2.Research progress on the role and clinical application of Siglecs in tumor immunity.
Hui CHEN ; Jialin LU ; Danru WANG ; Lihao SUI ; Sheng XU
Chinese Journal of Cellular and Molecular Immunology 2023;39(12):1125-1131
Lectins are proteins responsible for recognizing the signals of sugar molecules in the body. Sialic acid-binding immunoglobulin-like lectins (Siglecs) regulate the innate and adaptive immune responses in the tumor microenvironment by recognizing the glycan structure containing sialic acid and mediating downstream signals through immune receptor tyrosine inhibitory motifs. In recent years, a variety of tumor treatment strategies targeting the sialic acid-Siglecs axis have been introduced, including sialoglycoprotein-mediated drug delivery and antibody mediated inhibition of Siglecs from recognizing tumor surface ligands. In the future, by combining with glycoprotein nanotherapy, antibody therapy and gene therapy, Siglecs can be used to accurately locate tumor targets and release the anti-tumor immunity, so as to achieve the purpose of effective cure of tumors.
Sialic Acid Binding Immunoglobulin-like Lectins/metabolism*
;
N-Acetylneuraminic Acid
;
Immunoglobulins/metabolism*
;
Receptors, Immunologic
;
Ligands
3.Significance of Tim-3 and Its Ligand Galectin-9 in Th1/Th2 Imbalance in Patients with Multiple Myeloma.
Rui ZHANG ; Shuang CHEN ; Ting-Ting LUO ; Jian-Hua QU
Journal of Experimental Hematology 2023;31(6):1764-1770
OBJECTIVE:
To investigate the significance of Tim-3 and Galectin-9 in Th1/Th2 imbalance in patients with multiple myeloma (MM).
METHODS:
55 newly diagnosed MM patients and 20 healthy controls were included. Flow cytometry was used to detect the expression of Tim-3 on CD4+T cells, the proportion of Th1, Th2, Tim-3+Th1 and Tim-3+Th2 cells in peripheral blood. ELISA was used to detect the levels of cytokines IFN-γ and IL-4 in serum, and PCR was used to detect the level of Galectin-9 mRNA. Then the correlations between Galectin-9 mRNA expression and Th-cell subsets and related cytokine levels, as well as the relationship between Tim-3+Th1/Tim-3+Th2 ratio and corresponding clinical features were analyzed.
RESULTS:
Compared with the control group, the expression of Tim-3 on CD4+T cells in peripheral blood of MM patients was significantly increased (P<0.05), the proportions of Tim-3+Th1 cells, Tim-3+Th2 cells and Tim-3+Th1/Tim-3+Th2 ratio in MM patients were also increased (P<0.05), while the proportion of Th1 cells and Th1/Th2 ratio in MM patients were significantly decreased (P<0.05). The level of cytokine IFN-γ and IFN-γ/IL-4 ratio in MM patients were significantly decreased (P<0.05), while the level of cytokine IL-4 was increased (P<0.05). The mRNA levels of Galectin-9 in MM patients were significantly increased (P<0.05). The levels of Galectin-9 mRNA were positively correlated with Tim-3+CD4+T cells (r=0.663), Tim-3+Th2 cells (r=0.492) and IL-4 (r=0.470), while negatively correlated with IFN-γ (r=-0.593). The ratios of Tim-3+Th1/Tim-3+Th2 in MM patients were positively correlated with ISS stage (r=0.511), osteolytic damage (r=0.556) and chromosome abnormality (r=0.632).
CONCLUSION
These results suggest that Tim-3 and Galectin-9 are involved in Th1/Th2 imbalance in MM patients, and the high ratio of Tim-3+Th1/Tim-3+Th2 is associated with poor clinical prognosis.
Humans
;
Cytokines/metabolism*
;
Galectins/metabolism*
;
Hepatitis A Virus Cellular Receptor 2/metabolism*
;
Interleukin-4/metabolism*
;
Ligands
;
Multiple Myeloma/metabolism*
;
RNA, Messenger/metabolism*
;
Th1 Cells/metabolism*
;
Th2 Cells/metabolism*
4.The correlation between FCER2 gene polymorphism and the efficacy of inhaled corticosteroids in patients with chronic rhinosinusitis.
Shuangxi LIU ; Na CHE ; Ling JIN ; Yang WANG ; Kai FAN ; Ju LAI ; Shaoqing YU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(11):856-863
Objective:To investigate the correlation between FCER2(2206A>G) gene polymorphism and the efficacy of inhaled corticosteroids(ICS) in patients with chronic rhinosinusitis(CRS). Methods:A total of 208 CRS patients were routinely treated with functional endonasal sinus surgery and postoperative ICS. DNA extraction, PCR amplification and gene sequencing were performed to observe the FCER2(2206A>G) gene polymorphism and calculate the allele frequency. The visual analog scale(VAS) score, Lund-Kennedy score, and computed tomography(CT) Lund-Mackay score were determined 6 months after surgery among patients with different genotypes. Moreover, the polymorphism frequency was compared among different subgroups(chronic rhinosinusitis with nasal polyps versus chronic rhinosinusitis without nasal polyps, eosinophilic chronic rhinosinusitis versus non-eosinophilic chronic rhinosinusitis). Results:There were FCER2(2206A>G) gene polymorphism in patients with CRS, and the phenotypes included 3 genotypes, AA, AG and GG, with distribution frequencies of 68(32.7%), 116(55.8%) and 24(11.5%) cases, respectively. No significant differences were found in age, VAS score, nasal endoscopic Lund-Kennedy score and CT imaging Lund-Mackay score among patients with CRS of each genotype before surgery. In patients with the AA genotype, the changes in VAS score(5.74±1.10), Lund Kennedy score(5.92 ± 1.14), and CT imaging Lund-Mackay score(13.26±4.26) were significantly higher than in patients with the AG(4.37±0.86, 5.37±1.24, 10.82±3.77) and GG(4.26±0.80, 5.18±1.56, 10.10±3.53) genotype(P<0.05). However, there were no marked difference between patients with the AG genotype and those with the GG genotype(P>0.05). Compared with patients with non-eosinophilic sinusitis, Among them, the differences between the GG genotype and AG /AA genes were more significant in eosinophilic sinusitis compared to non-eosinophilic sinusitis(P<0.01). Conclusion:The FCER2(2206A>G) gene in patients with CRS has genetic polymorphism and is associated with the recovery of CRS patients after surgery, individual corticosteroid sensitivity, and subgroup variability.
Humans
;
Nasal Polyps/complications*
;
Rhinitis/complications*
;
Sinusitis/complications*
;
Adrenal Cortex Hormones/therapeutic use*
;
Polymorphism, Genetic
;
Endoscopy/methods*
;
Chronic Disease
;
Receptors, IgE
;
Lectins, C-Type
5.Effect of lime water processing of Pinelliae Rhizoma Praeparatum on toxic component lectin protein.
China Journal of Chinese Materia Medica 2023;48(4):951-957
The present study investigated the effect of immersion in the excipient lime water on the toxic component lectin protein and explained the scientific connotation of lime water detoxication during the processing of Pinelliae Rhizoma Praeparatum. Western blot was used to investigate the effects of immersion in lime water with different pH(pH 10, 11, and 12.4), saturated sodium hydroxide, and sodium bicarbonate solution on the content of lectin protein. The protein compositions of the supernatant and the precipitate after immersing lectin protein in lime water of different pH were determined by the SDS-PAGE method combined with the silver staining technique. The MALDI-TOF-MS/MS technique was used to detect the molecular weight distribution of peptide fragments in the supernatant and precipitate after immersing lectin protein in lime water of different pH, and circular dichroism spectroscopy was used to detect the ratio changes in the secondary structure of lectin protein during the immersion. The results showed that immersion in lime water at pH>12 and saturated sodium hydroxide solution could significantly reduce the content of lectin protein, while immersion in lime water at pH<12 and sodium bicarbonate solution had no significant effect on lectin protein content. The corresponding lectin protein bands and molecular ion peaks were not detected at the 12 kDa position in the supernatant and precipitate after immersing the lectin protein in lime water at pH>12, which was attributed to the fact that lime water immersion at pH>12 could significantly change the ratio of the secondary structure of lectin protein, resulting in irreversible denaturation, while lime water immersion at pH<12 did not change the ratio of the secondary structure of lectin protein. Therefore, pH>12 was the key condition for the detoxication of lime water during the processing of Pinelliae Rhizoma Praeparatum. Lime water immersion at pH>12 could cause irreversible denaturation of lectin protein, resulting in a significant decrease in the inflammatory toxicity of Pinelliae Rhizoma Praeparatum, which played a key role in detoxification.
Lectins
;
Pinellia
;
Sodium Bicarbonate
;
Sodium Hydroxide
;
Tandem Mass Spectrometry
;
Water
6.The Expression and Correlation of miR-195, miR-125 and Calreticulin in Diffuse Large B-Cell Lymphoma.
Yan LI ; Xiao-Yan LIU ; Gui-Rong CUI ; Xiao-Yang KONG ; Lin YANG ; Jian-Min LUO
Journal of Experimental Hematology 2023;31(1):120-124
OBJECTIVE:
To analyze the expression and correlation of microRNA-195 (miR-195), miR-125 and calreticulin in diffuse large B-cell lymphoma (DLBCL).
METHODS:
From April 2020 to April 2021, 80 DLBCL patients with complete data archived by the Pathology Department of Handan First Hospital and The Second Hospital of Hebei Medical University were selected as the study group, and 70 patients with reactive lymph node hyperplasia were selected as the control group. The expressions of miR-195 and miR-125 were detected by real-time fluorescence quantitative PCR, and the expression of calreticulin was detected by Western blot. Pearson correlation was used to analyze the correlation between miR-195, miR-125, calreticulin and DLBCL, and ROC curve was used to analyze the predictive value of miR-195, miR-125 and calreticulin for DLBCL.
RESULTS:
Compared with the control group, the expression of miR-195 decreased but miR-125 and calreticulin increased in the study group (P<0.001). The expression levels of miR-195, miR-125 and calreticulin were not related to sex, age, primary site and B symptoms of patients with DLBCL, but related to immunophenotype, Ann Arbor stage, lactate dehydrogenase, IPI score, nodule involvement and Ki-67 index. The expression of miR-195 decreased and the expression of miR-125 and calreticulin increased in DLBCL paitents with non-germinal center source, Ann Arbor stage III-IV, lactate dehydrogenase > 245 U/L, IPI score 3-5, nodule involvement≥2 and Ki-67 index≥75% (P<0.05). Pearson correlation analysis showed that miR-195 and miR-125 were negatively correlated (r=-0.536, P=0.001), miR-195 and calreticulin were negatively correlated (r=-0.545, P=0.001), while miR-125 and calreticulin were positively correlated (r=0.523, P=0.001). ROC curve showed that compared with the single diagnosis of miR-195, miR-125 and calreticulin, the combination of the three items had higher predictive value for DLBCL (P<0.001).
CONCLUSION
The expression of miR-195 decreases and the expression of miR-125 and calreticulin increase in patients with DLBCL. Along with the increase of disease stage and IPI score, the decrease of miR-195 and the increase of miR-125 and calreticulin aggravate gradually. The three items may participate in the occurrence and progress of DLBCL.
Humans
;
MicroRNAs/genetics*
;
Ki-67 Antigen/metabolism*
;
Calreticulin/metabolism*
;
Prognosis
;
Lymphoma, Large B-Cell, Diffuse/genetics*
;
Lactate Dehydrogenases/metabolism*
7.The In Vivo Intervention and Relative Mechanism of Genistein on the Inflammation and Thrombophilia in Lymphoma-Bearing Mice.
Zhi-Yue CHEN ; Qing-Qing SHI ; Xin SUN ; Jun NI ; Wei WU ; Lian-Jun SHEN ; Mei SUN ; Kai-Lin XU ; Jian GU ; Hao GU
Journal of Experimental Hematology 2023;31(1):125-129
OBJECTIVE:
To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.
METHODS:
Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX)drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.
RESULTS:
After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).
CONCLUSION
Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.
Mice
;
Female
;
Animals
;
Genistein
;
Lymphoma
;
Cyclophosphamide
;
Thrombophilia
;
Inflammation
;
Lectins, C-Type
8.Overexpression of CLEC5A inhibits cell proliferation and metastasis and reverses epithelial-mesenchymal transition in hepatocellular carcinoma.
Jie LIN ; Huo Hui OU ; Wei Dong WANG ; Jing MA ; Wei Jie ZHANG ; Qing Bo LIU
Journal of Southern Medical University 2023;43(1):85-91
OBJECTIVE:
To evaluate the effects of CLEC5A expression level on cell proliferation, migration and invasion and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) and explore the role of CLEC5A in the tumorigenesis and progression of HCC.
METHODS:
The expression level of CLEC5A was detected in 50 pairs of HCC and adjacent tissues using immunohistochemical staining, and its association with clinicopathological parameters of HCC patients was analyzed. Cultured HCC cell line SK-HEP-1 was transfected with a lentiviral vector overexpressing CLEC5A, and the transfection efficiency was verified using real-time fluorescence quantitative PCR and Western blotting. The changes in proliferation, migration and invasion abilities of the transfected cells were analyzed using CCK-8, 5-ethynyl-29-deoxyuridine (EdU) and Transwell assays, and EMT of the cells was determined using Western blotting.
RESULTS:
The protein expression level of CLEC5A was significantly lower in HCC tissues than in the adjacent tissues (P < 0.001). The expression level of CLEC5A was significantly correlated with tumor size (P=0.008), tumor number (P=0.010), histological differentiation (P=0.016), microvascular invasion (P=0.024) and BCLC stage (P=0.040). In SK-HEP-1 cells, overexpression of CLEC5A obviously inhibited the cell proliferation, migration and invasion and reversed EMT phenotype of the cells.
CONCLUSION
CLEC5A is a potential HCC suppressor gene and may serve as a promising therapeutic target for HCC.
Humans
;
Carcinoma, Hepatocellular/genetics*
;
Epithelial-Mesenchymal Transition
;
Liver Neoplasms/genetics*
;
Cell Proliferation
;
Cell Differentiation
;
Receptors, Cell Surface/genetics*
;
Lectins, C-Type/genetics*
9.Tinker, tailor, soldier, cell: the role of C-type lectins in the defense and promotion of disease.
James N ARNOLD ; Daniel A MITCHELL
Protein & Cell 2023;14(1):4-16
C-type lectins (CTLs) represent a large family of soluble and membrane-bound proteins which bind calcium dependently via carbohydrate recognition domains (CRDs) to glycan residues presented on the surface of a variety of pathogens. The deconvolution of a cell's glycan code by CTLs underpins several important physiological processes in mammals such as pathogen neutralization and opsonization, leukocyte trafficking, and the inflammatory response. However, as our knowledge of CTLs has developed it has become apparent that the role of this innate immune family of proteins can be double-edged, where some pathogens have developed approaches to subvert and exploit CTL interactions to promote infection and sustain the pathological state. Equally, CTL interactions with host glycoproteins can contribute to inflammatory diseases such as arthritis and cancer whereby, in certain contexts, they exacerbate inflammation and drive malignant progression. This review discusses the 'dual agent' roles of some of the major mammalian CTLs in both resolving and promoting infection, inflammation and inflammatory disease and highlights opportunities and emerging approaches for their therapeutic modulation.
Animals
;
Humans
;
Inflammation/metabolism*
;
Lectins, C-Type/metabolism*
;
Mammals/metabolism*
;
Membrane Proteins
;
Polysaccharides/metabolism*
10.Identification of immune-related prognostic signature for colon adenocarcinoma based on weighted gene co-expression network analysis.
Xiang HE ; Shouwei WAN ; Qiang HE ; Jixue HOU
Chinese Journal of Cellular and Molecular Immunology 2023;39(6):509-515
Objective To identify immune-related molecular markers in an attempt to predict prognosis of colon adenocarcinoma (COAD). Methods Immune related genes (IREGs) was analyzed based on the TCGA database. Weighted gene co-expression network analysis (WGCNA) and Cox regression analysis were used to establish risk models. According to the median risk score, COAD patients were divided into high risk and low risk groups. The prognostic difference were compared between the two groups. The function of the model was validated using GEO. Results A total of 1015 IREGs was obtained. The established model consisted of three genes: RAR related orphan receptor C (RORC), leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) and lectin galactoside-binding soluble galectin 4 (LGALS4). The high-risk group had significantly poorer prognosis than low-risk group in the GEO database, and it was validated using a GEO database. Further analysis via univariate and multivariate Cox regression analyses revealed that risk model could function as independent prognostic factor for COAD patients. Conclusion The risk model based on IREGs can predict the prognosis of patients with COAD.
Humans
;
Prognosis
;
Adenocarcinoma/genetics*
;
Colonic Neoplasms/genetics*
;
Gene Expression Profiling
;
Lectins

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