Macrophages are closely related to tumor progression,and can promote tumor growth and pro-liferation by promoting inflammation,angiogenesis and immunosuppression and so on,as well as killing tumors by directly killing tumor cells and triggering specific immune responses.Iron death,as an iron-depend-ent cell death caused by lipid peroxidation,can effectively kill tumor cells when regulated from the perspective of iron homeostasis,and can also release pro-inflammatory factors,trigger inflammatory reactions,change the survival environment of tumors as well as reduce the immune susceptibility of tumor cells.In recent years,more and more studies have shown that macrophages and iron death are closely related.In this paper,the rela-tionship between macrophages and iron death in terms of their functional properties and targeting of tumors are mainly introduced,and an overview of the functional properties of the two differentiated phenotypes of macrophages for the treatment of iron death in tumors is provided.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective: To investigate the prevalence and influencing factors of menopausal syndrome among postmenopausal women in Pan'an County, Zhejiang Province, so as to provide the basis for guiding the health management of postmenopausal women. Methods: From May 2023 to April 2024, the postmenopausal women aged 40 to 69 years in Pan'an County were selected using the random cluster sampling method. Demographic information, lifestyle and prevalence of gynecological diseases were collected through questionnaire surveys. The prevalence of menopausal syndrome was assessed by modified Kupperman Score Scale. Factors affecting menopausal syndrome were analyzed by a multivariable logistic regression model. Results: A total of 816 postmenopausal women were surveyed, with an mean age of (57.63±2.92) years and a mean natural menopause age of (49.85±2.13) years. There were 574 cases with menopausal syndrome, with a prevalence of 70.34%. Flashes and sweating, insomnia and irritability were common symptoms, accounting for 62.87%, 47.43% and 41.18%, respectively. Multivariable logistic regression analysis showed that monthly personal income of ≤5 000 yuan (<3 000 yuan, OR=3.124, 95%CI: 1.829-5.335; 3 000-5 000 yuan, OR=2.399, 95%CI: 1.370-4.201) and having gynecological diseases (OR=1.970, 95%CI: 1.292-3.004) were associated with a higher risk of menopausal syndrome, while average (OR=0.141, 95%CI: 0.072-0.276) or sufficient sleep quality (OR=0.095, 95%CI: 0.049-0.185) were associated with a lower risk of menopausal syndrome. Conclusion The prevalence of menopausal syndrome among postmenopausal women in Pan'an County is relatively high, and is mainly influenced by personal economic status, sleep quality and the presence of gynecological diseases.

AIM:To investigate the association between long noncoding RNA(lncRNA)growth arrest-specific transcript 5(GAS5)genetic polymorphism and the onset of polycystic ovary syndrome(PCOS).METHODS:The case-control study was performed,selecting 236 PCOS patients diagnosed at the Reproductive Medicine Center of the Affiliated Hospital of Guangxi Youjiang University for Nationalities from May 2018 to May 2019 as the case group,while 277 healthy women matched in sex and age during the same period were selected as the control group.The iMLDR single nucleotide polymorphism(SNP)was used to detected the genotypes of rs145204276 I/D,rs55829688 C/T and rs6790 G/A in GAS5 gene.The correlation between GAS5 gene polymorphism and PCOS was analyzed using logistic regression.RESULTS:The difference of GAS5 gene rs145204276 I/D polymorphism had statistical significance between control group and PCOS group.Logistic regression analysis showed that compared with the I/I genotype,the I/D and D/D genotypes,as well as the dominant model I/D+D/D,had a reduced risk of PCOS[I/D vs I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002].Compared with the I allele,the D allele significantly reduced the risk of PCOS[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001).There was no statistically significant difference in the polymorphism of rs55829688 C/T and rs6790 G/A between control group and PCOS group(P＞0.05).The combined analysis of haplotypes showed that the difference of D-T-A haplo-type distribution was statistically significant between control group and PCOS group[OR(95%CI)=0.61(0.45,0.84),P=0.002].CONCLUSION:The polymorphism of GAS5 gene rs145204276 I/D may be associated with genetic suscepti-bility to PCOS,and individuals carrying the D allele may have a reduced risk of developing PCOS.

AIM:To investigate the association between long noncoding RNA(lncRNA)growth arrest-specific transcript 5(GAS5)genetic polymorphism and the onset of polycystic ovary syndrome(PCOS).METHODS:The case-control study was performed,selecting 236 PCOS patients diagnosed at the Reproductive Medicine Center of the Affiliated Hospital of Guangxi Youjiang University for Nationalities from May 2018 to May 2019 as the case group,while 277 healthy women matched in sex and age during the same period were selected as the control group.The iMLDR single nucleotide polymorphism(SNP)was used to detected the genotypes of rs145204276 I/D,rs55829688 C/T and rs6790 G/A in GAS5 gene.The correlation between GAS5 gene polymorphism and PCOS was analyzed using logistic regression.RESULTS:The difference of GAS5 gene rs145204276 I/D polymorphism had statistical significance between control group and PCOS group.Logistic regression analysis showed that compared with the I/I genotype,the I/D and D/D genotypes,as well as the dominant model I/D+D/D,had a reduced risk of PCOS[I/D vs I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002].Compared with the I allele,the D allele significantly reduced the risk of PCOS[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001).There was no statistically significant difference in the polymorphism of rs55829688 C/T and rs6790 G/A between control group and PCOS group(P＞0.05).The combined analysis of haplotypes showed that the difference of D-T-A haplo-type distribution was statistically significant between control group and PCOS group[OR(95%CI)=0.61(0.45,0.84),P=0.002].CONCLUSION:The polymorphism of GAS5 gene rs145204276 I/D may be associated with genetic suscepti-bility to PCOS,and individuals carrying the D allele may have a reduced risk of developing PCOS.

Objective: This study aimed to determine whether surgery followed by adjuvant chemoradiotherapy has superior survival outcomes for node-positive patients with T1b1-T2a1 stage cervical cancer compared with those who undergo chemoradiation. Methods: We investigated the Surveillance, Epidemiology, and End Results database for 12,701 patients diagnosed between 2000 and 2018. Patients were stratified according to different T stages and different treatment strategies. Surgery included radical hysterectomy (RH) or total hysterectomy (TH). Radiotherapy (RT) included adjuvant chemoradiation or chemoradiation alone. Cox analyses were performed to select the clinically important factors of survival outcomes. Survival analysis was used to compare those who received different treatment methods. Results: A total of 12,701 International Federation of Gynecology and Obstetrics 2018 stage IIIC cervical cancer patients were identified. The risk of overall survival (OS) was significantly different between patients who received and did not receive chemoradiotherapy in the T categories. In the propensity-score matched dataset, early-T stage (T1b1 and T1b2) and node-positive patients in the “RH+RT” and “TH+RT” groups had better disease-specific survival (DSS) than those in the RT group. No difference in DSS was observed between the “surgery following RT” group and the RT group in locally advanced stage (T1b3 and T2a1, node positive) patients. Regarding T1b1-T2a1 node-positive patients, the RH+RT group had a similar survival outcome to that in the TH+RT group. Conclusion We showed that surgery following RT benefits early-T stage (T1b1 and T1b2) cervical cancer patients with lymph node metastasis. For locally advanced stages (T1b3 and T2a1), surgery and RT had similar survival outcomes.

Objective: This study aimed to determine whether surgery followed by adjuvant chemoradiotherapy has superior survival outcomes for node-positive patients with T1b1-T2a1 stage cervical cancer compared with those who undergo chemoradiation. Methods: We investigated the Surveillance, Epidemiology, and End Results database for 12,701 patients diagnosed between 2000 and 2018. Patients were stratified according to different T stages and different treatment strategies. Surgery included radical hysterectomy (RH) or total hysterectomy (TH). Radiotherapy (RT) included adjuvant chemoradiation or chemoradiation alone. Cox analyses were performed to select the clinically important factors of survival outcomes. Survival analysis was used to compare those who received different treatment methods. Results: A total of 12,701 International Federation of Gynecology and Obstetrics 2018 stage IIIC cervical cancer patients were identified. The risk of overall survival (OS) was significantly different between patients who received and did not receive chemoradiotherapy in the T categories. In the propensity-score matched dataset, early-T stage (T1b1 and T1b2) and node-positive patients in the “RH+RT” and “TH+RT” groups had better disease-specific survival (DSS) than those in the RT group. No difference in DSS was observed between the “surgery following RT” group and the RT group in locally advanced stage (T1b3 and T2a1, node positive) patients. Regarding T1b1-T2a1 node-positive patients, the RH+RT group had a similar survival outcome to that in the TH+RT group. Conclusion We showed that surgery following RT benefits early-T stage (T1b1 and T1b2) cervical cancer patients with lymph node metastasis. For locally advanced stages (T1b3 and T2a1), surgery and RT had similar survival outcomes.

Objective: This study aimed to determine whether surgery followed by adjuvant chemoradiotherapy has superior survival outcomes for node-positive patients with T1b1-T2a1 stage cervical cancer compared with those who undergo chemoradiation. Methods: We investigated the Surveillance, Epidemiology, and End Results database for 12,701 patients diagnosed between 2000 and 2018. Patients were stratified according to different T stages and different treatment strategies. Surgery included radical hysterectomy (RH) or total hysterectomy (TH). Radiotherapy (RT) included adjuvant chemoradiation or chemoradiation alone. Cox analyses were performed to select the clinically important factors of survival outcomes. Survival analysis was used to compare those who received different treatment methods. Results: A total of 12,701 International Federation of Gynecology and Obstetrics 2018 stage IIIC cervical cancer patients were identified. The risk of overall survival (OS) was significantly different between patients who received and did not receive chemoradiotherapy in the T categories. In the propensity-score matched dataset, early-T stage (T1b1 and T1b2) and node-positive patients in the “RH+RT” and “TH+RT” groups had better disease-specific survival (DSS) than those in the RT group. No difference in DSS was observed between the “surgery following RT” group and the RT group in locally advanced stage (T1b3 and T2a1, node positive) patients. Regarding T1b1-T2a1 node-positive patients, the RH+RT group had a similar survival outcome to that in the TH+RT group. Conclusion We showed that surgery following RT benefits early-T stage (T1b1 and T1b2) cervical cancer patients with lymph node metastasis. For locally advanced stages (T1b3 and T2a1), surgery and RT had similar survival outcomes.

Objective To investigate whether poly arginine as the carrier can carry foreign proteins to penetrate the cell membrane and even penetrate the eyeball barrier.Methods Poly-Args (R9) was used as a CPP in this study.R9-green fluorescent protein (GFP) and GFP were constructed.In vitro,human lens epithelial cells were treated with these two proteins.Then,MTT assay were used to detect whether the protein could affect the proliferation of the cells.Flow cytometry and laser confocal microscopy were used to detect the penetrability of CPPs on the cells.In vivo,eyes of mice were treated with protein in eye drops way for 7 days.Then total protein were extracted,ELISA were used to detect the penetrability of CPPs.Results The results of MTT,flow cytometry and laser confocal microscopy showed that CPPs could carry protein into cells in a dose dependent manner without affecting cell proliferation.In vivo,slit lamp showed that the mice eyeballs had no any abnormal after treated by GFP,R9-GFP,and ELISA results also showed that R9 could effectively get foreign protein into the eyeball.Conelusion R9 can carry foreign protein into the cell membrane and eyeball barrier.This study provides the basis for the eye medication and dosing mode improvement.

Polyhydroxyalkanoates (PHAs), as a novel class of biopolymer, are attracting more attention due to their diverse material properties and environment-independent biodegradability. Here we report the preparation of PHA exhibiting efficient antibacterial activity by embedding Nisin, a food additive generally recognized as safe, into poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), a type of PHA with high biocompatibility. We first prepared Nisin-containing PHBHHx films using solvent casting method. Confocal laser scanning microscopy analysis showed that a well-mixed integrated structure of the films with an even distribution of the Nisin particles in the PHBHHx matrices. Then the antimicrobial activity of PHBHHx/Nisin films against Micrococcus luteus was quantified on agar plate by measuring the size of inhibition zone. Cultivation in liquid media further confirmed the releasing of Nisin from the films and the long-time antibacterial activity. Results showed that the threshold of Nisin concentration for long-time and effective inhibition against bacteria growth is 25 μg/g. These results altogether establish a technological foundation for the application of PHA in biomedicine and food industry.
3-Hydroxybutyric Acid ; chemistry ; Anti-Bacterial Agents ; chemistry ; Caproates ; chemistry ; Micrococcus luteus ; drug effects ; Nisin ; chemistry ; Polyhydroxyalkanoates ; chemistry