Role of the tissue microenvironment as a therapeutic target in hepatocellular carcinoma

Hepatocellular carcinoma is difficult to treat,primarilybecause the underlying molecular mechanisms drivingclinical outcome are still poorly understood.Growingevidence suggests that the tissue microenvironmenthas a role in the biological behavior of the tumor.Themain clinical issue is to identify the best target fortherapeutic approaches.Here,we discuss the hypothesis that the entire tissue microenvironment might beconsidered as a biological target.However,the tissuemicroenvironment consists of several cellular and biochemical components,each of which displays a distinctbiological activity.We discuss the major components ofthis environment and consider how they may interactto promote tumor/host crosstalk.

Magnesium cationic cue enriched interfacial tissue microenvironment nurtures the osseointegration of gamma-irradiated allograft bone

Regardless of the advancement of synthetic bone substitutes,allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases.Nevertheless,the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure.Hence,improving osseointegration and transplantation efficiency remains important.The alteration of bone tissue microenvironment(TME)to facilitate osseointegration has been generally recognized.However,the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging.To address this concern,an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment.The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique.The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated.In the animal test,superior osseointegration between Mg-enriched graft and host bone was found,whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation.Furthermore,the bony in-growth appeared on magnesium-enriched allograft bone was significant higher.The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells.Lastly,our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.

Dynamic microenvironment and multiple damaged tissue regeneration in a de novo and synchronized manner

Regenerative medicine has rapidly developed over the past decade and created new opportunities to repair or replace tissue or organ function lost because of congenital defects, age, diseases, or serious damage （Cheng et al., 2016a; Cheng et al., 2016b）. Regenerative medicine strategies in- clude the transplantation of bioactive factors, stem cells, or biomaterials, even the induced regeneration in a de novo, depending on the application （Fu, 2014a; Huang and Fu, 2014）. However, there are several limitations to the use of regenerative medicine in the clinic with respect to using stem cells and biomaterials.

Antioxidant-enriched autologous biogel promoted diabetic wound healing by remodeling inherent posttraumatic inflammatory patterning and restoring compromised microenvironment homeostasis

Successful wound healing depends on the reconstruction of proper tissue homeostasis,particularly in the posttraumatic inflammatory tissue microenvironment.Diabetes jeopardizes tissues’immune homeostasis in cutaneous wounds,causing persistent chronic inflammation and cytokine dysfunction.Previously,we developed an autologous regeneration factor(ARF)technology to extract the cytokine composite from autologous tissue to restore immune homeostasis and promote wound healing.However,treatment efficacy was significantly compromised in diabetic conditions.Therefore,we proposed that a combination of melatonin and ARF,which is beneficial for proper immune homeostasis reconstruction,could be an effective treatment for diabetic wounds.Our research showed that the utilization of melatonin-mediated ARF biogel(AM gel)promoted diabetic wound regeneration at a more rapid healing rate.RNA-Seq analysis showed that AM gel treatment could restore more favorable immune tissue homeostasis with unique inflammatory patterning as a result of the diminished intensity of acute and chronic inflammation.Currently,AM gel could be a novel and promising therapeutic strategy for diabetic wounds in clinical practice through favorable immune homeostatic reconstructions in the tissue microenvironment and proper posttraumatic inflammation patterning.

Tissue-specific features of innate lymphoid cells in antiviral defense

Innate lymphocytes(ILCs)rapidly respond to and protect against invading pathogens and cancer.ILCs include natural killer(NK)cells,ILC1s,ILC2s,ILC3s,and lymphoid tissue inducer(LTi)cells and include type I,type II,and type III immune cells.While NK cells have been well recognized for their role in antiviral immunity,other ILC subtypes are emerging as players in antiviral defense.Each ILC subset has specialized functions that uniquely impact the antiviral immunity and health of the host depending on the tissue microenvironment.This review focuses on the specialized functions of each ILC subtype and their roles in antiviral immune responses across tissues.Several viruses within infection-prone tissues will be highlighted to provide an overview of the extent of the ILC immunity within tissues and emphasize common versus virus-specific responses.