1.Research advances on traditional Chinese medicine monomers and compounds intervening in ankylosing spondy-litis-related signaling pathways
Haidong ZHOU ; Yaohong LU ; Liangshen HU ; Li GONG ; Maohua LIN ; Shipeng HAO ; Jianbin YAN ; Weihui CHEN ; Shaoyong FAN
China Pharmacy 2025;36(3):373-378
Ankylosing spondylitis is a chronic immunoinflammatory disease that mainly affects the spine and the sacroiliac joint, the mechanism of which is closely related to signaling pathways, such as osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/RANK ligand, mitogen-activated protein kinase (MAPK), Wnt/β-catenin (β-catenin), phosphoinositide 3- kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR). Traditional Chinese medicine has the characteristics of multiple components and targets, and is widely used for the treatment of autoimmune diseases due to its low toxicity, strong specificity, and high efficacy. This review found that monomers and compounds of traditional Chinese medicine can exert anti ankylosing spondylitis effects by intervening in the aforementioned signaling pathways, regulating immune inflammatory responses, and inhibiting biological processes such as bone destruction, ectopic osteogenic differentiation, cell apoptosis, and autophagy.
2.Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis.
Shuran FAN ; Ming QI ; Qi QI ; Qun MIAO ; Lijuan DENG ; Jinghua PAN ; Shenghui QIU ; Jiashuai HE ; Maohua HUANG ; Xiaobo LI ; Jie HUANG ; Jiapeng LIN ; Wenyu LYU ; Weiqing DENG ; Yingyin HE ; Xuesong LIU ; Lvfen GAO ; Dongmei ZHANG ; Wencai YE ; Minfeng CHEN
Acta Pharmaceutica Sinica B 2024;14(2):682-697
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
3.The role of silent information regulator in periodontitis
Jinyi SUN ; Qinying WANG ; Ying LI ; Maohua MENG ; Helin CHEN ; Xiao ZENG ; Jiayu SHU ; Wenjie LI ; Yuncai LUO ; Qiang DONG
Chinese Journal of Tissue Engineering Research 2024;28(11):1737-1742
BACKGROUND:Periodontitis is an inflammatory and destructive disease with plaque biofilm as the main pathogenic material,which occurs in the gingiva,periodontal ligament,alveolar bone and cementum.The antigen of bacterial complex and its secreted toxin and enzyme directly lead to the destruction of periodontal tissue and trigger the host's immune response,causing indirect damage to the body tissue.Silence information regulatory factors(Sirtuins,SIRTs)play an important role in anti-aging,anti-oxidative stress,regulating inflammation,and mediating autophagy,and are closely related to the occurrence and development of periodontitis. OBJECTIVE:To review the research status of Sirtuins in periodontitis. METHODS:The first author used the computer to search the relevant research regarding the role of Sirtuins in periodontitis in PubMed,Web of Scene,CNKI and WanFang databases.The key words were"Sirtuins,Sirtuin1-7,periodontitis"in English and Chinese.After literature screening,57 articles were included for review and analysis. RESULTS AND CONCLUSION:SIRT1,SIRT2,SIRT3,and SIRT6 participate in regulating the occurrence and development of periodontitis.Inhibition of SIRT1 expression may be the target of periodontitis treatment,while overexpression of SIRT1 can inhibit periodontitis and protect periodontal tissue.The activator of SIRT1 can reduce the inflammation of periodontal tissue and improve the systemic pathological changes caused by periodontitis.SIRT2 is involved in nicotinamide phosphoribosyltransferase-mediated periodontal inflammation and plays a role in the treatment and prognosis of periodontal diseases.SIRT3 can improve age-related periodontal disease.Gastrodin promotes the osteogenic differentiation of periodontal ligament stem cells through the up-regulation of SIRT3.The activator of SIRT3 reduces the damage of periodontitis to periodontal and renal tissues by regulating the level of autophagy in the cells.SIRT6 can inhibit the inflammatory reaction of periodontal tissue and inhibit the differentiation and mineralization of cementoblasts.SIRT6 is beneficial to the prognosis of periapical periodontitis.The relationship between SIRT4,SIRT5,SIRT7 and periodontitis is rarely reported.
4.Research progress on food-derived antioxidants for alleviating toxicity of endocrine disrupting chemicals
Jiaxian CHEN ; Maohua MIAO ; Ziliang WANG
Journal of Environmental and Occupational Medicine 2024;41(1):110-117
Endocrine disrupting chemicals (EDCs) are a class of chemical substances widely present in daily-life environment, and can enter human body through various pathways, posing a threat to reproductive development and health. Oxidative stress (OS) is one of the most important fundamental mechanisms underlying the reproductive toxicity of EDCs. Numerous studies have found that exposure to EDCs can increase the levels of reactive oxygen species (ROS) in human reproductive system and reduce the activity and quantity of multiple enzymatic antioxidants, leading to oxidative stress and inducing damage to the reproductive system at various levels such as DNA and cells. Many research results have shown that supplementing food-derived non-enzymatic antioxidants can reduce ROS levels and increase the activity of enzymatic antioxidants, thereby reduce OS levels, and further repair EDCs-induced reproductive damage. In addition, many food-derived antioxidants are important elements involved in reproductive physiological activities and have protective effects on reproductive health. This paper summarized the reproductive toxicity of EDCs, including damage to reproductive cells, interference with hormone action, and influence on reproductive-related epigenetic regulation, elaborated the relationship between OS and reproductive toxicity of EDCs, and further summarized the alleviating effects and related mechanisms of food-derived antioxidants such as vitamins, trace elements, and plant polyphenols and pigments against reproductive toxicity of EDCs, aiming to provide a theoretical and scientific basis for prevention and treatment against reproductive toxicity of EDCs.
5.Effect of Tibetan Medicine Zuomaoxing with Different Origins and Characteristics on Rats with Pattern of Toxic Heat-induced Blood Stasis
Maohua YUAN ; Jing TAO ; Bixing GAO ; Jieyu SUN ; Diandian KANG ; Wenli CHEN ; Rui GU ; Guihua JIANG
Chinese Journal of Modern Applied Pharmacy 2024;41(5):599-605
OBJECTIVE
To investigate the effects of 3 different primitives or the same primitives with different characters of Tibetan medicine Zuomoxing[Caragana changduenais Liou f. with red heartwood, Caragana jubata(Pall.) Poir. with brown and white heartwood] on rats with pattern of toxic heat-induced blood stasis. METHODS Ninety SD rats were randomly divided into the blank group, model group, aspirin-positive group, Changdu low-dose group(CDD), Changdu high-dose group(CDG), whitewood of Guijian low-dose group(GJBD), whitewood of Guijian high-dose group(GJBG), brown wood of Guijian low-dose group(GJZD), Brown wood of Guijian high-dose group(GJZG). Models with heat toxicity and blood stasis pattern were established by intraabdominal injection of carrageenan combined with tail vein injection of lipopolysaccharide. The effects of each group on blood rheology, coagulation four indices and blood routine were determined, and the content of arachidonic acid(AA), IL-1β, IL-6, TNF-α and thromboxane B2(TXB2) were measured with ELISA.
RESULTS
①Blood rheology: Compared with model group, CDD and CDG significantly decreased whole blood viscosity(WBV), reduction viscosity of whole blood(WBRV), erythrocyte rigidity index(HGX), erythrocyte deformability index(EDI), whole blood relative index(WBRI) (P<0.01), and increased plasma viscosity(P<0.01). GJZG and GJZD significantly decreased HGX(P<0.01 or P<0.05), and increased plasma viscosity(P<0.01). GJBG and GJBG significantly decreased WBHSV, WBHSRV, HGX, EDI, and whole blood high shear relative index(WBHSRI)(P<0.01). ②Coagulation four indices: Compared with model group, CDD significantly reduced the thrombin time(TT)(P<0.01). GJZG significantly reduced activated partial thromboplastin time(APTT) and TT(P<0.01 or P<0.05). GJBD significantly reduced prothrombin time(PT) and APTT (P<0.01 or P<0.05). ③Blood routine: Compared with model group, GJZD and GJBD significantly decreased the percentage of monocytes(P<0.01 or P<0.05). The number of large platelets in CDD significantly increased(P<0.05). CDG significantly increased the platelet number, platelet hematocrit, and large platelet number(P<0.01 or P<0.05), and tended which to be normal. ④Inflammatory factors: Compared with model group, the levels of TNF-α, IL-6, TXB2 were significantly increased in CDD and CDG(P<0.01 or P<0.05). The levels of IL-6 and TXB2 were significantly increased in GJZD and GJZG(P<0.01). GJBD was significantly increased TXB2(P<0.01), and GJBG was significantly increased IL-1β, IL-6, and TXB2(P<0.01), while decreased AA(P<0.05).
CONCLUSION
Zuomoxing with separate sources have different degrees of effects on rats with pattern of toxic heat-induced blood stasis, and have different degrees of effects on hemorheology, coagulation factors, blood routine and inflammatory mediators, and the degree and trend of effects are different with different doses. The effect of promoting blood circulation and removing blood stasis was generally manifested as Changdu > whitewood of Guijian > Brown wood of Guijian. The effect of promoting blood circulation and removing blood stasis may be the result of multiple pathways and mechanisms.
6.Research progress on in-stent restenosis of carotid artery
Yuting TANG ; Feifan SUN ; Lingjia DONG ; Maohua CHEN
Chinese Journal of Cerebrovascular Diseases 2024;21(10):708-713
Carotid artery stenosis is one of the primary causes of ischemic stroke.At present,the main surgical treatments for carotid artery stenosis include carotid endarterectomy(CEA)and carotid artery stenting(CAS).In-stent restenosis(ISR)is a long-term complication after CAS,which significantly affects the long-term outcomes of the surgery and the prognosis of patients,with a relatively high incidence in clinical practice.Based on a review of domestic and international studies,the authors provided a comprehensive overview of ISR,covering its pathogenesis,risk factors,treatment options,and the latest research developments,in order to provide clinicians with guidance for the diagnosis and treatment of ISR.
7.Erratum: Author correction to "The FAPα-activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway" Acta Pharm Sin B 12 (2022) 1288-1304.
Geni YE ; Maohua HUANG ; Yong LI ; Jie OUYANG ; Minfeng CHEN ; Qing WENG ; Xiaobo LI ; Huhu ZENG ; Pei LONG ; Zepei FAN ; Junqiang YIN ; Wencai YE ; Dongmei ZHANG
Acta Pharmaceutica Sinica B 2023;13(3):1337-1339
[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].
8.The FAP α -activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway.
Geni YE ; Maohua HUANG ; Yong LI ; Jie OUYANG ; Minfeng CHEN ; Qing WEN ; Xiaobo LI ; Huhu ZENG ; Pei LONG ; Zepei FAN ; Junqiang YIN ; Wencai YE ; Dongmei ZHANG
Acta Pharmaceutica Sinica B 2022;12(3):1288-1304
Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties, a high incidence of pulmonary metastasis and a poor prognosis. Chemotherapy is the mainstay of treatment for osteosarcoma. Currently, there are no molecular targeted drugs approved for osteosarcoma treatment, particularly effective drugs for osteosarcoma with pulmonary metastases. It has been reported that fibroblast activation protein alpha (FAPα) is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis, demonstrating that FAPα-targeted agents might be a promising therapeutic strategy for osteosarcoma. In the present study, we reported that the FAPα-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPα-positive osteosarcoma cells in vitro and in vivo. Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells. Importantly, it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition (EMT) of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo. Mechanistically, Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway, leading to inhibition of the growth and metastatic spread of osteosarcoma cells. These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPα-positive osteosarcoma, particularly osteosarcoma with pulmonary metastases.
9.Study on Effects and Active Ingredients of Tibetan Medicine Lamiophlomis rotata against Rheumatoid Arthritis
Yanfei ZHANG ; Ruixin CHEN ; Maohua YUAN ; Zhizhong YANG ; Ting HUANG ; Suxian CHEN ; JIANG
China Pharmacy 2021;32(5):578-583
OBJECTIVE:To study the effects and active ingr edients of Tibetan medicine Lamiophlomis rotata against rheumatoid arthritis (RA). METHODS :Fifty-six SD rats were randomly divided into normal control group (0.5% sodium carboxymethylcellulose),model group (0.5% sodium carboxymethylcellulose ),methotrexate group (positive control group ,3 mg/kg),L. rotata water extract low-dose ,medium-dose and high-dose groups (0.5,1,2 g/kg,by crude drug ),L. rotata total flavonoid group (200 mg/kg,by flavonoid extat ),with 8 rats in each group. Except for normal control group ,other groups were given Freund ’s complete adjuvant (FCA)on the rat ’s right hind footpad to induce adjuvant-induced arthritis model. The next day after injection of FCA ,rats in all groups were given relevant medicine intragastrically ,once a day (once every 3 days for methotrexate group )for 30 days. At 15th and 30th day of administration ,the degree of paw swelling of left hind foot was measured,and the arthritis index ,spleen index were calculated. At the end of 30th day of administration ,the levels of TNF-α,IL-1β, IL-6 and IL- 10 in rat serum were determined by ELISA assay ,the thymus index and spleen index were calculated ,the pathological changes of the ankle joints were observed by HE staining. RESULTS :Compared with normal control group ,degree of paw swelling,arthritis index at 15th and 30th day of administration as well as the spleen index and the levels of TNF-α,IL-1β, msxmX0146) IL-6 in serum at 30th day of administration were significantly com increased in model group (P<0.01);while the thymus indexyunbinji- and IL- 10 level at 30th day of administration were ang@swu.edu.cn significantly decreased(P<0.01);synovial cell proliferation and infiltration of articular cavity were observed in ankle joint. Compared with model group ,degree of paw swelling ,arthritis index at 15th and 30th day of administration as well as the spleen index and the levels of TNF-α,IL-1β,IL-6 in serum at 30th day of administration were significantly decreased in each medicine group (P<0.01);while the thymus index and IL- 10 level at 30th day of administration were significantly increased (P<0.01);the pathological changes of arthritis were significantly improved. Compared with L. rotata water extract high-dose group ,there were no significant differences in degree of paw swelling at 15th day of administration as well as the arthritis index ,spleen index ,levels of inflammatory cytokines and pathological changes of ankle joint in L. rotata total flavonoid group (P>0.05). CONCLUSIONS :Tibetan medicine L. rotata shows well anti-RA activity ,and total flavonoids may be the active ingredients of its efficacy.
10.Analysis on influencing factors of vertebral body height reloss after pedicle screw fixation of thoracolumbar fracture
Kelyu SHEN ; Lichao JI ; Maohua CHENG ; Xiaozhong ZHOU ; Xinglei BEN ; Qiqi WEI ; Hainan CHEN ; Zhengfeng LU
Chinese Journal of Trauma 2021;37(11):990-996
Objective:To investigate the related factors of vertebral body height reloss after pedicle screw fixation of thoracolumbar fracture and to determe the optimum prediction point.Methods:A retrospective case control study was made on 215 patients with thoracolumbar fracture admitted to Second Affiliated Hospital of Soochow University from January 2010 to December 2017. There were 155 males and 60 females,aged 21-80 years[(48.6±10.4)years]. According to Denis fracture classification,there were 73 patients with compression fractures(type A in 15 patients,type B in 51,type C in 7),135 burst fractures(type A in 28 patients,type B in 87,type C in 20)and flexion distraction fractures(type A in 4,type B in 2,type C in 1). All patients were treated by pedicle screw fixation. Follow-up lasted for 12- 48 months[(23.8±8.2)months]. Vertebral body height loss occurred in 86 patients(loss group),but did not in 129 patients(non-loss group). The two groups were compared concerning sex,age,osteoporosis self-assessment tool for Asians(OSTA),body mass index(BMI),fracture types,number of fractured vertebrae,preoperative sagittal Cobb angle,preoperative degree of vertebral compression,number of screws placed in injured vertebrae,extent of vertebral reset and other related factors. Univariate analysis was used to identify the correlation of those factors with vertebral body height reloss. Multivariate Logistic regression analysis was performed to identify the independent factors for the height reloss with the receiver operating characteristic curve(ROC)and area under the curve(AUC)calculated to evaluate the optimum point in prediction of vertebral height reloss.Results:The two groups showed no significant differences in sex,age,BMI,fracture types,number of injured vertebrae,preoperative sagittal Cobb angle and number of screws placed in injured vertebrae( P>0.05),but the differences were statistically significant in OSTA,preoperative degree of vertebral compression and extent of vertebral reset( P<0.05). According to the univariate analysis,OSTA,preoperative degree of vertebral compression and extent of vertebral reset were significantly correlated with the occurrence of vertebral body height reloss( P<0.05). According to the multivariate Logistic regression,OSTA( OR=1.109,95% CI 0.527-0.685, P<0.05)and preoperative degree of vertebral compression( OR =0.038,95% CI 0.539-0.689, P<0.05)were significantly related to vertebral body height reloss. The AUC relating OSTA and preoperative degree of vertebral compression to vertebral body height reloss was 0.604 and 0.614,respectively. The optimum prediction point of OSTA and preoperative degree of vertebral compression for vertebral body height reloss was 1.9 and 31.3%,respectively. Conclusions:OSTA and the preoperative degree of vertebral compression are independent risk factors for vertebral body height reloss. OSTA≤1.9 or preoperative degree of vertebral compression ≥31.3% indicates a significantly higher risk of postoperative vertebral body height reloss.


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