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OBJECTIVE: To explore the clinical features of renal damage related to pregnancy and pregnancy after chronic kidney disease (CKD), providing clinical evidence for the relationship between renal damage and pregnancy. METHODS: A retrospective analysis was performed on patients admitted to our hospital between March 2013 and February 2021 who had both pregnancy and kidney damage. The study collected pathology results from renal biopsies, 24-hour urinary protein quantity, albumin (Alb), serum creatinine (Scr), blood lipids, coagulation function, blood routine, and other indicators during and after pregnancy. RESULTS: This study included 82 cases, with 48 cases in the pregnancy-related renal damage group. Thirty-four cases were in the post-CKD pregnancy group. Of the patients, 30 cases (88.24%) had CKD stage 1-2. Results showed better pregnancy and fetal outcomes in the post-CKD pregnancy group compared to the pregnancy-related renal damage group (Ρ was 0.029 and 0.036, respectively). Renal biopsy pathology revealed that 16 cases (33.33%) in the pregnancy-related renal damage group mainly had focal segmental glomerulosclerosis (FSGS), while the post-CKD pregnancy group was dominated by 14 cases (43.75%) of IgA nephropathy. The first blood test indicators revealed that the pregnancy-related renal damage group had lower estimated glomerular filtration (eGFR) and Alb levels compared to the post-CKD pregnancy group (Ρ was 0.003 and 0.000, respectively). Additionally, 24-hour urinary protein quantity, total cholesterol (Tch), triglyceride (TG), and platelet (PLT) counts were higher in the pregnancy-related renal damage group compared to the post-CKD pregnancy group (Ρ was 0.005, 0.001, 0.008, and 0.031, respectively). The abnormal rate of Scr during pregnancy was 41.67% (20/48) in the pregnancy-related renal damage group and 17.39% (4/23) in the post-CKD pregnancy group, with a statistically significant difference (Ρ was 0.043). CONCLUSION: The pregnancy-related renal damage group is mainly associated with FSGS, while the post-CKD pregnancy group is characterized by IgA nephropathy. Patients with CKD1-2 can have a successful pregnancy after achieving good control of eGFR, albumin, 24-hour urinary protein quantity and other indicators, resulting in better pregnancy and fetal outcomes. Abnormal Scr levels during pregnancy of pregnancy-related renal damage can be improved within 3 months after delivery.
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Glomerulonefrite por IGA , Glomerulosclerose Segmentar e Focal , Insuficiência Renal Crônica , Feminino , Gravidez , Humanos , Estudos Retrospectivos , Rim , Insuficiência Renal Crônica/etiologia , Prognóstico , AlbuminasRESUMO
BACKGROUND: Previous studies have shown that the hypoxia microenvironment significantly impacted tumor progression. However, the clinical prognostic value of hypoxia-related risk signatures and their effects on the tumor microenvironment (TME) in hepatocellular carcinoma (HCC) remains hazy. This study aimed to conduct novel hypoxia-related prognostic signatures and improve HCC prognosis and treatment. METHODS: Differentially expressed hypoxia-related genes (HGs) were identified with the gene set enrichment analysis (GSEA). Univariate Cox regression was utilized to generate the tumor hypoxia-related prognostic signature, which consists of 3 HGs, based on the least absolute shrinkage and selection operator (LASSO) algorithm. Then the risk score for each patient was performed. The prognostic signature's independent prognostic usefulness was confirmed, and systematic analyses were done on the relationships between the prognostic signature and immune cell infiltration, somatic cell mutation, medication sensitivity, and putative immunological checkpoints. RESULTS: A prognostic risk model of four HGs (FDPS, SRM, and NDRG1) was constructed and validated in the training, testing, and validation datasets. To determine the model's performance in patients with HCC, Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves analysis was implemented. According to immune infiltration analysis, the high-risk group had a significant infiltration of CD4+ T cells, M0 macrophages, and dendritic cells (DCs) than those of the low-risk subtype. In addition, the presence of TP53 mutations in the high-risk group was higher, in which LY317615, PF-562271, Pyrimethamine, and Sunitinib were more sensitive. The CD86, LAIR1, and LGALS9 expression were upregulated in the high-risk subtype. CONCLUSIONS: The hypoxia-related risk signature is a reliable predictive model for better clinical management of HCC patients and offers clinicians a holistic viewpoint when determining the diagnosis and course of HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Feminino , Prognóstico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Genes Reguladores , Hipóxia/genética , Hipóxia Fetal , Microambiente Tumoral/genéticaRESUMO
Pancreatic cancer (PC) ranked fourth among cancer-related death worldwide with a survival rate less than 5%. The abnormal proliferation and distant metastasis are major obstacles for the diagnosis and treatment of pancreatic cancer, therefore, it is urgent for researchers to uncover the molecular mechanisms underlying the PC proliferation and metastasis. In current study, we found that USP33, a member of deubiquitinating enzyme family, was upregulated among PC samples and cells, meanwhile, the high expression of USP33 correlated with poor prognosis of patients. Function experiments revealed that USP33 overexpression promoted the proliferation, migration and invasion of PC cells while the inhibition of USP33 expression in PC cells exhibited the opposite effect. The mass spectrum and luciferase complementation assay screened TGFBR2 as the potential binding protein of USP33. Mechanistically, USP33 triggered the deubiquitination of TGFBR2 and prevented its degradation by lysosome, therefore promoted TGFBR2 accumulation in cell membrane and eventually contributed to the sustained activation of TGF-ß signaling. Moreover, our results revealed that the activation of TGF-ß targeted gene ZEB1 promoted the transcription of USP33. In conclusion, our study found that USP33 contributed to the proliferation and metastasis of pancreatic cancer through a positive feedback loop with TGF-ß signaling pathway. Moreover, this study suggested that USP33 may serve as a potential prognostic and therapeutic target in PC.
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Neoplasias Pancreáticas , Transdução de Sinais , Humanos , Linhagem Celular Tumoral , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Movimento Celular/genética , Neoplasias Pancreáticas/genética , Fenótipo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Ubiquitina Tiolesterase/metabolismoRESUMO
Liver cancer is the main reason of cancer deaths globally, with an unfavorable prognosis. DNA methylation is one of the epigenetic modifications and maintains the right adjustment of gene expression and steady gene silencing. We aim to explore the novel signatures for prognosis by using DNA methylation-driven genes. To acquire the DNA methylation-driven genes, we perform the difference analysis from the gene expression data and DNA methylation data in TCGA or GEO databases. And we obtain the 31 DNA methylation-driven genes. Subsequently, consensus clustering analysis was utilized to identify the molecular subtypes based on the 31 DNA methylation-driven genes. So, two molecular subtypes were identified to perform those analyses: Survival, immune cell infiltration, and tumor mutation. Results showed that two subtypes were clustered with distinct prognoses, tumor-infiltrating immune cell and tumor mutation burden. Furthermore, the 31 DNA methylation-driven genes were applied to perform the survival analysis to select the 14 survival-related genes. Immediately, a five methylation-driven genes risk model was built, and the patients were divided into high and low-risk groups. The model was established with TCGA as the training cohort and GSE14520 as the validation cohort. According to the risk model, we perform the systematical analysis, including survival, clinical feature, immune cell infiltration, somatic mutation status, underlying mechanisms, and drug sensitivity. Results showed that the high and low groups possessed statistical significance. In addition, the ROC curve was utilized to measure the accuracy of the risk model. AUCs at 1-year, 3-years, and 5-years were respectively 0.770, 0.698, 0.676 in training cohort and 0.717, 0.649, 0.621 in validation cohort. Nomogram was used to provide a better prediction for patients' survival. Risk score increase the accuracy of survival prediction in HCC patients. In conclusion, this study developed a novel risk model of five methylation-driven genes based on the comprehensive bioinformatics analysis, which accurately predicts the survival of HCC patients and reflects the immune and mutation features of HCC. This study provides novel insights for immunotherapy of HCC patients and promotes medical progress.
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BACKGROUND: Hepatocellular carcinoma (HCC) originates from the hepatocytes and accounts for 90% of liver cancer. The study intends to identify novel prognostic biomarkers for predicting the prognosis of HCC patients based on TCGA and GSE14520 cohorts. METHODS: Differential analysis was employed to obtain the DEGs (Differentially Expressed Genes) of the TCGA-LIHC-TPM cohort. The lasso regression analysis was applied to build the prognosis model through using the TCGA cohort as the training group and the GSE14520 cohort as the testing group. Next, based on the prognosis model, we performed the following analyses: the survival analysis, the independent prognosis analysis, the clinical feature analysis, the mutation analysis, the immune cell infiltration analysis, the tumor microenvironment analysis, and the drug sensitivity analysis. Finally, the survival time of HCC patients was predicted by constructing nomograms. RESULTS: Through the lasso regression analysis, we obtained a prognosis model of ten genes including BIRC5 (baculoviral IAP repeat containing 5), CDK4 (cyclin-dependent kinase 4), DCK (deoxycytidine kinase), HSPA4 (heat shock protein family A member 4), HSP90AA1 (heat shock protein 90 α family class A member 1), PSMD2 (Proteasome 26S Subunit Ubiquitin Receptor, Non-ATPase 2), IL1RN (interleukin 1 receptor antagonist), PGF (placental growth factor), SPP1 (secreted phosphoprotein 1), and STC2 (stanniocalcin 2). First, we found that the risk score is an independent prognosis factor and is related to the clinical features of HCC patients, covering AFP (α-fetoprotein) and stage. Second, we observed that the p53 mutation was the most obvious mutation between the high-risk and low-risk groups. Third, we also discovered that the risk score is related to some immune cells, covering B cells, T cells, dendritic, macrophages, neutrophils, etc. Fourth, the high-risk group possesses a lower TIDE score, a higher expression of immune checkpoints, and higher ESTIMATE score. Finally, nomograms include the clinical features and risk signatures, displaying the clinical utility of the signature in the survival prediction of HCC patients. CONCLUSIONS: Through the comprehensive analysis, we constructed an immune-related prognosis model to predict the survival of HCC patients. In addition to predicting the survival time of HCC patients, this model significantly correlates with the tumor microenvironment. Furthermore, we concluded that these ten immune-related genes (BIRC5, CDK4, DCK, HSPA4, HSP90AA1, PSMD2, IL1RN, PGF, SPP1, and STC2) serve as novel targets for antitumor immunity. Therefore, this study plays a significant role in exploring the clinical application of immune-related genes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Feminino , Humanos , alfa-Fetoproteínas/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Quinase 4 Dependente de Ciclina/metabolismo , Desoxicitidina Quinase/metabolismo , Proteínas de Choque Térmico/metabolismo , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Osteopontina/metabolismo , Fator de Crescimento Placentário/metabolismo , Complexo de Endopeptidases do Proteassoma , Receptores de Interleucina-1 , Proteína Supressora de Tumor p53 , Ubiquitinas/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is one of the malignant tumors with high mortality and a worse prognosis globally. Necroptosis is a programmed death mediated by receptor-interacting Protein 1 (RIP1), receptor-interacting Protein 1 (RIP3), and Mixed Lineage Kinase Domain-Like (MLKL). Our study aimed to create a new Necroptosis-related lncRNAs (NRlncRNAs) risk model that can predict survival and tumor immunity in HCC patients. The RNA expression and clinical data originated from the TCGA database. Pearson correlation analysis was applied to identify the NRlncRNAs. The LASSO-Cox regression analysis was employed to build the risk model. Next, the ROC curve and the area under the Kaplan-Meier curve were utilized to evaluate the accuracy of the risk model. In addition, based on the two groups of risk model, we performed the following analysis: clinical correlation, differential expression, PCA, TMB, GSEA analysis, immune cells infiltration, and clinical drug prediction analysis. Plus, qRT-PCR was applied to test the expression of genes in the risk model. Finally, a prognosis model covering six necroptosis-related lncRNAs was constructed to predict the survival of HCC patients. The ROC curve results showed that the risk model possesses better accuracy. The 1, 3, and 5-years AUC values were 0.746, 0.712, and 0.670, respectively. Of course, we also observed that significant differences exist in the following analysis, such as functional signaling pathways, immunological state, mutation profiles, and medication sensitivity between high-risk and low-risk groups of HCC patients. The result of qRT-PCR confirmed that three NRlncRNAs were more highly expressed in HCC cell lines than in the normal cell line. In conclusion, based on the bioinformatics analysis, we constructed an NRlncRNAs associated risk model, which predicts the prognosis of HCC patients. Although our study has some limitations, it may greatly contribute to the treatment of HCC and medical progression.
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Canonical transient receptor potential-6 (TRPC6) has been reported to be involved in cell damage after ischemia/reperfusion (I/R) injury in target organs. While the effect and of TRPC6 on pyroptosis in renal I/R injury remain unclear. In our study, we first established the renal I/R mouse model and oxygen-glucose deprivation and re-oxygenation (OGD/R) cell model, and investigated the impacts of TRPC6 on the pyroptosis-related proteins using CCK-8, western blot, ELISA, and immunofluorescence probes. Besides, we also explored the mechanism of TRPC6 in pyroptosis of renal tubular epithelial cells through A20 knockdown or overexpression and zinc chloride (ZnCl2 ) or a zinc ion chelator (TPEN) treatment. Our results indicated that I/R injury could cause downregulation of TRPC6 both in vivo and in vitro. In the I/R injury murine model, TRPC6 inhibition exacerbated tissue damage and upregulated NLRP3, ASC, caspase-1, IL-18, and IL-1ß, which could be alleviated by the administration of ZnCl2 . In the OGD/R cell model, inhibitor of TRPC6 (SAR7334) reduced zinc ion influx, aggravated cell death and upregulated pyroptosis-related protein. The pyroptosis phenotype also could be alleviated by ZnCl2 and intensified by TPEN. Overexpression of A20 reduced the expression of pyroptosis-related protein, increased cell viability in the sh-TRPC6 and TPEN-treated OGD/R cell models, while A20 deficiency impaired the protective effect of zinc ion. Therefore, our results indicate that TRPC6 could promote zinc ion influx in renal tubular epithelial cells, thereby upregulating intracellular A20, inhibiting the activation of inflammasome NLRP3, and ultimately attenuating renal I/R injury.
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Piroptose , Traumatismo por Reperfusão , Animais , Células Epiteliais , Inflamassomos , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Canal de Cátion TRPC6 , ZincoRESUMO
Hepatocellular carcinoma (HCC) is regarded as one of the universal cancers in the world. Therefore, our study is based on clinical, molecular mechanism and immunological perspectives to analyze how NAP1L1 affects the progression of HCC. To begin with, the gene expression datasets and clinical data of GSE14520, GSE76427, ICGC, and TCGA are originated from GEO, ICGC, and TCGA databases. Subsequently, DEG screening was performed on data using R studio, and we finally found that 2,145 overlapping DEGs were screened from four datasets at the end. Then, we used R studio to filter the survival-related genes of the GSE76427 and ICGC datasets, and we screened out 101 survival-related genes. Finally, 33 common genes were screened out from 2,145 overlapping DEGs and 101 survival-related genes. Then, NAP1L1 was screened from 33 common genes using the CytoHubba plug-in in Cytoscape software. Furthermore, ground on GEO, ICGC, and TCGA databases, the survival analysis, clinical feature analysis, univariate/multivariate regression analysis, and multiple GSEA were used to study NAP1L1. The Conclusion claimed that HCC patients with higher expression levels of NAP1L1 had a poorer prognosis than those with lower expression levels. Thus, we believe that NAP1L1 is an independent prognostic factor for HCC. In order to shed light on NAP1L1's molecular mechanism promoting the progression of HCC closely, the GSEA tool was applied to complete the GSEA of the four datasets. Furthermore, the results confirmed that NAP1L1 could promote HCC progression by regulating the G2/M transition of the cell cycle and Wnt signaling pathway. Western blot and flow cytometry were also performed to understand those mechanisms in this study. The result of Western blot showed that NAP1L1 silencing led to downregulation of CDK1 and ß-catenin proteins; the result of flow cytometry showed that cell numbers in the G2 phase were significantly increased when NAP1L1 was silenced. Thus, we claimed that NAP1L1 might promote HCC progression by activating the Wnt signaling pathway and promoting cell cycle G2/M transition. In addition, ground on GSE14520 and GSE76427 datasets, and ICGC and TCGA databases, the correlation between NAP1L1 and immune cells was analyzed in HCC patients. At the same time, the TISIDB online database and the TIMER online database were testified to the association between NAP1L1 and immune cells. Hence, the summary shows that NAP1L1 was connected with a certain amount of immune cells. We can speculate that NAP1L1 may influence macrophages to promote HCC progression through some potential mechanisms.
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Purpose: This study aimed to reveal the multicomponent synergy mechanisms of SWP based on network pharmacology and metabolomics for exploring the relationships of active ingredients, biological targets, and crucial metabolic pathways. Materials: Network pharmacology, including TRRUST, GO, and KEGG, enrichment was used to discover the active ingredients and potential regulation mechanisms of SWP. LC-MS and multivariate data analysis method were further applied to analyze serum metabolomics profiling for discovering the potential metabolic mechanisms of SWP on AA induced by Cyclophosphamide (CTX) and 1-Acetyl-2-phenylhydrazine (APH). Results: A total of 27 important bioactive ingredients meeting the ADME (absorption, distribution, metabolism, and excretion) screening criteria from SWP were selected. Interaction networks were constructed and validated based on the 10 associated ingredients with the relevant targets. A total of 125 biomarkers were found by Metabolomics approach, which associated with the development of AA, mainly involved in amino acid metabolism and lipid metabolism. While SWP can reverse the above 12 metabolites changed by AA. Network analysis revealed the synergistic effects of SWP through the 43 crucial pathways, including Sphingolipid signaling pathway, Sphingolipid metabolism, Arginine and proline metabolism, VEGF signaling pathway, Estrogen signaling pathway. Conclusion: The study suggested that SWP is a useful alternative for the treatment of AA induced by CTX + APH. Its potential mechanisms are to improve hematopoietic microenvironment and promote bone marrow hematopoiesis therapies.
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Anemia Aplástica , Medicamentos de Ervas Chinesas , Anemia Aplástica/induzido quimicamente , Anemia Aplástica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Metabolômica/métodos , Farmacologia em Rede , EsfingolipídeosRESUMO
Huxie Huaji (HXHJ) Ointment is a famous traditional Chinese medicinal prescription and is commonly used for the clinical treatment of hepatocellular carcinoma by boosting immunity and detoxification. However, the scientific evidence for the effect of HXHJ Ointment on hepatocellular carcinoma and the underlying molecular mechanism are lacking. The present study aimed to identify the effects of HXHJ Ointment on hepatocellular carcinoma in vitro and in vivo as well as investigating the mechanistic basis for the anticancer effect of HXHJ ointment. First, liquid chromatography-mass spectrometry was used to verify the composition of HXHJ Ointment and quality control. Second, in vitro, Cell Counting Kit (CCK8) cell viability assay and Hoechst 33342 staining assay were performed to explain the cell apoptosis. The protein levels of tumor suppressor protein (p53), B-cell lymphoma 2 gene (Bcl-2), cytochrome C (Cyt-C), and aspartate proteolytic enzyme-3 (caspase-3) were examined by immunofluorescence. Finally, in vivo, hematoxylin and eosin (H&E) staining was used to observe the pathological changes in hepatocellular carcinoma samples. Western blots and immunohistochemistry were used to detect the anticancer properties of HXHJ ointment. The results in vitro showed that 20% HXHJ Ointment serum could significantly inhibit HepG2 cell proliferation, increased tumor suppressor gene p53, downregulated antiapoptotic protein Bcl-2, promoted the release of mitochondrial Cyt-C, activated caspase-3, and induced HepG2 cell apoptosis. Furthermore, in vivo experiments showed that HXHJ Ointment could effectively inhibit tumor growth in nude mice xenotransplanted with HepG2 cells, changed the morphology of tumor cells, and regulated the expression of apoptosis-related protein pathway p53/Bcl-2/Cyt-C/caspase-3. HXHJ Ointment can significantly inhibit the development of hepatocellular carcinoma, and its mechanism may be related to the regulation of p53/Bcl-2/Cyt-C/caspase-3 signaling pathway to induce cell mitochondrial apoptosis.
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Gastrointestinal (GI) malignancies, a series of malignant conditions originating from the digestive system, include gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. GI cancers have been regarded as the leading cancer-related cause of death in recent years. Therefore, it is essential to develop effective treatment strategies for GI malignancies. Mesenchymal stem cells (MSCs), a type of distinct non-hematopoietic stem cells and an important component of the tumor microenvironment, play important roles in regulating GI cancer development and progression through multiple mechanisms, such as secreting cytokines and direct interactions. Currently, studies are focusing on the anti-cancer effect of MSCs on GI malignancies. However, the effects and functional mechanisms of MSC-derived exosomes on GI cancer are less studied. MSC-derived exosomes can regulate GI tumor growth, drug response, metastasis, and invasion through transplanting proteins and miRNA to tumor cells to activate the specific signal pathway. Besides, the MSC-derived exosomes are also seen as an important drug delivery system and have shown potential in anti-cancer treatment. This study aims to summarize the effect and biological functions of MSC-derived exosomes on the development of GI cancers and discuss their possible clinical applications for the treatment of GI malignancies.
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Seven undescribed indole-based alkaloids, xuefengins A-D and xuefenglasins A-C, were isolated from natural Ophiocordyceps xuefengensis, along with six known alkaloids. Their structures were elucidated by comprehensive spectroscopy, with absolute configurations confirmed by comparison with calculated electronic circular dichroism spectra. Eleven of the isolates were tested for cytotoxicity against the U937, NB4, MCF-7, Hep G2, and A549 cancer cell lines. Two compounds exhibited moderate activities, with IC50 values of 2.83-25.68 µM and 1.54-12.16 µM. Further pharmacological studies showed that these two compounds inhibit cell proliferation by inducing apoptosis, and decreasing p38 and caspase-3 levels in A549 cells.
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Alcaloides , Alcaloides Indólicos , Células A549 , Alcaloides/farmacologia , Linhagem Celular Tumoral , Hypocreales , Alcaloides Indólicos/farmacologia , Estrutura MolecularRESUMO
Six flavonoid glycosides jixueqisus A-F, together with nine known flavonoids, were isolated from the rhizomes of the fern Pronephrium penangianum. Among them, two red pigments jixueqisus A and B possess the same rare 6,8-dimethyl-2-phenyl-7H-1-benzopyran-7-one skeleton (a long conjugated system). Jixueqisu Cwas a dihydrochalcone glycoside, jixueqisu D was a chalcone glycoside, jixueqisu E was an aurone glycoside, and jixueqisu F was a flavonone glycoside. Interestingly, jixueqisus D-F, (2S)-5,2',5'-trihydroxy-7-methoxyflavanone and 5,2',5'-trihydroxy-7-methoxyflavone possessed a 2,5-dihydroxy substituted benzene ring (B-ring). Their structures were elucidated by various spectroscopic and chemical methods. Furthermore, the plausible biosynthetic pathways of jixueqisus A-F were discussed, respectively. All isolated compounds were evaluated for their activities against the proliferation of MCF-7, HepG-2, HCT-116 and BGC-823 tumor cell lines, four known flavane-4-ol glycosides, abacopterins A and C, eruberin B and triphyllin A, exhibited moderate activities to various cell lines.
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Medicamentos de Ervas Chinesas , Gleiquênias , Flavonoides , Glicosídeos , Estrutura Molecular , RizomaRESUMO
BACKGROUND: Although stable microRNAs (miRNAs) are present in human peripheral blood and have been considered as novel biomarkers for various diseases. But there is little research about miRNAs as biomarkers of mesangial proliferative glomerulonephritis (MsPGN). This study aimed to identify whether there exist disordered circulating miRNAs that can function as biomarkers for MsPGN disease activity. METHODS: The candidate miRNAs were validated in 70 MsPGN patients and 70 healthy controls by quantitative real-time PCR (RT-qPCR). The specificity and sensitivity of the miRNA panel was assessed by receiver operating characteristic (ROC) curves. In addition, the candidate miRNA levels were measured in the different MsPGN progression and in the membranous nephropathy (MN) patients and the hypothetical role of the candidate miRNA on mesangial cell proliferation was analysed. Situ hybridization was performed to examine the candidate miRNA levels in the glomerulus. RESULTS: These results showed that miR-106a-5p and miR-30a-5p were highly expressed in MsPGN patients compared with healthy controls and could discriminate MsPGN from healthy controls with an area under the ROC curve (AUC) of 0.93. In addition, the two miRNAs were not only higher in moderate and severe MsPGN patients, but could distinguish MsPGN from MN. We also observed a decreased expression in MsPGN regression group after treatment. Plasma miR-106a-5p level was positively correlated with estimated glomerular filtration rate (eGFR). Furthermore, the two miRNAs were highly expressed in MsPGN glomerulus and their overexpression could prompt mesangial cell proliferation. CONCLUSION: Plasma miR-30a-5p and miR-106a-5p can serve as novel and potential diagnostic biomarkers for MsPGN.
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Glomerulonefrite Membranoproliferativa/sangue , MicroRNAs/sangue , Adulto , Biomarcadores Tumorais/sangue , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Feminino , Perfilação da Expressão Gênica/métodos , Glomerulonefrite/sangue , Glomerulonefrite/genética , Glomerulonefrite/patologia , Glomerulonefrite Membranoproliferativa/genética , Glomerulonefrite Membranoproliferativa/patologia , Humanos , Masculino , Células Mesangiais/metabolismo , Células Mesangiais/patologia , MicroRNAs/genética , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , TranscriptomaRESUMO
Glutathione (GSH) levels are closely related to the homeostasis of redox state which directly affects human disease occurrence by regulating cell apoptosis. Hence, real-time monitoring of dynamic changes in intracellular GSH levels is urgently needed for disease early diagnosis and evaluation of therapy efficiency. In this study, an endogenous cysteine (Cys)-assisted detection system based on GSH@AgNCs and reduced graphene oxide (rGO) with high sensitivity and specificity was developed for GSH detection. Compared with GSH, GSH@AgNCs with weaker affinity and bonding force was quite easier to extrude from the rGO surface when competing against GSH, leading to the obvious change in fluorescence signal. This phenomenon was termed as "a crowding out effect". Furthermore, the presence of Cys can improve GSH assay sensitivity by enhancing the quenching efficiency of rGO on the GSH@AgNCs. In vitro assay indicated that the efficiency of fluorescence recovery was positively related with GSH concentration in the range from 0 to 10 mM. In addition, the method was employed for real-time monitoring of the dynamic changes in GSH levels regulated by natural drugs. The imaging results showed that the natural compound 3 (C3) can downregulate GSH levels in HepG2 cells, which was accompanied by reactive oxygen species (ROS) release and apoptosis induction. Finally, the method was used to monitor the change of GSH levels in serum samples with chronic hepatitis B (CHB) infection. The results demonstrated that the occurrence and development of CHB may be positively correlated with GSH levels to some extent. Overall, the above results demonstrate the potential application of this new nanosystem in anticancer natural drug screening and clinical assay regarding GSH levels.
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Cisteína/química , Medicamentos de Ervas Chinesas/farmacologia , Corantes Fluorescentes/química , Glutationa/sangue , Grafite/química , Nanopartículas Metálicas/química , Doxorrubicina/farmacologia , Etilmaleimida/farmacologia , Glutationa/química , Glutationa/efeitos dos fármacos , Células Hep G2 , Humanos , Limite de Detecção , Espécies Reativas de Oxigênio/metabolismo , Prata/química , Espectrometria de Fluorescência/métodosRESUMO
Necroptosis, oxidative stress, and inflammation are major contributors to the pathogenesis of ischemic acute kidney injury. Necrostatin-1 (Nec-1), an inhibitor of the kinase domain of receptor-interacting protein kinase-1 (RIP1), has been reported to regulate renal ischemia and reperfusion (I/R) injury; however, its underlying mechanism of action remains unclear. HK-2 cells were used to create an in vitro I/R model, in which the cells were subjected to hypoxia, followed by 2, 6, and 12 h of reoxygenation. For the in vivo study, a rat model of renal I/R was established in which samples of rat blood serum and kidney tissue were harvested after reperfusion to assess renal function and detect histological changes. Cell viability and necroptosis were analyzed using the Cell Counting Kit (CCK)-8 assay and flow cytometry, respectively. The expression levels of molecules associated with necroptosis, oxidative stress, and inflammation were determined by real-time PCR, western blotting, immunofluorescence staining, and ELISA. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to confirm the relevant downstream signaling pathway. We found that pretreatment with Nec-1 significantly decreased hypoxia-inducible factor-1α (HIF-1α) and miR-26a expression, as well as the levels of factors associated with necroptosis (RIP1, RIP3, and Sirtuin-2), oxidative stress (malondialdehyde [MDA], NADP+/NADPH ratio), and inflammation (interleukin [IL]-1ß, IL-10, and tumor necrosis factor alpha [TNF-α]) in I/R injury cells and the rat model. However, these effects could be reversed by miR-26a overexpression or TRPC6 knockdown. Mechanistic studies demonstrated that HIF-1α directly binds to the promoter region of miR-26a, and that TRPC6 is a potential target gene for miR-26a. Our findings indicate that Nec-1 can effectively protect against renal I/R injury by inhibiting necroptosis, oxidative stress, and inflammation, and may exert its effects through mediation of the HIF-1α/miR-26a/TRPC6/PARP1 signaling pathway.
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PURPOSE: To evaluate whether perioperative N-acetylcysteine (NAC) administration reduces the risk of cardiac surgery associated acute kidney injury (CSA-AKI). MATERIALS AND METHODS: A systematic literature review (Medline, PubMed, Cochrane, Biomedical central, Google Scholar) identified 10 studies (1391 patients; 695 NAC and 696 placebo) that compared the efficacy and adverse effects of perioperative NAC administration for CSA-AKI prevention in adults undergoing elective cardiac surgery. Meta-analysis was performed using Comprehensive Meta-Analysis statistical software. RESULTS: Patients in the NAC-treated and placebo groups had similar rate of CSA-AKI occurrence, change in creatinine levels, as well as the in-hospital mortality rate (RR = 0.841, 95% CI = 0.691 to 1.023, p = 0.083; pooled difference in means = -0.328, 95% CI = -0.712 to 0.056, p = 0.094; RR = 0.741, 95% CI = 0.388 to 1.418, p = 0.366, respectively). CONCLUSIONS: Our study does not support perioperative NAC administration as a mean to reduce the risk of CSA-AKI.
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Acetilcisteína/uso terapêutico , Injúria Renal Aguda/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Sequestradores de Radicais Livres/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Injúria Renal Aguda/sangue , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Creatinina/sangue , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Mortalidade Hospitalar , Humanos , Assistência Perioperatória/efeitos adversos , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
Caterpillar fungi have numerous pharmacological and therapeutic applications in traditional medicine, due to a variety of active chemical constituents, such as cordycepin and adenosine. It is imperative to discover new resource for artificial cultivation and biometabolite production since the traditional natural species are endangered. In this study, a new strain HACM 001 was isolated and identified as Ophiocordyceps xuefengensis by rDNA-ITS sequencing. This strain showed the potential of artificial infection to caterpillar larvae leading to mummification, as well as fermentation mycelia in liquid culture and cultivation stromata in solid medium. Eight nucleosides and nucleobases, especially cordycepin and adenosine, were determined and analyzed with HPLC-DAD-Q-TOF-MS/MS technology. Cordycepin was detected in all forms of present O. xuefengensis strain at different contents, among which the highest content (37.1 µg/g) appeared in the stromata cultivated on solid medium. The content of adenosine in mycelia and stromata, respectively, reached 1155 µg/g and 1470 µg/g. Therefore, O. xuefengensis might be an alternative source for obtaining artificial fungus-caterpillar-larvae complex and producing cordycepin and adenosine.
Assuntos
Desoxiadenosinas/biossíntese , Hypocreales/crescimento & desenvolvimento , Larva/microbiologia , Lepidópteros/microbiologia , Micélio/crescimento & desenvolvimento , Adenosina/análise , Adenosina/biossíntese , Animais , Meios de Cultura , DNA Ribossômico/genética , Desoxiadenosinas/análise , Fermentação , Hypocreales/metabolismo , Micélio/metabolismoRESUMO
Fungal arteritis affecting graft arteries is a rare but life-threatening complication in kidney transplantation (KT). Here, we report the case of a patient with Aspergillus arteritis who experienced renal artery rupture 8 days after KT. We also reviewed 50 other reported cases of fungal arteritis after KT. We found that fungal contamination can occur during kidney graft harvest, preservation, and/or transplantation. Typically, early diagnosis, timely antifungal treatment, and emergency surgery seem crucial for avoiding life-threatening vascular complications.
Assuntos
Aloenxertos/microbiologia , Arterite/microbiologia , Aspergilose/microbiologia , Aspergillus flavus/isolamento & purificação , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Artéria Renal/microbiologia , Adulto , Aloenxertos/irrigação sanguínea , Aloenxertos/patologia , Aloenxertos/cirurgia , Antifúngicos/uso terapêutico , Arterite/patologia , Arterite/terapia , Aspergilose/patologia , Aspergilose/terapia , Aspergillus flavus/patogenicidade , Humanos , Rim/irrigação sanguínea , Rim/microbiologia , Rim/patologia , Rim/cirurgia , Transplante de Rim/métodos , Masculino , Necrose/microbiologia , Necrose/terapia , Nefrectomia , Ruptura Espontânea/microbiologia , Ruptura Espontânea/terapiaRESUMO
BACKGROUND: Lonicera macranthoides is a Chinese herb that contains a large number of bioactive spanions possessing important pharmacological activities, such as anti-tumour activity. However, detailed information about their anti-tumor activity and bioactive compounds is limited. METHODS: In order to evaluate the scientific basis, the method of high-speed counter-current chromatography (HSCCC) combined with high performance liquid chromatography mass spectrometry (HPLC-ESI-QTOF/MS) has been developed to separate, purify and analyze saponins from Lonicera macranthoides. Four main saponins, Macranthoidin B (I), Macranthoidin A (II), Macranthoides B (III) and Akebia saponin D (IV) were separated by HSCCC with the solvent systems of ethyl acetate-nbutanol- water (3:2:5) and n-butanol-water-methanol-ethyl acetate (1:6:0.5:4). The purities of these four bioactive ingredients (I-IV) identified and detected by HPLC-ESI-QTOF/MS were 95.1%, 92.7%, 91.8% and 96.3%, respectively. The separated saponins were evaluated for their cytotoxic activities against six tumor cell lines (MCF-7, Hela, A549, HepG2, HT29 and Eca109). RESULTS: Results show that compounds I-IV exhibited particular significant anti-tumor activities against human mammary adenocarcinoma MCF-7 cell with IC50 values ranging from 12.7 to 30.8 µM. CONCLUSION: It was demonstrated that the combinative method using HPLC-ESI-QTOF/MS and HSCCC was suitable for rapid screening and isolating saponins of Lonicera macranthoides and the isolated compounds have great potential for the development of new antitumor drugs.