Camellia formosensis is the only endemic Camellia species in Taiwan with established commercial cultivation. Despite its ecological importance and cultural prominence, the phytochemical composition and pharmacological properties of this species remain largely uncharacterized. This study fills this knowledge gap through systematic phytochemical investigation and comprehensive bioactivity profiling. Systematic phytochemical investigation of C. formosensis afforded ten structurally novel triterpenoids, cameterpenes A-J (1-10), together with eight known compounds (11-18). Notably, four of these new compounds (1-4) feature an unprecedented rearranged skeleton incorporating a seven-membered ring. X-ray crystallographic analysis (Cu Kα) provided conclusive evidence for the absolute configuration of 1, 7, and 9. ECD analysis supported the assignment of the absolute configurations of 2-4. A plausible biosynthetic pathway for compounds 1-4 is proposed, involving oxidative ring-opening followed by recyclization. Comprehensive bioactivity screening revealed structure-dependent pharmacological activities. Among the oleanane-type triterpenoids (12-14), 12 showed the strongest antiproliferative activity against Ca9-22 oral cancer cells (IC50: 20.11 ± 0.95 µg mL-1), 13 demonstrated potent anti-inflammatory activity by suppressing superoxide anion generation in fMLP/CB-stimulated human neutrophils (IC50: 3.40 ± 1.19 µM), and 14 exhibited exceptional inhibition of RANKL-induced osteoclast differentiation (IC50: 18.6 nM) without cytotoxicity. Lupane-type triterpenoid 16 exhibited comparable anti-osteoclastogenic activity (IC50: 27.4 nM) without cytotoxicity. These activities collectively target the interconnected processes of oxidative stress and inflammation underlying bone loss, chronic inflammatory conditions, and cancer progression. The active triterpenoids offer integrated therapeutic potential against inflammation-driven pathologies. Overall, this study establishes C. formosensis as a promising source for the development of multifunctional pharmaceuticals and nutraceuticals targeting inflammation-mediated diseases.
This journal is © The Royal Society of Chemistry.

In rheumatoid arthritis (RA), regulatory T cells (Tregs) within the synovium present a paradox: they are numerically enriched yet functionally impaired, leading to a loss of immune tolerance. Here, we report that synovial iron overload establishes a ferroptosis-permissive microenvironment that disrupts Treg homeostasis. Exposure to RA synovial fluid induced ferroptosis, autoimmune Treg-associated metabolic shifts through lipid peroxide-driven mitochondrial dysfunction, characterized by electron transport chain (ETC) collapse and impaired oxidative phosphorylation. Mechanistically, metabolic disturbance by ferroptotic stress or complex III blockade triggered TXK kinase upregulation, which is required for the phosphorylation of STAT3 (Tyr705) and PLCγ1 (Tyr783), activating a proinflammatory transcriptional program that destabilized Treg identity and promoted Th17-like conversion. Crucially, this pathogenic reprogramming was reversed through iron chelation or TXK inhibition in vitro and in vivo. Our findings unveil a ferroptosis-ETC-TXK/STAT3 axis as a core mechanism of synovial Treg failure. Targeting synovial iron homeostasis or inhibiting TXK signaling thus represents a promising therapeutic strategy to restore immune tolerance in RA by rescuing Treg functionality.
© 2026 The Author(s). Advanced Science published by Wiley‐VCH GmbH.

Omics' technologies have enabled clinicians to gain previously unprecedented insights into the molecular complexity and clinical heterogeneity of triple-negative breast cancer (TNBC). Increasingly it is being realized that TNBC does not respond well to current targeted therapies. This study aims to explore the antiproliferative effects and cancer regulatory mechanisms which underlie the drug resistance and aggressiveness of TNBC cells. Cryptocaryone (CPC) derived from Cryptocarya concinna demonstrated antiproliferative responses to TNBC cells (HCC1937 and MDA-MB-231), while normal breast cells (H184B5F5/M10) exhibited low cytotoxicity. In an in vivo assessment, CPC effectively reduced tumor growth in the MDA-MB-231 xenografted mouse model without significantly affecting body weight. Mechanistically, CPC triggered apoptosis, as indicated by an increase in sub-G1 and annexin V, as well as activated caspase 3 and 8. CPC also induced substantial oxidative stress by generating reactive oxygen species, mitochondrial superoxide, and membrane depolarization. CPC also induced oxidative DNA damage, as evidenced by the presence of γH2AX and 8-hydroxy-2-deoxyguanosine, in TNBC cells. All these CPC-induced changes were more pronounced in TNBC cells than normal cells. JNK and p38 MAPK inhibitors attenuate CPC-induced antiproliferation in TNBC cells. CPC upregulates phosphorylated JNK and p38 in TNBC cells. N-acetylcysteine pretreatment confirmed that oxidative stress plays a vital role in enhancing the antiproliferation, apoptosis, and DNA damage in TNBC cells. Moreover, the CPC-upregulated apoptosis and caspase 3/8 activations in TNBC cells were inhibited by JNK and p38 inhibitors. The impact of ERK activation on antiproliferation and apoptosis was evident in MDA-MB-231 cells, but not in HCC1937 cells. In conclusion, CPC demonstrated antiproliferative effects on TNBC cells through apoptosis and DNA damage induced by oxidative stress and MAPK activation, while showing drug safety in normal cells and breast cancer mouse model.
© 2026 The Author(s). Drug Development Research published by Wiley Periodicals LLC.

Inflammation drives early recurrent cardiovascular risk in type 2 diabetes mellitus (T2DM) patients following acute myocardial infarction (AMI), particularly within 30-90 days post-discharge. Sodium-glucose co-transporter 2 (SGLT2) inhibitors such as empagliflozin (EMPA) provide cardiometabolic benefits, but their anti-inflammatory effects and optimal timing after AMI remain unclear. Given the prognostic role of systemic markers like the neutrophil-to-lymphocyte ratio, we investigated whether early initiation of EMPA modulates NOD-like receptor protein-3 (NLRP3) inflammasome activity and inflammatory responses in monocyte-derived macrophages (MDMs) from T2DM-AMI patients.
Sixty-six participants were randomised to receive EMPA either at discharge (Arm-A) or following a 90-day delay (Arm B). Clinical data and biological samples were collected over 180 days. CD14+ MDMs and plasma were obtained at days 0, 30, and 90 (EMPA vs. no EMPA), and days 90, 120, and 180 (early vs. delayed). Inflammatory and metabolic markers were assessed using RT-qPCR, luminescence-based caspase-1 and ATP assays, and targeted immunoassays.
Early EMPA administration was associated with reduced NLRP3 priming (IL1β mRNA) and activation (caspase-1 activity), potentially linked to decreased release of ATP, a danger associated molecular pattern (DAMP). In the absence of EMPA, pro-inflammatory cytokines (TNFα, IL6, MCP1) and M1 macrophage markers (e.g., CD80) either increased or remained unchanged over time. Early EMPA treatment appeared to stabilise or reduce their expression. Markers of cell senescence (p21, IL8, BCL2) were also modulated. Plasma levels of senescence-associated markers (MMP9, OPN, Serpin E1) remained largely unchanged, highlighting the importance of evaluating macrophage-specific responses.
Early empagliflozin administration in T2DM-AMI patients was associated with modulation of NLRP3-related inflammatory and senescence pathways in patient-derived macrophages, benefits observed when cells were stimulated ex-vivo with an inflammatory stimulus. These findings provide mechanistic insight into the timing-dependent anti-inflammatory effects of EMPA and underscore its potential for immediate post-AMI use to reduce inflammation and lower residual cardiovascular risk, supporting further clinical investigation.
© 2026. The Author(s).

The results of a Phase 1 trial of autologous mitochondrial transplantation for the treatment of acute ischemic stroke during mechanical thrombectomy are presented. Standardized methods were used to isolate viable autologous mitochondria in the acute clinical setting, allowing for timely transplantation within the ischemic window. No significant adverse events were observed with the endovascular approach during reperfusion therapy. Safety outcomes in study participants were comparable to those of matched controls who did not undergo transplantation. This study represents the first use of mitochondrial transplantation in the human brain, highlighting specific logistical challenges related to the acute clinical setting, such as limited tissue samples and constrained time for isolation and transplantation. We also review the opportunities and challenges associated with further clinical translation of mitochondrial transplantation in the context of acute cerebral ischemia and beyond.