1.Analysis of factors associated with recurrence of macular edema secondary to branch retinal vein occlusion after anti-vascular endothelial growth factor treatment
Junmei WANG ; Shuna WANG ; Xuemin ZHANG ; Jianliang LIU ; Zhenhua FENG
International Eye Science 2025;25(9):1500-1504
AIM: To investigate the risk factors associated with the recurrence of macular edema secondary to branch retinal vein occlusion(BRVO-ME)after anti-vascular endothelial growth factor(anti-VEGF)therapy.METHODS:A total of 32 patients(32 eyes)with BRVO-ME who were treated at the ophthalmology department of the Affiliated Hospital of Shandong Second Medical University from February 2021 to June 2022 were selected. They were treated with a 3+pro re nata (PRN)anti-VEGF regimen and followed up for 6 mo. Following 3 consecutive anti-VEGF injections, patients were categorized into a non-recurrence group and a recurrence group based on central macular thickness(CMT)measured by optical coherence tomography(OCT)at 6 mo post-treatment. Aqueous humor levels of various cytokines levels were quantified using suspension assay method. Demographic characteristics, CMT, and cytokine levels were compared between the two groups, and their correlations with the recurrence of BRVO-ME after anti-VEGF treatment were analyzed.RESULTS:At 6 months post-treatment, ME resolved in 19 eyes(no recurrence group), while 13 eyes showed persistent or recurrent ME(recurrence group). Compared to baseline, the CMT significantly improved in both groups at 1 d, 1, and 6 mo post-treatment(all P<0.05). However, the recurrence group exhibited significantly higher baseline, 1 d and 6 mo post-treatment CMT values than the non-recurrence group(all P<0.05). The aqueous humor levels of VEGF and monocyte chemoattractant protein-1(MCP-1)at baseline were significantly higher in the recurrence group than the non-recurrence group(all P<0.05). Spearman correlation analysis revealed positive associations between baseline CMT and interlukin IL-1β, IL-5, IL-12, MCP-1 and IP-10 levels(all P<0.05). Multivariable Logistic regression analysis identified baseline CMT and MCP-1 levels as independent risk factors for BRVO-ME recurrence(OR>1, P<0.05).CONCLUSION: Elevated baseline CMT and aqueous humor MCP-1 levels were identified as independent risk factors for BRVO-ME recurrence after anti-VEGF therapy. Patients exhibiting higher baseline CMT and MCP-1 levels demonstrated significantly increased susceptibility to recurrence.
2.Early combination of Ranibizumab and Dexamethasone intravitreal implant in the treatment of macular edema secondary to retinal vein occlusion
Chaofan WANG ; Shuliang DING ; Junxing YANG ; Zijing FENG ; Dengfeng XU ; Jianliang LIU
International Eye Science 2025;25(4):644-649
AIM:To compare the efficacy and safety of early combination therapy with ranibizumab and dexamethasone intravitreal implants versus ranibizumab monotherapy for the treatment of macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: A retrospective cohort study was conducted on a total of 62 cases(64 eyes)of patients who were first diagnosed with RVO-ME at the Eye Centre of the Affiliated Hospital of Shandong Second Medical University between February 2022 and February 2023. The subjects were divided into two groups according to the different treatment regimens: 32 cases(34 eyes)in the monotherapy group received only ranibizumab [3+pro re nata(PRN)regimen], and 30 cases(30 eyes)in the combination therapy group were injected with ranibizumab once first, followed by dexamethasone intravitreal implant 3 wk later(1+DEX regimen). The best corrected visual acuity(BCVA), central retina thickness(CRT), foveal avascular zone(FAZ)area, macular vascular density(MVD)at the level of the deep vascular complex(DVC)of the retina, the incidence of ocular adverse effects, the number of drug injections, and the total cost between the two groups were compared before and after treatment.RESULTS: At 3 wk, 3 and 6 mo, and at the final follow-up of the two groups of patients, the improvement in BCVA, CRT, and MVD in the DVC layer was significantly better than that before treatment(all P<0.05); there were differences in the comparisons of BCVA and CRT between the two groups at 6 mo and the final follow-up(all P<0.05), and the increase in the number of letters of BCVA was the most pronounced in the combination therapy group at 6 mo of treatment. Statistical significant difference was observed in the comparison of MVD in the DVC layer between the two groups at 3 and 6 mo after treatment and at the final follow-up(all P<0.05). However, no significant change in FAZ area was evident before and after treatment in both groups(P>0.05). The combination therapy group exhibited a reduced number of injections and total cost in comparison to the monotherapy group. The combination therapy group exhibited a slightly higher incidence of high intraocular pressure and cataract progression compared to the monotherapy group, with no statistical significant difference(all P>0.05). Furthermore, no serious adverse events were observed in either group following treatment.CONCLUSION:Compared with ranibizumab alone, ranibizumab combined with dexamethasone intravitreal implant significantly improved vision, reduced macular edema, and lowered the frequency of injections and total treatment cost in patients with RVO-ME. CRT and MVD in the DVC layer are reliable prognostic indicators for patients with RVO-ME.
3.Mechanisms underlying the role of the TXNIP/Trx-1 pathway in microglial polarization in rat retinas after retinal ischemia reperfusion
Yuze ZHAO ; Yiwen WANG ; Lijun ZHANG ; Xinhao FU ; Peilun XIAO ; Xiaoli WANG ; Jianliang LIU ; Yansong ZHAO
Recent Advances in Ophthalmology 2025;45(3):177-182,201
Objective To explore the mechanism of the thioredoxin-interacting protein(TXNIP)/thioredoxin-1(Trx-1)pathway in regulating the polarization of retinal microglia in rats after retinal ischemia-reperfusion(RIR)in rats,and to provide new ideas for the prevention and treatment of retinal ischemia reperfusion injury(RIRI).Methods For-ty-two healthy adult male Sprague-Dawley rats were randomly divided into a Sham group,a RIRI group and a TXNIP siRNA group.The right eye of the rats was experimented.For RIRI and TXNIP siRNA groups,RIRI models were established using the anterior chamber high intraocular pressure method.Rats in the TXNIP siRNA group were given the intravitreal injection of TXNIP siRNA 3 d before modeling.Hematoxylin-eosin(HE)staining was used to analyze retinal histopathologic changes of rats in all groups 24 h after modeling.Immunohistochemical staining of brain-specific homeobox/POU domain proteins 3A(Brn-3a)was made to count the number of retinal ganglion cells(RGCs).The dynamical changes in the number of TXNIP+cells 6 h,24 h,72 h and 7 d after modelling were analyzed through immunohistochemical staining in the RIRI group.The retinal microglia polarization and changes in the expression of TXNIP and Trx-1 proteins in each group were de-tected by double immunofluorescence staining and Western blot 24 h after modeling.Results HE staining results showed that 24 h after modelling,the retinal cells were disordered and the inner retinal layer was thickened and swelled in RIRI and TXNIP siRNA groups,compared with those in the Sham group(all P<0.05).Immunohistochemical staining results of Brn-3a showed that 24 h after modeling,the number of Brn-3a+cells in RIRI and TXNIP siRNA groups significantly decreased,compared with that in the Sham group(both P<0.05).The number of Brn-3a+cells in the TXNIP siRNA group was signifi-cantly higher than that in the RIRI group(P<0.05).Immunohistochemical staining results of TXNIP at different time points after modeling showed that the expression of TXNIP+proteins started to increase 6 h after modeling.The TXNIP+protein level reached a peak at 24 h and then decreased gradually.Western blot results revealed that 24 h after modeling,RIRI and TXNIP siRNA groups had significantly higher TXNIP levels and significantly lower Trx-1 levels than the Sham group(all P<0.05).Compared with those in the RIRI group,the expression of TXNIP proteins was significantly lower and the expression of Trx-1 proteins was significantly higher in the TXNIP siRNA group(both P<0.05).Double immunofluores-cence staining showed that 24 h after modeling,Iba1+/CD206+cells were significantly more and Iba1+/CD16+cells were significantly less in the TXNIP siRNA group than those in the RIRI group(both P<0.05).RIRI and TXNIP siRNA groups had significantly more Ibal+/TXNIP+cells and significantly less Iba1+/Trx-1+cells than the Sham group(both P<0.05).The number of Iba1+/TXNIP+cells was significantly lower and the number of Iba1+/Trx-1+cells was significantly higher in the TXNIP siRNA group than those in the RIRI group(both P<0.05).Conclusion RIR activates the TXNIP/Trx-1 path-way to induce the activation of retinal microglia and regulate the polarization of microglia,thereby resulting in RIRI in rats.
4.The chain mediating effects of sleep quality and pleasure experience between childhood abuse and self-injury behavior in adolescents with depressive disorder
Ting WANG ; Daomin ZHU ; Li ZHU ; Li XU ; Xinyu LI ; Jianliang GAO ; Wen XIE
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(5):412-418
Objective:To explore the relationship between childhood abuse, pleasure experience, sleep quality and self-injury behavior in adolescents with depressive disorder.Methods:One hundred and twenty adolescent patients with depressive disorder hospitalized in the Fourth People's Hospital of Hefei City from January 2021 to February 2024 were selected as the study group, as well as 120 healthy controls matched with the patients' age, gender and education level were selected as the control group.The adolescent non-suicidal self-injury assessment questionnaire, Pittsburgh sleep quality index, temporal experience of pleasure scale, and childhood trauma questionnaire were used for assessment. Statistical analysis was performed using SPSS 26.0 software. Independent sample t-test was used for comparison between the two groups. Pearson correlation analysis was used to analyze correlations between scale scores. Chain mediating modeling was used with the PROCESS macro program. Results:The differences of the study group and the control group in childhood abuse ((53.33±15.21), (39.07±11.81), t=8.081, P<0.001), pleasure experience ((85.60±15.77), (67.44±19.46), t=7.941, P<0.001), self-injury behavior ((29.01±9.89), (3.76±0.49), t=8.811, P<0.001), sleep quality ((12.24±4.15), (6.56±4.05), t=10.711, P<0.001), and depression ((30.62±7.97), (5.88±3.28), t=31.451, P<0.001) were all statistically significant. The self-injury behavior of the study group was positively correlated with the sleep quality ( r=0.487, P<0.001) and childhood abuse ( r=0.553, P<0.001), and negatively correlated with the pleasure experience ( r=-0.483, P<0.001). Childhood abuse had a negative predictive effect on pleasure experience ( β=-0.491, P<0.001), there was a positive predictive effect of childhood abuse on sleep quality ( β=0.363, P<0.001), there was a negative predictive effect of pleasure experience on sleep quality ( β=-0.321, P<0.001), there was a simultaneous predictive effect of childhood abuse, pleasure experience and sleep quality on self-injury behaviors predictive effect ( β=0.343, P<0.001, β=-0.211, P<0.001, β=0.208, P<0.001).The total effect of childhood abuse on self-injury behavior mediated by pleasure experience and sleep quality was 0.555(95% CI=0.448-0.663), and the direct effect was 0.343(95% CI=0.219-0.468).The mediating effect of pleasure experience between childhood abuse and self-injury behavior was 0.104(95% CI=0.007-0.196), accounting for 18.74% of the total effect, the mediating effect of sleep quality between childhood abuse and self-injury behavior was 0.075(95% CI=0.028-0.133), accounting for 13.51% of the total effect, and the chain mediating effect of pleasure experience and sleep quality between childhood abuse and self-injury behavior was 0.033(95% CI=0.011-0.060), accounting for 5.95% of the total effect. Conclusion:Sleep quality and pleasure experience exert the chain mediating effect between the childhood abuse and self-injury behavior in adolescents with depressive disorders.
5.The chain mediating effects of sleep quality and pleasure experience between childhood abuse and self-injury behavior in adolescents with depressive disorder
Ting WANG ; Daomin ZHU ; Li ZHU ; Li XU ; Xinyu LI ; Jianliang GAO ; Wen XIE
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(5):412-418
Objective:To explore the relationship between childhood abuse, pleasure experience, sleep quality and self-injury behavior in adolescents with depressive disorder.Methods:One hundred and twenty adolescent patients with depressive disorder hospitalized in the Fourth People's Hospital of Hefei City from January 2021 to February 2024 were selected as the study group, as well as 120 healthy controls matched with the patients' age, gender and education level were selected as the control group.The adolescent non-suicidal self-injury assessment questionnaire, Pittsburgh sleep quality index, temporal experience of pleasure scale, and childhood trauma questionnaire were used for assessment. Statistical analysis was performed using SPSS 26.0 software. Independent sample t-test was used for comparison between the two groups. Pearson correlation analysis was used to analyze correlations between scale scores. Chain mediating modeling was used with the PROCESS macro program. Results:The differences of the study group and the control group in childhood abuse ((53.33±15.21), (39.07±11.81), t=8.081, P<0.001), pleasure experience ((85.60±15.77), (67.44±19.46), t=7.941, P<0.001), self-injury behavior ((29.01±9.89), (3.76±0.49), t=8.811, P<0.001), sleep quality ((12.24±4.15), (6.56±4.05), t=10.711, P<0.001), and depression ((30.62±7.97), (5.88±3.28), t=31.451, P<0.001) were all statistically significant. The self-injury behavior of the study group was positively correlated with the sleep quality ( r=0.487, P<0.001) and childhood abuse ( r=0.553, P<0.001), and negatively correlated with the pleasure experience ( r=-0.483, P<0.001). Childhood abuse had a negative predictive effect on pleasure experience ( β=-0.491, P<0.001), there was a positive predictive effect of childhood abuse on sleep quality ( β=0.363, P<0.001), there was a negative predictive effect of pleasure experience on sleep quality ( β=-0.321, P<0.001), there was a simultaneous predictive effect of childhood abuse, pleasure experience and sleep quality on self-injury behaviors predictive effect ( β=0.343, P<0.001, β=-0.211, P<0.001, β=0.208, P<0.001).The total effect of childhood abuse on self-injury behavior mediated by pleasure experience and sleep quality was 0.555(95% CI=0.448-0.663), and the direct effect was 0.343(95% CI=0.219-0.468).The mediating effect of pleasure experience between childhood abuse and self-injury behavior was 0.104(95% CI=0.007-0.196), accounting for 18.74% of the total effect, the mediating effect of sleep quality between childhood abuse and self-injury behavior was 0.075(95% CI=0.028-0.133), accounting for 13.51% of the total effect, and the chain mediating effect of pleasure experience and sleep quality between childhood abuse and self-injury behavior was 0.033(95% CI=0.011-0.060), accounting for 5.95% of the total effect. Conclusion:Sleep quality and pleasure experience exert the chain mediating effect between the childhood abuse and self-injury behavior in adolescents with depressive disorders.
6.Mechanisms underlying the role of the TXNIP/Trx-1 pathway in microglial polarization in rat retinas after retinal ischemia reperfusion
Yuze ZHAO ; Yiwen WANG ; Lijun ZHANG ; Xinhao FU ; Peilun XIAO ; Xiaoli WANG ; Jianliang LIU ; Yansong ZHAO
Recent Advances in Ophthalmology 2025;45(3):177-182,201
Objective To explore the mechanism of the thioredoxin-interacting protein(TXNIP)/thioredoxin-1(Trx-1)pathway in regulating the polarization of retinal microglia in rats after retinal ischemia-reperfusion(RIR)in rats,and to provide new ideas for the prevention and treatment of retinal ischemia reperfusion injury(RIRI).Methods For-ty-two healthy adult male Sprague-Dawley rats were randomly divided into a Sham group,a RIRI group and a TXNIP siRNA group.The right eye of the rats was experimented.For RIRI and TXNIP siRNA groups,RIRI models were established using the anterior chamber high intraocular pressure method.Rats in the TXNIP siRNA group were given the intravitreal injection of TXNIP siRNA 3 d before modeling.Hematoxylin-eosin(HE)staining was used to analyze retinal histopathologic changes of rats in all groups 24 h after modeling.Immunohistochemical staining of brain-specific homeobox/POU domain proteins 3A(Brn-3a)was made to count the number of retinal ganglion cells(RGCs).The dynamical changes in the number of TXNIP+cells 6 h,24 h,72 h and 7 d after modelling were analyzed through immunohistochemical staining in the RIRI group.The retinal microglia polarization and changes in the expression of TXNIP and Trx-1 proteins in each group were de-tected by double immunofluorescence staining and Western blot 24 h after modeling.Results HE staining results showed that 24 h after modelling,the retinal cells were disordered and the inner retinal layer was thickened and swelled in RIRI and TXNIP siRNA groups,compared with those in the Sham group(all P<0.05).Immunohistochemical staining results of Brn-3a showed that 24 h after modeling,the number of Brn-3a+cells in RIRI and TXNIP siRNA groups significantly decreased,compared with that in the Sham group(both P<0.05).The number of Brn-3a+cells in the TXNIP siRNA group was signifi-cantly higher than that in the RIRI group(P<0.05).Immunohistochemical staining results of TXNIP at different time points after modeling showed that the expression of TXNIP+proteins started to increase 6 h after modeling.The TXNIP+protein level reached a peak at 24 h and then decreased gradually.Western blot results revealed that 24 h after modeling,RIRI and TXNIP siRNA groups had significantly higher TXNIP levels and significantly lower Trx-1 levels than the Sham group(all P<0.05).Compared with those in the RIRI group,the expression of TXNIP proteins was significantly lower and the expression of Trx-1 proteins was significantly higher in the TXNIP siRNA group(both P<0.05).Double immunofluores-cence staining showed that 24 h after modeling,Iba1+/CD206+cells were significantly more and Iba1+/CD16+cells were significantly less in the TXNIP siRNA group than those in the RIRI group(both P<0.05).RIRI and TXNIP siRNA groups had significantly more Ibal+/TXNIP+cells and significantly less Iba1+/Trx-1+cells than the Sham group(both P<0.05).The number of Iba1+/TXNIP+cells was significantly lower and the number of Iba1+/Trx-1+cells was significantly higher in the TXNIP siRNA group than those in the RIRI group(both P<0.05).Conclusion RIR activates the TXNIP/Trx-1 path-way to induce the activation of retinal microglia and regulate the polarization of microglia,thereby resulting in RIRI in rats.
7.Mechanism of naringin on retinal microvascular endothelial cells injury based on adenosine-monophosphate-activated protein kinase/mammalian target of rapamycin pathway
Journal of Clinical Medicine in Practice 2024;28(3):23-28
Objective To investigate the mechanism of naringin (NAR) on retinal microvascular endothelial cells (HRMECs) injury based on adenosine-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. Methods HRMECs were randomly divided into control group, high glucose (HG) group, HG+NAR group (3 mg/L NAR), HG+activator (AICAR) group (1 mmol/L AICAR), and HG+NAR+AICAR group (3 mg/L NAR+1 mmol/L AICAR); the control group was treated with 5 mmol/L D-glucose added to the culture medium, while the other groups were treated with 30 mmol/L D-glucose added to the culture medium. CCK-8 and Transwell were used to detect cell proliferation and migration respectively; enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the supernatant; quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was applied to detect the expression levels of autophagy factors
8.Dosimetric study on 3D printed individualized molds in postoperative three-dimensional brachytherapy for endometrial cancer
Qingtao XU ; Pengrong LOU ; Jianliang ZHOU ; Binbing WANG ; Jiangping REN
Chinese Journal of Radiological Medicine and Protection 2024;44(5):410-414
Objective:To explore the dosimetric advantages of 3D printed individualized molds in assisting postoperative three-dimensional brachytherapy (3D BT) for endometrial cancer.Methods:The 3D BT plans of 21 postoperative patients with early-stage endometrial cancer at the First Affiliated Hospital of Ningbo University were retrospectively selected as the individualized mold group (the mold group). On this basis, virtual single-channel cylindrical applicator plans that employed a 3D inverse simulated annealing algorithm were designed for all the patients using the Beijing Colins Planning System (the single-channel group). Comparisons were made between the two groups of plans regarding the minimum doses exposed to 90%, 98%, and 100% of target area ( D90, D98, and D100), conformity index (CI), homogeneity index (HI), and overdose index (OI), as well as the maximum doses exposed to 0.01, 1, 2, and 5 cm 3organs at risk (bladder, rectum, small intestine, and urethra) ( D0.01 cm 3, D1 cm 3, D2 cm 3, and D5 cm 3). Results:Both groups met clinical requirements. For doses to target volumes, there was no significant difference in D90, D98, and D100 between both groups, with the mold group demonstrating superior CI and HI but lower OI compared to the single-channel group ( t = -3.21, -5.99, 6.25, P < 0.05). Concerning the doses exposed to organs at risk, the mold group displayed significantly reduced D1 cm 3, D2 cm 3, and D5 cm 3 for the bladder, rectum, and urethra compared to the single-channel group ( t = 3.18, 3.21, 3.77, 7.97, 8.92, 10.92, 2.54, 3.46, 4.28, P < 0.05). There was no significant difference in the doses exposed to the small intestine between both groups ( P > 0.05) due to the large distance from the small intestine to the target volumes. Conclusions:3D printed individualized molds exhibit advantages in terms of the homogeneity and conformity indices of target volumes in postoperative three-dimensional brachytherapy for endometrial cancer, accompanied by low doses exposed to the bladder, rectum, and urethra, thereby holding the potential for broader application.
9.The mechanism of N-acetylserotonin regulating microglial polarization via NOD1/Rip2 pathway in rats after retinal ischemia reperfusion
Ying XU ; Jianliang LIU ; Yuze ZHAO ; Chenxu WANG ; Xinhao FU ; Xiaoshuang LI ; Xiaoli WANG ; Yansong ZHAO
Chinese Journal of Ocular Fundus Diseases 2024;40(4):287-295
Objective:To investigate the effect of N-acetylserotonin (NAS) on the retinal microglia polarization in retinal ischemia-reperfusion injury (RIRI) rats and explore its mechanism via nucleotide-bound oligomeric domain 1 (NOD1)/receptor interacting protein 2 (Rip2) pathway.Methods:Healthy male Sprague Dawley rats were randomly divided into Sham ( n=21), RIRI ( n=21) and NAS (injected intraperitoneally 30 min before and after modeling with NAS, 10 mg/kg, n=18) groups, using random number table. And the right eye was used experimental eye. The RIRI model of rats in RIRI group and NAS group was established by anterior chamber high intraocular pressure method. Rats in NAS group were intraperitoneally injected with 10 mg/kg NAS before and 30 min after modeling, respectively. The retinal morphology and the number of retinal ganglion cell (RGC) in each group were detected by hematoxylin-eosin staining and immunohistochemical staining. The effect of NAS on polarization of retinal microglia was detected by immunofluorescence staining. Transcriptome sequencing technology was used to screen out the differentially expressed genes between Sham and RIRI groups. Western blot and real-time quantitative polymerase chain reaction (RT-PCR) were used to examine the differentially expressed genes. Immunohistochemical staining, Western blot and RT-PCR were used to investigate the effect of NAS on the expression of NOD1 and Rip2 protein and mRNA in retinal tissue and microglia of rats. General linear regression analysis was performed to determine the correlation between the number difference of NOD1 + cells and the number difference of M1 and M2 microglia in retinal tissues of rats in NAS group and RIRI group. Results:A large number of RGC were observed in the retina of rats in Sham group. 24 h after modeling, compared with Sham group, the inner retinal thickness of rats in RIRI group was significantly increased and the number of RGC was significantly decreased. The thickness of inner retina in NAS group was significantly thinner and the number of RGC was significantly increased. Compared with Sham group, the number of retinal microglia of M1 and M2 in RIRI group was significantly increased. Compared with RIRI group, the number of M1 microglia decreased significantly and the number of M2 microglia increased significantly in NAS group. There was statistical significance in the number of M1 and M2 microglia in the retina of the three groups ( P<0.05). Transcriptome sequencing results showed that retinal NOD1 and Rip2 were important differential genes 24 h after modeling. The mRNA and protein relative expressions of NOD1 and Rip2 in retina of RIRI group were significantly higher than those of Sham group, with statistical significance ( P<0.05). The number of NOD1 + and Rip2 + cells and the relative expression of mRNA and protein in retinal microglia in RIRI group were significantly higher than those in Sham group, and NAS group was also significantly higher than that in Sham group, but lower than that in RIRI group, with statistical significance ( P<0.05). The number of Iba-1 +/NOD1 + and Iba-1 +/Rip2 + cells in retinal microglia in RIRI group was significantly increased compared with that in Sham group, and the number of Iba-1 +/Rip2 + cells in NAS group was significantly decreased compared with that in RIRI group, but still significantly higher than that in Sham group, with statistical significance ( P<0.05). Correlation analysis results showed that the difference of retinal NOD1 + and Rip2 + cells in NAS group and RIRI group was positively correlated with that of M1 microglia ( r=0.851, 0.895), and negatively correlated with that of M2 microglia ( r=-0.797, -0.819). The differences were statistically significant ( P<0.05). Conclusion:NAS can regulate the microglial polarization from M1 to M2 phenotype, the mechanism is correlated with the NOD1/Rip2 pathway.
10.Loganin inhibits the ROS-NLRP3-IL-1β axis by activating the NRF2/HO-1 pathway against osteoarthritis
Miao LI ; Jiacong XIAO ; Baihao CHEN ; Zhaofeng PAN ; Fanchen WANG ; Weijian CHEN ; Qi HE ; Jianliang LI ; Shaocong LI ; Ting WANG ; Gangyu ZHANG ; Haibin WANG ; Jianfa CHEN
Chinese Journal of Natural Medicines (English Ed.) 2024;22(11):977-990
Loganin(LOG),a bioactive compound derived from Cornus officinalis Siebold & Zucc,has been understudied in the context of osteoarthritis(OA)treatment.In this study,we induced an inflammatory response in chondrocytes using lipopolysaccharide(LPS)and subsequently treated these cells with LOG.We employed fluorescence analysis to quantify reactive oxygen species(ROS)levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2(NRF2)using real-time quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunofluorescence(IF)techniques.Additionally,we developed an OA mouse model by performing medial meniscus destabilization(DMM)surgery and monitored disease progression through micro-com-puted tomography(micro-CT),hematoxylin and eosin(H&E)staining,safranin O and fast green(S&F)staining,and immunohisto-chemical(IHC)analysis.Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes,inhibited the activation of the NLRP3 inflammasome,and enhanced NRF2/heme oxygenase 1(HO-1)signaling.In vivo,LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery,decreased NLRP3 expression,and increased NRF2 expres-sion.These findings suggest that LOG has a protective effect against OA,potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.


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