed that CuB has a broad range of pharmacological activities, with significant therapeutic effects on a variety of diseases including inflammatory diseases, neurodegenerative diseases, diabetes mellitus, and cancers. In this study the PubMed, Web of Science, Science Direct, and China National Knowledge Infrastructure (CNKI) databases were searched from 1986 to 2022. After inclusion and exclusion criteria were applied, 98 out of 2484 articles were selected for a systematic review to comprehensively summarize the pharmacological activity, toxicity, and pharmacokinetic properties of CuB. The results showed that CuB exhibits potent anti-inflammatory, antioxidant, antiviral, hypoglycemic, hepatoprotective, neuroprotective, and anti-cancer activities mainly via regulating various signaling pathways, such as the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), nuclear factor (NF)-κB, AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt, focal adhesion kinase (FAK), Notch, and Hippo-Yes-associated protein (YAP) pathways. Studies of its toxicity and pharmacokinetic properties showed that CuB has non-specific toxicity and low bioavailability. In addition, derivatives and clinical applications of CuB are discussed in this paper.


Assuntos
Cucurbitacinas , Triterpenos , Cucurbitacinas/farmacologia , Cucurbitacinas/uso terapêutico , Proteína Fosfatase 2/metabolismo , Antioxidantes , Fosfatidilinositol 3-Quinases , Triterpenos/farmacologia , NF-kappa B
5.
Yi Chuan ; 45(8): 700-714, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37609820

RESUMO

The WUSCHEL-Related Homeobox (WOX) family is a group of transcription factors unique to plants that play an important role in regulating key developmental processes such as stem cell maintenance and organ morphogenesis. As a rare and valuable Chinese herb, Dendrobium catenatum has a unique epiphytic lifestyle and growth and developmental characteristics, and a functional investigation of its WOX family genes can help to further understand the conserved and specific development of D. catenatum. In this study, we analyzed the phylogeny, spatio-temporal expression pattern and heterologous expression function of D. catenatum WOX family genes (DcWOX). The results showed that members of the D. catenatum WOX gene family could be divided into three evolutionary branches with significantly different tissue expression profiles. In transgenic Arabidopsis, overexpression of DcWOX4 resulted in significant dwarfism, pinnately leaf margins, and delayed flowering for 2 weeks; overexpression of DcWOX9 resulted in plant dwarfing, serrated leaf margin, delayed flowering for 1 week, and even male and female sterility in strong phenotype plants; overexpression of DcWOX11 caused curl downward leaf. The abnormal morphogenesis of DcWOX4/9/11 overexpression Arabidopsis leaves are related to the down-regulation of TCP family genes, CUC family genes and the up-regulation of KNOX family genes; Postponement of flowering is related to down-regulation of early flowering genes such as FT, SOC1 and CO. Therefore, this study showed that D. catenatum WOX family genes have important functions in regulating plant morphogenesis, leaf development, flowering time and fertility, further expanding the understanding of the WOX gene family function, and providing clues for the conservation and specificity during orchid development and evolution.


Assuntos
Arabidopsis , Dendrobium , Dendrobium/genética , Fertilidade , Reprodução , Crescimento e Desenvolvimento
6.
J Integr Neurosci ; 21(1): 26, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35164462

RESUMO

Ischemic stroke is an acute cerebrovascular disease and the third most common cause of death after ischemic heart disease. Increasing attention is being paid to finding effective treatments through traditional medicine. Thus, studying the traditional medicine for the treatment of ischemic stroke is of great importance. Traditional medicine in China includes traditional Chinese medicine (TCM) and other ethnic medicines, which is rich in variety and resources. This review first introduces the treatment mechanisms associated with ischemic stroke, such as antioxidant nitrification, antiexcitotoxic, antiapoptotic, anti-inflammatory, antiplatelet and anticoagulation mechanisms. Then, we calculated the frequency of prescription use for ischemic stroke and summarized the treatments for ischemic stroke by investigating 13 drug monographs and standards. We found 192 prescriptions from the traditional medical system for ischemic stroke, including Angong Niuhuang pill, Qishiwei Zhenzhu Pills, Ginkgo biloba leaf, and other traditional Chinese patent medicines and national medicines. There were 398 kinds of traditional medicine, including 301 kinds of plant-based medicines, 54 kinds of animal-based medicines, 28 kinds of mineral-based medicines, and 15 kinds of other medicines. We introduced the names, families, medicinal components, traditional uses, phytochemical information, and pharmacological activities of the commonly used Chinese patent medicines and TCMs. In addition, some chemicals were introduced. These medicines may be potential candidates for the treatment of ischemic stroke. This work provides a reference for the research and clinical use of new drugs for ischemic stroke.


Assuntos
Produtos Biológicos , Medicamentos de Ervas Chinesas , AVC Isquêmico/tratamento farmacológico , Medicina Tradicional Chinesa , Produtos Biológicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa/métodos
7.
Phytother Res ; 36(6): 2375-2393, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35384105

RESUMO

Schisandrin A (SA) is a bioactive lignan isolated from the traditional Chinese medicine Fructus schisandrae chinensis. In recent years, it has attracted extensive attention because of its multiple pharmacological activities. This review is the first to provide an overview of SA-related pharmacological effects and pharmacokinetic characteristics. The results showed that SA had many pharmacological effects, such as antiinflammation, anticancer, hepatoprotection, antioxidation, neuroprotection, antidiabetes mellitus, and musculoskeletal protection. Among them, NF-κB, Nrf2, MAPK, NLRP3, PI3K/AKT, Wnt, miRNA, P-gp, CYP450, PXR, and other signal transduction pathways are involved. Pharmacokinetic studies showed that SA had good pharmacokinetic characteristics, but these were affected by other factors, such as drugs or hepatic fibrosis. Thus, SA has a variety of pharmacological effects and good pharmacokinetic characteristics, which is worthy of further research and development in the future.


Assuntos
Medicamentos de Ervas Chinesas , Lignanas , Schisandra , Ciclo-Octanos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Lignanas/farmacologia , Fosfatidilinositol 3-Quinases , Compostos Policíclicos
8.
Molecules ; 27(16)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36014482

RESUMO

The application of the seed oil of Prunus mira Koehne (Tibetan name ཁམབུ།), a plant belonging to the Rosaceae family, for the treatment of alopecia has been recorded in Jingzhu Materia Medica (ཤེལ་གོང་ཤེལ་ཕྲེང་།) (the classic of Tibetan medicine) and Dictionary of Chinese Ethnic Medicine. This study aims to reveal the effective components and mechanism of hair growth promotion in the kernel of Prunus mira Koehne. Network pharmacology was used to predict the mechanism of action and effective components in the treatment of the kernel of Prunus mira Koehne. The contents of amygdalin in 12 batches of the kernel of Prunus mira Koehne were determined by HPLC. An animal model of the depilation of KM mice induced by sodium sulfide was created, and five effective components that promoted hair growth were initially screened. In the study of the effectiveness and mechanism of action, KM and C57BL/6 mice are selected as experimental objects, three screening tests for active components of the kernel of P. mira are performed, and three effective components are screened out from the eight components. HE staining was used to detect the number of hair follicles and the thickness of the dermis. RT-PCR and immunohistochemistry were used to evaluate the influence of the expression of indicators in the Wnt/ß-catenin signaling pathway in skin, including ß-catenin, GSK-3ß, and mRNA and protein expression levels of Cyclin D 1 and LEF 1. The network pharmacology study showed 12 signaling pathways involving 25 targets in the treatment of alopecia by the kernel of Prunus mira Koehne. vitamin E (3.125 mg/cm2/d), ß-sitosterol (0.061 mg/cm2/d), and linoleic acid (0.156 mg/cm2/d) in the kernel of Prunus mira Koehne can promote hair growth in mice, and the mechanism of action may be related to the Wnt/ß-catenin pathway.


Assuntos
Prunus , beta Catenina , Alopecia/tratamento farmacológico , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Folículo Piloso , Camundongos , Camundongos Endogâmicos C57BL , Prunus/metabolismo , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo
9.
Nature ; 521(7550): 65-9, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25951285

RESUMO

Internal gravity waves, the subsurface analogue of the familiar surface gravity waves that break on beaches, are ubiquitous in the ocean. Because of their strong vertical and horizontal currents, and the turbulent mixing caused by their breaking, they affect a panoply of ocean processes, such as the supply of nutrients for photosynthesis, sediment and pollutant transport and acoustic transmission; they also pose hazards for man-made structures in the ocean. Generated primarily by the wind and the tides, internal waves can travel thousands of kilometres from their sources before breaking, making it challenging to observe them and to include them in numerical climate models, which are sensitive to their effects. For over a decade, studies have targeted the South China Sea, where the oceans' most powerful known internal waves are generated in the Luzon Strait and steepen dramatically as they propagate west. Confusion has persisted regarding their mechanism of generation, variability and energy budget, however, owing to the lack of in situ data from the Luzon Strait, where extreme flow conditions make measurements difficult. Here we use new observations and numerical models to (1) show that the waves begin as sinusoidal disturbances rather than arising from sharp hydraulic phenomena, (2) reveal the existence of >200-metre-high breaking internal waves in the region of generation that give rise to turbulence levels >10,000 times that in the open ocean, (3) determine that the Kuroshio western boundary current noticeably refracts the internal wave field emanating from the Luzon Strait, and (4) demonstrate a factor-of-two agreement between modelled and observed energy fluxes, which allows us to produce an observationally supported energy budget of the region. Together, these findings give a cradle-to-grave picture of internal waves on a basin scale, which will support further improvements of their representation in numerical climate predictions.

10.
Pharmacol Res ; 155: 104688, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32061838

RESUMO

Tibetan medicine (TM), the second largest traditional Chinese medicine system in China, boasts a long history and an integrated theoretical system. It abounds with classical medical works constituing a unique corpus of Tibetan materia medica (TMM). China has now conceived a modern education system of TM, and Tibetan medical hospitals at different levels have been set up. Many enterprises are granted the privileges to produce preparations of TM in compliance with Good Manufacturing Practices (GMP) regulations. However, there still exist unsolved issuess in TMM research as to the mechanism of action and the active constituents of TMM which are now been tackled through pharmacology and modern science and technology. Up till now, the mechanism of action and the active constituents of 141 medicines as well as 230 preparations of TM have been preliminarily revealed. This paper reviews in detail the development of TM and the status quo of TM's pharmacological research, in hope of serving a reference value for the promotion of the modernization of TM and understanding of TM among the medical scholars.


Assuntos
Medicina Tradicional Tibetana , Animais , Humanos , Materia Medica , Fitoterapia , Preparações de Plantas/uso terapêutico
11.
World J Surg Oncol ; 18(1): 115, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32473637

RESUMO

BACKGROUND: MiR-125 has been shown to be involved in a variety of cancers, including cervical cancer (CC). Here, our goal was to explore miR-125 functional role and molecular mechanism in cervical cancer development and progression. METHODS: qRT-PCR was employ to detect miR-125 and VEGF mRNA expression. Western blot was applied for testing protein levels (VEGF, E-cadherin, N-cadherin, vimentin, AKT, p-AKT, PI3K, and p-PI3K). MTT and transwell assays were used for detecting cervical cancer cell progression, including cell viability, migration, and invasion. RESULTS: We observed that miR-125 was downregulated, whereas VEGF was upregulated in cervical cancer tissues and cell lines (CaSki and SiHa). MiR-125 inhibited the proliferation, invasion, and migration by targeting VEGF in cervical cancer. Moreover, miR-125 negatively regulated VEGF expression in cervical cancer tissues. Finally, we demonstrated that miR-520d-5p inhibited the activation of PI3K/AKT signaling pathway. CONCLUSION: In conclusion, the findings demonstrated that miR-125 inhibited cervical cancer progression and development by suppression VEGF and PI3K/AKT signaling pathway.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias do Colo do Útero/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Colo do Útero/patologia , Progressão da Doença , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Regulação para Cima , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Ann Plast Surg ; 85(4): 430-436, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32931683

RESUMO

PURPOSE: This study aimed to investigate the repair of bone defects in rabbits with tissue-engineered bones using cocultured endothelial progenitor cells (EPCs) and bone marrow mesenchymal stem cells (BMSCs) as seeding cells. METHODS: Endothelial progenitor cells and BMSCs were isolated and purified from the peripheral blood and bone marrow, respectively, of New Zealand rabbits. The third passage of BMSCs was cultured alone or with EPCs. Cells were characterized using specific markers and then seeded on partially deproteinized biologic bones from pigs as a scaffold. The engineered bones were used to repair bone defects in rabbits. Hematoxylin and eosin and Masson staining were performed to examine vascularization and osteogenesis in the engineered bone. RESULTS: The cocultured EPCs and BMSCs grew well on the surface of the scaffold. Compared with monocultured BMSCs, cocultured EPCs and BMSCs promoted the formation of blood vessels and bone on the scaffold, in addition to accelerating the repair of bone defects. The collagen content was significantly increased in the scaffold with cocultured EPCs and BMSCs, compared with the scaffold seeded with mono-cultured BMSCs. CONCLUSIONS: Tissue-engineered bones seeded with cocultured EPCs and BMSCs may be used effectively for the repair of bone defects.


Assuntos
Medula Óssea , Células Progenitoras Endoteliais , Células-Tronco Mesenquimais , Engenharia Tecidual , Animais , Células da Medula Óssea , Células Cultivadas , Osteogênese , Coelhos , Suínos , Alicerces Teciduais
13.
J Nanosci Nanotechnol ; 18(5): 3693-3696, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442885

RESUMO

In this paper, graphene modified by Ag nanoparticles was successfully applied into dye sensitized solar cells. The morphologies and compositions of graphene and graphene-Ag nanoparticles were characterized by scanning electron microscope and energy dispersive X-ray spectroscopy. The optical and electrical properties were evaluated by UV-vis-NIR absorption spectroscopy, electrochemical impedance spectroscopy and current-voltage curve. The results indicated that the incorporation of graphene or graphene-Ag nanoparticles can improve the light absorption and decrease the charge recombination. The solar cells with graphene-Ag nanoparticles exhibited short-circuit current density of 14.34 mA cm-2, open-circuit voltage of 709 mV and conversion efficiency of 6.01%, which were higher than those of DSSCs with graphene or pure TiO2.

15.
J Nanosci Nanotechnol ; 16(2): 1477-82, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27433607

RESUMO

A new architecture of one dimensional ordered TiO2 nanorods modified by graphene oxide (GO) was assembled. The GO as the higher carrier mobility can reduce the recombination of carriers, which is more favourable for the methy orange (MO) degradation. Incorporating GO with the unblocked passageway for carrier transportation of the TiO2 nanorods can separate the transport pathway of electron and hole effectively. Furthermore, the large surface areas of TiO2 nanorods grown on the GO are beneficial to the enhancement of photocatalytic properties, and the reasonable band energy level can be obtained for the architecture, which is favorable for enhancing carrier separation and transportation. Finally, the higher transparency of the structure can enhance the light absorption. The photocatalyst grown on FTO substrates makes it easier to collect and recycle.


Assuntos
Grafite/química , Nanotubos/química , Processos Fotoquímicos , Titânio/química , Catálise
16.
ScientificWorldJournal ; 2014: 954849, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25302337

RESUMO

Recently, the frequent seasonal drought in Southwest China has brought considerable concerns and continuous heated arguments on the "water pump" viewpoint (i.e., the water demand from Hevea spp. and Eucalyptus spp. can be treated as a water pump) once again. However, such viewpoint just focused on water consumption from vegetation transpiration and its ecoenvironment impacts, which had not considered other attributes of vegetation, namely, water saving and drought resistance, and hydrological regulation (water conservation) into consideration. Thus, in this paper, the synthesized attributes of regional vegetation water use had been mainly discussed. The results showed that the study on such aspects as the characters of water consumption from vegetation transpiration, the potential of water saving and drought resistance, and the effects of hydrological regulation in Southwest China lagged far behind, let alone the report on synthesized attributes of water utilization with the organic combination of the three aspects above or the paralleled analysis. Accordingly, in this paper, the study on the synthesized attributes of water use by regional vegetation in Southwest China was suggested, and the objectives of such a special study were clarified, targeting the following aspects: (i) characters of water consumption from transpiration of regional typical artificial vegetation; (ii) potential of water saving and drought resistance of regional typical artificial vegetation; (iii) effects of hydrological regulation of regional typical artificial vegetation; (iv) synthesized attributes of water use by regional typical artificial vegetation. It is expected to provide a new idea for the scientific assessment on the regional vegetation ecoenvironment effects and theoretical guidance for the regional vegetation reconstruction and ecological restoration.


Assuntos
Eucalyptus/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Hevea/metabolismo , Água/metabolismo , Adaptação Fisiológica , Transporte Biológico , China , Conservação dos Recursos Naturais , Secas , Ecossistema , Monitoramento Ambiental , Eucalyptus/genética , Eucalyptus/crescimento & desenvolvimento , Hevea/genética , Hevea/crescimento & desenvolvimento , Transdução de Sinais , Solo
17.
Neural Netw ; 174: 106234, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38521015

RESUMO

Multivariate chaotic time series prediction is a challenging task, especially when multiple variables are predicted simultaneously. For multiple related prediction tasks typically require multiple models, however, multiple models are difficult to keep synchronization, making immediate communication between predicted values challenging. Although multi-task learning can be applied to this problem, the principles of allocation and layout options between shared and specific representations are ambiguous. To address this issue, a novel simplified multi-task learning method was proposed for the precise implementation of simultaneous multiple chaotic time series prediction tasks. The scheme proposed consists of a cross-convolution operator designed to capture variable correlations and sequence correlations, and an attention module proposed to capture the information embedded in the sequence structure. In the attention module, a non-linear transformation was implemented with convolution, and its local receptive field and the global dependency of the attention mechanism achieve complementarity. In addition, an attention weight calculation was devised that takes into account not only the synergy of time and frequency domain features, but also the fusion of series and channel information. Notably the scheme proposed a purely simplified design principle of multi-task learning by reducing the specific network to single neuron. The precision of the proposed solution and its potential for engineering applications were verified with the Lorenz system and power consumption. The mean absolute error of the proposed method was reduced by an average of 82.9% in the Lorenz system and 19.83% in power consumption compared to the Gated Recurrent Unit.


Assuntos
Engenharia , Aprendizagem , Fatores de Tempo , Neurônios
18.
Chem Asian J ; 19(5): e202301092, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38116862

RESUMO

A one-pot route to a novel azepane-fused tetrahydro-ß-carboline framework from tryptyl-4-pentenamide derivatives has been developed, featuring the Rh-catalyzed hydroformylation double cyclization. Subsequent alkylation in the tetracyclic system proceeded stereoselectively to form a quaternary carbon. The synthesis of (±)-20-epi-kopsiyunnanine K was accomplished through the strategy.

19.
Inflammation ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393550

RESUMO

Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C21H24O6) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-ß1 (TGF-ß1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24 h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-ß1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-ß1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/ß-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.

20.
J Ethnopharmacol ; 322: 117584, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38104874

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. AIM OF THE STUDY: The aim of this paper was to investigate the potential protective mechanism of CuB against CLI. METHODS: First, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. RESULTS: A total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. CONCLUSION: By combining network pharmacology with in vivo and in vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI.


Assuntos
Colestase , Cucumis melo , Medicamentos de Ervas Chinesas , Triterpenos , Animais , Camundongos , Interleucina-6 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fígado , Colestase/induzido quimicamente , Colestase/tratamento farmacológico , Inflamação
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