Publications by authors named "Xianghong Yang"

75 Publications

SOX17 Antagonizes the WNT Signaling Pathway and is Epigenetically Inactivated in Clear-Cell Renal Cell Carcinoma.

Onco Targets Ther 2021 24;14:3383-3394. Epub 2021 May 24.

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.

Background: SRY-box containing gene 17 (SOX17) was reported to be a candidate tumor suppressor gene in multiple tumors. Little is known about its role in clear-cell renal cell carcinoma (ccRCC). This study aims to identify the epigenetic regulation and tumor-suppressive function of SOX17 in ccRCC.

Patients And Methods: Fifty-five human ccRCC tissue samples, ten adjacent non-malignant kidney tissue samples, 20 paired paraffin section tissues and seven RCC cell lines were obtained. Immunohistochemistry (IHC) and real-time PCR were used to examine the expression of the target genes at the mRNA and protein levels. The methylation of SOX17 was analyzed using methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) assay. The functions of SOX17 were examined by using CCK8, colony formation, wound healing assay and Matrigel invasion assays. Luciferase assay was used to analyze the function of SOX17 in the WNT signaling pathway.

Results: We investigated the SOX17 expression in ccRCC tissues and adjacent non-malignant kidney tissues using PCR and IHC. The expression of SOX17 was lower in ccRCC tissues. Next, we analyzed the DNA promoter methylation of SOX17 in 55 human ccRCC tissues, 10 adjacent non-malignant kidney tissues and RCC cell lines using MSP. DNA methylation of the SOX17 promoter region occurred in 60% of ccRCC tissues and 10% of adjacent non-malignant kidney tissues. In vitro experiments showed that SOX17 suppressed the proliferation of RCC cells. Furthermore, SOX17 inhibited the migration of RCC cells as shown in the wound healing and migration assays. In addition, we found that SOX17 overexpression affected the WNT signaling pathway by downregulating c-myc and cyclinD1.

Conclusion: In summary, our study showed that SOX17 is downregulated in ccRCC and the loss of SOX17 expression is regulated via epigenetic mechanisms in ccRCC. In addition, SOX17 negatively regulates the WNT signaling pathway and function as a tumor suppressor in ccRCC.
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http://dx.doi.org/10.2147/OTT.S294164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163727PMC
May 2021

Domino effect of pituitary growth hormone tumor complicated by diabetic ketoacidosis and pituitary apoplexy: a case report.

BMC Endocr Disord 2021 May 26;21(1):109. Epub 2021 May 26.

Department of Emergency Medicine, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), 158 Shangtang Road, 310014, Hangzhou, Zhejiang, People's Republic of China.

Background: Patients with growth hormone (GH)-secreting adenoma usually develop glucose intolerance. GH increases metabolic rate and, when secreted aberrantly, may result in metabolic syndrome. Herein, we examine the associations of pituitary tumor-induced secretion of hormone with insulin resistance and metabolic syndrome, and determine the relation of pituitary tumor apoplexy-induced diabetic ketoacidosis (DKA) and acute pancreatitis.

Case Presentation: A 44-year-old male with a history of hypertension presented to the emergency department of our hospital on February 14, 2019 with symptoms of headache, dizziness, and vomiting. Computed tomography of the head revealed pituitary tumor with bleeding. An ultrasound scan of the abdomen revealed fatty liver and acute pancreatitis. Further examination revealed the presence of DKA, hypertriglyceridemia, cortical hypofunction crisis and acute kidney injury. Surgical endoscopic resection of the pituitary tumor resection via the transsphenoidal approach was performed. The patient's postoperative recovery was remarkable.

Conclusions: Long-term growth hormone abnormality may trigger insulin resistance, leading to metabolic syndrome and impaired glucose and lipid metabolism. The pituitary adenoma apoplexy may also directly induce DKA, creating a domino effect, which further deteriorate the aberrant metabolism of glucose and lipids.
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http://dx.doi.org/10.1186/s12902-021-00768-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157700PMC
May 2021

Distinct prognostic values of programmed death-ligand 1 and programmed cell death protein 1 in lung adenocarcinoma and squamous cell carcinoma patients.

Ann Transl Med 2021 Mar;9(5):397

Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.

Background: Although immunotherapy has demonstrated similar clinical activities in the treatment of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), several studies have shown programmed death-ligand 1 (PD-L1) to have different predictive roles in ADC and SCC. This study was conducted to compare the different functions of PD-L1/programmed cell death protein 1 (PD-1) pathway in these malignancies.

Methods: A multi-dimensional analysis based on public databases and 2 independent cohorts including 262 patients with lung cancer was performed. Immunohistochemistry (IHC) and fluorescence-based multiplexed staining were used to detect the immune factors.

Results: PD-L1 was observed to have different expressions and regulatory mechanisms between SCC and ADC. PD-L1 was significantly increased from the messenger RNA (mRNA) to protein levels in the SCC group compared with the ADC group. Also, PD-L1 on tumor cells (TCs) was positively correlated with CD8 tumor lymphocyte infiltrates in ADC, but not in SCC. More importantly, PD-L1 was considered to be an independent predictor of overall survival (OS) for ADC patients. In contrast, in SCC patients, PD-1 tumor-infiltrating lymphocytes (TILs) were considered a poor prognostic predictor.

Conclusions: These findings showed that PD-L1 in ADC and PD-1 TILs in SCC respectively indicates T-cell function, which plays a crucial role in determining prognosis. The distinct functions of the biomarkers between ADC and SCC might provide potential avenues for guiding anti-PD-1/PD-L1 immunotherapy.
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http://dx.doi.org/10.21037/atm-20-968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033326PMC
March 2021

Construction of Gene Modules and Analysis of Prognostic Biomarkers for Cervical Cancer by Weighted Gene Co-Expression Network Analysis.

Front Oncol 2021 18;11:542063. Epub 2021 Mar 18.

Department of Pathology, The Shengjing Hospital of China Medical University, Shenyang, China.

Background: Despite advances in the understanding of neoplasm, patients with cervical cancer still have a poor prognosis. Identifying prognostic markers of cervical cancer may enable early detection of recurrence and more effective treatment.

Methods: Gene expression profiling data were acquired from the Gene Expression Omnibus database. After data normalization, genes with large variation were screened out. Next, we built co-expression modules by using weighted gene co-expression network analysis to investigate the relationship between the modules and clinical traits related to cervical cancer progression. Functional enrichment analysis was also applied on these co-expressed genes. We integrated the genes into a human protein-protein interaction (PPI) network to expand seed genes and build a co-expression network. For further analysis of the dataset, the Cancer Genome Atlas (TCGA) database was used to identify seed genes and their correlation to cervical cancer prognosis. Verification was further conducted by qPCR and the Human Protein Atlas (HPA) database to measure the expression of hub genes.

Results: Using WGCNA, we identified 25 co-expression modules from 10,016 genes in 128 human cervical cancer samples. After functional enrichment analysis, the magenta, brown, and darkred modules were selected as the three most correlated modules for cancer progression. Additionally, seed genes in the three modules were combined with a PPI network to identify 31 tumor-specific genes. Hierarchical clustering and Gepia results indicated that the expression quantity of hub genes NDC80, TIPIN, MCM3, MCM6, POLA1, and PRC1 may determine the prognosis of cervical cancer. Finally, TIPIN and POLA1 were further filtered by a LASSO model. In addition, their expression was identified by immunohistochemistry in HPA database as well as a biological experiment.

Conclusion: Our research provides a co-expression network of gene modules and identifies TIPIN and POLA1 as stable potential prognostic biomarkers for cervical cancer.
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http://dx.doi.org/10.3389/fonc.2021.542063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016394PMC
March 2021

Succinylation Regulators Promote Clear Cell Renal Cell Carcinoma by Immune Regulation and RNA N6-Methyladenosine Methylation.

Front Cell Dev Biol 2021 18;9:622198. Epub 2021 Feb 18.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.

Succinylation is a newly discovered and multienzyme-regulated post-translational modification (PTM) that is associated with the initiation and progression of cancer. Currently, no systematic analyses on the role of succinylation regulators in tumors have been reported. In this study, we performed a comprehensive pan-cancer analysis on four well-known succinylation regulators (CPT1A, KAT2A, SIRT5, and SIRT7). We found that these regulators played specific and critical roles in the prognosis of clear cell renal cell carcinoma (ccRCC). We constructed a risk score (RS) based on two independent prognostic prediction factors, CPT1A and KAT2A, and subsequently developed a nomogram model containing the RS, which showed good accuracy in the prediction of overall survival (OS) in ccRCC patients. Furthermore, we used the similar expression pattern of four succinylation regulators according to consensus clustering analysis to divide the patients into three clusters that exhibited prominently different OS as well as clinicopathological characteristics. Differently expressed genes (DEGs) and pathway enrichment analyses of three clusters indicated that succinylation regulators might promote malignant progression of ccRCC by regulating the infiltration of immune cells and RNA N6-methyladenosine (m6A) methylation. Importantly, our data suggest that CPT1A and SIRT5 might up-regulate and down-regulate the expression of LRPPRC and EIF3B, respectively. Our study systematically analyzed the prognostic predictive values of four succinylation regulators and revealed their potential mechanisms in ccRCC aggressiveness. These data provide new insight into the understanding of succinylation modification and present clinical evidence for its role in ccRCC treatments.
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http://dx.doi.org/10.3389/fcell.2021.622198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935513PMC
February 2021

SHP1 Decreases Level of P-STAT3 (Ser727) and Inhibits Proliferation and Migration of Pancreatic Cancer Cells.

J Environ Pathol Toxicol Oncol 2021 ;40(1):17-27

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Purpose: To identify the direct effects and functional mechanisms of SHP1, plus its relationship with STAT3 in pancreatic cancer.

Methods: Immunohistochemistry and Western blot assays were used to test SHP1 expression in pancreatic cancer. The functions of SHP1 in pancreatic cancer cells were analyzed by cell viability, colony formation, flow cytometric analysis of apoptosis, migration and invasion assays. Co-immunoprecipitation, combined with shotgun mass spectrometry, verified the direct or indirect interactions with JAK1 and p-STAT3(Ser727). Non-labeling and quantitative proteomics analysis evaluated the effect of SHP1 on protein expression levels. PRM phosphorylation modification of quantitative proteomics analysis confirmed p-STAT3(Ser727) levels.

Results: SHP1 was missing or weakly expressed in human pancreatic ductal adenocarcinoma tissues and cells: PANC-1, AsPC-1, BxPC-3, and SW1990. SHP1 inhibited cell proliferation and migration. SHP1 had a slight effect on the protein expression level of PANC-1 cells. The level of p-STAT3(Ser727) was decreased by SHP1 at 0.53 multiple. Co-IP analysis revealed no direct or indirect interactions between SHP1and p-STAT3(Ser727) in protein complex patterns.

Conclusion: These results suggest that SHP1 negatively regulate pancreatic cancer cells progression. It inhibits STAT3 activation by decreasing STAT3 phosphorylation at serine 727.
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http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2020035980DOI Listing
March 2021

Association between fasting blood glucose levels at admission and overall survival of patients with pancreatic cancer.

BMC Cancer 2021 Feb 6;21(1):131. Epub 2021 Feb 6.

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.

Background: The associations between fasting blood glucose and staging and overall survival of patients with pancreatic cancer are still controversial. This study aimed to investigate the association between fasting blood glucose levels and overall survival (OS) of patients with pancreatic cancer and to evaluate the impact of differentiation and staging of pancreatic cancer.

Methods: This was a retrospective study of patients with pathologically confirmed pancreatic cancer admitted to Shengjing Hospital of China Medical University between 01/2012 and 12/2016. The outcome was the OS. The factors associated with OS were examined using univariable and multivariable Cox and logistic regression analyses.

Results: A total of 253 patients were included. Preoperative blood glucose levels were not significantly associated with the OS of patients with pancreatic cancer (HR = 1.04, 95%CI: 0.78-1.40, P = 0.781). Only CA199 > 1000 was independently associated with OS (HR = 1.86, 95%CI: 1.15-3.02, P = 0.012). The median survival in the normal glucose group was 20.5 months (95% confidence interval (CI): 14.2-26.9). The median survival in the high glucose group was 14.2 months (95% CI: 9.7-18.6). There was no statistically significant difference between the two groups (P = 0.573). Multivariable logistic regression analyses were performed to determine if blood glucose levels influenced the 1- and 2-year OS. No significant association was observed for 1-year (OR = 1.27, 95%CI: 0.71-2.29, P = 0.418) or 2-year (HR = 1.37, 95%CI: 0.76-2.46, P = 0.296) OS.

Conclusions: Fasting blood glucose levels are not associated with the OS of patients with pancreatic adenocarcinoma.
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http://dx.doi.org/10.1186/s12885-021-07859-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866692PMC
February 2021

The Prevalence, Associated Factors for Lung Metastases Development and Prognosis in Ovarian Serous Cancer Based on SEER Database.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820983801

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Ovarian carcinoma (OC) is one of the 3 most common gynecological malignancies, and the prognosis of patients with lung metastasis was the worst. SEER documented OC patients, diagnosed between 2010 and 2016, were included in the study. Univariable and multivariable logistic regression analyses were performed to identify associated factors for lung metastases (LM) development. Kaplan-Meier analysis was used to estimate the overall survival for OC patients with LM. A total of 10146 eligible serous ovarian cancer (SOC) patients were included, the prevalence of LM was 3.77% (N = 378). Patients with T4 stage (χ = 128.515; = 0.000), N1 stage (χ = 49.536; = 0.000), right laterality (χ = 18.756; = 0.000) (compared with left side), undifferentiated grade (χ = 36.174; = 0.000), bone metastasis (χ = 183.529); = 0.000), brain metastasis (χ = 117.539; = 0.000), liver metastasis (χ = 442.472; = 0.000) had a larger probability of LM than other groups. Results showed that T3/N1 stage, bone metastases, liver metastases, chemotherapy, surgery were positively correlated with LM. Multivariable cox analysis showed that age, bone metastasis, no chemotherapy, no surgery were independent risk factors in SOC-LM patients. This study provided new research insights on the prevalent LM in patients with SOC. The factors associated with LM development and prognosis can be potentially used for LM early screening and professional care.
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http://dx.doi.org/10.1177/1533033820983801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768314PMC
December 2020

Low-Power pH Sensor Based on Narrow Channel Open-Gated AlGaN/GaN HEMT and Package Integrated Polydimethylsiloxane Microchannels.

Materials (Basel) 2020 Nov 22;13(22). Epub 2020 Nov 22.

School of Microelectronics, Xi'an Jiaotong University, Xi'an 710049, China.

pH sensors with low-power and strong anti-interference are extremely important for industrial online real-time detection. Herein, a narrow channel pH sensor based on AlGaN/GaN high electron mobility transistor (HEMT) with package integrated Polydimethylsiloxane (PDMS) microchannels is proposed. The fabricated device has shown potential advantages in improving stability and reducing power consumption in response to pH changes of the solution. The performance of the pH sensor was demonstrated where the preliminary results showed an ultra-low power (<5.0 μW) at = 1.0 V. Meanwhile, the sensitivity was 0.06 μA/V·pH in the range of pH = 2 to pH = 10, and the resolution of the sensor was 0.1 pH. The improvement in performance of the proposed sensor can be related to the narrow channel and microchannel, which can be attributed to better surface GaO in a microchannel with larger H and HO concentration on the sensing surface during the detection process. The low-power sensor with excellent stability can be widely used in various unattended or harsh environments, and it is more conducive to integration and intelligence, which lays the foundation for online monitoring in vivo.
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http://dx.doi.org/10.3390/ma13225282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700280PMC
November 2020

LncRNA GA-Binding Protein Transcription Factor Subunit Beta-1 Antisense RNA 1 Inhibits Renal Carcinoma Growth Through an MiR-1246/Phosphoenolpyruvate Carboxykinase 1 Pathway.

Onco Targets Ther 2020 12;13:6827-6836. Epub 2020 Jul 12.

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.

Objective: To clarify the role and mechanism of GABPB1-AS1 in renal cell carcinoma.

Methods: We collected 48 pairs of tumor and adjacent normal tissues from patients with clear cell renal cell carcinoma (ccRCC). Both 786-o and caki-1 ccRCC cell lines were transfected with GA-binding protein transcription factor subunit beta-1 antisense RNA 1 (GABPB1-AS1), miR-1246, or small interfering RNA phosphoenolpyruvate carboxykinase 1 (siPCK1) vectors. RNA expression was examined by quantitative reverse transcription-PCR and protein expression by Western blot. Cell proliferation was measured by Cell Counting Kit-8 assays. Cell migration and invasion were measured by transwell assays. Targeting relationships between genes were tested by luciferase reporter gene assays.

Results: Lower GABPB1-AS1 expression was found in ccRCC cells and tissues. GABPB1-AS1 expression was inversely associated with tumor size, TNM stage, and Furhman stage. High GABPB1-AS1 expression was associated with a better prognosis. GABPB1-AS1 overexpression significantly inhibited proliferation, migration, and invasion by 786-o and caki-1 cells. GABPB1-AS1 overexpression reduced tumor weights in xenograft experiments. Luciferase reporter assays showed that miR-1246 overexpression significantly inhibited the luciferase activity of 786-o and caki-1 cells transfected with wild-type (WT)-GABPB1-AS1 or WT-PCK1. Knockdown of PCK1 weakened the inhibition of proliferation, migration, and invasion induced by GABPB1-AS1 overexpression in 786-o and caki-1 cells.

Conclusion: GABPB1-AS1 inhibits ccRCC growth and plays a tumor suppressor role through an miR-1246/PCK1 axis.
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http://dx.doi.org/10.2147/OTT.S257275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367931PMC
July 2020

A Comparison of Clinical Characteristics and Outcomes in Elderly and Younger Patients with COVID-19.

Med Sci Monit 2020 Jul 28;26:e925047. Epub 2020 Jul 28.

Intensive Care Unit, Zhejiang Hospital, Hangzhou, Zhejiang, China (mainland).

BACKGROUND The aim of this study was to describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and compare these parameters in an elderly group with those in a younger group. MATERIAL AND METHODS This retrospective, single-center observational study included 69 hospitalized patients with laboratory-confirmed COVID-19 from a tertiary hospital in Wuhan, China, between January 14, 2020, and February 26, 2020. Epidemiological, demographic, clinical, and laboratory data, as well as treatments, complications, and outcomes were extracted from electronic medical records and compared between elderly patients (aged ≥60 years) and younger patients (aged <60 years). Patients were followed until March 19, 2020. RESULTS Elderly patients had more complications than younger patients, including acute respiratory distress syndrome (ARDS; 9/25, 36% vs. 5/44, 11.4%) and cardiac injury (7/25, 28% vs. 1/44, 2.3%), and they were more likely to be admitted to the intensive care unit (6/25, 24% vs. 2/44, 4.5%). As of March 19, 2020, 60/69 (87%) of the patients had been discharged, 6/69 (8.7%) had died, and 3/69 (4.3%) remained in the hospital. Of those who were discharged or died, the median duration of hospitalization was 13.5 days (interquartile range, 10-18 days). CONCLUSIONS Elderly patients with confirmed COVID-19 were more likely to develop ARDS and cardiac injury than younger patients and were more likely to be admitted to the intensive care unit. In addition to routine monitoring and respiratory support, cardiac monitoring and supportive care should be a focus in elderly patients with COVID-19.
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http://dx.doi.org/10.12659/MSM.925047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412913PMC
July 2020

Prevalence and Impact of Coagulation Dysfunction in COVID-19 in China: A Meta-Analysis.

Thromb Haemost 2020 Nov 17;120(11):1524-1535. Epub 2020 Jul 17.

Department of Critical Care Medicine, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China.

Background:  The aim of this meta-analysis is to assess the prevalence of coagulation dysfunction in Chinese COVID-19 patients and to determine the association of coagulopathy with the severity and prognosis of COVID-19.

Methods:  A meta-analysis of the prevalence of different abnormal coagulation indicators in COVID-19 patients in China was performed. The difference of coagulation indicators and the incidence of DIC were compared between severe cases and nonsevere cases as well as nonsurvivors and survivors, respectively.

Results:  A total of 22 Chinese studies involving 4,889 confirmed COVID-19 inpatients were included. The average D-dimer value of COVID-19 patients is 0.67 µg/mL (95% confidence interval [CI]: 0.56-0.78), and 29.3% (95% CI: 20.1-38.5%) of patients showed elevated D-dimer values. Severe patients had significantly higher D-dimer levels and prolonged prothrombin time (PT) compared with nonsevere patients. Nonsurvivors had significantly higher D-dimer levels, prolonged PT, and decreased platelet count compared with survivors. In total, 6.2% (95% CI: 2.6-9.9%) COVID-19 patients were complicated by disseminated intravascular coagulation (DIC), in which the log risk ratio in nonsurvivors was 3.267 (95% CI: 2.191-4.342,  = 5.95,  < 0.05) compared with that in survivors.

Conclusion:  The prevalence of coagulopathy in Chinese COVID-19 inpatients is high, and both the abnormal coagulation indicators and DIC are closely associated with the severity and poor prognosis of these COVID-19 patients. Therefore, attention should be paid to coagulation dysfunction in COVID-19 patients. Closely monitoring of coagulation indicators and application of appropriate anticoagulation may improve the prognosis of COVID-19 inpatients in China.
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http://dx.doi.org/10.1055/s-0040-1714369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724576PMC
November 2020

Prevalence and impact of acute renal impairment on COVID-19: a systematic review and meta-analysis.

Crit Care 2020 06 18;24(1):356. Epub 2020 Jun 18.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.

Background: The aim of this study is to assess the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 patients and to determine the association of acute kidney injury (AKI) with the severity and prognosis of COVID-19 patients.

Methods: The electronic database of Embase and PubMed were searched for relevant studies. A meta-analysis of eligible studies that reported the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 was performed. The incidences of AKI were compared between severe versus non-severe patients and survivors versus non-survivors.

Results: A total of 24 studies involving 4963 confirmed COVID-19 patients were included. The proportions of patients with elevation of sCr and BUN levels were 9.6% (95% CI 5.7-13.5%) and 13.7% (95% CI 5.5-21.9%), respectively. Of all patients, 57.2% (95% CI 40.6-73.8%) had proteinuria, 38.8% (95% CI 26.3-51.3%) had proteinuria +, and 10.6% (95% CI 7.9-13.3%) had proteinuria ++ or +++. The overall incidence of AKI in all COVID-19 patients was 4.5% (95% CI 3.0-6.0%), while the incidence of AKI was 1.3% (95% CI 0.2-2.4%), 2.8% (95% CI 1.4-4.2%), and 36.4% (95% CI 14.6-58.3%) in mild or moderate cases, severe cases, and critical cases, respectively. Meanwhile, the incidence of AKI was 52.9%(95% CI 34.5-71.4%), 0.7% (95% CI - 0.3-1.8%) in non-survivors and survivors, respectively. Continuous renal replacement therapy (CRRT) was required in 5.6% (95% CI 2.6-8.6%) severe patients, 0.1% (95% CI - 0.1-0.2%) non-severe patients and 15.6% (95% CI 10.8-20.5%) non-survivors and 0.4% (95% CI - 0.2-1.0%) survivors, respectively.

Conclusion: The incidence of abnormal urine analysis and kidney dysfunction in COVID-19 was high and AKI is closely associated with the severity and prognosis of COVID-19 patients. Therefore, it is important to increase awareness of kidney dysfunction in COVID-19 patients.
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http://dx.doi.org/10.1186/s13054-020-03065-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300374PMC
June 2020

Knockdown of G-protein-signaling modulator 2 promotes metastasis of non-small-cell lung cancer by inducing the expression of Snail.

Cancer Sci 2020 Sep 10;111(9):3210-3221. Epub 2020 Aug 10.

Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, China.

Non-small-cell lung cancer (NSCLC) is the leading global cause of cancer-related death. Due to the lack of reliable diagnostic or prognostic biomarkers, the prognosis of NSCLC remains poor. Consequently, there is an urgent need to explore the mechanisms underlying this condition in order to identify effective biomarkers. G-protein-signaling modulator 2 (GPSM2) is widely recognized as a determinant of mitotic spindle orientation. However, its role in cancer, especially NSCLC, remains uncertain. In this study, we found that GPSM2 was downregulated in NSCLC tissues and was correlated with a poor prognosis. Furthermore, the knockdown of GPSM2 promoted NSCLC cell metastasis in vitro and in vivo and accelerated the process of epithelial-mesenchymal transition (EMT). Mechanistically, we showed that silencing GPSM2 induced cell metastasis and EMT through the ERK/glycogen synthase kinase-3β/Snail pathway. These results confirm that GPSM2 plays an important role in NSCLC. Moreover, GPSM2, as an independent prognostic factor, could be a potential prognostic biomarker and drug target for NSCLC.
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http://dx.doi.org/10.1111/cas.14519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469834PMC
September 2020

Management of critically ill patients with COVID-19 in ICU: statement from front-line intensive care experts in Wuhan, China.

Ann Intensive Care 2020 Jun 6;10(1):73. Epub 2020 Jun 6.

Department of Critical Care Medicine, Shanghai Jiaotong University, School of Medicine, Ruijin Hospital North, No. 197 Ruijin 2nd Road, Huangpu District, Shanghai, 201801, China.

Background: The ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept all over the world, posing a great pressure on critical care resources due to large number of patients needing critical care. Statements from front-line experts in the field of intensive care are urgently needed.

Methods: Sixteen front-line experts in China fighting against the COVID-19 epidemic in Wuhan were organized to develop an expert statement after 5 rounds of expert seminars and discussions to provide trustworthy recommendation on the management of critically ill COVID-19 patients. Each expert was assigned tasks within their field of expertise to provide draft statements and rationale. Parts of the expert statement are based on epidemiological and clinical evidence, without available scientific evidences.

Results: A comprehensive document with 46 statements are presented, including protection of medical personnel, etiological treatment, diagnosis and treatment of tissue and organ functional impairment, psychological interventions, immunity therapy, nutritional support, and transportation of critically ill COVID-19 patients. Among them, 5 recommendations were strong (Grade 1), 21 were weak (Grade 2), and 20 were experts' opinions. A strong agreement from voting participants was obtained for all recommendations.

Conclusion: There are still no targeted therapies for COVID-19 patients. Dynamic monitoring and supportive treatment for the restoration of tissue vascularization and organ function are particularly important.
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http://dx.doi.org/10.1186/s13613-020-00689-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275657PMC
June 2020

Biological characteristics and whole-genome analysis of the phage PEf771.

Can J Microbiol 2020 Sep 6;66(9):505-520. Epub 2020 May 6.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, P.R. China.

is a common pathogen causing refractory periapical periodontitis and secondary intraradicular infections. In this study, YN771 isolated from a re-treated root canal at a stomatology department was used as the host bacterium and was co-cultured with wastewater from the same department and patient samples to isolate a phage that lyses . We studied the biological and genomic characteristics of this phage. Transmission electron microscopy showed that this phage's head is icosahedral in structure, with a head diameter of around 98.4 nm, and a contractile tail of around 228.5 nm in length and a diameter of 17.3 nm. The phage was identified as a member of the family and named PEf771. It is sensitive to proteinase K but resistant to chloroform and Triton X-100. Its lytic cycle is 45 min, burst size is 78, optimal multiplicity of infection is 0.1, lysis spectrum is narrow, and host strain specificity is strong. Its optimal growth temperature is 37 °C, most suitable pH is 6.0, and is sensitive to ultraviolet radiation. Whole-genome sequencing of PEf771 indicated it has a genome size of 151 052 bp, with a GC content of 36.97%, and encodes 197 proteins plus 26 tRNAs. PEf771 is most closely related to phage EFDG1. Phage PEf771 has strong host specificity and lytic ability, so it is important to further characterize this phage and its interaction with .
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http://dx.doi.org/10.1139/cjm-2019-0336DOI Listing
September 2020

Therapeutic strategies for critically ill patients with COVID-19.

Ann Intensive Care 2020 Apr 20;10(1):45. Epub 2020 Apr 20.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.

Since the 2019 novel coronavirus disease (COVID-19) outbreak originated from Wuhan, Hubei Province, China, at the end of 2019, it has become a clinical threat to the general population worldwide. Among people infected with the novel coronavirus (2019-nCoV), the intensive management of the critically ill patients in intensive care unit (ICU) needs substantial medical resource. In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and influenza. These treatments are referable before the vaccine and specific drugs are available for COVID-19.
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http://dx.doi.org/10.1186/s13613-020-00661-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167303PMC
April 2020

β-Elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through miR-1323/Cbl-b/EGFR pathway.

Phytomedicine 2020 Apr 10;69:153184. Epub 2020 Feb 10.

Department of Respiratory and Infectious Disease of Geriatrics, the First Hospital of China Medical University, Shenyang 110001, China. Electronic address:

Background: β-Elemene is a natural agent extracted from the traditional Chinese herbal medicine Curcuma wenyujin that is a promising novel plant-derived drug with broad-spectrum anticancer activity. Our previous study identified an enhanced capacity for metastasis in multidrug resistant (MDR) gastric cancer and breast cancer cells. However, the anti-metastatic effects of β-Elemene on MDR cancer cells remain unknown.

Purpose: In this study, we posit the hypothesis that β-elemene possesses antimetastatic effects on MDR cancer cells.

Methods: Cell viability assay was used to assess the resistance of SGC7901/ADR cells and the cytotoxic effects of β-Elemene. Wound healing, transwell assay and lung metastatic mice model were used to the anti-metastasis effects of β-Elemene. MicroRNA microarray analysis was used to explore potential regulated miRNAs. Luciferase reporter assay was used to identify the direct target. Human MMP antibody array, western blot, immunoprecipitation, qRT-PCR analyses and immunohistochemistry were conducted to investigate the underlying anti-metastasis mechanism of β-Elemene.

Results: In this study, we found that β-Elemene significantly inhibited the metastatic capacity of MDR gastric cells in vivo and in vitro. Mechanistically, we found that β-Elemene regulated MMP-2/9 expression and reversed epithelial-mesenchymal transition. Further studies showed that β-Elemene upregulated Cbl-b expression, resulting in inhibition of the EGFR-ERK/AKT pathways, which regulate MMP-2/9. Additionally, we confirmed that β-Elemene upregulated Cbl-b by inhibiting miR-1323 expression. Finally, we found that numbers of metastatic tumor nodules were significantly decreased in the lungs of nude mice after β-Elemene treatment.

Conclusion: Our results suggested that β-Elemene inhibits the metastasis of MDR gastric cancer cells by modulating the miR-1323/Cbl-b/EGFR signaling axis.
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http://dx.doi.org/10.1016/j.phymed.2020.153184DOI Listing
April 2020

Dexmedetomidine protects against acute kidney injury in patients with septic shock.

Ann Palliat Med 2020 Mar 2;9(2):224-230. Epub 2020 Mar 2.

Department of Intensive Care Unit, Zhejiang Provincial People's Hospital, Hangzhou 310014, China; Department of Intensive Care Unit, People's Hospital of Hangzhou Medicine College, Hangzhou 310014, China; Department of Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310014, China.

Background: This study aimed to assess the relationship between the use of dexmedetomidine and the incidence of acute kidney injury (AKI) in septic shock patients undergoing mechanical ventilation and reveal the potential mechanism.

Methods: Septic shock patients undergoing mechanical ventilation were included. Patients were randomized into two groups including propofol group and dexmedetomidine group. Plasma samples were obtained from veins at 0, 12, 24, 72 and 120 h after receiving mechanical ventilation in ICU.

Results: Cohorts with septic shock after mechanical ventilation in ICU had similar baseline and demographic characteristics. Serum creatinine (SCr) and blood urea nitrogen (BUN) was lower in dexmedetomidine group (P<0.05) and also lower renal injury markers were detected in the dexmedetomidine group, compared with propofol group (P<0.05). Dexmedetomidine infusion reduced the TNF-α, IL-1 level in blood samples and maintained the balance of proportion of CD4+ and CD8+ T-lymphocytes. Patients receiving dexmedetomidine were less likely to develop AKI. The median ICU stay was decreased in dexmedetomidine group (P<0.05). Moreover, the case and duration of CRRT was also decreased by using dexmedetomidine (P<0.05). There was no significant difference between the cohorts with respect to the duration of mechanical ventilation.

Conclusions: The use of dexmedetomidine infusion in ICU patients was associated with a decreased incidence of AKI and reduced ICU stay and CRRT performance. The mechanism may be related to antiinflammatory reaction and immunoregulation.
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http://dx.doi.org/10.21037/apm.2020.02.08DOI Listing
March 2020

miR-1323 Promotes Cell Migration in Lung Adenocarcinoma by Targeting Cbl-b and Is an Early Prognostic Biomarker.

Front Oncol 2020 21;10:181. Epub 2020 Feb 21.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.

MicroRNAs are known to regulate cellular processes in non-small cell lung cancer (NSCLC) cells and predict prognosis. However, identification of specific microRNAs in NSCLC as potential therapeutic targets is controversial. We aim to determine the clinical significance of miR-1323 in the prognosis of patients with lung cancer and the potential mechanism. A bioinformatics approach was used to screen the importance microRNA in NSCLC through the online GEO database (GSE42425). The relationship between expression level of miR-1323 and overall survival of lung cancer patients was analyzed. Additionally, an independent corhort including 53 NSCLC cases that underwent resection validated the connection between miR-1323 and LUAD patients' overall survival. Next, the function of miR-1323 was studied by transient transfection. A more in-depth mechanism was studied through luciferase reporter gene experiments. High miR-1323 expression correlated with poor survival in NSCLC patients ( = 0.011), and in lung adenocarcinoma (LUAD) patients ( = 0.015) based on GEO database (GSE42425). In the independent cohort based on our hospital, high miR-1323 expression was associated with LUAD patients ( = 0.025). Moreover, transfection with mimics of miR-1323 showed an increased migratory capacity in LUAD A549 and HCC827 cells. In addition, E3 ubiquitin-protein ligase Casitas B-lineage Lymphoma-b (Cbl-b) was found to be the target genes of miR-1323 and significantly down regulated after mimics of miR-1323 transfection, and high Cbl-b expression predicted better prognosis in NSCLC and LUAD ( = 0.00072 and = 0.02, respectively). The miR-1323 promoted LUAD migration through inhibiting Cbl-b expression. High miR-1323 expression predicted poor prognosis in LUAD patients.
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http://dx.doi.org/10.3389/fonc.2020.00181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047338PMC
February 2020

Polyploidization-driven differentiation of freezing tolerance in Solidago canadensis.

Plant Cell Environ 2020 06 4;43(6):1394-1403. Epub 2020 Mar 4.

Weed Research Laboratory, Nanjing Agricultural University, Nanjing, China.

Solidago canadensis, originating from the temperate region of North America, has expanded southward to subtropical regions through polyploidization. Here we investigated whether freezing tolerance of S. canadensis was weakened during expansion. Measurement of the temperature causing 50% ruptured cells (LT ) in 35 S. canadensis populations revealed ploidy-related differentiation in freezing tolerance. Freezing tolerance was found to decrease with increasing ploidy. The polyploid populations of S. canadensis had lower ScICE1 gene expression levels but more ScICE1 gene copies than the diploids. Furthermore, more DNA methylation sites in the ScICE1 gene promoter were detected in the polyploids than in the diploids. The results suggest that promoter methylation represses the expression of multi-copy ScICE1 genes, leading to weaker freezing tolerance in polyploid S. canadensis compared to the diploids. The study provides empirical evidence that DNA methylation regulates expression of the gene copies and supports polyploidization-driven adaptation to new environments.
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http://dx.doi.org/10.1111/pce.13745DOI Listing
June 2020

Loss of G-protein-signaling modulator 2 accelerates proliferation of lung adenocarcinoma via EGFR signaling pathway.

Int J Biochem Cell Biol 2020 05 11;122:105716. Epub 2020 Feb 11.

Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang 110001, China. Electronic address:

G-protein-signaling modulator 2 (GPSM2) belongs to a protein family that regulates activation of G proteins and plays an important role in mitotic spindle orientation. However, the role of GPSM2 in lung adenocarcinoma (LUAD) is still unclear. In this study, it was found that GPSM2 correlates with clinicopathological features and patient's prognosis in LUAD. Knocking down GPSM2 promoted LUAD cell proliferation in vitro and in vivo. Mechanistically, it was demonstrated that GPSM2 knockdown accelerates cell proliferation via the EGFR pathway. These results confirmed that GPSM2 played an important role in LUAD. Moreover, GPSM2, as an independent prognostic factor, may serve as a potential drug target and prognostic biomarker in LUAD.
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http://dx.doi.org/10.1016/j.biocel.2020.105716DOI Listing
May 2020

Twist1 promotes astrocytoma development by stimulating vasculogenic mimicry.

Oncol Lett 2019 Jul 21;18(1):846-855. Epub 2019 May 21.

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

Astrocytomas are one of the most vascularized types tumor in human cancers. Micro-vascular proliferation is an important factor for the classification of astrocytoma. Vasculogenic mimicry (VM) is a novel tumor vascular model that develops independently of endothelial cells, and serves an important role in astrocytoma. Twist family bHLH transcription factor 1 (Twist1) is able to regulate the formation of VM; thus in the present study, the expression and importance of Twist1 was studied in astrocytoma tissues. The present study confirmed that the expression of Twist1 was associated with the grade of astrocytoma. Twist1 promotes the formation of VM and the development of astrocytomas, and may also regulate the formation of VM via vascular endothelial-cadherin and matrix metalloproteinase-9.
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http://dx.doi.org/10.3892/ol.2019.10380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546978PMC
July 2019

Primary Amebic Meningoencephalitis: A Case Report.

Korean J Parasitol 2019 Jun 30;57(3):291-294. Epub 2019 Jun 30.

Department of Critical Care Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.

Primary amebic encephalitis (PAM) is a devastating central nervous system infection caused by Naegleria fowleri, a free-living amoeba, which can survive in soil and warm fresh water. Here, a 43-year-old healthy male was exposed to warm freshwater 5 days before the symptom onset. He rapidly developed severe cerebral edema before the diagnosis of PAM and was treated with intravenous conventional amphotericin B while died of terminal cerebral hernia finally. Comparing the patients with PAM who has similar clinical symptoms to those with other common types of meningoencephalitis, this infection is probably curable if treated early and aggressively. PAM should be considered in the differential diagnosis of purulent meningoencephalitis, especially in patients with recent freshwater-related activities during the hot season.
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http://dx.doi.org/10.3347/kjp.2019.57.3.291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616161PMC
June 2019

MicroRNA‑214 upregulates HIF‑1α and VEGF by targeting ING4 in lung cancer cells.

Mol Med Rep 2019 Jun 16;19(6):4935-4945. Epub 2019 Apr 16.

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

Previous reports have indicated a potential link between microRNA (miR)‑214 and hypoxia. In the present study, the biological functions and potential mechanisms of miR‑214 were determined, as well as its correlation with HIF‑1α signaling in non‑small cell lung cancer (NSCLC) cells. Quantitative polymerase chain reaction revealed that miR‑214 expression was upregulated in lung cancer tissues compared with adjacent normal tissues. miR‑214 mimics were transfected into A549 cells, and MTT, colony formation, invasion and wound healing assays were performed. It was demonstrated that miR‑214 mimic transfection promoted the invasion, proliferation and migration of A549 cells. Furthermore, miR‑214 inhibitor transfection decreased H1299 cell invasion, proliferation and migration. Next, the association between miR‑214 expression and the HIF‑1α signaling cascade was examined. It was demonstrated that miR‑214 mimics upregulated the expression of hypoxia‑inducible factor (HIF)‑1α, vascular endothelial growth factor (VEGF), adenylate kinase 3 and matrix metalloproteinase (MMP)2, whereas miR‑214 inhibitor downregulated the expression of these factors. Using prediction software, it was demonstrated that tumor suppressor ING4 was a target of miR‑214. A luciferase reporter assay confirmed that ING4 was a direct target of miR‑214. There was a negative correlation between ING4 and miR‑214 expression in lung cancer tissues. In addition, ING4 siRNA and plasmid was transfected into cells in order to validate its effect on HIF‑1α, MMP2 and VEGF expression. ING4 overexpression downregulated HIF‑1α and its targets MMP2 and VEGF, while ING4 siRNA upregulated HIF‑1α, MMP2 and VEGF. In conclusion, it was demonstrated that miR‑214 targeted ING4 in lung cancer cells, and upregulated the HIF‑1α cascade, leading to MMP2 and VEGF upregulation. This approach may help to clarify the role of miRNA in non‑small lung cancer and may be a new therapeutic target for non‑small lung cancer.
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http://dx.doi.org/10.3892/mmr.2019.10170DOI Listing
June 2019

MicroRNA-1224 Inhibits Tumor Metastasis in Intestinal-Type Gastric Cancer by Directly Targeting FAK.

Front Oncol 2019 4;9:222. Epub 2019 Apr 4.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.

Intestinal-type gastric cancer (GC) of the Lauren classification system has specific epidemiological characteristics and carcinogenesis patterns. MicroRNAs (miRNAs) have prognostic significance, and some can be used as prognostic biomarkers in GC. In this study, we identified miR-1224 as a potential survival-related miRNA in intestinal-type GC patients by The Cancer Genome Atlas (TCGA) analysis. Using quantitative real-time PCR (qRT-PCR), we showed that the relative expression of miR-1224 was significantly decreased in intestinal-type GC tissues compared to matched adjacent normal mucosa tissues ( < 0.01). We found that high miR-1224 expression was associated with no lymph-node metastasis ( < 0.05) and good prognosis ( = 0.028) in 90 intestinal-type GC tissues. Transfection of intestinal-type GC cells with miR-1224 mimics showed that miR-1224 suppressed cell migration (wound healing assay and Transwell migration assay), whereas the transfection of cells with miR-1224 inhibitor promoted cell migration . miR-1224 also suppressed intestinal-type GC cell metastasis in a xenograft mouse model. Furthermore, bioinformatics, luciferase reporter, Western blotting, and immunohistochemistry (IHC) studies demonstrated that miR-1224 directly bound to the focal adhesion kinase (FAK) gene, and downregulated its expression, which decreased STAT3 and NF-κB signaling and subsequent the epithelial-to-mesenchymal transition (EMT). Repression of FAK is required for the miR-1224-mediated inhibition of cell migration in intestinal-type GC. The present study demonstrated that miR-1224 is downregulated in intestinal-type GC. miR-1224 inhibits the metastasis of intestinal-type GC by suppressing FAK-mediated activation of the STAT3 and NF-κB pathways, and subsequent EMT. miR-1224 could represent an important prognostic factor in intestinal-type GC.
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http://dx.doi.org/10.3389/fonc.2019.00222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458237PMC
April 2019

Vimentin acetylation is involved in SIRT5-mediated hepatocellular carcinoma migration.

Am J Cancer Res 2018 1;8(12):2453-2466. Epub 2018 Dec 1.

Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Shantou 515000, Guangdong, China.

Sirtuin 5 (SIRT5) belongs to the sirtuin family of protein deacetylases and contributes to tumorigenesis and migration. However, the underlying molecular mechanism of SIRT5 in hepatocellular carcinoma (HCC) migration is not fully understood. Here we report that SIRT5 was significantly downregulated in HCC, based on analysis of RNA-seq data from the liver HCC dataset of The Cancer Genome Atlas (TCGA). In addition, as compared to adjacent non-tumor tissues, SIRT5 was also significantly downregulated in HCC tissues. , gain and loss-of-function studies were performed to evaluate the role of SIRT5 in epithelial-mesenchymal transition (EMT). Knockdown of SIRT5 promoted EMT, as indicated by the upregulation of Snail and downregulation of E-cadherin, whereas overexpression of SIRT5 decreased Snail and upregulated E-cadherin. Mechanistically, SIRT5 was found to bind to and deacetylate vimentin at lysine 120. Cell migration was enhanced by overexpression of either wild-type vimentin or acetylation mimetic vimentin (K120Q), whereas cell migration was inhibited by overexpression of the non-acetylation vimentin (K120R). Taken together, these findings indicated that downregulated SIRT5-mediated vimentin acetylation may be involved in the EMT in HCC. Better understanding of SIRT5 may lead to its clinical application as a biomarker for prognosis of prediction of prognosis, as well as a novel therapeutic target.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325486PMC
December 2018

Fibrosis of mesothelial cell-induced peritoneal implantation of ovarian cancer cells.

Cancer Manag Res 2018 4;10:6641-6647. Epub 2018 Dec 4.

Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China,

Background: Peritoneal metastasis frequently occurs in patients with advanced ovarian cancer and is the main basis for a poor prognosis. The mechanism underlying preferential ovarian cancer spread to the peritoneum is not well understood.

Methods: Herein, we investigated the significance and mechanism underlying fibrosis of mesothelial cells promoting peritoneal implantation of ovarian cancer. We have assessed the mesothelial cell fibroblast transformation process in peritoneal tissues of omentum and fibrotic mesothelial cell release of chemokines to promote dissemination by scanning electron microscopy, ELISA, Western blot, and Transwell chamber assay.

Results: We showed that the fibrosis of mesothelial cells exists in the peritoneum of ovarian cancer patients with peritoneal metastasis. Fibrosis of the mesothelial cells was induced by TGF-β1, which upregulates the CXCL12-CXCR4 and CXCL16-CXCR6 axes of mesothelial cells.

Conclusion: CXCL12-CXCR4 and CXCL16-CXCR6 may be important signaling pathways closely involved in peritoneal metastasis of ovarian cancer that require further investigation. The findings may lead to developing alternative strategies aimed at preventing and treating the metastasis of ovarian cancer.
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http://dx.doi.org/10.2147/CMAR.S183043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284525PMC
December 2018

Evaluation of paliperidone on social function in patients with chronic schizophrenia.

Gen Psychiatr 2018 1;31(2):e000011. Epub 2018 Nov 1.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: The impairment of social function is widespread in the patients with chronic schizophrenia, which seriously affects family, life and work conditions.

Aims: The main purpose of this study was to investigate the efficacy of paliperidone in the treatment of social function in chronic schizophrenia.

Methods: A total of 81 patients who met the standard criteria for schizophrenia and long-term hospitalised inpatients were randomly divided into the treatment group and normal control group following a 1- year prospective follow-up study. The reatment group (41 cases) used paliperidone extended-release tablets for reducing dosage, as appropriate, based on the original treatment strategy; and the control group (40 cases) used the former drugs. All patients were assessed using the Positive and Negative Symptom Scales (PANSS), and the Treatment Emergent Symptom Scale (TESS) was used to assess adverse drug reactions. The Hospitalised Psychiatric Patients' Social Functions Rating Scale (SSPI) was used to assess social function of participants before and after 8  weeks, 6  months and 1 year of treatment.

Results: At baseline there were no significant differences between the two groups in age, duration of illness, educational background and dosage of antipsychotic drugs (converted into chlorpromazine equivalency). There was statistically significant difference in PANSS positive symptoms by interaction effect (F=18.24, df=3237, <0.001) and time effect (F=21.66, df=3, <0.01) and the difference in PANSS positive symptoms by grouping effect (F=0.68, df=1, =0.41) was not statistically significant. The difference of grouping effect of PANSS negative symptoms (F=9.93, df=1, =0.002), time effect (F=279.15, df=3, <0.001) and interaction effect (F=279.15, df=3237, <0.001) were statistically significant. There were statistically significant differences in the grouping effect (F=6.59, df=1, =0.012), time effect (F=152.97, df=3, p<0.001) and interaction effect (F=148.82, df=3237, <0.001) of PANSS general pathological symptoms, the same as the total score of the PANSS, which showed large differences in grouping effect (F=7.04, df=1, =0.001), time effect (F=210.78, df=3, <0.001) and interaction effect (F=205.20, df=3237, <0.01). We found in the total SSPI score, grouping effect (F=31.70, df=1, <0.001), time effect (F=161.84, df=3, <0.001) and interaction effect (F=132.74, df=3237, <0.001) were demonstrated to be significantly different. Even though adverse reactions occurred 7 times in the treatment group and 44 times in the control group based on the Treatment Emergent Symptom Scale (TESS), incidence rate was significantly lower than that of the control group (χ²=18.854, <0.001).

Conclusion: Paliperidone can safely and effectively improve negative symptoms and social function in patients with chronic schizophrenia.
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http://dx.doi.org/10.1136/gpsych-2018-000011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234969PMC
November 2018

FUT4 is involved in PD-1-related immunosuppression and leads to worse survival in patients with operable lung adenocarcinoma.

J Cancer Res Clin Oncol 2019 Jan 24;145(1):65-76. Epub 2018 Oct 24.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, China.

Purpose: As an important glycosyltransferase, fucosyltransferase IV (FUT4) is abnormally upregulated in different types of cancers, but its clinical role remains inexplicit. This work aimed to determine the predictive ability of FUT4 in lung adenocarcinoma (LUAD) after curative resection, as well as to explore the role of a possible FUT4 molecular mechanism on LUAD malignant behavior.

Methods: A total of 273 LUAD patients after curative resection with complete clinicopathological and RNAseq data from The Cancer Genome Atlas (TCGA) cohort were collected. Correlation of FUT4 with overall survival (OS) was analyzed based on TCGA and further validated by online "Kaplan-Meier Plotter" database and IHC in 70 LUAD patients recruited in the First Hospital of China Medical University cohort. Multivariate Cox regression analysis and 1000 bootstrapping were performed to verify the predictive value of FUT4. Gene set enrichment assay (GSEA) was performed to investigate the biological characteristics. Correlation between PD-1 and FUT4 was analyzed based on TCGA cohort and validated by IHC on cohort from our hospital.

Results: Increased FUT4 expression led to reduced overall survival (OS) of LUAD patients based on TCGA (p = 0.006 and 0.001 for dichotomous and trichotomous modeling, respectively) and externally validated in KMPLOTTER (p = 0.01) and by IHC based on cohort from our hospital (p = 0.005 and p = 0.019 for dichotomous and trichotomous modeling, respectively). FUT4 overexpression was an independent high risk factor for OS along with advanced pT stage and pTNM stage (p = 0.001, p = 0.037, and p < 0.001, respectively). GSEA revealed that FUT4 overexpression might correlate with shortened survival of LUAD patients by promoting cell proliferation via ERBB signaling, and suppressing immune response-related pathways. FUT4 expression positively correlated with PD-1 in TCGA (p = 0.026) and validated by IHC on cohort from our hospital (p = 0.029).

Conclusions: Increased FUT4 expression led to reduced OS in operable LUAD. FUT4 showed significant correlation with immune response and PD-1 expression.
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http://dx.doi.org/10.1007/s00432-018-2761-yDOI Listing
January 2019