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*

Objective To explore the anti-inflammatory mechanism of the active ingredients of Gubi Formula in treating osteoarthritis.Methods Normal human chondrocytes were cultured in vitro,and lipopolysaccharide(LPS)stimulated inflammation.The cells were divided into control group(normal culture),model group(10 μg·mL-1 LPS),quercetin group(10 μg·mL-1 LPS+8 μmol·L-1 quercetin),formononetin group(10 μg·mL-1 LPS+50 μmol·L-1 formononetin),naringin group(10 μg·mL-1 LPS+10 μmol·L-1 naringin),asperosaponin Ⅵ group(10 μg·mL-1 LPS+50 pmol·L-1 asperosaponin Ⅵ),β-ecdysterone group(10 μg·mL-1 LPS+50 μmol·L-1β-ecdysterone).Cell counting kit-8(CCK8)was used to detect the viability of chondrocytes.Western blot was used to detect the expression of nuclear factor NF-kappa-B p65 subunit(p65),nuclear factor erythroid 2-related factor 2(Nrf2)nuclear protein.Results The cell viability of control group,model group,quercetin group,formononetin group,naringin group,Dipsacoside Ⅵ group,β-ecdysterone group were(103.10±8.55)％,(62.41±2.35)％,(76.92±1.74)％,(77.01±0.60)％,(80.39±3.06)％,(79.43±0.94)％,(55.20±0.99)％;the relative expression of Nrf2 protein were 1.00±0.00,1.01±0.09,1.30±0.15,0.91±0.15,1.23±0.25,0.71±0.19,1.51±0.13,1.26±0.15;the relative expression of P65 protein were 1.00±0.00,2.24±0.85,0.74±0.33,1.49±0.29,0.97±0.06,1.33±0.07,1.67±0.22,1.52±0.17;the relative expression of inflammatory mediators iNOS were 1.00±0.00,1.52±0.27,1.07±0.24,1.25±0.12,1.01±0.30,1.44±0.12,1.07±0.18,1.11±0.16.The above indexes in quercetin group,formononetin group and naringin group were significantly different from those in model group(P＜0.05,P＜0.01 and P＜0.001).Compared with the model group,there was no significant difference in the above indexes between the Asperosaponin Ⅵ group and theβ-ecdysterone group(all P＞0.05).Conclusion The active components of Gubi Formula,including quercetin,mangiferin,and naringin,can activate Nrf2-HO-1 signaling and inhibit the activation of the Nuclear factor-κB(NF-κB)pathway plays an anti-inflammatory role in alleviating osteoarthritis.

At present, there is no cure for acquired immune deficiency syndrome (AIDS) due to HIV-1 latent reservoirs. Therefore, it urgently requires novel HIV-1 latency-regulating agents with high potency, low toxicity and favorable drug-like properties to achieve a functional cure for AIDS. Herein, we reviewed the advances in HIV-1 latency-regulating agents since 2019, including the drug discovery strategies, bioactivities, and mechanisms of these compounds. It is of great guiding significance in the development of latency-regulating agents with clinical value.

Objective To develop a portable collection device of human exhaled breath condensate(EBC)based on natural breathing to meet the needs for rapid screening of human respiratory tract(especially lower respiratory tract)infections.Methods The device consisted of a refrigeration unit,a heat dissipation unit and a condensation unit.The refrigeration unit adopted a TES1-7102 thermoelectric Peltier cooler semiconductor as the refrigeration element;the heat dissipation unit was composed of a high thermal conductivity aluminum heat sink and a high-speed brushless cooling fan;the condensation unit was made up of a cold guide plate and a condenser,in which the cold guide plate was made of thin sheet of aluminum alloy,and the condenser was prepared by 3D printing technology and made of hydrophobic polylactic acid,with primary and secondary 2-stage guide grooves and an ultra-thin condensing surface.The performance of the device was verified in terms of cooling,thermal conductivity,condensation and human EBC collection and content analysis.Results Performance analysis showed that after refrigeration began the temperature difference between the condenser surface and the exhaled gas met the requirements of the condenser,and no obvious thermal resistance was found on the condensing surface so that large droplets could be formed rapidly and then be collected after the gas-liquid phase change of the exhaled gas on the condensing surface.Human EBC collection and content analysis indicated the device realized home self-collection of EBCs from people of all ages,and the concentrations of interleukins,C-reactive protein and other inflammation-related indexes and the pH value of the collected EBC samples were all correlated with respiratory infections in the subjects.Conclusion The device developed with easy operation avoids the discomfort of blowing collection and the risk of saliva contamination,and is worthy promoting for rapid diagnosis and dynamic monitoring of respiratory tract infection and other related diseases.[Chinese Medical Equipment Journal,2024,45(8):32-37]

Pelvic acetabular fractures(PAFs)are one of the most common types of pelvic fractures,mostly high-energy injuries,with complex pelvic acetabular structure and limited surgical methods.The trauma of the acetabular fracture itself and the need for long-term bed rest after surgery cause particularly complicated clinical complications.Venous thromboembolism(VTE)is one of its high incidence and serious complications.This review mainly focuses on VTE after PAFs,and describes the epidemiology,risk factors and prevention measures of VTE,aiming to help improve the prognosis and avoid the occurrence of serious complications.

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.

Effectively assessing oxygen delivery and demand is one of the key targets for fluid resuscitation in sepsis. Clinical signs and symptoms, blood lactic acid levels, and mixed venous oxygen saturation (S O 2) or central venous oxygen saturation (ScvO 2) all have their limitations. In recent years, these limitations have been overcome through the use of derived indicators from carbon dioxide (CO 2) such as mixed veno-arterial carbon dioxide partial pressure difference (P -aCO 2, PCO 2 gap, or ΔPCO 2), the ratio of mixed veno-arterial carbon dioxide partial pressure difference to arterial-mixed venous oxygen content difference (P -aCO 2/Ca- O 2). P -aCO 2, PCO 2 gap or ΔPCO 2 is not a purely anaerobic metabolism indicator as it is influenced by oxygen consumption. However, it reliably indicates whether blood flow is sufficient to carry CO 2 from peripheral tissues to the lungs for clearance, thus reflecting the adequacy of cardiac output and metabolism. The P -aCO 2/Ca- O 2 may serve as a marker of hypoxia. S O 2 and ScvO 2 represent venous oxygen saturation, reflecting tissue oxygen utilization. When oxygen delivery decreases but tissues still require more oxygen, oxygen extraction rate usually increases to meet tissue demands, resulting in decreased S O 2 and ScvO 2. But in some cases, even if the oxygen delivery rate and tissue utilization rate of oxygen are reduced, it may still lead to a decrease in S O 2 and ScvO 2. Sepsis is a classic example where tissue oxygen utilization decreases due to factors such as microcirculatory dysfunction, even when oxygen delivery is sufficient, leading to decrease in S O 2 and ScvO 2. Additionally, the solubility of CO 2 in plasma is approximately 20 times that of oxygen. Therefore, during sepsis or septic shock, derived variables of CO 2 may serve as sensitive markers for monitoring tissue perfusion and microcirculatory hemodynamics. Its main advantage over blood lactic acid is its ability to rapidly change and provide real-time monitoring of tissue hypoxia. This review aims to demonstrate the principles of CO 2-derived variables in sepsis, assess the available techniques for evaluating CO 2-derived variables during the sepsis process, and discuss their clinical relevance.

Objective To investigate the effect of minocycline(Mino)on the polarization of types M1/M2 microglia(pro-and anti-inflammatory type)in the spinal dorsal horn of rats with neuropathic pain(NP)induced by spinal nerve ligation(SNL)and its underlying mechanism.Methods A total of 36 adult male SD rats were randomly stratified into Sham-operation(Sham)group,SNL group and Mino+SNL group by stratified random sampling based on body weight.Mechanical pain threshold and cold nociceptive thresholds of rat hind paw were measured in 1 d before and 14 d after modelling.Spinal cord tissue at the lumbar 5(L5)segment was taken at 14 d after modelling,and the total number of microglia as well as the numbers of M1 and M2 microglia in the spinal dorsal horn were measured with immunohistochemistry and stereology.With aid of bioinformatics techniques,the core target in the spinal cord,Cst7,was selected.Then,the protein levels of microglia marker Iba-1,M1 microglia marker iNOS,M2 microglia marker CD206,Cst7 encoded protein cystatin F(CF)and pathway CatS/CX3CL1/CX3CR1 were detected with Western blotting.The expression levels of TNF-α,IL-6 and IL-10 in the spinal cord tissues were measured with ELISA.Results The mechanical pain and cold nociceptive thresholds were both significantly higher in the M+SNL group than the SNL group at 7～14 d after modelling(P＜0.01).The total number of microglia and the numbers of M1/M2 microglia in the spinal dorsal horn as well as the expression levels of CatS,CX3CL1,CX3CR1,TNF-α,IL-6,and IL-10 in the spinal cord tissues were obviously increased,and the expression level of CF was notably decreased in the SNL model group than the Sham group(P＜0.01).While,Mino treatment remarkably reversed above phenomena,with decreased total number of microglia and number of M1 microglia as well as expression levels of CatS,CX3CL1,CX3CR1,TNF-α and IL-6,and increased number of M2 microglia as well as CF and IL-10 levels when compared with the SNL group(P＜0.05).Conclusion Mino alleviates SNL induced neuropathic pain,probably through up-regulating CF in the microglia,and thus inhibiting the CatS/CX3CL1/CX3CR1 signaling pathway,promoting the conversion of microglia from type M1 to M2 to balance the imbalance in the M1/M2 polarization,and thus reducing neuroinflammation.

Purpose::Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. Methods::The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group ( n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group ( n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. Results::In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) μm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) μm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels.Conclusions::NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.