1.Mechanism of Yiqi Huoxue Therapy Regulating IL-33/ST2/IL-1RAP to Improve Nasal Mucosal Tissue Remodeling and Intervene in Allergic Rhinitis
Huan WANG ; Hongping LUO ; Meiya WANG ; Yuyin LIU ; Chenlin WANG ; Chao LIAO ; Fangqi LIANG ; Peizheng XIONG ; Li TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):298-307
ObjectiveTo explore the mechanism by which Qidan Yifei Tongqiao granules (QDYF) alleviate nasal mucosal remodeling in allergic rhinitis (AR) via the interleukin-33 (IL-33)/growth stimulation expressed gene 2 (ST2)/interleukin-1 receptor accessory protein (IL-1RAP) signaling pathway from the perspective of Qi-replenishing and blood-activating therapy. MethodsFirst, according to the previous network pharmacology results, this study predicted the potential mechanisms of QDYF in treating AR by screening key pathways, components, and targets. Molecular docking was performed via AutoDock and PyMOL 2.5.5. Subsequently, a rat model of ovalbumin (OVA)-induced AR was used for validation through in vivo experiments. Forty-eight rats were assigned into 6 groups: Control, model, low-dose QDYF (QDYF-L, 4.04 g·kg-1), medium-dose QDYF (QDYF-M, 8.08 g·kg-1), high-dose QDYF (QDYF-H, 16.16 g·kg-1), and loratadine (0.9 mg·kg-1). After 14 days of intervention, behavioral scores of the rats were observed. The morphological changes of nasal mucosa tissue were observed by hematoxylin-eosin (HE) staining. Masson staining was used to observe collagen fiber deposition in the nasal mucosal tissue and to calculate the collagen volume fraction (CVF). The expression of E-cadherin (E-cad) in the nasal mucosa tissue was detected by immunofluorescence. The serum levels of helper T cell 2 (Th2) cytokines interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) as well as helper T cell 1 (Th1) cytokines interleukin-2 (IL-2) and interferon-γ (INF-γ) were quantified by enzyme-linked immunosorbent assay (ELISA). The protein levels of transforming growth factor-beta 1 (TGF-β1), IL-33, ST2, and IL-1RAP in the nasal mucosa tissue were determined by Western blot. ResultsIL-33, ST2, and IL-1RAP had strong binding ability with the main active ingredients—wogonin, 7-methoxy-2-methylisoflavone, formononetin, naringenin, stigmasterol, and beta-sitosterol of QDYF, with the binding energy < -4.25 kcal⋅mol-1(1 cal≈4.184 J). The results of in vivo experiments showed that compared with the control group, the model group exhibited increased behavioral scores (P<0.05), aggravated pathological damage of nasal mucosa, increased collagen fiber deposition and CVF (P<0.05), elevated serum levels of IL-4, IL-5, and IL-13, up-regulated protein levels of TGF-β1, IL-33, ST2, and IL-1RAP in the nasal mucosa (P<0.05), down-regulated expression of E-cad, and declined serum levels of IL-2, IFN-γ, and IFN-γ/IL-4 ratio (P<0.05). Compared with the model group, the QDYF groups and loratadine group showed reduced behavioral scores (P<0.05), alleviated pathological damage of nasal mucosa, reduced collagen fiber deposition and CVF (P<0.05), and up-regulated E-cad expression (P<0.05). Compared with the model group, the QDYF-H group and the loratadine group showed raised levels of INF-γ and IFN-γ/IL-4 ratio (P<0.05), declined serum levels of IL-4, IL-5, and IL-13, and down-regulated protein levels of TGF-β1, IL-33, ST2, and IL-1RAP in the nasal mucosa (P<0.05). In addition, the QDYF-H group exhibited an elevated serum IL-2 level (P<0.05). The QDYF-M group showed down-regulated protein levels of TGF-β1, IL-33 and IL-1RAP in the nasal mucosa (P<0.05). The QDYF-L group demonstrated a down-regulated protein level of ST2 in the nasal mucosa (P<0.05). ConclusionQDYF may regulate the Th1/Th2 balance through the IL-33/ST2/IL-1RAP signaling pathway, thereby ameliorating nasal mucosal tissue remodeling and alleviating AR.
2.Correlation analysis of serum VEGF, vWF and coagulation indexes with prognosis of thyroid cancer
Wei DING ; Yongmin MIAO ; Wei WANG ; Meiya LIU
Chinese Journal of Endocrine Surgery 2024;18(6):835-840
Objective:To investigate the correlation between serum vascular endothelial growth factor (VEGF), von Willebrand factor (vWF) and coagulation index and prognosis of differentiated thyroid cancer (TC) .Methods:136 TC patients admitted in Department of Head and Neck Surgery Shanxi Cancer Hospital from Jan. 2021 to Dec. 2022 were selected as TC group, and 80 patients with confirmed thyroid benign nodule during the same period were selected as control group. VEGF, vWF and coagulation indexes were compared between the two groups. The tumor free survival was calculated by Kaplan-Meier method.Results:Compared with the control group, the levels of VEGF, vWF, TT, Fbg in TC group were higher, and the levels of PT, APTT were lower ( P < 0.001). Compared with patients < 55 years old, the levels of VEGF, vWF, TT and Fbg were higher in patients ≥55 years old, and the levels of PT and APTT were lower ( P < 0.001). Compared with papillary carcinoma, the levels of VEGF, vWF, TT and Fbg were higher in follicular carcinoma patients, and the levels of PT and APTT were lower ( P < 0.001). The levels of VEGF, vWF, TT and Fbg were higher and the levels of PT and APTT were lower in patients with TNM stage III to IV than in patients with TNM stage I to II ( P < 0.001). Compared with patients without lymph node metastasis, VEGF, vWF, TT, Fbg levels were higher in patients with lymph node metastasis, and PT, APTT levels were lower ( P < 0.001). Compared with patients with tumor size < 2 cm, VEGF and vWF levels were higher in patients with tumor size ≥ 2 cm ( P < 0.001). Survival curve analysis showed that the tumor free survival of high VEGF, high vWF, high TT and high Fbg groups was shorter than that of low VEGF, low vWF, low TT and low Fbg groups (Log-rank=9.149, 8.856, 4.683, 5.867, P < 0.001) . Conclusion:VEGF, vWF and coagulation indexes in TC patients were correlated with clinicopathological features, and were helpful to predict postoperative tumor-free survival.
3.Correlation analysis of serum VEGF, vWF and coagulation indexes with prognosis of thyroid cancer
Wei DING ; Yongmin MIAO ; Wei WANG ; Meiya LIU
Chinese Journal of Endocrine Surgery 2024;18(6):835-840
Objective:To investigate the correlation between serum vascular endothelial growth factor (VEGF), von Willebrand factor (vWF) and coagulation index and prognosis of differentiated thyroid cancer (TC) .Methods:136 TC patients admitted in Department of Head and Neck Surgery Shanxi Cancer Hospital from Jan. 2021 to Dec. 2022 were selected as TC group, and 80 patients with confirmed thyroid benign nodule during the same period were selected as control group. VEGF, vWF and coagulation indexes were compared between the two groups. The tumor free survival was calculated by Kaplan-Meier method.Results:Compared with the control group, the levels of VEGF, vWF, TT, Fbg in TC group were higher, and the levels of PT, APTT were lower ( P < 0.001). Compared with patients < 55 years old, the levels of VEGF, vWF, TT and Fbg were higher in patients ≥55 years old, and the levels of PT and APTT were lower ( P < 0.001). Compared with papillary carcinoma, the levels of VEGF, vWF, TT and Fbg were higher in follicular carcinoma patients, and the levels of PT and APTT were lower ( P < 0.001). The levels of VEGF, vWF, TT and Fbg were higher and the levels of PT and APTT were lower in patients with TNM stage III to IV than in patients with TNM stage I to II ( P < 0.001). Compared with patients without lymph node metastasis, VEGF, vWF, TT, Fbg levels were higher in patients with lymph node metastasis, and PT, APTT levels were lower ( P < 0.001). Compared with patients with tumor size < 2 cm, VEGF and vWF levels were higher in patients with tumor size ≥ 2 cm ( P < 0.001). Survival curve analysis showed that the tumor free survival of high VEGF, high vWF, high TT and high Fbg groups was shorter than that of low VEGF, low vWF, low TT and low Fbg groups (Log-rank=9.149, 8.856, 4.683, 5.867, P < 0.001) . Conclusion:VEGF, vWF and coagulation indexes in TC patients were correlated with clinicopathological features, and were helpful to predict postoperative tumor-free survival.
4.Application value of different methods of segmented latissimus dorsi myocutaneous flap in repairing chest wall defect after local advanced breast cancer surgery (with video)
Meiya LIU ; Yongjing CHEN ; Junjie MA ; Zhenhua ZHAO ; Fei LUO ; Xinzheng LI
Chinese Journal of Endocrine Surgery 2023;17(5):550-553
Objective:To explore the application value of different methods of segmented latissimus dorsi myocutaneous flap in repairing chest wall defects after local advanced breast cancer surgery.Methods:The clinical data of 64 patients with unilateral locally advanced breast cancer admitted to Shanxi Cancer Hospital from Feb. 2019 to Jan. 2020 were selected. All patients underwent modified radical mastectomy for breast cancer. The patients were divided into two groups according to the random number table method. Antegrade (group A, n=32 cases) and retrograde (group B, n=32 cases) were used to design and cut the segmented latissimus dorsi myocutaneous flap to repair the defects. The range of skin island cut was 14 cm×6 cm-19 cm×7 cm; The donor area of the flap was closed directly. The application effects of the two groups of methods were compared. Results:In group A, one antegrade flap was partially necrotic, while in group B, six retrograde flaps were partially necrotic ( P>0.05). The delayed healing rate of donor site incision in group A was 6.25%, significantly lower than that in group B (25.00%) ( χ2=4.267, P=0.039). All the patients in both groups were followed up for 12 to 24 months, and the appearance and texture of the flaps were satisfactory; Only linear scar was left in the donor area, and the shoulder joint activity was not affected. The mean survival time was 20.8 months. Conclusion:The antegrade latissimus dorsi myocutaneous flap can repair the large area defect of chest wall after LABC, which can ensure the blood supply of the flap to the greatest extent, reduce the closing tension of the donor area, the incidence of postoperative complications, and promote the healing of the incision.
5.Retrograde nerve growth factor signaling modulates tooth mechanical hyperalgesia induced by orthodontic tooth movement via acid-sensing ion channel 3.
Meiya GAO ; Xinyu YAN ; Yanzhu LU ; Linghuan REN ; Shizhen ZHANG ; Xiaoqi ZHANG ; Qianyun KUANG ; Lu LIU ; Jing ZHOU ; Yan WANG ; Wenli LAI ; Hu LONG
International Journal of Oral Science 2021;13(1):18-18
Orthodontic tooth movement elicits alveolar bone remodeling and orofacial pain that is manifested by tooth mechanical hyperalgesia. Nerve growth factor (NGF) is upregulated in periodontium and may modulate tooth mechanical hyperalgesia. The objectives were to examine the role of NGF in tooth mechanical hyperalgesia and to elucidate the underlying mechanisms. Tooth mechanical hyperalgesia was induced by ligating closed coil springs between incisors and molars in Sprague-Dawley rats. Retrograde labeling was performed by periodontal administration of fluor-conjugated NGF and the detection of fluorescence in trigeminal ganglia (TG). Lentivirus vectors carrying NGF shRNA were employed to knockdown the expression of NGF in TG. The administration of agonists, antagonists, and virus vectors into TG and periodontium was conducted. Tooth mechanical hyperalgesia was examined through the threshold of biting withdrawal. Our results revealed that tooth movement elicited tooth mechanical hyperalgesia that could be alleviated by NGF neutralizing antibody and that NGF was upregulated in periodontium (mainly in periodontal fibroblasts) and TG. Retrograde labeling revealed that periodontal NGF was retrogradely transported to TG after day 1. Acid-sensing ion channel 3 (ASIC3) and NGF were co-expressed in trigeminal neurons and the percentage of co-expression was significantly higher following tooth movement. The administration of NGF and NGF neutralizing antibody into TG could upregulate and downregulate the expression of ASIC3 in TG, respectively. NGF aggravated tooth mechanical hyperalgesia that could be alleviated by ASIC3 antagonist (APETx2). Moreover, NGF neutralizing antibody mitigated tooth mechanical hyperalgesia that could be recapitulated by ASIC3 agonist (GMQ). NGF-based gene therapy abolished tooth mechanical hyperalgesia and downregulated ASIC3 expression. Taken together, in response to force stimuli, periodontal fibroblasts upregulated the expressions of NGF that was retrogradely transported to TG, where NGF elicited tooth mechanical hyperalgesia through upregulating ASIC3. NGF-based gene therapy is a viable method in alleviating tooth-movement-induced mechanical hyperalgesia.
6.Effect of sodium chloride on growth and lipid accumulation of Chlorella protothecoides CS-41.
Jieli PAN ; Li'na GAO ; Shuangshuang ZHAO ; Qiao LIU ; Jifeng YU ; Yijun HE ; Meiya LI
Chinese Journal of Biotechnology 2017;33(7):1101-1108
With basal medium, we studied the growth status, lipid droplet distribution, total lipid content of Chlorella protothecoides CS-41 treated with different concentrations of sodium chloride (0, 150, 300 and 600 mmol/L) by optical microscopy, electron microscopy, confocal laser focusing and Nile red staining. Results show that the addition of NaCl affected the growth of Chlorella protothecoides CS-41. With the increase of NaCl concentration, the growth rate of Chlorella was inhibited. Chlorella cell wall became thicker, and lipid droplets increased. At the early stage, the amount of lipid droplets in the 600 mmol/L NaCl culture was the highest, but at the late-log stage, the amount of lipid droplets increased with the increase of the biomass of culture in 150 and 300 mmol/L NaCl culture. At the stable stage, biomass (dry weight) in 300 mmol/L NaCl culture was 73.55% of that in the control, but the total lipid content was 2.22 times higher than that in the control. A certain concentration of sodium chloride treatment can significantly increase the lipid content of Chlorella protothecoides CS-41.
7.Tougu Xiaotong capsule promotes the proliferation and differentiation of osteoblasts
Yunmei HUANG ; Wenlie CHEN ; Ruhui LIN ; Meiya HUANG ; Zuanfang LI ; Naishun LIAO ; Xianxiang LIU
Chinese Journal of Tissue Engineering Research 2013;(33):5923-5928
BACKGROUND:Tougu Xiaotong capsule is the clinical prescription for the treatment of osteoarthritis in Fujian University of Traditional Chinese Medicine, and the previous studies mainly focus on effect to cartilage.
OBJECTIVE:To observe the effect of Tougu Xiaotong capsule on the proliferation and differentiation of osteoblasts as wel as the expressions of bone remodeling correlated factors.
METHODS:Rat osteoblast-like cel line ROS17/2.8 cel s were incubated with Tougu Xiaotong capsule. The ROS17/2.8 cel s were divided into blank control group and Tougu Xiaotong capsule groups with different
concentrations. The cel proliferation was determined by methylthiazolyldiphenyl-tetrazolium bromide assay. Osteoblast differentiation biomarkers alkaline phosphatase activity, osteocalcin and bone mineralized nodules were measured with colorimetry, enzyme-linked immunosorbent assay and alizarin red staining, respectively. The real-time PCR and enzyme-linked immunosorbent assay were used to detect the expressions of bone remodeling factors osteoprotegerin/receptor activator of nuclear factorκB ligand.
RESULTS AND CONCLUSION:Compared with the control group, the Tougu Xiaotong capsule with the
concentration of 0.25-2 g/L could significantly promote the ROS17/2.8 cel proliferation (P<0.05), up-regulate the alkaline phosphatase activity, osteocalcin expression level and mineralized nodules area, and increase the
percentage of bone remodeling factors osteoprotegerin/receptor activator of nuclear factorκB ligand (P<0.05). The mechanism of Tougu Xiaotong capsule protecting osteoarthritis may partly result from the regulation of
proliferation and differentiation of osteoblasts and bone remodeling.

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