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

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

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

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

OBJECTIVETo observe the clinicopathologic and genetic features of follicular variant of peripheral T-cell lymphoma (FV-PTCL), with particular attention to the relationship of this type of lymphoma with angioimmunoblastic T-cell lymphoma (AITL).

METHODSThe clinical data, hematoxylin and eosin-stained sections of lymph node biopsies from 2 FV-PTCL cases were reviewed. Immunohistochemical phenotyping and detection of EBV-encoded RNAs (EBER) through in situ hybridization (ISH) were performed. The EnVision two-step method was used for all antibodies except CXCL13 (by using three-step streptavidin immunoperoxidase method). Analysis of clonality and ITK/SYK gene rearrangement was conducted using PCR and RT-PCR assays, respectively.

RESULTSClinically, the two patients presented with superficial lymphadenopathy similarly. Histologically, case 1 showed a follicular/nodular lymphoid proliferation without marked germinal centers. The neoplastic cells comprised mainly medium sized cells with abundant, sometimes clear cytoplasms. Similar histologic findings were seen in case 2 in addition to a concurrent component mimicking typical AITL noticed. Of both cases, the neoplastic cells showed positive reactivity to CD3, CD4, CD10, PD1, and CXCL13. Positive hybridization signals for EBER were only seen in case 2, and double stains demonstrated that those EBV-positive cells were mostly the reactive transformed B-cells. Monoclonal T-cell proliferation was proved by the rearranged TCR gene detection in both cases. Neither of the current cases expressed ITK/SYK fusion transcripts.

CONCLUSIONFV-PTCL shows the similar or overlapped morphological and immunophenotypic features to those of AITL, possibly suggesting the presence of a potential relationship between these two types of lymphomas.

Aged ; Antigens, CD ; metabolism ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Apoptosis Regulatory Proteins ; metabolism ; Chemokine CXCL13 ; metabolism ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Endostatins ; therapeutic use ; Female ; Gene Rearrangement, T-Lymphocyte ; Humans ; Immunoblastic Lymphadenopathy ; genetics ; metabolism ; pathology ; Intracellular Signaling Peptides and Proteins ; genetics ; Keratins ; metabolism ; Lymphoma, Follicular ; drug therapy ; genetics ; metabolism ; pathology ; Lymphoma, T-Cell ; genetics ; metabolism ; pathology ; Lymphoma, T-Cell, Peripheral ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; metabolism ; Prednisone ; therapeutic use ; Programmed Cell Death 1 Receptor ; Protein-Tyrosine Kinases ; genetics ; Remission Induction ; Syk Kinase ; Vincristine ; therapeutic use

Allergic diseases have become global social health problems. The binding of IgE with its high affinity receptor FcepsilonRI plays a key step in I-type allergy. Recently, more and more key molecules on the IgE/FcepsilonRI signaling transduction pathway were to be the drug candidates against allergic diseases, with in-depth study of FcepsilonRI signal pathway gradually. The main drugs include molecule antibodies, peptides, vaccines, fusion proteins, small molecules, and other drugs related to IgE/FcepsilonRI. The recent progress in the study of mechanisms of representative drugs targeting on IgE/FcepsilonRI signaling pathway was reviewed in this article.
Aminophenols ; pharmacology ; therapeutic use ; Animals ; Anti-Allergic Agents ; pharmacology ; therapeutic use ; Antibodies, Anti-Idiotypic ; pharmacology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; pharmacology ; therapeutic use ; Humans ; Hypersensitivity ; drug therapy ; immunology ; Immunoglobulin E ; metabolism ; Intracellular Signaling Peptides and Proteins ; antagonists & inhibitors ; Molecular Targeted Therapy ; Omalizumab ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; pharmacology ; therapeutic use ; Receptors, IgE ; metabolism ; Signal Transduction ; Syk Kinase

OBJECTIVETo investigate the effect of Syk on the VEGF-C expression in breast cancer.

METHODSImmunohistochemical EnVision method was used to detect the protein expression of Syk, NFκB and VEGF-C in breast carcinoma; and the relationship between protein expression of Syk, NFκB, VEGF-C and lymph node metastasis was analysed. MDA-MB-231 cells were transfected with pcDNA3.1(-)-Syk, and the effect of Syk gene on the VEGF-C and NFκB expression was determined.

RESULTSIn the lymph node metastatic group, a lower expression rate of Syk and higher expression rate of VEGF-C and NFκB were detected as compared to the non-metastatic group. The expression of Syk was negatively associated with NFκB (r = -0.448, P = 0.002) and VEGF-C (r = -0.620, P = 0.000) expression, and VEGF-C was associated with the nuclear expression of NFκB (r = 0.310, P = 0.036). Compared with the non-transfected cells, the pcDNA3.1(-)-Syk transfected MDA-MB-231 cells showed significantly lower transcriptional level of VEGF-C mRNA, expression level of VEGF-C protein and NFκB activity (P < 0.05).

CONCLUSIONSSyk may play an important role in the lymph node metastasis of breast cancer. It may down-regulate the expression of VEGF-C by inhibiting the activity of NFκB, which thus suppresses lymph node metastasis of breast cancer.

Adult ; Aged ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Carcinoma, Lobular ; genetics ; metabolism ; pathology ; Carcinoma, Medullary ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Genetic Vectors ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; physiology ; Lymphatic Metastasis ; Middle Aged ; NF-kappa B ; metabolism ; Plasmids ; Protein-Tyrosine Kinases ; genetics ; metabolism ; physiology ; RNA, Messenger ; metabolism ; Syk Kinase ; Transfection ; Vascular Endothelial Growth Factor C ; genetics ; metabolism

OBJECTIVETo investigate the role of spleen tyrosine kinase (syk) in the phenotypic modulation induced by platelet-derived growth factor (PDGF-BB) in rat pulmonary vascular smooth muscle cells (VSMC).

METHODSVascular smooth muscles were isolated from pulmonary media of SD rats, cultured, adopted, and divided into 3 groups: blank control group, control group and medicine intervention group. The changes of proliferation and ultrastructure of vascular smooth muscle cells by using [(3)H] thymidine incorporation and electron microscopy. The mRNA and protein expression level of syk, alpha-smooth muscle-actin (α-SM-actin) and smooth muscle protein 22alpha (SM22α) were detected by RT-PCR and Western blotting. The change of fluorescence intensity was detected by laser scanning confocal microscope.

RESULTSTreatment with PDGF-BB for 24 h resulted in a significant increase in [(3)H] thymidine incorporation (2429.25 ± 253.36 vs. 242.75 ± 14.33,P < 0.01) and marked change in phenotype and cytoskeleton, the level of average optical density decreased significantly (263.75 ± 19.21 vs.1146.23 ± 62.61, P < 0.01). Meanwhile, the mRNA (1.70 ± 0.25 vs. 1.01 ± 0.12, P < 0.05) and protein level of syk significantly increased, the mRNA and protein expression of α-SM-actin (0.10 ± 0.00 vs. 1.00 ± 0.00, P < 0.01) and SM22α (0.18 ± 0.00 vs. 1.00 ± 0.01, P < 0.01) significantly decreased in VSMC induced by PDGF-BB. Piceatannol could inhibit significantly these biological effects. Compared with control group, the level of [(3)H] thymidine incorporation (527.00 ± 27.76 vs. 2429.25 ± 253.36,P < 0.01) was significantly down-regulated and the VSMC presented an apoptotic status in medicine intervention group, the level of average optical density increased significantly (810.65 ± 37.94 vs. 263.75 ± 19.21,P < 0.01) in medicine intervention group. Meanwhile, the mRNA (0.36 ± 0.07 vs. 1.70 ± 0.25, P < 0.01) and protein level of syk significantly decreased. The mRNA and protein levels of α-SM-actin (0.22 ± 0.00 vs. 0.10 ± 0.00, P < 0.01) and SM22α (0.31 ± 0.00 vs. 0.18 ± 0.00, P < 0.01) were significantly higher in medicine intervention group than in control group. The level of average optical density increased significantly (810.65 ± 37.94 vs. 263.75 ± 19.21, P < 0.01).

CONCLUSIONSyk plays an important role in vascular remodeling by changing the phenotypes and cytoskeleton of VSMC stimulated by PDGF-BB.

Animals ; Cells, Cultured ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Myocytes, Smooth Muscle ; metabolism ; Phenotype ; Platelet-Derived Growth Factor ; genetics ; Protein-Tyrosine Kinases ; genetics ; Proto-Oncogene Proteins c-sis ; Rats ; Rats, Sprague-Dawley ; Syk Kinase