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1.
EJNMMI Res ; 11(1): 120, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851463

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies to date. The impressively developed stroma that surrounds and modulates the behavior of cancer cells is one of the main factors regulating the PDAC growth, metastasis and therapy resistance. Here, we postulate that stromal and cancer cell compartments differentiate in protein/lipid glycosylation patterns and analyze differences in glycan fragments in those compartments with clinicopathologic correlates. RESULTS: We analyzed native glycan fragments in 109 human FFPE PDAC samples using high mass resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometric imaging (MALDI-FT-ICR-MSI). Our method allows detection of native glycan fragments without previous digestion with PNGase or any other biochemical reaction. With this method, 8 and 18 native glycans were identified as uniquely expressed in only stromal or only cancer cell compartment, respectively. Kaplan-Meier survival model identified glycan fragments that are expressed in cancer cell or stromal compartment and significantly associated with patient outcome. Among cancer cell region-specific glycans, 10 predicted better and 6 worse patient survival. In the stroma, 1 glycan predicted good and 4 poor patient survival. Using factor analysis as a dimension reduction method, we were able to group the identified glycans in 2 factors. Multivariate analysis revealed that these factors can be used as independent survival prognostic elements with regard to the established Union for International Cancer Control (UICC) classification both in tumor and stroma regions. CONCLUSION: Our method allows in situ detection of naturally occurring glycans in FFPE samples of human PDAC tissue and highlights the differences among glycans found in stromal and cancer cell compartment offering a basis for further exploration on the role of specific glycans in cancer-stroma communication.

2.
Oxid Med Cell Longev ; 2021: 5391706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745418

RESUMO

Ischemia-reperfusion injury (IRI) is defined as the total combined damage that occurs during a period of ischemia and following the recovery of blood flow. Oxidative stress, mitochondrial dysfunction, and an inflammatory response are factors contributing to IRI-related damage that can each result in cell death. Irisin is a polypeptide that is proteolytically cleaved from the extracellular domain of fibronectin type III domain-containing protein 5 (FNDC5). Irisin acts as a myokine that potentially mediates beneficial effects of exercise by reducing oxidative stress, improving mitochondrial fitness, and suppressing inflammation. The existing literature also suggests a possible link between irisin and IRI, involving mechanisms similar to those associated with exercise. This article will review the pathogenesis of IRI and the potential benefits and current limitations of irisin as a therapeutic strategy for IRI, while highlighting the mechanistic correlations between irisin and IRI.

3.
Zhongguo Zhong Yao Za Zhi ; 46(20): 5194-5200, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738419

RESUMO

Arisaematis Rhizoma included in the Chinese Pharmacopoeia is the dried tuber of Arisaema erubescens, A. heterophyllum or A. amurense in the family Araceae. This paper mainly focuses on the classification and summary of the chemical components and structures reported in recent years in the above three varieties of this medicinal material included in the pharmacopoeia, including alkaloids, flavonoids, phenylpropanoids, lignans and benzene ring derivatives, steroids and terpenes, glycosides and esters, etc. Then we reviewed the reported biological activities of these chemical components, including cytotoxicity, antitumor activity, antibacterial activity, nematicidal activity, etc. Although there have been reports on the review of the chemical composition of the medicinal material, the structure and classification of the chemical composition in these reviews are not clear enough. This review provides a basis for the later study of the chemical composition of this medicinal material, especially the identification of the chemical structures. And most of the current reviews on the biological activity of this medicinal material are mainly for the crude extract. This paper mainly summarized the biological activity of related monomer compounds and expected to lay a foundation for the development of novel high-efficiency and low-toxicity active leading compounds from Arisaematis Rhizoma.


Assuntos
Arisaema , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides , Glicosídeos , Rizoma
4.
Front Neurosci ; 15: 743207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803588

RESUMO

Opioids are the last option for the pharmacological treatment of neuropathic pain, but their antinociceptive effects are limited. Decreased mu opioid receptor (MOR) expression in the peripheral nervous system may contribute to this. Here, we showed that nerve injury induced hypermethylation of the Oprm1 gene promoter and an increased expression of methyl-CpG binding protein 2 (MeCP2) in injured dorsal root ganglion (DRG). The downregulation of MOR in the DRG is closely related to the augmentation of MeCP2, an epigenetic repressor, which could recruit HDAC1 and bind to the methylated regions of the Oprm1 gene promoter. MeCP2 knockdown restored the expression of MOR in injured DRG and enhanced the analgesic effect of morphine, while the mimicking of this increase via the intrathecal infusion of viral vector-mediated MeCP2 was sufficient to reduce MOR in the DRG. Moreover, HDAC1 inhibition with suberoylanilide hydroxamic acid, an HDAC inhibitor, also prevented MOR reduction in the DRG of neuropathic pain mice, contributing to the augmentation of morphine analgesia effects. Mechanistically, upregulated MeCP2 promotes the binding of a high level of HDCA1 to hypermethylated regions of the Oprm1 gene promoter, reduces the acetylation of histone H3 (acH3) levels of the Oprm1 gene promoter, and attenuates Oprm1 transcription in injured DRG. Thus, upregulated MeCP2 and HDAC1 in Oprm1 gene promoter sites, negatively regulates MOR expression in injured DRG, mitigating the analgesic effect of the opioids. Targeting MeCP2/HDAC1 may thus provide a new solution for improving the therapeutic effect of opioids in a clinical setting.

5.
Front Pharmacol ; 12: 761086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803704

RESUMO

Introduction: Online sales of antibiotics have increased public access to these medicines. This study aimed to analyze the online antibiotic purchase behavior of the Chinese residents and identify its associated factors. Methods: We conducted a nationwide cross-sectional online survey among Chinese community residents from January 20 to February 28, 2019. A structured questionnaire was used to collect data on their sociodemographic characteristics, health-related variables, and the online antibiotic purchase behavior in the past 3 months. Descriptive statistics and logistic regression analyses were used. The statistical analyses were performed using SAS version 9.4 (SAS Institute Inc.). Results: A total of 101,120 respondents were included in the analysis. The weighted prevalence of antibiotic purchase online was 3.71% (95% CI, 3.53-3.88%). Residents who purchased antibiotics online were more likely to be older (age≥65 years), be a male, live in rural areas, have a higher education level, report an excellent economic status, suffer from chronic diseases, and search for health information on the internet. Conclusion: Numerous residents had purchased antibiotics online in the past 3 months throughout China. We should pay more attention to this behavior. There is a need to strengthen regulation of antibiotic sales online and improve public education on antibiotic purchase online. More comprehensive information on antibiotic purchase online as well as the advantages and disadvantages of online sales of antibiotics should be investigated in the future studies.

6.
Free Radic Biol Med ; 177: 326-336, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34748910

RESUMO

This study aimed to investigate the dipeptide amino acid profiles correlated with xanthine oxidase (XOD) inhibitory activity and guide screening to determine suitable sources for XOD inhibitor protein hydrolysate preparation. The XOD inhibitory activities of 400 dipeptides were predicted via molecular docking and measured in vitro, and amino acids containing aromatic structures and charged residues were correlated with high XOD inhibitory properties. Subsequently, the effects of Cys-Glu and Lys-Glu, which showed the highest in vitro activities, were examined in hyperuricaemic mice, and were found to alleviate hyperuricaemia and modulate the gut microbiota. Furthermore, a suitable protein from Oreochromis mossambicus with high contents of charged (8.6%) and aromatic (1.67%) amino acids was screened, and the in vitro inhibitory rates of protein hydrolysate prepared from O. mossambicus against XOD were found to be 21.90% and 44.51% at 40 and 100 mg/ml, respectively. This study provides a strategy for screening protein hydrolysate sources with certain activities based on amino acid profiles.

7.
J Exp Med ; 218(12)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34762123

RESUMO

Nerve injury-induced changes of gene expression in dorsal root ganglion (DRG) are critical for neuropathic pain genesis. However, how these changes occur remains elusive. Here we report the down-regulation of zinc finger protein 382 (ZNF382) in injured DRG neurons after nerve injury. Rescuing this down-regulation attenuates nociceptive hypersensitivity. Conversely, mimicking this down-regulation produces neuropathic pain symptoms, which are alleviated by C-X-C motif chemokine 13 (CXCL13) knockdown or its receptor CXCR5 knockout. Mechanistically, an identified cis-acting silencer at distal upstream of the Cxcl13 promoter suppresses Cxcl13 transcription via binding to ZNF382. Blocking this binding or genetically deleting this silencer abolishes the ZNF382 suppression on Cxcl13 transcription and impairs ZNF382-induced antinociception. Moreover, ZNF382 down-regulation disrupts the repressive epigenetic complex containing histone deacetylase 1 and SET domain bifurcated 1 at the silencer-promoter loop, resulting in Cxcl13 transcriptional activation. Thus, ZNF382 down-regulation is required for neuropathic pain likely through silencer-based epigenetic disinhibition of CXCL13, a key neuropathic pain player, in DRG neurons.

8.
Stem Cell Res Ther ; 12(1): 584, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809715

RESUMO

BACKGROUND: Ischemic heart diseases is one of the leading causes of death worldwide. Although revascularization timely is an effective therapeutic intervention to salvage the ischemic myocardium, reperfusion itself causes additional myocardial injury called ischemia/reperfusion (I/R) injury. Bone marrow-derived mesenchymal stem cells (MSCs) is one of the promising cells to alleviate ischemic myocardial injury. However, this cell therapy is limited by poor MSCs survival after transplantation. Here, we investigated whether sevoflurane preconditioning could promote MSCs to attenuate myocardial I/R injury via transient receptor potential canonical channel 6 (TRPC6)-induced angiogenesis. METHODS: The anti-apoptotic effect of sevoflurane preconditioning on MSCs was determined by Annexin V-FITC/propidium iodide staining. TRPC6, hypoxia-inducible factor-1α (HIF-1α), Chemokine receptor 4 (CXCR4) and vascular endothelial growth factor (VEGF) protein expressions and VEGF release from MSCs were determined after hypoxia and reoxygenation (H/R). Small interfering RNA (siRNA) was used to knock down TRPC6 gene expression in MSCs. The angiogenesis of human umbilical vein endothelial cells (HUVECs) co-cultured with MSCs was determined by Matrigel tube formation. Myocardial I/R mouse model was induced by occluding left anterior descending coronary artery for 30 min and then reperfusion. MSCs or sevoflurane preconditioned MSCs were injected around the ligature border zone 5 min before reperfusion. Left ventricle systolic function, infarction size, serum LDH, cTnI and inflammatory cytokines were determined after reperfusion. RESULTS: Sevoflurane preconditioning up-regulated TRPC6, HIF-1α, CXCR4 and VEGF expressions in MSCs and VEGF release from MSCs under H/R, which were reversed by knockdown of TRPC6 gene using siRNA in MSCs. Furthermore, sevoflurane preconditioning promoted the angiogenic and anti-inflammatory effect of HUVECs co-cultured with MSCs. Sevoflurane preconditioned MSCs improved left ventricle systolic function and alleviated myocardial infarction and inflammation in mice subjected to I/R insult. CONCLUSION: The current findings reveal that sevoflurane preconditioned MSCs boost angiogenesis in HUVECs subjected to H/R insult and attenuate myocardial I/R injury, which may be mediated by TRPC6 up-regulated HIF-1α, CXCR4 and VEGF.

9.
Med Oncol ; 39(1): 16, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837558

RESUMO

The present study investigates the underlying mechanisms of treatment with osthole (OST) combined with lobaplatin in human triple-negative MDA-MB-231 breast cancer cells. Human triple-negative MDA-MB-231 breast cancer cells were treated with different concentrations of OST (0.1, 1, 5, 10, 20, 50, and 100 µM) alone or in combination with 10 µM lobaplatin for 48 h. Cell viability was determined and compared between the treatment groups with the Cell Counting Kit-8 assay. Transcriptome sequencing (Project Number: M-GSGC0250521) was employed to elucidate the gene expression profile of the control group and the OST treatment group, and differentially expressed genes (DEGs) were identified based on the following criteria: log2FC > 0, P < 0.05. KEGG enrichment analysis was employed to determine the biological functions of these DEGs and the related signaling pathways. Finally, flow cytometry and western blotting were used to assess differences in the apoptosis rate and protein expression in MDA-MB-231 cells subjected to different treatments. The findings showed that OST inhibited the growth of MDA-MB-231 cells in a concentration-dependent manner and cell proliferation was significantly inhibited (as indicated by a decrease of 40%) at the OST concentration of 50 µM (P < 0.05). Transcriptome sequencing identified 4712 DEGs, including 2169 upregulated DEGs and 2543 downregulated DEGs. Enrichment analysis indicated that the DEGs played a role in apoptosis, p53 signaling, DNA replication, and cell cycle. In vitro experiments showed that OST and lobaplatin could significantly induce apoptosis in the MDA-MB-231 cells (P < 0.05), as indicated by elevation in the translation level of p53/Bax/caspase-3 p17 and downregulation of the Bcl-2 protein. Finally, combined treatment with OST and lobaplatin had an enhanced anti-tumor effect (P < 0.05) on proliferation and apoptosis, as well as more obvious effects on the related proteins (p53, Bax, Bcl-2, and caspase-3 p17). Thus, OST enhanced the apoptosis-mediated growth inhibitory effect of lobaplatin on breast cancer cells and has potential for the treatment of breast cancer in the future.

10.
Cell Discov ; 7(1): 105, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34725333

RESUMO

Hepatitis B Virus (HBV) constitutes a major threat to global public health. Current understanding of HBV-host interaction is yet limited. Here, ribosome profiling, quantitative mass spectrometry and RNA-sequencing were conducted on a recently established HBV replication system, through which we identified multiomic differentially expressed genes (DEGs) that HBV orchestrated to remodel host proteostasis networks. Our multiomics interrogation revealed that HBV induced significant changes in both transcription and translation of 35 canonical genes including PPP1R15A, PGAM5 and SIRT6, as well as the expression of at least 15 non-canonical open reading frames (ncORFs) including ncPON2 and ncGRWD1, thus revealing an extra coding potential of human genome. Overexpression of these five genes but not the enzymatically deficient SIRT6 mutants suppressed HBV replication while knockdown of SIRT6 had opposite effect. Furthermore, the expression of SIRT6 was down-regulated in patients, cells or animal models of HBV infection. Mechanistic study further indicated that SIRT6 directly binds to mini-chromosome and deacetylates histone H3 lysine 9 (H3K9ac) and histone H3 lysine 56 (H3K56ac), and chemical activation of endogenous SIRT6 with MDL800 suppressed HBV infection in vitro and in vivo. By generating the first multiomics landscape of host-HBV interaction, our work is thus opening a new avenue to facilitate therapeutic development against HBV infection.

11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(11): 973-980, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34809736

RESUMO

Objective To investigate the effect and mechanism of urolithin A (UA) on the inflammation and lipid accumulation induced by hyperlipidemia in L02 hepatocytes. Methods Nuclear erythroid 2-related factor 2 (Nrf2) short hairpin RNA (shRNA) lentivirus was used to establish a stable Nrf2 knockdown cell line in L02 cells. Empty vector control cells and Nrf2 knockdown cells were treated with free fatty acids (FFAs) or bovine serum albumin (BSA) to establish the hyperlipidemic cell model, and Urolithin A was treated on this basis. Specifically, they were divided into control group (BSA treatment), FFA treatment group (0.6 mmol/L), FFA (0.6 mmol/L) combined with UA low-dose group (10 µmol/L) and FFA (0.6 mmol/L) combined with UA high-dose group (20 µmol/L). All of these groups were treated for 48 h. The dye of BODIPY493/503 was used to detect the accumulation of lipid droplets in the cell. The levels of triglyceride (TG) was detected by TG assay kit. TNF-α and IL-6 in the supernatant of the cells were detected by ELISA. The level of cellular reactive oxygen species (ROS) was detected by flow cytometry combined with DCFH-DA. Malondialdehyde (MDA) kit was used to test the level of MDA. Total superoxide dismutase (SOD) kit and catalase (CAT) kit were used to detect the activities of total SOD and CAT, respectively. The mRNA levels of SOD2 and CAT were detected by real-time quantitative PCR. The protein levels of SOD2, CAT, Nrf2 as well as P62, LC3 were detected by Western blot analysis. The adenovirus of RFP-GFP-LC3 was used to measure the autophagy flux in the cells. Results FFA increased the levels of TNF-α, IL-6 and TG as well as the positive rate of BODIPY493/503 staining in L02 cells. The levels of MDA and ROS increased, while the mRNA and protein expressions of SOD2, CAT and Nrf2 decreased when treated with FFA. FFA treatment also suppressed the levels of autophagy markers LC33-II and promoted the level of P62, and blocked autophagy flux. UA treatment could reverse the above effects of FFA, with significant difference. When Nrf2 was knocked down, the above effects of UA disappeared. Conclusion Through activating autophagy and antioxidative pathways which are mediated by Nrf2 pathway, urolithin A alleviates inflammation and oxidative stress induced by high lipid in L02 hepatocytes.


Assuntos
Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Autofagia , Cumarínicos , Hepatócitos/metabolismo , Humanos , Inflamação , Lipídeos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio
12.
Foods ; 10(11)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34828847

RESUMO

With the current study, we aimed to determine the characteristics and calcium absorption capacity of egg white peptide-calcium complex (EWP-Ca) and determine the effect of sterilization on EWP-Ca to study the possibility of EWP-Ca as a new potential calcium supplement. The results of SEM and EDS showed a high calcium chelating ability between EWP and calcium, and the structure of EWP-Ca was clustered spherical particles due its combination with calcium. The FTIR and Raman spectrum results showed that EWP could chelate with calcium by carboxyl, phosphate, and amino groups, and peptide bonds may also participate in peptide-calcium binding. Moreover, the calcium absorption of EWP-Ca measured by the intestinal everted sac model in rats was 32.38 ± 6.83 µg/mL, significantly higher than the sample with CaCl2, and the mixture of EWP and Ca (p < 0.05) revealed appropriate calcium absorption capacity. The fluorescence spectra and CD spectra showed that sterilization caused a decrease in the content of α-helix and ß-sheet and a significant increase in ß-turn (p < 0.05). Sterilization changed the EWP-Ca structure and decreased its stability; the calcium-binding capacity of EWP-Ca after sterilization was decreased to 41.19% (p < 0.05). Overall, these findings showed that EWP could bind with calcium, form a peptide-calcium chelate, and serve as novel carriers for calcium supplements.

13.
Biochem Biophys Res Commun ; 579: 168-174, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34607170

RESUMO

Rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), displays a robust hypoglycemic action in patients with type 2 diabetes mellitus (T2DM) and elicits serious adverse reactions, especially hepatotoxicity and cardiotoxicity. Here, we aims to find a new natural PPAR-γ agonist with less adverse reactions than rosiglitazone in db/db mice. The method of virtual screening was used to identify a PPAR-γ agonist 18:0 Lyso PC from an in-house natural product library. We verified its pharmacological effects and adverse reactions comparing with rosiglitazone in vivo and in vitro. 18:0 Lyso PC exhibited pharmacological effects similar to those of rosiglitazone in db/db mice. Moreover, 18:0 Lyso PC showed a lower extent of liver injury and cardiotoxicity in db/db mice. The mechanism, by which this natural compound alleviates metabolic syndrome, involves a reduction in fatty acid synthesis mediated by activation of the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase-alpha (AMPKα) and acetyl-CoA carboxylase (ACC) and an increase expression of uncoupled protein 1 (UCP1) and PPAR-γ coactivator-1 alpha (PGC1-α). 18:0 Lyso PC, a natural compound, can show a similar hypoglycemic effect to rosiglitazone by activating PPAR-γ, while eliciting markedly fewer adverse reactions than rosiglitazone.

14.
J Agric Food Chem ; 69(41): 12333-12343, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34633809

RESUMO

Memory impairment is becoming a potential health issue with the delicacy of diet and social stress. Sea cucumber peptides (SCP) prevent memory impairment, as previously reported. In this study, further research was performed using hippocampal lysine-acetylome to explore molecular regulation mechanisms. C57BL/6 mice were treated with scopolamine via intraperitoneal injection to simulate memory impairment. To determine the influence of SCP on the total acetylated-protein level of the hippocampus, acetylated-proteomics was performed. SCP increased the acetylation level of histone (H3 and H4). Meanwhile, for non-histones, the differentially acetylated proteins were involved in multiple memory-related pathways, as shown by KEGG enrichment analysis. Additionally, long-term potentiation was confirmed by western blotting. Finally, a combined analysis of proteome and lysine acetylome revealed that SCP contributed to synaptic vesicle cycle regulation and dopamine metabolism. Consequently, our findings revealed that SCP was potentially neuroprotective by regulating post-transcriptional hippocampal protein acetylation.


Assuntos
Lisina , Pepinos-do-Mar , Acetilação , Animais , Hipocampo/metabolismo , Lisina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos , Processamento de Proteína Pós-Traducional , Proteoma/genética , Proteoma/metabolismo , Pepinos-do-Mar/metabolismo
15.
Int J Gen Med ; 14: 6059-6076, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594130

RESUMO

Purpose: Selenophosphate synthetase 2 (SEPHS2) has been shown to regulate selenoprotein biosynthesis by catalyzing the synthesis of active selenium donor selenophosphate. SEPHS2 influences the survival of tumor cells. However, few studies have explored the expression level and prognostic of SEPHS2 in various cancers. Methods: The expression of SEPHS2 in human tumor tissues and normal adjacent tissues was analyzed in The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN databases. Cox regression analysis and Kaplan-Meier curve analysis were performed to analyze the association of SEPHS2 expression with the prognosis of cancer patients. The expression and prognosis of SEPHS2 in gliomas were further verified using the Chinese Glioma Genome Atlas (CGGA) dataset. The relationship between SEPHS2 and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens was comprehensively explored using a TCGA cohort. The mechanism by which SEPHS2 regulates tumor progression was explored by using the STRING database. A nomogram was constructed using the R software to predict the overall survival (OS) of patients with brain lower grade glioma (LGG). Results: SEPHS2 was highly expressed in many cancers including LGG. Its high expression was significantly associated with poor OS, disease-free survival (DFS), and progression-free survival (PFS). Univariate and multivariate Cox analyses showed that SEPHS2 was an independent prognostic factor for LGG. Concordance index and calibration curves revealed that the nomogram had good predictive performance (concordance index: 0.791; 95% CI: 0.732-1). A significant correlation was found between SEPHS2 and immune infiltration, TMB, MSI, and tumor neoantigens across diverse cancers. Enrichment analysis showed that SEPHS2 may regulate the PPAR signaling pathway. Conclusion: SEPHS2 expression regulates tumor development and it is a potential treatment target and prognostic biomarker, especially for lower grade glioma.

16.
Ecotoxicol Environ Saf ; 227: 112865, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34634598

RESUMO

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.


Assuntos
Zearalenona , Animais , Apigenina/farmacologia , Feminino , Glucuronatos , Células da Granulosa , Humanos , Simulação de Acoplamento Molecular , Zearalenona/toxicidade
17.
J Trace Elem Med Biol ; 69: 126880, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34717166

RESUMO

BACKGROUND: This updated and comprehensive meta-analysis study sought to explore the changes of seven essential trace elements, including selenium (Se), iron (Fe), zinc (Zn), manganese (Mn), fluorine (F), iodine (I) and copper (Cu) in Kashin-Beck disease (KBD) patients compared with healthy individuals. The findings of the current study will provide a valuable reference for implementation of early clinical intervention and prevention of KBD. METHODS: All related articles included in this review were retrieved from the following databases: Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data, China Biology Medicine disc (CBM disc), PubMed and Web of Science up to April 30, 2020. The following combination keywords were used as the search criteria: "(Kashin-Beck disease OR KBD) AND ((selenium OR iron OR zinc OR manganese OR fluorine OR iodine OR copper) OR (Se OR Fe OR Zn OR Mn OR F OR I OR Cu))". All statistical analyses were performed using RevMan 5.3 and Stata 16.0 software. RESULTS: A total of 55 articles were included in the current study. Meta-analysis showed that the levels of serum Se (SMD = -2.37, 95 % CI: -1.58 to -0.72, P < 0.00001), hair Se (SMD = -2.19, 95 % CI: -3.05 to -1.33, P < 0.00001), urinary Se (SMD = -2.36, 95 % CI: -3.26 to -1.46, P < 0.00001) and erythrocyte Se (SMD = -5.12, 95 % CI: -9.55 to -0.69, P = 0.02) were significantly lower in KBD patients compared with the levels in healthy controls. Then, the findings showed that the levels of serum F (SMD = -0.58, 95 % CI: -1.04 to -0.12, P = 0.01) and hair I (SMD = -0.57, 95 % CI: -1.06 to -0.08, P = 0.02) in patients were substantially lower than that in controls. Analysis showed that the levels of hair Zn (SMD = 0.26, 95 % CI: 0.04 to 0.49, P = 0.02) and hair Mn (SMD = 0.55, 95 % CI: 0.24 to 0.85, P = 0.0005) were markedly higher in patients compared with the levels in healthy controls. Notably, urinary Se (AUC = 0.7851, P = 0.0235, Sensitivity = 81.82 %, Specificity = 81.82 %) showed a good diagnostic value for KBD. CONCLUSIONS: The findings of the current study showed that the levels of Se, serum F and hair I were lower in patients with KBD compared with those in healthy controls, whereas the levels of hair Zn and hair Mn were higher in KBD patients compared with the levels in controls. This outcome would be further validated in our future studies. Of note, these results indicated that Se, F and I deficiencies were associated with the pathogenesis of KBD.

18.
Cancer Res ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666994

RESUMO

Asymptomatic anthracosis is the accumulation of black carbon particles in adult human lungs. It is a common occurrence, but the pathophysiological significance of anthracosis is debatable. Using in situ high mass resolution matrix-assisted laser desorption/ionization (MALDI) fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging analysis, we discovered noxious carbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines, or aromatic amines, in a series of 330 lung cancer patients in highly variable and unique patterns. The characteristic nature of carbon-bound exogenous compound had a strong association with patient outcome, tumor progression, the tumor immune microenvironment, PD-L1 expression, and DNA damage. Spatial correlation network analyses revealed substantial differences in the metabolome of tumor cells compared to tumor stroma depending on carbon-bound exogenous compounds. Overall, the bioactive pool of exogenous compounds is associated with several changes in lung cancer pathophysiology and correlates with patient outcome. Given the high prevalence of anthracosis in the lungs of adult humans, future work should investigate the role of carbon-bound exogenous compounds in lung carcinogenesis and lung cancer therapy.

19.
Liver Transpl ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34664394

RESUMO

Numerous studies in hepatocellular carcinoma (HCC) have proposed tissue-based gene signatures for individualized prognostic assessments. Here, we develop a novel circulating tumor cell (CTC)-based transcriptomic profiling assay to translate tissue-based messenger RNA (mRNA) signatures into a liquid biopsy setting for noninvasive HCC prognostication. The HCC-CTC mRNA scoring system combines the NanoVelcro CTC Assay for enriching HCC CTCs and the NanoString nCounter platform for quantifying the HCC-CTC Risk Score (RS) panel in enriched HCC CTCs. The prognostic role of the HCC-CTC RS was assessed in The Cancer Genome Atlas (TCGA) HCC cohort (n = 362) and validated in an independent clinical CTC cohort (n = 40). The HCC-CTC RS panel was developed through our integrated data analysis framework of 8 HCC tissue-based gene signatures and identified the top 10 prognostic genes (discoidin domain receptor tyrosine kinase 1 [DDR1], enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase [EHHADH], androgen receptor [AR], lumican [LUM], hydroxysteroid 17-beta dehydrogenase 6[HSD17B6], prostate transmembrane protein, androgen induced 1 [PMEPA1], tsukushi, small leucine rich proteoglycan [TSKU], N-terminal EF-hand calcium binding protein 2 [NECAB2], ladinin 1 [LAD1], solute carrier family 27 member 5 [SLC27A5]) highly expressed in HCC with low expressions in white blood cells. The panel accurately discriminated overall survival in TCGA HCC cohort (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.4-2.9). The combined use of the scoring system and HCC-CTC RS panel successfully distinguished artificial blood samples spiked with an aggressive HCC cell type, SNU-387, from those spiked with PLC/PRF/5 cells (P = 0.02). In the CTC validation cohort (n = 40), HCC-CTC RS remained an independent predictor of survival (HR, 5.7; 95% CI, 1.5-21.3; P = 0.009) after controlling for Model for End-Stage Liver Disease score, Barcelona Clinic Liver Cancer stage, and CTC enumeration count. Our study demonstrates a novel interdisciplinary approach to translate tissue-based gene signatures into a liquid biopsy setting. This noninvasive approach will allow real-time disease profiling and dynamic prognostication of HCC.

20.
Int J Gen Med ; 14: 5441-5448, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526811

RESUMO

Objective: To find the predictors for persistent inflammation-immunosuppression catabolism syndrome in ICU surgical septic patients. Design: Single center observation study. Participants: Inclusion: 1) patients ≥18, 2) admitted to the ICU after major surgery or transferred to the ICU within 48 hours after the diagnosis of sepsis following the definition of sepsis-3.0. Exclusion: 1) pregnant or lactating patients, 2) patients with severe immune deficiency, 3) patients that expired within 14 days after the diagnosis of sepsis. Results: A total of 169 participants were included. After propensity score matching, PICS patients were found to have higher intensive care unit (ICU) mortality (32.4% vs 12.4%, p=0.046), 90-day mortality (32.4% vs 9.1%, p=0.006), and ICU-acquired infection rate (44.1% vs 12.7%, p<0.001), and longer ICU stays (29 vs 11 days, p<0.001) comparing to non-PICS patients. In multivariate logistic regression, it demonstrated that the SOFA score, Charlson co-morbidity index (CCI), albumin level on the ICU day 1, and lymphocyte count on the ICU day 3 were statistically significant. Sensitivity analysis was conducted with the receiver operating characteristic curve for a combination of the four parameters and the area under the curve was 0.838 (95% confidence interval 0.774-0.901). Conclusion: The chronic disease condition and decreased immunity in the early course of sepsis were crucial for PICS. The combination of CCI, SOFA score, albumin level on ICU Day 1 and lymphocyte count on ICU Day 3 can be early predictor for PICS.

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