Asiatic acid induces ferroptosis of RA-FLS via the Nrf2/HMOX1 pathway to relieve inflammation in rheumatoid arthritis.

BACKGROUND: Ferroptosis is a distinct iron-dependent non-apoptotic type of programmed cell death that is implicated in the pathophysiology of rheumatoid arthritis (RA). Although asiatic acid (AA) is documented to have significant anti-inflammatory effects in various diseases, it is not known whether it can regulate RA via ferroptosis. METHODS: The effects of AA on rheumatoid arthritis fibroid-like synoviocytes (RA-FLS) were assessed in vitro, and a rat model of type II collagen-induced arthritis (CIA) was established to evaluate the effectiveness of AA treatment in vivo. RESULTS: AA significantly reduced both viability and colony formation in cultured RA-FLS, while increasing the levels of reactive oxygen species (ROS), ferrous iron (Fe2+), malondialdehyde (MDA), and lactate dehydrogenase (LDH), as well as the expression of COX2. Furthermore, AA induced ferroptosis in RA-FLS by promoting Fe2+ accumulation through downregulation of the expression of Keap1 and FTH1 and upregulation of Nrf2 and HMOX1. In vivo, AA treatment was found to reduce toe swelling and the arthritis score in CIA rats, as well as relieve inflammation and ankle damage and significantly upregulate the expression of Nrf2 and HMOX1 in the synovial fluid. CONCLUSION: Treatment with AA significantly reduced the viability of RA-FLS and triggered ferroptosis by promoting accumulation of Fe2+via the Nrf2-HMOX1 pathway, and was effective in relieving inflammation in CIA model rats. These findings suggest that the use of AA may be a promising strategy for the clinical treatment of RA.

The clinicopathological features, treatment outcomes and follow-up results of 47 ectopic thyroid gland cases: a single-center retrospective study.

Background: Ectopic thyroid gland (ETG) is an uncommon clinical condition, presenting various challenges and limitations in its regulate diagnosis and treatment currently. This study aims to enhance our understanding of ETG and improve the strategies for its diagnosis and treatment. Methods: The retrospective single-center study was conducted, encompassing clinical data from ETG patients screened at our institution between 2013 and 2022. Patients were categorized based on the location of the disease, and follow-ups were performed on each. Results: This study included a total of 47 patients who were confirmed to hav confirmed to have ETG. Among them, we found 29 cases of accessory thyroid and 18 cases of aberrant thyroid. Furthermore, 42 cases exhibited the single ETG, while 5 cases displayed the double ETG. The distribution of the ETG was as follows: 20 were lingual, 10 were submandibular, 10 were lateral cervical, 4 were thoracic mediastinal, 1 was esophageal, and 7 were ovarian. Of these cases, 22 patients underwent surgery, 18 received thyroid hormone replacement therapy, and 7 were placed under observation. All patients were followed up for 59.4 (12-117) months. No significant abnormalities were detected at the conclusion of the follow-up period. Conclusion: ETG is frequently observed in the head and neck, particularly in lingual. Accessory thyroid glands are commonly reported, with most cases being single ETG. Notably, these glands usually do not manifest specific clinical symptoms. Therefore, the appropriate and comprehensive examinations during the initial diagnosis are crucial to avoid misdiagnosis. Treatment should be individualized, and long-term follow-up is essential for managing ETG effectively.

Dual mode assay of glutathione with Tb-doped g-C3N4/MnO2 nanoconjugates as fluorescence probe and Mn as elemental target.

Glutathione (GSH) plays important roles in various physiological processes, thus highly sensitive assay of GSH and timely warning of its variation at trace level in complex biological matrixes is of great significance. However, this is challenging due to the coexisting reductive biomolecules and dynamic change of GSH levels in responding to various stimuli which remain largely unexploited. Herein, we report a dual mode protocol for the assay of GSH based on nanoconjugate g-C3N4:Tb/MnO2 between MnO2 nanosheets and terbium-doped g-C3N4 (g-C3N4:Tb) nanosheets. MnO2 moiety effectively quenches the emission at 546 nm from Tb3+ in the nanoconjugate, which is restored under the reduction of MnO2 by GSH to ensure fluorescence turn-on assay of GSH. Meanwhile, the generated Mn2+ facilitates inductively coupled plasma mass spectrometry (ICP-MS) detection to endow indirect highly sensitive assay of GSH. Fluorescence mode derived a limit of detection (LOD) of 0.17 µmol L-1 within a linear range of 0.5-160 µmol L-1, while ICP-MS resulted in a superior LOD of 0.016 µmol L-1 within 0.05-160 µmol L-1. Both detection modes provide excellent selectivity to GSH. The dual mode platform was validated by GSH assay in cell lysates. It was further demonstrated by monitoring the variation of dynamic change of GSH level under CuSO4 or cisplatin induced GSH consumption.

Dual-mode imaging of copper transporter 1 in HepG2 cells by hyphenating confocal laser scanning microscopy with laser ablation ICPMS.

Copper transporter 1 (CTR1) is a transport protein involved in copper and cisplatin uptake. The visualization of cellular CTR1 migration and its redistribution is highly important in copper/cisplatin exposure/transport. However, to the best of our knowledge, this is a highly challenging task. Herein, a dual-mode imaging strategy for CTR1 is developed by hyphenating confocal laser scanning microscopy (CLSM) and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) with a fluorescent/elemental bifunctional tag conjugated with anti-CTR1 antibody. The tag consists of rhodamine B and zirconium metal-organic frameworks (Zr-MOF) for CLSM fluorescence imaging and LA-ICPMS element imaging for a same group of HepG2 cells in a designated visual zone. This dual-mode imaging strategy facilitates visualization of CTR1 migration and meanwhile provides information of CTR1 redistribution in HepG2 cells by uptake of divalent copper or cisplatin. The present dual-mode imaging strategy provides in-depth information for the elucidation of CTR1 involved biological processes. Graphical abstract.

CuS@PDA-FA nanocomposites: a dual stimuli-responsive DOX delivery vehicle with ultrahigh loading level for synergistic photothermal-chemotherapies on breast cancer.

In this study, CuS@PDA nanoparticles were synthesized and used to create a novel tumor-targeting nanocomposite platform composed of copper sulfide@polydopamine-folic acid/doxorubicin (CuS@PDA-FA/DOX) for performing both photothermal and chemotherapeutic cancer treatment. The nanocomposite platform has ultrahigh loading levels (4.2 ± 0.2 mg mg-1) and a greater photothermal conversion efficiency (η = 42.7%) than CuS/PDA alone. The uptake of CuS@PDA-FA/DOX nanocomposites is much higher in MCF-7 cells than in A549 cells because MCF-7 cells have much higher folic acid receptors than A549. Under near infrared (NIR) irradiation, the CuS@PDA-FA/DOX system using a synergistic combination of photothermal therapy and chemotherapy yields a better therapeutic effect than either photothermal therapy or chemotherapy alone. The treatment is very effective with the cell viability is only 5.6 ± 1.4%.

Single cell analysis for elucidating cellular uptake and transport of cobalt curcumin complex with detection by time-resolved ICPMS.

It is of great importance to elucidate the fate of drugs, e.g., their cellular uptake, transport and metabolism/excretion at single cell level. In the present work, cellular uptake and excretion of curcumin in HepG2 and MCF-7 cells were investigated by measuring 59Co in a curcumin cobalt complex ([Co(tpa)(cur)](ClO4)2) with inductively coupled plasma mass spectrometry (ICPMS). The uptake and distribution pattern of the metal drug complex in single cells were thoroughly studied, demonstrating extremely large discrepancy of uptake behavior among individual cells. The complex concentration-dependent uptake and excretion behavior is observed for both HepG2 and MCF-7 cells. The uptake of ([Co(tpa)(cur)](ClO4)2) by HepG2 cells is firstly increased with the concentration of the complex followed by level-off at certain level. On the other hand, however, the uptake by MCF-7 cells increases exponentially with the complex concentration within a same concentration range. The present study provides important information on the transport process of the metal drug complex at single cell level, it may be promising for further applications in the elucidation of metal drug effectiveness in vivo.