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1.
Org Lett ; 23(23): 9151-9156, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34780172

RESUMO

A cooperative Rh(II)/Pd(0) dual-catalysis strategy that promotes a cyclization/allylic alkylation cascade of stable α-diazo-δ-keto-esters has been developed. Highly substituted 3(2H)-furanones with a C2-quaternary center can be obtained efficiently under mild conditions via one-pot synthesis. Remarkably, this binary catalytic system shows high chemo-, regio-, and stereoselectivity and excellent tolerance to various functionalities.

2.
Biomed Res Int ; 2021: 6669570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671679

RESUMO

Objective: This study is aimed at identifying stemness-related genes in pancreatic ductal adenocarcinoma (PDAC). Methods: The RNA-seq data of PADC patients were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The mRNA expression-based stemness index (mRNAsi) and epigenetically regulated mRNAsi (EREG-mRNAsi) of PADC patients were evaluated. The mRNAsi-related gene sets in PADC were identified by weighted gene coexpression network analysis (WGCNA). The key genes were further analyzed using functional enrichment analysis. The Kaplan-Meier survival analysis and the Cox proportional hazards model were used to evaluate the prognostic value of the key genes. Prognostic hub genes were used to establish nomograms. The receiver operating characteristic (ROC) curves, concordance index (C-index), and calibration curves were used to assess the discrimination and accuracy of the nomogram. Finally, these results were validated in the Gene Expression Omnibus (GEO) database. Results: A total of 36 key genes related to mRNAsi were identified by WGCNA. A prognostic gene signature compromising seven genes (TPX2, ZWINT, UBE2C, CCNB2, CDK1, BUB1, and BIRC5) was established to predict the overall survival (OS) of PADC patients. The Cox regression analysis revealed that the risk score was an independent prognostic factor for PADC. Patients were then divided into the high-risk and low-risk groups. The ROC curves, C-index, and calibration curves indicated good performance of the prognostic signature in the TCGA and GEO datasets. Moreover, the nomogram incorporating clinical parameters showed better sensitivity and specificity for predicting the OS of PADC patients. Conclusion: The stemness-related prognostic model successfully predicted the OS of PADC patients and could be used for the treatment of PADC.

3.
Bioorg Chem ; 117: 105441, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34695731

RESUMO

Under the guidance of bioassay against HSC-LX2, the EtOH extract and the EtOAc fraction of Artemisia capillaris (Yin-Chen) exhibited cytotoxic activity against HSC-LX2 with inhibitory ratios of 39.7% and 68.7% at the concentration of 400.0 µg/mL. Bioassay-guided investigation of Fr. D (the active fraction) yielded 14 new coumaric acid analogues, artemicapillasins A-N (1-14). The structures of the isolates were elucidated by spectroscopic analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. Cytotoxic activity against HSC-LX2 cells of these isolates was performed to reveal that 12 compounds demonstrated cytotoxicity with inhibitory ratios more than 50% at 400 µM. The most active artemicapillasin B (2) gave an IC50 value of 24.5 µM, which was about 7 times more toxic than the positive drug silybin (IC50, 162.3 µM). Importantly, artemicapillasin B (2) showed significant inhibition on the deposition of human collagen type I (Col I), human laminin (HL) and human hyaluronic acid (HA) with IC50 values of 11.0, 14.4 and 13.8 µM, which was about 7, 11 and 5 times more active than silybin. Artemicapillasin B (2) as an interesting antihepatic fibrosis candidate is worth in-depth study.

4.
Mol Ther ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534693

RESUMO

Chemoresistance is the major cause of gastric adenocarcinoma (GA) treatment failure. The mechanisms underlying chemoresistance remain incompletely understood. Here, we sought to identify genes differentially expressed between chemoresistant and chemosensitive GA and to validate the function of the top hit. High-throughput RNA sequencing was performed to detect chemoresistance-related genes. The function of the only gene overexpressed in both chemoresistant tumors and tumor tissue relative to normal gastric epithelia, forkhead box C1 (FOXC1), was examined in GA cells, mouse xenograft models, and patient-derived organoid (PDO) systems, focusing on cancer stem-like cell (CSC) phenotypes, metastasis, and chemoresistance. FOXC1 was expressed at significantly higher levels in GA patient tumors that were resistant to chemotherapy, and high FOXC1 tumor expression was significantly correlated with poor survival among patients undergoing resection (p = 0.011). FOXC1 activity was significantly higher in spheroid-forming or CD44+ GA CSCs than in unselected cells. Inhibition of FOXC1 decreased the expression of CD44 and Sox2, decreased spheroid size by 78%-82%, and decreased spheroid number (>100 µm) by 75%-86%. GA CSC chemotherapy resistance was reversed with FOXC1 inhibition in vitro and in vivo and in PDOs. Mechanistic studies indicated that FOXC1 acts via the hedgehog and epithelial-to-mesenchymal transition (EMT) pathways. Our results imply that FOXC1 mediates the CSC phenotypes, metastasis, and chemotherapy resistance of GA through hedgehog and EMT signaling. FOXC1 inhibitors may thus represent a novel strategy to overcome chemoresistance.

5.
Inflammation ; 44(5): 2106-2119, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34091806

RESUMO

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease and a common complication of SLE is lupus nephritis (LN) during which lupus autoantibodies and proinflammatory cytokines attack the kidney and cause renal dysfunction. The current treatments to LN are limited due to a poor understanding of the pathogenesis. Here, we studied the molecular mechanisms of LN by investigating the function of circELK4/miR-27b-3p axis. MRL/lpr mice and LPS-treated HK-2 cells were used as the mouse model and cell model of LN, respectively. Blood samples were collected from LN patients. qRT-PCR and western blot were used to measure expression levels of circELK4, miR-27b-3p, apoptosis-related proteins, cytokines, and STING/IRF-3/IFN-I signaling. ELISA was performed to examine levels of cytokines including IL-6 and TNF-α. H&E staining was used to examine kidney morphology. TUNEL staining and flow cytometry were used to determine cell apoptosis. Dual luciferase activity assay and RNA pull down were employed to validate the interactions of circELK4/miR-27b-3p and miR-27b-3p/STING. CircELK4 was elevated in LN mice, patients, and LPS-treated HK-2 cells. Knockdown of circELK4 attenuated renal injury in LN mice and LPS-induced HK-2 cell injury. CircELK4 directly bound to miR-27b-3p while miR-27b-3p targeted STING. Moreover, overexpression of circELK4 could partially reverse the effects of miR-27b-3p mimics on cell apoptosis and inflammation. Furthermore, circELK4/miR-27b-3p regulated renal cell damage via modulating STING/IRF3/IFN-I signaling. CircELK4 contributes to renal injury by promoting inflammation and cell apoptosis via acting as a miR-27b-3p sponge to modulate STING/IRF3/IFN-I signaling in LN.

6.
Bioorg Chem ; 114: 105072, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34144276

RESUMO

Random screening revealed that the EtOH extract of Artemisia atrovirens showed significant cytotoxicity against two human hepatoma cell lines (HepG2 and Huh7) with the inhibitory ratio of 98.9% and 99.7% at the concentration of 100 µg/mL. Further bioactivity-guided isolation of active fraction led to 16 new guaiane-type sesquiterpenoids, artematrovirenins A-P (1-16). Their structures were elucidated by extensive spectroscopic data. The absolute stereochemistry of compounds 1 and 14 was determined by single-crystal X-ray diffraction analyses. Pharmacological evaluation suggested that five compounds (3, 5, 8, 10, and 15) exhibited cytotoxicity, compounds 3 and 5 displayed cytotoxicity against HepG2 cell line with an IC50 values of 8.0 and 16.0 µM, as well as against Huh7 cell line with values of 18.2 and 32.2 µM.

7.
Surg Endosc ; 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34076769

RESUMO

BACKGROUND: It remains inconclusive whether laparoscopic gastrectomy (LG) has better long-term outcomes when compared with open gastrectomy (OG) for elderly gastric cancer (EGC). We attempted to explore the influence of the immune prognostic index (IPI) on the prognosis of EGCs treated by LG or OG to identify a population among EGC who may benefit from LG. METHODS: We included 1539 EGCs treated with radical gastrectomy from January 2007 to December 2016. Propensity score matching was applied at a ratio of 1:1 to compare the LG and OG groups. The IPI based on dNLR ≥ cut-off value (dNLR) and sLDH ≥ cut-off value (sLDH) was developed, characterizing two groups (IPI = 0, good, 0 factors; IPI = 1, poor, 1 or 2 factors). RESULTS: Of the 528 EGCs (LG: 264 and OG: 264), 271 were in the IPI = 0 group, and 257 were in the IPI = 1 group. In the entire cohort, the IPI = 0 group was associated with good 5-year overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p = 0.003) compared to the IPI = 1 group; no significant differences in 5-year OS and PFS between the LG and OG groups were observed. In the IPI = 1 cohort, there was no significant difference in OS or PFS between the LG and OG groups across all tumor stages. However, in the IPI = 0 cohort, LG was associated with longer OS (p = 0.015) and PFS (p = 0.018) than OG in stage II EGC, but not in stage I or III EGC. Multivariate analysis showed that IPI = 0 was an independent protective factor for stage II EGC receiving LG, but not for those receiving OG. CONCLUSION: The IPI is related to the long-term prognosis of EGC. Compared with OG, LG may improve the 5-year survival rate of stage II EGC with a good IPI score. This hypothesis needs to be further confirmed by prospective studies.

8.
Bioorg Med Chem Lett ; 41: 127994, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33775837

RESUMO

Liver fibrosis is a final result of extensive deposition of extracellular matrix (ECM) and starts with the activation and proliferation of hepatic stellate cells (HSCs). Our previous study showed that eudesmane sesquiterpenoid santamarin had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values of 16.5 ± 0.7 µM. To explore the structure-activity relationships, twenty-six derivatives were synthesized by modifying the hydroxyl group, double-bond and unsaturated lactone. Cytotoxicity evaluation suggested that eight derivatives (6, 9, 13, 17, 20 and 25-27) increased activity against HSC-LX2. Especially, derivatives 17, 20 and 25 displayed obvious cytotoxicity with IC50 values of 6.4 ± 0.4, 4.6 ± 0.1, and 3.5 ± 0.1 µM, which were 3 to 5-fold higher than santamarin. Preliminary mechanisms study revealed that the active compound 20 exhibited more than 8-fold and 6-fold enhancement of inhibitory effect on the deposition of human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 7.6 ± 0.6 and 3.3 ± 1.2 µM.


Assuntos
Citotoxinas/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Sesquiterpenos/farmacologia , Linhagem Celular , Citotoxinas/síntese química , Citotoxinas/química , Relação Dose-Resposta a Droga , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Estrutura Molecular , Sesquiterpenos/síntese química , Sesquiterpenos/química , Relação Estrutura-Atividade
9.
Neurol Sci ; 42(5): 1653-1659, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33523320

RESUMO

OBJECTIVE: To explore the activity changes in neurology clinical practice that have occurred in tertiary public hospitals during the COVID-19 pandemic. METHODS: Outpatient and inpatient data from the neurology department were extracted from the electronic medical record system of three tertiary Grade A hospitals in Wenzhou. Data were analyzed across 5 months following the beginning of the pandemic (from January 13 to May 17) and compared with the same period in 2019. Data on reperfusion therapy for acute infarction stroke were extracted monthly from January to April. RESULTS: The number of outpatients declined from 102,300 in 2019 to 75,154 in 2020 (26.54%), while the number of inpatients in the three tertiary Grade A hospitals decreased from 4641 to 3437 (25.94%). The latter trend showed a significant drop from the 3rd week to the 7th week. The number of patients in these hospitals decreased significantly, and a significant drop was seen in the neurology department. As usual, stroke was the most common disease observed; however, anxiety/depression and insomnia increased dramatically in the outpatient consultation department. CONCLUSIONS: The results of our study revealed the effects of the COVID-19 pandemic in the clinical practice of neurology in Wenzhou during the outbreak. Understanding the pandemic's trends and impact on neurological patients and health systems will allow for better preparation of neurologists in the future.


Assuntos
COVID-19 , Neurologia , Humanos , Neurologistas , Pandemias , SARS-CoV-2
10.
Immun Inflamm Dis ; 9(2): 547-559, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33631054

RESUMO

Gastric cancer (GC) is one of the most common cancers in the world, and the tumor microenvironment (TME) plays a vital role in the occurrence and development of GC. In this study, we obtained differential expressed genes in GC tissues from The Cancer Genome Atlas. After ESTIMATE and weighted correlation network analysis, we obtained differentially expressed genes (DEGs). With further screening DEGs of immune infiltration and then through Kaplan-Meier survival analysis, least absolute shrinkage and selection operator regression analysis and COX analysis, we found that VCAN was a gene positively correlated with high immune infiltration and poor prognosis of patients in GC. In addition, we selected a Gene Expression Omnibus dataset (GSE84433) to verify the effect of VCAN on the patient's prognosis, and analyzed the value of VCAN in immunotherapy through TIMER database and TISIDB. In conclusion, we hold the view that VCAN may affect the development of GC by regulating the TME, which may act as a potential therapeutic target for GC.


Assuntos
Neoplasias Gástricas , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Neoplasias Gástricas/genética , Microambiente Tumoral/genética , Versicanas
11.
Transpl Immunol ; 65: 101371, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33545333

RESUMO

INTRODUCTION: Acute renal rejection usually fails to be diagnosed before the increase in the serum creatinine levels, and the resultant damage to the renal tissues occur in varying degrees. We hypothesized that the combined detection of human leucocyte antigen-G (HLA-G) 14-bp insertion/deletion genotypes and kidney injury molecule-1 (KIM-1) and osteopontin (OPN) levels in serum might facilitate the prediction of acute renal allograft rejections in kidney transplant recipients. METHODS: HLA-G 14-bp insertion/deletion genotypes and the serum KIM-1 and OPN levels of 77 kidney transplant recipients were determined and compared before operation and on days 1, 4, and 7 after the operation (32 in acute rejection [AR] group and 45 in stable allograft function [STA] group). These 3 indicators were combined to establish a model for the early prediction of AR. RESULTS: The KIM-1 levels in the serum of patients were significantly higher in the AR group than in the STA group. The area under the receiver operator characteristics (ROC) curve (AUC) of KIM-1 for the prediction of rejection was maximized on the1st day after operation, with a sensitivity of 84.4% and a specificity of 86.7%. The OPN levels in the serum of patients were significantly higher in the AR group than in the STA group only before operation and on the 7th day after operation. The AUC of OPN for the prediction of rejection was maximized on 7th day after operation, with a sensitivity of 68.8% and a specificity of 88.9%. The HLA-G + 14-bp allele frequency was also significantly higher in the AR group than in the STA group. The results of these three indicators were converted into a qualitative method. If any two of the three indicators show as positive, it was diagnosed as acute rejection, and it has the highest ability to predict acute rejection with a sensitivity and specificity of 84.38% and 91.11%, respectively. CONCLUSIONS: The HLA-G 14-bp insertion/deletion genotype and KIM-1 and OPN levels in the patients' serum were significantly different between the AR and STA groups. The power of predicting acute renal allograft rejection could be improved by combined these three biomarkers.

12.
World J Urol ; 39(9): 3631-3642, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33495865

RESUMO

PURPOSE: To analyze various compositions of urinary stones using revolution spectral CT (rapid kV switching dual-energy CT) in vivo. METHODS: 202 patients with urinary stones underwent spectral CT before surgery. Zeff peak, overall scope and CT values were detected. Moreover, water/iodine attenuating material images were obtained. Removed stones were subjected to infrared spectroscopy after surgery. The results of infrared spectroscopy were compared with CT. RESULTS: 28 stones (14.08%) with single composition, 165 stones with two mixed compositions (81.68%), and 9 stones with three mixed compositions (4.46%) were observed. When Zeff peaks of stones with single/mixed compositions were summarized together, 146 peaks of calcium oxalate monohydrate, 119 peaks of calcium oxalate dihydrate, 55 peaks of carbapatite, 38 peaks of urate, 16 peaks of struvite, and 11 peaks of brushite were totally observed. 93.8% of calcium oxalate monohydrate had Zeff peaks between 13.3 and 14.0. 91.6% of calcium oxalate dihydrate had peaks between 12.0 and 13.3. For carbapatite, 90.9% of stones had peaks from 14.0 to 15.0. A total of 94.8% of urate had peaks between 7.0 and 11.0. 93.8% of struvite had peaks between 11.0 and 13.0, and 90.9% of brushite had peaks between 12.0 and 14.0. Moreover, densities of urate, struvite and brushite were low density in iodine-based images and high-density in water-based images. CONCLUSION: The in-vivo analysis of spectral CT in urinary stone revealed characteristics of different compositions, especially mixed compositions. An in-vivo predictive model may be constructed to distinguish stone compositions.

13.
Clin Hemorheol Microcirc ; 77(3): 259-265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33337352

RESUMO

This study aimed to investigate the effects of arachidonic acid metabolite epoxyeicosatrienoic acid (EETs) in the apoptosis of endothelial cells induced by tumor necrosis factor-alpha (TNF-α). After human umbilical vein endothelial cells were cultured, TNF-α/ActD, 14, 15-EET, and HMR-1098 were added, respectively, into the culture medium. The apoptosis level of endothelial cells was detected by flow cytometry. After TNF-α/ActD induced endothelial cell apoptosis, flow cytometry staining showed that endothelial cell apoptosis increased significantly, and the apoptotic cells were significantly reduced after the addition of 14, 15-EET. However, the apoptotic cells significantly increased after the addition of HMR-1098. Western Blot results showed that the phosphorylation levels of LC3-II and AMPK were increased after TNF-α/ActD induction, and the increase was noticeable after the addition of 14, 15-EET. However, the phosphorylation levels of LC3-II and AMPK significantly decreased after the addition of HMR-1098. The activity of Caspase-8 and -9 decreased significantly after the addition of 14, 15-EET but increased after the addition of HMR-1098. Arachidonic acid can inhibit TNF-α induced endothelial cell apoptosis by upregulating autophagy.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Araquidônico/uso terapêutico , Células Endoteliais/metabolismo , Fator de Necrose Tumoral alfa/efeitos adversos , Ácido Araquidônico/farmacologia , Linhagem Celular Tumoral , Humanos
14.
Radiat Oncol ; 15(1): 260, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33168045

RESUMO

PURPOSE: The gross tumor volume (GTV) could be an independent prognostic factor for unresectable locally advanced non-small cell lung cancer (LANSCLC). We aimed to develop and validate a novel integrated GTV-TNM stratification system to supplement LANSCLC sub-staging in patients treated with concurrent chemoradiotherapy (CCRT). METHODS: We performed a retrospective review of 340 patients with unresectable LANSCLC receiving definitive CCRT. All included patients were divided into two randomized cohorts. Then the Kaplan-Meier method and Cox regression were calculated to access the prognostic value of the integrated GTV-TNM stratification system, which was further validated by the area under the receiver operating characteristic curve (AUC) score and F1-score. RESULTS: The optimal outcome-based GTV cut-off values (70 and 180 cm3) of the modeling cohort were used to determine each patient's integrated GTV-TNM stratum in the whole cohort. Our results indicated that a lower integrated GTV-TNM stratum could had better overall survival and progression-free survival (all P < 0.001), which was recognized as an independent prognostic factor. Also, its prognostic value was robust in both the modeling and validation cohorts. Furthermore, the prognostic validity of the integrated GTV-TNM stratification system was validated by significantly improved AUC score (0.636 vs. 0.570, P = 0.027) and F1-score (0.655 vs. 0.615, P < 0.001), compared with TNM stage. CONCLUSIONS: We proposed a novel integrated GTV-TNM stratification system to supplement unresectable LANSCLC sub-staging due to its prognostic value independent of TNM stage and other clinical characteristics, suggesting that it could be considered in individual treatment decision-making process.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/terapia , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
15.
Am J Transl Res ; 12(10): 6931-6940, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194083

RESUMO

BACKGROUND: Acute kidney injury (AKI) was found in some patients with COVID-19 pneumonia and accompanied with poor outcomes. The objective of this study was to investigate the association of AKI with clinical outcomes in COVID-19 patients. METHODS: In this cohort study, we reviewed electronic medical data from patients with COVID-19 in Shenzhen from January 11 to February 19, 2020. Clinical features and clinical outcomes in COVID-19 patients with and without AKI were analyzed. Further, we evaluated the association between AKI development and clinical outcomes. RESULTS: In this study, 9.6% patients developed AKI during hospitalization. Those with AKI presented older age, severer pneumonia, more comorbidity and lower lymphocyte count. Totally, more patients (77.5%) had primary composite outcomes (intensive care unit (ICU) admission, use of high-flow nasal cannula (HFNC) and mechanical ventilation) in AKI group compared to non-AKI group (2.9%) during the observation period. The median length of stay (LOS) and ICU stay were longer among those with AKI. After adjusted for related covariates, AKI development was independently correlated with LOS (ß (95% CI): 9.16 (3.87-14.46)), rather than primary outcomes (HR (95% CI): 1.34 (0.56-3.21)) in COVID-19 patients. CONCLUSIONS: The development of AKI was not one of the reasons for ICU admission, use of HFNC and mechanical ventilation, but a kind of manifestation of severe illness in COVID-19 hospitalized patients.

16.
Aging (Albany NY) ; 12(19): 18982-19011, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052878

RESUMO

The effect of POC1 centriolar protein A (POC1A) on gastric cancer (GC) has not been clearly defined. In this study, POC1A expression and clinical information in patients with GC were analyzed. Multiple databases were used to investigate the genes that were co-expressed with POC1A and genes whose changes co-occurred with genetic alternations of POC1A. Moreover, the TISIDB and TIMER databases were used to analyze immune infiltration. The GSE54129 GC dataset and LASSO regression model (tumor vs. normal) were employed, and 6 significant differentially expressed genes (LAMP5, CEBPB, ARMC9, PAOX, VMP1, POC1A) were identified. POC1A was selected for its high expression in adjacent tissues, which was confirmed with IHC. High POC1A expression was related to better overall and recurrence-free survival. GO and KEGG analyses demonstrated that POC1A may regulate the cell cycle, DNA replication and cell growth. Furthermore, POC1A was found to be correlated with immune infiltration levels in GC according to the TISIDB and TIMER databases. These findings indicate that POC1A acts as a tumor suppressor in GC by regulating the cell cycle and cell growth. In addition, POC1A preferentially regulates the immune infiltration of GC via several immune genes. However, the specific mechanism requires further study.

18.
J Org Chem ; 85(21): 13466-13471, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33089682

RESUMO

Artatrovirenols A and B (1 and 2), two novel cagelike sesquiterpenoids, possess a unique 5/5/6/5/5-pentacyclic and a 5/5/6/5-tetracyclic system with an unprecedented tetracyclo[5.3.1.1.4,1101,5]dodecane scaffold from Artemisia atrovirens. The structures of compounds 1 and 2 including their absolute stereochemistry were elucidated through extensive spectroscopic analyses, X-ray crystallography, and quantum chemical calculations. Plausible biosynthetic pathways for the new isolates were proposed from the naturally occurring arglabin (3) via the key intramolecular Diels-Alder cycloaddition. Compound 1 showed cytotoxicity against three human hepatoma cell lines (HepG2, SMMC-7721, and Huh7) with half maximal inhibitory concentration values of 123.8, 44.0, and 142.6 µΜ, respectively.


Assuntos
Artemisia , Sesquiterpenos , Linhagem Celular , Cristalografia por Raios X , Humanos , Sesquiterpenos/farmacologia
19.
Bioorg Chem ; 103: 104107, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745752

RESUMO

The preliminary assay suggested that the EtOH extract of Artemisia lavandulaefolia had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with an inhibitory ratio of 94.1% at 400 µg/mL. Bioassay-guided investigation led to eleven new sesquiterpenoids, artemilavanolides C-F (1-4) and artemlavandulolides A-G (5-11), as well as thirteen known compounds (12-24). Their structures were elucidated by extensive spectroscopic data and X-ray crystallographic analysis. Cytotoxicity evaluation suggested that fourteen compounds exhibited activity against HSC-LX2; compounds 22, 23 and 24 were comparable to the positive control, silybin (IC50, 162.3 µM); compounds 6, 9 and 16 showed moderate activity with IC50 values of 109.3, 114.0 and 124.2 µM. Importantly, compounds 14, 15 and 18 displayed significant cytotoxicity against HSC-LX2 with IC50 values of 52.1, 16.5 and 21.3 µM, and inhibitory activity on the deposition of human collagen type I (Col I) and human laminin (HL) with IC50 values ranging from 7.3 to 71.6 µM and from 18.6 to 72.9 µM.


Assuntos
Artemisia/química , Sesquiterpenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1307-1311, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798417

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of different types of red blood cell (RBC) transfusion and hormone therapy in patients with autoimmune hemolytic anemia (AIHA). METHODS: The clinical data and serological characteristics of 40 patients with AIHA treated in our hospital from 2014 to 2018 were collected and analyzed retrospectively. The efficacy and safety of different type of RBC transfusion and hormone therapy were evaluated according to the principle of minimally incompatible RBC transfusion after cross-matching. RESULTS: Among 40 patients with AIHA, the female cases were more than the male cases, the cases of secondary AIHA was more than cases of primary AIHA, and the warm autoantibodies were in the majority. 11 cases of AIHA underwent 26 times minimally incompatible red blood cell transfusions. The total effective rate was 46.2%, the partial efficiency was 23.1%, and total inefficiency was 30.8%. Among them, the same type of non-washing red blood cell group showed efficiency of 42.1%, partial effective rate of 21.1%, and inefficiency of 36.8%; the same type of washed red blood cell group showed efficiency of 57.1%, partial effective rate of 28.6%, and inefficiency of 14.3%. the infusion effects was not significanly different between the two groups, and no hemolytic transfusion reaction occurred. In the hormone-treated group, the complete remission rate was 15.2%, the partial remission rate was 63.6%, and the ineffective rate was 21.2%. Among them, the side effects appeared in 2 patients after using hormones. CONCLUSION: When AIHA patients need blood transfusion, use the same type of non-washed red blood cells or homologous washed cells is relatively safe, and the difference in efficacy is not significant. The partial remission of patients received hormone therapy is much higher than that of red blood cell transfusion, but the side effects easily happen.


Assuntos
Anemia Hemolítica Autoimune , Autoanticorpos , Transfusão de Sangue , Transfusão de Eritrócitos , Eritrócitos , Feminino , Humanos , Masculino , Estudos Retrospectivos
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