1.The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer
Xin-Die WANG ; Da-Li FENG ; Xiang CUI ; Su ZHOU ; Peng-Fei ZHANG ; Zhi-Qiang GAO ; Li-Li ZOU ; Jun WANG
Progress in Biochemistry and Biophysics 2025;52(4):804-819
Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.
2.Study of adsorption of coated aldehyde oxy-starch on the indexes of renal failure
Qian WU ; Cai-fen WANG ; Ning-ning PENG ; Qin NIE ; Tian-fu LI ; Jian-yu LIU ; Xiang-yi SONG ; Jian LIU ; Su-ping WU ; Ji-wen ZHANG ; Li-xin SUN
Acta Pharmaceutica Sinica 2025;60(2):498-505
The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure
3.Vanillin down-regulates cGAS/STING signaling pathway to improve liver tissue injury in rats with intrahepatic cholestasis
Ning JIANG ; Lan-Xiang PU ; Feng HUANG ; Yan WANG ; Xin PEI ; Jun-Ya SONG ; En-Sheng ZHANG
Chinese Pharmacological Bulletin 2024;40(9):1695-1700
Aim To investigate the effect of vanillin on the regulation of cyclic guanylate adenylate synthetase(cGAS)/stimulator of interferon gene(STING)signa-ling pathway on hepatic tissue injury in rats with intra-hepatic cholestasis(IC).Methods SD rats were randomly divided into normal group,IC group,vanillin group,cGAS overexpression group,and vanillin+cGAS overexpression group,with continuous adminis-tration for seven days.The body weight,liver weight and liver to body weight ratio of rats were measured.Liver function(ALT,AST,ALP,LDH),IC(TBIL,TBA)and liver fibrosis(HA,LN,PC Ⅲ)index were determined by ELISA.Liver pathology and fibrosis were observed using HE and Masson staining,and col-lagen volume fraction was calculated.The expression of cGAS/STING pathway related proteins in liver tissue was detected by Western blot.Results Vanillin could improve liver pathology and fibrosis,increase body weight,and decrease liver weight,ALT,AST,ALP,LDH,TBIL,TBA,HA,LN,PC Ⅲ,collagen volume fraction,cGAS,STING protein in IC rats(P<0.05).Overexpression of cGAS could reverse the effects of vanillin on the above indicators in IC rats(P<0.05).Conclusions Vanillin may improve liver function,IC,liver fibrosis,and liver tissue damage in IC rats by downregulating the cGAS/STING signaling pathway.
4.Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract improves radiation-induced pulmonary fibrosis in rats by regulating NLRP3/caspase-1/GSDMD pyroptosis pathway
Chun-Zhen REN ; Jian-Fang YUAN ; Chun-Ling WANG ; Xiao-Dong ZHI ; Qi-Li ZHANG ; Qi-Lin CHEN ; Xin-Fang LYU ; Xiang GAO ; Xue WU ; Xin-Ke ZHAO ; Ying-Dong LI
Chinese Pharmacological Bulletin 2024;40(11):2124-2131
Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P<0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P<0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P<0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P<0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.
5.Clinical efficacy of double-bundle and double-tunnel enhanced reconstruction in the treatment of anterior cruciate ligament injury
Bao LI ; Xin-Wei LIU ; Yang SUN ; Ning SUN ; Yu WANG ; Ying-Chao DUAN ; Xiang-Hong CUI ; Yi-Peng SUN ; Hong YUAN
China Journal of Orthopaedics and Traumatology 2024;37(7):649-654
Objective To explore the clinical efficacy of double beam double tunnel enhanced reconstruction technique in the treatment of knee anterior cruciate ligament(ACL)training injuries.Methods Twenty-nine cases of ACL injury of knee joint from January 2021 to December 2021 were retrospectively analyzed.All the cases were underwent ligament reconstruc-tion surgery.Cases were grouped by surgical technique:there were 14 patients in conventional reconstruction group,including 13 males and 1 female,aged from 22 to 31 years old with an average of(27.07±7.28)years old,autogenous hamstring tendon was used for ligament reconstruction.There were 15 patients in the enhanced reconstruction group,including 13 males and 2 females,aged from 25 to 34 years old with an average of(29.06±4.23)years old,double tunnel ligament reconstruction,the autogenous hamstring muscle was used as the anteromedial bundle,and the posterolateral bundle was replaced by a high-strength line.The difference between knee tibial anterior distance,Lysholm score,International Knee Literature Committee(IKDC)subjective score,Tegner motor level score and visual analog scale(VAS)at 6th and 12th months after the surgery,limb symmetry index(LSI)were recorded at the last follow-up and surgery-related adverse effects during follow-up.Results All patients were followed up,ranged from 13 to 15 months with an average of(13.7±0.8)months.There were no serious adverse reactions related to surgery during the period.There was no statistical difference between the preoperative general data and the observation index of the two groups(P>0.05).The difference in tibial anterior distance at 6 and 12 months in the enhanced re-construction group(1.45±0.62)mm and(1.74±0.78)mm which were lower those that in the conventional reconstruction group(2.42±0.60)mm and(2.51±0.63)mm(P<0.05).There was no significant difference in postoperative Lysholm score,Tegner motor level score,IKDC score,VAS,and limb symmetry index at the last follow-up(P>0.05).Conclusion The enhanced recon-struction technique can more effectively maintain the stability of the knee joint and has no significant effect on the postoperative knee joint function compared with the traditional ligament reconstruction technique.The short-term curative effect is satisfac-tory,and it is suitable for the group with high sports demand.
6.Genetic characterization of varicella-zoster virus in Jilin province from 2010 to 2023
Xiang LI ; Leilei WEI ; Biao HUANG ; Tao CHENG ; Yuanchun SHAN ; Guixiang QIN ; Hongyan SUN ; Shangwei JI ; Xin TIAN ; Simei FU ; Shuang WANG
Chinese Journal of Experimental and Clinical Virology 2024;38(5):521-526
Objective:This study aimed to analyze the genomic characteristics of Varicella-Zoster Virus (VZV) strains circulating in Jilin province from 2010 to 2023.Methods:Vesicle fluid from 78 sporadic cases with VZV infection were collected in Jilin province from 2010 to 2023, after detecting by Real-time PCR, 26 specimens (CT<25) were detected by PCR. Open reading frame 22(ORF22), ORF38 and ORF62 were amplified and analyzed. Genotyping was confirmed by SNPs ORF22 (37902, 38019, 38055, 38081 and 38177) and ORF38 (69424). Vaccine strains were indentified from wild-type strains according to ORF38 (69349) and ORF62 (106262, 107252, and 108111). Sequences were analyzed by homologous comparison and phylogenetic analysis.Results:The comparison with Dumas sequence revealed that SNPs (37902, 38055, 38081 and 38177) in ORF22 and ORF38 (69424) have mutations similar to the pOka strain, which belong to clade 2. Compared to the Dumas and Baike strains, all 26 samples were wild-type strains. JL2016-4 strain changes from threonine to asparaginyl at position 38059, JL2021-4 strain changes from arginine to proline at position 37933, from aspartic acid to tyrosine at position 37935, and from aspartic acid at base 38031 to tyrosine. JL2023-1 strain changes from arginine to leucine at position 37933.Conclusions:VZV has been prevalent for 14 years in Jilin province. The main epidemic strains belong to the clade 2. We should strengthen the monitoring of VZV outbreaks and raise the coverage rate of VZV vaccination.
7.SS-3DUNet model based on spatially separable convolutions for automatically segmenting anal fistula on enhanced MR T1WI
Lei WANG ; Xiuqiang YIN ; Xiang LONG ; Xin QIU ; Huanluo TONG
Chinese Journal of Interventional Imaging and Therapy 2024;21(11):696-701
Objective To observe the value of SS-3DUNet model based on spatially separable convolutions for automatically segmenting anal fistula in enhanced MR T1WI.Methods Totally 2 405 pelvic axial enhanced MR T1WI of 29 patients with anal fistula were retrospectively analyzed,and 1 537 images from 19 cases were randomly selected as training set,424 images from 5 cases were as validation set,444 images from 5 cases were as test set.A SS-3DUNet model was constructed based on spatially separable convolutions to automatically segment anal fistula in enhanced MR T1WI,and inter-layer feature enhancement module was incorporated to improve the location of fistula features.The model was trained in training set and the best one was selected based on validation set.Taking the results of manual labeling by clinicians,the efficacy of SS-3DUNet model for automatically segmenting anal fistulas was observed based on test set.Results The time of SS-3DUNet automatically segmenting anal fistula in a single image in test set was 0.59-0.61 s,and the coincidence of the boundary of fistula segmented by the model and manual label was high.The average Dice similarity coefficient,sensitivity and accuracy of SS-3DUNet for automatically segmenting anal fistula in test set was 0.746,70.04%and 82.93%,respectively.Conclusion SS-3DUNet model based on spatially separable convolutions could effectively automatically segmenting anal fistula in enhanced T1WI.
8.Meta-analysis comparing the efficacy of pancreaticoduodenectomy with Heidelberg triangle operation and standard pancreaticoduodenectomy in the treatment of pancreatic cancer
Qiang SHU ; Bo XU ; Qinghai WANG ; Sheng ZHONG ; Xiaoling LIU ; Xin XIANG
Chinese Journal of General Surgery 2024;33(9):1440-1450
Background and Aims:There is currently no consensus on whether the pancreaticoduodenectomy with Heidelberg triangle operation(PDTRIANGLE)or the standard radical pancreaticoduodenectomy(PDSTANDARD)is more beneficial for patients with pancreatic cancer,and no large-scale multicenter studies have confirmed this.Therefore,this study was conducted to compare the clinical efficacy and safety of PDTRIANGLE and PDSTANDARD for treating pancreatic cancer through a Meta-analysis. Methods:Relevant literature comparing the two surgical approaches comparing the two surgical approaches for treating pancreatic cancer was screened from Chinese and English databases based on inclusion criteria.The search timeframe extended from the inception of the databases to May 2024,and Review Manager 5.3 software was used for Meta-analysis of the extracted outcome variables. Results:A total of 6 retrospective studies were included,comprising 658 patients,with 315 in the PDTRIANGLE group and 343 in the PDSTANDARD group.The Meta-analysis results showed that the operative time in the PDTRIANGLE group was longer than that in the PDSTANDARD group(OR=1.52,95%CI=0.42-2.61,P=0.007),the lymph node dissection rate was higher in the PDTRIANGLE group(OR=0.70,95%CI=-0.4-1.01,P<0.000 01),and the R0 resection rate was also higher in the PDTRIANGLE group(OR=1.63,95%CI=1.03-2.58,P=0.04).The incidence rates of postoperative lymphatic fistula and diarrhea were higher in the PDTRIANGLE group compared to the PDSTANDARD group(OR=5.60,95%CI=1.81-17.29,P=0.003;OR=0.13,95%CI=0.07-0.20,P<0.000 1).The length of hospital stay was longer in the PDTRIANGLE group(OR=0.40;95%CI=-0.14-0.65,P=0.003).The overall survival rates at 1 and 2 years were significantly better in the PDTRIANGLE group compared to the PDSTANDARD group(OR=2.19,95%CI=-1.27-3.76,P=0.005;OR=1.65,95%CI=-1.01-2.67,P=0.04),and the 1-year disease-free survival rate was also significantly higher in the PDTRIANGLE group(OR=3.71,95%CI=2.27-6.07,P<0.000 01),although the difference in the 2-year disease-free survival rate between the two groups was not statistically significant(OR=2.63,95%CI=-0.91-7.59,P=0.07). Conclusion:PDTRIANGLE is a safe and effective treatment for pancreatic cancer.Compared to PDSTANDARD,PDTRIANGLE significantly improves the R0 resection rate,thereby enhancing the postoperative disease-free survival rate and achieving a better long-term prognosis.
9.Research progress in Brucella main outer membrane proteins
Xue-Qiang XIN ; Tong TONG ; Yu-Jin WANG ; Yu-Jie SHENG ; Zheng-Zhong XU ; Xiang CHEN
Chinese Journal of Zoonoses 2024;40(9):872-879
Brucellosis,a worldwide epidemic bacterial zoonotic infectious disease caused by bacteria of the genus Brucella,jeopardizes livestock production and poses a major threat to public health safety.Among the various components of Brucella,the outer membrane proteins play crucial roles as the primary immune and protective antigens.These proteins are closely asso-ciated with Brucella's virulence,regulation of the immune response,and ability to survive and multiply within host cells.This article summarizes recent research progress in the primary outer membrane proteins of Brucella,and offers a synthesized view of the current knowledge landscape.Understanding the antigenic characteristics of Brucella outer membrane proteins may sub-stantially contribute to the establishment of new diagnostic methods and the design of new vaccines,thus potentially leading to more effective prevention strategies against brucellosis.The review provides a reference for future studies and may aid in brucel-losis control efforts.
10.Perilla AP2 Gene Family PfWRI1 Promotes Oil Accumulation in Plant Seeds
Xiao-Yan FENG ; Qi-Feng WANG ; Ke-Xin YUE ; Fu-Peng HOU ; Hua-Xiang XU ; Jun-Xing LU ; Jian HU ; Tao ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(8):1161-1172
AP2 transcription factors belong to the AP2/ERF superfamily and are involved in the regula-tion of various biological processes in plant growth and development,as well as in response to biotic and abiotic stresses.However,studies on the AP2 transcription factor family of Perilla frutescens have not been reported.In this study,totally 18 AP2 family members were identified from the Perilla frutescens ge-nome and analyzed for gene structure,conserved motifs,and cis-acting elements using bioinformatics.WRINKLED1(WRI1)is a key regulator of lipid biosynthesis in many plant species and plays an impor-tant role in the regulation of lipid synthesis.Sequence comparison revealed that one member of WRI1 is highly homologous to AtWRI1 and contains two conserved AP2 domains,named PfWRI1.The expression levels of PfAP2 family genes were analyzed in different tissues of Perilla frutescens and at different stages of seed development in conjunction with the transcriptome data,and the results showed that PfWRI1 is highly expressed only in the seeds of Perilla frutescens,suggesting that PfWRI1 may be related to the de-velopmental process of the seeds.The overexpression vector of plant pCAMBIA1303-PfWRI1 was con-structed,and wild-type(Col)and mutant(wri1-1)Arabidopsis thaliana were transformed by Agrobacte-rium tumefaciens to obtain overexpression and complementation lines,respectively.The results showed that the expression of P fWRI1 led to an increase in oil content of Arabidopsis seeds by 8.90%-13.57%compared with Col,and promoted the accumulation of oleic acid(C18:1)and linoleic acid(18:2)and reduced the accumulation of palmitic acid(C16:0),arachidonic acid(C20:0),and cis-11-Eicosenoic acid(C20:1)in transgenic Arabidopsis seeds.In addition,PfWRI1 gene expression increased the ex-pression of glycolysis and fatty acid biosynthesis-related genes AtPKP-α,AtPKP-β1,AtBCCP2,AtSUS2,and AtLIP1.Taken together,PfWRI1 may promote lipid accumulation by increasing unsaturated fatty acid content through interaction with the above genes.

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