OBJECTIVE: To observe the effects of point-moxibustion with Zhuang medicinal thread on differentially expressed genes (DEGs) in the dorsal root ganglion (DRG), tissue morphology, and the expression of Fc epsilon RI (FcεRI) pathway proteins spleen tyrosine kinase (Syk) and membrane spanning 4-domain A2 (MS4A2) in rat model of postherpetic neuralgia (PHN), and to explore the potential mechanism by which this therapy alleviates pain sensitization. METHODS: Thirty-nine male Sprague-Dawley (SD) rats were randomly divided into a control group, a model group, and a moxibustion group, with 13 rats in each group. The PHN model was established in the model and moxibustion groups by intraperitoneal injection of resiniferatoxin. In the moxibustion group, bilateral L₄-L₆ "Jiaji" (EX-B2) points were treated with point-moxibustion with Zhuang medicinal thread from day 7 post-modeling, with two cones per acupoint per session, every other day for a total of 10 sessions. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured at 1 day before modeling and on days 1, 4, 7, 13, 19, and 25 after modeling. After intervention, HE staining was used to observe DRG morphology. RNA sequencing was performed to analyze DEGs in DRG and conduct bioinformatics analysis. The expression of Syk and MS4A2 mRNA and proteins in the FcεRI pathway in DRG was detected by quantitative PCR and Western blot. RESULTS: Compared with the control group, the model group exhibited decreased MWT (P<0.05) and increased TWL (P<0.05); histopathological analysis revealed neuronal atrophy, nuclear displacement, and intracellular vacuoles, with a slightly loose arrangement; the RNA-Seq identified 3,207 DEGs (1,997 upregulated and 1,210 downregulated); the mRNA and protein expression levels of Syk and MS4A2 were significantly increased (P<0.01). Compared with the model group, the moxibustion group showed increased MWT (P<0.05) and decreased TWL (P<0.05), with relatively normal neuronal morphology; the RNA-Seq identified 426 DEGs (250 upregulated and 176 downregulated); the mRNA and protein expression levels of Syk and MS4A2 were significantly decreased (P<0.05). Venn diagram analysis identified 156 DEGs that showed a reversal in expression trends after treatment, including Syk and MS4A2, which are associated with pain sensitization. KEGG pathway analysis indicated that these DEGs were primarily enriched in the FcεRI pathway. CONCLUSION Point-moxibustion with Zhuang medicinal thread could alleviate pain sensitization in PHN rats, possibly by inhibiting the FcεRI signaling pathway and downregulating the expression of Syk and MS4A2.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; Moxibustion ; Neuralgia, Postherpetic/physiopathology* ; Syk Kinase/metabolism* ; Acupuncture Points ; Humans ; Ganglia, Spinal/metabolism* ; Signal Transduction

OBJECTIVE: To analyze the pathogens distribution in patients with ventilator-associated pneumonia (VAP), and their association with anti-β-glucan receptor-1 (Dectin-1)/spleen tyrosine kinase (Syk) signaling pathway, and to provide scientific basis for formulating more effective treatment strategies and preventive measures. METHODS: A prospective study was conducted. 160 patients with VAP admitted to the department of critical care medicine of Xingtai People's Hospital from January 2021 to March 2023 were enrolled. The respiratory secretions of patients were collected for Candida colonization analysis, and then the bacteria in the respiratory secretions were identified by automatic microbial identification instrument. The expression levels of Dectin-1 and Syk in peripheral blood mononuclear cells were detected by fluorescent immunopolymerase chain reaction. Clinical pulmonary infection score (CPIS) was performed based on imaging, clinical and microbiological criteria. The basic data, pathogen distribution, Dectin-1 and Syk expression levels and CPIS score of the two groups were compared. Spearman test was used to analyze the correlation between the expression levels of Dectin-1 and Syk and respiratory Candida colonization and CPIS score. RESULTS: 160 VAP patients, 97 were Candida colonized (colonized group) and 63 were not (non-colonized group). There were significantly differences in gender (males: 57.73% vs. 41.27%, P = 0.042) and age (years: 57.98±12.46 vs. 62.09±10.61, P = 0.029) between the colonized group and the non-colonized group, while there were no significantly differences in the data of duration of mechanical ventilation, underlying diseases and primary diseases. The distribution of pathogenic bacteria showed that the infection rate of Staphylococcus aureus in the colonized group was significantly higher than that in the non-colonized group (24.74% vs. 7.94%, P < 0.05), and there was no significantly difference in the infection rate of other G-positive and G-negative bacteria between the two groups. The CPIS score in the colonized group was significantly higher than that in the non-colonized group (8.73±0.43 vs. 7.31±0.39, P < 0.01), and the expression levels of Dectin-1 and Syk in peripheral blood mononuclear cells were significantly higher than those in the non-colonized group (Dectin-1/U6: 0.86±0.22 vs. 0.47±0.16, Syk/U6: 0.77±0.18 vs. 0.42±0.11, both P < 0.01). The expression levels of Dectin-1 and Syk in peripheral blood mononuclear cells of VAP patients were significantly positively correlated with the colonization of respiratory Candida (r values were 0.754 and 0.631, respectively, both P < 0.05), and were significantly positively correlated with CPIS score (r values were 0.594 and 0.618, respectively, both P < 0.05). CONCLUSION The proportion of Staphylococcus aureus in VAP patients with respiratory Candida colonization is higher, and Dectin-1/Syk signaling pathway is significantly positively correlated with respiratory Candida colonization and CPIS score.
Humans ; Syk Kinase ; Lectins, C-Type/metabolism* ; Signal Transduction ; Pneumonia, Ventilator-Associated/metabolism* ; Prospective Studies ; Male ; Female ; Middle Aged ; Candida ; Aged

Syk Kinase ; Tyrosine/metabolism* ; Phosphorylation

OBJECTIVES: To study the antitumor effect of piceatannol (PIC) on malignant melanoma METHODS: B16F10 cells were cultured RESULTS: The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. CONCLUSIONS PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.
Animals ; Cell Line, Tumor ; Cell Movement ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; Melanoma/drug therapy* ; Mice ; Neoplasm Invasiveness ; Stilbenes/pharmacology* ; Syk Kinase ; Vascular Endothelial Growth Factor A

Abstract　　Spleen tyrosine kinase (SYK) is not only a key kinase in the B-cell receptor (BCR) signaling pathway, but also a critical component of other signal transduction pathways such as Fc receptor, complement receptor and integrin. Abnormal activation of SYK closely related to the occurrence and development of hematological malignancies, thus targeting SYK has become a research hotspot. Several SYK inhibitors including Fostamatinib, Entospletinib and Cerdulatinib were being evaluated in clincal trials. As a second generation SYK inhibitor, Entospletinib has achieved good efficacy in lymphoid and myeloid hematologic tumors. Furthermore, Entospletinib can significantly relieve hematopoietic stem cell transplantation(HCT) related graft versus host disease (GVHD). In this review the role of SYK inhibitors in treatment of hematological malignancies is summarized brifely.
Graft vs Host Disease ; Hematologic Neoplasms ; Humans ; Protein Kinase Inhibitors ; Spleen ; Syk Kinase

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on the expressions of tyrosine kinase Lyn and spleen tyrosine kinase (Syk) in mast cells of subcutaneous loose connective tissue in the rats with urticaria and explore the potential biological mechanism of EA in the intervention of urticaria. METHODS: A total of 32 SD rats were randomized into a blank group, a model group, an EA group and a positive medication group, 8 rats in each one. Except of the blank group, the passive cutaneous anaphylaxis (PCA) was adopted to prepare the model of urticaria in the rats of the rest three groups. In the EA group, EA was applied to bilateral "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36), with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity, once daily, for 20 min each time, consecutively for 7 days. In the positive medication group, loratadine (1 mg•kg•d) was for intragastric administration, once daily, consecutively for 7 days. The samples were collected for index detection 30 min after PCA antigen challenge in the rats of each group. Spectrophotometer was adopted to determine the effusion quantity of Evans blue in the allergized site of skin. HE staining was used to observe the morphological changes in the allergized site of skin. Toluidine blue staining was provided to observe mast cell degranulation in subcutaneous loose connective tissue in the allergized site of skin. Immunohistochemistry was applied to determine the protein expressions of Lyn and Syk during degranulation of mast cells. RESULTS: In the rats of the odel group, the eipdermis of allergized site was thickening, cells were disorganized in hierarchy and inflammatory cells were infiltrated largely in the dermis. In the positive medication group and the EA group, the epidermis was getting thin, cell arrangement was clear and the inflammatory cell infiltration was obviously alleviated as compared with the model group. Compared with the blank group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all increased in the model group (<0.01). Compared with the model group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all reduced in the EA group and the positive medication group (<0.01). Compared with the positive medication group, the degranulation rate of mast cells was increased significantly in the EA group (<0.01). CONCLUSION Electroacupuncture at "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36) reduces vascular permeability and gives play to the role of anti-allergy by the way of regulating and controlling the degranulation of mast cells in the rats with urticaria and the effect mechanism of electroacupuncture may be related to the inhibition of protein expressions of Lyn and Syk in mast cells.
Acupuncture Points ; Animals ; Connective Tissue ; metabolism ; Electroacupuncture ; Mast Cells ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Syk Kinase ; metabolism ; Urticaria ; therapy ; src-Family Kinases ; metabolism

The present paper was aimed to study the role of spleen tyrosine kinase (Syk) in angiogenesis in hepatopulmonary syndrome (HPS) and the underlying mechanism. Sprague Dawley (SD) rats were randomly divided into three groups: sham operation group (sham group), common bile duct ligation (CBDL) 5-week group (5W group) and R788 intervention group (R788 group). HPS model was established by CBDL. Rats in R788 group were intraperitoneally injected with R788 (20 mg/kg) once daily to week 5 after CBDL operation. The protein expression levels and distribution of Syk, p-Erk1/2, and p-Akt in lung tissue were detected by Western blot and immunohistochemistry. Immunofluorescence staining was used to observe the location of Syk expression and the number of angiogenesis in lung tissue. The results showed that, compared with sham group, 5W group exhibited up-regulated protein expression level of Syk, increased phosphorylation levels of Erk1/2 and Akt, and increased number of pulmonary microvessels. Compared with 5W group, R788 group exhibited down-regulated protein expression level of Syk, decreased phosphorylation levels of Erk1/2 and Akt, and decreased number of pulmonary microvessels. These results suggest that Syk may promote pulmonary angiogenesis in HPS model rats by activating downstream Erk1/2 and Akt signaling pathways, which provides a theoretical basis and potential drug therapeutic targets for the clinical treatment of HPS.
Animals ; Disease Models, Animal ; Hepatopulmonary Syndrome ; Lung ; Rats ; Rats, Sprague-Dawley ; Syk Kinase

P-selectin engagement of P-selectin glycoprotein ligand-1 (PSGL-1) causes circulating leukocytes to roll on and adhere to the vascular surface, and mediates intracellular calcium flux, a key but unclear event for subsequent arresting firmly at and migrating into the infection or injured tissue. Using a parallel plate flow chamber technique and intracellular calcium ion detector (Fluo-4 AM), the intracellular calcium flux of firmly adhered neutrophils on immobilized P-selectin in the absence of chemokines at various wall shear stresses was investigated here in real time by fluorescence microscopy. The results demonstrated that P-selectin engagement of PSGL-1 induced the intracellular calcium flux of firmly adhered neutrophils in flow, increasing P-selectin concentration enhanced cellular calcium signaling, and, force triggered, enhanced and quickened the cytoplasmic calcium bursting of neutrophils on immobilized P-selectin. This P-selectin-induced calcium signaling should come from intracellular calcium release rather than extracellular calcium influx, and be along the mechano-chemical signal pathway involving the cytoskeleton, moesin and Spleen tyrosine kinase (Syk). These results provide a novel insight into the mechano-chemical regulation mechanism for P-selectin-induced calcium signaling of neutrophils in flow.
Calcium Signaling ; Female ; Humans ; Male ; Membrane Glycoproteins ; metabolism ; Neutrophils ; metabolism ; P-Selectin ; metabolism ; Stress, Mechanical ; Syk Kinase ; metabolism

OBJECTIVEThis study explores the mechanism of cyclooxygenase-2 (COX-2) upregulation in oral cancers associated with macrophage by using molecular biology techniques and primary culture of murine macrophage.

METHODSMurine macrophage was induced by macrophage colony-stimulating factor (M-CSF) and Cal27 conditional medium (CM). Purity of the macrophage was detected through CD68 immunofluorescence staining. Inhibitors of spleen tyrosine kinase (Syk) and nuclear factor κB (NFκB) were used to inhibit these pathways. In addition, real-time polymerase chain reaction and Western blot analysis were used to detect alterations in COX-2 and pathway-related proteins.

RESULTSAll of the induced cells specifically expressed CD68. Cal27 CM could significantly induce COX-2 expression (P<0.001). Moreover, inhibition of Syk pathway attenuated NFκB-P65 phosphorylation and reduced COX-2 expression (P<0.01), and inhibition of NFκB pathway exerted no effects on Syk phosphorylation but significantly inhibited COX-2 upregulation (P<0.01).

CONCLUSIONSSyk-NFκB is responsible for COX-2 overexpression in oral cancer associated with macrophages. Targeting this pathway is possibly a new approach to control oral cancer-related pain.
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Animals ; Cancer Pain ; Cyclooxygenase 2 ; Macrophage Colony-Stimulating Factor ; Macrophages ; Mice ; Mouth Neoplasms ; NF-kappa B ; Phosphorylation ; Signal Transduction ; Spleen ; Syk Kinase ; Up-Regulation

OBJECTIVETo investigate the expression of full-length spleen tyrosine kinase [SYK (L)] mRNA and protein in human oral squamous cell carcinoma (OSCC) as well as its possible effects on the invasion and metastasis of OSCC.

METHODSThe expression of SYK (L) was detected in 27 cases of OSCC tissues and its matched adjacent non-cancerous tissues by real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry. Fourteen cases of normal oral gingival tissues were also analyzed as a normal control.

RESULTSReduced mRNA and protein expression of SYK (L) in OSCC tissues was observed compared with that in normal oral gingival tissues (P<0.01) and adjacent non-cancerous tissues (P<0.05). SYK(L) expression was significantly associated with lymph-node metastasis (P<0.05).

CONCLUSIONSYK(L) is a candidate tumor suppressor for OSCC tissues, and has an inhibitive effect on the initiation, proliferation, and lymph-node metastasis of human OSCC.

Blotting, Western ; Carcinoma, Squamous Cell ; metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Mouth Neoplasms ; metabolism ; RNA, Messenger ; Syk Kinase ; metabolism