Natural polymers are complex organic molecules that occur in the natural environment and have not been subjected to artificial synthesis. They are frequently encountered in various creatures, including mammals, plants, and microbes. The aforementioned polymers are commonly derived from renewable sources, possess a notable level of compatibility with living organisms, and have a limited adverse effect on the environment. As a result, they hold considerable significance in the development of sustainable and environmentally friendly goods. In recent times, there has been notable advancement in the investigation of the potential uses of natural polymers in the field of biomedicine, specifically in relation to natural biomaterials that exhibit antibacterial and antioxidant characteristics. This review provides a comprehensive overview of prevalent natural polymers utilized in the biomedical domain throughout the preceding two decades. In this paper, we present a comprehensive examination of the components and typical methods for the preparation of biomaterials based on natural polymers. Furthermore, we summarize the application of natural polymer materials in each stage of skin wound repair. Finally, we present key findings and insights into the limitations of current natural polymers and elucidate the prospects for their future development in this field.

Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects. Currently, the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene therapy. For this purpose, stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection, prolonged blood circulation, specific tumor accumulation, and controlled release profile of nucleic acid drugs. Besides, synergistic therapy could be achieved when combined with other therapeutic regimens. This review summarizes recent advances in various stimuli-responsive nanocarriers for gene delivery. Particularly, the nanocarriers responding to endogenous stimuli including pH, reactive oxygen species, glutathione, and enzyme, etc., and exogenous stimuli including light, thermo, ultrasound, magnetic field, etc., are introduced. Finally, the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well discussed. The major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable.

Background: Ischemia reperfusion injury (IRI) has been shown to increase the risk of tumor recurrence after liver surgery. Also, nonalcoholic fatty liver disease (NAFLD) is associated with increased HCC recurrence. ALOX12–12-HETE pathway is activated both in liver IRI and NASH. Also, ALOX12–12-HETE has been shown to mediate tumorigenesis and progression. Therefore, our study aims to investigate whether the ALOX12–12-HETE-GPR31 pathway involved in IRI induced HCC recurrence in NAFLD. Methods: HCC mouse model was used to mimic the HCC recurrence in NAFLD. Western Blot, qPCR, Elisa and Immunofluorescence analysis were conducted to evaluate the changes of multiple signaling pathways during HCC recurrence, including ALOX12–12-HETE axis, EMT, MMPs and PI3K/AKT/NF-κB signaling pathway. We also measured the expression and functional changes of GPR31 by siRNA. Results: ALOX12–12-HETE pathway was activated in liver IRI and its activation was further enhanced in NAFLD, which induced more severe HCC recurrence in fatty livers than normal livers. Inhibition of ALOX12–12-HETE by ML355 reduced the HCC recurrence in fatty livers. In vitro studies showed that 12-HETE increased the expression of GPR31 and induced epithelial-mesenchymal transition (EMT) and matrix metalloprotein (MMPs) by activating PI3K/AKT/NF-κB pathway. Furthermore, knockdown of GPR31 in cancer cells inhibited the HCC recurrence in NAFLD. Conclusions: ALOX12–12-HETE-GPR31 played an important role in HCC recurrence and might be a potential therapeutic target to reduce HCC recurrence after surgery in fatty livers.

Background: Hepatic ischemia-reperfusion injury (IRI) is considered as an effecting factor for hepatocellular carcinoma (HCC) recurrence. Th17/Treg cells are a pair of essential components in adaptive immune response in liver IRI, and forkhead box O1 (FOXO1) has the properties of maintaining the function and phenotype of immune cells. Herein, we illuminated the correlation and function between Th17/Treg cell balance and FOXO1 in IRI-induced HCC recurrence. Methods: RNA sequencing was performed on naive CD4+ T cells from normal and IRI model mice to identify relevant transcription factors. Western blotting, qRT-PCR, immunohistochemical staining, and flow cytometry were performed in IRI models to indicate the effect of FOXO1 on the polarization of Th17/Treg cells. Then, transwell assay of HCC cell migration and invasion, clone formation, wound healing assay, and Th17 cells adoptively transfer was utilized to assess the function of Th17 cells in IRI-induced HCC recurrence in vitro and in vivo. Results: Owning to the application of RNA sequencing, FOXO1 was screened and assumed to perform a significant function in hepatic IRI. The IRI model demonstrated that up-regulation of FOXO1 alleviated IR stress by attenuating inflammatory stress, maintaining microenvironment homeostasis, and reducing the polarization of Th17 cells. Mechanistically, Th17 cells accelerated IRI-induced HCC recurrence by shaping the hepatic pre-metastasis microenvironment, activating the EMT program, promoting cancer stemness and angiogenesis, while the upregulation of FOXO1 can stabilize the liver microenvironment homeostasis and alleviate the negative effects of Th17 cells. Moreover, the adoptive transfer of Th17 cells in vivo revealed its inducing function in IRI-induced HCC recurrence. Conclusions: These results indicated that FOXO1-Th17/Treg axis exerts a crucial role in IRI-mediated immunologic derangement and HCC recurrence, which could be a promising target for reducing the HCC recurrence after hepatectomy.