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1.
Chin Med Sci J ; 36(2): 127-134, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34231461

RESUMO

Objective To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma (ccRCC) via bioinformatics analysis. Methods The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were available from the Gene Expression Omnibus database: GSE12606, GSE36895 and GSE66272. The differentially expressed genes were screened with GEO2R and J Venn online tools. Functional annotation including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was applied to identify the possible function of the hub genes involved in prognosis of ccRCC. In protein protein interaction network (PPI network), the STRING online tool was used to visualize the network of the differentially expressed genes, and the core gene was selected by MCODE App in Cytoscape software. Finally, GEPIA Survival Plot was performed to assess genes associated with worse survival. Results We totally found 648 differentially expressed genes, including 222 up-regulated genes and 426 down-regulated genes. PPI network showed that in 28 up-regulated genes 7 (CCNE2, CDK1, CDC6, CCNB2, BUB1, TTK and PTTG1) enriched in cell cycle and 4 genes (CCNE2, CDK1, CCNB2 and RRM2) enriched in p53 signaling pathway. GEPIA Survival Plot assay revealed that ccRCC patients carrying CDK1, CCNB2, RRM2, BUB1, and PTTG1 had a worse survival. GEPIA Box Plot showed that BUB1, CCNB2, PTTG1, and RRM2 were over expressed in the ccRCC tissues in contrast to the normal tissues (P<0.05). Conclusion ccRCC patients with the four up-regulated differentially expressed genes including BUB1,CCNB2,PTTG1, and RRM2might manifest a poor prognosis.

2.
Cancer ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231883

RESUMO

BACKGROUND: Although stratifying individuals with respect to nasopharyngeal carcinoma (NPC) risk with Epstein-Barr virus-based markers is possible, the performance of diagnostic methods for detecting lesions among screen-positive individuals is poorly understood. METHODS: The authors prospectively evaluated 882 participants aged 30 to 70 years who were enrolled between October 2014 and November 2018 in an ongoing, population-based NPC screening program and had an elevated NPC risk. Participants were offered endoscopy and magnetic resonance imaging (MRI), and lesions were identified either by biopsy at a follow-up endoscopy or further contact and linkage to the local cancer registry through December 31, 2019. The diagnostic performance characteristics of endoscopy and MRI for NPC detection were investigated. RESULTS: Eighteen of 28 identified NPC cases were detected by both methods, 1 was detected by endoscopy alone, and 9 were detected by MRI alone. MRI had significantly higher sensitivity than endoscopy for NPC detection overall (96.4% vs 67.9%; Pdifference = .021) and for early-stage NPC (95.2% vs 57.1%; P = .021). The sensitivity of endoscopy was suggestively lower among participants who had previously been screened in comparison with those undergoing an initial screening (50.0% vs 81.2%; P = .11). The authors observed a higher overall referral rate by MRI versus endoscopy (17.3% vs 9.1%; P < .001). Cases missed by endoscopy had early-stage disease and were more commonly observed for tumors originating from the pharyngeal recess. CONCLUSIONS: MRI was more sensitive than endoscopy for NPC detection in the context of population screening but required the referral of a higher proportion of screen-positive individuals. The sensitivity of endoscopy was particularly low for individuals who had previously been screened.

3.
J Virol Methods ; : 114228, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34224754

RESUMO

High-throughput serological tests that can detect neutralizing antibodies against SARS-CoV-2 are desirable for serosurveillance and vaccine efficacy evaluation. Although the conventional neutralization test (cVNT) remains the gold standard to confirm the presence of neutralizing antibodies in sera, the test is too labour-intensive for massive screening programs and less reproducible as live virus and cell culture is involved. Here, we performed an independent evaluation of a commercially available surrogate virus neutralization test (sVNT, GenScript cPass™) that can be done without biosafety level 3 containment in less than 2 hours. When using the cVNT and a Luminex multiplex immunoassay (MIA) as reference, the sVNT obtained a sensitivity of 94% (CI 90-96%) on a panel of 317 immune sera that were obtained from hospitalized and mild COVID-19 cases from Belgium and a sensitivity of 89% (CI 81-93%) on a panel of 184 healthcare workers from the Democratic Republic of Congo. We also found strong antibody titer correlations (rs>0.8) among the different techniques used. In conclusion, our evaluation suggests that the sVNT could be a powerful tool to monitor/detect neutralising antibodies in cohort and population studies. The technique could be especially useful for vaccine evaluation studies in sub-Saharan Africa where the basic infrastructure to perform cVNTs is lacking.

4.
Pathol Oncol Res ; 27: 582443, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257530

RESUMO

The expression of Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) has been reported to be dysregulated in non-small cell lung carcinoma, especially in lung adenocarcinoma (LUAD). Therefore, we aimed to investigate the functional and prognostic roles of PELP1 in LUAD in this study. We first immunolocalized PELP1 in 76 cases of LUAD and 17 non-pathological or tumorous lung (NTL) tissue specimens and correlated the findings with the clinicopathological parameters of the patients. We then performed in vitro analysis including MTT, flow cytometry, wound healing, and transwell assays in order to further explore the biological roles of PELP1 in 17-ß-estradiol (E2) induced cell proliferation, migration, and invasion of LUAD cells. We subsequently evaluated the prognostic significance of PELP1 in LUAD patients using the online survival analysis tool Kaplan-Meier Plotter. The status of PELP1 immunoreactivity in LUAD was significantly higher than that in the NTL tissues and significantly positively correlated with less differentiated features of carcinoma cells, positive lymph node metastasis, higher clinical stage as well as the status of ERα, ERß, and PCNA. In vitro study did reveal that E2 promoted cell proliferation and migration and elevated PELP1 protein level in PELP1-high A549 and H1975 cells but not in PELP1-low H-1299 cells. Knock down of PELP1 significantly attenuated E2 induced cell proliferation, colony formation, cell cycle progress as well as migration and invasion of A549 and H1975 cells. Kaplan-Meier Plotter revealed that LUAD cases harboring higher PELP1 expression had significantly shorter overall survival. In summary, PELP1 played a pivotal role in the estrogen-induced aggressive transformation of LUAD and could represent adverse clinical outcome of the LUAD patients.

5.
Pathol Oncol Res ; 27: 596899, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257547

RESUMO

Esophageal cancer (ESCA) is a leading cause of cancer-related mortality, with poor prognosis worldwide. DNA damage repair is one of the hallmarks of cancer. Loss of genomic integrity owing to inactivation of DNA repair genes can increase the risk of cancer progression and lead to poor prognosis. We aimed to identify a novel gene signature related to DNA repair to predict the prognosis of ESCA patients. Based on gene expression profiles of ESCA patients from The Cancer Genome Atlas and gene set enrichment analysis, 102 genes related to DNA repair were identified as candidates. After stepwise Cox regression analysis, we established a five-gene prognostic model comprising DGCR8, POM121, TAF9, UPF3B, and BCAP31. Kaplan-Meier survival analysis confirmed a strong correlation between the prognostic model and survival. Moreover, we verified the clinical value of the prognostic signature under the influence of different clinical parameters. We found that small-molecule drugs (trametinib, selumetinib, and refametinib) could help to improve patient survival. In summary, our study provides a novel and promising prognostic signature based on DNA-repair-related genes to predict survival of patients with ESCA. Systematic data mining provides a theoretical basis for further exploring the molecular pathogenesis of ESCA and identifying therapeutic targets.

6.
Pathol Oncol Res ; 27: 603838, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257562

RESUMO

Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is overexpressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer. A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray and the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patients prognosis were analyzed. We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictive factor for pathological response to neoadjuvant chemotherapy and for prognosis in patients with gastric cancer. Our results suggest that GP73 expression correlates with the effect of neoadjuvant chemotherapy and is a promising biomarker to identify patients with poor prognosis.

7.
Zhongguo Zhen Jiu ; 41(7): 742-6, 2021 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-34259405

RESUMO

OBJECTIVE: To compare the efficacy between acupuncture-moxibustion treatment by stages and femoston for premature ovarian insufficiency (POI). METHODS: A total of 66 patients with POI were randomly divided into an observation group (33 cases, 3 cases dropped off) and a control group (33 cases, 2 cases dropped off). The patients in the observation group, based on the theory of "transformation of yin and yang", were treated with acupuncture-moxibustion by stages in the postmenstrual period, ovulatory period, premenstrual period and menstrual period, once every other day, 3 times a week. The patients in the control group were treated with oral administration of femoston (estradiol tablets/estradiol and dydrogesterone tablets, 1 tablet per day). Both groups were treated for 3 menstrual cycles. The ovarian function (serum follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol [E2], anti-mullerian hormone [AMH] and antral follicle count [AFC]) and perimenopausal symptoms [modified Kupperman index (KI) scale score] were observed before and after treatment, and the menstrual improvement of the two groups was compared. RESULTS: Compared before treatment, the serum levels of FSH and LH were decreased (P<0.01), the levels of E2 were increased (P<0.01) in the two groups after treatment; the serum level of AMH and AFC in the observation group were increased after treatment (P<0.01). After treatment, the serum level of AMH and AFC in the observation group were higher than those in the control group (P<0.05). After treatment, there was no significant difference in the menstrual return rate and menstrual regularity rate between the amenorrhea patients of the two groups (P>0.05). After treatment, the modified KI scale scores in the two groups were reduced (P<0.01), and the modified KI scale score in the observation group was lower than that in the control group (P<0.05). CONCLUSION: Acupuncture- moxibustion treatment by stages based on the theory of "transformation of yin and yang" has similar efficacy with femoston in improving serum sex hormone level and menstrual symptoms in patients with POI, and has advantages in improving serum AMH level, AFC and perimenopausal symptoms.

8.
PLoS One ; 16(7): e0253567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214104

RESUMO

OBJECTIVE: To investigate effects of taping techniques on arch deformation in adults with pes planus. METHODS: The following databases were searched up to March 2020, including Web of Science, Pubmed, EBSCO, CNKI and Cochrane Library. Heterogeneity and publication bias were assessed by I2 index and funnel plots, respectively. In addition, Cochrane scale was used to evaluate the quality of research. RESULTS: Navicular height for three antipronation taping techniques significantly increased immediately post tape compared with baseline (mean difference = 4.86 mm, 95% CI = 2.86-6.87 mm, Z = 4.75, p < 0.001). The highest increase was observed in Augmented low-Dye (ALD). Modified low-Dye (MLD) was second only to ALD (p<0.001). Navicular height after walking for 10 min was much higher than baseline (p<0.001), with MLD decreased smaller than ALD. CONCLUSIONS: ALD was the most effective taping technique for controlling foot arch collapse immediately post tape compared with baseline, followed by MLD. By contrast, MLD could possibly performed better than ALD in maintaining immediate navicular height after walking for 10 min. Low-Dye could make resting calcaneal stance position closer to neutral position. Although positive effects of Navicular sling, low-Dye and Double X taping interventions were observed, they could not maintain this immediate navicular height effect after a period of higher intensity weight-bearing exercise.

9.
Biochem Biophys Res Commun ; 569: 61-65, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34229124

RESUMO

For the beneficial pharmacological properties of isoflavonoids and their related glycoconjugates, there is increasingly interest in their enzymatic conversion. In this study, a novel ß-glucosidase gene isolated from metagenomic library of mangrove sediment was cloned and overexpressed in Escherichia coli BL21(DE3). The purified recombination ß-glucosidase, designated as r-Bgl66, showed high catalytic activity for soy isoflavone glycosides. It converted soy isoflavone flour extract with the productivities of 0.87 mM/h for daidzein, 0.59 mM/h for genistein and 0.42 mM/h for glycitein. The kcat/Km values for daidzin, genistin and glycitin were 208.73, 222.37 and 288.07 mM-1 s-1, respectively. In addition, r-Bgl66 also exhibited the characteristic of glucose-tolerance, and the inhibition constant Ki was 471.4 mM. These properties make it a good candidate in the enzymatic hydrolysis of soy isoflavone glycosides. This study also highlights the utility of metagenomic approach in discovering novel ß-glucosidase for soy isoflavone glycosides hydrolysis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34275082

RESUMO

The development of water-stable metal-organic frameworks is a critical issue for their photocatalysis applications in water treatment. A phenyl-ethyl side chain with low surface energy was grafted into NH2-MIL-101(Fe) through a post-synthetic modification (PSM) method. As a result, a novel MIL-101(Fe)-1-(4-(ethyl)phenyl)urea (named MIL-101(Fe)-EPU) was synthesized. Basic morphology, crystal structure, and chemical bond features of MIL-101(Fe)-EPU were retained after PSM. Nitrogen X-ray photoelectron spectroscopy analysis confirmed the successful introduction of the phenyl-ethyl side chain, and this transformation increased its hydrophobicity and water stability. Contact angles of MIL-101(Fe)-EPU to water raised from 59.6 to 140.4°. And its structure maintained intact after 72 h water exposure, indicating higher stability than parent NH2-MIL-101(Fe). In the photocatalysis reaction with visible light and oxidant donor (H2O2), MIL-101(Fe)-EPU demonstrated a degradation efficiency of tetrabromobisphenol A with a reaction rate at 0.0313 min-1. The predominant reaction mechanism was OH·oxidation. The acid condition was beneficial for this photocatalysis reaction and high stability was observed. Besides, photocatalysis efficiency, crystal structure, and chemical structures were all retained in different actual water mediums, suggesting high adaptability of MIL-101(Fe)-EPU. In general, hydrophobic group grafting using a PSM method endows MIL-101(Fe)-EPU the potentiality as photocatalyst for organic contaminant elimination from water.

11.
Medicine (Baltimore) ; 100(27): e26608, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232215

RESUMO

RATIONALE: Patients preparing for surgery may have isolated, prolonged activated partial thromboplastin time (APTT). Cause analysis is warranted in patients who had neither bleeding symptom nor thromboembolic events because isolated prolongation of APTT may lead to unnecessary delayed surgical intervention or invasive procedure, even ineffective plasma infusion treatments. Here, we report a case of Hashimoto thyroiditis-associated thyroid cancer whose APTT was isolated prolonged and discuss the challenges of diagnosis and clinical management of this patient. PATIENT CONCERNS: A 57-year-old woman was admitted to the hospital due to thyroid cancer. Anticoagulant assay was performed for this patient before surgery, she had normal values for prothrombin time, thrombin time, and fibrinogen, but had isolated prolonged APTT value (20 seconds longer than normal). However, the routine laboratory of the local hospital showed normal APTT and she did not have any abnormal bleeding or thrombotic episodes. Lupus anticoagulant (LA) was strongly positive according to mixing studies and modified dilute Russell viper venom time method, it was responsible for prolonged APTT. DIAGNOSES: Hashimoto thyroiditis-associated thyroid cancer whose APTT was isolated prolonged. INTERVENTIONS: The isolated prolongation of APTT in this patient was due to LA. She had no history of anticoagulant medications and no spontaneous bleeding episodes. There should be no specific intervention before thyroidectomy. OUTCOMES: This thyroid cancer patient had an uneventful surgery and was discharged after a week. LESSONS: Prolonged APTT is not considered an absolute indication for plasma infusion therapy in patients with LA. The correct identification of the cause of APTT prolongation is essential for proper treatment of the individuals.


Assuntos
Gerenciamento Clínico , Doença de Hashimoto/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Diagnóstico Diferencial , Feminino , Doença de Hashimoto/sangue , Humanos , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/etiologia
12.
Food Funct ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34223585

RESUMO

Bioactive peptides are a class of peptides with special physiological functions and have potential applications in human health and disease prevention. Bioactive peptides have gained much research attention because they affect the cardiovascular, endocrine, immune, and nervous systems. Recent research has reported that bioactive peptides are of great value for physiological function regulation, including antioxidation, anti-hypertension, antithrombosis, antibacterial properties, anti-cancer, anti-inflammation, anti-diabetic, anti-obesity, cholesterol-lowering, immunoregulation, mineral binding and opioid activities. The production of food-derived bioactive peptides is mainly through the hydrolysis of digestive enzymes and proteolytic enzymes or microbial fermentation. The purpose of this review is to introduce the production, function, application, challenges, and prospects of food-derived bioactive peptides.

13.
Am J Med Sci ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-34266644

RESUMO

BACKGROUND: The prevalence of Fabry disease (FD) in Chinese patients with hypertrophic cardiomyopathy (HCM) is unclear. We aimed to evaluate the prevalence, clinical characteristics, and outcomes of FD in Chinese patients with HCM. METHODS: Of 217 patients with HCM, FD probands were screened by next-generation sequencing at Fuwai Hospital. Medical data from α-galactosidase A activity, electrocardiography, echocardiography, coronary angiography, cardiac magnetic resonance, pathological examination, and follow up was analyzed. RESULTS: Two FD probands were observed (0.93% of patients with HCM), both of which were diagnosed with symptomatic obstructive HCM at 49 years of age. One proband had a GLA mutation (c.887T>C [p.M296T]) with a late-onset cardiac variant, which was characterized by dual ventricular hypertrophy and conduction disease with a permanent pacemaker. The other patient had a GLA mutation (c.758T>C [p.I253T]) with a classic phenotype and dual ventricular hypertrophy, atrioventricular block, renal failure, and recurrent cerebral infarction. Both probands had late gadolinium enhancement mainly in the basal segment of the inferolateral wall. Follow up revealed no exertional symptoms or outflow obstruction after surgical septal myectomy in the two probands, and stable renal function was observed after 6 months of migalastat therapy in the later one. A family study revealed six female carriers and three sudden cardiac deaths. CONCLUSIONS: FD is not uncommon in Chinese patients with HCM. Multiple organic involvement, dual ventricular hypertrophy, and conduction disease provide clinical clues for suspected FD, and early genetic screening is necessary. Surgical septal myectomy and migalastat improve the long-term prognosis of patients with FD.

14.
ACS Nano ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269058

RESUMO

Spatially controlled preparation of heterostructures composed of layered materials is important in achieving interesting properties. Although vapor-phased deposition methods can prepare vertical and lateral heterostructures, liquid-phased methods, which can enable scalable production and further solution processes, have shown limited controllability. Herein, we demonstrate by using wet chemical methods that metallic Sn0.5Mo0.5S2 nanosheets can be deposited epitaxially on the edges of semiconducting SnS2 nanoplates to form SnS2/Sn0.5Mo0.5S2 lateral heterostructures or coated on both the edges and basal surfaces of SnS2 to give SnS2@Sn0.5Mo0.5S2 core@shell heterostructures. They also showed good light-to-heat conversion ability due to the metallic property of Sn0.5Mo0.5S2. In particular, the core@shell heterostructure showed a higher photothermal conversion efficiency than the lateral counterpart, largely due to its randomly oriented and polycrystalline Sn0.5Mo0.5S2 layers with larger interfacing area for multiple internal light scattering.

15.
J Virol Methods ; : 114228, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: covidwho-1294030

RESUMO

High-throughput serological tests that can detect neutralizing antibodies against SARS-CoV-2 are desirable for serosurveillance and vaccine efficacy evaluation. Although the conventional neutralization test (cVNT) remains the gold standard to confirm the presence of neutralizing antibodies in sera, the test is too labour-intensive for massive screening programs and less reproducible as live virus and cell culture is involved. Here, we performed an independent evaluation of a commercially available surrogate virus neutralization test (sVNT, GenScript cPass™) that can be done without biosafety level 3 containment in less than 2 hours. When using the cVNT and a Luminex multiplex immunoassay (MIA) as reference, the sVNT obtained a sensitivity of 94% (CI 90-96%) on a panel of 317 immune sera that were obtained from hospitalized and mild COVID-19 cases from Belgium and a sensitivity of 89% (CI 81-93%) on a panel of 184 healthcare workers from the Democratic Republic of Congo. We also found strong antibody titer correlations (rs>0.8) among the different techniques used. In conclusion, our evaluation suggests that the sVNT could be a powerful tool to monitor/detect neutralising antibodies in cohort and population studies. The technique could be especially useful for vaccine evaluation studies in sub-Saharan Africa where the basic infrastructure to perform cVNTs is lacking.

16.
J Cell Mol Med ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34213077

RESUMO

Pulmonary tuberculosis (PTB) is a major global public health problem. The purpose of this study was to find biomarkers that can be used to diagnose tuberculosis. We used four NCBI GEO data sets to conduct analysis. Among the four data sets, GSE139825 is lung tissue microarray, and GSE83456, GSE19491 and GSE50834 are blood microarray. The differential genes of GSE139825 and GSE83456 were 68 and 226, and intersection genes were 11. Gene ontology (GO) analyses of 11 intersection genes revealed that the changes were mostly enriched in regulation of leucocyte cell-cell adhesion and regulation of T-cell activation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs revealed that the host response in TB strongly involves cytokine-cytokine receptor interactions and folate biosynthesis. In order to further narrow the range of biomarkers, we used protein-protein interaction to establish a hub gene network of two data sets and a network of 11 candidate genes. Eventually, IRF1 was selected as a biomarker. As validation, IRF1 levels were shown to be up-regulated in patients with TB relative to healthy controls in data sets GSE19491 and GSE50834. Additionally, IRF1 levels were measured in the new patient samples using ELISA. IRF1 was seen to be significantly up-regulated in patients with TB compared with healthy controls with an AUC of 0.801. These results collectively indicate that IRF1 could serve as a new biomarker for the diagnosis of pulmonary tuberculosis.

17.
Skelet Muscle ; 11(1): 17, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229732

RESUMO

BACKGROUND: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia. METHODS: The CT26 and LLC tumor cells were subcutaneously injected into mice to induce colon cancer cachexia and lung cancer cachexia, respectively. Amiloride was intraperitoneally injected daily once tumors were formed. Cachexia features of the CT26 model and the LLC model were separately characterized by phenotypic, histopathologic and biochemical analyses. Plasma exosomes and muscle atrophy-related proteins were quantitatively analyzed. Integrative NMR-based metabolomic and transcriptomic analyses were conducted to identify significantly altered metabolic pathways and distinctly changed metabolism-related biological processes in gastrocnemius. RESULTS: The CT26 and LLC cachexia models displayed prominent cachexia features including decreases in body weight, skeletal muscle, adipose tissue, and muscle strength. The amiloride treatment in tumor-bearing mice distinctly alleviated muscle atrophy and relieved cachexia-related features without affecting tumor growth. Both the CT26 and LLC cachexia mice showed increased plasma exosome densities which were largely derived from tumors. Significantly, the amiloride treatment inhibited tumor-derived exosome release, which did not obviously affect exosome secretion from non-neoplastic tissues or induce observable systemic toxicities in normal healthy mice. Integrative-omics revealed significant metabolic impairments in cachectic gastrocnemius, including promoted muscular catabolism, inhibited muscular protein synthesis, blocked glycolysis, and impeded ketone body oxidation. The amiloride treatment evidently improved the metabolic impairments in cachectic gastrocnemius. CONCLUSIONS: Amiloride ameliorates cachectic muscle wasting and alleviates cancer cachexia progression through inhibiting tumor-derived exosome release. Our results are beneficial to understanding the underlying molecular mechanisms, shedding light on the potentials of amiloride in cachexia therapy.

18.
Int J Biol Sci ; 17(9): 2135-2146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239344

RESUMO

The phenotypic transformation of hepatic myofibroblasts (MFs) is involved in the whole process of the progression and regression of liver fibrosis. Notch signaling has been demonstrated to modulate the fibrosis. In this study, we found that Notch signaling in MFs was overactivated and suppressed with the progression and regression of hepatic fibrosis respectively, by detecting Notch signaling readouts in MFs. Moreover, we inactivated Notch signaling specifically in MFs with Sm22αCreER-RBPjflox/flox mice (RBPjMF-KO), and identified that MFs-specific down-regulation of Notch signaling significantly alleviated CCl4-induced liver fibrosis during the progression and regression. During the progression of liver fibrosis, MFs-specific blockade of Notch signaling inhibited the activation of HSCs to MFs and increases the expression of MMPs to reduce the deposition of ECM. During the regression of fibrosis, blocking Notch signaling in MFs increased the expression of HGF to promote proliferation in hepatocytes and up-regulated the expression of pro-apoptotic factors, Ngfr and Septin4, to induce apoptosis of MFs, thereby accelerating the reversal of fibrosis. Collectively, the MFs-specific disruption of Notch signaling attenuates liver fibrosis by modulating fibrosis progression and regression, which suggests a promising therapeutic strategy for liver fibrosis.

19.
Bioengineered ; 12(1): 3426-3433, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34227915

RESUMO

Stabilin-2 has been found to regulate the progression of cancer. It was not fully understood whether it shows some roles in non-small-cell lung cancer (NSCLC). We used the immunohistochemical staining to evaluate Stabilin-2 protein expression in formalin-fixed paraffin-embedded tissue of NSCLC patients' primary lesion. And we carried out χ2 test to detect relationships between Stabilin-2 expression and various clinical factors. Besides, the survival difference between patients with high and low Stabilin-2 expression was also analyzed. The expression of Stabilin-2 was associated with N stage and age. Higher Stabilin-2 expression exists in poorer survival patients. It revealed that Stabilin-2 expression was a significant predictor for both OS and DFS by univariate and multivariate analyses. High stabilin-2 expression in NSCLC predicts poor tumor prognosis.

20.
Environ Sci Technol ; 55(14): 9794-9804, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34235924

RESUMO

Particulate nitrite is a critical source of hydroxyl radicals; however, it lacks high-resolution methods due to its low abundance and stability to explore its formation mechanism. In this study, a modified versatile aerosol concentration enrichment system (VACES) coupled with ion chromatography (IC) was used to measure particulate NO2- hourly online and achieve a lowered detection limit of 10-3 µg m-3. VACES-IC was used to observe a high- and low-concentration events of PM1.0-NO2- in Shanghai, corresponding to the ambient-level concentrations of 0.34 and 0.05 µg m-3, respectively. The morning peak concentrations of NO2- even exceeded 3σ (standard deviation) in the high-concentration event due to the reduction of NO2 by aerosol SO32- based on kinetics and regression analysis. This implies that controlling SO2 emissions would be an effective strategy to decrease morning NO2- concentrations, correspondingly reducing the kinetic formation of SO42- by 20.8-34.8%. However, after sunrise, NO2- formation was primarily attributed to NO2 hydrolysis at pH 4.97-6.14. In the low-concentration event, NO2 hydrolysis also accounted for an overwhelming proportion (∼90%) of NO2- formation. This work estimates the contribution of different paths to particulate NO2- formation based on newly established high-resolution measurements.

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