Metastasis is a major contributor of death in cancer patients, and there is an urgent need for effective treatments of metastatic malignancies. Herein, ketoprofen (KP) and loxoprofen (LP) platinum(IV) complexes with antiproliferative and antimetastatic properties were designed and prepared by integrating chemotherapy and immunotherapy targeting cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), and programmed death ligand 1 (PD-L1), besides DNA. A mono-KP platinum(IV) complex with a cisplatin core is screened out as a candidate possessing potent anti-proliferative and anti-metastasis activities both in vitro and in vivo. It induces serious DNA damage and further leads to high expression of γ-H2AX and p53. Moreover, it promotes apoptosis of tumor cells through mitochondrial apoptotic pathway Bcl-2/Bax/caspase3. Then, COX-2, MMP-9, NLRP3, and caspase1 as pivotal enzymes igniting inflammation and metastasis are obviously inhibited. Notably, it significantly improves immune response through restraining the expression of PD-L1 to increase CD3 + and CD8 + T infiltrating cells in tumor tissues.
Summary
Interleukin‐35 (IL‐35) is a recently identified heterodimeric cytokine in the IL‐12 family. It consists of an IL‐12 subunit α chain (P35) and IL‐27 subunit Epstein–Barr virus‐induced gene 3 (EBI3) β chain. Unlike the other IL‐12 family members, it signals through four unconventional receptors: IL‐12Rβ2–IL‐27Rα, IL‐12Rβ2–IL‐12Rβ2, IL‐12Rβ2–GP130, and GP130–GP130. Interleukin‐35 signaling is mainly carried out through the signal transducer and activator of transcription family of proteins. It is secreted not only by regulatory T (Treg) cells, but also by CD8+ Treg cells, activated dendritic cells and regulatory B cells. It exhibits immunosuppressive functions distinct from those of other members of the IL‐12 family; these are mediated primarily by the inhibition of T helper type 17 cell differentiation and promotion of Treg cell proliferation. Interleukin‐35 plays a critical role in several immune‐associated diseases, such as autoimmune diseases and viral and bacterial infections, as well as in tumors. In this review, we summarize the structure and function of IL‐35, describe its role in immune‐related disorders, and discuss the mechanisms by which it regulates the development and progression of diseases, including inflammatory bowel disease, collagen‐induced arthritis, allergic airway disease, hepatitis, and tumors. The recent research on IL‐35, combined with improved techniques of studying receptors and signal transduction pathways, allows for consideration of IL‐35 as a novel immunotherapy target.
Many advanced cancers are characterized by metabolic disorders. A dietary therapeutic strategy was proposed to inhibit tumor growth through administration of low-carbohydrate, average-protein, and high-fat diet, which is also known as ketogenic diet (KD). In vivo antitumor efficacy of KD on transplanted CT26 + tumor cells in BALB/c mice was investigated. The results showed that the KD group had significantly higher blood β-hydroxybutyrate and lower blood glucose levels when compared with the normal diet group. Meanwhile, KD increased intratumor oxidative stress, and TUNEL staining showed KD-induced apoptosis against tumor cells. Interestingly, the distribution of CD16/32 + and iNOS + M1 tumor-associated macrophages (TAMs) increased in the KD-treated group, with concomitantly less arginase-1 + M2 TAMs. Moreover, KD treatment downregulated the protein expression of matrix metalloproteinase-9 in CT26 + tumor-bearing mice. Western blot analysis demonstrated that the expression levels of HDAC3/PKM2/NF-κB 65/p-Stat3 proteins were reduced in the KD-treated group. Taken together, our results indicated that KD can prevent the progression of colon tumor via inducing intratumor oxidative stress, inhibiting the expression of the MMP-9, and enhancing M2 to M1 TAM polarization. A novel potential mechanism was identified that KD can prevent the progression of colon cancer by regulating the expression of HDAC3/PKM2/NF-κB65/p-Stat3 axis.
Naproxen platinum(iv) hybrids display effective antitumor activities by inhibiting cycloxygenases and matrix metalloproteinases and by causing DNA damage.
Three-dimensional
honeycomb-like carbon network-encapsulated Fe/Fe3C/Fe3O4 composites are constructed via
a facile pyrolysis of ferrite nitrate–poly(vinyl pyrrolidone)
precursors. The nanostructures of the composites form in terms of
the iron catalysis in the pyrolysis process, which greatly depends
on the reaction temperature and contents of raw materials. The Fe/Fe3C/Fe3O4/C composite obtained at 700
°C possesses a high surface area, outstanding structural stability,
and fast electron/Li ion transportability. As the anode for lithium-ion
batteries, it displays a high specific capacity (1295 mAh g–1 at 0.2 A g–1), long cycling stability, and fast
kinetics (345 mAh g–1 after 500 cycles at 5 A g–1). Besides the nanostructures, the marriage of different
components also contributes to the superior electrochemical performance.
The integral carbon matrix supplies a fast electron/Li transportation
pathway. Fe/Fe3C acts as an electrocatalyst in the electrode,
which may bring extra capacity. The satisfied performance and facile
fabrication with low cost make it a competitive material in practical
applications.
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