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1.
Food Funct ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35527507

RESUMO

Soluble polysaccharides derived from microbial fermentation of agricultural by-products were considered as potential functional ingredients, primarily having probiotic properties. Herein, soluble polysaccharides (FSRP) were isolated from soybean residue fermented by Neurospora crassa, and FSRP mainly contained rhamnose, arabinose, fucose, mannose, glucose, and galactose, according to GC-MS analysis. To further investigate the protective effect of FSRP against colitis, dextran sulfate sodium induction (DSS)-treated mice were orally gavaged with FSRP (200 mg kg-1 d-1) or inulin (400 mg kg-1 d-1, a positive control) for 7 d. The results showed that DSS-treated mice displayed symptoms of body weight loss, atrophy, and histopathological changes of colon, as well as gut barrier damage, which were recovered after FSRP supplementation (similar to inulin). Furthermore, the beneficial effects of FSRP were linked to a decreased inflammatory response and increased protein expression of E-cadherin, claudin-1 and ZO-1. Illumina-MiSeq sequencing analysis revealed that FSRP increased microbial diversity and altered community structure. Specifically, FSRP could modulate the abundance of inflammation-related bacteria (such as Tenericutes, Clostridia, and Bacilli) to ameliorate colitis symptoms. Therefore, FSRP can relieve DSS-induced colitis, which is closely associated with reduced levels of inflammatory factors, improved gut barrier function and gut microbiota homeostasis.

2.
Front Cell Dev Biol ; 10: 898132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531095
3.
Artigo em Inglês | MEDLINE | ID: mdl-35518350

RESUMO

Diabetic nephropathy (DN) is one of the leading causes of end-stage renal disease and lacks effective clinical treatment for its complicated pathogenesis. In this study, the gene expression profiles downloaded from the GEO database were used to identify the key regulatory gene through bioinformatics analyses, and the potential mechanism in regulating DN was revealed via the gene set enrichment analysis, pathway analysis, and in vitro phenotype detection. The effect of the screened drug on DN was analyzed through in vitro and in vivo model experiments. Interferon regulatory factor 4 (IRF4) in DN was identified to be upregulated compared with that in normal control tissues. Further results revealed that IRF4 promoted the DN progression through inflammation, immunity, and extracellular matrix remodeling. The screening results of the TCM library showed that aloe-emodin (Ae) should be a potentially active target drug, and the in vitro and in vivo experiment results demonstrated that Ae could ameliorate DN by targeting IRF4. In conclusion, this study revealed the mechanism of the DN progression and demonstrated that Ae could be a potential target drug in ameliorating DN, providing ideas for the clinical treatments for DN.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35579171

RESUMO

CONTEXT: Calorie restriction plus dietary advice is suggested as a preventive strategy for individuals with obesity and prediabetes, however, optimal diet is still debatable. We aimed to compare the effects of Mediterranean diet (MD) and Chinese diets high or low in plants on body weight and glucose homeostasis among high risk Chinese. SUBJECTS AND METHODS: In this parallel-arm randomized controlled trial, 253 Chinese adults aged 25-60 years with BMI ≥24.0 kg/m 2 and fasting blood glucose ≥5.6 mmol/L were randomly assigned to three isocaloric-restricted diets: MD (n = 84), a traditional Jiangnan Diet high in plants (TJD, n = 85), or a control diet low in plants (CD, n = 84). During the 6-month trial, a 5-weekday full feeding regimen was followed, along with mobile app-based monitoring. Abdominal fat measurement (magnetic resonance imaging), oral glucose tolerance test (OGTT), and continuous glucose monitoring (CGM) were conducted at baseline, 3- and 6-month. RESULTS: With a 25% calorie-restriction for 6 months, weight deduction was 5.72 kg (95% CI: 5.03, 6.40) for MD, 5.05 kg (4.38, 5.73) for TJD and 5.38 kg (4.70, 6.06) for CD (Ptime < 0.0001). No between-group differences were found for fasting glucose, insulin, and the Matsuda index from OGTT. Notably, CD had significantly longer time below range (glucose < 3.9 mmol/L) than MD [0.81% ( 0.21, 1.40), P = 0.024] and marginally longer time than TJD [0.56% (-0.03,1.15), P = 0.065], as measured by CGM. CONCLUSIONS: With the 6-month isocaloric-restricted feeding, TJD and MD achieved comparable weight deduction and improved glucose homeostasis, whereas CD showed a higher risk for hypoglycemia.

5.
Analyst ; 147(9): 1968-1975, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35416808

RESUMO

Acquiring information on telomerase activity at multiple levels contributes to a better understanding of its role in various physiological and pathological processes. Herein, a primer extension activating 3D DNAzyme walker is developed for in situ imaging and sensitive detection of telomerase activity. This walker is constructed via co-modifying specially designed hairpin structured walking strands and track strands on a gold nanoparticle (AuNP). The walking strand contains a pre-blocked DNAzyme sequence and a telomerase primer hybridized to its root. The track strand embeds at an RNA cleavage site and is labeled with the FAM group. After this walker is taken up by cells, the telomerase primer is extended under the action of endogenous telomerase to liberate DNAzyme. The liberated DNAzyme cuts track strands in the presence of the cofactor Mn2+ to drive the walker's processive operation, resulting in an enhanced fluorescence recovery of the AuNP-quenched FAM fluorophore. In situ imaging of telomerase activity in three different cell lines (MCF-7 cells, HeLa cells and HL-7702 cells) was well implemented. The discrimination of cancer cells from normal cells and the screening of telomerase inhibitors have been achieved. The sensitive detection of telomerase activity in HeLa cell lysate has also been realized with a detection limit of 10 cells. This walker performed a new approach for monitoring telomerase activity from different levels, providing a potential tool for clinical diagnosis, prognostic evaluation and drug screening.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Nanopartículas Metálicas , Telomerase , Técnicas Biossensoriais/métodos , DNA Catalítico/genética , Ouro/metabolismo , Células HeLa , Humanos , Telomerase/metabolismo
6.
Appl Environ Microbiol ; 88(9): e0018222, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35435716

RESUMO

The detoxification system of reactive oxygen species (ROS) plays critical roles in the survival and virulence of fungal pathogens in infected hosts, while superoxide dismutase (SOD) is the primary ROS scavenger. In the model yeast Saccharomyces cerevisiae, the metal chaperone protein Mtm1 is required for mitochondrial Sod2 activation and responses to oxidative stress. However, the function of the S. cerevisiae Mtm1 homolog in the human fungal pathogen Aspergillus fumigatus has not yet been clarified. In this study, we found that mitochondria-localized MtmA in A. fumigatus, a putative homolog of yeast Mtm1, not only has a similar function to Mtm1 in responding to oxidative stress resistance by affecting SodB (MnSOD) activity but is also essential for hyphal growth such that repressed expression of MtmA results in severe growth defects in A. fumigatus. In addition, the chelation of Zn2+ can obviously rescue growth defects caused by repression of MtmA, suggesting that MtmA may be involved in hyphal growth by affecting cellular Zn2+ detoxification. Moreover, MtmA contains four Mito-carr domains, whereas only the first Mito-carr domain is required for the function of MtmA. Therefore, the findings in this study suggest that MtmA in A. fumigatus has an important and unique function that is different from that in yeast. IMPORTANCE Knowledge of the key factors required for the viability of pathogenic fungi can help to explore new antifungal drugs. Here, we demonstrate that MtmA is involved in responding to oxidative stress by activating mitochondrial SodB activity. MtmA, especially for the first Mito-carr domain, is essential for colony growth by regulating cellular Zn2+ equilibrium and responses to oxidative stress in A. fumigatus. This is the first report of the vital and unique role of the MtmA protein in pathogenic fungi, indicating that it might be a potential antifungal drug target.

7.
Redox Biol ; 52: 102305, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35367811

RESUMO

Hepatocellular cell death and macrophage proinflammatory activation contribute to the pathology of various liver diseases, during which XBP1 plays an important role. However, the function and mechanism of XBP1 in thioacetamide (TAA)-induced acute liver injury (ALI) remains unknown. Here, we investigated the effects of XBP1 inhibition on promoting hepatocellular pyroptosis to activate macrophage STING signaling during ALI. While both TAA- and LPS-induced ALI triggered XBP1 activation in hepatocytes, hepatocyte-specific XBP1 knockout mice exhibited exacerbated ALI with increased hepatocellular pyroptosis and enhanced macrophage STING activation. Mechanistically, mtDNA released from TAA-stressed hepatocytes could be engulfed by macrophages, further inducing macrophage STING activation in a cGAS- and dose-dependent manner. XBP1 deficiency increased ROS production to promote hepatocellular pyroptosis by activating NLRP3/caspase-1/GSDMD signaling, which facilitated the extracellular release of mtDNA. Moreover, impaired mitophagy was found in XBP1 deficient hepatocytes, which was reversed by PINK1 overexpression. Mitophagy restoration also inhibited macrophage STING activation and ALI in XBP1 deficient mice. Activation of XBP1-mediated hepatocellular mitophagy and pyroptosis and macrophage STING signaling pathway were observed in human livers with ALI. Collectively, these findings demonstrate that XBP1 deficiency promotes hepatocyte pyroptosis by impairing mitophagy to activate mtDNA/cGAS/STING signaling of macrophages, providing potential therapeutic targets for ALI.


Assuntos
Mitofagia , Piroptose , Animais , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Macrófagos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/farmacologia , Transdução de Sinais
8.
Exp Cell Res ; 417(1): 113161, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35447102

RESUMO

Breast cancer, the most prevalent malignancy in women, is also the leading cause of cancer-related deaths in women worldwide. The activation of the Wnt pathway plays a pivotal role in the metastatic abilities of breast cancer. In this study, IL1F6, MRGPRX1, and SEC14L3 were significantly correlated to breast cancer patients'overall survival based on TCGA-BRCA dataset. Although IL1F6, MRGPRX1 and SEC14L3 high expression were associated with better survival in breast cancer patients, SEC14L3 had the biggest survival benefit for breast cancer; therefore, SEC14L3 was selected for the subsequent investigation. SEC14L3 mRNA expression and protein levels within breast cancer cell lines decreased compared with normal human breast epithelial cells. Overexpressing SEC14L3 in breast cancer cells inhibited the malignant phenotypes of cancer cells, including the capacity of cells to migrate and invade. SEC14L3 overexpression decreased the levels of mesenchymal markers, whereas SEC14L3 knockdown facilitated the malignant behaviors of breast cancer cells. SEC14L3 overexpression also inhibited Wnt/ß-catenin activation. The Wnt agonist strengthened the malignant phenotypes of breast cancer cells; moreover, the anti-tumor effects of SEC14L3 overexpression were partially attenuated by the Wnt agonist. Conclusively, SEC14L3, which is underexpressed in breast cancer cells and tissues, could play a tumor-suppressive role in a Wnt/ß-catenin-related way.

9.
Front Oncol ; 12: 845703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463362

RESUMO

Circular RNAs (circRNAs) are non-coding single-stranded covalently closed circular RNA, mainly produced by reverse splicing of exons of precursor mRNAs (pre-mRNAs). The characteristics of high abundance, strong specificity, and good stability of circRNAs have been discovered. A large number of studies have reported its various functions and mechanisms in biological events, such as the occurrence and development of cancer. In this review, we focus on the classification, characterization, biogenesis, functions of circRNAs, and the latest advances in cancer research. The development of circRNAs as biomarkers in cancer diagnosis and treatment also provides new ideas for studying circRNAs research.

10.
PeerJ ; 10: e13295, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35469197

RESUMO

Background: Gut microbiota has been proposed to be related to the pathogenesis of pulmonary diseases such as asthma and lung cancer, according to the gut-lung axis. However, little is known about the roles of gut microbiota in the pathogenesis of bronchopulmonary dysplasia (BPD). This study was designed to investigate the changes of gut microbiota in neonatal mice with BPD. Methods: BPD model was induced through exposure to high concentration of oxygen. Hematoxylin and eosin (H&E) staining was utilized to determine the modeling efficiency. Stool samples were collected from the distal colon for the sequencing of V3-V4 regions of 16S rRNA, in order to analyze the gut microbiota diversity. Results: Alpha diversity indicated that there were no statistical differences in the richness of gut microbiota between BPD model group and control group on day 7, 14 and 21. Beta diversity analysis showed that there were statistical differences in the gut microbiota on day 14 (R = 0.368, p = 0.021). Linear discriminant analysis effect size (LEfSe) showed that there were 22 markers with statistical differences on day 14 (p < 0.05), while those on day 7 and 21 were 3 and 4, respectively. Functional prediction analysis showed that the top three metabolic pathways were signal transduction (PFDR = 0.037), glycan biosynthesis and metabolism (PFDR = 0.032), and metabolism of terpenoids and polyketides (PFDR = 0.049). Conclusions: BPD mice showed disorder of gut microbiota, which may involve specific metabolic pathways in the early stage. With the progression of neonatal maturity, the differences of the gut microbiota between the two groups would gradually disappear.

11.
BMC Pregnancy Childbirth ; 22(1): 306, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-35399065

RESUMO

BACKGROUND: This study aimed to evaluate the association between homocysteine-related dietary patterns and gestational diabetes mellitus. METHODS: A total of 488 pregnant women at 24-28 weeks of gestation between January 2019 and December 2020 were included. Demographic characteristics, dietary intake, and multivitamin supplement intake information were collected using a food frequency questionnaire (FFQ); fasting venous blood samples were collected for serum index detection. Serum homocysteine (Hcy), folic acid, and B12 were selected as response variables, and hyperhomocysteinemia (hHcy)-related dietary patterns were extracted using the reduced rank regression.. The relationship between the score of hHcy-related dietary patterns and GDM was analyzed using a multivariate logistic regression model. RESULTS: Three hHcy-related dietary patterns were extracted. Only mode 2 had a positive and significant relationship with the risk of developing GDM. After adjusting for confounding factors, the risk of GDM was significantly increased in the highest quartile array compared with the lowest quartile of the pattern (OR = 2.96, 95% Confidence Interval: 0.939-9.356, P = 0.004). There was no significant correlation between dietary pattern 1 and GDM risk (P > 0.05). CONCLUSIONS: Homocysteine-related dietary patterns were positively associated with gestational diabetes mellitus. Adjusting dietary patterns may contribute to the intervention and prevention of GDM.


Assuntos
Diabetes Gestacional , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/prevenção & controle , Dieta , Jejum , Feminino , Homocisteína , Humanos , Gravidez , Análise de Regressão , Fatores de Risco
12.
Food Chem ; 383: 132640, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35413767

RESUMO

Eucommia ulmoides seed oil with high health potential is prone to oxidative rancidity due to its rich unsaturated fatty acids. In this work, three natural antioxidants were selected for exploring the oxidation resistance of the oil compared with the common synthetic antioxidant BHT. Antioxidant activity and its dispersion and migration as well as oxygen barrier performance were predicted via the bond dissociation enthalpy (BDE), mean square displacement (MSD), binding energy (Ebinding) and permeability coefficient (S). The predicted comprehensive performance is as follows: myricetin > epicatechin > caffeic acid > BHT. Free radical scavenging assay and Rancimat assay confirmed the antioxidant activity and protective effect on oil. That is the protective effect of three natural antioxidants on Eucommia ulmoides seed oil is better than BHT and myricetin shows the optimal comprehensive performance. The induction period of myricetin/lipid system increased 164.5% compared with the control. The experimental results are in good consistent with the simulation predictions.


Assuntos
Eucommiaceae , Antioxidantes/química , Hidroxitolueno Butilado , Eucommiaceae/química , Oxirredução , Estresse Oxidativo , Óleos Vegetais/química , Óleos Vegetais/farmacologia
13.
Front Immunol ; 13: 773291, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265067

RESUMO

Neutrophil infiltration plays an important role in the initial phase of hepatic ischemia and reperfusion injury (HIRI). Despite many different key molecules that have been reported to meditate neutrophil trafficking in HIRI, the mechanism of this process has not been fully elucidated. In this study, we found that Carabin deficiency in myeloid cells (LysMCre : Carabinfl/fl) aggravated IRI-induced hepatic injury and apoptosis through increasing the infiltration of CD11b+Ly6G+ neutrophils. ImmGen Datasets further revealed that Carabin was expressed in bone marrow neutrophils (GM.BM) but was significantly downregulated in thio-induced peripheral neutrophils (GN.Thio.PC), which was consistently verified by comparing GM.BM and liver-infiltrating neutrophils induced by IRI. Mechanistically, up-regulation of Carabin in GM.BM in vitro reduced the expression levels of P-selectin, E-selectin, and αvß3 integrin through inhibiting Ras-ERK and Calcineurin-NFAT signaling. Furthermore, blocking P-selectin, E-selectin, and αvß3 integrin in LysMCre : Carabinfl/fl mice decreased the frequency and number of CD11b+Ly6G+ neutrophils and reversed hepatic ischemia-reperfusion damage. In conclusion, our results provide a new understanding of Carabin, such that it is expressed and functions not only in adaptive immune cells (T and B cells) but also in innate immune cells (neutrophils), contributing to the migration of neutrophils. These findings provide novel and promising therapeutic targets for the prevention of HIRI during liver transplantation or hepatic surgery.


Assuntos
Neutrófilos , Traumatismo por Reperfusão , Animais , Calcineurina/metabolismo , Selectina E/metabolismo , Integrinas/metabolismo , Isquemia/metabolismo , Fígado/metabolismo , Camundongos , Neutrófilos/metabolismo , Traumatismo por Reperfusão/metabolismo
14.
Comput Biol Med ; 144: 105387, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35305502

RESUMO

Multi-modality magnetic resonance imaging (MRI) can reveal distinct patterns of tissue in the human body and is crucial to clinical diagnosis. But it still remains a challenge to obtain diverse and plausible multi-modality MR images due to expense, noise, and artifacts. For the same lesion, different modalities of MRI have big differences in context information, coarse location, and fine structure. In order to achieve better generation and segmentation performance, a dual-scale multi-modality perceptual generative adversarial network (DualMMP-GAN) is proposed based on cycle-consistent generative adversarial networks (CycleGAN). Dilated residual blocks are introduced to increase the receptive field, preserving structure and context information of images. A dual-scale discriminator is constructed. The generator is optimized by discriminating patches to represent lesions with different sizes. The perceptual consistency loss is introduced to learn the mapping between the generated and target modality at different semantic levels. Moreover, generative multi-modality segmentation (GMMS) combining given modalities with generated modalities is proposed for brain tumor segmentation. Experimental results show that the DualMMP-GAN outperforms the CycleGAN and some state-of-the-art methods in terms of PSNR, SSMI, and RMSE in most tasks. In addition, dice, sensitivity, specificity, and Hausdorff95 obtained from segmentation by GMMS are all higher than those from a single modality. The objective index obtained by the proposed methods are close to upper bounds obtained from real multiple modalities, indicating that GMMS can achieve similar effects as multi-modality. Overall, the proposed methods can serve as an effective method in clinical brain tumor diagnosis with promising application potential.


Assuntos
Neoplasias Encefálicas , Processamento de Imagem Assistida por Computador , Artefatos , Neoplasias Encefálicas/diagnóstico por imagem , Coleta de Dados , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética
15.
J Hepatol ; 2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35292349

RESUMO

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is associated with the dysregulation of lipid metabolism and hepatic inflammation. The mechanism underlying NASH is unclear. We aim to investigate the role of X-box binding protein-1 (XBP1) in the progression of NASH. METHODS: Human liver tissues obtained from patients with NASH and control group were used to assess XBP1 expression. NASH models were developed in hepatocyte-specific Xbp1 knockout (Xbp1ΔHep), macrophage specific Xbp1 knockout (Xbp1ΔMϕ), macrophage-specific Nlrp3 knockout, and wild-type (Xbp1FL/FL or Nlrp3FL/FL) mice fed with high-fat diet for 26 weeks or methionine/choline deficient diet for 6 weeks. RESULTS: The expression of XBP1 was significantly upregulated in the liver samples from NASH patients. Hepatocyte-specific Xbp1 deficiency inhibited the development of steatohepatitis in the mice fed with the high-fat or methionine/choline deficient diets. Meanwhile, macrophage specific Xbp1 knockout mice developed less severe steatohepatitis and fibrosis than wild-type Xbp1FL/FL mice in response to the high-fat or methionine/choline deficient diets. Macrophage-specific Xbp1 knockout mice showed M2 anti-inflammatory polarization. Xbp1 deleted macrophages reduced steatohepatitis through decreased expression of NLRP3 and secretion of pro-inflammatory cytokines, which mediate M2 macrophage polarization in macrophage-specific Xbp1 knockout mice. Steatohepatitis was less severe in macrophage-specific Nlrp3 knockout mice than in wild-type Nlrp3FL/FL mice. Xbp1 deleted macrophages prevented the hepatic stellate cells activation through decreased expression of TGF-ß1. Less fibrotic changes were observed in macrophage-specific Xbp1 knockout mice than in the wild-type Xbp1FL/FL mice. Inhibition of XBP1 suppressed the development of NASH. CONCLUSION: XBP1 regulates the development of NASH. XBP1 inhibitors protect against steatohepatitis. XBP1 thus is a potential target for the treatment of NASH. LAY SUMMARY: XBP1 is a distinct basic-region leucine zipper transcription factor whose dynamic form is dominated by splicing response upon breakdown by homeostasis in the endoplasmic reticulum and activation of the unfolded protein response. Our study demonstrated that XBP1 is upregulated in liver tissues of patients with NASH. Conditional knockout of Xbp1 in the hepatocytes resulted in decreased lipid accumulation in mice. Genetic specific deletion of Xbp1 in macrophages ameliorated nutritional steatohepatitis and fibrosis in mice by reducing the secretion of pro-inflammatory cytokine, increasing M2 macrophage polarization, and decreasing TGF-ß1 expression. Pharmacological inhibition of XBP1 protects against steatohepatitis and fibrosis, highlighting a promising strategy for NASH therapy.

16.
J Inflamm Res ; 15: 1757-1769, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300216

RESUMO

Introduction: Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a rare and aggressive form of mature B-cell lymphoma commonly found in elder males, but its genetic features are poorly understood. In this study, we had performed target-sequencing of 360 lymphoma-related genes on 76 PT-DLBCL patients with a median age of 65 (33-89). Our data provide a comprehensive understanding of the landscape of mutations in a small subset of PT-DLBCL. Methods: A total of 76 PT-DLBCL patients were sequenced, and their clinical data and follow-up data were collected. The relationship between mutated genes, clinical data and prognosis and survival of PT-DLBCL patients was retrospectively analyzed by statistical software. Results: We observed a median of 15 protein-altering variants per patient in our data and was identified recurrent oncogenic mutations of 360 lymphoma-related genes involved in PT-DLBCL, including PIM1 (74%), MYD88 (50%), KMT2D (38%), KMT2C (34%), BTG2 (34%), TBL1XR1 (34%) and ETV6 (24%). Compared with classic DLBCL, PT-DLBCL showed an increased mutation frequency of PIM1, MYD88, BTG2, while NOTCH1 appeared exclusive mutated with PIM1, MSH3 and ETV6. Cox risk model regression analysis showed that age ≥60 years, IPI 3-5 points, BTG2 gene mutation and extranodal organ invasion suggested poor prognosis. Finally, we constructed an OS predict model of PT-DLBCL patients using above factors with a high accuracy. Conclusion: In conclusion, our results revealed genomic characterization of PT-DLBCL, and the mutation of BTG2 was an independent factor predicting a poor prognosis.

17.
Biomed Res Int ; 2022: 9961412, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35111850

RESUMO

BACKGROUND: MicroRNAs (miRNAs) play important roles in the initiation and progression of cancers. The purpose of the present study was to evaluate the use of serum miRNA biomarkers in the early diagnosis of breast cancer. METHODS: The expression levels of miR-9-5p, miR-17-5p, and miR-148a-3p were analyzed by quantitative reverse transcription-polymerase chain reaction in 49 patients with newly diagnosed breast cancer and 49 healthy controls. The associations between miR-9-5p, miR-17-5p, and miR-148a-3p levels and clinicopathological parameters were also analyzed. Regression analysis and sensitivity and specificity analyses were used to determine the diagnostic efficacy of the miRNAs. RESULTS: Serum levels of miR-9-5p and miR-148a-3p were significantly higher in breast cancer patients than in healthy controls (both P < 0.05), but miR-17-5p levels were not different between the two groups (P = 0.996). Serum miR-9-5p levels were markedly higher in patients with human epidermal growth factor receptor 2- (HER2-) positive breast cancer than in those with HER2-negative breast cancer (P = 0.049). Serum levels of miR-9-5p and miR-148a-3p were positively correlated with the presence of breast cancer, and both miRNAs had high sensitivity and specificity for the diagnosis of breast cancer. CONCLUSIONS: These findings provide evidence that serum miR-9-5p and miR-148a-3p levels may be used as noninvasive biological markers for the clinical diagnosis of breast cancer.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , MicroRNAs/sangue , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade
18.
Plant Cell Environ ; 45(4): 1065-1081, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35129212

RESUMO

Various types of transcription factors have been reported to be involved in plant-pathogen interactions by regulating defence-related genes. GRAS proteins, plant- specific transcription factors, have been shown to play essential roles in plant growth, development and stress responses. By performing a transcriptome study on rice early defence responses to Magnaporthe oryzae, we identified a GRAS protein, OsSCL7, which was induced by M. oryzae infection. We characterized the function of OsSCL7 in rice disease resistance. OsSCL7 was upregulated upon exposure to M. oryzae and pathogen-associated molecular pattern treatments, and knocking out OsSCL7 resulted in decreased disease resistance of rice to M. oryzae. In contrast, overexpression of OsSCL7 could improve rice disease resistance to M. oryzae. OsSCL7 was mainly localized in the nucleus and showed transcriptional activity. OsSCL7 can interact with GF14c, a 14-3-3 protein, and loss-of-function GF14c leads to enhanced susceptibility to M. oryzae. Additionally, OsSCL7 protein levels were reduced in the gf14c mutant and knocking out OsSCL7 affected the expression of a series of defence-related genes. Taken together, these findings uncover the important roles of OsSCL7 and GF14c in plant immunity and a potential mechanism by which plants fine-tune immunity by regulating the protein stability of a GRAS protein via a 14-3-3 protein.


Assuntos
Magnaporthe , Oryza , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Magnaporthe/metabolismo , Oryza/metabolismo , Doenças das Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteostase , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Cytokine Growth Factor Rev ; 63: 34-43, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35115233

RESUMO

Recent studies have identified an association between perturbed type I interferon (IFN) responses and the severity of coronavirus disease 2019 (COVID-19). IFNα intervention may normalize the dysregulated innate immunity of COVID-19. However, details regarding its utilization and therapeutic evidence have yet to be systematically evaluated. The aim of this comprehensive review was to summarize the current utilization of IFNα for COVID-19 treatment and to explore the evidence on safety and efficacy. A comprehensive review of clinical studies in the literature prior to December 1st, 2021, was performed to identify the current utilization of IFNα, which included details on the route of administration, the number of patients who received the treatment, the severity at the initiation of treatment, age range, the time from the onset of symptoms to treatment, dose, frequency, and duration as well as safety and efficacy. Encouragingly, no evidence was found against the safety of IFNα treatment for COVID-19. Early intervention, either within five days from the onset of symptoms or at hospital admission, confers better clinical outcomes, whereas late intervention may result in prolonged hospitalization.


Assuntos
COVID-19 , COVID-19/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , SARS-CoV-2 , Resultado do Tratamento
20.
Gut ; 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35140065

RESUMO

OBJECTIVE: Follistatin-like protein 1 (FSTL1) is widely recognised as a secreted glycoprotein, but its role in modulating macrophage-related inflammation during liver fibrosis has not been documented. Herein, we aimed to characterise the roles of macrophage FSTL1 in the development of liver fibrosis. DESIGN: Expression analysis was conducted with human liver samples obtained from 33 patients with liver fibrosis and 18 individuals without fibrosis serving as controls. Myeloid-specific FSTL1-knockout (FSTL1M-KO) mice were constructed to explore the function and mechanism of macrophage FSTL1 in 3 murine models of liver fibrosis induced by carbon tetrachloride injection, bile duct ligation or a methionine-deficient and choline-deficient diet. RESULTS: FSTL1 expression was significantly elevated in macrophages from fibrotic livers of both humans and mice. Myeloid-specific FSTL1 deficiency effectively attenuated the progression of liver fibrosis. In FSTL1M-KO mice, the microenvironment that developed during liver fibrosis showed relatively less inflammation, as demonstrated by attenuated infiltration of monocytes/macrophages and neutrophils and decreased expression of proinflammatory factors. FSTL1M-KO macrophages exhibited suppressed proinflammatory M1 polarisation and nuclear factor kappa B pathway activation in vivo and in vitro. Furthermore, this study showed that, through its FK domain, FSTL1 bound directly to the pyruvate kinase M2 (PKM2). Interestingly, FSTL1 promoted PKM2 phosphorylation and nuclear translocation, reduced PKM2 ubiquitination to enhance PKM2-dependent glycolysis and increased M1 polarisation. Pharmacological activation of PKM2 (DASA-58) partially countered FSTL1-mediated glycolysis and inflammation. CONCLUSION: Macrophage FSTL1 promotes the progression of liver fibrosis by inducing M1 polarisation and inflammation based on the intracellular PKM2 reprogramming function of macrophages.

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