1.Clinical characteristics and risk factors for adverse outcomes in omphalocele
Wei SHI ; Mingyu HAN ; Zheng CHEN ; Xiaoying CHENG ; Junjin CHEN ; Peng WANG ; Jinfa TOU ; Liping SHI ; Xiaolu MA
Chinese Journal of Pediatrics 2025;63(1):43-49
Objective:To investigate the clinical characteristics of omphalocele, and to assess the risk factors associated with adverse outcomes.Methods:A retrospective cohort study was conducted. Clinical data of 224 patients diagnosed with omphalocele, who were hospitalized at Children′s Hospital, Zhejiang University School of Medicine from January 2013 to December 2022, were collected. Based on their discharge outcomes, the patients were classified into 2 groups: favorable outcomes and unfavorable outcomes. Chi-square test or continuity correction χ2 test or Fisher exact probability method, and Mann-Whitney U test were used for intergroup comparisons. Logistic regression analysis was performed to identify risk factors associated with adverse outcomes in omphalocele. Results:Among the 224 patients with omphalocele, 126 were male. A total of 208 patients (92.9%) had favorable outcomes, while 16 patients (7.1%) had unfavorable outcomes. In the unfavorable outcomes group, 14 patients had giant omphaloceles, while 100 patients had giant omphaloceles in the favorable outcomes group. The rates of herniation of more than two intra-abdominal organs in the hernial sac, congenital heart defects, patent ductus arteriosus, pulmonary hypertension, sepsis and infection of the hernial sac, were all higher in the unfavorable outcomes group compared to the favorable outcomes group (all P<0.05). Patients with unfavorable outcomes had longer mechanical ventilation time, duration of oxygen use, duration of parenteral nutrition, hospital stays, and higher rates of parenteral nutrition-associated cholestasis compared to those with favorable outcomes (all P<0.01). Multivariate Logistic regression analysis indicated that pulmonary hypertension ( OR=9.39, 95% CI 1.20-73.32), sepsis ( OR=8.59, 95% CI 1.32-55.86), and congenital heart defects ( OR=6.55, 95% CI 1.11-38.73) were all independent risk factors for adverse outcomes in omphalocele (all P<0.05). Conclusions:Infants with omphalocele are prone to complications such as cardiovascular malformations, infections, and pulmonary hypertension. Adverse outcomes in omphalocele are associated with pulmonary hypertension, sepsis, and congenital heart defects.
2.Oral Herombopag Olamine and subcutaneous recombinant human thrombopoietin after haploidentical hematopoietic stem cell transplantation
Dai KONG ; Xinkai WANG ; Wenhui ZHANG ; Xiaohang PEI ; Cheng LIAN ; Xiaona NIU ; Honggang GUO ; Junwei NIU ; Zunmin ZHU ; Zhongwen LIU
Chinese Journal of Tissue Engineering Research 2025;29(1):1-7
BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.
3.Application and regulatory challenges of organoid technology in medical field
Weilu CHENG ; Zehua WANG ; Yidan ZHANG ; Yinghui LIU
Chinese Journal of Tissue Engineering Research 2025;29(1):202-210
BACKGROUND:3D organoids have characteristics that resemble physiological tissues and to some extent mimic organ function,making them excellent models for applications ranging from basic development/stem cell research to personalized medicine. OBJECTIVE:To review and discuss the types of diseases and application areas such as tumor modeling that organoids can be applied to,as well as their regulatory status and challenges. METHODS:With"organoid,stem cell,disease model,3D printing technology,medical field"as Chinese and English search terms,we searched PubMed,Elsevier,WanFang,and CNKI databases to summarize and analyze organoid products at home and abroad,summarize the application of organoid technology in the medical field,and prospect the future development of organoid products in the medical field. RESULTS AND CONCLUSION:Organoids can break the limitations of traditional cell and animal models,avoid the ethical problems existing in clinical research,and have a high similarity to the source organ,a more similar performance to the physiology and pathology of human systems,and genetic stability,which has great advantages in current research.Organoids have been applied in the following fields:efficacy evaluation studies(preclinical models),including intestinal organoids,kidney organoids,liver organoids,gallbladder organoids,lung organoids,brain organoids,heart organoids,skin organoids,and reproductive system organoids;research on infectious diseases;cancer research and precision therapy;regenerative medicine;immune organoids.Although the United States,the European Union and China do not have perfect regulatory provisions,they are trying to promote the formulation of organoid regulatory laws and regulations.In China,although no organoid medical device products have been listed for the time being,its related regenerative medicine products have made breakthroughs.
4.Effects of different exercise interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats
Shujuan HU ; Ping CHENG ; Xiao ZHANG ; Yiting DING ; Xuan LIU ; Rui PU ; Xianwang WANG
Chinese Journal of Tissue Engineering Research 2025;29(2):269-278
BACKGROUND:Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis.However,the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed. OBJECTIVE:To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats. METHODS:Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group(n=12)and modeling group(n=20)after 1 week of adaptive feeding.Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin.After successful modeling,the rats were randomly divided into diabetic control group(n=6),moderate-intensity exercise group(n=6)and high-intensity intermittent exercise group(n=6).The latter two groups were subjected to treadmill training at corresponding intensities,once a day,50 minutes each,and 5 days per week.Exercise intervention in each group was carried out for 6 weeks.After the intervention,ELISA was used to detect blood glucose and blood lipids of rats.The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining.The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR.The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,insulin resistance index in the diabetic control group were significantly increased(P<0.01),insulin activity was decreased(P<0.05),and the mRNA and protein levels of carboxylesterase 1,never in mitosis gene A related kinase 7(NEK7)and interleukin 18 in skeletal muscle tissue were upregulated(P<0.05).Compared with the diabetic control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated(P<0.05),and insulin activity was increased(P<0.05).Moreover,compared with the diabetic control group,the mRNA level of NEK7 and the protein levels of carboxylesterase 1,NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group(P<0.05),while the mRNA levels of carboxylesterase 1,NEK7,NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group(P<0.05).Hematoxylin-eosin staining showed that compared with the diabetic control group,the cavities of myofibers in the moderate-intensity exercise group became smaller,the number of internal cavities was reduced,and the cellular structure tended to be more intact;the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged,with irregular tissue shape and increased cavities in myofibers.To conclude,both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose,lipid,insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats.Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle,while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle.In addition,the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.
5.Ferroptosis and osteoporosis
Cheng YANG ; Weimin LI ; Dongcheng RAN ; Jiamu XU ; Wangxiang WU ; Jiafu XU ; Jingjing CHEN ; Guangfu JIANG ; Chunqing WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):554-562
BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.
6.Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats
Lin ZHENG ; Wenjun JIN ; Shanshan LUO ; Rui HUANG ; Jie WANG ; Yuting CHENG ; Zheqing AN ; Yue XIONG ; Zipeng GONG ; Jian LIAO
Chinese Journal of Tissue Engineering Research 2025;29(6):1159-1167
BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P<0.05),and trabecular separation was elevated(P<0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P<0.05),and the level of osteocalcin was decreased(P<0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P<0.05);protein expression of β-Catenin and Frizzled9 was decreased(P<0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P<0.05)and a decrease in trabecular separation(P<0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P<0.05)and the serum level of osteocalcin was elevated(P<0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P<0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P<0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P<0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.
7.Effects of erythropoietin on restorative dentin formation and expression of bone morphogenetic protein 2 after pulp injury
Ruiqing CHENG ; Honglei SUN ; Shuangshuang GENG ; Chao WANG ; Junke LI ; Yanfang CHEN
Chinese Journal of Tissue Engineering Research 2025;29(11):2231-2242
BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.
8.Combination of Components from Tripterygii Radix et Rhizoma-Chuanxiong Rhizoma Affects RA-FLSs by Regulating NF-κB, Nrf2/HO-1 Signaling Pathways and Bcl-2/Caspase-3 Expression
Yongmei GUAN ; Zhiyan WAN ; Shuhui WANG ; Weifeng ZHU ; Zhiyong LIU ; Cheng JIANG ; Zhenzhong ZANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):17-26
ObjectiveTo investigate the effects of the combination of components from Tripterygii Radix et Rhizoma and Chuanxiong Rhizoma on rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and the underlying mechanism. MethodsRA-FLSs were grouped as follows: blank control, positive control (methotrexate), Tripterygii Radix et Rhizoma components, Chuanxiong Rhizoma components, and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma. The cell-counting kit-8 (CCK-8) assay was employed to the cell proliferation, invasion, and apoptosis. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, reactive oxygen species (ROS), and malondiadehyde (MDA) in cells were measured. Western blot was employed to determine the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB) p65, phosphorylated inhibitory subunit of NF-κBα (p-IκBα), cysteinyl aspartate-specific protease-3 (Caspase-3), and B-cell lymphoma 2 (Bcl-2). Real-time PCR was employed to determine the mRNA levels of Nrf2, HO-1, and NF-κB p65. ResultsThe cells in the groups of positive control, Tripterygii Radix et Rhizoma components, Chuanxiong Rhizoma components, and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma were treated with 2.50 mg·L-1 methotrexate, 0.20 mg·L-1 triptolide + 0.20 mg·L-1 celastrol, 5.00 mg·L-1 ferulic acid + 20.00 mg·L-1 ligustrazine, 0.20 mg·L-1 triptolide + 0.20 mg·L-1 celastrol + 5.00 mg·L-1 ferulic acid + 20.00 mg·L-1 ligustrazine, respectively. Compared with the blank control group, drug administration reduced the proliferation and invasion and increased the apoptosis of cells (P<0.01), lowered the levels of TNF-α, IL-6, ROS, and MDA (P<0.01), up-regulated the mRNA and protein levels of Caspase-3, Nrf2, and HO-1 (P<0.01), and down-regulated the mRNA and protein levels of Bcl-2, NF-κB p65, and p-IκBα (P<0.01). Compared with the Tripterygii Radix et Rhizoma components group, the combination of components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma inhibited the proliferation and invasion (P<0.05) and promoted the apoptosis of RA-FLSs, up-regulated the mRNA levels of Nrf2 and HO-1 and protein levels of Nrf2 and Caspase-3 (P<0.05), and down-regulated the protein levels of NF-κB p65 and p-IκBα (P<0.05). ConclusionThe combination of components from Chuanxiong Rhizoma and Tripterygii Radix et Rhizoma can inhibit the proliferation and invasion and promote the apoptosis of RA-FLSs and alleviate oxidative stress and inflammation by inhibiting the NF-κB signaling pathway, activating the Nrf2/HO-1 pathway, and regulating the expression of Bcl-2/Caspase-3.
9.Effect of Wulao Qisun Prescription on Proliferation and Osteogenic Differentiation of AS Fibroblasts by Regulating Wnt/β-catenin Signaling Pathway
Juanjuan YANG ; Ping CHEN ; Haidong WANG ; Zhendong WANG ; Haolin LI ; Zhimin ZHANG ; Yuping YANG ; Weigang CHENG ; Jin SU ; Jingjing SONG ; Dongsheng LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):67-73
ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis (AS). MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group, low drug-containing serum group, medium drug-containing serum group, high drug-containing serum group, and positive drug group. After drug intervention, cell proliferation was measured using the cell counting kit-8 (CCK-8) assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase (ALP) activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (Runx2) was detected by Western blot. The mRNA expression levels of Wnt5a, β-catenin, and Dickkopf-1 (DKK-1) were measured by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the blank group, each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression (P<0.01). Compared with the blank group, the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression (P<0.05). The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression (P<0.05, P<0.01), with the positive drug group showing the most pronounced effect (P<0.01). The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression (P<0.01). Compared with the blank group, the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins (P<0.05, P<0.01), while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN, OPN, and Runx2 proteins (P<0.05, P<0.01). ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts, thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression, further inhibiting the transcription of downstream target genes.
10.Active Components of Salviae Miltiorrhizae Radix et Rhizoma and Its Compound in Treatment of Nervous System Diseases: A Review
Weining SONG ; Shuxiang ZHANG ; Fang LU ; Zhize WANG ; Ruyang CHENG ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):303-313
Nervous system diseases, also known as neuropathies, encompass a wide range of conditions, primarily including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and other neurodegenerative disorders, as well as depression, subarachnoid hemorrhage, cerebral ischemia-reperfusion injury, vascular dementia, and other neurological diseases. These diseases pose serious threats to the health and lives of patients, bringing heavy burdens to society and families. The pathogenesis of nervous system diseases is highly complex, involving mechanisms such as neuroinflammation, oxidative stress, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, brain-derived neurotrophic factor deficiency, reduced cholinergic activity, axonal injury, and demyelination. In recent years, the incidence and mortality of nervous system diseases have been rising annually. Currently, western medicine primarily focuses on symptomatic treatment, often accompanied by many adverse reactions, including lethargy, excessive sedation, dizziness, headaches, tachycardia, liver function damage, metabolic disorders, and incomplete recovery after surgery. As a traditional Chinese medicine, Salviae Miltiorrhizae Radix et Rhizoma has effects such as promoting blood circulation, removing blood stasis, cooling the blood, clearing the heart, nourishing the blood, and calming the nerves. It can play a role in the treatment and protection against nervous system diseases through multiple targets, pathways, and mechanisms. Studies have found that the water-soluble phenolic acids and fat-soluble diterpenoid quinones in Salviae Miltiorrhizae Radix et Rhizoma are the main active ingredients for the treatment of nervous system diseases. This paper summarized the effects of the active components and compounds of Salviae Miltiorrhizae Radix et Rhizoma on nervous system diseases over the past ten years, aiming to provide a theoretical basis and research ideas for the development and application of active components and compounds of Salviae Miltiorrhizae Radix et Rhizoma in nervous system diseases.

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