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 X_c^--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.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

Objective To investigate the role of heme oxygenase-1(HO-1)on HBV replication and the antiviral effect of HO-1 combined with α-interferon(IFN-α).Methods HepG2.2.15 cells and HBV1.3-transfected HepG2 cells(HepG2-HBV1.3)were used as HBV replicating cell models;Hemin treated HepG2.2.15 and HepG2-HBV1.3 cells,to induce the expression of HO-1 molecules.CCK-8 method was used to assess the toxic effects of Hemin on HepG2 and HepG2.2.15;chemiluminescence method was used to analyze HBsAg and HBeAg in the supernatants of Hemin-treated group and si-HO-1 and other experimental groups;RT-qPCR was used to ana-lyze HO-1,IFN-β and HBV-DNA;Western blot was used to analyze the expression of IRF-3 and the expression of related molecules in the JAK/STAT signaling pathway;Hemin combined with IFN-α treated HepG2.2.15 to moni-tor whether HO-1 had synergistic IFN-α antiviral effect.Results Hemin dose-dependently induced HO-1,and HO-1 was induced to exert a significant anti-HBV effect,while the expression of IFN-β,IRF-3,and IRF-9 and MxA,downstream molecules of the JAK/STAT signaling pathway,were all increased.Silencing HO-1 expression reversed the antiviral effect in the Hemin-induced group,and at the same time,type Ⅰ interferon IFN-β showed low expression,and the expression of IRF-9 and MxA in the JAK/STAT signaling pathway was inhibited as well.He-min combined with IFN-α exerted stronger antiviral effects.Conclusion HO-1 can exert an anti-HBV effect,which may be due to increased phosphorylation of IRF-3 to induce type Ⅰ interferon expression and thus activate the JAK/STAT signaling pathway to exert an antiviral effect;HO-1 can synergize with IFN-α to exert an antiviral effect.

Objective To explore the relationship between the types of bicuspid aortic valves(BAV)and the outcome of functional mitral regurgitation(FMR)and the affecting factors of FMR.Methods From Jun 2018 to Sep 2022,patients with severe BAV aortic valve stenosis(AS)complicated with FMR underwent post transcatheter aortic valve replacement(TAVR)in Zhongshan Hospital,Fudan University were retrospectively analyzed.The baseline information and imaging data of different BAV patients were collected.Logistic regression was used to analyze the factors affecting the outcome of FMR(improvement and non-improvement).Result A total of 100 patients with TAVR were included,including 49 patients with type 0 of BAV and 51 patients with type 1 of BAV.Compared with patients of type 1,patients of type 0 had younger age[(72.78±6.09)y vs.(77.00±8.35)y,P=0.050],lower male ratio(47%vs.73%,P= 0.009)higher BMI[(23.19±2.62)kg/m2 vs.(21.99±3.13)kg/m2,P=0.041],and lower incidence of aortic regurgitation(69%vs.92%,P=0.040).Compared with the non-improvement group,the improvement group had a lower incidence of coronary heart disease(5%vs.18%,P=0.042),higher incidence of pulmonary hypertension(20%vs.2%,P=0.007),larger left ventricular diastolic diameter[(51.98±6.74)mm vs.(48.04±7.72)mm,P=0.009]and higher maximum flow velocity[(4.86±0.95)cm/s vs.(4.47±0.75)cm/s,P= 0.023]of the aortic valve.The results of Logistic regression analysis showed that preoperative pulmonary hypertension,left ventricular end-diastolic diameter and maximum valvular flow velocity of BAV patients were the potential affecting factors of FMR improvement after TAVR.Conclusion No significant difference was found in FMR improvement between BAV patients of type 0 and type 1 after TAVR.For BAV patients with AS,preoperative pulmonary hypertension,larger left ventricular end-diastolic diameter,and faster aortic valve flow velocity were associated with higher FMR improvement rate.

Tricuspid regurgitation(TR)cases are widely distributed in China.Poor clinical drug efficacy,high surgical risk,and poor prognosis for right heart failure are found in patients with moderate or severe TR.In recent years,with the innovation of valve instruments and the development of technology,transcatheter tricuspid valve treatment could be a new choice for high-risk TR patients in surgery.Many TR animal models have emerged these years for the research of the mechanism of TR and for the clinical verification of instruments.Therefore,this review focuses on how to develop an animal model of TR and discusses the advantages and disadvantages of these techniques.

Based on WANG Xugao's “thirty methods of treating the liver”， it is believed that the occurrence and development of childhood tic disorders follow the dynamic progression from liver qi disease to liver fire disease and then liver wind disease. The basic pathogenesis of three stages are characterized by binding constraint of liver qi， liver fire hyperactivity， and internal stirring of liver wind. Moreover， liver-blood deficiency and stagnation， and malnutrition of liver yin as the main point in terms of the imbalance of liver qi， blood， yin， and yang should be considered， as well as the imbalance relationship of the five zang organs such as the involvement of other organs and the gradually reach of the other organs. Guided by the principles of “thirty methods of treating the liver”， the treatment of tic disorders in liver qi stage should focus on soothing the liver and rectifying qi， soothing the liver and unblocking the collaterals， using Xiaochaihu Decoction （小柴胡汤） and Sini Powder （四逆散）. The treatment of tic disorders in liver fire stage involves clearing， draining and resolving liver heat， using Longdan Xiegan Decoction （龙胆泻肝汤）， Xieqing Pill （泻青丸）， Danggui Longhui Pill （当归龙荟丸）， and Huagan Decoction （化肝煎）. The treatment of tic disorders in liver wind stage involves extinguishing wind and subduing yang， using Lingjiao Gouteng Decoction （羚角钩藤汤） and Liuwei Dihuang Pill （六味地黄丸）. Throughout the treatment process， attention should be paid to harmonizing the liver's qi， blood， yin， and yang， as well as addressing the pathology of other organs.

ObjectiveProtein arginine methyltransferases (PRMTs) play pivotal roles in numerous cellular biological processes. However, the precise regulatory effects of PRMTs on the fate determination of mesenchymal stromal/stem cells (MSCs) remain elusive. Our previous studies have shed light on the regulatory role and molecular mechanism of PRMT5 in MSC osteogenic differentiation. This study aims to clarify the role and corresponding regulatory mechanism of PRMT7 during the adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Methods(1) Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured in a medium that induces adipogenesis. We used qRT-PCR and Western blot to monitor changes in PRMT7 expression during adipogenic differentiation. (2) We created a cell line with PRMT7 knocked down and assessed changes in PRMT7 expression and adipogenic capacity using Oil Red O staining, qRT-PCR and Western blot. (3) We implanted hBMSCs cell lines mixed with a collagen membrane subcutaneously into nude mice and performed Oil Red O staining to observe ectopic lipogenesis in vivo. (4) A cell line overexpressing PRMT7 was generated, and we examined changes in PRMT7 expression using qRT-PCR and Western blot. We also performed Oil Red O staining and quantitative analysis after inducing the cells in lipogenic medium. Additionally, we assessed changes in PPARγ expression. (5) We investigated changes in insulin-like growth factor 1 (IGF-1) expression in both PRMT7 knockdown and overexpressing cell lines using qRT-PCR and Western blot, to understand PRMT7’s regulatory effect on IGF-1 expression. siIGF-1 was transfected into the PRMT7 knockdown cell line to inhibit IGF-1 expression, and knockdown efficiency was confirmed. Then, we induced cells from the control and knockdown groups transfected with siIGF-1 in lipogenic medium and performed Oil Red O staining and quantitative analysis. Finally, we assessed PPARγ expression to explore IGF-1’s involvement in PRMT7’s regulation of adipogenic differentiation in hBMSCs. Results(1) During the adipogenesis process of hBMSCs, the expression level of PRMT7 was significantly reduced (P<0.01). (2) The adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group (P<0.001). (3) The ectopic adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group. (4) The adipogenic differentiation ability of the PRMT7 overexpression group was significantly weaker than that of the control group (P<0.01). (5) The expression level of IGF-1 increased after PRMT7 knockdown (P<0.000 1). The expression level of IGF-1 decreased after PRMT7 overexpression (P<0.000 1), indicating that PRMT7 regulates the expression of IGF-1. After siIGF-1 transfection, the expression level of IGF-1 in all cell lines decreased significantly (P<0.001). The ability of adipogenic differentiation of knockdown group transfected with siIGF-1 was significantly reduced (P<0.01), indicating that IGF-1 affects the regulation of PRMT7 on adipogenic differentiation of hBMSCs. ConclusionIn this investigation, our findings elucidate the inhibitory role of PRMT7 in the adipogenic differentiation of hBMSCs, as demonstrated through both in vitro cell-level experiments and in vivo subcutaneous transplantation experiments conducted in nude mice. Mechanistic exploration revealed that PRMT7’s regulatory effect on the adipogenic differentiation of hBMSCs operates via modulation of IGF-1 signaling pathway. These collective findings underscore PRMT7 as a potential therapeutic target for fatty metabolic disorders, thereby offering a novel avenue for leveraging PRMT7 and hBMSCs in the therapeutic landscape of relevant diseases.

Objective To establish an ultra high performance liquid chromatography-tandem mass spectrometry method for the determination of lacidipine in plasma of beagle dogs was established.Methods It was pretreated by protein precipitation method and the internal standard was nimodipine.Chromatographic column:ACQUITYUPLC? BEH C8(2.1 mm x50.0 mm,1.7 μm),mobile phase:100％water containing 5 mmol·L-1 ammonium acetate-100％acetonitrile,flow rate:0.7 mL·min-1,column temperature:40 ℃,automatic injector temperature:4 ℃,injection volume:20 μL.Electrospray ionization source,positive ion mode,multi-reaction monitoring.The specificity,residual effect,standard curve and quantitative lower limit,precision and recovery,matrix effect and stability of the method were investigated.Results Lacidipine has a good linear relationship in the range of 0.10-50.0 ng·mL-1,r=0.996 6,the lower limit of quantification was 0.10 ng·mL-1.The specificity was good.The intra-and inter-relative standard deviation was less than 12％.The extraction recovery was higher than 80％,and the stability was good.Conclusion The method has the advantages of high sensitivity,simple operation and short analysis time,and was suitable for the pharmacokinetic study of lacidipine in Beagle dog plasma.