1.The Regulatory Effects and Mechanisms of Piezo1 Channel on Chondrocytes and Bone Metabolic Dysregulation in Osteoarthritis
Yan LI ; Tao LIU ; Yu-Biao GU ; Hui-Qing TIAN ; Lei ZHANG ; Bi-Hui BAI ; Zhi-Jun HE ; Wen CHEN ; Jin-Peng LI ; Fei LI
Progress in Biochemistry and Biophysics 2026;53(3):564-576
Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca2+, K+, and Na+, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca2+ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca2+ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca2+ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.
2.Moxibustion combined with low-dose tadalafil for diabetes mellitus-induced erectile dysfunction:A prospective,single-center,three-arm randomized controlled trial
Tao LIU ; Zhao-xu YANG ; Yan XU ; Qi ZHAO ; Xue LIU ; Xin-fei HUANG ; Zhi-xing SUN ; Yun CHEN ; Jian-huai CHEN
National Journal of Andrology 2025;31(1):55-60
Objective:To investigate the clinical efficacy of moxibustion(Mox)combined with low-dose tadalafil(TAD)in the treatment of diabetes mellitus-induced erectile dysfunction(DMED)with the syndrome of Qi deficiency and blood stasis.Meth-ods:According to the inclusion and exclusion criteria,we selected 90 patients with DMED for this trial and equally randomized them into a Mox,a TAD,and a Mox combined with TAD(Mox+TAD)group to be treated by mild Mox applied to the acupoints Zusanli,Sanyinjiao and Yinlingquan qd alt,oral medication with low-dose TAD at 5 mg per dose qd,and combination of the above two thera-pies,respectively,all for 4 weeks.We obtained from the patients their IIEF-5 scores,traditional Chinese medicine(TCM)symptoms scores,Erectile Hardness Scale(EHS)scores,corpus cavernosal hemodynamic indexes,and the peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of the corpus cavernosal arteries before and after treatment,and compared them among the three groups.Results:The total effectiveness rate was significantly higher in the Mox+TAD(90.0%)than in the Mox(46.7%)and TAD groups(60.0%)(P<0.05).Compared with the baseline,the IIEF-5 and EHS scores were increased,while the TCM symptoms scores decreased in all the three groups after treatment,more significantly in the Mox+TAD group than in the other two(P<0.05).And the PSV and RI were remarkably increased,while the EDV decreased(P<0.05)in all the three groups(P<0.05)after treatment,with PSV even higher in the Mox+TAD than in the Mox and TAD groups(P<0.05).Conclusion:Moxi-bustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED,which can effectively improve the erectile function of the patients by increasing penile blood supply,benefiting qi and activating blood circulation.
3.Effects of different exercise acclimatization durations on liver injuries and inflammation responses in exertional heatstroke mice
Zhi DAI ; Jie HU ; Xiao-Chen WANG ; Zi-Wei HAN ; Zhi MAO ; Fei-Hu ZHOU
Medical Journal of Chinese People's Liberation Army 2025;50(5):599-606
Objective To compare the effects of different exercise acclimatization(EA)durations on liver injury and inflammatory response in mice with exertional heatstroke(EHS).Methods A total of 168 male C57BL/6 mice were randomly assigned to four groups using a random number table:no exercise acclimation group(EA0W,n=54),1-week exercise acclimation group(EA1W,n=54),2-week exercise acclimation group(EA2W,n=54),and blank control group(n=6).The blank control group did not undergo acclimatization training or EHS modeling.The EA1W and EA2W groups underwent daily 2-hour exercise training at a speed of 10 m/min in an environment maintained at(26.0±0.5)℃for 1 and 2 weeks,respectively,followed by a 2-day rest after training completion.EHS modeling was performed in mice of EA0W,EA1W,and EA2W groups through running at 10 m/min under controlled environmental conditions(39.5℃ambient temperature,65%relative humidity).The modeling endpoint was defined as loss of consciousness accompanied by a core body temperature≥42.7℃.All modeling procedures were systematically documented.Following modeling,18 mice from EA0W,EA1W,and EA2W groups underwent 24-hour survival analysis.Blood samples from the abdominal aorta and liver tissues were collected at 6,12 and 24 hours post-modeling(6 mice per time point for each group).Plasma levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatine kinase(CK)were quantified.Interleukin(IL)-1β and IL-6 concentrations were determined using enzyme-linked immunosorbent assay(ELISA).Liver tissue specimens underwent hematoxylin-eosin(HE)staining and pathological scoring.Results The EHS model was successfully established in all EA groups.When all mice in EA0W group developed EHS(65 min after the modeling initiation),the incidence rates in EA1W and EA2W groups were 50.0%and 22.2%,respectively,with a statistically significant difference between EA0W group and the latter two groups(P<0.05).When all mice in the three groups developed EHS,the time to EHS onset was significantly longer in both EA1W and EA2W groups compared to EA0W group,with EA2W group showing a longer onset time than EA1W group(P<0.05).Survival analysis revealed a significantly higher 24-hour survival rate in EA2W group(61.1%)compared to EA0W group(33.3%)(P<0.05),while no significant difference was observed between EA1W group and the other two groups(P>0.05).The levels of IL-1β,IL-6,and CK were highest at 6 h post-modeling in all EA groups(P<0.05),and liver injury was most severe at 12 h post-modeling(P<0.05).Compared to EA0W group,the levels of ALT,AST,and IL-1β,as well as liver pathology scores,were significantly lower at 12 h post-modeling in both EA1W and EA2W groups(P<0.05),with EA2W group showing significantly lower ALT and AST levels,as well as liver pathology scores than EA1W group(P<0.05).At 6 h post-modeling,CK levels were significantly higher in EA1W and EA2W groups compared to EA0W group(P<0.05),with EA2W group exhibiting higher CK levels than in EA1W group(P<0.05).Conclusions Exercise acclimation helps reduce the incidence of EHS.Following EHS onset,the survival rate of exercise-acclimated mice is higher than that non-acclimated mice,with a significantly higher survival rate in mice acclimated for 2 weeks compared to non-acclimated mice.However,no significant difference in survival rate is observed between mice acclimated for 1 week and non-acclimated mice.Additionally,exercise acclimation for 2 weeks is more effective in reducing liver injury and inflammatory responses compared to 1-week acclimation.
4.Analysis of the predictive value of serum SAA/CRP,LDH,and YKL-40 combined with conventional influencing factors for the prognosis of children with refractory mycoplasmal pneumonia
Rui-Fang HAN ; Ling GAO ; Fei CHEN ; Zhi-Xin ZHENG
Medical Journal of Chinese People's Liberation Army 2025;50(8):943-948
Objective To analyze the predictive value of the serum amyloid A/C-reactive protein ratio(SAA/CRP),lactate dehydrogenase(LDH),and chitinase-40(YKL-40)combined with conventional influencing factors for the prognosis of children with refractory mycoplasmal pneumonia(RMPP).Methods A retrospective study was conducted on 180 children with RMPP admitted to the First People's Hospital of Nanyang from January to December 2023,serving as study group,and 90 children with general mycoplasmal pneumonia(GMPP)as control group.The clinical data of the two groups,including age,gender,and serum levels of SAA/CRP,LDH,and YKL-40,were compared.On the day of admission,the disease severity of the children in study group was assessed and divided into mild(n=102)and severe(n=78)groups.After treatment,they were further categorized into poor prognosis(n=52)and good prognosis(n=128)groups based on the occurrence of adverse events.The levels of serum SAA/CRP,LDH,and YKL-40 were compared between mild-case and severe-case children in study group,as well as between children with good and poor prognosis.A binary logistic regression model was used to analyze the influencing factors for poor prognosis in children with RMPP.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum SAA/CRP,LDH,and YKL-40 for the prognosis of children with RMPP.Conventional influencing factors[disease severity,oxygen therapy duration,pneumonia severity index(PSI)score,and acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score]were used as the conventional prediction scheme,and the conventional prediction scheme combined with the levels of serum SAA/CRP,LDH,and YKL-40 was used as the new prediction scheme.The predictive values of the two prediction schemes for the prognosis of children with RMPP were compared.Results The levels of serum SAA/CRP,LDH,and YKL-40 in study group were higher than those in control group(P<0.05),and the levels of serum SAA/CRP,LDH,and YKL-40 in children with severe RMPP were higher than those in children with mild RMPP(P<0.05).In study group,the proportion of children with pleural effusion,the proportion of severe-case disease severity,oxygen therapy duration,PSI score,APACHE Ⅱ score,and the levels of serum SAA/CRP,LDH,and YKL-40 in children with poor prognosis were higher than those in children with good prognosis(P<0.05).Binary logistic regression analysis showed that disease severity,oxygen therapy duration,PSI score,APACHE Ⅱ score,and the levels of serum SAA/CRP,LDH,and YKL-40 were all factors affecting poor prognosis in children with RMPP(P<0.05).The areas under the curves(AUCs)of serum SAA/CRP,LDH,and YKL-40 for predicting the prognosis of children with RMPP were 0.756,0.749,and 0.734,respectively.The AUC of the new prediction scheme was 0.945,which was significantly higher than that of the conventional prediction scheme(AUC=0.859),with a statistically significant difference(P=0.011).Conclusion Serum SAA/CRP,LDH,and YKL-40 levels combined with the conventional prediction scheme have a high predictive efficacy for the prognosis of children with RMPP.
5.Mechanistic studies on the involvement of trimethylamine oxide in the pathogenesis of chronic spontaneous urticaria
Huiyang TANG ; Zhi YANG ; Xi YANG ; Zhengqiu YAO ; Fei HAO ; Bangtao CHEN
Chinese Journal of Dermatology 2025;58(6):515-522
Objective:To investigate the possible mechanisms underlying the involvement of the gut microbiota metabolite trimethylamine oxide (TMAO) in the pathogenesis of chronic spontaneous urticaria (CSU) .Methods:From June 2023 to June 2024, 67 CSU patients were enrolled from the Dermatology and Cosmetic Center, the Third Affiliated Hospital of Chongqing Medical University, and 69 age-matched healthy controls were also collected at the same time. Serum TMAO levels in both groups were measured using enzyme-linked immunosorbent assay (ELISA) , and D-dimer levels were collected from the CSU patients. A degranulation model was established in rat basophilic leukemia RBL-2H3 cells using anti-DNP IgE/DNP-BSA (IgE/Ag group) ; these cells were additionally grouped to be treated with different concentrations of TMAO (IgE/Ag+10 μmol/L TMAO group, IgE/Ag + 50 μmol/L TMAO group, IgE/Ag + 100 μmol/L TMAO group) ; untreated RBL-2H3 cells served as a blank control group. To investigate the effect of the extracellular signal-regulated kinase (ERK) phosphorylation inhibitor U0126 on the action of TMAO, RBL-2H3 cells were divided into another 5 groups: blank group, IgE/Ag group, IgE/Ag + 1 μmol/L U0126 group, IgE/Ag + 100 μmol/L TMAO group, and IgE/Ag + 100 μmol/L TMAO + 1 μmol/L U0126 group. In vivo, a localized allergic reaction model was established in the ears of C57BL/6 mice using anti-DNP IgE/DNP-BSA (IgE/Ag group) , and additional groups included blank group, IgE group, IgE/Ag + solvent (DMSO) group, and IgE/Ag + 10 μg/μl TMAO group. ELISA was performed to detect levels of inflammatory mediators in cell culture supernatants and mouse serum. Toluidine blue staining was employed to observe mast cell degranulation in the cell experiment and mouse ear tissue samples, Evans blue staining to assess vascular permeability in mouse ear tissue samples, and Western blot analysis to detect the ERK phosphorylation levels. The t test was used for comparisons between two groups, and one-way analysis of variance for multiple comparisons. Results:Serum TMAO levels were significantly higher in the 67 CSU patients than in the 69 healthy controls ( t = 13.27, P < 0.001) . Among the 32 CSU patients with available data about D-dimer, serum TMAO levels were positively correlated with D-dimer levels ( r = 0.62, P < 0.001) . In RBL-2H3 cell experiments, degranulation rates were significantly higher in the IgE/Ag + 10, 50, and 100 μmol/L TMAO groups than in the IgE/Ag group; morphologically, RBL-2H3 cells treated with 10, 50, and 100 μmol/L TMAO became increasingly rounded; 50 and 100 μmol/L TMAO significantly promoted the production of β-hexosaminidase (β-Hex) , interleukin-6 (IL-6) , and tumor necrosis factor-α (TNF-α) (all P < 0.01) , and upregulated ERK phosphorylation levels ( P < 0.01) ; the levels of ERK phosphorylation, IL-6, TNF-α, and β-Hex were significantly lower in the IgE/Ag + U0126 group than in the IgE/Ag group, as well as lower in the IgE/Ag + TMAO + U0126 group than in the IgE/Ag + TMAO group (all P < 0.001) . In the mouse model of localized allergic reaction, the IgE/Ag + TMAO group showed increased vascular permeability, edema degree, and mast cell degranulation, as well as significantly elevated ERK phosphorylation levels and TNF-α expression in mouse ear tissues compared with the IgE/Ag + DMSO group (both P < 0.05) . Conclusion:Elevated serum TMAO may participate in the pathogenesis of CSU by upregulating ERK phosphorylation levels in mast cells and skin tissues, thereby promoting IgE/Ag-mediated degranulation of effector cells and production of inflammatory mediators.
6.Impact of high-risk cytogenetic abnormalities on the efficacy of allogeneic hematopoietic stem cell transplantation with post-transplantation Cyclophosphamide in pediatric patients with acute myeloid leukemia
Fei LONG ; Zhi CHEN ; Li YANG ; Zhuo WANG ; Yan CHEN ; Yu DU ; Wenjie LU ; Ming SUN ; Shanshan QI ; Hao XIONG
Chinese Journal of Applied Clinical Pediatrics 2025;40(12):939-945
Objective:To explore the influence of initial high-risk cytogenetic abnormalities on the outcomes of children with acute myeloid leukemia (AML) after post-transplant Cyclophosphamide (PTCy)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective cohort study.AML children who underwent PTCy-based allo-HSCT after the first complete remission at Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology between April 2017 and April 2024 were enrolled.Patients were divided into intermediate-risk and high-risk groups based on their initial cytogenetic features.These patients were further divided into complex karyotype, 11q23 rearrangement, and other karyotype groups.Clinical characteristics and survival outcomes were compared among these groups.Measurement and count data were analyzed using Wilcoxon rank-sum/Kruskal-Wallis and χ2 tests, respectively.Survival and risk factor analyses were performed using Kaplan-Meier and Cox proportional hazards methods, respectively. Results:A total of 51 AML children who underwent allo-HSCT were included in this study.The median age at transplantation was 3.2 years and the median follow-up time was 4.6 years.There were 26 cases in the intermediate-risk group and 25 cases in the high-risk group; 8 cases in the complex karyotype group, 14 cases in the 11q23 rearrangement group, and 29 cases in the other karyotype groups.By the end of the follow-up on November 30, 2024, 11 patients relapsed, 8 patients died, and 13 patients developed grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD).The 3-year overall survival (OS), relapse-free survival (RFS), and grades Ⅱ-Ⅳ acute GVHD-free and relapse-free survival (GRFS) were 84.0% (95% CI: 74.4%-94.8%), 74.5% (95% CI: 63.4%-87.5%), and 58.8% (95% CI: 46.7%-74.0%), respectively.The 3-year OS of the high-risk group was significantly lower than that of the intermediate-risk group (71.8% vs.96.2%, P=0.022), while differences in 3-year RFS and GRFS between the 2 groups were not statistically significant (68.0% vs.80.8%, P=0.400; 52.0% vs.65.4%, P=0.420).The 3-year OS, RFS and GRFS of the complex karyotype group were significantly lower than those of 11q23 rearrangement and other karyotype groups (50.0% vs.85.7%, 93.1%, P=0.009; 37.5% vs.85.7%, 79.3%, P=0.022; 25.0% vs.64.3%, 65.5%, P=0.049).Multivariate analysis showed that a complex karyotype was an independent prognostic factor affecting 3-year OS and GRFS [OS: HR=6.79 (95% CI: 1.13-43.80), P=0.044; GRFS: HR=3.72(95% CI: 1.13-12.20), P=0.030]. Conclusions:High-risk cytogenetic features are significant predictors of survival outcomes in pediatric AML patients undergoing PTCy-based allo-HSCT.
7.Clinical Efficacy of Tianma Xiongling Zhixuan Tablets in Treating Patients with Hypertension of the Type of Hyperactivity of Liver Yang or Combined with Phlegm and Blood Stasis,and Analysis of Plasma Metabolomics
Zhi-xiang CHEN ; Jun-liu HU ; Man WANG ; Fei-ying WANG ; Yao-wu CHEN ; Mao-wen WANG ; Meng-li JI ; Hui-hui LIU ; Jian-min FAN ; Wen ZHANG
Progress in Modern Biomedicine 2025;25(13):2138-2153
Objective:To evaluate the clinical efficacy of Tianma Xionglin Zhixuan Tablets in treating hypertension patients with liver yang hyperactivity or comorbid phlegm-stasis syndrome and explore its therapeutic mechanisms through plasma metabolomics.Methods:Thirty-six hypertension patients(4 dropouts)diagnosed with liver yang hyperactivity or phlegm-stasis syndrome were enrolled as the treatment group from June 2022 to September 2023 at the First Affiliated Hospital of Hunan University of Chinese Medicine,while 30 healthy volunteers with balanced constitutions were recruited as the blank group.Plasma samples were collected from patients pre-and post-treatment and from healthy volunteers.Clinical outcomes,including syndrome scores,office blood pressure(BP),and 24-hour ambulatory BP,were recorded.Plasma metabolomic profiling was performed using liquid chromatography-mass spectrometry(LC-MS).Results:Compared with baseline,Tianma Xionglin Zhixuan Tablets significantly reduced traditional Chinese medicine syndrome scores(P<0.01),office systolic/diastolic BP(P<0.01),and 24-hour ambulatory BP parameters(24-hour mean BP,daytime/nighttime mean BP;all P<0.01).Metabolomic analysis identified 45 differential metabolites between the blank group and pretreatment patients,and 64 metabolites altered post-treatment(VIP>1,P<0.05).Enrichment analysis of 16 overlapping endogenous metabolites revealed that Tianma Xionglin Zhixuan Tablets primarily modulated arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion:Tianma Xionglin Zhixuan Tablets demonstrates significant clinical efficacy in hypertension patients with liver yang hyperactivity or phlegm-stasis syndrome,potentially mediated through regulation of arachidonic acid and sphingolipid metabolism.
8.Effect of curcumin on immune balance of Th17/Treg cells in acne mice by regulating JAK2/STAT3 signaling pathway
Zhi LI ; Suhong CHEN ; Fei MIAO ; Jianxin XU
Chinese Journal of Immunology 2025;41(6):1371-1375
Objective:To investigate the effect of curcumin on Th17/Treg cell immune balance in acne mice by regulating the JAK2/STAT3 signaling pathway.Methods:An acne mouse model was established by injecting propionibacterium suspension.The suc-cessfully established mice were randomly separated into the acne group,low(curcumin-L,50 mg/kg curcumin),medium(curcumin-M,100 mg/kg curcumin),high dose(curcumin-H,150 mg/kg curcumin)curcumin groups,and curcumin-H+JAK2/STAT3 pathway activator-olivelin group(150 mg/kg curcumin+1.0 mg/kg colivelin),with healthy mice as the control group,after intervention,the mice were scored for skin lesions;blood was taken from the orbit,ELISA and flow cytometry were applied to detect serum levels of IL-6 and IL-10,and the ratios of Th17 and Treg cells;HE was applied to detect pathological changes in auricle tissue;Western blot was applied to detect the expressions of p-JAK2,p-STAT3,JAK2,STAT3,Treg transcription factor forked transcription factor 3(FOXP3)and Th17 transcription factor retinoic acid related solitary receptor(RORγt)proteins in auricle tissue.Results:Compared with the control group,the pathological damage in the acne group was severe,the skin lesion and pathological scores,IL-6 level,Th17 cells ratio,p-JAK2/JAK2,p-STAT3/STAT3,and RORγt expression were obviously increased,the IL-10 level,Treg cells ra-tio,and FOXP3 expression were obviously reduced(P<0.05);compared with the acne group,the skin lesion and pathological scores,IL-6 level,Th17 cells ratio,p-JAK2/JAK2,p-STAT3/STAT3 and RORγt expression in curcumin-L,curcumin-M,and curcumin-H groups were obviously reduced,the IL-10 level,Treg cells ratio,and FOXP3 expression were obviously increased(P<0.05);com-pared with the curcumin-H group,the skin lesion and pathological scores,IL-6 level,Th17 cells ratio,p-JAK2/JAK2,p-STAT3/STAT3,and RORγt expression in curcumin-H+colivelin group were obviously increased,the IL-10 level,Treg cells ratio,and FOXP3 expression were obviously reduced(P<0.05).Conclusion:Curcumin can improve the immune balance of Th17/Treg cells in acne mice,which may be related to the inhibition of the JAK2/STAT3 signaling pathway.
9.Icaritin Targets P53 to Regulate DNA Damage Repair and FOXO Signaling Pathways to Inhibit Glioma Cell Growth
Zhi-Qiong LUO ; Zhuo-Yi WANG ; Yong-Ping WANG ; Xiao-Zhong CHEN ; Jia YU ; Sha CHENG ; Ning-Ning ZAN ; Bao-Fei SUN ; Heng LUO
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):753-763
Icaritin(ICT)is an 8-isopentenylflavonoid,which is the main effective component of the tra-ditional Chinese medicine Epimedium.Previously,we found that Icaritin inhibits the growth of glioblasto-ma(GBM)cells.Herein we aim to study the in vivo anti-GBM effectiveness of Icaritin and explore its mechanism.The results of MTT assay,flow cytometry,comet assay and cellular immunofluorescence as-say in vitro showed that ICT inhibited the proliferation of four kinds of GBM cells,U87,U251,U118 and A172,induced early apoptosis(P<0.001)and late apoptosis(P<0.05)in U87 cells,induced DNA damage in U87 cells,and blocked the growth of U87 cells at the G0/G1 phase(P<0.0001)in a concen-tration-time-dependent manner.In vivo subcutaneous tumor transplantation tumor experiments showed that feeding 200 mg/kg(P<0.01)and 400 mg/kg(P<0.001)ICT had a significant inhibitory effect on the growth of GBM subcutaneous tumors,and had no significant toxic effects on heart,liver,spleen,lung and kidney tissues.The results of network pharmacological analysis,molecular docking and cellular thermodynamic experiments showed that there were 26 possible target proteins between ICT and GBM,a-mong which the expression of p53 in GBM tissues was significantly(P<0.001)higher than in normal tis-sues,and the binding energy of ICT and p53 was lower;cellular thermodynamic experiments verified that ICT significantly enriched the level of p53 in the living cells of GBM,which indicated that ICT could tar-get p53.The expression of key proteins in the DNA damage repair and apoptosis-associated FOXO signa-ling pathway was detected by ICT.The results showed that the expression of ATR(P<0.01),P53(P<0.001),P21(P<0.05)and γ-H2AX(P<0.05)was up-regulated,whereas the expression of Cyc-lin E1(P<0.01),E2F1(P<0.05),CDK2(P<0.01),Rb(P<0.001),p-Rb(P<0.0001)and WRN(P<0.0001)expression were down-regulated.There was no significant change in the expres-sion of FOXO 1 in the FOXO pathway or a significant down-regulation of its phosphorylation level.This study demonstrated that ICT could effectively inhibit the growth of GBM cells in vivo.It targets p53 to regulate the DNA damage repair pathway and FOXO signaling pathway to induce GBM cell cycle arrest and apoptosis.
10.Moxibustion combined with low-dose tadalafil for diabetes mellitus-induced erectile dysfunction:A prospective,single-center,three-arm randomized controlled trial
Tao LIU ; Zhao-xu YANG ; Yan XU ; Qi ZHAO ; Xue LIU ; Xin-fei HUANG ; Zhi-xing SUN ; Yun CHEN ; Jian-huai CHEN
National Journal of Andrology 2025;31(1):55-60
Objective:To investigate the clinical efficacy of moxibustion(Mox)combined with low-dose tadalafil(TAD)in the treatment of diabetes mellitus-induced erectile dysfunction(DMED)with the syndrome of Qi deficiency and blood stasis.Meth-ods:According to the inclusion and exclusion criteria,we selected 90 patients with DMED for this trial and equally randomized them into a Mox,a TAD,and a Mox combined with TAD(Mox+TAD)group to be treated by mild Mox applied to the acupoints Zusanli,Sanyinjiao and Yinlingquan qd alt,oral medication with low-dose TAD at 5 mg per dose qd,and combination of the above two thera-pies,respectively,all for 4 weeks.We obtained from the patients their IIEF-5 scores,traditional Chinese medicine(TCM)symptoms scores,Erectile Hardness Scale(EHS)scores,corpus cavernosal hemodynamic indexes,and the peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of the corpus cavernosal arteries before and after treatment,and compared them among the three groups.Results:The total effectiveness rate was significantly higher in the Mox+TAD(90.0%)than in the Mox(46.7%)and TAD groups(60.0%)(P<0.05).Compared with the baseline,the IIEF-5 and EHS scores were increased,while the TCM symptoms scores decreased in all the three groups after treatment,more significantly in the Mox+TAD group than in the other two(P<0.05).And the PSV and RI were remarkably increased,while the EDV decreased(P<0.05)in all the three groups(P<0.05)after treatment,with PSV even higher in the Mox+TAD than in the Mox and TAD groups(P<0.05).Conclusion:Moxi-bustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED,which can effectively improve the erectile function of the patients by increasing penile blood supply,benefiting qi and activating blood circulation.

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