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1.
Chem Commun (Camb) ; 60(31): 4226-4229, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38526318

RESUMO

We introduce a straightforward, yet effective strategy to combat the performance decline of proton-exchange membrane fuel cells in low-humidity environments. Our method centers on air-oxidizing carbon supports, significantly improving proton and oxygen transport within the cathode catalyst layer.

2.
Free Radic Biol Med ; 214: 115-128, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331008

RESUMO

Sestrins are metabolic regulators that respond to stress by reducing the levels of reactive oxygen species (ROS) and inhibiting the activity of target of rapamycin complex 1 (mTORC1). Previous research has demonstrated that Sestrin2 mitigates ischemia-reperfusion (IR) injury in the heart, liver, and kidneys. However, its specific role in intestinal ischemia-reperfusion (IIR) injury remains unclear. To elucidate the role of Sestrin2 in IIR injury, we conducted an experimental study using a C57BL/6J mouse model of IIR. We noticed an increase in the levels of Sestrin2 expression and indicators associated with ferroptosis. Our study revealed that manipulating Sestrin2 expression in Caco-2 cells through overexpression or knockdown resulted in a corresponding decrease or increase, respectively, in ferroptosis levels. Furthermore, our investigation revealed that Sestrin2 alleviated ferroptosis caused by IIR injury through the activation of the Keap1/Nrf2 signal pathway. This finding highlights the potential of Sestrin2 as a therapeutic target for alleviating IIR injury. These findings indicated that the modulation of Sestrin2 could be a promising strategy for managing prolonged IIR injury.


Assuntos
Ferroptose , Isquemia Mesentérica , Traumatismo por Reperfusão , Animais , Humanos , Camundongos , Células CACO-2 , Ferroptose/genética , Isquemia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Reperfusão , Traumatismo por Reperfusão/genética , Transdução de Sinais
3.
Biomed Pharmacother ; 172: 116222, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38310653

RESUMO

Alzheimer's disease (AD) is a high-incidence neurodegenerative disorder, characterized by cognitive impairment, memory loss, and psychiatric abnormalities. Ganoderma lucidum is a famous medicinal fungus with a long history of dietary intake, containing various bioactive components, and have been documented to exhibit antioxidant, anti-inflammatory, anti-tumor, anti-aging, and immunomodulatory effects, among others. Recent studies have shown that G. lucidum and its components have promising therapeutic potential against AD from various aspects, which can delay the progression of AD, improve cognitive function and quality of life. The underlying mechanisms mainly include inhibiting tau hyperphosphorylation, inhibiting Aß formation, affecting activated microglia, regulating NF-κB/MAPK signalling pathway, inhibiting neuronal apoptosis, modulating immune system, and inhibiting acetylcholinesterase, etc. This paper systematically reviewed the relevant studies on the therapeutic potential of G. lucidum and its active components for treatment of AD, key points related with the mechanism studies and clinical trials have been discussed, and further perspectives have been proposed. Totally, as a natural medicinal mushroom, G. lucidum has the potential to be developed as effective adjuvant for AD treatment owing to its therapeutic efficacy against multiple pathogenesis of AD. Further mechanical investigation and clinical trials can help unlock the complete potential of G. lucidum as a therapeutic option for AD.


Assuntos
Agaricales , Doença de Alzheimer , Reishi , Doença de Alzheimer/tratamento farmacológico , Acetilcolinesterase , Qualidade de Vida
5.
Cancer Cell ; 41(11): 1927-1944.e9, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37738973

RESUMO

Although polymorphic microbiomes have emerged as hallmarks of cancer, far less is known about the role of the intratumor mycobiome as living microorganisms in cancer progression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomic sequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancer mice models, we find that A. sydowii promotes lung tumor progression via IL-1ß-mediated expansion and activation of MDSCs, resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulation of PD-1+ CD8+ T cells. This is mediated by IL-1ß secretion via ß-glucan/Dectin-1/CARD9 pathway. Analysis of human samples confirms that enriched A. sydowii is associated with immunosuppression and poor patient outcome. Our findings suggest that intratumor mycobiome, albeit at low biomass, promotes lung cancer progression and could be targeted at the strain level to improve patients with LUAD outcome.


Assuntos
Neoplasias Pulmonares , Micobioma , Células Supressoras Mieloides , Humanos , Animais , Camundongos , Neoplasias Pulmonares/genética , Linfócitos T CD8-Positivos , Pulmão
6.
Zhen Ci Yan Jiu ; 48(2): 180-4, 2023 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-36858415

RESUMO

OBJECTIVE: To investigate the effect of moxibustion on the proteins related with apoptosis and nuclear transcription factor kappa B (NF-κB) in hippocampus of diabetic rats with cognitive impairment (CI), so as to explore its mechanism underlying improvement of learning-memory ability. METHODS: Thirty SD rats were randomly divided into normal, model and moxibustion groups (n=10 rats/group). The diabetic model was established by i.p. injection of streptozotocin solution (25 mg·kg-1·d-1), followed by high-fat diet raising for 4 weeks, and the CI model was confirmed by Morris water maze test. The rats in the moxibustion group were given moxibustion at "Shenting" (GV24), "Baihui" (GV20) and "Dazhui" (GV14) for 20 min each time, the treatment was conducted 6 times a week for 4 weeks. The learning-memory ability was detected by Morris water maze test, the random blood glucose of rats was measured by glucometer and test strips. The protein and mRNA expression levels of Bcl-2, Bax, Caspase-3 and NF-κB p65 in hippocampus were detected by Western blot and quantitative real-time PCR, separately. RESULTS: After modeling, the random blood glucose, escape latency, and the expression levels of Bax, Caspase-3 and NF-κB p65 proteins and mRNAs in the model group were significantly increased, while the expression levels of Bcl-2 protein and mRNA were decreased (P<0.001,P<0.01, P<0.05) in comparison with the normal group. Following the treatment, the modeling induced increase of blood glucose, escape latency, and the expression levels of Bax, Caspase-3 and NF-κB p65 proteins and mRNAs, as well as decrease of Bcl-2 protein and mRNA expression levels were reversed (P<0.05, P<0.01, P<0.001). CONCLUSION: Moxibustion can improve learning-memory ability in diabetic rats with cognitive impairment, which may be related to its function in regulating the expression levels of hippocampal Bcl-2, Bax, Caspase-3 and NF-κB.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Experimental , Moxibustão , Animais , Ratos , Ratos Sprague-Dawley , Caspase 3 , NF-kappa B , Glicemia , Proteína X Associada a bcl-2 , Proteínas Proto-Oncogênicas c-bcl-2 , Apoptose , Hipocampo
7.
Foods ; 12(5)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36900432

RESUMO

To significantly improve the polysaccharide production of Nostoc flagelliforme, a total of 12 chemicals were evaluated for their effects on polysaccharide accumulation. The results showed that salicylic acid and jasmonic acid increased the accumulation of the polysaccharides in N. flagelliforme significantly, by more than 20%. Three polysaccharides, namely control-capsule polysaccharide, salicylic acid-capsule polysaccharide, and jasmonic acid-capsule polysaccharide, were extracted and purified from N. flagelliforme under normal, salicylic acid, and jasmonic acid culture conditions, respectively. Their chemical compositions slightly differed regarding the total sugar and uronic acid contents, with average molecular weights of 2.06 × 103, 2.16 × 103 and 2.04 × 103 kDa, respectively. They presented similar Fourier transform infrared spectra and no significant difference in antioxidant activity. It was revealed that the salicylic acid and jasmonic acid significantly increased the level of nitric oxide. By investigating the effects of the exogenous nitric oxide scavenger and nitric oxide donor on the nitric oxide levels and polysaccharide yield of N. flagelliforme, the results showed that the increase in intracellular nitric oxide levels might be an important factor promoting the accumulation of polysaccharides. These findings provide a theoretical foundation for enhancing the yield of secondary metabolites by regulating the intracellular nitric oxide levels.

8.
J Ethnopharmacol ; 310: 116401, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-36965543

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the Podocarpus species belong to the Podocarpaceae family and are largely distributed in the southern hemisphere. Beside the commercially and ecologically valuable, plants of the Podocarpus species are also used in traditional medicines in some countries for treating asthma, fever, venereal diseases, eye diseases, etc. AIM OF THE STUDY: In recent decades, the identities and pharmacological activities of phytochemicals extracted from Podocarpus plants have been widely studied. However, there have been no comprehensive and systematic reviews. This article aims to systematically review the latest research on the putative mechanisms underlying pharmacological actions of phytochemicals from the Podocarpus species, as well as to lay a foundation for promoting the development of plant resources from this genus, further drug research, and product development. MATERIALS AND METHODS: A comprehensive search of PubMed, Google Scholar, Web of Science, Elsevier and CNKI databases was conducted using the keywords "Podocarpus", "traditional usage", "phytochemistry", "pharmacology", "nagilactone", etc. Related papers published among July 1964 to February 2023 were collected to summarize the research progress. All plant names were determined through the "The Plant List" (http://www.theplantlist.org/). RESULTS: To date, 262 chemical constituents have been isolated and identified from 26 Podocarpus plants; among these, norditerpene bilactone is the main pharmacologically active component. Norditerpene bilactones are reported to have anti-cancer, anti-inflammatory, antioxidant, antibacterial, anti-tyrosinase, neuroprotective, anti-plasmodial, anti-mutagenic, and anti-atherosclerotic properties as well as other pharmacological activities, which support its traditional uses. CONCLUSION: Extensive studies on phytochemistry and pharmacology of Podocarpus species lead to discovery of a series of hopeful leading compounds with unique chemical structure, especially the nor- and bis-norditerpenoid dilactones with four isoprene units. These compounds have been proved to possess various pharmacological activities. This review will provide a reference for further research and promote the idea of combining modern research with traditional medicinal applications of Podocarpus plants.


Assuntos
Plantas Medicinais , Etnofarmacologia , Fitoterapia , Medicina Tradicional , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/química
9.
Org Biomol Chem ; 21(9): 1903-1909, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36757292

RESUMO

The C2 sulfonylation of quinoxalinones via a metal-free oxidative S-O cross-coupling strategy for synthesizing 2-sulfonyloxylated quinoxalines is established. It effectively solved the long-standing problems in the C2 transformation of quinoxalinones via a metal-free oxidative O-S coupling strategy. Compared with the traditional C2 transformed quinoxalinones-C2 chlorination method, this protocol is mild, facile, and environmentally friendly and exhibits good atomic economy and excellent functional group tolerance. Moreover, the utility of this methodology and the sulfonyloxyl handles was demonstrated through the synthesis of 2-substituted quinoxaline-based bioactive molecules.

10.
J Ethnopharmacol ; 305: 116113, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36581165

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Medical abortions using mifepristone and misoprostol have been approved in many countries for early pregnancy loss. Despite its high success rate, this medication regimen can result in incomplete abortion, which is responsible for endometrial damage, prolonged uterine bleeding, abdominal pain, etc. Buxue Yimu Pills (BYP) is a famous Chinese medicine prescription that is widely used in the field of gynecology and obstetrics for treating patients with postpartum complications. However, the therapeutic effect and mechanism of BYP remain to be explored. AIM OF THE STUDY: This study aimed to clarify the therapeutic effect and mechanism of action of BYP in postpartum complications using mifepristone and misoprostol-induced incomplete abortion in rats. MATERIALS AND METHODS: Experimental medical-induced incomplete abortion model rats were constructed using mifepristone and misoprostol, and further treated with saline or BYP by intragastric administration. Detailed information regarding the changes in mRNA and protein levels in the uterine tissues of rats regulated by BYP was illustrated by RNA sequencing (RNA-seq) analysis and quantitative proteomics analysis. The differentially expressed genes and proteins were further subjected to Gene Ontology (GO) and pathway enrichment analyses and further verified using quantitative Real-time PCR (qRT-PCR) analysis and western blot assay. RESULTS: BYP administration markedly alleviated the increase in serum prostaglandin F2α (PGF2α) and expression of PGF2α receptor (PGF2αR) in uterine tissues and inhibited the decrease in serum chorionic gonadotrophin (CG). Compared with the model group, 674 genes were upregulated and 344 genes were downregulated by BYP administration; 108 proteins were upregulated and 48 proteins were downregulated by BYP administration. qRT-PCR analysis of the uterine tissues showed that BYP treatment reversed the variation tendency of genes, including Mmp7, Mmp14, Timp2, Col6a4, Jak2, Wnt7a, and Mylk compared with the model group. Western blot analysis showed that BYP administration affected PKCδ, Collagen VI, MMP7, TIMP2, MLCK, and p-MLC protein levels. CONCLUSION: BYP administration facilitated uterine recovery in medical-induced incomplete abortion rats, and this therapeutic effect involved various targets and biological processes, including the TIMP2/MMP7 and MLCK/p-MLC signaling pathways, etc.


Assuntos
Aborto Incompleto , Aborto Induzido , Aborto Espontâneo , Misoprostol , Animais , Feminino , Gravidez , Ratos , Dinoprosta , Metaloproteinase 7 da Matriz , Mifepristona/farmacologia , Mifepristona/uso terapêutico , Misoprostol/farmacologia , Misoprostol/uso terapêutico , Proteômica , Transcriptoma
11.
Food Sci Nutr ; 10(11): 3876-3889, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36348812

RESUMO

In recent years, biologically active ingredients derived from natural plants or functional foods have raised considerable interests for its anti-obesity effect. Quinoa (Chenopodium quinoa Willd.) is a traditional staple food in the Andean regions of Peru which contains a variety of bioactive components. This study aimed to investigate the potential therapeutic effect of total saponins extracted from quinoa bran (TSQ) on obese rats and explore whether the underlying mechanism is related to intestinal microbiota. Results showed that TSQ could decrease the body weight gain and visceral fat accumulation in the obese rats. Moreover, trends in ameliorating insulin resistance and improved glucose tolerance were observed. Indeed, Pearson's correlations analysis revealed that the variation in gut microbial composition was highly correlated to insulin resistance, IL-6, and LPS levels. Collectively, these results suggest that the prevention of obesity and inflammation by TSQ may be mediated by the modulation of gut microbial composition.

12.
MedComm (2020) ; 3(3): e152, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35978854

RESUMO

Lung cancer is the leading cause of cancer death worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Metastasis is the major cause of poor prognosis and mortality for lung cancer patients, which urgently needs great efforts to be further explored. Herein, glutathione peroxidase 8 (GPX8) was identified as a novel potential pro-metastatic gene in LUAD metastatic mice models from GEO database. GPX8 was highly expressed in tumor tissues, predicting poor prognosis in LUAD patients. Knockdown of GPX8 inhibited LUAD metastasis in vitro and in vivo, while it did not obviously affect tumor growth. Knockdown of GPX8 decreased the levels of p-FAK and p-Paxillin and disturbed the distribution of focal adhesion. Furthermore, GPX8 was overexpressed in cancer-associated fibroblast (CAF) and associated with CAF infiltration in tumor microenvironment of lung cancer. GPX8 silence on fibroblasts suppressed lung cancer cell migration in the coculture system. BRD2 and RRD4 were the potential transcriptionally regulators for GPX8. Bromodomain extra-terminal inhibitor JQ1 downregulated GPX8 expression and suppressed lung cancer cell migration. Our findings indicate that highly expressed GPX8 in lung cancer cells and fibroblasts functions as a pro-metastatic factor in lung cancer. JQ1 is identified as a potential inhibitor against GPX8-mediated lung cancer metastasis.

13.
Molecules ; 27(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35684437

RESUMO

Bacterial cellulose (BC) is well known as a high-performance dietary fiber. This study investigates the adsorption capacity of BC for cholesterol, sodium cholate, unsaturated oil, and heavy metal ions in vitro. Further, a hyperlipidemia mouse model was constructed to investigate the effects of BC on lipid metabolism, antioxidant levels, and intestinal microflora. The results showed that the maximum adsorption capacities of BC for cholesterol, sodium cholate, Pb2+ and Cr6+ were 11.910, 16.149, 238.337, 1.525 and 1.809 mg/g, respectively. Additionally, BC reduced the blood lipid levels, regulated the peroxide levels, and ameliorated the liver injury in hyperlipidemia mice. Analysis of the intestinal flora revealed that BC improved the bacterial community of intestinal microflora in hyperlipidemia mice. It was found that the abundance of Bacteroidetes was increased, while the abundance of Firmicutes and Proteobacteria was decreased at the phylum level. In addition, increased abundance of Lactobacillus and decreased abundance of Lachnospiraceae and Prevotellaceae were obtained at the genus level. These changes were supposed to be beneficial to the activities of intestinal microflora. To conclude, the findings prove the role of BC in improving lipid metabolism in hyperlipidemia mice and provide a theoretical basis for the utilization of BC in functional food.


Assuntos
Hiperlipidemias , Metabolismo dos Lipídeos , Animais , Bactérias , Bacteroidetes , Celulose/farmacologia , Colesterol , Hiperlipidemias/tratamento farmacológico , Camundongos , Colato de Sódio
14.
Acta Pharm Sin B ; 12(3): 1240-1253, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35530150

RESUMO

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

15.
Small ; 18(26): e2201838, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35618445

RESUMO

Nanostructured carbon materials with high porosity and desired chemical functionalities are of immense interest because of their wide application potentials in catalysis, environment, and energy storage. Herein, a top-down templating strategy is presented for the facile synthesis of functional porous carbons, based on the direct carbonization of diverse organic precursors with commercially available metal oxide powders. During the carbonization, the metal oxide powders can evolve into nanoparticles that serve as in situ templates to introduce nanopores in carbons. The porosity and heteroatom doping of the prepared carbon materials can be engineered by varying the organic precursors and/or the metal oxides. It is further demonstrated that the top-down templating strategy is applicable to prepare carbon-based single-atom catalysts with iron-nitrogen sites, which exhibit a high power density of 545 mW cm-2 in a H2 -air proton exchange membrane fuel cell.


Assuntos
Carbono , Nanoporos , Óxidos , Porosidade , Pós
16.
Biochem Pharmacol ; 197: 114940, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35120895

RESUMO

Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints induced by interferon-γ (IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. In this study, MY was identified to inhibit IFN-γ-induced PD-L1 expression in human lung cancer cells. It also reduced the expression of IDO1 and the production of kynurenine which is the product catalyzed by IDO1, while didn't show obvious effect on the expression of major histocompatibility complex-I (MHC-I), a crucial molecule for antigen presentation. In addition, the function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line overexpressing PD-1. MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. Together, our research revealed a new mechanism of MY mediated anti-tumor activity and highlighted the potential implications of MY in tumor immunotherapy.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Interferon gama/farmacologia , Neoplasias Pulmonares/metabolismo , Células A549 , Antígeno B7-H1/biossíntese , Antígeno B7-H1/genética , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/fisiologia , Células HCT116 , Células HEK293 , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/biossíntese , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Células Jurkat , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologia
17.
J Clin Med ; 11(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35054086

RESUMO

BACKGROUND: Previous studies have demonstrated that long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. This study aims to investigate the function and mechanism of MEG3 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explores the use of MEG3 in skull defects bone repairing. METHODS: Endogenous expression of MEG3 during BMSCs osteogenic differentiation was detected by quantitative real-time polymerase chain reaction (qPCR). MEG3 was knockdown in BMSCs by lentiviral transduction. The proliferation, osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs were assessed by Cell Counting Kit-8 (CCK-8) assay, qPCR, alizarin red and alkaline phosphatase staining. Western blot was used to detect ß-catenin expression in MEG3 knockdown BMSCs. Dickkopf 1 (DKK1) was used to block wnt/ß-catenin pathway. The osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs after wnt/ß-catenin inhibition were assessed by qPCR, alizarin red and alkaline phosphatase staining. MEG3 knockdown BMSCs scaffold with PHMG were implanted in a critical-sized skull defects of rat model. Micro-computed tomography(micro-CT), hematoxylin and eosin staining and immunohistochemistry were performed to evaluate the bone repairing. RESULTS: Endogenous expression of MEG3 was increased during osteogenic differentiation of BMSCs. Downregulation of MEG3 could promote osteogenic differentiation of BMSCs in vitro. Notably, a further mechanism study revealed that MEG3 knockdown could activate Wnt/ß-catenin signaling pathway in BMSCs. Wnt/ß-catenin inhibition would impair MEG3-induced osteogenic differentiation of BMSCs. By using poly (3-hydroxybutyrate-co-3-hydroxyhexanoate, PHBHHx)-mesoporous bioactive glass (PHMG) scaffold with MEG3 knockdown BMSCs, we found that downregulation of MEG3 in BMSCs could accelerate bone repairing in a critical-sized skull defects rat model. CONCLUSIONS: Our study reveals the important role of MEG3 during osteogenic differentiation and bone regeneration. Thus, MEG3 engineered BMSCs may be effective potential therapeutic targets for skull defects.

18.
Int J Biol Macromol ; 202: 224-233, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35038468

RESUMO

Two capsular polysaccharides (WL-CPS-1 and GLU-CPS-1) purified from Nostoc flagelliforme under normal and mixotrophic culture conditions were used to investigate the hypolipidemic activity and effect on intestinal flora in C57BL/6J mice respectively. Their molecular weight and monosaccharide composition have been determined in previous studies. They both improved the lipid level by affecting the expression of lipid metabolism genes. They down-regulated the TNF-α and IL-1ß levels in serum and up-regulated the activity of antioxidant enzymes in liver thus decreased the atherosclerosis index and MDA content. They up-regulated the short chain fatty acids (SCFAs) synthesis. They decreased the abundance of pathogenic bacteria and increased the abundance of probiotics positively correlated with SCFAs. Compared with WL-CPS-1, GLU-CPS-1 exhibited higher in vivo activity and enriched Odoribacter and Alloprevotella correlating with the gene expression of lipid metabolism, suggesting that the bioactivity of polysaccharides could be regulated by culture conditions. These findings contributed to application of N. flagelliforme polysaccharides with higher activity in hypolipidemia by adjusting culture conditions.


Assuntos
Microbioma Gastrointestinal , Hiperlipidemias , Animais , Hiperlipidemias/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Nostoc , Polissacarídeos/farmacologia
19.
J Ethnopharmacol ; 289: 115002, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35065249

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Buxue Yimu Pills (BYP) is a well-known traditional Chinese medicine prescription which is clinical used in gynecology and obstetrics, and is documented to exhibit therapeutic potential to defective angiogenesis and impaired blood flow. AIM OF THE STUDY: This study aimed to investigate the effects and biological mechanisms of BYP in improvement of defective angiogenesis and impaired blood flow which represent major health issues associated with various diseases including postpartum or abortion complications. MATERIALS AND METHODS: In this study, VEGFR tyrosine kinase inhibitor II (VRI) was used to establish blood vessel loss model in Tg(fli-1a:EGFP) zebrafish embryos. Blood vessel loss was calculated, and quantitative real-time PCR (qRT-PCR) assay was performed to detect gene expression. Mifepristone and misoprostol were applied to construct a medical-induced incomplete abortion rats model. Whole blood viscosity indexes, hemorheology and coagulation function of the rats were investigated. Immunohistochemistry analysis was used for evaluation of the uterine tissues. RESULTS: BYP treatment significantly promoted angiogenesis as evidenced by the restoration of VRI-induced blood vessel loss in zebrafish embryos. BYP treatment effectively reversed VRI-induced down-regulation of the VEGFRs (Kdr, Kdrl and Flt1). Furthermore, BYP administration significantly suppressed the increase of whole blood viscosity indexes, and remarkably shortened the levels of prothrombin time and activated partial thromboplastin time in the medical-induced incomplete abortion rats, indicating the improvement of hemorheology and coagulation function. Immunohistochemistry analysis suggested that BYP administration increased the expression level of VEGFR2 in uterus tissues of the rats. CONCLUSION: BYP exhibits therapeutic effects in promoting angiogenesis and blood circulation, and mitigating blood stasis, supporting its clinical application for postpartum or abortion complications.


Assuntos
Indutores da Angiogênese/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neovascularização Patológica/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Aborto Incompleto/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Gravidez , Ratos , Ratos Sprague-Dawley , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
20.
Food Chem ; 367: 130697, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34365248

RESUMO

Metabolomics is an important branch of systems biology, which can detect changes in the body's metabolism before and after the intervention of functional foods, identify effective metabolites, and predict the interventional effects and the mechanism. This review summarizes the latest research outcomes regarding interventional effects of functional foods on metabolic diseases via metabolomics analysis. Since metabolomics approaches are powerful strategies for revealing the changes in bioactive compounds of functional foods during processing and storage, we also discussed the effects of these parameters on functional food metabolites using metabolomics approaches. To date, a number of endogenous metabolites related to the metabolic diseases after functional foods intervention have been discovered. Unfortunately, the mechanisms of metabolic disease-related molecules are still unclear and require further studies. The combination of metabolomics with other omics technologies could further promote its ability to fully understand the precise biological processes of functional food intervention on metabolic diseases.


Assuntos
Alimento Funcional , Doenças Metabólicas , Humanos , Metabolômica
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