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.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR. RESULTS: The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01). CONCLUSIONS EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Phosphatidylinositol 3-Kinase/metabolism* ; Facial Nerve Injuries/therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Beclin-1 ; Glial Cell Line-Derived Neurotrophic Factor ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Mammals/metabolism*

Sesquiterpenes are natural terpenoids with 15 carbon atoms in the basic skeleton, which mainly exist in plant volatile oil and have important physiological and medicinal value. Cytochrome P450 (CYP450) is a kind of monooxygenase encoded by supergene family, which is one of the largest gene families in plants. It is involved in the synthesis and metabolism of terpenoids, alkaloids and other secondary metabolites. In the process of terpene biosynthesis, CYP450 participates in the post-modification stage of terpenes by introducing functional groups such as hydroxyl, carboxyl and carbonyl, which plays an important role in enriching the diversity of terpenes. The CYP450 enzymes involved in sesquiterpene synthesis and their substrate catalytic specificity mechanisms have been partially investigated. In this paper, the biosynthetic pathway of plant sesquiterpenes, the structure and classification of CYP450 enzymes were briefly introduced, and the CYP450 enzymes involved in sesquiterpene biosynthesis were summarized, in order to provide a reference for intensive study of the role of CYP450 enzymes in the synthesis of sesquiterpenoids.

Objective To analyze the clinical efficacy of non-inflatable transaxillary approach and transthoracic approach surgery for thyroid cancer,and analyze the occurrence of postoperative complications in patients.Methods The clinical data of 88 patients with thyroid cancer who underwent surgical treatment in our hospital from October 2019 to November 2022 were analyzed.They were divided into group A and B according to the surgical method.Forty-five patients in group A received complete endoscopic thyroidectomy through the non-inflatable axillary approach,while 43 patients in group B received endoscopic thyroidectomy through the thoracic approach.The perioperative indicators,satisfaction with surgical incision,postoperative pain,and incidence of complications of patients in the two groups were compared.And the main influence factors for the occurrence of complications were analyzed.Results The total satisfaction rate for surgical incision of patients in group A was significantly higher than that in group B(P<0.05);while the intraoperative bleeding volume and postoperative drainage volume of patients in group A were significantly lower than those in group B(P<0.05).The VAS score 3 and 5 days after surgery were significantly lower than that 1 day after surgery(P<0.05),and the VAS score 5 days after surgery was lower than that 3 days after surgery(P<0.05).The incidence of postoperative complications in group A was significantly lower than that in group B(P<0.05).Logistic regression results showed that intraoperative bleeding volume was the independent influencing factor for postoperative complications(P<0.05).Conclusion Both non-inflatable transaxillary approach and transthoracic approach surgery are effective for thyroid cancer,but the non-inflatable transaxillary approach surgery has the advantages of concealed incision,higher postoperative aesthetics,and less intraoperative bleeding volume,postoperative drainage volume and postoperative complications.Excessive intraoperative bleeding is the main factor leading to postoperative complications.

Objective To investigate the role and mechanism of NLRP3/Caspase-1/IL-1 β inflammasome pathway in the formation of aortic dissection in mice.Methods Fifty male C57BL/6 mice(3 weeks old,body weight 10～13 g)were divided into control group(n =10,normal diet),β-aminopropionitrile(BAPN)group[n =20,drink water containing 1 g/(kg·d)BAPN],and BAPN+MCC950 group[n=20,drink water containing 1 g/(kg·d)BAPN and intraperitoneal injection of 20 mg/(kg·d)NLRP3 inhibitor,MCC950]by random sampling.Water intake,body weight,incidence of aortic dissection and aortic dissection-related mortality were recorded.The inflammatory infiltration in the aorta was observed with HE staining,elastic fiber breakage was observed by elastic Van Gieson(EVG)staining,average fluorescence intensity of NLRP3,IL-1β,α-SMA and OPN was detected by immunofluorescence assay,and protein expression levels of NLRP3,Caspase-1,ASC,IL-1β,α-SMA and OPN were measured with Western blotting.Results No aortic dissection or death was observed in the control group.The BAPN group had an incidence of aortic dissection of 80％,aortic dissection-related mortality of 35％,and obvious broken elastic fibers and inflammatory infiltrate in the aortic wall,and increased expression levels of NLRP3,Caspase-1,ASC and IL-1 β,decreased contractile α-SMA and increased synthetic protein OPN when compared with the control group(P<0.05).While MCC950 treatment decreased the incidence of aortic dissection(80％vs 35％,P=0.004)and aortic dissection-related mortality(35％vs 15％,P=0.144),alleviated the broken elastic fibers and inflammatory infiltrate in the aortic wall,and down-regulated the expression of NLRP3,Caspase-1,ASC and IL-1β,enhanced contractile α-SMA and decreased the synthetic protein when compared with the BAPN group(P<0.05).Conclusion The occurrence of aortic dissection in mice is associated with activation of NLRP3/Caspase-1/IL-1 β inflammasome pathway.NLRP3 inhibitor,MCC950,can reduce the occurrence of aortic dissection and show a protective effect on blood vessels.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

Objective To observe the clinical efficacy of successive trigger needling combined with fire needling in the treatment of rheumatoid arthritis of cold-damp obstruction type.Methods A total of 72 patients with rheumatoid arthritis of cold-damp obstruction type were randomly divided into observation group and control group,36 cases in each group.The control group was treated with fire needling combined with ordinary acupuncture,and the observation group was treated with fire needling combined with filiform needle.The treatments were performed once every other day,3 times a week,2 weeks as a course of treatment,continuous treatment for 2 courses.After 4 weeks of treatment,the clinical efficacy of the two groups was evaluated.The changes of pain Visual Analogue Scale(VAS)score and Self-Rating Anxiety Scale(SAS)score before and after treatment,and the time of morning stiffness of the joints were observed in the two groups.The changes of the number of joint swelling and the number of joint tenderness were compared before and after treatment between the two groups.Results(1)After treatment,the time of morning stiffness of the joints of the two groups of patients was significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving morning stiffness of the joints,and the difference was statistically significant(P＜0.05).(2)After treatment,the number of swollen joints and the number of joint pressure and pain in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving swollen joints and joint pressure and pain,and the difference was statistically significant(P＜0.05).(3)After treatment,the VAS and SAS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the VAS and SAS scores,and the difference was statistically significant(P＜0.05).(4)The total effective rate of the observation group was 91.66%(33/36),while that of the control group was 77.78%(28/36).The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Successive trigger needling combined with fire needling treating rheumatoid arthritis of cold-damp obstruction type can significantly improve the clinical symptoms of patients,reduce their anxiety,and thus improve the quality of life of patients,with remarkable efficacy.

Objective To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts(RAGE)of astrocytes after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the effects of gastrodin(GAS)intervention on them.Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group,HIBD group and HIBD+GAS group(100 mg/kg),and the expressions of Al type astrocyte marker C3,A2 type astrocyte marker S100A10,RAGE,tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF),and insulin-like growth factor(IGF-1)in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group,oxygen glucose deprivation(OGD)group,OGD+GAS(0.34 mmol/L)group and GAS group,and then the protein expressions of RAGE,TNF-α,BDNF and IGF-1 were detected by Western blotting and immunofluorescence.Results In vivo,Western blotting showed that compared with the sham group,the protein expression levels of C3,S100A10,RAGE,TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group(P＜0.05),but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group(P＜0.05).Compared with the HIBD group,the C3,RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group(P＜0.05),and the protein expression levels of BDNF and IGF-1 further increased(P＜0.05).The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment(P＜0.05).The immunohistochemical staining results of C3,S100A10,and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results.Furthermore,the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes(P＜0.05).After GAS intervention,while the expressions of both RAGE and TNF-α decreased significantly(P＜0.05),the expressions of BDNF and IGF-1 increased significantly(P＜0.05).Conclusion With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors,gastrodin can promot the expressions of A2 astrocyte and nutritional factors,which play an important role in neuro-protective effect.

Objective To develop an intelligent horizontal rotating cell culture device with high modularity,easy operation,easy disinfection,low cost and high stability.Methods The cell culture device consisted of a rotating culture module,a dirve module,a control module and control software,with the shells of all the modules being manufactured by 3D printing.The rotating culture module was composed of a tubular electrospun scaffold,a cell culture chamber,a magnetic coupling rotor and polypropylene pipeline;the drive module was made up of a N20 reduction motor and a magnetic coupling rotor;the control module included an ESP-8266 chip and a printed circuit board;the control software was developed with Blinker IoT platform and C++language.The device was used to culture human intrahepatic bile duct epithelial cells to verify its effects.Results Light microscopy and scanning electron microscopy images showed that a uniform and continuous cell layer was formed on the surface of the tubular electrospun scaffold.Conclusion The intelligent horizontal rotating cell culture device achieves uniform growth of cells on the inner surface of tubular electrospun scaffolds,and can be used as an effective platform for cell culture on tubular scaffolds.[Chinese Medical Equipment Journal,2024,45(9):41-45]

Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.