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1.
Artigo em Inglês | MEDLINE | ID: mdl-34725557

RESUMO

Though widely used in the treatment of coronary heart disease (CHD), the mechanism of traditional Chinese medicine (TCM) is still unclear because of its complex prescription rules. This study prospectively collected 715 prescriptions of TCM for the treatment of CHD. The characteristics of TCM in prescriptions were described and analyzed, and the rules of prescriptions were analyzed by using association rules. Frequency statistics showed that the high-frequency herbs with a frequency of more than 60% were Gan-cao, Huang-qi, Dang-gui, Chuan-xiong, Yan-hu-suo, and San-qi. The high-frequency herb combinations were summarized by using association rules. By using the method of the "Top N groups" to excavate the empirical prescriptions, the basic prescriptions for treating CHD were summarized. We named the intersection herbs of the basic prescriptions and the high frequency herbs as the core herbal prescription. To explore the possible mechanisms underlying the anti-CHD effect of the core herbal prescription, the bioactive components of core herbal prescription and their targets were screened out by using network pharmacology. Molecular docking was performed between the bioactive components and core targets. A total of 28 potential active ingredients and 5 core targets were identified for the treatment of CHD with core herbal prescription. The enrichment analysis results indicated that the mechanism of action mainly involved neuroactive ligand-receptor interaction and calcium signaling pathway. The commonly used herbal pairs for CHD with qi deficiency and blood stasis syndrome were Huang-qi and Dang-gui. The mechanism of action of common herbal pairs was also studied by network pharmacology. This study summarized the prescription rule of TCM in the treatment of CHD and may provide a new idea for the treatment of CHD.

2.
J Cell Mol Med ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34750955

RESUMO

Melanoma is one of the most aggressive and life-threatening skin cancers, and in this research, we aimed to explore the functional role of circular RNA VANGL1 (circVANGL1) in melanoma progression. The expression levels of circVANGL1 were observed to be significantly increased in clinical melanoma tissues and cell lines. Moreover, circVANGL1 knockdown suppressed, while circVANGL1 overexpression promoted the proliferation, migration and invasion abilities of melanoma cells. Further investigations confirmed the direct binding relation between circVANGL1 and miR-150-5p in melanoma, and restoration of miR-150-5p blocked the effects of circVANGL1 overexpression in melanoma cells. We further found that circVANGL1 was up-regulated by TGF-ß treatment, and the enhanced EMT of TGF-ß-treated melanoma cells was blocked by circVANGL1 knockdown. In conclusion, these results indicated that circVANGL1 might serve as a promising therapeutic target for melanoma.

3.
Ann Transl Med ; 9(20): 1532, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790738

RESUMO

Background: This study uses the tandem mass tag (TMT)-labeled quantitative proteomic analysis to identify potential therapeutic protein targets of a Chinese prescription called Tang-Yi-Ping (TYP) for the treatment of impaired glucose tolerance (IGT) in rats. Methods: A total of 31 specific-pathogen free (SPF) male Wistar rats were used in our study. Ten were randomly selected as a control group, while 21 received a high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish IGT subjects. After eliminating 2 rats without successful modeling, 19 were randomly divided into a TYP group (n=9) and IGT model group (n=10). The TYP group was given a TYP decoction of 6.36 mg/kg-1/d-1. After 8 weeks of intervention, blood glucose-related indicators were measured, and cell morphology was observed by hematoxylin and eosin (HE) staining. TMT-labeled proteomic analysis was applied to detect the differentially expressed proteins (DEPs) in the pancreases of the three groups. The intersection of the DEPs in both the TYP group and IGT model group underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify the related biological functions and signal transduction pathways. Finally, western blot (WB) was used to verify the TMT proteomics results. Results: TYP can effectively reduce blood glucose and improve islet morphology in IGT rats. We identified a total of 16 potential therapeutic protein targets of TYP, 4 of which were upregulated, while 12 were downregulated, including Rbp4, Fam3b, Flot2, etc. [fold change (FC) >1.1, P<0.05]. The significant signal transduction pathways included arginine and proline metabolism, glyceride metabolism, glycerophospholipid metabolism, mTOR, Wnt, and insulin signaling pathways. Conclusions: For anti-IGT therapy, we found TYP regulates 16 protein targets, multiple biological functions, and multiple signal transduction pathways. This study thus makes a significant contribution to identifying new potential therapeutic targets for treating IGT.

4.
Sci Rep ; 11(1): 20849, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675276

RESUMO

This study systematically explored the underlying mechanism of Rhizoma Coptidis against type 2 diabetes mellitus (T2DM) by using network pharmacology and molecular docking and experimental validation. We retrieved and screened active compounds of Rhizoma Coptidis and corresponding T2DM-related targets across multiple databases. PPI networks of the genes were constructed using STRING, and the core targets were screened via topological analysis. GO and KEGG enrichment analyses were performed by using DAVID. Finally, molecular docking and experimental studies were performed after bioinformatic analysis for verification. There were 14 active compounds and 19 core targets of Rhizoma Coptidis-T2DM, of which quercetin was identified as the main compound and IL6, VEGFA and TNF were the most significant core targets. GO and KEGG enrichment analyses showed that Rhizoma Coptidis ameliorated T2DM by regulating multiple biological processes and pathways. Docking studies indicated that IL6, VEGFA and TNF could stably bind with all active compounds of Rhizoma Coptidis. The results of our experiments revealed that Rhizoma Coptidis could inhibit the expression of IL6 and TNFα and enhance islet cell viability. This study suggests anti-inflammatory therapeutic effects of Rhizoma Coptidis on T2DM, thereby providing a scientific basis and new insight for further research on the antidiabetic effect of Rhizoma Coptidis.

5.
Signal Transduct Target Ther ; 6(1): 368, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645784

RESUMO

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Memória Imunológica , Modelos Imunológicos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , COVID-19/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X
6.
Medicine (Baltimore) ; 100(42): e27569, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34678897

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is 1 of the most serious complications of diabetes mellitus and the leading cause of end-stage renal disease in the world. Huangkui capsule, extracted from Abelmoschus manihot (L.) medic (AM), has been widely used to treat DN. However, there is no consensus on the efficacy of Huangkui capsule for DN. This study aims to perform meta-analysis to systematically review the efficacy and safety of Huangkui capsule. METHODS: The following 9 electronic databases will be comprehensively searched: PubMed, web of science, MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang data, and Chinese BioMedicine Literature Database. The retrieval time is from their inception to May 2021. According to the inclusion and exclusion criteria, 2 reviewers independently completed the study selection, data extraction, risk of bias assessment, and data synthesis. Review Manager Version 5.3 software will be used to conduct meta-analysis. RESULTS: This study provides a high-quality synthesis to assess the efficacy of Huangkui capsule for treating diabetic nephropathy. CONCLUSION: The result of this systematic review will provide objective evidence-based basis to judge the effectiveness and safety of Huangkui capsule on diabetic nephropathy.


Assuntos
Abelmoschus , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Extratos Vegetais/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
7.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641272

RESUMO

High hydrostatic pressure (HHP) treatment is a non-thermal processing technology, which is widely used in the food processing field at present. In this study, the effects of HHP treatment (100~500 MPa for 5 min) on the physicochemical properties, texture parameters, and volatile flavor compounds of oysters were investigated. The results showed that HHP treatment increased the water content while reducing the crude protein and ash content of the oyster. Texture parameters showed that HHP treatment improved the hardness, springiness, chewiness, and cohesiveness of oysters, compared with the control group. In addition, the saturated fatty acid (SFA) content was slightly increased after HHP treatment, while the difference in monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) content was not significant. Furthermore, HHP increased hexenoic aldehyde, 2,4-heptadienal, 1-octene-3-ol, and 2-octen-1-ol and decreased the contents of 3. 6-nadien-1-ol, 3-octanone, and 2-undecanone, suggesting that HHP might inhibit the fishiness of oyster and showed a positive effect on its flavor. Based on the above results, HHP improved the edible qualities such as texture properties and volatile flavor of oysters. This meets the requirements of consumers on the edible quality of seafood and provides new ideas for the development of seafood.


Assuntos
Ácidos Graxos/análise , Ostreidae/química , Compostos Orgânicos Voláteis/isolamento & purificação , Animais , Manipulação de Alimentos , Qualidade dos Alimentos , Pressão Hidrostática
8.
J Food Sci ; 86(10): 4316-4329, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34519066

RESUMO

Squid are commercial marine species that have high nutritional value. This study aimed to compare the influences of vacuum frying and atmospheric frying on the physicochemical properties and protein oxidation of three main parts (ring, tentacle, and fin) of the squid Loligo chinensis. The results showed that the vacuum-fried (VF) group had lower moisture and total fat contents and looser microstructures than the atmospheric-fried (AF) group. The amino acid contents and molecular weight revealed that the proteins were well preserved during vacuum frying. Carbonyl content in the VF ring, tentacle, and fin samples increased nearly 2.53-, 1.54-, and 2.56-fold, respectively, compared to that in the corresponding fresh group, but these increases were lower than those of the corresponding AF group. In addition, the secondary structures of proteins revealed a slight decrease in the α-helix and ß-turn contents and a significant increase in the ß-sheet content during vacuum frying. Therefore, vacuum frying can be used as an efficient processing method to conserve the high nutritive quality of the product. PRACTICAL APPLICATION: As a developing alternative technology to prepare healthier fried products, vacuum frying has been the focus of recent researches. Vacuum frying produced squid products that had lower TBARS values, carbonyl contents, and Schiff base substances compared to atmospheric frying. And the protein secondary structures of the vacuum-fried group retained better. The study proved that vacuum frying could be an effective method with the advantages of high protein stability and product quality.


Assuntos
Culinária , Decapodiformes , Proteínas na Dieta , Qualidade dos Alimentos , Loligo , Animais , Decapodiformes/química , Proteínas na Dieta/metabolismo , Análise de Alimentos , Loligo/química , Oxirredução , Vácuo
9.
Diabetes Metab Syndr Obes ; 14: 3795-3807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511953

RESUMO

Purpose: To analyze the effect and potential therapeutic targets of liraglutide in type 2 diabetes through miRNA expression profiling. Methods: Ten of 30 SPF Wistar rats, males at 4 weeks old, were randomly selected as the control group and given conventional feed, the other rats adopted high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish a T2DM model. One unsuccessful rat was excluded, and the remaining rats were randomized to the model and the liraglutide group. Liraglutide group was subcutaneously injected with liraglutide 0.11 mg/kg for 8 weeks. The biochemical indicators and staining HE were detected. The expression of miRNA in pancreatic tissue was detected by miRNA sequencing. The intersection of miRNA difference was used to predict the target gene, then functional enrichment was performed to identify its possible biological functions and signal transduction paths. Finally, qRT-PCR was used to verify the results. Results: Compared to the model group, the level of fasting blood glucose (FBG), glucagon and insulin resistance index (HOMA-IR) in the liraglutide group were significantly decreased, fasting insulin (FINS) and insulin sensitivity index (ISI) were increased. Nine differential miRNAs (miR-135a-5p, miR-144-5p, miR-21-3p, miR-215, miR-451-5p, miR-486, miR-122-5p, miR-181d-5p and miR-345-5p) were identified at the intersection through two miRNA sequencing. A total of 3359 related target gene predictions were obtained. GO and pathway analyses demonstrated that differentially expressed genes were closely related to cell proliferation, angiogenesis, and proteolysis. Significant signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway. Conclusion: Liraglutide could improve islet function by regulating nine miRNAs, and the related signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway. Our study provided the basis and direction for further exploring the molecular mechanism of liraglutide on T2DM.

10.
J Ethnopharmacol ; 281: 114495, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34364968

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Allium macrostemon Bunge. is an edible Chinese herb traditionally used for the treatment of thoracic pain, stenocardia, heart asthma and diarrhea. Although its biological potential has been extensively proven such as antioxidant activity, antiplatelet aggregation, vasodilation and antidepressant-like activity, there are no reports in the literature regarding its pharmacological analgesic activity. AIM OF THE STUDY: The study was carried out to examine the anti-nociceptive activity of the crude extract of A. macrostemon bulbs and interpret its likely molecular target. MATERIALS AND METHODS: The bulbs of A. macrostemon were gathered, dried-up, and extracted with water (AMWD). AMWD was subjected to activity testing, using chemical-induced (acetic acid and formalin test) and heat-induced (hot plate) pain models. To evaluate the likely mechanistic strategy involved in the analgesic effect of AMWD, whole-cell patch clamp recordings were conducted in acutely dissociated dorsal root ganglion (DRG) neurons and human embryonic kidney 293T (HEK293T) cells expressing pain-related receptors. Electrophysiological methods were employed to detect the action potentials of DRG neurons and potential targets of A. macrostemon. RESULTS: AMWD showed significant palliative effect in all heat and chemical induced pain assays. Moreover, AMWD significantly reduces the excitability of dorsal root ganglion neurons by reducing the firing frequency of action potentials. Further analysis revealed that voltage-gated sodium channel Nav1.7 is the potential target of A. macrostemon for its analgesic activity. CONCLUSION: This study has brought new scientific evidence of preclinical efficacy of A. macrostemon as an anti-nociceptive agent. Apparently, these effects are involved with the inhibition of the voltage-sensitive Nav1.7 channel contributing to the reduction of peripheral neuronal excitability. Our present study justifies the folkloric usage of A. macrostemon as a remedy for several pain states. Furthermore, A. macrostemon is a good resource for the development of analgesic drugs targeting Nav1.7 channel.

11.
J Sci Food Agric ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34402073

RESUMO

BACKGROUND: Acerola cherry is a famous functional fruit containing plentiful antioxidants and other nutrients. However, studies on the variations among nutrients during the ripening process of acerola fruit are scare. RESULTS: Comparative metabolomic and transcriptomic analyses were performed and identified 31 331 unigenes and 1896 annotated metabolite features in acerola cherry fruit. K Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that several antioxidant and nutrient-related metabolic pathways, such as the flavonoids, vitamins, carotenoids, amino acids, and fatty acids metabolic pathways, were significantly changed during the ripening process. The metabolites related to the vitamin, carotenoid, and fatty acid metabolic pathways were downregulated during the ripening process. Several flavonoid biosynthesis-related genes (including dihydroflavonol 4-reductase, chalcone synthase, flavanone 3-hydroxylase, and anthocyanidin synthase), were significantly upregulated, suggesting their essential functions in the accumulation of flavonoids in mature fruit. CONCLUSION: Most of the vitamin and carotenoid metabolism-related metabolites significantly accumulated in immature fruit, suggesting that immature acerola fruit is a good material for the extraction of vitamins and carotenoids. For macronutrients, most of the amino acids accumulated in mature fruit and most of the fatty acids greatly accumulated in immature fruit. Our data revealed the differential accumulation of antioxidants and nutrients during the ripening process of acerola cherry fruit. © 2021 Society of Chemical Industry.

12.
Front Bioeng Biotechnol ; 9: 723490, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368109

RESUMO

Immunotherapy has emerged as a promising strategy for cancer treatment, in which durable immune responses were generated in patients with malignant tumors. In the past decade, biomaterials have played vital roles as smart drug delivery systems for cancer immunotherapy to achieve both enhanced therapeutic benefits and reduced side effects. Hydrogels as one of the most biocompatible and versatile biomaterials have been widely applied in localized drug delivery systems due to their unique properties, such as loadable, implantable, injectable, degradable and stimulus responsible. Herein, we have briefly summarized the recent advances on hydrogel-by-design delivery systems including the design of hydrogels and their applications for delivering of immunomodulatory molecules (e.g., cytokine, adjuvant, checkpoint inhibitor, antigen), immune cells and environmental regulatory substances in cancer immunotherapy. We have also discussed the challenges and future perspectives of hydrogels in the development of cancer immunotherapy for precision medicine at the end.

13.
Materials (Basel) ; 14(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34443195

RESUMO

Cell-penetrating peptides (CPPs), as non-viral gene delivery vectors, are considered with lower immunogenic response, and safer and higher gene capacity than viral systems. In our previous study, a CPP peptide called RALA (arginine rich) presented desirable transfection efficacy and owns a potential clinic use. It is believed that histidine could enhance the endosome escaping ability of CPPs, yet RALA peptide contains only one histidine in each chain. In order to develop novel superior CPPs, by using RALA as a model, we designed a series of peptides named HALA (increased histidine ratio). Both plasmid DNA (pDNA) and siRNA transfection results on three cell lines revealed that the transfection efficacy is better when histidine replacements were on the C-terminal instead of on the N-terminal, and two histidine replacements are superior to three. By investigating the mechanism of endocytosis of the pDNA nanocomplexes, we discovered that there were multiple pathways that led to the process and caveolae played the main role. During the screening, we discovered a novel peptide-HALA2 of high cellular transfection efficacy, which may act as an exciting gene delivery vector for gene therapy. Our findings also bring new insights on the development of novel robust CPPs.

14.
Mol Med Rep ; 23(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33846800

RESUMO

Tryptophan 2,3­dioxygenase (TDO2) is a key rate­limiting enzyme in the kynurenine pathway and promotes tumor growth and escape from immune surveillance in different types of cancer. The present study aimed to investigate whether TDO2 serves a role in the development of ovarian cancer. Reverse transcription­quantitative PCR and western blotting were used to detect the expression of TDO2 in different cell lines. The effects of TDO2 overexpression, TDO2 knockdown and TDO2 inhibitor on ovarian cancer cell proliferation, migration and invasion were determined by MTS, colony formation and Transwell assays. The expression of TDO2 in ovarian cancer tissues, normal ovarian tissues and fallopian tube tissues were analyzed using the gene expression data from The Cancer Genome Atlas and Genotype­Tissue Expression project. Immune cell infiltration in cancer tissues was evaluated using the single sample gene set enrichment analysis algorithm. The present study found that RasV12­mediated oncogenic transformation was accompanied by the upregulation of TDO2. In addition, it was demonstrated that TDO2 was upregulated in ovarian cancer tissues compared with normal ovarian tissues. TDO2 overexpression promoted proliferation, migration and invasion of ovarian cancer cells, whereas TDO2 knockdown repressed these phenotypes. Treatment with LM10, a TDO2 inhibitor, also repressed the proliferation, migration and invasion of ovarian cancer cells. The present study indicated that TDO2 can be used as a new target for the treatment of ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Ovarianas/metabolismo , Triptofano Oxigenase/metabolismo , Triptofano Oxigenase/farmacologia , Carcinogênese , Carcinoma Epitelial do Ovário/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Cinurenina , Neoplasias Ovarianas/genética , Triptofano Oxigenase/genética , Regulação para Cima
15.
Signal Transduct Target Ther ; 6(1): 107, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658482

RESUMO

Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system. In contrast, interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids. To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity, we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids. Among patients receiving glucocorticoids, early interferon therapy was associated with earlier hospital discharge (adjusted HR 1.68, 95% CI 1.19-2.37) and symptom relief (adjusted HR 1.48, 95% CI 1.06-2.08), while these associations were insignificant among glucocorticoids nonusers. Early interferon therapy was also associated with lower prevalence of prolonged viral shedding (adjusted OR 0.24, 95% CI 0.10-0.57) only among glucocorticoids users. Additionally, these associations were glucocorticoid cumulative dose- and timing-dependent. These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.


Assuntos
COVID-19/tratamento farmacológico , Dexametasona/administração & dosagem , Interferons/administração & dosagem , SARS-CoV-2 , Adulto , COVID-19/diagnóstico , COVID-19/mortalidade , Teste de Ácido Nucleico para COVID-19 , Dexametasona/agonistas , Sinergismo Farmacológico , Feminino , Humanos , Interferons/agonistas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Aging (Albany NY) ; 12(23): 23996-24008, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33221744

RESUMO

Although circular RNAs (circRNAs) are known to play key roles in non-alcoholic fatty liver disease, much about their targets and mechanisms remains unknown. We therefore investigated the actions and mechanisms of hsa_circ_0048179 in an in vitro model of NAFLD. HepG2 cells were exposed to oleate/palmitate (2:1 ratio) for 24 h to induce intracellular lipid accumulation. Using CCK-8 assays, flow cytometry, fluorescence microscopy, western blotting, RT-qPCR, and Oil red O staining, we found that oleate/palmitate treatment reduced cell viability while increasing apoptosis and lipid accumulation in HepG2 cells. Levels of the antioxidant enzyme GPX4 were decreased in oleate/palmitate-treated HepG2 cells, and there were corresponding increases in reactive oxygen species and damage to mitochondrial cristae. Levels of hsa_circ_0048179 expression were also suppressed by oleate/palmitate treatment, and GPX4 levels were markedly increased in HepG2 cells following transfection with hsa_circ_0048179. Analysis of its mechanism revealed that hsa_circ_0048179 upregulated GPX4 levels by acting as a competitive "sponge" of miR-188-3p and that hsa_circ_0048179 attenuated oleate/palmitate-induced lipid accumulation in HepG2 cells by sponging miR-188-3p. Collectively, our findings suggest that hsa_circ_0048179 may play a key role in the pathogenesis of steatosis and may thus be a useful target for drug development.


Assuntos
Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ácido Oleico/toxicidade , Palmitatos/toxicidade , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , RNA Circular/metabolismo , Apoptose/efeitos dos fármacos , Regulação da Expressão Gênica , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , RNA Circular/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
17.
Am J Transl Res ; 12(10): 6027-6042, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194012

RESUMO

OBJECTIVES: Cervical cancer is the second leading cause of cancer death in women, which is closely related to persistent infection with high-risk Human papillomavirus (HPV). Therefore, it is important to develop new adjuvants for HPV vaccines. This research aimed to establish two new adjuvants which can enhance the immune effect of vaccines. MATERIALS AND METHODS: C57BL/6 mice were divided into 5 groups and immunized by intramuscular injection of plasmid once every 2 weeks, three times in all. The growth and metastasis of tumors in mice was observed by in vivo imaging system (IVIS). Then, the mice were sacrificed and the pathological changes of organs were observed. In addition, the lymphocyte suspension was used for CLT killing test. IFN-γ level and the number of splenocytes which secrete IFN-γ were detected. Additionally, the specific antibody level of HPV16/18 E6 E7 L1 L2 was also detected. RESULTS: The constructed nucleic acid vaccines had no significant effect on both the physiological and biochemical indexes, while it significantly increased the survival period and survival rate of mice. Flt3L and GM-CSF enhanced the immune effect of HPV16/18 vaccine via increasing the specific antibodies and IFN-γ cytokines. CONCLUSIONS: These data suggested that Flt3L and GM-CSF enhanced the anti-tumor effect of vaccines via increasing immune response. Thereby, our findings may hope to provide new perspective for the treatment of cervical cancer.

18.
Medicine (Baltimore) ; 99(40): e22564, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019468

RESUMO

BACKGROUND: At present, the prevalence of type 2 diabetes mellitus (T2DM) has become a major public health issue throughout the world, especially in developing countries. Notably, traditional Chinese patent medicines (TCPMs) are of great significance in the treatment of T2DM combined with conventional Western medicine therapy. However, there is a lack of comparison among all the current common TCPMs for treating T2DM. Therefore, this study intends to explore the efficacy and safety of different TCPMs against T2DM through the Bayesian network meta-analysis (NMA). METHODS: We will conduct a comprehensive and systematic search for randomized controlled trials (RCTs) of TCPM for the treatment of T2DM in both Chinese and English databases published till August 2020. Two researchers will be responsible for screening eligible literature, extracting data, and assessing the risk of bias of included studies independently. Then, pairwise meta-analyses and Bayesian network meta-analyses will be conducted to assess all available evidence. In the end, data will be analyzed using STATA15.0 and WinBUGS1.4.3 software. CONCLUSION: This study will compare the efficacy and safety of different TCPMs against T2DM in detail. Our findings will provide a reliable evidence for selecting clinical treatment program and guideline development of T2DM.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Medicina Tradicional Chinesa/métodos , Medicamentos sem Prescrição/efeitos adversos , Teorema de Bayes , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Metanálise em Rede , Medicamentos sem Prescrição/uso terapêutico , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
19.
Exp Cell Res ; 396(1): 112277, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32918895

RESUMO

Human papillomavirus (HPV) infection and viral protein expression cause several epigenetic alterations that lead to cervical carcinogenesis. Our previous study identified that upregulated lysine-specific demethylase (KDM) 2 A promotes cervical cancer progression by inhibiting mircoRNA (miR)-132 function. However, the roles of histone methylation modifiers in HPV-related cervical cancer remain unclear. In the present study, changes in the expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E6/E7 in CaSki cells. The dysregulated expression of KDM5A was identified, and its function in cervical cancer was investigated in vitro and in vivo. E7 oncoprotein-induced upregulation of KDM5A promoted cervical cancer cell proliferation and invasiveness in vitro and in vivo, which was correlated with poor prognosis in patients with cervical cancer. KDM5A was found to physically interact with the promoter region of miR-424-5p, and to suppress its expression by removing the tri- and di-methyl groups from H3K4 at the miR-424-5p locus. Furthermore, miR-424-5p repressed cancer cell proliferation and invasiveness by targeting suppressor of zeste 12 (Suz12). KDM5A upregulation promoted cervical cancer progression by repressing miR-424-5p, which resulted in a decrease in Suz12. Therefore, KDM5A functions as a tumor activator in cervical cancer pathogenesis by binding to the miR-424-5p promoter and inhibiting its tumor-suppressive function. These results indicate a function for KDM5A in cervical cancer progression and suggest its candidacy as a novel prognostic biomarker and target for the clinical management of this malignancy.


Assuntos
Papillomavirus Humano 16/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/genética , Proteína 2 de Ligação ao Retinoblastoma/genética , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/genética , Adulto , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Feminino , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Papillomavirus Humano 16/metabolismo , Papillomavirus Humano 16/patogenicidade , Humanos , Metástase Linfática , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Carga Tumoral , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Food Sci ; 85(11): 3679-3689, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32990386

RESUMO

Sea urchin Mesocentrotus nudus, Glyptocidaris crenularis, and Strongylocentrotus intermedius gonad protein isolates (mnGPIs, gcGPIs, and siGPIs) were extracted by isoelectric solubilization/precipitation (ISP) from the defatted gonads, and their functional properties were compared. Sodium dodecyl sulfate polyacrylamide gel electrophoresis results showed the similar protein pattern between each protein isolate and defatted gonad, indicating the high efficiency of ISP processing for protein recovery. Amino acid profileconfirmed that the mnGPIs and siGPIs could be potential sources of essential amino acid in nature. As regard to functional properties, mnGPIs showed higher water- and oil- holding capacities followed bysiGPIs and gcGPIs and all protein isolates presented great foaming property. As for emulsifying activity index (EAI), mnGPIs, gcGPIs, and siGPIs showed the minimum solubility and EAI at pH 5, 3, and 4, respectively, and behaved a pH-dependent manner. The gcGPIs revealed the highest EAI from pH 6 to 8 among the samples. In addition, circular dichroism showed increased content of ß-sheet at the expense of α-helix and ß-turn, suggesting the structure denaturation of the protein isolates. Indeed, no statistical difference was observed between secondary structure of mnGPIs and siGPIs. Moreover, ISP processing increased free sulfhydryl content of sea urchin protein isolates, but no difference was observed among the samples. Furthermore, siGPIs revealed the highest amount of total sulfhydryl and disulfide bonds, whereas both defatted gonads and protein isolates from G. crenularis presented the maximum surface hydrophobicity. These results suggest that gonad protein isolates from three species of sea urchin possess various functionalities and therefore can be potentially applied in food system. PRACTICAL APPLICATION: Sea urchin M. nudus, G. crenularis, and S. intermedius gonads are edible, whereas the functional properties of protein isolates from sea urchin gonad remain unknown. In this case, the extraction and comparison of three species of sea urchin gonad protein isolates will not only confirm functional properties but also screen food ingredients with suitable functions. In this study, functionalities of protein isolates derived from M. nudus, G. crenularis, and S. intermedius gonads would provide potential application in bakery food and meat products or as emulsifier candidates in food system.


Assuntos
Gônadas/química , Proteínas/química , Ouriços-do-Mar/química , Animais , Ouriços-do-Mar/classificação , Strongylocentrotus/química
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