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1.
Phytomedicine ; 94: 153810, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34798519

RESUMO

BACKGROUND: Osteoporosis affects more than half the patients with type 2 diabetes mellitus (T2DM). Up to data, there is no effective clinical practice in managing type 2 diabetes osteoporosis (T2DOP) because of its complex pathogenesis. Gegen Qinlian Decoction (GQD) has been used for the long-term management of T2DM. However, the underlying mechanism of GQD in the treatment of T2DOP remains unknown. PURPOSE: To reveal the role of GQD in T2DOP and its potential therapeutic targets in the management of T2DOP. STUDY DESIGN: The effect of GQD on T2DOP was observed in db/db mice in four groups: model group, GQD low-dose group (GQD-L), GQD high-dose group (GQD-H), and metformin (positive control) group. C57BL/6J mice were used as the negative control group. METHODS: Quantitative phytochemical analysis of GQD was performed using high-performance liquid chromatography (HPLC). Micro-CT and hematoxylin-eosin (H&E) staining were used to evaluate bone histomorphometry. To screen for candidate targets of GQD, a cytokine antibody array was used, followed by bioinformatics analysis. Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to determine expression levels. RESULTS: The major active components of GQD were confirmed by HPLC. Micro-CT and H&E staining showed that bone mass was significantly increased in the GQD-H group compared with the model group. Antibody arrays revealed that the expression of insulin-like growth factor binding protein 3 (IGFBP3) was elevated in the GQD-H group. The MAPK pathway was identified using bioinformatics analysis. Additionally, the levels of osteoclastogenesis-related genes, including cathepsin K (Ctsk), acid phosphatase 5 (Acp5), matrix metallopeptidase 9 (Mmp9), and ATPase H+ transporting V0 subunit D2 (Atp6v0d2) were significantly decreased in the GQD-H group. Compared with the model group, high-dosage GQD inhibited phosphorylation of extracellular signal-regulated kinases (ERKs) and P38 mitogen-activated protein kinase (MAPK) and the expression of c-Fos and nuclear factor of activated T cells 1 (NFATc1). CONCLUSION: GQD plays a protective role in T2DOP by upregulating IGFBP3 expression and downregulating the IGFBP3/MAPK/NFATc1 signaling pathway. IGFBP3 in serum may also be a novel biomarker in the treatment of T2DOP. Our current findings not only expand the application of GQD, but also provide a theoretical basis and guidance for T2DOP.

2.
BMC Cancer ; 21(1): 1216, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774014

RESUMO

BACKGROUND: Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. However, the correlation between SEC61G and lung adenocarcinoma (LUAD) remains unclear. In the current study, we aimed to demonstrate the prognostic value and potential biological function of the SEC61G gene in LUAD. METHODS: Public datasets were used for SEC61G expression analyses. The prognostic value of SEC61G in LUAD was investigated using the Kaplan-Meier survival and Cox analyses. The correlation between the methylation level of SEC61G and its mRNA expression was evaluated via cBioPortal. Additionally, MethSurv was used to determine the prognostic value of the SEC61G methylation levels in LUAD. Functional enrichment analysis was conducted to explore the potential mechanism of SEC61G. Also, single sample GSEA (ssGSEA) and TIMER online tool were applied to identify the correlation between SEC61G and immune filtration. Furthermore, cell functional experiments were conducted to verify the biological behavior of SEC61G in lung adenocarcinoma cells (LAC). RESULTS: SEC61G was upregulated in pan-cancers, including LUAD. High SEC61G expression was significantly correlated with worse prognosis in LUAD patients. Multivariate analysis demonstrated that high SEC61G expression was an independent prognostic factor in the TCGA cohort. (HR = 1.760 95% CI: 1.297-2.388, p < 0.001). The methylation level of SEC61G negatively correlated with the SEC61G expression (R = - 0.290, p < 0.001), and patients with low SEC61G methylation had worse overall survival. (p = 0.0014). Proliferation-associated terms such as cell cycle and cell division were significantly enriched in GO and KEGG analysis. Vitro experiments demonstrated that knockdown of SEC61G resulted in decreased cell proliferation, invasion and facilitated apoptosis in LAC. GSEA analysis found that SEC61G expression was associated with the E2F targets. Moreover, SEC61G expression was negatively correlated with the immune cell infiltration including CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell. CONCLUSION: Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of LUAD patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD.

3.
BMC Neurol ; 21(1): 440, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34753435

RESUMO

BACKGROUND: Patients with acute non-lacunar single subcortical infarct (SSI) associated with mild intracranial atherosclerosis (ICAS) have a relatively high incidence of early neurological deterioration (END), resulting in unfavorable functional outcomes. Whether the early administration of argatroban and aspirin or clopidogrel within 6-12 h after symptom onset is effective and safe in these patients is unknown. METHODS: A review of the stroke database of Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University and Qingdao Center Hospital, Qingdao University Medical College in China was undertaken from May 2017 to January 2020 to identify all patients with non-lacunar SSI caused by ICAS within 6-12 h of symptom onset based on MRI screening. Patients were divided into two groups, one comprising those who received argatroban and mono antiplatelet therapy with aspirin or clopidogrel on admission (argatroban group), and the other those who received dual antiplatelet therapy (DAPT) with aspirin and clopidogrel during hospitalization (DAPT group). The primary outcome was recovery by 90 days after stroke based on a modified Rankin scale (mRS) score (0 to 1). The secondary outcome was END incidence within 120 h of admission. Safety outcomes were intracranial hemorrhage (ICH) and major extracranial bleeding. The probability of clinical benefit (mRS score 0-1 at 90 days) was estimated using multivariable logistic regression analysis. RESULTS: A total of 304 acute non-lacunar SSI associated with mild ICAS patients were analyzed. At 90 days, 101 (74.2%) patients in the argatroban group and 80 (47.6%) in the DAPT group had an mRS score that improved from 0 to 1 (P < 0.001). The relative risk (95% credible interval) for an mRS score improving from 0 to 1 in the argatroban group was 1.50 (1.05-2.70). END occurred in 10 (7.3%) patients in the argatroban group compared with 37 (22.0%) in the DAPT group (P < 0.001). No patients experienced symptomatic hemorrhagic transformation. CONCLUSIONS: Early combined administration of argatroban and an antiplatelet agent (aspirin or clopidogrel) may be beneficial for patients with non-lacunar SSI associated with mild ICAS identified by MRI screening and may attenuate progressive neurological deficits. TRIAL REGISTRATION: Our study is a retrospectively registered trial.


Assuntos
Arteriosclerose Intracraniana , Inibidores da Agregação Plaquetária , Acidente Vascular Cerebral Lacunar , Arginina/análogos & derivados , Quimioterapia Combinada , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/tratamento farmacológico , Ácidos Pipecólicos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/tratamento farmacológico , Sulfonamidas/uso terapêutico , Resultado do Tratamento
4.
BMC Infect Dis ; 21(1): 1040, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620102

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a declared global pandemic, causing a lot of death. How to quickly screen risk population for severe patients is essential for decreasing the mortality. Many of the predictors might not be available in all hospitals, so it is necessary to develop a simpler screening tool with predictors which can be easily obtained for wide wise. METHODS: This retrospective study included all the 813 confirmed cases diagnosed with COVID-19 before March 2nd, 2020 in a city of Hubei Province in China. Data of the COVID-19 patients including clinical and epidemiological features were collected through Chinese Disease Control and Prevention Information System. Predictors were selected by logistic regression, and then categorized to four different level risk factors. A screening tool for severe patient with COVID-19 was developed and tested by ROC curve. RESULTS: Seven early predictors for severe patients with COVID-19 were selected, including chronic kidney disease (OR 14.7), age above 60 (OR 5.6), lymphocyte count less than < 0.8 × 109 per L (OR 2.5), Neutrophil to Lymphocyte Ratio larger than 4.7 (OR 2.2), high fever with temperature ≥ 38.5℃ (OR 2.2), male (OR 2.2), cardiovascular related diseases (OR 2.0). The Area Under the ROC Curve of the screening tool developed by above seven predictors was 0.798 (95% CI 0.747-0.849), and its best cut-off value is > 4.5, with sensitivity 72.0% and specificity 75.3%. CONCLUSIONS: This newly developed screening tool can be a good choice for early prediction and alert for severe case especially in the condition of overload health service.


Assuntos
COVID-19 , Humanos , Masculino , Programas de Rastreamento , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
5.
Sheng Wu Gong Cheng Xue Bao ; 37(9): 3310-3322, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34622638

RESUMO

The effect of altering the promoter region of ubiquitous chromatin-opening element (UCOE) and matrix attachment region (MAR) on stable and efficient expression of genes was investigated. Four different promoters were tested, namely, oct4 containing an enhancer region, sox2 having a CpG island, nanog having no regulatory elements, and CMV containing a CpG island and an enhancer region. Eight reporter plasmids were constructed: pOCT4-UCOE, pOCT4-MAR, pSOX2-UCOE, pSOX2-MAR, pNANOG-UCOE, pNANOG-MAR, pCMV-UCOE, and pCMV-MAR. Stable and efficient expression was observed when UCOE combined with the oct4 promoter, whereas the sox2 was the best promoter suited for MAR. Comparison of the stable clones of oct4-UCOE and sox2-MAR showed that UCOE-regulated expression is more stable and efficient than MAR-regulated expression. When CpG island-containing promoter is linked with UCOE, stable and efficient expression could be observed. These data suggest that an enhancer region in the promoter leads to high, yet unstable expression when combined with UCOE, whereas CpG islands stabilize expression. In conclusion, UCOE and MAR interact with regulatory elements on the promoter by altering the chromatin open state and chromatin loop to regulate gene expression.


Assuntos
Cromatina , Regulação da Expressão Gênica , Cromatina/genética , Ilhas de CpG/genética , Expressão Gênica , Regiões Promotoras Genéticas/genética
6.
Diagn Pathol ; 16(1): 97, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706737

RESUMO

BACKGROUND: Adult-onset Still's disease (AOSD) often presents with systemic multiple lymphadenopathy. In addition to the common paracortical and mixed patterns in AOSD lymph node histopathological features, other morphological patterns include diffuse, necrotic, and follicular patterns. However, to date, there have been few reports on the histopathological description of AOSD lymph nodes. CASE PRESENTATION: An 18-year-old woman presented 2 months earlier with pain in her large joints with painless rash formation; bilateral posterior cervical lymph node, left supraclavicular lymph node, and left posterior axillary lymph node enlargement, and no tenderness. Left cervical lymph node resection was performed for pathological examination. The lymph node structure was basically preserved, and subcapsular and medullary sinus structures were observed. Many histiocytes in the sinus were observed, the cortical area was reduced, a few lymphoid follicles of different sizes were observed, and some atrophy and hyperplasia were noted. The lymphoid tissue in the paracortical region of the lymph node was diffusely proliferative and enlarged, mainly comprising histiocytes with abundant cytoplasm, immunoblasts and numerous lymphocytes with slightly irregular, small- to medium-sized nuclei. Nuclear karyorrhexis was easily observed, showing a few nuclear debris and the "starry sky" phenomenon, accompanied by abundantly branching high endothelial small vessels with few scattered plasma cells and eosinophil infiltration. Lymphoid follicle immunophenotype with reactive proliferative changes was observed. Approximately 40% of the cells in the paracortical region were positive for Ki-67, and the histiocytes expressed CD68, CD163, and some expressed S-100, with the absence of myeloperoxidase. The immunoblasts expressed CD30 and CD20, not ALK or CD15. Background small- to medium-sized T cells expressed CD2, CD3, CD5, CD7, CD4, and CD8; the number of CD8-positive T cells was slightly predominant, and a small number of T cells expressed granzyme B and T-cell intracellular antigen 1. The patient received a comprehensive medical treatment after the operation, and her condition was stable without progression at the 11-month follow-up evaluation. CONCLUSIONS: The pathological features of AOSD lymphadenopathy raises the awareness of AOSD among pathologists and clinicians and aids in the diagnosis and differential diagnosis of AOSD lymphadenopathy from other reactive lymphadenopathies (lupus lymphadenitis, etc.) and lymphomas.

7.
Radiat Oncol ; 16(1): 207, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717670

RESUMO

OBJECTIVE: There is still no definitely therapeutic evidence of a beneficial effect of chemotherapy with radiotherapy for older patients with esophageal squamous cell carcinoma (ESCC). We aim to determine the influence of chemoradiotherapy (CRT) and radiotherapy (RT) alone in patients aged 65 years or older with locally advanced ESCC. METHODS: We retrospectively analyzed 581 ESCC patients who underwent CRT and RT alone. Univariate and multivariate Cox regression analysis was used to analyze the impact of clinical factors on long-term overall survival (OS) and progression-free survival (PFS). Finally, we compared the toxicity rates of these patients. RESULTS: The median OS and PFS of the overall population were 23.2 months (2.0-162.6 months) and 18.6 months (1.1-159.6 months). Multivariate Cox regression analysis showed that chemotherapy (p < 0.05), tumor thickness (p < 0.01), and N stage (p < 0.05) were independent prognostic factors associated with both OS and PFS. In the chemotherapy subgroup, patients who received 2-8 cycles of chemotherapy had better OS than those who received 1 cycle (p = 0.015). The results also revealed that the CRT group has better OS and PFS than RT alone group for patients aged 65-74 years (both p < 0.01). However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone (both p > 0.05). Besides, higher staged ESCC has the inferior OS and PFS than lower staged ESCC for patients received RT alone and aged 65-74 years (both p < 0.05). Finally, there were significantly more severe hematologic toxicities in the CRT group than in those treated with RT alone in this study (p < 0.001). CONCLUSIONS: The present study suggested that CRT for locally advanced ESCC in patients aged 65 years or older had a significant benefit over RT alone in terms of OS and PFS. However, for patients aged 75 years or older, there was no statistically significant difference between CRT and RT alone. CRT should be performed with special attention in patients aged 75 years or older.

8.
Int J Infect Dis ; 113: 243-250, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34673215

RESUMO

OBJECTIVES: We aimed to comprehensively explore the etiology of granulomatous lobular mastitis (GLM) to optimize treatment programs. METHODS: We collected 30 fresh mastitis samples for metagenomic next-generation sequencing, morphological observation, and analysis of the clinical information. RESULTS: Of the 30 samples, 25 were GLM; pathogens were detected in 17, these were: Corynebacterium kroppenstedtii (10 of 25, 40%); C. kroppenstedtii and Pseudomonas oleovorans (3 of 25, 12%); C. kroppenstedtii and human gammaherpesvirus 4 (1 of 25, 4%); Acinetobacter baumannii and C. kroppenstedtii (1 of 25, 4%); P. oleovorans (1 of 25, 4%); and Tepidiphilus thermophilus (1 of 25, 4%). Abnormal sex hormone levels (mainly prolactin) and/or autoimmune function were found in 12 of the 25 samples. Lipophilic antibiotics (rifampicin) were found to work effectively in patients with slow-healing wounds after surgery. CONCLUSIONS: The main pathogenic factor of GLM is C. kroppenstedtii infection, but other unusual pathogens (P. oleovorans, human gammaherpesvirus 4, A. baumannii, T. thermophilus) are likely to be closely related to GLM, particularly human gammaherpesvirus 4 (Epstein-Barr virus)-associated mastitis, which may be a new entity of mastitis. Abnormal levels of sex hormones and autoimmune function are also common causes. Therefore, lipophilic antibiotics (rifampicin) and prolactin inhibitors may be an effective treatment.

9.
Biomed Res Int ; 2021: 5538643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557547

RESUMO

Background: Systemic lupus erythematosus (SLE) is a refractory immune disease, which is often complicated with osteonecrosis of the femoral head (ONFH). Curcumin, the most active ingredient of Curcuma longa with a variety of biological activities, has wide effects on the body system. The study is aimed at exploring the potential therapeutic targets underlying the effect of curcumin on SLE-ONFH by utilizing a network pharmacology approach and molecular docking strategy. Methods: Curcumin and its drug targets were identified using network analysis. First, the Swiss target prediction, GeneCards, and OMIM databases were mined for information relevant to the prediction of curcumin targets and SLE-ONFH-related targets. Second, the curcumin target gene, SLE-ONFH shared gene, and curcumin-SLE-ONFH target gene networks were created in Cytoscape software followed by collecting the candidate targets of each component by R software. Third, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Eventually, a gene-pathway network was constructed and visualized by Cytoscape software; key potential central targets were verified and checked by molecular docking and literature review. Results: 201 potential targets of curcumin and 170 related targets involved in SLE-ONFH were subjected to network analysis, and the 36 intersection targets indicated the potential targets of curcumin for the treatment of SLE-ONFH. Additionally, for getting more comprehensive and accurate candidate genes, the 36 potential targets were determined to be analyzed by network topology and 285 candidate genes were obtained finally. The top 20 biological processes, cellular components, and molecular functions were identified, when corrected by a P value ≤ 0.05. 20 related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. Molecular docking showed that the top three genes (TP53, IL6, VEGFA) have good binding force with curcumin; combined with literature review, some other genes such as TNF, CCND1, CASP3, and MMP9 were also identified. Conclusion: The present study explored the potential targets and signaling pathways of curcumin against SLE-ONFH, which could provide a better understanding of its effects in terms of regulating cell cycle, angiogenesis, immunosuppression, inflammation, and bone destruction.

10.
Pharmacol Res ; 173: 105868, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34481974

RESUMO

Diabetes-related cardiovascular disease (CVD) is a global health issue that causes thousands of people's death around the world annually. Diabetes-related CVD is still prevailing despite the progression being made in its diagnosis and treatment. Therefore it is urgent to find therapeutic strategies.to prevent it. MicroRNA (miRNA) is a single-stranded non-coding RNA involved in the process of post-transcriptional control of gene expression in eukaryotes. A large number of literatures reveal that miRNAs are implicated in diabetes-related CVD. The increase of miRNAs in exosomes may promote the occurrence and development of diabetes-related cardiovascular complication. However, some other studies identify that miRNAs in exosomes are supposed to be involved in cardiac regeneration and confer cardiac protection effect. Therefore, targeting the miRNA in exosome is regarded as a potent therapeutic measure to alleviate diabetes-related CVD. In this article, we review current knowledge about the role of exosomal miRNAs in diabetes-related cardiovascular complication, such as coronary heart disease, Peripheral artery disease, stroke, diabetic cardiomyopathy, diabetic nephropathy and diabetic retinopathy. Exosomal miRNAs are considered to be central regulators of diabetes-Related CVD and provide a therapeutic tool for diagnosis and treatment of diabetes-related cardiovascular complication.

11.
DNA Repair (Amst) ; 106: 103172, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34298489

RESUMO

The transcription-related DNA damage response was visualized on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a small proportion of mature RNA transcripts undergo changes, with significant activation of DNA repair factors. Notably, an increase of chromatin accessibility is observed at the immediate early recovery phase and serves as binding sites for selective stage-specific transcription factors. Whole genome analysis of DNA methylation (5mC) delineates pervasive dynamics during DNA repair process, and hypomethylation at gene bodies and 3'UTR is accompanied by induction of DNA damage response genes. Furthermore, temporal-specific m6A RNA methylation has been defined and appears to affect DNA repair by modulation of translation. These findings provide a resource for identifying players required for transcription-coupled nucleotide excision repair and reveal insights into the epigenetic regulation of the transcriptional programs in response to genotoxic stress.


Assuntos
Metilação de DNA , Reparo do DNA , Epigênese Genética , Fibroblastos/efeitos da radiação , RNA/metabolismo , Transcriptoma , Raios Ultravioleta , Adenosina/análogos & derivados , Linhagem Celular , DNA/metabolismo , Dano ao DNA , Epigenômica , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Humanos , Metilação , Processamento Pós-Transcricional do RNA , Transcrição Genética
12.
Front Oncol ; 11: 687035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249736

RESUMO

Objective: Radiation esophagitis (RE) is common in patients treated with radiotherapy (RT) for locally advanced esophageal squamous cell carcinoma (ESCC). We aim to construct a nomogram predicting the severe RE (grade ≥2) in patients with ESCC receiving definitive chemoradiotherapy (dCRT). Materials and Methods: Logistic regression was performed to evaluate the risk factors in predicting RE. Nomogram was built based on the multivariate analysis result. The model was validated using the area under the receiver operating curve (ROC) curve (AUC), calibration curves, and decision curve analyses (DCA). Spearman correlation analysis was used to evaluate the correlation between inflammation indexes. Results: A total of 547 patients with stage II-IVA ESCC treated with dCRT from the retrospective study were included. Two hundred and thirty-two of 547 patients (42.4%) developed grade ≥2 RE. Univariate analysis indicated that gender (p = 0.090), RT dose (p < 0.001), targeted therapy (p = 0.047), tumor thickness (p = 0.013), lymphocyte-monocyte ratio (LMR, p = 0.016), neutrophil-lymphocyte ratio (NLR, p < 0.001), and platelet-lymphocyte ratio (PLR, p < 0.001) were the significant factors for a higher incidence of RE. In multivariate analysis, RT dose [p < 0.001; odds ratio (OR), 4.680; 95% confidence interval (CI), 2.841-6.709], NLR (p < 0.001; OR, 0.384; 95% CI, 0.239-0.619), and PLR (p < 0.001; OR, 3.539; 95% CI: 2.226-5.626) were independently associated grade ≥2 RE and were involved in the nomogram. ROC curves showed the AUC of the nomogram was 0.714 (95% CI, 0.670-0.757), which was greater than each factor alone (RT dose: 0.615; NLR: 0.596; PLR: 0.590). Calibration curves showed good consistency between the actual observation and the predicted RE. DCA showed satisfactory positive net benefits of the nomogram among most threshold probabilities. Conclusions: The study demonstrated that RT dose, NLR, and PLR were independent risk factors for grade ≥2 RE in patients with locally advanced ESCC receiving dCRT. A predictive model including all these factors was built and performed better than it based on each separately. Further validation in large patient populations is still warranted.

13.
Plant Mol Biol ; 106(6): 491-503, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34165673

RESUMO

KEY MESSAGE: Anthocyanin was highly accumulated in the leaves of red-leaved poplars; Many structural genes involved in anthocyanin synthesis were significantly up-regulated in 'Quanhong' and 'Xuanhong'; TTG2, HYH, and HY5 may be directly involved in the regulation of anthocyanin synthesis in both red-leaved poplars. The red-leaved poplar cultivars 'Quanhong' and 'Xuanhong' are bud mutations of Populus deltoides cv. 'Zhonglin 2025'. These cultivars are valued for their beautiful shape, lack of flying catkins, and ornamental leaf colors. However, the understanding of the molecular mechanism of anthocyanin accumulation in the leaves of red-leaved poplars is still unclear. Here, we profiled the changes of pigment content, transcriptome and proteome expression in the leaves of three poplar cultivars and the results showed that the ratios of anthocyanin to total chlorophyll in both red-leaved poplars were higher than that in 'Zhonglin 2025', indicating that the anthocyanin was highly accumulated in the leaves of red-leaved poplars. Based on the results of combined transcriptome and proteome analysis, 15 and 11 differentially expressed genes/proteins involved in anthocyanin synthesis were screened in 'Quanhong' and 'Xuanhong', respectively, indicating that the two red-leaved poplar cultivars have slightly different patterns of regulating anthocyanin biosynthesis. Among the 120 transcription factors, 3 (HY5, HYH, and TTG2), may be directly involved in the regulation of anthocyanin synthesis in both red-leaved poplars. This study screens the candidate genes involved in anthocyanin accumulation in the leaves of red-leaved poplars and lays a foundation for further exploring the molecular mechanism of leaf red coloration in red-leaved poplars.


Assuntos
Antocianinas/metabolismo , Folhas de Planta/genética , Populus/genética , Proteoma/análise , Transcriptoma/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas , Pigmentação/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Populus/classificação , Populus/metabolismo , Mapas de Interação de Proteínas/genética , Proteômica/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Especificidade da Espécie , Espectrometria de Massas em Tandem/métodos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
J Cell Commun Signal ; 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34101112

RESUMO

Numb (Nb) and Numb-like (Nbl) are functionally redundant adaptor proteins that critically regulate cell fate and morphogenesis in a variety of organs. We selectively deleted Nb and Nbl in testicular germ cells by breeding Nb/Nbl floxed mice with a transgenic mouse line Tex101-Cre. The mutant mice developed unilateral or bilateral cystic dilation in the rete testis (RT). Dye trace indicated partial blockages in the testicular hilum. Morphological and immunohistochemical evaluations revealed that the lining epithelium of the cysts possessed similar characteristics of RT epithelium, suggesting that the cyst originated from dilation of the RT lumen. Spermatogenesis and the efferent ducts were unaffected. In comparisons of isolated germ cells from mutants to control mice, the Notch activity considerably increased and the expression of Notch target gene Hey1 significantly elevated. Further studies identified that germ cell Fgf4 expression negatively correlated the Notch activity and demonstrated that blockade of FGF receptors mediated FGF4 signaling induced enlargement of the RT lumen in vitro. The crucial role of the FGF4 signaling in modulation of RT development was verified by the selective germ cell Fgf4 ablation, which displayed a phenotype similar to that of germ cell Nb/Nbl null mutant males. These findings indicate that aberrant over-activation of the Notch signaling in germ cells due to Nb/Nbl abrogation impairs the RT development, which is through the suppressing germ cell Fgf4 expression. The present study uncovers the presence of a lumicrine signal pathway in which secreted/diffusible protein FGF4 produced by germ cells is essential for normal RT development.

15.
Nanoscale ; 13(19): 8693-8706, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33949576

RESUMO

Cancer remains a significant challenge despite the progress in developing different therapeutic approaches. Nanomedicine has been explored as a promising novel cancer therapy. Recently, biomimetic camouflage strategies have been investigated to change the bio-fate of therapeutics and target cancer cells while reducing the unwanted exposure on normal tissues. Endogenous components (e.g., proteins, polysaccharides, and cell membranes) have been used to develop anticancer drug delivery systems. These biomimetic systems can overcome biological barriers and enhance tumor cell-specific uptake. The tumor-targeting mechanisms include ligand-receptor interactions and stimuli-responsive (e.g., pH-sensitive and light-sensitive) delivery. Drug delivery carriers composed of endogenous components represent a promising approach for improving cancer treatment efficacy. In this paper, different biomimetic drug delivery strategies for cancer treatment are reviewed with a focus on the discussion of their advantages and potential applications.


Assuntos
Nanopartículas , Neoplasias , Biomimética , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Ligantes , Nanomedicina , Neoplasias/tratamento farmacológico
16.
Sci Rep ; 11(1): 8653, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883568

RESUMO

In this study, 0, 0.5, 1, 1.5, 2, 4, 6 and 8 mg·kg-1 of cadmium were added to the cultivation materials. In order to study the effects of different concentrations of Cd stress on J1 and J77, the contents of antioxidant enzymes, proline and malondialdehyde, Cd content, agronomic traits and yield of fruiting bodies of Agaricus brasiliensis were determined, and the nutritional components such as polysaccharide, triterpene, protein, total sugar and total amino acid were determined. The results showed that the physiological indexes of strain J1 and J77 changed regularly under different concentrations of Cd stress. J1 was a high absorption and low tolerance variety, while J77 was a low absorption and high tolerance variety. Low concentration of Cd promoted the growth of strain J1, and higher concentration of Cd promoted the growth of strain J77. The contents of protein and total amino acids in the two strains changed greatly, followed by polysaccharides, which indicated that Cd stress had the greatest impact on the three nutrients, and other nutrients were not sensitive to Cd stress.


Assuntos
Agaricus/efeitos dos fármacos , Cádmio/efeitos adversos , Agaricus/química , Agaricus/crescimento & desenvolvimento , Agaricus/fisiologia , Qualidade dos Alimentos , Malondialdeído/metabolismo , Prolina/metabolismo , Estresse Fisiológico/efeitos dos fármacos
17.
Clin Chim Acta ; 517: 127-132, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33711326

RESUMO

Diabetic cardiomyopathy is an important irreversible chronic cardiovascular complication in diabetic patients. This condition is described as early diastolic dysfunction, myocardial fibrosis, cardiac hypertrophy, systolic dysfunction and other complex pathophysiological events, which ultimately lead to heart failure. Despite these characteristics, the underlying mechanisms resulting in diabetic cardiomyopathy are still unknown. With the developments in molecular biotechnology, increasing evidence shows that circRNAs play critical roles in the pathogenesis of diabetic cardiomyopathy. The purpose of this review is to summarize recent studies on the role of circRNAs in the pathophysiological process to provide novel prevention and treatment strategies for diabetic cardiomyopathy, oxidative stress, inflammation, endothelial dysfunction, myocardial fibrosis and cell death in diabetic cardiomyopathy.


Assuntos
Diabetes Mellitus , Cardiomiopatias Diabéticas , Cardiopatias , Cardiomiopatias Diabéticas/genética , Fibrose , Humanos , Estresse Oxidativo , RNA Circular
18.
BMC Plant Biol ; 21(1): 17, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407132

RESUMO

BACKGROUND: Carex L. is one of the largest genera in the Cyperaceae family and an important vascular plant in the ecosystem. However, the genetic background of Carex is complex and the classification is not clear. In order to investigate the gene function annotation of Carex, RNA-sequencing analysis was performed. Simple sequence repeats (SSRs) were generated based on the Illumina data and then were utilized to investigate the genetic characteristics of the 79 Carex germplasms. RESULTS: In this study, 36,403 unigenes with a total length of 41,724,615 bp were obtained and annotated based on GO, KOG, KEGG, NR databases. The results provide a theoretical basis for gene function exploration. Out of 8776 SSRs, 96 pairs of primers were randomly selected. One hundred eighty polymorphic bands were amplified with a polymorphism rate of 100% based on 42 pairs of primers with higher polymorphism levels. The average band number was 4.3 per primer, the average distance value was 0.548, and the polymorphic information content was ranged from 0.133 to 0.494. The number of observed alleles (Na), effective alleles (Ne), Nei's (1973) gene diversity (H), and the Shannon information index (I) were 2.000, 1.376, 0.243, and 0.391, respectively. NJ clustering divided into three groups and the accessions from New Zealand showed a similar genetic attribute and clustered into one group. UPGMA and PCoA analysis also revealed the same result. The analysis of molecular variance (AMOVA) revealed a superior genetic diversity within accessions than between accessions based on geographic origin cluster and NJ cluster. What's more, the fingerprints of 79 Carex species are established in this study. Different combinations of primer pairs can be used to identify multiple Carex at one time, which overcomes the difficulties of traditional identification methods. CONCLUSIONS: The transcriptomic analysis shed new light on the function categories from the annotated genes and will facilitate future gene functional studies. The genetic characteristics analysis indicated that gene flow was extensive among 79 Carex species. These markers can be used to investigate the evolutionary history of Carex and related species, as well as to serve as a guide in future breeding projects.


Assuntos
Carex (Planta)/genética , Fluxo Gênico , Genes de Plantas , Marcadores Genéticos , Repetições de Microssatélites , Análise de Sequência de DNA , China , Perfilação da Expressão Gênica , Variação Genética , Genótipo , Alemanha , Nova Zelândia , América do Norte , Filogenia , Polimorfismo Genético , Análise de Sequência de RNA
19.
Int Immunopharmacol ; 90: 107224, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33302036

RESUMO

Previous studies reported that antibiotics inhibit the growth of Gram-positive bacteria and alleviate ulcerative colitis (UC). But how Gram-positive bacteria are involved in the occurrence of inflammatory bowel disease (IBD) and which component of it causes inflammation remain unclear. This work aims to demonstrate that Gram-positive bacteria may be an underlying cause of experimental colitis in mice through the muramyl dipeptide (MDP)-nucleotide-binding oligomerization domain-containing protein-2 (NOD2) pathway and paeoniflorin inhibits the pathway above to alleviate experimental colitis. In this study, colitis mice were established by oral administration of 3% dextran sulfate sodium (DSS) and paeoniflorin (25, 50,100 mg/kg per day, ig) was administered to the mice for 10 days. Results shown that the abundance and the infiltration of Gram-positive bacteria in intestinal tissues increased in UC mice. Paeoniflorin treatment significantly alleviated DSS-induced experimental colitis mice, reduced the abundance of Gram-positive bacteria in feces and the infiltration of Gram-positive bacteria in intestinal tissues. Paeoniflorin also inhibited mRNA and protein expression of MDP-NOD2 pathway components and decreased the levels of related inflammatory cytokines. In vitro experiments showed that MDP strongly stimulated RAW264.7 cells to secrete tumor necrosis factor α (TNF-α), and induced translocation of nuclear factor-kappa B (NF-κB p65) from the cytoplasm to nucleus using immunofluorescence co-localization experiments. Overall, the results indicated that Gram-positive bacteria promote the occurrence of colitis via up-regulation of MDP-NOD2 pathway, and paeoniflorin is able to decrease the infiltration of Gram-positive bacteria in intestine and inhibit Gram-positive bacteria-dependent MDP-NOD2 pathway to alleviate mice colitis.


Assuntos
Acetilmuramil-Alanil-Isoglutamina , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Glucosídeos/uso terapêutico , Bactérias Gram-Positivas/efeitos dos fármacos , Monoterpenos/uso terapêutico , Proteína Adaptadora de Sinalização NOD2/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana , Fezes/microbiologia , Intestinos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , RNA Mensageiro/antagonistas & inibidores , Fator de Transcrição RelA/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos
20.
Brain Behav ; 11(1): e01922, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33314753

RESUMO

BACKGROUND: Inflammation plays an important role in the pathophysiology of stroke. The aim of the present study was to investigate the association between various inflammatory risk markers and ischemic stroke outcome and subtype. METHODS: A total of 3,013 ischemic stroke patients who were admitted to our hospital from 01/01/2016 to 12/30/2018 were retrospectively studied. Stroke subtypes were defined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Levels of five common inflammatory markers including white blood cell (WBC) count, neutrophil, lymphocyte, serum C-reactive protein (CRP), and interleukin-6 (IL-6) were measured, and eleven conventional risk factors were further evaluated in the prediction of overall mortality as well as three functional outcomes defined by the National Institute of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI). Independent predictors of outcome were identified by multivariate logistic regression, and an importance score measured by the area under the receiver operating characteristics curve for each predictor using a Naive Bayes model was reported. RESULTS: Neutrophil and WBC were significantly higher in large-artery atherosclerosis (LAA) and cardioembolism (CE) subtype. In contrast, lymphocyte was significantly higher in small-artery occlusion (SAO). Neutrophil-lymphocyte ratio and CRP level were the best independent predictors, after adjustment for traditional risk factors and TOAST subtype for all four types of outcomes. CONCLUSION: Inflammatory risk markers including neutrophil, lymphocyte, and CRP may have strong independent prediction values for stroke outcome.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Teorema de Bayes , Biomarcadores , Humanos , Estudos Retrospectivos
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