Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism

Oral potentially malignant disorders(OPMDs)are precursors of oral squamous cell carcinoma(OSCC).Deregulated cellular energy metabolism is a critical hallmark of cancer cells.Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC1α)plays vital role in mitochondrial energy metabolism.However,the molecular mechanism of PGC1αon OPMDs progression is less unclear.Therefore,we investigated the effects of knockdown PGC1αon human dysplastic oral keratinocytes(DOKs)comprehensively,including cell proliferation,cell cycle,apoptosis,xenograft tumor,mitochondrial DNA(mtDNA),mitochondrial electron transport chain complexes(ETC),reactive oxygen species(ROS),oxygen consumption rate(OCR),extracellular acidification rate(ECAR),and glucose uptake.We found that knockdown PGC1αsignificantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo,induced S-phase arrest,and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis.Mechanistically,downregulated of PGC1αdecreased mtDNA,ETC,and OCR,while enhancing ROS,glucose uptake,ECAR,and glycolysis by regulating lactate dehydrogenase A(LDHA).Moreover,SR18292(an inhibitor of PGC1α)induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression.Thus,our work suggests that PGC1αplays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism,acting as a potential therapeutic target for OPMDs.

Review of a new bone tumor therapy strategy based on bifunctional biomaterials

Bone tumors,especially those in osteosarcoma,usually occur in adolescents.The standard clinical treatment includes chemotherapy,surgical therapy,and radiation therapy.Unfortunately,surgical resection often fails to completely remove the tumor,which is the main cause of postoperative recurrence and metastasis,resulting in a high mortality rate.Moreover,bone tumors often invade large areas of bone,which cannot repair itself,and causes a serious effect on the quality of life of patients.Thus,bone tumor therapy and bone regeneration are challenging in the clinic.Herein,this review presents the recent developments in bifunctional biomaterials to achieve a new strategy for bone tumor therapy.The selected bifunctional materials include 3D-printed scaffolds,nano/microparticle-containing scaffolds,hydrogels,and bone-targeting nanomaterials.Numerous related studies on bifunctional biomaterials combining tumor photothermal therapy with enhanced bone regeneration were reviewed.Finally,a perspective on the future development of biomaterials for tumor therapy and bone tissue engineering is discussed.This review will provide a useful reference for bone tumor-related disease and the field of complex diseases to combine tumor therapy and tissue engineering.

The design,mechanism and biomedical application of self-healing hydrogels

Hydrogels are promising materials with outstanding characteristics such as tunable and reversible physical/chemical properties,stimuli-responsiveness,biomimetic,and biocompatibility.However,the structural and functional integrity of the hydrogels can be compromised by external mechanical forces or chemical erosion when used,especially in sophisticated in vivo environment.To address this problem,self-healing hydrogels which possess the intrinsic ability of self-repair have been developed to adapt to destructive factors.In this review,we focused on the current advances made in self-healing hydrogels.First,the testing methods for self-healing hydrogels were summarized.Then,we looked into the designing strategies of self-healing hydrogels and illustrated the self-healing mechanism.What＇s more,the biomedical application of self-healing hydrogels in vivo was discussed.