1. MW-9, a chalcones derivative bearing heterocyclic moieties, ameliorates ulcerative colitis via regulating MAPK signaling pathway
Zhao WU ; Nan-Ting ZOU ; Chun-Fei ZHANG ; Hao-Hong ZHANG ; Qing-Yan MO ; Ze-Wei MAO ; Chun-Ping WAN ; Ming-Qian JU ; Chun-Ping WAN ; Xing-Cai XU
Chinese Pharmacological Bulletin 2024;40(3):514-520
Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.
2.Data Mining of Medication Rules for the Treatment of Atopic Dermatitis the Children by Chinese Medical Master XUAN Guo-Wei
Jin-Dian DONG ; Cheng-Cheng GE ; Yue PEI ; Shu-Qing XIONG ; Jia-Fen LIANG ; Qin LIU ; Xiu-Mei MO ; Hong-Yi LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):752-758
Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency>100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.
3.Regulation effect of dopamine on sepsis-associated macrophage functions and the mechanisms involved
Wenting SONG ; Yinfeng ZHANG ; Bailu DU ; Xi MO ; Qing CAO
Chinese Pediatric Emergency Medicine 2024;31(1):52-56
Sepsis is a life-threatening organ dysfunction caused by the host disordered response to infections.As one of the most important innate immune cells in the body,macrophages can maintain the immune homeostasis by recruiting other immune cells,clearing pathogens,presenting antigens,and play important regulatory roles in infectious diseases such as sepsis by releasing inflammatory factors.As a critical neurotransmitter,dopamine not only participates in the neurological processes such as learning and cognition,but also regulates the immune processes,including regulating the activation,proliferation and functional changes of immune cells such as neutrophils,lymphocytes,monocytes and macrophages.Current studies demonstrate that during the infection and inflammation process of sepsis,the phagocytosis,polarization,and release of inflammatory factors of macrophages are regulated by dopamine.This review summarized the recent research progress on the regulatory functions and the underlying mechanisms of dopamine on macrophages in sepsis.
4.Application Effect of A New Modified 3D PSI in Total Knee Arthroplasty for Knee Osteoarthritis
Qing HU ; Chuan LI ; Chong SHI ; Mo RUAN ; Jingze YANG
Journal of Kunming Medical University 2024;45(3):84-91
Objective To explore the application effect of new improved 3D printing individualized guidance(3D psi)in total knee arthroplasty(TKA)for knee osteoarthritis(KOA).Methods A total of 100 patients with KOA in 920th Hospital of Joint Logistics Support Force,PLA from January 2021 to January 2022 were selected,and were divided into 2 groups of 50 patients each using the randomized numerical table method.The control group was treated with conventional TKA,and the study group was treated with new improved 3D psi assisted TKA.The operation conditions,postoperative rehabilitation,complications,prosthesis component position deviation,knee range of motion(ROM),lower limb force line parameters[coronal distal femoral mechanical axis lateral angle(mldfa),lower limb mechanical axis angle(HKA)],gait parameters(percentage of support time,stride,pace),knee function(HSS score),quality of life(AIMS2 score)were observed.Results Com-pared with control group,the amount of intraoperative and postoperative blood loss and drainage volume 2 days after operation were less in the study group,and the operation time and hospital stay were shorter(P<0.05).The deviations of LTC Angle,FFC Angle,HKA Angle,LFC Angle and FTC Angle in the study group were smaller than those in the control group(P<0.05).At 3 months,6 months and 12 months after surgery,the percentage of knee ROM,supporting time,stride length and walking speed of the research group were higher than those of the control group,while the coronal-position mLDFA and HKA were lower than those of the control group(P<0.05).The proportion of WBC and PMN in joint fluid at 3 months,6 months and 12 months after surgery was lower than that in control group(P<0.05).The HSS score of the study group was higher than that of the control group at 3 months,6 months and 12 months after operation,and the AIMS2 score was lower than that of the control group(P<0.05).There was no statistically significant difference in the incidence of complications between the study group and the control group(P>0.05).Conclusion The new improved 3D PSI-assisted TKA treatment of KOA can optimize the surgical situation,improve operating accuracy,improve the patient's lower limb alignment,promote limb function recovery,help improve the quality of life,and has high safety.
5.miR-375 Attenuates The Migration and Invasion of Osteosarcoma Cells by Targeting MMP13
Zhong LIU ; Lei HE ; Jian XIAO ; Qing-Mei ZHU ; Jun XIAO ; Yong-Ming YANG ; Yong-Jian LUO ; Zhong-Cheng MO ; Yi-Qun ZHANG ; Ming LI
Progress in Biochemistry and Biophysics 2024;51(5):1203-1214
ObjectiveTo explore whether miR-375 regulates the malignant characteristics of osteosarcoma (OS) by influencing the expression of MMP13. MethodsPlasmid DNAs and miRNAs were transfected into OS cells and HEK293 cells using Lipofectamine 3000 reagent. Real-time quantitative polymerase chain reaction was performed to measure the expression of miR-375 and MMP13 in OS patients and OS cells. Western blot was performed to analyze the MMP13 protein in the patients with OS and OS cells. The targeting relationship between miR-375 and MMP13 was analyzed by luciferase assay. Migration and invasion were analysed by heal wound and transwell assays, respectively. ResultsmiR-375 expression in OS tissues was lower than that in normal tissues. The expression of MMP13 was upregulated in OS tissues. MMP13 expression was negatively correlated withmiR-375 expression in patients with OS. Migration and invasion were significantly inhibited in OS cells with the miR-375 mimic compared with OS cells with the miRNA control. MMP13 partially reversed the inhibition of migration and invasion induced by miR-375 in the OS cells. ConclusionmiR-375 attenuates migration and invasion by downregulating the expression of MMP13 in OS cells.
6.Tumor Therapy: Targeted Substances Metabolism Reprogramming Induces Tumor Ferroptosis
Jin-Ping ZHANG ; Yue-Qing WANG ; Mo WANG ; Xin-Yue WANG ; Xiao-Qin MOU ; Xi ZHENG ; Chuang CHENG ; Jing HE ; Li-Li ZOU ; Xiao-Wen LIU
Progress in Biochemistry and Biophysics 2024;51(7):1540-1550
There are huge differences between tumor cells and normal cells in material metabolism, and tumor cells mainly show increased anabolism, decreased catabolism, and imbalance in substance metabolism. These differences provide the necessary material basis for the growth and reproduction of tumor cells, and also provide important targets for the treatment of tumors. Ferroptosis is an iron-dependent form of cell death characterized by an imbalance of iron-dependent lipid peroxidation and lipid membrane antioxidant systems in cells, resulting in excessive accumulation of lipid peroxide, causing damage to lipid membrane structure and loss of function, and ultimately cell death. The regulation of ferroptosis involves a variety of metabolic pathways, including glucose metabolism, lipid metabolism, amino acid metabolism, nucleotide metabolism and iron metabolism. In order for tumor cells to grow rapidly, their metabolic needs are more vigorous than those of normal cells. Tumor cells are metabolically reprogrammed to meet their rapidly proliferating material and energy needs. Metabolic reprogramming is mainly manifested in glycolysis and enhancement of pentose phosphate pathway, enhanced glutamine metabolism, increased nucleic acid synthesis, and iron metabolism tends to retain more intracellular iron. Metabolic reprogramming is accompanied by the production of reactive oxygen species and the activation of the antioxidant system. The state of high oxidative stress makes tumor cells more susceptible to redox imbalances, causing intracellular lipid peroxidation, which ultimately leads to ferroptosis. Therefore, in-depth study of the molecular mechanism and metabolic basis of ferroptosis is conducive to the development of new therapies to induce ferroptosis in cancer treatment. Ferroptosis, as a regulated form of cell death, can induce ferroptosis in tumor cells by pharmacologically or genetically targeting the metabolism of substances in tumor cells, which has great potential value in tumor treatment. This article summarizes the effects of cellular metabolism on ferroptosis in order to find new targets for tumor treatment and provide new ideas for clinical treatment.
7.Mechanism of Kechuanting granules in suppressing IL-33/ILC2s and pathogenic T cells to intervene in allergic airway inflammation
Nan-Ting ZOU ; Zhao WU ; Xiao-Dong YAN ; Chun-Fei ZHANG ; Hao-Hong ZHANG ; Qing-Yan MO ; Ming-Qian JU ; Jin-Zhu XU ; Chun-Ping WAN
Chinese Pharmacological Bulletin 2024;40(7):1350-1357
Aim To investigate the mechanisms of Ke-chuanting granules(KCT)inhibiting the IL-33/ILC2s pathway and pathogenic T cells to intervene in allergic airway inflammation.Methods Network pharmacolo-gy was utilized to analyze the potential targets and mechanisms of KCT-treated asthma.Allergic asthma models were induced in mice using OVA.Lung histo-pathology was conducted to observe injury changes.ELISA and quantitative PCR were utilized to measure key inflammatory factors and their mRNA expression levels in Th2-type asthma.Western blot was used to detect the phosphorylation levels of relevant proteins in the MAPK pathway.Flow cytometry was performed to evaluate the proportions of ILC2s,Th1,Th 17,Th2 and Treg cells.Results Network pharmacology iden-tified 227 main active components and 143 key targets of KCT in treating asthma,primarily enriched in signa-ling pathways such as MAPK and IL-17.Further vali-dation experiments demonstrated that KCT significantly alleviated lung inflammatory injury in asthmatic mice,reduced the number of B cells,production of I L-4,TNF-α and TGF-β,downregulated JNK phosphoryla-tion levels in lung tissue,as well as mRNA levels of Il-33,Bcl11b,Rorα,Tcf-7,Jun,Mapk3 and Mapk14.KCT intervention reduced the numbers of ILC2s and Th 17 cells in lungs and spleens of mice,and inhibited Th2 cell infiltration in lungs.Conclusions KCT ex-hibits therapeutic effects on allergic airway inflamma-tion in asthma,closely associated with the inhibition of the IL-33/ILC2s pathway,pathogenic T cell subsets,and JNK-MAPK signaling pathway.
8.Effect of early vitamin D supplementation on the incidence of preeclampsia in primigravid women
Yanan LI ; Mo YANG ; Huanhuan MIAO ; Qing YANG
China Pharmacist 2024;27(5):810-816
Objective This study aims to evaluate the effect of vitamin D supplementation in the earliest stages of pregnancy(12-16 weeks)on the development of preeclampsia(PE)in primiparous women.Methods Primiparous women who visited Maternal and Child Care Center of Qinhuangdao from January 1,2019 to January 31,2022 were recruited as study subjects.According to the random number table method,primiparous women were randomly divided into the control group(calcium carbonate D3 tablets)and the experimental group(calcium carbonate D3 tablets+vitamin D).The main observed outcome of the study was the incidence of preeclampsia.Preterm birth,neonatal birth weight,neonatal height at birth,mode of delivery,and neonatal Apgar scores were the secondary observed outcomes.A Logistic regression was used to explore the relationship between vitamin D supplementation and study outcomes.In addition,serum 25 hydroxyvitamin D was measured by ELISA before and after the intervention.Results A total of 586 primiparas were recruited,70 were lost,and 516 were included(264 in the control group and 252 in the experimental group).The incidences of PE,preterm birth,cesarean birth,and birth weight in the experimental group were significantly lower than those of the control group(P<0.05).After the end of the intervention,the serum level of 25 hydroxyvitamin D had increased significantly in both groups(P<0.05),while there was no significant change in calcium ions(P>0.05).Furthermore,serum 25 hydroxyvitamin D levels were significantly higher in the experimental group than in the control group(P<0.05).In addition,the birth length,1-minute Apgar,5-minute Apgar and 10-minute Apgar scores of the experimental group were all higher than the control group(P<0.05).Multivariate Logistic analysis showed that vitamin D supplementation was the independent protective factor for PE[OR=0.336,95%CI(0.120,0.939),P=0.037],cesarean section[OR=0.539,95%CI(0.364,0.798),P=0.002],misoprostol-induced delivery[OR=0.066,95%CI(0.009,0.504),P=0.009],preterm birth[OR=0.487,95%CI(0.238,0.995),P=0.048]and low birth weight[OR=0.391,95%CI(0.189,0.806,P=0.011].Conclusion Vitamin D supplementation reduces the incidence of PE and reduces the incidence of adverse pregnancy and fetal outcomes.
9.Effect of Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the Changes of Gastric Mucosal Pathological Scores and Gastrointestinal Hormones in Patients with Chronic Atrophic Gastritis of Liver Stagnation and Spleen Deficiency Type
Ming-He LIU ; Dong-Qing YIN ; Yong-Qing ZHANG ; Xiao BAI ; Chen MO ; Li XU ; Jing ZHAO ; Jian-Tang GUO ; Shu-Fang FENG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(9):2326-2332
Objective To investigate the effect of Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the changes of gastric mucosal pathological score and gastrointestinal hormones in patients with chronic atrophic gastritis(CAG)of liver stagnation and spleen deficiency type.Methods A total of 156 cases of CAG patients with liver stagnation and spleen deficiency syndrome were randomly divided into a control group and an observation group,78 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The changes in the scores of traditional Chinese medicine(TCM)symptoms such as epigastric distention and pain,poor appetite,loose stools,limb weakness,belching and acid regurgitation,gastric mucosal pathological scores and serum levels of gastrointestinal hormones of motilin(MTL)and gastrin(GAS)in the two groups were observed before and after treatment.The negative conversion rate of Helicobacter pylori(Hp)in the two groups was compared,and the clinical efficacy and safety of the two groups were evaluated.Results(1)After four weeks of treatment,the total effective rate of the observation group was 93.59%(73/78),which was significantly higher than 82.05%(64/78)of the control group,and the difference between the two groups was statistically significant(P<0.05).(2)After treatment,the scores of TCM symptoms such as epigastric distention and pain,poor appetite,loose stool,limb weakness,belching and acid regurgitation in the two groups were significantly decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.05).(3)After treatment,the pathological scores of gastric mucosa in the two groups were significantly decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was more significant than that in the control group(P<0.01).(4)After four weeks of treatment,the negative conversion rate of Hp in the observation group was 91.03%(71/78),which was significantly higher than that in the control group(75.64%,59/78),and the difference between the two groups was statistically significant(P<0.05).(5)After treatment,the level of serum GAS in the two groups was significantly decreased(P<0.05)and the serum MTL level was significantly increased compared with that before treatment(P<0.05);the decrease of serum GAS level and the increase of serum MTL level in the observation group were significantly superior to those in the control group(P<0.05).(6)There were no obvious abnormalities in the routine test of blood,urine,stool,kidney function,and liver function,electrocardiograph and other safety indicators during the treatment of the two groups of patients,no adverse reactions such as dizziness,rash and chest distress occurred either,with high safety.Conclusion Xiao Chaihu Decoction combined with Xiangsha Liujunzi Decoction exerts a significant therapeutic effect on GAS of liver stagnation and spleen deficiency type,which can effectively relieve the clinical symptoms,improve the pathological changes of gastric mucosa and promote Hp negative conversion.The therapeutic mechanism may be related to the regulation of gastrointestinal hormone levels.
10.Research progress on tumor necrosis factor receptor 2 in psoriasis
Nian MO ; Yating ZHANG ; Junhong ZHANG ; Qing WANG ; Panyu ZHOU ; Ling HAN ; Chuanjian LU
Chongqing Medicine 2024;53(15):2370-2375
Psoriasis is a refractory disease mainly co-acted by immune,genetic and environment.Tumor necrosis factor α (TNF-α)-related biologics have brought the landmark advances in the treatment of psoriasis;however,the anti-TNF-α therapy has the adverse response,its limitation may be related to the different bio-logical functions exerted by activation of TNF-α different receptors.Tumor necrosis factor receptor 2 (TNFR2) is one of the key receptors for TNF-α,and after binding to TNF-α,it can activate multiple signaling pathways such as NF-κB,PI3K/Akt,MAPK,STAT3,etc.,which are involved in the regulation of inflamma-tion,epidermal homeostasis,cellular apoptosis,cellular proliferation,cellular autophagy and other biological processes.It is suggested that TNFR2 is closely related to the occurrence and development of psoriasis.Previ-ous studies have often overlooked the role of TNFR2 in anti-TNF-α therapies;therefore,this article reviews the structure and signaling pathways of TNFR2,research advances in the disease,and its relationship with psoriasis to provide new references for exploring the pathogenesis and treatment of psoriasis.

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