Silencing of ZNF610 suppresses cell proliferation and migration in lung adenocarcinoma.

Zinc finger proteins (ZNFs) play a significant role in the initiation and progression of tumors. Nevertheless, the specific contribution of ZNF610 to lung adenocarcinoma (LUAD) remains poorly understood. This study sought is to elucidate the role of ZNF610 in LUAD. Transcript data of LUAD were obtained from The Cancer Genome Atlas Program (TCGA) database and processed via R program. The expression of ZNF610 was assessed in various cell lines. To compare the proliferative capacity of cells with or without ZNF610 silencing, CCK8, cell colony formation assay, and Celigo label-free cell counting assay were employed. Furthermore, transwell migration and invasion assays were conducted to evaluate the migratory and invasive abilities of the cells. The expression levels of genes and proteins were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot techniques. In different LUAD cells, the expression level of ZNF610 was found to be significantly higher in LUAD cells compared to MRC-5 and BASE-2B cells. Moreover, the silencing of ZNF610 resulted in a decrease in cell proliferation and migration abilities. Additionally, the apoptosis rate of cells increased upon silencing ZNF610. Notably, the proportion of cells in the G0/G1 phase increased, while the proportion of cells in the S phase decreased following ZNF610 silencing. Finally, ß-catenin and snail were identified as downstream targets of ZNF610 in cells. Our findings suggest that silencing ZNF610 could inhibit LUAD cell proliferation and migration, possibly through the downregulation of ß-catenin and snail.

Dual-targeting of tumor cells and subcellular endoplasmic reticulum via AgPPIX-based Janus nanoparticles for photodynamic/immunotherapy against TNBC.

Triple-negative breast cancer (TNBC) is known for its strong invasiveness, high recurrence rates, and poor prognosis. Heme oxygenase-1 (HO-1) is closely related to tumor invasion, metastasis, recurrence and formation of tumor immunosuppression. The expression of HO-1 is high in TNBC and low in normal tissues. In this study, AgPPIX was synthesized as a heme oxygenase-1 (HO-1) inhibitor and a photosensitizer for TNBC therapy. PDA nanoparticles were synthesized and modified with anti-CD24 and p-toluenesulfonamide (PTSC) on their both sides to obtain PTSC@AgPPIX/PDA@anti-CD24 Janus nanoparticles (PAPC) for AgPPIX-targeted delivery. Anti-CD24 is targeted to CD24 on tumor cells and the PTSC moiety is targeted to endoplasmic reticulum (ER), where HO-1 is located. The results indicated that PAPC Janus nanoparticles exhibited higher cytotoxicity in 4T1 cells than that of the mono-modified nanoparticles. PAPC not only inhibited the expression of HO-1 and VEGF but also reduced TrxR activity significantly. Furthermore, PAPC not only promoted intracellular ROS production under laser irradiation for tumor photodynamic therapy (PDT) but also polarized TAMs from M2-type to M1 for tumor immunotherapy. In vivo experiments confirmed that PAPC could remodel the tumor immune microenvironment and almost completely inhibit the tumor growth in mouse models. Therefore, PAPC Janus nanoparticles are a promising nanoplatform with a dual-targeting capacity for TNBC immune/PDT synergistic therapy.

Increased LOXL2 expression is related to poor prognosis in lung squamous cell carcinoma.

Background: The lysyl oxidate-like (LOXL) family was reported to be involved in the process of cancer development. However, the prognostic value of LOXL in lung cancer is unknown. We aimed to study the expression pattern and prognostic value of LOXL family members in lung squamous cell carcinoma (LUSC). Methods: The Wilcoxon test and logistic regression analysis were used to study the expression level of LOXLs and its correlation with clinical characteristics. The Kaplan-Meier method and Cox regression analysis were performed to estimate the correlation of LOXsL expression with the survival of LUSC patients. Receiver operator characteristic (ROC) curves were plotted, and areas under the curves (AUCs) were calculated to estimate the diagnostic and prognostic power of LOXL. Cell Counting Kit-8 (CCK-8) assays, wound healing assays and Transwell assays were used to estimate the impact of LOXL2 on LUSC cells. Results: LOXL1 and LOXL2 expression was upregulated in LUSC tissues (P<0.001). LOXL1 and LOXL2 showed high diagnostic power in LUSC patients, with AUCs of 0.784 and 0.751, respectively. Patients with high LOXL2 expression levels showed poor overall survival (OS) (P=0.019) and progression-free survival (PFS) (P=0.015). High LOXL2 expression was an independent prognostic factor for poor survival (P=0.026). Inhibition of LOXL2 suppressed proliferation, migration and invasion in LUSC cell lines. Conclusions: Increased LOXL2 was related to poor survival in LUSC. LOXL2 may be a potential prognostic biomarker and therapeutic target in LUSC.

Integrated Smart Gas Tracking Device with Artificially Tailored Selectivity for Real-Time Monitoring Food Freshness.

The real-time monitoring of food freshness in refrigerators is of significant importance in detecting potential food spoiling and preventing serious health issues. One method that is commonly reported and has received substantial attention is the discrimination of food freshness via the tracking of volatile molecules. Nevertheless, the ambient environment of low temperature (normally below 4 °C) and high humidity (90% R.H.), as well as poor selectivity in sensing gas species remain the challenge. In this research, an integrated smart gas-tracking device is designed and fabricated. By applying pump voltage on the yttria-stabilized zirconia (YSZ) membrane, the oxygen concentration in the testing chamber can be manually tailored. Due to the working principle of the sensor following the mixed potential behavior, distinct differences in sensitivity and selectivity are observed for the sensor that operated at different oxygen concentrations. Typically, the sensor gives satisfactory selectivity to H2S, NH3, and C2H5OH at the oxygen concentrations of 10%, 30%, and 40%, respectively. In addition, an acceptable response/recovery rate (within 24 s) is also confirmed. Finally, a refrigerator prototype that includes the smart gas sensor is built, and satisfactory performance in discriminating food freshness status of fresh or semi-fresh is verified for the proposed refrigerator prototype. In conclusion, these aforementioned promising results suggest that the proposed integrated smart gas sensor could be a potential candidate for alarming food spoilage.

Chondroitin Polymerizing Factor (CHPF) promotes cell proliferation and tumor growth in human osteosarcoma by inhibiting SKP2's ubiquitination while activating the AKT pathway.

Osteosarcoma is a common malignant tumor occurring in children and young adults. Chondroitin sulfate (CS) participates in cell adhesion, cell division, and the formation of neural networks in the body, the biosynthesis of which requires the participation of glycosyltransferases. CHPF, a glycosyltransferase, plays a role in the extension of CS. Recently, CHPF's biological roles and functional importance in human diseases including malignant tumors have been widely discussed. However, whether CHPF is involved in osteosarcoma development and growth has not been revealed. The present work aimed to investigate the expression levels, functional significance and molecular mechanism of CHPF in osteosarcoma progression. Our results revealed that CHPF is strongly expressed in osteosarcoma tissues and cells. Furthermore, CHPF serves as a tumor promoter in the development and progression of osteosarcoma through enhancing cell proliferation and migration while suppressing apoptosis. Exploration of the mechanism by which CHPF promotes osteosarcoma indicated that CHPF promotes osteosarcoma through counteracting SKP2's ubiquitination and activating the Akt signaling pathway. For the first time, we clarified the roles of CHPF in osteosarcoma, and our results suggested that CHPF might be a novel therapeutic target in the treatment strategies for osteosarcoma.

Type I Photosensitization with Strong Hydroxyl Radical Generation in NIR Dye Boosted by Vigorous Intramolecular Motions for Synergistic Therapy.

Development of type I photosensitizers (PSs) with strong hydroxyl radical (· OH) formation is particularly important in the anaerobic tumor treatment. On the other hand, it is challenging to obtain an efficient solid-state intramolecular motion to promote the development of molecular machine and molecular motor. However, the relationship between them is never revealed. In this work, a pyrazine-based near-infrared type I PS with remarkable donor-acceptor effect is developed. Notably, the intramolecular motions are almost maximized by the combination of intramolecular and intermolecular engineering to simultaneously introduce the unlimited bond stretching vibration and boost the group rotation. The photothermal conversion caused by the intramolecular motions is realized with efficiency as high as 86.8%. The D-A conformation of PS can also induce a very small singlet-triplet splitting of 0.07 eV, which is crucial to promote the intersystem crossing for the triplet sensitization. Interestingly, its photosensitization is closely related to the intramolecular motions, and a vigorous motion may give rise to a strong · OH generation. In view of its excellent photosensitization and photothermal behavior, the biocompatible PS exhibits a superior imaging-guided cancer synergistic therapy. This work stimulates the development of advanced PS for the biomedical application and solid-state intramolecular motions.

Local Corrosion Behaviors in the Coarse-Grained Heat-Affected Zone in a Newly Developed Zr-Ti-Al-RE Deoxidized High-Strength Low-Alloy Steel.

Oxide metallurgy technology can improve the microstructure of a coarse-grained heat-affected zone (CGHAZ) but introduces extra inclusions. Local corrosion behavior of the CGHAZ of a Zr-Ti-Al-RE deoxidized steel was investigated in this work using theoretical calculations and experimental verification. The modified inclusions have a (Zr-Mg-Al-Ca-RE)Ox core claded by a CaS and TiN shell. CaS dissolves first, followed by the oxide core, leaving TiN parts. This confirms that the addition of rare earth can reduce lattice distortion and prevent a galvanic couple between the inclusions and the matrix, while the chemical dissolution of CaS causes localized acidification, resulting in the pitting corrosion initiation.

[Comparison of Two-dimensional and Three-dimensional Features of Chest CT
 in the Diagnosis of Invasion of Pulmonary Ground Glass Nodules].

BACKGROUND: At present, more and more studies predict invasive adenocarcinoma (IAC) through three-dimensional features of pulmonary nodules, but few studies have confirmed that three-dimensional features have more advantages in diagnosing IAC than traditional two-dimensional features of pulmonary nodules. This study analyzed the differences of chest computed tomography (CT) features between IAC and minimally invasive adenocarcinoma (MIA) from three-dimensional and two-dimensional levels, and compared the ability of diagnosing IAC. The non-invasive adenocarcinoma group includes precursor glandular lesions (PGL) and minimally invasive adenocarcinoma (MIA). METHODS: The clinical data of 1,045 patients with ground glass opacity (GGO) from January to December 2019 were collected. Then the correlation between preoperative CT image characteristics and pathological results were analyzed retrospectively. The independent influencing factors for the identification of IAC were screened out according to two-dimensional and three-dimensional classification by multivariate Logistic regression and the cut-off point for the identification of IAC was found out through the receiver operating characteristic (ROC) curve. At last, the ability of diagnosing IAC was evaluated by Yoden index. RESULTS: The diameter of nodule, the diameter of solid component, the diameter of mediastinal window nodule in two-dimensional factors, and the volume of nodule, the volume of solid part and the average CT value in three-dimensional factors were independent risk factors for the diagnosis of IAC. These factors were arranged by Yoden index: solid partial volume (0.601)>nodule volume (0.536)>solid component diameter (0.525)>nodule diameter (0.518)>mediastinal window nodule diameter (0.488)>proportion of solid component volume (0.471)>1-tumor disappearance ratio (TDR) (0.468)>consolidation tumor ratio (CTR) (0.394)>average CT value (0.380). CONCLUSIONS: The CT features of three-dimensional are better than two-dimensional in the diagnosis of IAC, and the size of solid components is better than the overall size of nodules.

Dual-Responsive multifunctional "core-shell" magnetic nanoparticles promoting Fenton reaction for tumor ferroptosis therapy.

Ferroptosis is a newly found promising cell death pathway, which bypasses apoptosis and overcomes multidrug resistance of tumor. In this study, acid and redox dual-responsive multifunctional magnetic nanoparticles loading with Sorafenib (Sor), namely FMMHG/Sor, were prepared for tumor ferroptosis therapy. Fe3O4 nanoparticles as the core provided sufficient iron ion for ferroptosis and magnetic targeting. Mesoporous organosilica nanoparticles (MON) was coated on the outside of Fe3O4 to form "core-shell" structure, which contained the disulfidebond with redox-responsive. MnO2 was dropped on the surface of MON as gatekeeper, which was decomposed at low pH into O2 to promote drug release. Glucose oxidase (GOD) catalyzed glucose to produce H2O2, which reacted with iron ion to generate hydroxylradical (OH•) vie Fenton reaction. OH• inhibited GPX4 expression to induce ferroptosis with Sor as a synergistic inducer. Hyaluronic acid (HA) protected nanoparticles from removed by immune system and actively targeted to tumor cells. Overall, pH and redox dual-responsive FMMHG/Sor is a promising antitumor nanomedicine with magnetic targeting and active targeting for efficient tumor ferroptosis therapy.

Effect of Heat-Input on Microstructure and Toughness of CGHAZ in a High-Nb-Content Microalloyed HSLA Steel.

The effect of various heat inputs on the microstructure and impact toughness of the simulated coarse-grained heat-affected zone (CGHAS) of a niobium microalloyed (0.14 wt.%) low-carbon steel was studied. The results showed that higher impact toughness was achieved at a low heat input of 20 kJ/cm, which resulted from the formation of acicular ferrite laths/plates. They sectioned large prior austenite grains into many smaller regions, resulting in smaller crystallographic grains and high-angle grain boundaries. Conversely, when specimens were simulated with larger heat-inputs (100, 200 kJ/cm), the microstructure of the CGHAZ was predominantly composed of granular bainite plus massive MA constituents, thus impairing the impact toughness.

New adjustable modular hemipelvic prosthesis replacement with 3D-print osteotomy guide plate used in periacetabular malignant tumors: a retrospective case series.

BACKGROUND: Periacetabular malignant tumor seriously endangers the life and health of patients. Hemipelvic replacement provides a good method for patients who want complete resection of the tumor while retaining or restoring the function of the affected limb. OBJECTIVE: To investigate the performance and clinical application of the new adjustable modular hemipelvic prosthesis and to compare the effects of three kinds of hemipelvic prosthesis. METHODS: In this study, 23 patients, with an average age of 44.6 years (21-75 years), were collected, who received hemipelvic replacement with new adjustable, modular, and screw-rod system hemipelvic prosthesis. Preoperative preparation was conducted on them, and operative complications were recorded. Postoperative functional follow-up was performed regularly. RESULTS: The average operation time was 319 min (170-480 min), and the average blood loss was 2813 ml (1000 mL-8000 ml). The incidence of complications was 47.8%, and type A (wound-related complications) had the highest incidence (34.8%). Postoperative dislocation occurred in 3 cases (13.0%), and no dislocation occurred in the new adjustable modular hemipelvic prosthesis group. The average MSTS score of the patients was 18.6 (10-23), and the average Harris score was 73.7 (53-87). CONCLUSIONS: The new adjustable modular hemipelvic prosthesis has the feasibility of reconstruction and good functional outcome, making it ideal for periacetabular tumors. Furthermore, preoperative tumor-feeding artery embolization and abdominal aortic balloon implantation may be an effective choice to reduce intraoperative blood loss and facilitate the operation of tumor resection.

Multifunctional "ball-rod" Janus nanoparticles boosting Fenton reaction for ferroptosis therapy of non-small cell lung cancer.

Ferroptosis is a newly found cell death mechanism, which could bypass apoptosis and reverse multidrug resistance of tumors. However, efficient induction of tumor ferroptosis remains a challenge. In this study, multifunctional "ball-rod" Janus nanoparticles (FTG/L&SMD) were constructed for non-small cell lung cancer (NSCLC) ferroptosis treatment. Protected by tannic acid (TA), FTG/L&SMD maintains long-term function in blood circulation, while modification by 2, 3-dimethylmaleic anhydride (DMMA) confers the FTG/L&SMD with pH-responsive charge reversal. Glucose oxidase (GOD) on FTG/L&SMD catalyzes glucose to produce H2O2. Then, iron ion converts H2O2 to highly active hydroxyl radicals (OH•) via Fenton reaction, leading to lethal lipid peroxidation (LPO) accumulation. Meanwhile, TA reduces Fe3+ to Fe2+ to boost Fenton reaction cycle. Sor down-regulated glutathione peroxidase 4 (GPX4) expression in another pathway to induce ferroptosis synergistically. In vitro studies have shown that compared with sorafenib (Sor), FTG/L&SMD not only has more efficient tumor targeting and higher cytotoxicity, but also inhibits tumor migration. In vivo antitumor therapy experiments demonstrate that FTG/L&SMD inhibits tumor growth efficiently, and its toxicity is negligible. In general, FTG/L&SMD can initiate Fenton reaction cycle and reinforced ferroptosis to kill tumor cells, which is a promising anti-tumor nano-drug for NSCLC.

[Relationship between EGFR, ALK Gene Mutation and Imaging 
and Pathological Features in Invasive Lung Adenocarcinoma].

BACKGROUND: At present, the research progress of targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations in lung adenocarcinoma is very rapid, which brings new hope for the treatment of advanced lung adenocarcinoma patients. However, the specific imaging and pathological features of EGFR and ALK gene mutations in adenocarcinoma are still controversial. This study will further explore the correlation between EGFR, ALK gene mutations and imaging and pathological features in invasive lung adenocarcinoma. METHODS: A total of 525 patients with lung adenocarcinoma who underwent surgery in our center from January 2018 to December 2019 were included. According to the results of postoperative gene detection, the patients were divided into EGFR gene mutation group, ALK gene mutation group and wild group, and the EGFR gene mutation group was divided into exon 19 and exon 21 subtypes. The pathological features of the mutation group and wild group, such as histological subtype, lymph node metastasis, visceral pleural invasion (VPI) and imaging features such as tumor diameter, consolidation tumor ratio (CTR), lobulation sign, spiculation sign, pleural retraction sign, air bronchus sign and vacuole sign were analyzed by univariate analysis and multivariate Logistic regression analysis to explore whether the gene mutation group had specific manifestations. RESULTS: EGFR gene mutation group was common in women (OR=2.041, P=0.001), with more pleural traction sign (OR=1.506, P=0.042), and had little correlation with lymph node metastasis and VPI (P>0.05). Among them, exon 21 subtype was more common in older (OR=1.022, P=0.036), women (OR=2.010, P=0.007), and was associated with larger tumor diameter (OR=1.360, P=0.039) and pleural traction sign (OR=1.754, P=0.029). Exon 19 subtype was common in women (OR=2.230, P=0.009), with a high proportion of solid components (OR=1.589, P=0.047) and more lobulation sign (OR=2.762, P=0.026). ALK gene mutations were likely to occur in younger patients (OR=2.950, P=0.045), with somking history (OR=1.070, P=0.002), and there were more micropapillary components (OR=4.184, P=0.019) and VPI (OR=2.986, P=0.034) in pathology. CONCLUSIONS: The EGFR and ALK genes mutated adenocarcinomas have specific imaging and clinicopathological features, and the mutations in exon 19 or exon 21 subtype have different imaging features, which is of great significance in guiding the clinical diagnosis and treatment of pulmonary nodules.

Click Synthesis Enabled Sulfur Atom Strategy for Polymerization-Enhanced and Two-Photon Photosensitization.

Facile tailoring of photosensitizers (PSs) with advanced and synergetic properties is highly expected to broaden and deepen photodynamic therapy (PDT) applications. Herein, a catalyst-free thiol-yne click reaction was employed to develop the sulfur atom-based PSs by using the in situ formed sulfur "heavy atom effect" to enhance the intersystem crossing (ISC), while such an effect can be remarkably magnified by the polymerization. The introduction of a tetraphenylpyrazine-based aggregation-induced emission (AIE) unit was also advantageous in PS design by suppressing their non-radiative decay to facilitate the ISC in the aggregated state. Besides, the resulting sulfur atom electron donor, together with a double-bond π bridge and AIE electron acceptor, created a donor-π-acceptor (D-π-A) molecular system with good two-photon excitation properties. Combined with the high singlet oxygen generation efficiency, the fabricated polymer nanoparticles exhibited an excellent in vitro two-photon-excited PDT towards cancer cells, therefore possessing a huge potential for the deep-tissue disease therapy.

[Research Progress in 3D-reconstruction Based Imaging Analysis 
in Partial Solid Pulmonary Nodule].

The incidence and mortality of lung cancer rank first among all malignant tumors in China. With the popularization of high resolution computed tomography (CT) in clinic, chest CT has become an important means of clinical screening for early lung cancer and reducing the mortality of lung cancer. Imaging findings of early lung adenocarcinoma often show partial solid nodules with ground glass components. With the development of imaging, the relationship between the imaging features of some solid nodules and their prognosis has attracted more and more attention. At the same time, with the development of 3D-reconstruction technology, clinicians can improve the accuracy of diagnosis and treatment of such nodules.This article focuses on the traditional imaging analysis of partial solid nodules and the imaging analysis based on 3D reconstruction, and systematically expounds the advantages and disadvantages of both.
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Combination of nitrous oxide and the modified inflation-deflation method for identifying the intersegmental plane in segmentectomy: A randomized controlled trial.

BACKGROUND: During thoracoscopic segmentectomy, accurately and rapidly identifying the intersegmental plane (ISP) is of great importance. This study aimed to investigate the effect and safety of a nitrous oxide (N2 O)/oxygen (O2 ) inspired mixture on the appearance time of the ISP (TISP ) via the modified inflation-deflation method. METHODS: A total of 65 participants who underwent segmentectomy were randomized into three groups: 75% N2 O (n = 24), 50% N2 O (n = 23) or 0% N2 O (n = 18). The 75% N2 O group received a gas mixture of N2 O/O2 (Fio2 = 0.25), the 50% N2 O group received N2 O/O2 (Fio2 = 0.5), and the 0% N2 O group received 100% oxygen during lung expansion. The appearance time of satisfactory and ideal planes was recorded. Furthermore, arterial blood gas at breathing room air, one-lung ventilation (OLV) before lung expansion, 5 and 15 min after lung expansion were also recorded. RESULTS: TISP was significantly shorter in the 75% N2 O group (320.2 ± 65.9 s) compared with that of the 50% N2 O group (552.4 ± 88.9 s, p < 0.001) and the 0% N2 O group (968.3 ± 85.5 s, p < 0.001), while the 50% N2 O group was shorter than that of the 0% N2 O group (p < 0.001). Arterial oxygenation was significantly improved in the 0% N2 O group only after lung expansion, before which there were no differences in mean PaO2 values among groups. CONCLUSIONS: The use of N2 O in the inspired gas mixture during lung expansion is an applicable strategy to rapidly identify the ISP via the modified inflation-deflation method without any adverse effect on OLV related arterial oxygenation during segmentectomy.

Effect of Cisplatin Arterial Infusion (CAI) on Primary Nonmetastatic Pelvic Osteosarcoma: A Preliminary Study.

PURPOSE: The critical role of arterial infusion chemotherapy in the multimodal treatment of extremity bone cancer has been investigated extensively, but few studies have focused on pelvic osteosarcoma. Therefore, we attempted to evaluate the clinical significance of arterial infusion chemotherapy in the treatment of pelvic osteosarcoma. PATIENTS AND METHODS: We combined a cisplatin arterial infusion regimen with multidrug systematic chemotherapy as a neoadjuvant protocol for the treatment of pelvic osteosarcoma. The course number and dosage of cisplatin arterial infusion were adjusted to achieve a maximal tumor response evaluated by contrast-enhanced MRI per RECIST 1.1. Good responders received the same systematic combination for postoperative chemotherapy, and poor responders received second-line therapy. Twelve patients with nonmetastatic high-grade pelvic osteosarcoma were included. Survival, chemotherapy response and adverse events data were analyzed. RESULTS: The mean follow-up period was 56.1 months. Four patients died of refractory tumor progression, and 1 patient with local recurrence had no evidence of disease for 27 months after receiving secondary amputation and resection. Kaplan-Meier survival analysis demonstrated a 57.8% overall survival and 52.5% event-free survival rate at 5 years. Eight of 12 patients had a >90% tumor necrosis rate according to histopathologic examinations. The rates of local adverse events were lower than those reported for extremity osteosarcoma. CONCLUSION: Our study initially indicated that the cisplatin arterial infusion regimen was a potential therapy with good tolerance in the treatment of pelvic osteosarcoma.

Ferroptosis and its emerging role in tumor.

Ferroptosis is a novel form of programmed cell death characterized by iron-dependent lipid peroxidation accumulation. It is morphologically, biochemically, and genetically distinct from other known cell death, such as apoptosis, necrosis, and pyroptosis. Its regulatory mechanisms include iron metabolism, fatty acid metabolism, mitochondrial respiration, and antioxidative systems eliminating lipid peroxidation, such as glutathione synthesis, selenium-dependent glutathione peroxidase 4, and ubiquinone. The disruption of cellular redox systems causes damage to the cellular membrane leading to ferroptotic cell death. Recent studies have shown that numerous pathological diseases, like tumors, neurodegenerative disorders, and ischemia-reperfusion injury are associated with ferroptosis. As such, pharmacological regulation of ferroptosis either by activation or by suppression will provide a vast potential for treatments of relevant diseases. This review will discuss the advanced progress in ferroptosis and its regulatory mechanisms from both the antioxidative and oxidative sides. In addition, the roles of ferroptosis in various tumorigenesis, development, and therapeutic strategies will be addressed, particularly to chemotherapy and immunotherapy, as well as the discoveries from Traditional Chinese Medicine. This review will lead us to have a comprehensive understanding of the future exploration of ferroptosis and cancer therapy.

Tussilagone Inhibits Osteoclastogenesis and Periprosthetic Osteolysis by Suppressing the NF-κB and P38 MAPK Signaling Pathways.

BACKGROUND: Aseptic prosthetic loosening is one of the main factors causing poor prognosis of limb function after joint replacement and requires troublesome revisional surgery. It is featured by wear particle-induced periprosthetic osteolysis mediated by excessive osteoclasts activated in inflammatory cell context. Some natural compounds show antiosteoclast traits with high cost-efficiency and few side effects. Tussilagone (TUS), which is the main functional extract from Tussilago farfara generally used for relieving cough, asthma, and eliminating phlegm in traditional medicine has been proven to appease several RAW264.7-mediated inflammatory diseases via suppressing osteoclast-related signaling cascades. However, whether and how TUS can improve aseptic prosthetic loosening via modulating osteoclast-mediated bone resorption still needs to be answered. METHODS: We established a murine calvarial osteolysis model to detect the preventative effect of TUS on osteolysis in vivo. Micro-CT scanning and histomorphometric analysis were used to determine the variation of bone resorption and osteoclastogenesis. The anti-osteoclast-differentiation and anti-bone-resorption bioactivities of TUS in vitro were investigated using bone slice resorption pit evaluation, and interference caused by cytotoxicity of TUS was excluded according to the CCK-8 assay results. Quantitative polymerase chain reaction (qPCR) analysis was applied to prove the decreased expression of osteoclast-specific genes after TUS treatment. The inhibitory effect of TUS on NF-κB and p38 MAPK signaling pathways was testified by Western blot and NF-κB-linked luciferase reporter gene assay. RESULTS: TUS better protected bones against osteolysis in murine calvarial osteolysis model with reduced osteoclasts than those in the control group. In vitro studies also showed that TUS exerted antiosteoclastogenesis and anti-bone-resorption effects in both bone marrow macrophages (BMMs) and RAW264.7 cells, as evidenced by the decline of osteoclast-specific genes according to qPCR. Western blotting revealed that TUS treatment inhibited IκBα degradation and p38 phosphorylation. CONCLUSIONS: Collectively, our studies proved for the first time that TUS inhibits osteoclastogenesis by suppressing the NF-κB and p38 MAPK signaling pathways, therefore serving as a potential natural compound to treat periprosthetic osteolysis-induced aseptic prosthetic loosening.