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1.
Ann Med ; 56(1): 2320863, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38373214

RESUMO

Hypertension is a prevalent chronic condition worldwide that can impact patients' quality of life. Oral antihypertensive drugs are widely used to manage high blood pressure, primarily by regulating the renin-angiotensin-aldosterone system. Nevertheless, limited efficacy and low compliance represent significant obstacles, arising primarily from dose, duration, and medication type restrictions. Furthermore, the prolonged use of antihypertensive medication may result in dependence and adverse effects, without any substantial improvement in achieving targeted blood pressure leves. As a result, research has focused on using exercise therapy to treat hypertension. Tai Chi, a widely-practiced Chinese health exercise, has evolved into a form of exercise therapy that might help alleviate the risk associated with hypertension. Therefore, this article aims to outline the role of Tai Chi in preventing and managing hypertension.


Assuntos
Hipertensão , Tai Chi Chuan , Humanos , Qualidade de Vida , Hipertensão/prevenção & controle , Pressão Sanguínea , Atenção Primária à Saúde
2.
Comb Chem High Throughput Screen ; 27(1): 90-100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37190798

RESUMO

INTRODUCTION: Fu-Fang-Jin-Qian-Cao is a Chinese herbal preparation used to treat urinary calculi. Fu-Fang-Jin-Qian-Cao can protect renal tubular epithelial cells from calcium oxalateinduced renal injury by inhibiting ROS-mediated autopathy. The mechanism still needs further exploration. Metabonomics is a new subject; the combination of metabolomics and network pharmacology can find pathways for drugs to act on targets more efficiently. METHODS: Comprehensive metabolomics and network pharmacology to study the mechanism of Fu-Fang-Jin-Qian-Cao inhibiting autophagy in calcium oxalate-induced renal injury. Based on UHPLC-Q-TOF-MS, combined with biochemical analysis, a mice model of Calcium oxalateinduced renal injury was established to study the therapeutic effect of Fu-Fang-Jin-Qian-Cao. Based on the network pharmacology, the target signaling pathway and the protective effect of Fu- Fang-Jin-Qian-Cao on Calcium oxalate-induced renal injury by inhibiting autophagy were explored. Autophagy-related proteins LC3-II, BECN1, ATG5, and ATG7 were studied by immunohistochemistry. RESULTS: Combining network pharmacology and metabolomics, 50 differential metabolites and 2482 targets related to these metabolites were found. Subsequently, the targets enriched in PI3KAkt, MAPK and Ras signaling pathways. LC3-II, BECN1, ATG5 and ATG7 were up-regulated in Calcium oxalate-induced renal injury. All of them could be reversed after the Fu-Fang-Jin-Qian- Cao treatment. CONCLUSIONS: Fu-Fang-Jin-Qian-Cao can reverse ROS-induced activation of the MAPK signaling pathway and inhibition of the PI3K-Akt signaling pathway, thereby reducing autophagy damage of renal tubular epithelial cells in Calcium oxalate-induced renal injury.


Assuntos
Oxalato de Cálcio , Medicamentos de Ervas Chinesas , Camundongos , Animais , Oxalato de Cálcio/metabolismo , Oxalato de Cálcio/farmacologia , Cálcio/metabolismo , Cromatografia Líquida de Alta Pressão , Farmacologia em Rede , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rim/metabolismo , Autofagia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/metabolismo
3.
Adv Mater ; 36(9): e2307006, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37924225

RESUMO

The ferroptosis pathway is recognized as an essential strategy for tumor treatment. However, killing tumor cells in deep tumor regions with ferroptosis agents is still challenging because of distinct size requirements for intratumoral accumulation and deep tumor penetration. Herein, intelligent nanocapsules with size-switchable capability that responds to acid/hyperthermia stimulation to achieve deep tumor ferroptosis are developed. These nanocapsules are constructed using poly(lactic-co-glycolic) acid and Pluronic F127 as carrier materials, with Au-Fe2 C Janus nanoparticles serving as photothermal and ferroptosis agents, and sorafenib (SRF) as the ferroptosis enhancer. The PFP@Au-Fe2 C-SRF nanocapsules, designed with an appropriate size, exhibit superior intratumoral accumulation compared to free Au-Fe2 C nanoparticles, as evidenced by photoacoustic and magnetic resonance imaging. These nanocapsules can degrade within the acidic tumor microenvironment when subjected to laser irradiation, releasing free Au-Fe2 C nanoparticles. This enables them to penetrate deep into tumor regions and disrupt intracellular redox balance. Under the guidance of imaging, these PFP@Au-Fe2 C-SRF nanocapsules effectively inhibit tumor growth when exposed to laser irradiation, capitalizing on the synergistic photothermal and ferroptosis effects. This study presents an intelligent formulation based on iron carbide for achieving deep tumor ferroptosis through size-switchable cascade delivery, thereby advancing the comprehension of ferroptosis in the context of tumor theranostics.


Assuntos
Compostos Inorgânicos de Carbono , Ferroptose , Hipertermia Induzida , Compostos de Ferro , Nanocápsulas , Nanopartículas , Neoplasias , Humanos , Linhagem Celular Tumoral , Neoplasias/terapia , Sorafenibe , Hipertermia/terapia , Hipertermia Induzida/métodos , Microambiente Tumoral
4.
Int J Biol Macromol ; 258(Pt 2): 128990, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38158057

RESUMO

Plantago asiatica L. (PAL), a traditional herb, has been used in East Asia for thousands of years. In recent years, polysaccharides extracted from PAL have garnered increased attention due to their outstanding pharmacological and biological properties. Previous research has established that PAL-derived polysaccharides exhibit antioxidant, anti-inflammatory, antidiabetic, antitumor, antimicrobial, immune-regulatory, intestinal health-promoting, antiviral, and other effects. Nevertheless, a comprehensive summary of the research related to Plantago asiatica L. polysaccharides (PALP) has not been reported to date. In this paper, we review the methods for isolation and purification, physiochemical properties, structural features, and biological activities of PALP. To provide a foundation for research and application in the fields of medicine and food, this review also outlines the future development prospects of plantain polysaccharides.


Assuntos
Plantago , Plantago/química , Antioxidantes/farmacologia , Polissacarídeos/química , Extratos Vegetais/farmacologia , Ásia Oriental
5.
Int J Mol Sci ; 24(23)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38069099

RESUMO

Garlic, originating in the mountains of Central Asia, has undergone domestication and subsequent widespread introduction to diverse regions. Human selection for adaptation to various climates has resulted in the development of numerous garlic varieties, each characterized by specific morphological and physiological traits. However, this process has led to a loss of fertility and seed production in garlic crops. In this study, we conducted morpho-physiological and transcriptome analyses, along with whole-genome resequencing of 41 garlic accessions from different regions, in order to assess the variations in reproductive traits among garlic populations. Our findings indicate that the evolution of garlic crops was associated with mutations in genes related to vernalization and the circadian clock. The decline in sexual reproduction is not solely attributed to a few mutations in specific genes, but is correlated with extensive alterations in the genetic regulation of the annual cycle, stress adaptations, and environmental requirements. The regulation of flowering ability, stress response, and metabolism occurs at both the genetic and transcriptional levels. We conclude that the migration and evolution of garlic crops involve substantial and diverse changes across the entire genome landscape. The construction of a garlic pan-genome, encompassing genetic diversity from various garlic populations, will provide further insights for research into and the improvement of garlic crops.


Assuntos
Alho , Humanos , Alho/genética , Alho/metabolismo , Domesticação , Fenótipo , Perfilação da Expressão Gênica , Produtos Agrícolas/genética , Reprodução/genética
6.
Ann Med ; 55(2): 2294935, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38109929

RESUMO

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, second only to Alzheimer's disease. Drugs and deep brain stimulation (DBS) are the main treatments for PD. However, the long-term side effects of drugs and the risks of surgery cannot be ignored. It is therefore important to research safe and effective complementary and alternative therapies for PD. Yoga, an ancient mind-body exercise, has been widely used in health promotion. Although, yoga can address a range of health problems, little is known about its role in people with PD. This article reviews the evidence that yoga improves PD symptoms, including movement disorders, balance function and emotional disturbance. The authors analyze the role and shortcomings of the yoga intervention process, with the aim of providing a scientific basis for the application of yoga training to people with PD.


Assuntos
Doença de Parkinson , Yoga , Humanos , Doença de Parkinson/terapia , Terapia por Exercício
7.
Physiol Plant ; 175(6): e14112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148228

RESUMO

With the intensification of the greenhouse effect and the continuous rise of global temperature, high temperatures in summer seriously affect the growth of green onion (Allium fistulosum L.var.caespitosum Makino) and reduce its yield and quality. It is important to study the mechanism of heat tolerance in green onion for selecting and breeding new varieties with high-temperature tolerance. In this study, we used the heat-tolerant green onion variety AF60 and heat-sensitive green onion variety AF35 and measured their physiological indexes under different durations of heat stress. The results showed that high-temperature stress adversely affected the water content, protein composition and antioxidant system of green onion. In addition, a comprehensive analysis using transcriptomics and metabolomics showed that heat-tolerant green onions responded positively to heat stress by up-regulating the expression of heat shock proteins, whereas heat-sensitive green onions responded to heat stress by activating the galactose metabolic pathway and maintained normal physiological activities. This study revealed the physiological performance and high-temperature response pathways of different heat-tolerant green onion cultivars under heat stress. The results further deepen the understanding of the molecular mechanism of green onion's heat stress response.


Assuntos
Biodiversidade , Multiômica , Temperatura , Cebolas/genética , Antioxidantes
8.
Pharmaceuticals (Basel) ; 16(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38139793

RESUMO

Ruan Hua Tang (RHT) and Ruan Hua Fang (RHF) are two Chinese herbal mixtures that have been used in clinical cancer treatment for decades. This study validated our hypothesis that RHT and RHF can inhibit lung tumor development in the mouse model of Benzo(a)pyrene-induced lung tumorigenesis. An RHT oral solution was diluted to 9% and 18% in water. RHF was mixed into the diet at 15% and 30% of total food in the final doses. Two weeks after injecting BP into mice, we administered RHT and RHF for eighteen weeks. We found that 9% and 18% RHT reduced tumor multiplicity by 36.05% and 38.81% (both p < 0.05) and the tumor load by 27.13% and 55.94% (p < 0.05); 15% and 30% RHF inhibited tumor multiplicity by 12.75% and 39.84% (p < 0.01) and the tumor load by 18.38% and 61.68% (p < 0.05). Ki67 expressions in the 9% and 18% RHT groups were 19.55% and 11.51%, significantly lower than in the control (33.64%). The Ki67 levels in the 15% and 30% RHF groups were 15.56% and 14.04%, significantly lower than in the control (27.86%). Caspase 3 expressions in the 9% and 18% RHT groups were 5.24% and 7.32%, significantly higher than in the control (2.39%). Caspase 3 levels in the 15% and 30% RHF groups were 6.53% and 4.74%, significantly higher than in the control (2.07%). The bio-absorption was confirmed via a pharmacokinetic test. This study showed that RHT and RHF are safe and can inhibit lung tumor development, with anti-proliferative and pro-apoptotic effects.

9.
J Am Chem Soc ; 145(42): 23257-23274, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37831944

RESUMO

Phototheranostics have emerged as a promising subset of cancer theranostics owing to their potential to provide precise photoinduced diagnoses and therapeutic outcomes. However, the design of phototheranostics remains challenging due to the nature of tumors and their microenvironment, including limitations to the oxygen supply, high rates of recurrence and metastasis, and the immunosuppressive state of cancer cells. Here we report a dual-functional oxygen-independent phototheranostic agent, Ni-2, rationally designed to provide a near-infrared (NIR) photoactivated thermal- and hydroxyl radical (•OH)-enhanced photoimmunotherapeutic anticancer response. Under 880 nm laser irradiation, Ni-2 exhibited high photostability and excellent photoacoustic and photothermal effects with a photothermal conversion efficacy of 58.0%, as well as novel photoredox features that allowed the catalytic conversion of H2O2 to •OH upon photooxidation of Ni(II) to Ni(III). As a multifunctional photoagent, Ni-2 was found not only to inhibit tumor growth in a CT26 tumor-bearing mouse model but also to activate an immune response via a combination of photothermal- and H2O2-induced effects. When combined with an antiprogrammed death-ligand 1 (aPD-L1), Ni-2 treatment allowed for the suppression of distant tumor growth and cancer metastasis. Collectively, the present results provide support for the proposition that Ni-2 or its analogues could emerge as useful tools for photoimmunotherapy. They also highlight the potential of appropriately designed 3d transition metal complexes as "all- in-one" phototheranostics.


Assuntos
Nanopartículas , Neoplasias , Camundongos , Animais , Níquel , Peróxido de Hidrogênio , Nanomedicina Teranóstica/métodos , Fototerapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Oxigênio , Imunoterapia , Linhagem Celular Tumoral , Microambiente Tumoral
10.
J Agric Food Chem ; 71(41): 14967-14978, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37803933

RESUMO

The synthesis of a hapten and antigen for the preparation of a monoclonal antibody (mAb) for buprofezin is described. The recognition mechanism of hapten and buprofezin by monoclonal antibodies (mAb-19F2) is described. The effectiveness of the mAb-19F2 immunoassay technique was assessed, and the effective detection of buprofezin in tea samples was achieved through the establishment of indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and colloidal gold immunochromatography assay (GICA). The mAb-19F2 subtype was IgG1, with an IC50 of 1.8 ng/mL and a linear range (IC20-IC80) of 0.6-5.4 µg/L, and had a cross-reaction rate of less than 0.18% with 29 other pesticides (neonicotinoids and insect growth regulators). The study identified π-π stacking interactions between hapten and TYR-61 at the mAb-19F2 site and alkyl/phosphate interactions with TRP-105 and ARG-103. The ic-ELISA had an IC50 of 12.9 ng/mL in green tea and 5.65 ng/mL in black tea, with a recovery rate of 92.4%-101.0% and RSD of 2.1%-4.8%. The GICA had a limit of detection (LOD) was 500 ng/mL, with the complete disappearance of the test lines visible to the naked eye. The limit of quantitation (LOQ, IC20) was determined to be 16.8 ng/mL. Additionally, the developed GICA showed no cross-reactivity with neonicotinoid pesticides. The recovery rate of tea spiked recovered samples was 83.6%-92.2%, with an RSD of 5.3%-12.6%, and the results were consistent with the LC/MS method. This study is important for the real-time detection of buprofezin residues to ensure food safety and human health.


Assuntos
Anticorpos Monoclonais , Praguicidas , Humanos , Anticorpos Monoclonais/química , Imunoensaio/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Haptenos , Neonicotinoides , Chá
11.
J Pharm Pharmacol ; 75(11): 1478-1491, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37738315

RESUMO

OBJECTIVES: Safflower is a traditional Chinese medicine for the treatment of gynecological diseases and its flavonoids have potential anti-inflammatory effects. The purpose is to explore the possible effects of safflower total flavonoids (STF) on lipopolysaccharide (LPS)-induced inflammatory damage of Ishikawa cells. METHOD: In this study, LPS-induced endometrial carcinoma Ishikawa cells were used to establish an inflammatory injury model. The effective concentration of STF was screened by CCK-8 and enzyme-linked immunosorbent assay. The apoptosis of damaged Ishikawa cells was detected by flow cytometry. The contents of caspase11 and caspase 3 in Ishikawa cells were observed by fluorescence imaging. Western blot and RT-qPCR were used to detect the expression of related proteins and mRNA in damaged Ishikawa cells, and the possible mechanism of safflower flavonoids against LPS-induced endometrial carcinoma Ishikawa cells was analyzed by cell transcriptomics. KEY FINDINGS: The STF-reduced tumor necrosis factor α, interleukin-1ß, and interleukin-6 expression level; the expression level of the proteins ASK1, Caspase3, and Caspase11 was also significantly decreased, and the proteins ERα, p-PI3K, and p-AKT were significantly increased. The transcriptome results showed that the PI3K-Akt signal pathway may be the main signal pathway for the STF. CONCLUSION: The STF could regulate the PI3K/AKT signal pathway to treat the inflammatory injury of Ishikawa cells.


Assuntos
Carthamus tinctorius , Neoplasias do Endométrio , Endometrite , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carthamus tinctorius/metabolismo , Flavonoides/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Lipopolissacarídeos , Transcriptoma , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia
12.
Curr Drug Metab ; 24(6): 422-433, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37592799

RESUMO

BACKGROUND: Chemotherapeutic drugs used in cancer treatment often result in gastrointestinal toxicity, notably diarrhea, impacting patients' quality of life. Complementary and Alternative Medicine (CAM) has garnered increasing interest as an alternative to conventional approaches as a potential solution for managing chemotherapyinduced diarrhea (CID). OBJECTIVE: To summarize current research focusing on herbal medicines as adjuvant therapy to prevent or treat chemotherapy-induced diarrhea, including clinical assessments, mechanism of actions, active components, and potential pharmacokinetic interactions between herbal medicines and chemotherapeutic drugs. METHODS: We performed the literature review from PubMed, CNKI, Google Scholar, Web of Science, and Scopus using "Chemotherapy", "Diarrhea," and "Complementary and Alternative Medicine" as the search keywords. RESULTS: Using herbal medicines as adjuvants provides an effective approach to treating or preventing CID with improved or unaffected antitumor activity of chemotherapeutic drugs. Among these herbal formulations, scutellaria, ginger, and ginseng are the most frequently used herbs in the prescriptions for CID. The main antidiarrheal components in herbs include wogonin, baicalin, chrysin, quercetin, gingerol, and ginsenosides. These herbs, formulations, and bioactive components relieved CID through different mechanisms, including directly decreasing local drug exposure, anti-inflammation, inhibiting epithelial apoptosis, or promoting epithelium stem cell regeneration. The application of herbal medicines as adjunctive therapies showed efficacy in preventing or treating CID in multiple clinical trials. However, more well-designed clinical studies are expected to validate the results further. Despite some clinical studies demonstrating that certain herbal medicines could potentially attenuate CID and improve efficacy, it remains necessary to evaluate herbal safety. The interactions between herbs and drugs are also potential concerns, but few clinical trials have focused on investigating this aspect. CONCLUSION: In clinical practise, herbal medications show potential as adjuvant treatments for gastrointestinal toxicities induced by chemotherapy, particularly diarrhoea. Further well-designed clinical studies are needed to validate their efficacy, ensure safety, and explore potential drug-herb interactions.


Assuntos
Antineoplásicos , Medicamentos de Ervas Chinesas , Gastroenteropatias , Plantas Medicinais , Humanos , Qualidade de Vida , Medicamentos de Ervas Chinesas/farmacologia , Gastroenteropatias/tratamento farmacológico , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Fitoterapia
13.
Artigo em Inglês | MEDLINE | ID: mdl-37287284

RESUMO

BACKGROUND: A network pharmacology study on the biological action of ginseng in the treatment of colorectal cancer (CRC) by regulating the tumor microenvironment (TME). OBJECTIVE: To investigate the potential mechanism of action of ginseng in the treatment of CRC by regulating TME. METHOD: This research employed network pharmacology, molecular docking techniques, and bioinformatics validation. Firstly, the active ingredients and the corresponding targets of ginseng were retrieved using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Traditional Chinese Medicine Integrated Database (TCMID), and the Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan). Secondly, the targets related to CRC were retrieved using Genecards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM). Tertiary, the targets related to TME were derived from screening the GeneCards and National Center for Biotechnology Information (NCBI)-Gene. Then the common targets of ginseng, CRC, and TME were obtained by Venn diagram. Afterward, the Protein-protein interaction (PPI) network was constructed in the STRING 11.5 database, intersecting targets identified by PPI analysis were introduced into Cytoscape 3.8.2 software cytoHubba plugin, and the final determination of core targets was based on degree value. The OmicShare Tools platform was used to analyze the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets. Autodock and PyMOL were used for molecular docking verification and visual data analysis of docking results. Finally, we verified the core targets by Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases in bioinformatics. RESULTS: A total of 22 active ingredients and 202 targets were identified to be closely related to the TME of CRC. PPI network mapping identified SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 as possible core targets. Go enrichment analysis showed that it was mainly involved in T cell co-stimulation, lymphocyte co-stimulation, growth hormone response, protein input, and other biological processes; KEGG pathway analysis found 123 related signal pathways, including EGFR tyrosine kinase inhibitor resistance, chemokine signaling pathway, VEGF signaling pathway, ErbB signaling pathway, PD-L1 expression and PD-1 checkpoint pathway in cancer, etc. The molecular docking results showed that the main chemical components of ginseng have a stable binding activity to the core targets. The results of the GEPIA database showed that the mRNA levels of PIK3R1 were significantly lowly expressed and HSP90AA1 was significantly highly expressed in CRC tissues. Analysis of the relationship between core target mRNA levels and the pathological stage of CRC showed that the levels of SRC changed significantly with the pathological stage. The HPA database results showed that the expression levels of SRC were increased in CRC tissues, while the expression of STAT3, PIK3R1, HSP90AA1, and AKT1 were decreased in CRC tissues. CONCLUSION: Ginseng may act on SRC, STAT3, PIK3R1, HSP90AA1, and AKT1 to regulate T cell costimulation, lymphocyte costimulation, growth hormone response, protein input as a molecular mechanism regulating TME for CRC. It reflects the multi-target and multi-pathway role of ginseng in modulating TME for CRC, which provides new ideas to further reveal its pharmacological basis, mechanism of action and new drug design and development.

14.
Phytomedicine ; 117: 154897, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37307738

RESUMO

BACKGROUND: Natural products are an important source for discovering novel drugs due to their various pharmacological activities. Salvia miltiorrhiza Burge (Danshen) has been shown to have promising therapeutic potential in the management of heart diseases, making it a candidate for cardiovascular drug discovery. Currently, there is limited quantitative analysis of the phosphorylation levels of Danshen-derived natural products on a proteome-wide, which may bias the study of their mechanisms of action. PURPOSE: This study aimed to evaluate the global signaling perturbation induced by Danshen-derived bioactive compounds and their potential relationship with myocardial ischemia/reperfusion (IR) injury therapy. STUDY DESIGN: We employed quantitative proteome and phosphoproteome analysis to identify dysregulated signaling in IR injury hearts from mice. We compared changes induced by Danshen-derived compounds based on IR-associated phospho-events, using an integrative approach that maps relative abundance of proteins and phosphorylation sites. METHODS: Isobaric chemical tandem mass tags (TMT) labeled multiplexing strategy was used to generate unbiased quantitative proteomics and phosphoproteomics data. Highly accurate and precise TMT quantitation was performed using the Orbitrap Fusion Tribrid Mass Spectrometer with synchronous precursor selection MS3 detection mode. Mass spectrometric raw files were analyzed with MaxQuant (2.0.1.0) and statistical and bioinformatics analysis was conducted with Perseus (1.6.15). RESULTS: We quantified 3661 proteins and over 11,000 phosphosites in impaired heart tissue of the IR mice model, expanding our knowledge of signaling pathways and other biological processes disrupted in IR injury. Next, 1548 and 5545 differently expressed proteins and phosphosites were identified by quantifying the proteome and phosphoproteome of H9c2 cells treated by five Danshen bioactive compounds respectively. Results revealed the vast differences in abilities of five Danshen-derived bioactive compounds to regulate phosphorylation modifications in cardiomyocytes, with dihydrotanshinone I (DHT) showing potential for protecting against IR injury by modulating the AMPK/mTOR signaling pathway. CONCLUSIONS: This study provides a new strategy for analyzing drug/natural product-regulated phosphorylation modification levels on a proteome-wide scale, leading to a better understanding of cell signaling pathways and downstream phenotypic responses.


Assuntos
Salvia miltiorrhiza , Camundongos , Animais , Salvia miltiorrhiza/química , Proteoma/metabolismo , Proteômica/métodos , Fosforilação , Miócitos Cardíacos/metabolismo
15.
J Ethnopharmacol ; 315: 116639, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37201664

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Safflower is a traditional Chinese medicine used for treating gynaecological diseases. However, its material basis and mechanism of action in the treatment of endometritis induced by incomplete abortion are still unclear. AIM OF THE STUDY: This study aimed to reveal the material basis and mechanism of action of safflower in the treatment of endometritis induced by incomplete abortion through comprehensive methods, including network pharmacology and 16S rDNA sequencing. MATERIALS AND METHODS: Network pharmacology and molecular docking methods were used to screen the main active components and potential mechanisms of action of safflower in the treatment of endometritis induced by incomplete abortion in rats. A rat model of endometrial inflammation by incomplete abortion was established. The rats were treated with safflower total flavonoids (STF) based on forecasting results, serum levels of inflammatory cytokines were analysed, and immunohistochemistry, Western blots, and 16S rDNA sequencing were performed to investigate the effects of the active ingredient and the treatment mechanism. RESULTS: The network pharmacology prediction results showed 20 active components with 260 targets in safflower, 1007 targets related to endometritis caused by incomplete abortion, and 114 drug-disease intersecting targets, including TNF, IL6, TP53, AKT1, JUN, VEGFA, CASP3 and other core targets, PI3K/AKT, MAPK and other signalling pathways may be closely related to incomplete abortion leading to endometritis. The animal experiment results showed that STF could significantly repair uterine damage and reduce the amount of bleeding. Compared with the model group, STF significantly down-regulated the levels of pro-inflammatory factors (IL-6, IL-1ß, NO, TNF-α) and the expression of JNK, ASK1, Bax, caspase3, and caspase11 proteins. At the same time, the levels of anti-inflammatory factors (TGF-ß and PGE2) and the protein expression of ERα, PI3K, AKT, and Bcl2 were up-regulated. Significant differences in the intestinal flora were seen between the normal group and the model group, and the intestinal flora of the rats was closer to the normal group after the administration of STF. CONCLUSIONS: The characteristics of STF used in the treatment of endometritis induced by incomplete abortion were multi-targeted and involved multiple pathways. The mechanism may be related to the activation of the ERα/PI3K/AKT signalling pathway by regulating the composition and ratio of the gut microbiota.


Assuntos
Aborto Incompleto , Aborto Espontâneo , Carthamus tinctorius , Medicamentos de Ervas Chinesas , Endometrite , Feminino , Gravidez , Humanos , Animais , Ratos , Receptor alfa de Estrogênio , Endometrite/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , DNA Ribossômico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
16.
J Agric Food Chem ; 71(16): 6389-6397, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37052370

RESUMO

Squalene is a triterpene that can be obtained from fish and plant oils. It is important in cosmetics and vaccines and is a precursor for many high-value terpenes and steroids. In order to increase squalene accumulation, the mevalonate pathway was systematically enhanced. Accumulation of squalene tended to increase when ethanol was added as a carbon source during fermentation, but a high concentration of ethanol affected both the strain growth and accumulation of products. By overexpressing the key trehalose synthesis gene TPS1 and the heat shock protein gene HSP104, the content of trehalose by Saccharomyces cerevisiae (S. cerevisiae) was enhanced, and stress caused by ethanol was relieved. The OD600 value of the modified S. cerevisiae strain was increased by 80.2%, its ethanol tolerance was increased to 30 g/L, and it retained excellent activity with 50 g/L ethanol. After optimizing the fermentation conditions, the squalene titer in a 5 L bioreactor reached 27.3 g/L and the squalene content was 650 mg/g dry cell weight, the highest squalene production parameters reported to date for a microorganism.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Esqualeno/metabolismo , Etanol/metabolismo , Trealose/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fermentação , Engenharia Metabólica , Proteínas de Choque Térmico/genética
17.
Acta Pharmaceutica Sinica ; (12): 1988-1999, 2023.
Artigo em Chinês | WPRIM | ID: wpr-999119

RESUMO

Cardiovascular disease (CVD) is a major contributor to patient deaths worldwide, and its pathogenesis is complex and mortality rates are increasing every year. Numerous researches have shown that the gut microbiota and its metabolites were closely associated with the development of CVD, and gut microbiota was expected to be a potential new target for the treatment of CVD. Traditional Chinese medicine (TCM), characterized by its multi-component, multi-target and integrity, can play a therapeutic role in CVD by regulating the gut microbiota, which has obvious advantages in stabilizing the disease, improving heart function and enhancing quality of life, and is an ideal intestinal microecological regulator. Therefore, this review will mainly discuss the intimate association of gut microbiota and its metabolites with CVD, and the therapeutic strategies of TCM targeting gut microbiota to improve CVD, including regulating the composition of gut microbiota, protecting the intestinal mucosal barrier, influencing the intestinal immune function and modulating the metabolites of gut microbiota, in order to provide a reference for the research of TCM targeting gut microbiota for CVD.

18.
Front Neurol ; 13: 931460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119693

RESUMO

Parkinson's disease (PD) is an important health problem caused by the degeneration of brain neurons. Bradykinesia and lower balance ability seriously affect the quality of life of people with PD. Non-motor symptoms, such as cognitive impairment, accompany the course of the disease but still lack sufficient attention. In general, drugs combined with cognitive training are the most common ways to improve cognitive impairment in people with PD. However, long-term use of psychiatric drugs may lead to side effects such as brain death and movement disorders. Recently, mindfulness has been used by researchers in the treatment of cognitive impairment, because healthy older adults who engage in mind-body exercises for a long time have higher cognitive levels than normal aging populations. Mind-body exercise, as a therapy that combines concentration, breath control, and physical activity, is beneficial for improving practitioners' brain and mental health. Mind-body exercises such as Tai Chi, yoga, dance, and Pilates can improve cognitive performance in older adults with or without cognitive impairment. Therefore, mind-body exercise may be a feasible strategy for the treatment of cognitive impairment in people with PD. This study summarizes the latest evidence that mind-body exercises including Tai Chi, Qigong, yoga, and dance improve cognitive impairment associated with PD. We also explored the limitations of current mind-body exercise research, aiming to provide new ideas for improving mind-body exercise as a strategy to alleviate cognitive impairment in people with PD.

19.
Genome Biol ; 23(1): 188, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071507

RESUMO

BACKGROUND: Garlic is an entirely sterile crop with important value as a vegetable, condiment, and medicine. However, the evolutionary history of garlic remains largely unknown. RESULTS: Here we report a comprehensive map of garlic genomic variation, consisting of amazingly 129.4 million variations. Evolutionary analysis indicates that the garlic population diverged at least 100,000 years ago, and the two groups cultivated in China were domesticated from two independent routes. Consequently, 15.0 and 17.5% of genes underwent an expression change in two cultivated groups, causing a reshaping of their transcriptomic architecture. Furthermore, we find independent domestication leads to few overlaps of deleterious substitutions in these two groups due to separate accumulation and selection-based removal. By analysis of selective sweeps, genome-wide trait associations and associated transcriptomic analysis, we uncover differential selections for the bulb traits in these two garlic groups during their domestication. CONCLUSIONS: This study provides valuable resources for garlic genomics-based breeding, and comprehensive insights into the evolutionary history of this clonal-propagated crop.


Assuntos
Alho , Alho/genética , Genoma de Planta , Genômica , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único
20.
J Ethnopharmacol ; 295: 115442, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35688255

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dingkun Pill (DKP), a traditional Chinese medicine prescription, was modified from Bujing decoction and Xusijiangsheng pill by the imperial physician in the Qing dynasty (1700' s). It was believed to treat various gynecological diseases by nourishing qi and blood. Accumulating evidence indicates that it is effective in treating polycystic ovary syndrome (PCOS). However, the therapeutic efficacy and mechanism of action DKP against PCOS need to be further elucidated. AIM OF THE STUDY: To investigate the therapeutic effect and action mechanism of DKP against PCOS using an integrated approach of metabolomics and network pharmacology. MATERIALS AND METHODS: The rat model of PCOS was established by dehydroepiandrosterone. An integrated metabolomics and network pharmacology strategy was applied to systemically clarify the mechanism of DKP against PCOS. Theca cells were prepared to evaluate the effect of DKP and its ingredients on testosterone synthesis in vitro. RESULTS: The pharmacological experiments demonstrated that DKP could effectively convert the disordered estrous cyclicity, decrease the level of testosterone and the luteinizing hormone/follicle stimulating hormone ratio, and inhibit abnormal follicle formation in PCOS rats. By metabolomics analysis, 164 serum endogenous differential metabolites and 172 urine endogenous differential metabolites were tentatively identified. Steroid hormone biosynthesis and ovarian steroidogenesis were the most significantly impacted pathways. Based on network pharmacology and metabolomics studies, the ingredient-target-pathway network of DKP in the treatment of PCOS was constructed. Among the 10 key targets, CYP17A1, CYP19A1, STS, AR, ESR1, and MYC were closely involved in ovarian androgen synthesis. In theca cell-based assay of testosterone synthesis, DKP and its two active compounds (ligustilide and picrocrocin) showed inhibitory effects. CONCLUSION: DKP effectively improved symptoms in rats with dehydroepiandrosterone-induced PCOS. The mechanism of DKP in the treatment of PCOS is related to the CYP17A1 enzyme required for androgen synthesis.


Assuntos
Síndrome do Ovário Policístico , Androgênios , Animais , Desidroepiandrosterona/uso terapêutico , Feminino , Humanos , Metabolômica , Farmacologia em Rede , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Ratos , Testosterona/uso terapêutico
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