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1.
Plant Physiol ; 192(3): 2419-2435, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-36932696

RESUMO

Terpene synthases (TPSs) play pivotal roles in conferring the structural diversity of terpenoids, which are mainly emitted from flowers, whereas the genetic basis of the release of floral volatile terpenes remains largely elusive. Though quite similar in sequence, TPS allelic variants still function divergently, and how they drive floral terpene diversity in closely related species remains unknown. Here, TPSs responsible for the floral scent of wild Freesia species were characterized, and the functions of their natural allelic variants, as well as the causal amino acid residues, were investigated in depth. Besides the 8 TPSs previously reported in modern cultivars, 7 additional TPSs were functionally evaluated to contribute to the major volatiles emitted from wild Freesia species. Functional characterization of allelic natural variants demonstrated that allelic TPS2 and TPS10 variants changed the enzymatic capacity while allelic TPS6 variants drove the diversity of floral terpene products. Further residue substitution analysis revealed the minor residues determining the enzyme catalytic activity and product specificity. The clarification of TPSs in wild Freesia species reveals that allelic TPS variants evolved differently to determine the interspecific floral volatile terpenes in the genus and might be used for modern cultivar improvement.


Assuntos
Alquil e Aril Transferases , Terpenos , Terpenos/metabolismo , Filogenia , Alquil e Aril Transferases/genética
2.
Dev Biol ; 487: 122-133, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525303

RESUMO

In females, the establishment of the primordial follicle pool is accompanied by a remarkable programmed oocyte loss for unclear reasons. In this study, the role of autophagy was investigated to serve as a protective mechanism for oocyte survival during chicken folliculogenesis. Inhibition of autophagy by 3-methyladenine (3-MA) led to a remarkable delay in germ cell cyst breakdown that resulted in fewer primordial follicles and retarded sequent follicular development either in vivo or in the ovarian organ culture. Furthermore, the glycolysis level was downregulated in ovaries treated with 3-MA, while Recilisib (a specific activator of Akt) reversed this inhibiting effect of 3-MA on primordial folliculogenesis. Collectively, these data indicate that autophagy functions to maintain germ cell cyst breakdown and primordial follicle assembly by regulating ovarian glycolysis involving Akt signaling in the ovaries of newly-hatched chickens.


Assuntos
Galinhas , Ovário , Animais , Autofagia/fisiologia , Galinhas/metabolismo , Feminino , Células Germinativas/metabolismo , Glicólise , Oócitos , Ovário/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
3.
Cell Commun Signal ; 21(1): 298, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904236

RESUMO

Diabetic vascular complications (DVCs), including macro- and micro- angiopathy, account for a high percentage of mortality in patients with diabetes mellitus (DM). Endothelial dysfunction is the initial and role step for the pathogenesis of DVCs. Hyperglycemia and lipid metabolism disorders contribute to endothelial dysfunction via direct injury of metabolism products, crosstalk between immunity and inflammation, as well as related interaction network. Although physiological and phenotypic differences support their specified changes in different targeted organs, there are still several common mechanisms underlying DVCs. Also, inhibitors of these common mechanisms may decrease the incidence of DVCs effectively. Thus, this review may provide new insights into the possible measures for the secondary prevention of DM. And we discussed the current limitations of those present preventive measures in DVCs research. Video Abstract.


Assuntos
Diabetes Mellitus , Angiopatias Diabéticas , Hiperglicemia , Humanos , Endotélio Vascular/metabolismo , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Hiperglicemia/complicações , Inflamação/complicações , Inflamação/metabolismo
4.
Prev Sci ; 24(1): 50-63, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35939179

RESUMO

Early tobacco smoke exposure (TSE) in utero and/or during the first years after birth poses threats to the development of child executive functioning and self-regulation skills, including inhibitory control. Efforts are still needed to examine under what conditions such effects may occur and thus identify modifiable intervention targets. In addition, a distinction between cool and hot inhibitory control is also important to obtain greater nuance in such links. The cool inhibitory control refers to children's suppression of prepotent automatic responses to a distracting stimulus in solving arbitrary and decontextualized problems, whereas the hot inhibitory control refers to children's control of impulse in motivationally and emotionally high-stake situations. Using data derived from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, we examined the links between early risk of TSE and preschoolers' hot and cool inhibitory control and tested the potential promotive/protective roles of maternal positivity in early mother-child interactions. Results indicate that early risk of TSE was negatively linked to child cool inhibitory control when maternal positivity was low, but this link was nonsignificant when maternal positivity was high (i.e., the protective role of maternal positivity). The link between early risk of TSE and child later hot inhibitory control was not moderated by maternal positivity; instead, early risk of TSE and maternal positivity were negatively and positively associated with child hot inhibitory control above and beyond each other, respectively (i.e., the promotive role of maternal positivity). Accordingly, building a tobacco-free environment during pregnancy and infancy likely yields long-term benefits for child self-regulation development. Improving early mothering may offset the negative link between early TSE and child cool inhibitory control and also facilitate child hot inhibitory control even in the face of early TSE.


Assuntos
Poluição por Fumaça de Tabaco , Feminino , Gravidez , Adolescente , Humanos , Mães , Função Executiva , Desenvolvimento Infantil , Relações Mãe-Filho
5.
Int J Mol Sci ; 24(13)2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37446199

RESUMO

ß-Carbonic anhydrase (ßCA) is very important for plant growth and development, but its function in immunity has also been examined. In this study, we found that the expression level of Solanum lycopersicum ßCA1 (SlßCA1) was significantly upregulated in plants treated with Xanthomonas euvesicatoria 85-10. The protein was localized in the nucleus, cell membrane and chloroplast. Using tomato plants silenced with SlßCA1, we demonstrated that SlßCA1 plays an active role in plant disease resistance. Moreover, we found that the elicitor PopW upregulated the expression of SlßCA1, while the microbe-associated molecular pattern response induced by PopW was inhibited in TRV-SlßCA1. The interaction between PopW and SlßCA1 was confirmed. Here, we found that SlßCA1 was positively regulated during PopW-induced resistance to Xanthomonas euvesicatoria 85-10. These data indicate the importance of SlßCA1 in plant basic immunity and its recognition by the Harpin protein PopW as a new target for elicitor recognition.


Assuntos
Solanum lycopersicum , Xanthomonas , Solanum lycopersicum/genética , Xanthomonas/fisiologia , Proteínas de Bactérias/metabolismo , Imunidade Vegetal/genética , Doenças das Plantas/genética
6.
Stat Med ; 40(29): 6577-6589, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34561895

RESUMO

Performance goals are numerical target values pertaining to effectiveness or safety endpoints in single-arm medical device clinical studies. Typically, performance goals are determined at the planning stage of the investigational study under consideration based on summarized outcome information from existing relevant clinical trials. In recent years, there is a growing interest in leveraging real-world evidence in medical product development. In this article, we introduce a new method for proposing performance goals by leveraging real-world evidence. The method applies entropy balancing to address possible patient dissimilarities between the study's target patient population and existing real-world patients, and can take into account operation differences between clinical studies and real-world clinical practice. An illustrative example is provided to demonstrate how to implement the proposed method for performance goal determination while leveraging real-world evidence.


Assuntos
Objetivos , Projetos de Pesquisa , Humanos
7.
J Cell Mol Med ; 24(23): 13876-13898, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33140562

RESUMO

This research utilized the systematic biological and proteomics strategies to explore the regulatory mechanism of Danshen Yin Modified (DSYM) on atherosclerosis (AS) biological network. The traditional Chinese medicine database and HPLC was used to find the active compounds of DSYM, Pharmmapper database was used to predict potential targets, and OMIM database and GeneCards database were used to collect AS targets. String database was utilized to obtain the other protein of proteomics proteins and the protein-protein interaction (PPI) data of DSYM targets, AS genes, proteomics proteins and other proteins. The Cytoscape 3.7.1 software was utilized to construct and analyse the network. The DAVID database is used to discover the biological processes and signalling pathways that these proteins aggregate. Finally, animal experiments and proteomics analysis were used to further verify the prediction results. The results showed that 140 active compounds, 405 DSYM targets and 590 AS genes were obtained, and 51 differentially expressed proteins were identified in the DSYM-treated ApoE-/- mouse AS model. A total of 4 major networks and a number of their derivative networks were constructed and analysed. The prediction results showed that DSYM can regulate AS-related biological processes and signalling pathways. Animal experiments have also shown that DSYM has a therapeutic effect on ApoE-/-mouse AS model (P < .05). Therefore, this study proposed a new method based on systems biology, proteomics, and experimental pharmacology, and analysed the pharmacological mechanism of DSYM. DSYM may achieve therapeutic effects by regulating AS-related signalling pathways and biological processes found in this research.


Assuntos
Aterosclerose/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Proteoma/efeitos dos fármacos , Proteômica , Biologia de Sistemas , Animais , Apolipoproteínas E/deficiência , Aterosclerose/sangue , Aterosclerose/etiologia , Biomarcadores , Biologia Computacional/métodos , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/ultraestrutura , Perfilação da Expressão Gênica , Ontologia Genética , Imuno-Histoquímica , Medicina Tradicional Chinesa , Camundongos , Camundongos Knockout , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteômica/métodos , Salvia miltiorrhiza , Biologia de Sistemas/métodos
8.
Plant Cell Physiol ; 61(10): 1733-1749, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726442

RESUMO

Lathyrus odoratus (sweet pea) is an ornamental plant with exceptional floral scent, previously used as an experimental organism in the early development of Mendelian genetics. However, its terpene synthases (TPSs), which act as metabolic gatekeepers in the biosynthesis of volatile terpenoids, remain to be characterized. Auto-Headspace Solid-phase Microextraction/Gas chromatography-mass spectrometry analysis of floral volatile terpene constituents from seven sweet pea cultivars identified α-bergamotene, linalool, (-)-α-cubebene, geraniol, ß-caryophyllene and ß-sesquiphellandrene as the dominant compounds. RNA sequencing was performed to profile the transcriptome of L. odoratus flowers. Bioinformatic analysis identified eight TPS genes (acronymed as LoTPS) that were successfully cloned, heterologously expressed and functionally analyzed. LoTPS4 and LoTPS7, belonging to the TPS-b clade, biochemically catalyzed the formation of monoterpenes and sesquiterpenes. LoTPS3 and LoTPS8, placed in the TPS-a clade, also generated monoterpenes and sesquiterpenes, while LoTPS12 belonging to the TPS-g clade showed linalool/nerolidol synthase activity. Notably, biochemical assays of the recombinant LoTPS proteins revealed their catalytic promiscuity, and the enzymatic products were basically consistent with major volatile compounds released from sweet pea flowers. The data from our study lay the foundation for the chemical ecology, molecular genetics and biotechnological improvement of sweet pea and other legumes (Fabaceae).


Assuntos
Alquil e Aril Transferases/metabolismo , Flores/metabolismo , Lathyrus/metabolismo , Terpenos/metabolismo , Alquil e Aril Transferases/genética , Arabidopsis/genética , Cromatografia Gasosa-Espectrometria de Massas , Sequenciamento de Nucleotídeos em Larga Escala , Lathyrus/enzimologia , Lathyrus/genética , Filogenia , Alinhamento de Sequência , Compostos Orgânicos Voláteis/metabolismo
9.
J Exp Bot ; 71(14): 4140-4158, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32275056

RESUMO

Previously, linalool was found to be the most abundant component among the cocktail of volatiles released from flowers of Freesia hybrida. Linalool formation is catalysed by monoterpene synthase TPS1. However, the regulatory network developmentally modulating the expression of the TPS1 gene in Freesia hybrida remains unexplored. In this study, three regulatory genes, FhMYB21L1, FhMYB21L2, and FhMYC2, were screened from 52 candidates. Two MYB transcription factor genes were synchronously expressed with FhTPS1 and could activate its expression significantly when overexpressed, and the binding of FhMYB21L2 to the MYBCORE sites in the FhTPS1 promoter was further confirmed, indicating a direct role in activation. FhMYC2 showed an inverse expression pattern compared with FhTPS1; its expression led to a decreased binding of FhMYB21 to the FhTPS1 promoter to reduce its activation capacity when co-expressed, suggesting a role for an MYB-bHLH complex in the regulation of the FhTPS1 gene. In Arabidopsis, both MYB21 and MYC2 regulators were shown to activate the expression of sesquiterpene synthase genes, and the regulatory roles of AtMYB21 and AtMYC2 in the expression of the linalool synthase gene were also confirmed, implying conserved functions of the MYB-bHLH complex in these two evolutionarily divergent plants. Moreover, the expression ratio between MYB21 and MYC2 orthologues might be a determinant factor in floral linalool emission.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Alquil e Aril Transferases , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Flores/genética , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/metabolismo , Fatores de Transcrição/genética
10.
Med Sci Monit ; 25: 8152-8171, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31666500

RESUMO

Osteoporosis is an important health problem worldwide. Siwu decoction (SWD) and its modification have a good clinical effect on osteoporosis. However, the molecular mechanism of SWD on osteoporosis has not been thoroughly explained. A systematic pharmacological methodology was utilized to predict the active compounds and potential targets of SWD, collect the genes of osteoporosis and the known targets of SWD, and analyze the osteoporosis and SWD's network. Five networks were constructed and analyzed: (1) Osteoporosis genes' protein-protein interaction (PPI) network; (2) Compound-compound target network of SWD; (3) SWD-osteoporosis PPI network; (4) Compound-known target network of SWD; and (5) SWD known target- osteoporosis PPI network. Several osteoporosis and treatment-related targets (eg.,. HSP90AB1, FGFR1, HRAS, GRB2, and PGF), clusters, biological processes, and signaling pathways (e.g., PI3K-Akt signaling pathway, insulin signaling pathway, MAPK signaling pathway and FoxO signaling pathway) were found. The therapeutic effect of SWD on osteoporosis may be achieved by interfering with the biological processes and signaling pathways related to the development of osteoporosis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Osteoporose/tratamento farmacológico , China , Humanos , Fenômenos Farmacológicos , Farmacologia/métodos , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos
11.
Reprod Biol Endocrinol ; 16(1): 27, 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29580250

RESUMO

OBJECTIVE: To assess the effectiveness and safety of omega-3 fatty acid for patients with PCOS. METHODS: In this meta-analysis, data from randomized controlled trials were obtained to assess the effects of omega-3 fatty acid versus placebo or western medicine in women with PCOS. The study's registration number is CRD42017065859. The primary outcomes included the change of homeostatic model assessment (HOMA) of insulin resistance, total cholesterol (TC), triglyceride (TG) and adiponectin. RESULT: Nine trials involving 591 patients were included. Comparing with the control group, omega-3 fatty acid may improve HOMA index (WMD -0.80; 95% CI -0.89, - 0.71; P<0. 00001), decrease TC and TG level [TC: (WMD -9.43; 95% CI -11.90, - 6.95; P<0. 00001); TG: (WMD -29.21; 95% CI -48.08, - 10.34; P = 0. 002)], and increase adiponectin level (WMD 1.34; 95% CI 0.51, 2.17; P = 0. 002). CONCLUSION: Based on current evidence, omega-3 fatty acid may be recommended for the treatment of PCOS with insulin resistance as well as high TC (especially LDL-C) and TG.


Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adiponectina/sangue , Colesterol/sangue , Feminino , Humanos , Resistência à Insulina , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
12.
J Ethnopharmacol ; 323: 117589, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38104875

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.


Assuntos
Aborto Habitual , Fosfatidilinositol 3-Quinases , Camundongos , Animais , Gravidez , Feminino , Humanos , Placenta , Camundongos Endogâmicos DBA , Camundongos Endogâmicos CBA , Aborto Habitual/tratamento farmacológico
13.
J Ethnopharmacol ; 306: 116143, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-36632855

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Natural herbs are gradually gaining recognition for their efficacy and safety in preventing diabetes and improving quality of life. Morus alba L. is a plant widely grown in Asia and is a traditional Chinese herb with a long history of use. Furthermore, several parts of Morus alba L. have been found to have significant health benefits. In particular, mulberry (Morus alba L.) leaves (ML) have been shown in human and animal studies to be promising hypoglycemic agents that can reduce or prevent glucolipid metabolism disorders caused by imbalances in the gut microbiota, inflammation, and oxidative stress and have demonstrated significant improvements in glucose metabolism-related markers, effectively lowering blood glucose, and reducing hyperglycemia-induced target organ damage. AIM OF THE STUDY: This review briefly summarizes the methods for obtaining ML's bioactive components, elaborates on the clinical potential of the relevant components in managing type 2 diabetes mellitus (T2DM), and focuses on the therapeutic mechanisms of gut microbiota, inflammation, oxidative stress, and metabolism, to provide more inspiration and directions for future research in the field of traditional natural plants for the management of T2DM and its complications. MATERIALS AND METHODS: Research on ML and its bioactive components was mainly performed using electronic databases, including PubMed, Google Scholar, and ScienceNet, to ensure the review's quality. In addition, master's and doctoral theses and ancient documents were consulted. RESULTS: In clinical studies, we found that ML could effectively reduce blood glucose, glycated hemoglobin, and homeostasis model assessment of insulin resistance in T2DM patients. Furthermore, many in vitro and in vivo experiments have found that ML is involved in various pathways that regulate glucolipid metabolism and resist diabetes while alleviating liver and kidney damage. CONCLUSIONS: As a potential natural anti-diabetic phytomedicine, an in-depth study of ML can provide new ideas and valuable references for applying traditional Chinese medicine to treat T2DM. While continuously exploring its clinical efficacy and therapeutic mechanism, the extraction method should be optimized to improve the efficacy of the bioactive components. in addition, further research on the dose-response relationship of drugs to determine the effective dose range is required.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Morus , Animais , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicemia/metabolismo , Qualidade de Vida , Extratos Vegetais/farmacologia , Inflamação/tratamento farmacológico , Folhas de Planta/metabolismo
14.
J Oncol ; 2023: 3876342, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153834

RESUMO

Gastric cancer (GC) is the third most lethal and fifth most common cancer in the world. In a variety of cancers, the hexokinase domain component 1 (HKDC1) is carcinogenic. This study was to investigate into how HKDC1 contributes to the development and progression of GC. Three different datasets (GSE103236, GSE13861, and GSE55696) were extracted from the Gene Expression Omnibus (GEO) database and then analyzed using the sva package. The R software was used to identify 411 differentially expressed genes (DEGs) in the pooled dataset. We discovered 326 glycolysis-related genes (glyGenes) in the cancer genome atlas-stomach adenocarcinoma (TCGA-STAD) cohort using gene set enrichment analysis set (GSEA). HKDC1 is one of the most prevalent glyGenes in GC tumor tissues and cells, as seen in the Venn diagram. According to the results of the Cell Count Kit-8 assay, the proliferation of AGS and MKN-45 cells decreased when HKDC1 was knocked down. Lack of HKDC1 in cells enhanced oxygen consumption and decreased glycolytic protein expression while suppressing glucose absorption, lactate production, ATP level, and extracellular acidification ratio. As an oncogene in gastric cancer development, HKDC1 influences cell proliferation and glycolysis.

15.
Biomed Pharmacother ; 157: 113999, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36455455

RESUMO

Ischemic stroke (IS) is one of the leading causes of death and disability. Its pathogenesis is not completely clear, and inflammatory cascade is one of its main pathological processes. The current clinical practice of IS is to restore the blood supply to the ischemic area after IS as soon as possible through thrombolytic therapy to protect the vitality and function of neurons. However, blood reperfusion further accelerates ischemic damage and cause ischemia-reperfusion injury. The pathological process of cerebral ischemia-reperfusion injury involves multiple mechanisms, and the exact mechanism has not been fully elucidated. Pyroptosis, a newly discovered form of inflammatory programmed cell death, plays an important role in the initiation and progression of inflammation. It is a pro-inflammatory programmed death mediated by caspase Caspase-1/4/5/11, which can lead to cell swelling and rupture, release inflammatory factors IL-1ß and IL-18, and induce an inflammatory cascade. Recent studies have shown that pyroptosis and its mediated inflammatory response are important factors in aggravating ischemic brain injury, and inhibition of pyroptosis may alleviate the ischemic brain injury. Furthermore, studies have found that natural plant components may have a regulatory effect on pyroptosis. Therefore, this review not only summarizes the molecular mechanism of pyroptosis and its role in ischemic stroke, but also the role of natural plant components as regulator of pyroptosis, in order to provide reference information on pyroptosis for the treatment of IS in the future.


Assuntos
Lesões Encefálicas , AVC Isquêmico , Traumatismo por Reperfusão , Humanos , AVC Isquêmico/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Caspases/metabolismo , Lesões Encefálicas/metabolismo , Estruturas Vegetais/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
16.
Biomed Pharmacother ; 168: 115544, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37820566

RESUMO

Ferroptosis, as a way of cell death, participates in the body's normal physiological and pathological regulation. Recent studies have shown that ferroptosis may damage glucose-stimulated islets ß Insulin secretion and programmed cell death of T2DM target organs are involved in the pathogenesis of T2DM and its complications. Targeting suppression of ferroptosis with specific inhibitors may provide new therapeutic opportunities for previously untreated T2DM and its target organs. Current studies suggest that natural bioactive compounds, which are abundantly available in drugs, foods, and medicinal plants for the treatment of T2DM and its target organs, have recently received significant attention for their various biological activities and minimal toxicity, and that many natural compounds appear to have a significant role in the regulation of ferroptosis in T2DM and its target organs. Therefore, this review summarized the potential treatment strategies of natural compounds as ferroptosis inhibitors to treat T2DM and its complications, providing potential lead compounds and natural phytochemical molecular nuclei for future drug research and development to intervene in ferroptosis in T2DM.


Assuntos
Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Ferroptose , Humanos , Apoptose , Morte Celular , Diabetes Mellitus Tipo 2/tratamento farmacológico
17.
Phytomedicine ; 112: 154707, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36805483

RESUMO

BACKGROUND: Qimai Feiluoping decoction (QM), a Traditional Chinese Medicine formula, has been included in rehabilitation program for functional disorders of discharged COVID-19 patients. QM has been proved to effectively improve the clinical symptoms and imaging signs of PF in COVID-19 convalescent patients. PURPOSE: This study to explore the pharmacological effect of QM against PF from the perspectives of imaging, pathological staining, and molecular mechanisms, and identify possible active components. METHODS: Micro-CT imaging and immunohistochemical staining were investigated to verify the therapeutic effect of QM in the bleomycin (BLM)-induced PF mouse model. The 4D-label-free proteomics analysis of lung tissues was then conducted to explore the novel mechanisms of QM against PF, which were further validated by a series of experiments. The possible components of QM in plasma and lung tissues were identified with UHPLC/IM-QTOF-MS analysis. RESULTS: The results from micro-CT imaging and pathological staining revealed that QM treatment can inhibit BLM-induced lung injury, extracellular matrix accumulation and TGF-ß expression in the mouse model with PF. The 4D-label-free proteomics analysis demonstrated that the partial subunit proteins of mitochondrial complex I and complex II might be potential targets of QM against PF. Furthermore, QM treatment can inhibit BLM-induced mitochondrial ROS content to promote ATP production and decrease oxidative stress injury in the mouse and cell models of PF, which was mediated by the inhibition of mitochondrial complex I. Finally, a total of 13 protype compounds and 15 metabolites from QM in plasma and lung tissues were identified by UHPLC/IM-QTOF-MS, and liquiritin and isoliquiritigenin from Glycyrrhizae radix et rhizoma could be possible active compounds against PF. CONCLUSION: It concludes that QM treatment could treat PF by inhibiting mitochondrial complex I-mediated mitochondrial oxidated stress injury, which could offer new insights into the pharmacological mechanisms of QM in the clinical application of PF patients.


Assuntos
COVID-19 , Fibrose Pulmonar , Camundongos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Bleomicina/toxicidade , COVID-19/patologia , Pulmão/patologia , Estresse Oxidativo
18.
Front Oncol ; 12: 868164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463357

RESUMO

Background: With advances in high-throughput computational mining techniques, various quantitative predictive models that are based on ultrasound have been developed. However, the lack of reproducibility and interpretability have hampered clinical use. In this study, we aimed at developing and validating an interpretable and simple-to-use US nomogram that is based on quantitative morphometric features for the prediction of breast malignancy. Methods: Successive 917 patients with histologically confirmed breast lesions were included in this retrospective multicentric study and assigned to one training cohort and two external validation cohorts. Morphometric features were extracted from grayscale US images. After feature selection and validation of regression assumptions, a dynamic nomogram with a web-based calculator was developed. The performance of the nomogram was assessed with respect to calibration, discrimination, and clinical usefulness. Results: Through feature selection, three morphometric features were identified as being the most optimal for predicting malignancy, and all regression assumptions of the prediction model were met. Combining all these predictors, the nomogram demonstrated a good discriminative performance in the training cohort and in the two external validation cohorts with AUCs of 0.885, 0.907, and 0.927, respectively. In addition, calibration and decision curves analyses showed good calibration and clinical usefulness. Conclusions: By incorporating US morphometric features, we constructed an interpretable and easy-to-use dynamic nomogram for quantifying the probability of breast malignancy. The developed nomogram has good generalization abilities, which may fit into clinical practice and serve as a potential tool to guide personalized treatment. Our findings show that quantitative morphometric features from different ultrasound machines and systems can be used as imaging surrogate biomarkers for the development of robust and reproducible quantitative ultrasound dynamic models in breast cancer research.

19.
Comput Math Methods Med ; 2022: 8438131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602346

RESUMO

Objective: A case-control study was conducted to explore the clinical value of three-dimensional transvaginal ultrasound in the diagnosis of endometrial receptivity (ER) and ovarian function in patients with infertility. Methods: A total of 308 infertile women treated in our hospital from March 2020 to June 2021 were enrolled as the observation group, and another 300 women of childbearing age who underwent physical examination in the same period were enrolled as the control group. The clinical value of three-dimensional transvaginal ultrasound in ER in patients with infertility was analyzed by comparing the classification of endometrial and subendometrial blood perfusion, endometrial AUC value and Pi value, and subendometrial AUC value and Pi value. According to the number of oocytes obtained, the patients were assigned into the normal response group (182 cases, ≥5 oocytes) and the low response group (126 cases, <5 oocytes). The levels of some hormones, such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and FSH/LH, were measured. Transvaginal ultrasonography was performed to detect ovarian volume (OV), antral follicle count (AFC), and peak flow rate of the ovarian interstitial artery (PSV). The peak of end-diastolic flow velocity (EDV) and other indexes were analyzed. The correlation between FSH level, FSH/LH, and ultrasound indexes was analyzed, and the ROC curve was established to analyze the value of transvaginal Doppler ultrasound in evaluating ovarian reserve function and predicting ovulation. Results: There were significant differences in late proliferation type I and type III, ovulatory type II and type III (P < 0.05). There exhibited no significant difference in late proliferation type II, ovulation stage type I, and implantation window stage type I, type II, and type III (P > 0.05). Regarding the endometrial AUC and Pi values, the endometrial AUC and Pi values in the observation group were lower compared to the control group during late proliferation and ovulation (P < 0.05). There exhibited no significant difference in AUC and Pi (P > 0.05). Regarding the subintimal AUC and Pi values, the subintimal AUC and Pi values in the observation group were higher compared to the control group during late proliferation and ovulation (P < 0.05). There exhibited no significant difference in AUC and Pi during the implantation window (P > 0.05). There exhibited no significant difference in menarche age, age, body mass index, and menstrual cycle between the normal response group and the low response group (P > 0.05). The levels of EDV, OV, AFC, and PSV in the normal response group were higher compared to the low response group (P < 0.01). Compared with the low response group, the levels of FSH and FSH/LH in the normal response group were lower, but the levels of LH and E2 in the normal response group were higher (P < 0.05). The results of correlation analysis of FSH, FSH/LH, and ultrasound parameters between the normal response group and the low response group indicated that FSH was negatively correlated with E2, EDV, OV, AFC, and PSV in 308 infertile women (r = -0.817, -0.846, -0.707, -0.845, -0.911, P < 0.01), but it was positively correlated with FSH/LH (r = 0.714, P < 0.01). The ultrasound parameters of ovarian reserve function in the normal response group and the low response group were compared with the indexes that predicted ovulation. The results of ROC curve analysis indicated that the cutoff values of EDV, OV, AFC, and PSV were 4.141, 3.726, 4.106, and 13.944, respectively, the specificity of each index was higher than 90.00%, and the sensitivity was higher than 80.00% except PSV. Conclusion: Transvaginal ultrasound can not only accurately evaluate the ER of infertile women but also directly observe follicular development and monitor ovulation, which is of high value in evaluating ovarian reserve function and predicting ovulation.


Assuntos
Infertilidade Feminina , Estudos de Casos e Controles , Feminino , Hormônio Foliculoestimulante , Humanos , Infertilidade Feminina/diagnóstico por imagem , Folículo Ovariano/diagnóstico por imagem , Ultrassonografia
20.
Mitochondrial DNA B Resour ; 7(5): 747-749, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528255

RESUMO

In this study, the complete mitochondrial genome (mitogenome) of the Woodland Brown, Lopinga achine Scopoli, 1763 (Nymphalidae: Satyrinae) was determined to be 15,284 bp in size, including 37 typical mitochondrial genes and a control region. The gene content and arrangement of the mitogenome are identical to that of the majority of other sequenced nymphalids. All protein-coding genes (PCGs) are started with the conventional ATN codons, except for cox1 gene which is initiated by atypical CGA(R) codon. Nine PCGs use a typical stop codon of TAA, whereas the remaining PCGs (cox1, cox2, nad4, nad5) end with an incomplete T. The length of rrnL and rrnS are 1333 and 755 bp, respectively, separated by trnV. The phylogenetic tree inferred with Bayesian inference method reveals the phylogenetic relationships among the four tribes of Satyrinae analyzed as ((Satyrini + Melanitini) + (Elymniini + Amathusiini)). The newly sequenced species L. achine was clustered together with other two species of Parargina and formed a sister group with two species of the genus Lethe within Satyrini.

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