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1.
Front Plant Sci ; 13: 944364, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072318

RESUMO

Four P4-ATPase flippase genes, VdDrs2, VdNeo1, VdP4-4, and VdDnf1 were identified in Verticillium dahliae, one of the most devastating phytopathogenic fungi in the world. Knock out of VdDrs2, VdNeo1, and VdP4-4, or knock down of VdDnf1 significantly decreased the pathogenicity of the mutants in cotton. Among the mutants, the greatest decrease in pathogenicity was observed in ΔVdDrs2. VdDrs2 was localized to plasma membrane, vacuoles, and trans-Golgi network (TGN). In vivo observation showed that the infection of the cotton by ΔVdDrs2 was significantly delayed. The amount of two known Verticillium toxins, sulfacetamide, and fumonisin B1 in the fermentation broth produced by the ΔVdDrs2 strain was significantly reduced, and the toxicity of the crude Verticillium wilt toxins to cotton cells was attenuated. In addition, the defect of VdDrs2 impaired the synthesis of melanin and the formation of microsclerotia, and decreased the sporulation of V. dahliae. Our data indicate a key role of P4 ATPases-associated vesicle transport in toxin secretion of disease fungi and support the importance of mycotoxins in the pathogenicity of V. dahliae.

2.
J Clin Lab Anal ; : e24703, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129029

RESUMO

BACKGROUND: Aerobic glycolysis is a main characteristic of tumors, and inhibited glycolysis impedes the tumor development. Farnesoid X Receptor (FXR) mainly regulates bile acid metabolism. In this research, we mainly investigated whether FXR was involved in the regulation of glycolysis in colon cancer. METHODS: The differential expression analysis was performed on FXR and Enhancer Binding Protein Beta (CEBPB) data in colon cancer downloaded from The Cancer Genome Atlas (TCGA) database. Western blot and qRT-PCR were used to detect the expression levels of CEBPB and FXR. The upstream gene of FXR was predicted through bioinformatic analysis. ChIP and dual luciferease assays were performed to confirm the targeted relationship between CEBPB and FXR. Gene Set Enrichment Analysis (GSEA) was performed on FXR. Finally, the glycolysis capabilities of cells in each treatment group were detected. CCK-8, colony formation assay and flow cytometry were performed to test proliferation and apoptosis of colon cancer cells. RESULTS: FXR was lowly expressed at the cell level in colon cancer. In vitro assays verified the antitumor effect of FXR on colon cancer. ChIP and dual luciferase assays verified that transcription factor CEBPB bound with the promotor region of FXR, and negatively regulated the expression of FXR. Cell function assays proved that silenced expression of FXR promoted glycolysis, which promoted the development of colon cancer cells. CONCLUSION: The study on FXR-regulated glycolysis of colon cancer cells helps us to further understand the molecular mechanism by which FXR regulated the development of colon cancer cells.

3.
J Agric Food Chem ; 70(33): 10121-10133, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35960196

RESUMO

Myostatin (MSTN) is a growth and differentiation factor that regulates proliferation and differentiation of myoblasts, which in turn controls skeletal muscle growth. It may regulate myoblast differentiation by influencing miRNA expression, and the present study aimed to clarify its precise mechanism of action. Here, we found that MSTN-/- pigs showed an overgrowth of skeletal muscle and upregulated miR-455-3p level. Intervention of MSTN expression using siMSTN in C2C12 myoblasts also showed that siMSTN significantly increased the expression of miR-455-3p. It was found that miR-455-3p directly targeted the 3'-untranslated region of Smad2 by dual-luciferase assay. qRT-PCR, Western blotting, and immunofluorescence analyses indicated that miR-455-3p overexpression or Smad2 silencing in C2C12 myoblasts significantly promoted myoblast differentiation. Furthermore, siMSTN significantly increased the expression of GATA3. The levels of miR-455-3p were considerably reduced in C2C12 myoblasts following GATA3 knockdown. Consistently, GATA3 knockdown also reduced the enhanced miR-455-3p expression caused by siMSTN. Finally, we illustrated that GATA3 has a role in myoblast differentiation regulation. Taken together, we identified the expression profiles of miRNAs in MSTN-/- pigs and found that miR-455-3p positively regulates myoblast differentiation. In addition, we revealed that MSTN acts through the GATA3/miR-455-3p/Smad2 cascade to regulate muscle development.


Assuntos
MicroRNAs , Miostatina , Regiões 3' não Traduzidas , Animais , Diferenciação Celular , Proliferação de Células/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Miostatina/genética , Miostatina/metabolismo , Suínos/genética
4.
Cell Biol Int ; 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36030536

RESUMO

MYH9 encodes the heavy chain of nonmuscle myosin IIA, a ubiquitously expressed cytoplasmic myosin that regulates the actin cytoskeleton, cell migration, cell polarization, and signal transduction in cancer cells. Here, we investigated the role of MYH9 in cancer stem cells (CSCs) associated with esophageal cancer (EC). The subcellular localization of MYH9 was investigated in SKGT-4 cells through immunofluorescent analysis. MYH9+ and MYH9- spheroid cells were derived from SKGT-4 cells by flow cytometry and compared for self-renewal capacity, tumorigenicity, CD133 positivity, cisplatin resistance, and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) activity. MYH9 messenger RNA expression was assessed in 30 EC patients by quantitative reverse transcription-polymerase chain reaction. Kaplan-Meier curves were plotted to explore the influence of MYH9 on EC survival. MYH9 localized to the plasma membrane, cytoplasm, and nucleus of SKGT-4 cells. Spheroid cells displayed higher MYH9 expression and positivity compared to parental SKGT-4 cells. MYH9+ cells showed strong CSC characteristics, including in vivo tumorigenicity, migration, invasion, cisplatin resistance, and CD133+ positivity. MYH9 activated the PI3K/AKT/mTOR axis in CSCs and was upregulated in EC patients with poor survival. Collectively, these data show that MYH9 significantly promotes tumorigenesis by regulating PI3K/AKT/mTOR signaling in EC. MYH9 expression remarkably correlates with poor prognosis and represents a novel biomarker and drug target for the diagnosis and treatment of EC.

5.
Biochem Genet ; 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35984539

RESUMO

Circular RNA_0004712 (circ_0004712) is reported to be up-regulated in rheumatoid arthritis (RA) patients. Nevertheless, its role and mechanism in RA pathology remain to be clarified. RNA and protein expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell viability, proliferation, apoptosis, migration, and inflammation were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-20-deoxyuridine assay, flow cytometry, scratch test, and enzyme-linked immunosorbent assay. The target correlation between microRNA-633 (miR-633) and circ_0004712 or TNF receptor associated factor 6 (TRAF6) was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ_0004712 was up-regulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0004712 silencing suppressed the viability, proliferation, migration and inflammatory response and facilitated the apoptosis of RA-FLSs. miR-633 was confirmed to be a direct target of circ_0004712, and miR-633 knockdown reversed circ_0004712 silencing-mediated protective effects on the dysfunction and inflammation of RA-FLSs. TRAF6 was a direct target of miR-633, and miR-633 overexpression suppressed the aggressive changes of RA-FLSs by down-regulating TRAF6. Circ_0004712 could up-regulate TRAF6 expression by sponging miR-633 in RA-FLSs. Circ_0004712 interference inactivated nuclear factor (NF)-κB signaling by targeting miR-633/TRAF6 axis. Circ_0004712 silencing inhibited the aggressive changes of RA-FLSs by targeting miR-633/TRAF6 axis and NF-κB signaling, which provided new targets for RA therapy.

6.
Res Vet Sci ; 152: 228-235, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-36027840

RESUMO

Current studies on myostatin (MSTN), a well-known negative regulator of skeletal muscle, studies mainly focus on the its effects on skeletal muscle.However, its effects on smooth muscle are less studied, especially in the uterine horns. To identify the role of MSTN in uterine horn smooth muscle, this study used 6-8-month-old homozygous MSTN mutant (MSTN-/-) gilts in anoestrum as animal models. Histochemical and immunofluorescence staining, western blotting, and RT-qPCR were performed. The results showed that the uteri of the MSTN-/- gilts were morphologically normal, and the uterine horn smooth muscle content was increased (MSTN-/-: 75.19%, Wild type: 51.52%, P < 0.01). In vivo immunofluorescence staining showed that the expression of the uterine horn smooth muscle-specific marker proteins, namely α-smooth muscle actin (ACTA2) and calponin, increased after MSTN knockout (1.41- and 1.21-fold, respectively, P < 0.05). Increased gene expression was also seen in MSTN-/- gilts in vivo for ACTA2 (approximately 2-fold), smooth muscle myosin heavy chain (7.14-fold), myocardin (9.32-fold), and serum response factor (2.17-fold). Protein expression of smooth muscle-specific markers was increased (1.51-fold for ACTA2, 1.57-fold for calponin, P<0.05). MSTN knockout promoted proliferation of the smooth muscle cell and the gene expression of c-kit, a peristaltic marker (2.43-fold, P < 0.05). The results of the in vitro experiments were consistent with those of the in vivo experiments. The present study indicates that MSTN knockout can increase the smooth muscle content of uterine horns, thus providing potential therapeutic targets for pregnancy disorders caused by increased smooth muscle content.

7.
J Food Biochem ; : e14298, 2022 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-35780305

RESUMO

This study aims to analyze the flavor differences of freeze-dried sea cucumber powder, processed for different time intervals, under vibration mill-assisted complex enzyme hydrolysis using electronic nose (E-nose) and gas chromatography-ion mobility spectrometry (GC-IMS). The results of principal component analysis by E-nose showed distinction among the four groups of freeze-dried sea cucumber powder (papain-neutral protease (PN) and flavorzyme-neutral protease (FN), processed for 60 and 80 min). The GC-IMS revealed 35 volatile compounds. Subsequently, based on the fingerprint and heat map results, the flavor differences among the samples were clearly distinguished. When compared to the other three groups, the 60-FN group exhibited a greater variety and quantity of volatile compounds such as octanal, heptanal, hexanal, (E, Z)-2,6-nonadienal, and nonanal. The 80-PN group exhibited high amounts of 2-propanone, ethylbenzene, ethyl acetate, and 2,5-dimethylpyrazine. In addition, the vibration mill technique was considered to be a mild enzyme-assisted method. PRACTICAL APPLICATIONS: This study found that different enzyme types and physical technology operation time can affect the different volatile flavor compounds of freeze-dried sea cucumber powder, which can be quickly and effectively be identified by E-nose and GC-IMS technology to improve the flavor and quality of the product, while facilitating the rapid adjustment and development of the industry. Meanwhile, the results of the study could provide a reference for the deep processing and flavor improvement of the sea cucumber industry and make an important contribution to the related literature. In addition, this could also promote the development and application of non-thermal processing technologies such as vibratory mill in the freeze-dried sea cucumber powder industry.

8.
J Fungi (Basel) ; 8(6)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35736117

RESUMO

Lipid assimilation, storage, and turnover impact growth, development, and virulence in many microbial pathogens including fungi. Perilipins are proteins associated with lipid droplets (LDs) that mediate their assembly and turnover. Here, we characterized the Beauveria bassiana (BbPlin1) perilipin. BbPlin1 expression was higher in minimal media than in rich media, and, using a BbPlin1::eGFP fusion protein, the protein was shown to be co-localized to LDs, with the high expression seen during infection and proliferation within the insect (Galleria mellonella) host that dramatically decreased to almost no expression during fungal outgrowth on cadavers including in conidia, but that BbPlin1 production resumed in the conidia once placed in nutrient-containing media allowing for germination and growth. Characterization of a targeted gene deletion strain (ΔBbPlin1) revealed a dramatic (>30%) reduction in cellular LD content, promotion of aerial hyphal growth, and a small decrease in virulence, with little to no effects on vegetative growth and stress responses. However, in the ΔBbPlin1 strain, expression of the complementary LD-associated caleosin gene, BbCal1, was enhanced under nutrient-poor conditions, although no changes in BbPlin1 expression were seen in a ΔBbCal1 strain and the expression of BbPlin1 in the ΔBbCal1 strain did not change LD patterns in cells. Transcriptome and RT-PCR analyses indicated increased expression of lipid metabolism-related genes, including triacylglyercol lipase 3, enoyl-CoA isomerase, and diacylglycerol-O-acetyl transferase in the BbPlin1 deletion mutant. Lipid profile analyses confirmed that the loss of BbPlin1 significantly reduced the cellular levels of contents of triacylglycerol, diacylglycerol, and phosphatidylethanolamine as compared to the wild-type strain. These results demonstrate the involvement of the B. bassiana perilipin in mediating lipid homeostasis, fungal aerial hyphal growth, and virulence, revealing critical cycling from high expression during nutrient utilization within host cadavers to low expression during growth on the surface of the cadaver during the infection process.

9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(6): 559-564, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35732613

RESUMO

Inflammatory bowel disease (IBD) is a non-specific intestinal inflammatory disease with slow onset, varying severity and recurrence. Even though the causes of IBD are still unknown, studies have indicated that the pathogenesis of IBD is associated with multiple factors, including environment, genetics, infection and immunity. Autophagy is involved in regulating the immune response of IBD through a variety of ways such as pathogen removal, immune function, regulation of inflammatory signals, or inhibition of inflammasomes. Recent studies suggested that autophagy-related genes including ATG16L1, IRGM, and NOD2 are highly susceptible genes related to IBD, and gene deletion and mutation affect the occurrence and development of IBD. Hereby, we review the mechanism of autophagy and its related genes regulating the cytokines secretion and adjusting the immune response in IBD.


Assuntos
Predisposição Genética para Doença , Doenças Inflamatórias Intestinais , Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Humanos , Inflamassomos , Doenças Inflamatórias Intestinais/genética
10.
iScience ; 25(7): 104522, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35754714

RESUMO

Compared with the conventional DNA probe immobilization on the planar surface, nanoparticles-based DNA probes enable more RNA molecules to be anchored to the sensor surface, thereby improving the detection sensitivity. In this work, we report phosphorodiamidate morpholino oligomers (PMO)-graphene quantum dots (GQDs)-functionalized reduced graphene oxide (RGO) field effect transistor (FET) biosensors for ultrasensitive detection of exosomal microRNAs. After the RGO FET sensor was fabricated, polylysine (PLL) film was deposited onto the RGO surface. GQDs-PMO hybrid was prepared and covalently bound to PLL surface, enabling detection of exosomal microRNAs (miRNAs). The method achieved a detection limit as low as 85 aM and high specificity. Furthermore, the FET sensor was able to detect exosomal miRNAs in plasma samples and distinguish breast cancer samples from healthy samples. Compared with other methods, we use GQDs to further improve the sensitivity of FET, making it a potential tool for early diagnosis of breast cancer.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(6): 626-630, 2022 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-35762427

RESUMO

OBJECTIVES: To evaluate the effectiveness of induction therapy with exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD). METHODS: A retrospective analysis was performed on the medical data of 62 children with CD who received EEN in Children's Hospital, Zhejiang University School of Medicine, from March 2013 to August 2021. The medical data included general information and height, weight, Pediatric Crohn's Disease Activity Index (PCDAI), Crohn's Disease Endoscopic Index of Severity, C-reactive protein, erythrocyte sedimentation rate, and serum albumin level before treatment and after 8 weeks of treatment. The changes in the above indicators were compared before and after treatment. RESULTS: Among the 62 children with CD, there were 39 boys (63%) and 23 girls (37%), with a mean age of (11.9±3.0) years at diagnosis. Among the 55 children who completed EEN treatment for at least 8 weeks, 48 (87%) achieved clinical remission at week 8. PCDAI at week 8 was significantly lower than that before treatment (P<0.001). Except for 17 children with involvement of the small intestine alone and 3 children with involvement of the colon who did not receive colonoscopy reexamination, the remaining 35 children with involvement of the colon received colonoscopy reexamination after the 8-week EEN treatment. Of the 35 children, 29 (83%) achieved mucosal healing. As for the 48 children who achieved clinical remission at week 8, there were significant improvements in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P<0.01). As for the 7 children who did not achieve clinical remission at week 8, there were no significant changes in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P>0.05). CONCLUSIONS: The 8-week EEN treatment has a good effect on clinical remission and mucosal healing in children with CD. For the children with CD achieving clinical remission, EEN can improve their height and body mass index.


Assuntos
Doença de Crohn , Nutrição Enteral , Adolescente , Criança , Doença de Crohn/terapia , Feminino , Humanos , Quimioterapia de Indução , Masculino , Estudos Retrospectivos
13.
Inflamm Res ; 71(7-8): 911-922, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35731253

RESUMO

BACKGROUND: The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism. METHODS: C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines. RESULTS: The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866. CONCLUSION: In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.


Assuntos
Nicotinamida Fosforribosiltransferase , Sepse , Animais , Citocinas/metabolismo , Via de Sinalização Hippo , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo
14.
World J Pediatr ; 18(8): 538-544, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35771382

RESUMO

BACKGROUND: Severe acute hepatitis of unknown etiology in children has recently exhibited a global trend of concentrated occurrence. This review aimed to summarize the current available information regarding the outbreak of severe acute hepatitis and introduce our hospital's previous experiences with the diagnosis and treatment of severe acute hepatitis for reference. DATA SOURCES: Websites including the UK Health Security Agency, European Centre for Disease Prevention and Control, CDC, WHO, and databases including PubMed/Medline, Cochrane Library, Embase and Web of Science were searched for articles on severe acute hepatitis in children. RESULTS: As of May 26, 2022, a total of 650 cases have been reported in 33 countries; at least 38 (6%) children required liver transplantation, and nine (1%) died. Cases are predominantly aged between 3 and 5 years old, and there are no epidemiological links among them. The common manifestations are jaundice, vomiting and pale stools. Adenovirus tested positive in most cases, and SARS-CoV-2 and other viruses were detected in a few cases, but virus particles were not found in liver tissue. Adenovirus immunohistochemistry showed immunoreactivity in the intrasinusoidal lumen from some liver samples. The hierarchical treatment includes symptomatic and supportive therapy, management of coagulation disorders and hepatic encephalopathy, artificial liver support, and liver transplantation (approximately 6%-10% of cases require liver transplant). CONCLUSIONS: The etiology of this severe acute hepatitis in children is not clear. The clinical features are severe acute hepatitis with significantly elevated liver enzymes. Clinicians need to be alert to children with hepatitis.


Assuntos
Hepatite , Doença Aguda , Criança , Pré-Escolar , Hepatite/diagnóstico , Hepatite/prevenção & controle , Hepatite/terapia , Humanos
15.
Med Oncol ; 39(5): 72, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35568747

RESUMO

Renal cell carcinoma (RCC) is the most common form of malignancy affecting the kidneys. Circular RNAs (circRNAs) are non-coding RNAs that are derived from exonic or intronic sequences through a selective shearing process. There is growing evidence that these circRNAs can influence a range of biological pathways by serving as protein decoys, microRNA sponges, regulators of transcriptional activity, or templates for protein translation. The dysregulation of circRNA expression patterns is a hallmark of RCC and other cancer types, and there is strong evidence that these RNA species can play central roles in the onset and progression of RCC tumors. In the present review, we summarized recent findings on the functional roles and clinical impacts of circRNAs in RCC. Further, we discussed their potential utility as diagnostic biomarkers or targets for therapeutic intervention.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Carcinogênese/genética , Carcinoma de Células Renais/genética , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , MicroRNAs/genética , RNA Circular/genética
16.
Immunopharmacol Immunotoxicol ; : 1-9, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35635075

RESUMO

BACKGROUND: The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. METHOD: Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. RESULTS: AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing alanine aminotransferase, aspartate aminotransferase, serum urea nitrogen, and serum creatinine and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1ß, and IL-6 and regulating MDA, SOD, and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1ß, and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. CONCLUSIONS: AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.

17.
Front Oncol ; 12: 869895, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35515110

RESUMO

Purpose: To develop deep learning (DL) models based on multiphase dual-energy spectral CT for predicting lymph nodes metastasis preoperatively and noninvasively in papillary thyroid cancer patients. Methods: A total of 293 lymph nodes from 78 papillary thyroid cancer patients who underwent dual-energy spectral CT before lymphadenectomy were enrolled in this retrospective study. The lymph nodes were randomly divided into a development set and an independent testing set following a 4:1 ratio. Four single-modality DL models based on CT-A model, CT-V model, Iodine-A model and Iodine-V model and a multichannel DL model incorporating all modalities (Combined model) were proposed for the prediction of lymph nodes metastasis. A CT-feature model was also built on the selected CT image features. The model performance was evaluated with respect to discrimination, calibration and clinical usefulness. In addition, the diagnostic performance of the Combined model was also compared with four radiologists in the independent test set. Results: The AUCs of the CT-A, CT-V, Iodine-A, Iodine-V and CT-feature models were 0.865, 0.849, 0.791, 0.785 and 0.746 in the development set and 0.830, 0.822, 0.744, 0.739 and 0.732 in the testing set. The Combined model had outperformed the other models and achieved the best performance with AUCs yielding 0.890 in the development set and 0.865 in the independent testing set. The Combined model showed good calibration, and the decision curve analysis demonstrated that the net benefit of the Combined model was higher than that of the other models across the majority of threshold probabilities. The Combined model also showed noninferior diagnostic capability compared with the senior radiologists and significantly outperformed the junior radiologists, and the interobserver agreement of junior radiologists was also improved after artificial intelligence assistance. Conclusion: The Combined model integrating both CT images and iodine maps of the arterial and venous phases showed good performance in predicting lymph nodes metastasis in papillary thyroid cancer patients, which could facilitate clinical decision-making.

18.
Int J Biochem Cell Biol ; 147: 106212, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35439649

RESUMO

Loss of muscle mass can lead to diseases such as sarcopenia, diabetes, and obesity, which can worsen the quality of life and increase the incidence of disease. Therefore, understanding the mechanism underlying skeletal muscle differentiation is vital to prevent muscle diseases. We previously found that microRNA-320 (miR-320) is highly expressed in the lean muscle-type pigs, but its regulatory role in myogenesis remains unclear. The bioinformatics prediction indicated that miR-320 could bind to the 3 'untranslated region of growth factor receptor-bound protein-2 (Grb2). We hypothesized that miR-320 targets Grb2 to regulate myoblasts differentiation. To verify this, we transfected miR-320 mimic and inhibitor into C2C12 myoblasts to assess the role of miR-320 during myoblasts differentiation. We used real-time qPCR, luciferase reporter assays, and western blotting to confirm that miR-320 directly targets Grb2 to promote myoblasts differentiation. Moreover, by using a dexamethasone-induced atrophic model of myotubes, we discovered that miR-320 promotes the repair of damaged myotubes. Our findings expand understanding of miRNAs and genes related to regulating skeletal muscle differentiation, and provide insight into underlying therapeutic strategies for muscle diseases.


Assuntos
MicroRNAs , Qualidade de Vida , Regiões 3' não Traduzidas , Animais , Atrofia/metabolismo , Diferenciação Celular/genética , Proliferação de Células/genética , Proteína Adaptadora GRB2/genética , Proteína Adaptadora GRB2/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Desenvolvimento Muscular/genética , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Suínos
19.
Anim Genet ; 53(3): 307-316, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35285059

RESUMO

Obesity is associated with increased serum fibrinogen level. Myostatin (MSTN), a strong inhibitor of skeletal muscle growth, is recognized as a potential target for obesity. However, the effect of MSTN inhibition on fibrinogen is not largely known. The objective of the present study was to explore fibrinogen levels after MSTN inhibition. Fibrinogen levels and the fibrin clot structure of MSTN homozygous knockout (KO) and wild-type (WT) pigs (n = 4 in each group) were investigated. The protein expression of fibrinogen in the serum and liver of KO pigs decreased greatly (1.6-fold loss for serum and 2.5-fold loss for liver). KO pigs showed significantly decreased gene expression of fibrinogen chains: FGA (fibrinogen-α; 11-fold), FGB (fibrinogen-ß; 8-fold) and FGG (fibrinogen-γ; 7.4-fold). The basal transcriptional regulators of fibrinogen, HNF1 (hepatocyte nuclear factor 1) and CEBP-α (CCAAT/Enhancing-binding protein-alpha) were remarkably down-regulated after interruption of MSTN expression by siRNA (small interfering RNA) in cultured hepatocytes (about 2- and 4-fold, respectively). Compared with WT pigs, KO pigs displayed altered fibrin clot structure with thinner fibers, decreased turbidity and increased permeability. The findings indicate that the inhibition of MSTN could affect fibrinogen levels and the fibrin clot structure.


Assuntos
Miostatina , Doenças dos Suínos , Animais , Fibrina/genética , Fibrina/metabolismo , Fibrinogênio/genética , Fibrinogênio/metabolismo , Homozigoto , Músculo Esquelético/metabolismo , Miostatina/genética , Obesidade , Suínos/genética
20.
Int J Gen Med ; 15: 2377-2387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35264875

RESUMO

Objective: The aim of this study is to determine if cervical cerclage administration reduces the preterm birth (PTB) rate at a gestational age (GA) of 16-28 weeks in women with twin pregnancy. Methods: This is a retrospective cohort study on asymptomatic twin pregnancy with an ultrasound-identified cervix length (CL) of ≦25 mm. The patients were divided into two groups: ultrasound-indicated cerclage (UIC) group and control (expectant management) group. The primary outcome was a PTB rate at <34 weeks. A logistic regression was also performed, and a subgroup analysis stratified by CL and GA at first short cervix diagnosis was planned. Results: In all 320 women, there were no differences in the overall <34-week PTB rates and neonatal outcomes between the UIC group and control group. After performing a multivariate logistic regression analysis, the subgroup analyses were planned. In patients with a CL of ≦15 mm, the <34-week PTB rate was significantly decreased in the UIC subgroup compared with the control subgroup (60.78% vs 78.26%; odds ratio (OR) = 0.43, confidence interval (CI) = 95% [0.22-0.86]; and p = 0.020). In patients with a first short cervix diagnosis GA of ≦24 weeks, the <34-week PTB rate was significantly decreased in the UIC subgroup when compared with the control subgroup (61.54% vs 84.75%; OR = 0.29; CI = 95% [0.13-0.63]; and p = 0.001). Furthermore, compared with the control groups, the UIC groups had higher mean birth weight, lower perinatal mortality, and lower NICU admission, and the differences were statistically significant. Conclusion: UIC could significantly reduce the <34-week PTB rate and improve perinatal outcomes in patients with a CL of ≦15mm or first short cervix diagnosis GA of ≦24 weeks with asymptomatic twin pregnancy during the second trimester.

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