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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 375-382, 2024 Mar 20.
Article in Chinese | MEDLINE | ID: mdl-38645842

ABSTRACT

Objective: Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection. Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes. Recently, it has been reported that the T cell immunoglobulin and mucin domain protein 3 (Tim-3) and its ligand galactose lectin 9 (galectin-9) play crucial roles in immune dysfunction caused by various tumors, such as colorectal cancer. However, their expressions, biological functions, and prognostic value in colorectal cancer are still unclear. This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer. Methods: A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected. Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients. The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly. Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival (RFS) and the overall survival (OS) of colorectal cancer patients. Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients. Results: The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18% (120/171) and 32.16% (55/171), respectively, of the colorectal cancer tissues, whereas the low expression levels were 29.82% (51/171) and 67.84% (116/171), respectively. Furthermore, the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues, while the expression score of galectin-9 was lower than that in the paracancerous tissues (P<0.05). Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration, vascular infiltration, and clinical staging (P<0.05). During the follow-up period of 14-63 months, 7 out of 171 patients were lost to follow-up. Among the remaining patients, 49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9, respectively, whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9, respectively. Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did (RFS: log-rank=22.66, P<0.001; OS: log-rank=19.71, P<0.001). Conversely, patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did (RFS: log-rank=19.45, P<0.001; OS: log-rank=22.24, P<0.001). Cox multivariate analysis indicated that TNM stage Ⅲ (HR=2.26, 95% CI: 1.20-5.68), high expression of Tim-3 (HR=0.80, 95% CI: 0.33-0.91), and low expression of galectin-9 (HR=1.80, 95% CI: 1.33-4.70) were independent risk factors affecting RFS and OS in patients (P<0.05). Conclusion: Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues. High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis. They are identified as independent influencing factors that may trigger adverse prognostic events in patients. These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.


Subject(s)
Colorectal Neoplasms , Galectins , Hepatitis A Virus Cellular Receptor 2 , Humans , Galectins/metabolism , Hepatitis A Virus Cellular Receptor 2/metabolism , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Prognosis , Male , Female , Middle Aged , Neoplasm Recurrence, Local/metabolism , Biomarkers, Tumor/metabolism , Aged
2.
J Environ Manage ; 342: 118142, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37182485

ABSTRACT

In this study, a laboratory-scale vacuum membrane distillation (VMD) system coupled with microbubble aeration (MBA) was developed for the treatment of high-salinity brine containing organic matters. Herein, at the beginning, feedwater only containing model organics such as humic acid (HA), bovine serum albumin (BSA) and sodium alginate (SA) was utilized to investigate the organic-fouling behavior, results indicated that the permeate flux was not affected by a thin and loose contaminated layer deposited on the membrane surface. Furthermore, dissolved organics in the feed brine inhibited the occurrence of membrane wetting due to the existence of a compact and protective crystals/organic-fouling layer, which can prevent the intrusion of scaling ions into membrane substrates. Besides, organics in the feedwater have a high tendency to adsorb on the membrane surface based on molecular dynamics simulations, thus, forming an organic-fouling layer prior to inorganic scaling. Finally, the effect of MBA on fouling alleviation was evaluated in VMD system, nearly 50% of salt precipitation from fouled membrane was effectively removed with the introduction of MBA, which can be ascribed to a combination of mechanisms, including surface shear forces and electrostatic attractions induced by microbubbles, meanwhile, about 2.2% of the total energy was only consumed, when using MBA. Together, these results demonstrated that MBA was a promising approach to alleviate membrane fouling in VMD.


Subject(s)
Microbubbles , Water Purification , Dissolved Organic Matter , Distillation/methods , Vacuum , Salinity , Membranes, Artificial , Water Purification/methods
3.
Pharmacol Res Perspect ; 10(2): e00914, 2022 04.
Article in English | MEDLINE | ID: mdl-35171536

ABSTRACT

Despite advantages of arsenic trioxide (ATO) in oncological practice, its clinical applications have been hampered by severe cardiotoxicity. The general mechanism of ATO-induced cardiotoxicity has been attributed to its damage to mitochondria, resulting in cardiac remodeling. Honokiol (HKL) is a naturally occurring compound derived from Magnolia bark. Previous studies have demonstrated that HKL exerts cardio-protective effects on ischemia/reperfusion (I/R) or chemical-induced cardiotoxicity by counteracting the toxic effects on mitochondria. The present study was conducted to investigate whether HKL pretreatment protects against ATO-induced cardiac oxidative damage and cell death. For the in vitro study, we evaluated the effects of ATO and/or Honokiol on reactive oxygen species (ROS) production and apoptosis induction in primary cultured cardiomyocytes; for the in vivo study, BALB/c mice were administrated with ATO and/or HKL for a period of 4 weeks, myocardial apoptosis, cardiac function, and cardiac remodeling (cardiac hypertrophy and cardiac fibrosis) were assessed at the end of administration. Our results demonstrated Honokiol pretreatment alleviated the ATO-induced boost in ROS concentration and the following apoptosis induction in primary cultured cardiomyocytes. In the mouse model, Honokiol pretreatment ameliorated ATO-induced myocardial apoptosis, cardiac dysfunction, and cardiac remodeling. Collectively, these results indicated that Honokiol provide a protection against ATO-induced cardiotoxicity by reducing mitochondrial damage. In addition, given that Honokiol has shown considerable suppressive effects on leukemia cells, our data also imply that ATO and Honokiol combination may possibly be a superior avenue in leukemia therapy.


Subject(s)
Apoptosis/drug effects , Arsenic Trioxide/toxicity , Biphenyl Compounds/pharmacology , Cardiotoxicity/prevention & control , Lignans/pharmacology , Animals , Biphenyl Compounds/isolation & purification , Cardiotoxicity/etiology , Lignans/isolation & purification , Magnolia/chemistry , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mitochondria/drug effects , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism
4.
Front Oncol ; 12: 1018617, 2022.
Article in English | MEDLINE | ID: mdl-36698409

ABSTRACT

Osteoclast-like giant cell tumor (OGCT) is a common bone tumor, occasionally observed in some extraosseous organs, but rarely involving the digestive system, especially the liver. Previously reported osteoclast-like giant cell carcinoma of the liver often coexists with sarcomatoid or hepatocellular carcinoma. Undifferentiated liver tumors with osteoclast-like giant cells (OGCs) are extremely rare. Due to its rarity, there is no consensus for diagnosis and treatment of undifferentiated liver tumors with OGCs. Definitive diagnosis comes from surgery, so there is often a long delay in diagnosis following the occurrence of symptoms. This case describes an extremely rare case of an undifferentiated liver tumor with OGCs in detail. It also summarizes the previously published cases based on liver tumors with OGCs from August 1980 to June 2021, providing extensive evidence to improve preoperative diagnosis and management options.

5.
Proteomics Clin Appl ; 13(4): e1800038, 2019 07.
Article in English | MEDLINE | ID: mdl-30485682

ABSTRACT

PURPOSE: To screen the novel biomarkers for gastric cancer and to determine the values of glutaminase 1 (GLS1) and gamma-glutamylcyclotransferase (GGCT) for detecting gastric cancer. EXPERIMENTAL DESIGN: A discovery group of four paired gastric cancer tissue samples are labeled with Isobaric tag for relative and absolute quantitation agents and identified with LC-ESI-MS/MS. A validation group of 168 gastric cancer samples and 30 healthy controls are used to validate the expression of GLS1 and GGCT. RESULTS: Four hundred and thirty-one proteins are found differentially expressed in gastric cancer tissues. Of these proteins, GLS1 and GGCT are found overexpressed in gastric cancer patients, with sensitivity of 75.6% (95% CI: 69-82.2%) and specificity of 81% (95% CI: 75-87%) for GLS1, and with sensitivity of 63.1% (95% CI: 55.7-71.5%) and specificity of 60.7% (95% CI: 53.3-68.2%) for GGCT. The co-expression of GLS1 and GGCT in gastric cancer tissues has sensitivity of 78.1% (95% CI: 70.1-86.1%) and specificity of 86.5% (95% CI: 79.5-93.4%). Moreover, both GLS1 and GGCT present higher expression of 82.6% (95% CI: 68.5-99.4%) and 73.9% (95% CI: 54.5-93.3%) in lymph node metastasis specimen than those in non-lymph node metastasis specimen. The areas under ROC curves are up to 0.734 for the co-expression of GLS1 and GGCT in gastric cancer. The co-expression of GLS1 and GGCT is strongly associated with histological grade, lymph node metastasis, and TNM stage Ⅲ/Ⅳ. CONCLUSIONS AND CLINICAL RELEVANCE: The present study provides the quantitative proteomic analysis of gastric cancer tissues to identify prognostic biomarkers of gastric cancer. The co-expression level of GLS1 and GGCT is of great clinical value to serve as diagnostic and therapeutic biomarkers for early gastric cancer.


Subject(s)
Biomarkers, Tumor/biosynthesis , Gene Expression Regulation, Developmental , Gene Expression Regulation, Neoplastic , Glutaminase/biosynthesis , Glutamine/metabolism , Neoplasm Proteins/biosynthesis , Stomach Neoplasms/metabolism , gamma-Glutamylcyclotransferase/biosynthesis , Chromatography, Liquid , Female , Humans , Male , Mass Spectrometry , Proteomics , Stomach Neoplasms/pathology
6.
Med Sci Monit ; 24: 1633-1641, 2018 Mar 20.
Article in English | MEDLINE | ID: mdl-29555895

ABSTRACT

BACKGROUND Fibrosis is the common pathological feature in most kinds of chronic kidney disease (CKD). TGF-ß/Smads signaling is the master pathway regulating kidney fibrosis pathogenesis, in which Smad3 acts as the integrator of various pro-fibrosis signals. In this study, we analyzed the role of SIS3, a specific inhibitor of Smad3, in mouse unilateral ureteral obstruction (UUO) kidneys. MATERIAL AND METHODS UUO mice were intraperitoneally injected with 0.2 mg/kg/day or 2 mg/kg/day of SIS3 or control saline for 7 days, followed by analysis of structure injury, fibrosis status, inflammation, apoptosis, and TGF-ß/Smads signaling activity. RESULTS Our results indicated that SIS3 treatment dosage-dependently relieved the gross structure injury and tubular necrosis in UUO kidneys. Masson staining, immunohistochemistry, and real-time PCR showed significantly decreased extracellular matrix deposition, fibronectin staining intensity, and RNA levels of collagen I and collagen III in SIS3-treated UUO kidneys. SIS3 treatment also suppressed the activation of myofibroblasts, as evidenced by decreased expression levels of a-SMA and vimentin in UUO kidneys. The TGF-ß/Smads signaling activity analysis showed that SIS3 inhibited the phosphorylation of Smad3 but not Smad2 and decreased the protein level of TGF-ß1, suggesting specific inhibition of the TGF-ß/Smad3 pathway in UUO kidneys. Furthermore, SIS3 treatment also ameliorated the increased pro-inflammatory TNF-α and COX2 in UUO kidneys and circulating IL-1ß in UUO mice, and inhibited caspase-3 activity and the number of apoptotic cells. CONCLUSIONS SIS3 ameliorated fibrosis, apoptosis, and inflammation through inhibition of TGF-b/Smad3 signaling in UUO mouse kidneys.


Subject(s)
Apoptosis , Inflammation/drug therapy , Isoquinolines/therapeutic use , Kidney/pathology , Pyridines/therapeutic use , Pyrroles/therapeutic use , Signal Transduction , Smad3 Protein/metabolism , Transforming Growth Factor beta/metabolism , Ureteral Obstruction/drug therapy , Animals , Apoptosis/drug effects , Fibrosis , Inflammation/metabolism , Inflammation/pathology , Isoquinolines/pharmacology , Male , Mice, Inbred BALB C , Myofibroblasts/drug effects , Myofibroblasts/metabolism , Myofibroblasts/pathology , Pyridines/pharmacology , Pyrroles/pharmacology , Signal Transduction/drug effects , Ureteral Obstruction/metabolism , Ureteral Obstruction/pathology
7.
Mol Biotechnol ; 60(2): 134-140, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29318516

ABSTRACT

IgA protease is secreted by various mucosal pathogenic bacteria which can cleave human immunoglobulin A1 (IgA1) in its hinge region. In addition to be considered as a virulence factor, it's reported that IgA protease can also be used for IgA nephropathy (IgAN) treatment. Our previous study identified bacteria H. influenzae 49247 expressed high activity of IgA protease with promised application in IgAN therapy. In this study, we cloned the IgA protease gene of H. influenzae 49247 with degenerate primers. Alignment analysis indicated that H. influenzae 49247 IgA protease showed unique DNA and amino acid sequence but with typical endopeptidase domain and beta transporter domain compared with known IgA proteases from the same species. To facilitate expression and purification, the H. influenzae 49247 IgA protease gene was sub-cloned into the pET28-A(+) vector with insertion of a 6xHis tag downstream of the endopeptidase domain and upstream of the potential autocleavage site. The recombined IgA protease can be constitutively expressed in E. coli and secreted into the culture medium. With a simple nickel affinity binding, the secreted IgA protease can be purified with high purity (95%) and a molecular weight of about 130 kDa. The identity of the IgA protease was validated by the presence of 6xHis tag in the purified protein by western blotting and its ability to cleave human IgA1 molecule. Collectively, the successful cloning, expression and purification of H. influenzae 49247 IgA protease will augment its therapeutic study in IgAN treatment.


Subject(s)
Cloning, Molecular/methods , DNA Primers/genetics , Escherichia coli/genetics , Haemophilus influenzae/genetics , Recombinant Fusion Proteins/genetics , Serine Endopeptidases/genetics , Amino Acid Sequence , Chromatography, Affinity , DNA Primers/chemical synthesis , Escherichia coli/enzymology , Gene Expression , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Glomerulonephritis, IGA/therapy , Haemophilus influenzae/enzymology , Histidine/genetics , Histidine/metabolism , Humans , Immunoglobulin A/chemistry , Immunoglobulin A/metabolism , Molecular Weight , Oligopeptides/genetics , Oligopeptides/metabolism , Protein Domains , Proteolysis , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Serine Endopeptidases/chemistry , Serine Endopeptidases/metabolism
8.
Clin Chim Acta ; 471: 29-37, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28502558

ABSTRACT

BACKGROUND: The sensitivities and specificities of biomarkers for gastric cancer are insufficient for clinical detection, and new diagnostics are therefore urgently required. METHODS: A discovery set of gastric cancer tissues was labeled with iTRAQ reagents, separated using SCX chromatography, and identified using LC-ESI-MS/MS. A validation set of gastric cancer tissues was used to confirm the expression levels of potential markers. RESULTS: The present study detected metastasis-associated protein 2 (MTA2) and Histone deacetylases 1 (HDAC1) proteins that were overexpressed in gastric cancer tissues compared with that in adjacent gastric tissue. The sensitivity and specificity of MTA2 in detecting 76 cases gastric cancers were 57.9% (95% CI: 46.5%-69.3%) and 55.3% (95% CI: 43.8%-66.7%), respectively. The sensitivity and specificity of HDAC1 were 61.8% (95% CI: 50.7%-73%) and 63.2% (95% CI: 52.1%-74.3%), respectively. The co-expression of MTA2 and HDAC1 in gastric cancer achieved 65.3% sensitivity (95% CI: 51.5%-79.1%) and 65.2% specificity (95% CI: 50.9%-79.5%), which was strongly associated with lymph node metastasis and TNM staging. CONCLUSION: The present findings indicated a tight correlation between the MTA2 and HDAC1 expression level and lymph node metastasis and TNM staging in gastric cancers. Therefore, MTA2 and HDAC1 might be predictors of lymph node metastasis phenotype and possible target molecule for anticancer drug design in human gastric cancer.


Subject(s)
Biomarkers, Tumor/genetics , Epigenesis, Genetic/genetics , Gene Expression Regulation, Neoplastic/genetics , Proteomics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Transcription, Genetic , Amino Acid Sequence , Biomarkers, Tumor/chemistry , Biomarkers, Tumor/metabolism , Female , Histone Deacetylase 1/chemistry , Histone Deacetylase 1/genetics , Histone Deacetylase 1/metabolism , Histone Deacetylases/chemistry , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Humans , Male , Mass Spectrometry , Middle Aged , Repressor Proteins/chemistry , Repressor Proteins/genetics , Repressor Proteins/metabolism , Sensitivity and Specificity , Stomach Neoplasms/metabolism
9.
Data Brief ; 11: 122-126, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28180141

ABSTRACT

We provide detailed datasets from our analysis of proteins that are differentially expressed in gastric cancer tissues compared with adjacent normal gastric tissues, as identified by iTRAQ-based quantitative proteomics. Also included is a set of representative images of immunohistochemical staining of gastric cancer tissues showing four levels of expression of fatty acid binding protein (FABP1) and fatty acid synthase (FASN). The data presented in this paper support the research article "Quantitative proteomic analysis reveals that proteins required for fatty acid metabolism may serve as diagnostic markers for gastric cancer" (Jiang et al., 2017) [1]. We expect that the data will contribute to the identification of sensitive and specific biomarkers for early detection of gastric cancer.

10.
Clin Chim Acta ; 464: 148-154, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27884752

ABSTRACT

BACKGROUND: Gastric cancer is one of the leading causes of cancer-related deaths worldwide. The sensitivities and specificities of current biomarkers for gastric cancer are insufficient for clinical detection, and new diagnostic tests are therefore urgently required. METHODS: A discovery set of gastric cancer and adjacent normal tissues were analyzed for differentially expressed proteins by labeling of peptide digests with isobaric tag for relative and absolute quantitation (iTRAQ) reagents followed by liquid chromatography-electrospray ionization-tandem mass spectrometry. A validation set of 70 pairs of gastric cancer and adjacent normal tissues were examined to confirm the expression levels of the potential biomarkers identified by iTRAQ labeling. RESULTS: We detected 431 proteins associated with 16 KEGG pathways that were differentially expressed in gastric cancer tissues, of which 224 were upregulated and 207 were downregulated in gastric cancer tissues. Coexpression of fatty acid binding protein (FABP1) and fatty acid synthase (FASN) in gastric cancer tissues (61.4% sensitivity and 77.1% specificity) was strongly associated with lymph node metastasis and Tumor, Node, Metastasis stage I/II. CONCLUSION: Quantitative proteomic analysis of gastric cancer tissues revealed that coexpression of FABP1 and FASN may serve as a biomarker for detection of early gastric cancer.


Subject(s)
Biomarkers, Tumor/metabolism , Fatty Acids/metabolism , Proteomics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/metabolism , Early Detection of Cancer , Fatty Acid Synthase, Type I/metabolism , Fatty Acid-Binding Proteins/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Staging , Stomach Neoplasms/pathology
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