Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 127
Filtrar
1.
J Nanobiotechnology ; 19(1): 309, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627291

RESUMO

BACKGROUND: Skin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds. METHODS: In the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine and burn wounds in mice. RESULTS: Our results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis. CONCLUSIONS: Based on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy.

2.
J Nanobiotechnology ; 19(1): 304, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600530

RESUMO

BACKGROUND: Although the treatments of skin wounds have greatly improved with the increase in therapeutic methods and agents, available interventions still cannot meet the current clinical needs. Therefore, the development of new pro-regenerative therapies remains urgent. Owing to their unique characteristics, both nanomaterials and peptides have provided novel clues for the development of pro-regenerative agents, however, more efforts were still be awaited and anticipated. RESULTS: In the current research, Hollow polydopamine (HPDA) nanoparticles were synthesized and HPDA nanoparticles loading with RL-QN15 (HPDAlR) that was an amphibian-derived peptide with obvious prohealing activities were prepared successfully. The characterization, biodistribution and clearance of both HPDA nanoparticles and HPDAlR were evaluated, the loading efficiency of HPDA against RL-QN15 and the slow-releasing rate of RL-QN15 from HPDAlR were also determined. Our results showed that both HPDA nanoparticles and HPDAlR exerted no obvious toxicity against keratinocyte, macrophage and mice, and HPDA nanoparticles showed no prohealing potency in vivo and in vitro. Interestingly, HPDAlR significantly enhanced the ability of RL-QN15 to accelerate the healing of scratch of keratinocytes and selectively modulate the release of healing-involved cytokines from macrophages. More importantly, in comparison with RL-QN15, by evaluating on animal models of full-thickness injured skin wounds in mice and oral ulcers in rats, HPDAlR showed significant increasing in the pro-regenerative potency of 50 and 10 times, respectively. Moreover, HPDAlR also enhanced the prohealing efficiency of peptide RL-QN15 against skin scald in mice and full-thickness injured wounds in swine. CONCLUSIONS: HPDA obviously enhanced the pro-regenerative potency of RL-QN15 in vitro and in vivo, hence HPDAlR exhibited great potential in the development of therapeutics for skin wound healing.

3.
Biomed Pharmacother ; 143: 112153, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34507117

RESUMO

Exposure to the toxic herbicide paraquat (PQ) can lead to the active absorption and enrichment of alveolar epithelial cells, resulting in pulmonary fibrosis and respiratory failure. At present, no effective clinical treatment is available. Notably, however, patients infected with human acquired immunodeficiency virus (HIV) (with T lymphocyte deficiency) do not show pulmonary fibrosis after PQ poisoning, suggesting that T lymphocytes may be involved in the occurrence and pathological development of lung fibers following PQ exposure, although relevant studies remain limited. Here, we found that the degree of pulmonary fibrosis induced by intragastric administration of PQ in congenital immunodeficiency BALB/C (nu/nu) nude (T lymphocyte loss) mice was lower than that in normal mice. However, pulmonary fibrosis was aggravated after transplantation of BALB/C (nu/nu) T lymphocytes into congenital immunodeficiency mice. This study is the first to report on the involvement of T lymphocytes in the occurrence and pathological development of lung fibers induced by PQ exposure. Thus, T cells may be an important cellular target for the clinical treatment of pulmonary fibrosis caused by PQ.

4.
Life Sci ; 280: 119698, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34111466

RESUMO

AIMS: The purpose of this study was to investigate the effects of miR-431-5p on hepatocyte apoptosis in AIH. MATERIALS AND METHODS: We used intraperitoneal injection of S100 to establish AIH mouse model and injected AAV into tail vein on day 14 of modeling to regulate miR-431-5p expression. The expression of ALT, AST, IgG and apoptosis-related proteins Bax, Bcl-2 and cleaved caspase 3 were measured in each group. Cellular experiments were performed using miR-431-5p mimics or inhibitors to transfect LPS-stimulated AML12 cells, and apoptosis was verified using Western blot and Hoechst 33342/PI Double Staining. The target of miR-431-5p, KLF15, was screened using databases and verified by the luciferase reporter assay. The relationship between KLF15 and p53 was verified by si-KLF15 and PFTß (a p53-specific inhibitor). KEY FINDINGS: Here, we observed that the increase in the level of miR-431-5p was accompanied by a decrease in the expression of Krüppel-like zinc finger transcription factor 15 (KLF15). In addition, the deletion of miR-431-5p significantly reduced hepatocyte apoptosis in AIH mice induced by liver S100 and apoptosis of AML12 cells induced by LPS stimulation, accompanied by decreased expression of Bax and cleaved caspase-3 as well as increased expression of Bcl-2. Moreover, KLF15 was the direct and functional target of miR-431-5p. Furthermore, miR-431-5p negatively regulated the expression of KLF15, and KLF15 deletion partially abolished the inhibitory effect of miR-431-5p deletion on apoptosis by activating p53 signaling. SIGNIFICANCE: In summary, miR-431-5p may be a potential therapeutic target for AIH.


Assuntos
Apoptose , Hepatite Autoimune/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fígado/patologia , MicroRNAs/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Regulação para Baixo , Hepatite Autoimune/etiologia , Hepatite Autoimune/patologia , Fatores de Transcrição Kruppel-Like/genética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , Proteínas S100/efeitos adversos , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Regulação para Cima
7.
Eur J Pharmacol ; 901: 174072, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33823184

RESUMO

Glucagon-like peptide-2 (GLP-2) is secreted from enteroendocrine L-type cells of the gut and also released from preproglucagonergic (PPG) neurons in the nucleus tractus solitarius (NTS) and adjacent medial reticular nucleus of the brain stem. The neurons in the NTS express GLP-2, and the neurons send extensive projections to the hypothalamus. Recent studies show that the intracerebroventricular administration of GLP-2 significantly suppresses food intake in animals and some evidence suggest that the melanocortin receptor-4 (MC4-R) signaling in the hypothalamus is required for intracerebroventricular GLP-2-mediated inhibition of feeding. There is proopiomelanocortin (POMC) positive neurons expressing MC4-R in the NTS. Suppression of MC4-R expressing neurons in the brain stem inhibits gastric emptying. In this study, we tested the effects of NTS GLP-2R activation and blockade on feeding behavior and evaluated the endogenous melanocortin system's role in the NTS in mediating effects of GLP-2 on feeding behavior in fed and fasted rats. Our results demonstrated that microinjection of GLP-2 into the NTS suppressed food intake in fasted-refeeding rats but did not affect food intake in free-feeding rats, and this inhibition was blocked by pretreatment of either Exendin (9-39) or SHU 9119, suggesting the GLP-2 system in the NTS exerts an inhibitory action on food intake. MC4-R mediates this action in the NTS.


Assuntos
Depressores do Apetite/farmacologia , Peptídeo 2 Semelhante ao Glucagon/farmacologia , Receptor Tipo 4 de Melanocortina/efeitos dos fármacos , Núcleo Solitário , Animais , Ingestão de Alimentos/efeitos dos fármacos , Jejum , Peptídeo 2 Semelhante ao Glucagon/administração & dosagem , Peptídeo 2 Semelhante ao Glucagon/antagonistas & inibidores , Masculino , Hormônios Estimuladores de Melanócitos/farmacologia , Microinjeções , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley
8.
Aging (Albany NY) ; 13(3): 3866-3885, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33461166

RESUMO

Long non-coding RNAs (lncRNA) play a vital role in colorectal cancer (CRC) progression. To investigate the role of long intergenic non-coding RNA LINC00485 in CRC, we performed in vitro functional experiments. LoVo tumor-bearing and liver metastasis mice were used as in vivo models. We found that LINC00485 expression was significantly lower in CRC tissues and cancer cells than in paired normal samples and human normal colonic epithelial cells. Lower expression of LINC00485 predicted poor prognosis in CRC patients. LINC00485 knockdown promoted the proliferation, migration, and invasion of FHC cells, while LINC00485 overexpression weakened these abilities of LoVo cells. MicroRNA miR-581 was the downstream target of LINC00485, which was downregulated in CRC samples and cancer cells compared to normal tissues and normal colonic epithelial cells. MiR-581 overexpression induced proliferation, migration, and invasion of FHC cells, while miR-581 antagomir treatment produced opposite results. MiR-581 directly targeted the 3'UTR of EDEM1 and inhibited its expression and induction of epithelial-mesenchymal transition of CRC. In mouse models, LINC00485 knockdown or down-regulation of miR-581 significantly repressed CRC cell growth and prevented CRC liver metastasis. Overall, LINC00485 suppressed CRC tumorigenesis and progression by targeting the miR-581/EDEM1 axis. LINC00485 may be a potential therapeutic target for CRC.


Assuntos
Carcinoma/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Membrana/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Carcinoma/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Transplante de Neoplasias
9.
Transbound Emerg Dis ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417745

RESUMO

Infectious hematopoietic necrosis virus (IHNV) is a major fish viral pathogen causing acute clinical disease and death in a variety of salmonids. IHNV isolates have been classified into five major genogroups according to the phylogenetic analysis of partial G gene fragments or the complete G gene sequence: U, M, E, L and J. Genogroup U strains have been reported in North America and Japan prior to 1982, and genogroup J is the only genogroup that has been reported in China. Here, one of IHNV strain (BjLL) was isolated from a local farm in China and were characterized in this study. The homogenate tissues of infected fry induced IHNV-positive cytopathic effects in epithelioma papulosum cyprinid (EPC) cells that were confirmed by RT-PCR and sequencing. The complete genome sequence of BjLL comprised 11,129 nucleotides, which had been submitted to GenBank (accession no. MF509592). By the sequence comparison and phylogenetic analysis for the G gene sequence of BjLL with 51 reference sequences in GenBank, we confirmed that this Chinese isolate belonged to genogroup U. Furthermore, virus exposure experiments with juvenile rainbow trout were conducted to assess the virulence and pathogenicity of BjLL. Compared with GS-2014 of genogroup J, BjLL was an obviously less virulent strain that could result in lower mortality. Besides, typical clinical symptoms and pathological damages could be seen in fish following infection of BjLL. The present study is the first report of genogroup U IHNV infection in China and will provide essential information for future studies on pathogenesis of IHNV BjLL and development of efficient control strategies.

10.
Biomed Pharmacother ; 136: 111258, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33482615

RESUMO

Although the application potential of amphibian skin-derived active peptides in alleviating ultraviolet B (UVB)-induced damage has attracted increasing attention, research remains in its infancy. In this study, a new peptide (OM-GL15, GLLSGHYGRASPVAC) was identified from the skin of the green odorous frog (Odorrana margaretae). Results showed that OM-GL15 scavenged free radicals (2,2'-diazo-bis-3-ethylbenzothiazoline-6-sulfonic acid and 1,1-diphenyl-2-trinitrophenylhydrazine) and reduced Fe3+ to Fe2+. Moreover, topical administration of OM-GL15 significantly alleviated UVB-induced skin photodamage in mice. Exploration of the underlying mechanisms further showed that OM-GL15 exerted antioxidant potency. Specifically, the peptide reduced the levels of lipid peroxidation and malondialdehyde and protected epidermal cells from UVB-induced apoptosis by inhibiting DNA damage via down-regulation of p53, caspase-3, caspase-9, and Bax and up-regulation of Bcl-2. Our results highlight the potential application of amphibian skin-derived peptides in protection against UVB-induced photodamage and provide a novel peptide candidate for the development of anti-photodamage agents.


Assuntos
Proteínas de Anfíbios/farmacologia , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Ranidae , Queimadura Solar/prevenção & controle , Proteínas de Anfíbios/isolamento & purificação , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Epiderme/metabolismo , Epiderme/patologia , Epiderme/efeitos da radiação , Feminino , Sequestradores de Radicais Livres/isolamento & purificação , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Ranidae/metabolismo , Queimadura Solar/metabolismo , Queimadura Solar/patologia , Proteína Supressora de Tumor p53/metabolismo , Raios Ultravioleta
11.
Biochem Biophys Res Commun ; 534: 442-449, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33248693

RESUMO

Ischemic stroke is a severe threat to human health due to its high recurrence, mortality, and disability rates. As such, how to prevent and treat ischemic stroke effectively has become a research hotspot in recent years. Here, we identified a novel peptide, named HsTx2 (AGKKERAGSRRTKIVMLKCIREHGH, 2 861.855 Da), derived from the scorpion Heterometrus spinifer, which showed obvious anti-apoplectic effects in rats with ischemic stroke. Results further demonstrated that HsTx2 significantly reduced formation of infarct area and improved behavioral abnormalities in ischemic stroke rats. These protective effects were likely exerted via activation of the mitogen-activated protein kinase (MAPK) signaling pathway, i.e., up-regulation of phosphorylated ERK1/2 in both rat cerebral cortex and activated microglia (AM); up-regulation of phosphorylated p38 (p-p38) in the cerebral cortex; and inhibition of phosphorylated JNK and p-p38 levels in the AM. In conclusion, this study highlights HsTx2 as a potential neuroprotective agent for stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Venenos de Escorpião/uso terapêutico , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Venenos de Escorpião/química , Venenos de Escorpião/isolamento & purificação , Escorpiões/química
12.
Physiol Behav ; 229: 113253, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33220330

RESUMO

Glucagon-like peptide 2 (GLP-2), a member of Glucagon peptide family involved in regulating energy metabolism, can be produced and secreted by preproglucagonergic (PPG) neurons in the brain. GLP-2 reduces food intake but at which brain sites GLP-2 exerts its feeding-suppress effects are still unclear. In this study, we used the stereological microinjection technique and behavioral test to examine the functions of locally delivered GLP-2 into DMH on feeding behavior. We compared effects of different concentration of GLP-2 on the food intake behavior in free-feeding rats and fasted-refeeding rats. We found that GLP-2 inhibited food intake in fasted rats after a short-term intervention in a dose-dependent manner. Importantly, the effects of locally delivered GLP-2 can be blocked by specific GLP-1 receptor antagonist Exendin(9-39), but not the melanocortin-4 receptor antagonist SHU9119, indicating the involvement of specificity of GLP-2 signaling in regulating the feeding behavior. Taken together, our data revealed that GLP-2 peptide pharmacologically inhibited food intake in DMH and this effect could be blocked functionally by Exendin(9-39).


Assuntos
Núcleo Hipotalâmico Dorsomedial , Peptídeo 2 Semelhante ao Glucagon , Animais , Núcleo Hipotalâmico Dorsomedial/metabolismo , Ingestão de Alimentos , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
13.
Neurol Sci ; 42(6): 2397-2409, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33057978

RESUMO

Stroke-associated infection (SAI) is a major medical complication in acute ischemic stroke patients (AIS) treated with endovascular therapy (EVT). Three hundred thirty-three consecutive patients with AIS caused by a large vessel occlusion in the anterior circulation who received EVT (142 (42.6%) of them were given IV tPA as bridging therapy) and 337 AIS patients who received IV tPA only (non-EVT) were enrolled in the study and evaluated to determine the association of inflammatory factors on admission with SAI. Among the 333 AIS patients undergoing EVT, SAI occurred in 219 (65.8%) patients. Patients with SAI had higher baseline National Institutes of Health Stroke Scale (NIHSS) total scores, white blood cell (WBC) and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without SAI (P < 0.05). The multivariable logistic regression analyses showed that older age in addition to higher diastolic blood pressure (DBP), NIHSS score, fasting blood glucose, WBC and neutrophil counts, NLR, and PLR were significantly associated with SAI (P < 0.05). However, these associations were not revealed in 337 non-EVT AIS patients. Furthermore, based on the inflammatory markers, we developed a nomogram that provided the opportunity for more accurate predictions (compared with conventional factors) and appeared a better prognostic tool for SAI according to the decision curve analysis. In summary, if proven externally valid, our nomogram that included WBC count, NLR, and PLR may be a useful tool for SAI prediction in clinical practice.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/terapia , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
14.
Pathol Res Pract ; 217: 153268, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33246290

RESUMO

BACKGROUND: A growing number of studies have shown that long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of tumors. In this study, we explored the function and molecular mechanism of lncRNA SPINT1-AS1 in breast cancer progression. METHODS: A total of 30 patients and 25 healthy controls were enrolled to detect the expression of SPINT1-AS1 in the serum by RT-qPCR. CCK-8 assay, clone formation assay, EdU assay, Transwell assay, Flow cytometry for apoptosis assay and wound healing assays were used to explore the effects of SPINT1-AS1 on the proliferation and migration of breast cancer cells. Bioinformatics analysis were used to enrich the downstream target genes and related pathways of miRNAs interacting with SPINT1-AS1, construct a competitive endogenous RNA (ceRNA) network diagram. RESULTS: SPINT1-AS1 is up-regulated in the serum of breast cancer patients and breast cancer cell lines. The proliferation and migration ability of breast cancer cells were decreased significantly after SPINT1-AS1 knockdown, and it may inhibit its expression by sponging miR-let-7a/b/i-5p, thereby promoting breast cancer progression. CONCLUSIONS: SPINT1-AS1 can promote the proliferation and migration of breast cancer cells by regulating miR-let-7a/b/i-5p, suggesting that it may be an important regulator of breast cancer progression.

15.
Front Immunol ; 11: 585254, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304349

RESUMO

Mast cells play pivotal roles in the pathogenesis of influenza A virus (IAV) infections. Defective viral particles (DPs) often arise during IAV replication, which can interfere with the replication of infectious viruses and stimulate the antiviral response of host cells. Therefore, DPs are expected to have immune-protective functions in clinic. However, the potent immunogenicity and effectiveness of DPs arising in mast cells during IAV replication have not been reported. In the present study, we showed that DPs generated in the human mastocytoma cell line HMC-1 following H1N1 infection were safe to mice after vaccination. Compared with lung adenocarcinoma cells, A549, DPs generated in infected mast cells had much better immunostimulatory activity, enhancing both humoral and cellular immunity of hosts. Notably, they could significantly increase the expression of immune-associated cytokines, especially the IFN-γ. Due to the robust immunogenicity, thus DPs generated in infected mast cells could stimulate the robust protective immune reaction effectively to fight against lethal IAV re-challenge after vaccination, which result in the high survival, decreased lung injury as well as inhibition of viral replication and inflammatory response in lungs. This study is the first to illustrate and explore the safety, immunogenicity, and effectiveness of DPs arising in mast cells against influenza as favorable potential vaccination. The results provide insight into the advances of new prophylactic strategies to fight influenza by focusing on DPs generated in mast cells.


Assuntos
Vírus Defeituosos/imunologia , Vacinas contra Influenza/imunologia , Mastócitos/virologia , Infecções por Orthomyxoviridae/imunologia , Vírion/imunologia , Animais , Linhagem Celular , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Camundongos , Infecções por Orthomyxoviridae/prevenção & controle
16.
Pharmgenomics Pers Med ; 13: 563-570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154659

RESUMO

Background: Paraoxonases (PONs) are a family of orphan enzymes with multiple functions, including anti-inflammatory, antioxidative, antiatherogenic activities. Studies have suggested that genetic variations in PON1 and PON2 are associated with ischemic stroke (IS) risk; however, the conclusion remains unclear in the Chinese population. Methods: To investigate the susceptibility of genetic variations in PON1 and PON2 to risk of IS and its subtypes, this case-control study was carried out on a Chinese population comprising 300 IS patients and 300 healthy controls. Genotypes of six genetic variations in PON1 and PON2 were identified with an improved multiplex ligase detection-reaction technique. Results: PON1 rs662 was associated with increased risk of IS (CT vs. TT - ORadjusted 1.79, 95% CI 1.08-2.97; p=0.025). Stratified analysis for patients by sex revealed that the significant association of PON1 rs662 with IS risk was maintained in the male cohort (CT vs. TT - ORadjusted 2.59, 95% CI 1.29-5.21 [p=0.009]; CT/CC vs. TT - ORadjusted 2.03, 95% CI 1.05-3.93 [p=0.036]), but not in the female cohort. Analysis according to IS subtype revealed that PON1 rs662 genetic variation was an increased risk in the subcohort of patients with large-artery atherosclerosis (CT/CC vs. TT - ORadjusted 2.31, 95% CI 1.09-4.91; p=0.029), but not in patients with other types of IS. Conclusion: This study suggested that PON1 rs662 presented a potential risk of IS, especially for males, and this association was more obvious for large-artery atherosclerosis.

17.
Aging (Albany NY) ; 12(21): 21638-21659, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159022

RESUMO

N6-methyladenosine (m6A) RNA methylation is the most prevalent modification of messenger RNAs (mRNAs) and catalyzed by a multicomponent methyltransferase complex (MTC), among which methyltransferase-like 3 (METTL3) and METTL14 are two core molecules. However, METTL3 and METTL14 play opposite regulatory roles in hepatocellular carcinoma (HCC). Based on The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, we conducted a multi-omics analysis of METTL3 and METTL14 in HCC, including RNA-sequencing, m6ARIP-sequencing, and ribosome-sequencing profiles. We found that the expression and prognostic value of METTL3 and METTL14 are opposite in HCC. Besides, after METTL3 and METTL14 knockdown, most of the dysregulated mRNAs, signaling pathways and biological processes are distinct in HCC, which partly explains the contrary regulatory role of METTL3 and METTL14. Intriguingly, these mRNAs whose stability or translation efficiency are influenced by METTL3 or METTL14 in an m6A dependent manner, jointly regulate multiple signaling pathways and biological processes, which supports the cooperative role of METTL3 and METTL14 in catalyzing m6A modification. In conclusion, our study further clarified the contradictory role of METTL3 and METTL14 in HCC.


Assuntos
Adenosina/análogos & derivados , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , Metiltransferases/metabolismo , RNA Mensageiro/metabolismo , Adenosina/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Metilação , Metiltransferases/genética , Estabilidade de RNA , RNA Mensageiro/genética , Transdução de Sinais , Transcriptoma
18.
Mol Ther Nucleic Acids ; 22: 750-765, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230473

RESUMO

Hepatocellular carcinoma (HCC), one of the most aggressive malignancies, ranks as the fourth leading cause of cancer-related deaths worldwide. Emerging evidence indicates that RNA N6-methyladenosine (m6A) plays a critical role in tumor progression. However, the biological function of YTHDF1 in HCC remains unclear. Here, we found that YTHDF1 expression was strikingly elevated in HCC tissues and cell lines and significantly associated with prognosis of HCC patients. Moreover, YTHDF1 expression was transcriptionally regulated by USF1 and c-MYC in HCC. Functional studies showed that YTHDF1 can promote HCC cell proliferation and metastasis both in vitro and in vivo. Multi-omics analysis revealed that YTHDF1 can accelerate the translational output of FZD5 mRNA in an m6A-dependent manner and function as an oncogene through the WNT/ß-catenin pathway. Taken together, our study revealed an essential role of YTHDF1 in the progression of HCC cells, which indicated that targeting YTHDF1 may be a potential therapeutic strategy in HCC.

19.
J Agric Food Chem ; 68(27): 7143-7151, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32543191

RESUMO

Gout and hyperuricemia can seriously affect the quality of life; at present, however, existing medicines are unable to meet all clinical needs. In the current study, a novel peptide (i.e., rice-derived-peptide-3 (RDP3), AAAAMAGPK-NH2, 785.97 Da) in water extract obtained from shelled Oryza sativa fruits was identified. Testing revealed that RDP3 (minimum effective concentration 100 µg/kg) did not show both hemolytic and acute toxicity, and reduced uric acid levels in the serum of hyperuricemic mice by inhibiting xanthine oxidase activity and decreasing urate transporter 1 expression. RDP3 also alleviated renal injury in hyperuricemic mice by decreasing NLRP3 inflammasome expression. Furthermore, RDP3 alleviated formalin-induced paw pain and reduced monosodium urate crystal-induced paw swelling and inflammatory factors in mice. Thus, this newly identified peptide reduced uric acid levels and renal damage in hyperuricemic mice and showed anti-inflammatory and analgesic activities, indicating the potential of RDP3 as an antigout medicine candidate.


Assuntos
Oryza/química , Peptídeos/química , Extratos Vegetais/química , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Edema/tratamento farmacológico , Edema/metabolismo , Gota/tratamento farmacológico , Gota/metabolismo , Supressores da Gota/administração & dosagem , Supressores da Gota/química , Supressores da Gota/isolamento & purificação , Humanos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Camundongos , Camundongos Nus , Peptídeos/administração & dosagem , Peptídeos/isolamento & purificação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Ácido Úrico/metabolismo , Xantina Oxidase/metabolismo
20.
Biomark Med ; 14(3): 239-248, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31984757

RESUMO

Aim: To investigate the role of miR-485-5p in colorectal cancer (CRC). Methodology: The level of miR-485-5p in serum and cell lines were measured by quantitative real-time polymerase chain reaction, and analyzed the diagnostic and prognostic value. Additionally, the biological effect of miR-485-5p on CRC cells was also explored in vitro. Results: The receiver operating characteristic (ROC) curves analysis revealed that miR-485-5p was a diagnostic candidate. Kaplan-Meier analyses demonstrated that patients with low serum miR-485-5p had shorter overall survival. In addition, the result of cox regression model indicated that miR-485-5p was not an independent risk factor for progression. Functional study revealed that overexpression of miR-485-5p could inhibit CRC cell proliferation, invasion and facilitates cell apoptosis. Conclusion: Our study revealed that miR-485-5p was a tumor suppressor and it could serve as a potential prognostic biomarker in CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Prognóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...