Pyropia haitanensis polysaccharide extends lifespan by inhibiting protein aggregation in Caenorhabditis elegans

Pyropia haitanensis polysaccharide(LP)have been found for having many excellent functions such as anti-aging.Using Caenorhabditis elegans models,we evaluated the anti-aging activity of LP by observing the lifespan,reproduction,pharyngeal pumping,stress response,quantitative fluorescence of polyglutamic acid,and nuclear localization of DAF-16 of worms.The results reveal that LP could extend the adult lifespan of wild-type and polyQ nematodes,indicating a connection of its anti-aging benefit with the toxicity-suppressing effect.The number of polyglutamic acid aggregates in high concentration groups decreased by 24.39%(P<0.05)to the control.The high-dose group strongly induced DAF-16 nuclear translocation over intermediate and cytosolic localizations compared with the control(P<0.001).Therefore,we believe that LP could extend the lifespan and reduce the protein aggregation in C.elegans through nuclear DAF-16∷GFP expression.

Fucoidan sulfate from Sargassum fusiforme regulates the SARS-CoV-2 receptor AXL expression in human embryonic lung diploid fibroblast cells

Coronavirus disease 2019(COVID-19)is a global infectious disease that seriously endangers human life and health and affects normal social activities.Since the pandemic outbreak from December 2019 to February 2023,the total number of confirmed cases has exceeded 753 million,and the deaths caused by COVID-19 have reached 6.6 million(https://covid19.who.int;accessed on Feb.16,2023).

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5

Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed.Here we identified berberine(BBR),a proven anti-inflammation drug,as a negative regulator of PDL1 from a set of traditional Chinese medicine(TCM)chemical monomers.BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells.In addition,BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumorinfiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells(MDSCs)and regulatory T-cells(Tregs).BBR triggered PD-L1 degradation through ubiquitin(Ub)/proteasome-dependent pathway.Remarkably,BBR selectively bound to the glutamic acid76 of constitutive photomorphogenic-9 signalosome 5(CSN5)and inhibited PD-1/PD-L1 axis through its deubiquitination activity,resulting in ubiquitination and degradation of PD-L1.Our data reveals a previously unrecognized antitumor mechanism of BBR,suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.

DZNep inhibits the proliferation of colon cancer HCT116 cells by inducing senescence and apoptosis

EZH2 is over-expressed in human colon cancer and is closely associated with tumor proliferation,metastasis and poor prognosis.Targeting and inhibiting EZH2 may be an effective therapeutic strategy for colon cancer.3-Deazaneplanocin A(DZNep),as an EZH2 inhibitor,can suppress cancer cell growth.However,the anti-cancer role of DZNep in colon cancer cells has been rarely studied.In this study,we demonstrate that DZNep can inhibit the growth and survival of colon cancer HCT116 cells by inducing cellular senescence and apoptosis.The study provides a novel view of anti-cancer mechanisms of DZNep in human colon cancer cells.

Tubeimoside-1 induces TFEB-dependent lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting mTOR

Programmed cell death ligand 1(PD-L1)/programmed cell death protein 1(PD-1)cascade is an effective therapeutic target for immune checkpoint blockade(ICB)therapy.Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity.Using flow cytometry-based assay,we identify tubeimoside-1(TBM-1)as a promising antitumor immune modulator that negatively regulates PD-L1 level.TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1.Furthermore,TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma(LLC)and B16 melanoma tumor xenograft via activating tumor-infiltrating T-cell immunity.Mechanistically,TBM-1 triggers PD-L1 lysosomal degradation in a TFEB-dependent,autophagy-independent pathway.TBM-1 selectively binds to the mammalian target of rapamycin(m TOR)kinase and suppresses the activation of m TORC1,leading to the nuclear translocation of TFEB and lysosome biogenesis.Moreover,the combination of TBM-1 and anti-CTLA-4 effectively enhances antitumor T-cell immunity and reduces immunosuppressive infiltration of myeloid-derived suppressor cells(MDSCs)and regulatory T(Treg)cells.Our findings reveal a previously unrecognized antitumor mechanism of TBM-1 and represent an alternative ICB therapeutic strategy to enhance the efficacy of cancer immunotherapy.

BSA stabilized photothermal-fenton reactor with cisplatin for chemo/chemodynamic cascade oncotherapy

Cisplatin(CDDP)-based chemotherapy is substantially limited in the clinic due to its high postoperative recurrence rate.Synergy therapy has been proven as a potent approach to minimize recurrence and achieve enhanced treatment effects.Herein,chemotherapy drug CDDP is assembled with the photothermal-Fenton agent of bovine serum albumin(BSA)stabilized gallic acid-functionalized iron nanoparticles(GA-Fe NPs)to achieve chemo/chemodynamic synergistic cascade oncotherapy.The Pt-GA-Fe NPs can be utilized to generate H_(2)O_(2) via the activation of nicotinamide adenine dinucleotide phosphate(NADPH)oxidases(NOXs)in the tumor microenvironment(TME),which would then greatly boost H2O2-depending chemodynamic therapy(CDT).The generated cytotoxic reactive oxygen species(hydroxyl radicals,·OH)and the depletion of glutathione(GSH)would further promote CDDP-induced DNA damage.Moreover,benefiting from the absorption in the near-infrared(NIR)region,Pt-GA-Fe NPs exhibit excellent photothermal conversion efficiency(η=45.5%)and allow photoacoustic imaging(PAI)guided photothermal therapy(PTT).In vitro and in vivo experiments show that synergy therapy can effectively kill cancer cells and successfully cure cancer without systemic toxicity.The work highlights a new type of therapeutic agent based on CDDP with the ability of H_(2)O_(2) self-generation,thermal responsiveness,and enhanced CDT effects for applications in cancer therapy.