Military Medical Research最新文献

Bone tissue relies on the intricate interplay between blood vessels and nerve fibers, both are essential for many physiological and pathological processes of the skeletal system. Blood vessels provide the necessary oxygen and nutrients to nerve and bone tissues, and remove metabolic waste. Concomitantly, nerve fibers precede blood vessels during growth, promote vascularization, and influence bone cells by secreting neurotransmitters to stimulate osteogenesis. Despite the critical roles of both components, current biomaterials generally focus on enhancing intraosseous blood vessel repair, while often neglecting the contribution of nerves. Understanding the distribution and main functions of blood vessels and nerve fibers in bone is crucial for developing effective biomaterials for bone tissue engineering. This review first explores the anatomy of intraosseous blood vessels and nerve fibers, highlighting their vital roles in bone embryonic development, metabolism, and repair. It covers innovative bone regeneration strategies directed at accelerating the intrabony neurovascular system over the past 10 years. The issues covered included material properties (stiffness, surface topography, pore structures, conductivity, and piezoelectricity) and acellular biological factors [neurotrophins, peptides, ribonucleic acids (RNAs), inorganic ions, and exosomes]. Major challenges encountered by neurovascularized materials during their clinical translation have also been highlighted. Furthermore, the review discusses future research directions and potential developments aimed at producing bone repair materials that more accurately mimic the natural healing processes of bone tissue. This review will serve as a valuable reference for researchers and clinicians in developing novel neurovascularized biomaterials and accelerating their translation into clinical practice. By bridging the gap between experimental research and practical application, these advancements have the potential to transform the treatment of bone defects and significantly improve the quality of life for patients with bone-related conditions.

Cancer recurrence, driven by the phenomenon of tumor dormancy, presents a formidable challenge in oncology. Dormant cancer cells have the ability to evade detection and treatment, leading to relapse. This review emphasizes the urgent need to comprehend tumor dormancy and its implications for cancer recurrence. Despite notable advancements, significant gaps remain in our understanding of the mechanisms underlying dormancy and the lack of reliable biomarkers for predicting relapse. This review provides a comprehensive analysis of the cellular, angiogenic, and immunological aspects of dormancy. It highlights the current therapeutic strategies targeting dormant cells, particularly combination therapies and immunotherapies, which hold promise in preventing relapse. By elucidating these mechanisms and proposing innovative research methodologies, this review aims to deepen our understanding of tumor dormancy, ultimately facilitating the development of more effective strategies for preventing cancer recurrence and improving patient outcomes.

Background: Radiofrequency ablation (RFA) is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality. Understanding the biological process related with RFA treatment is important for improving treatment strategy. This study aimed to identify the critical targets for regulating the efficacy of RFA.

Methods: The RFA treatment in hepatocellular carcinoma (HCC) tumor models in vivo, was analyzed by RNA sequencing technology. The heat treatment in vitro for HCC tumor cells was also constructed to explore the mechanism after RFA treatment in tumor cells. Nanoparticles with high affinity to tumor cells were applied as a new therapy to interfere with the expression of maternal embryonic leucine zipper kinase (MELK).

Results: It was found that RFA treatment upregulated MELK expression, and MELK inhibition promoted RFA efficacy by immunogenic cell death and the antitumor response, including anti-tumoral macrophage polarization and increased CD8⁺ T cell cytotoxicity in HCC. Mechanically, MELK binds to fatty acid-binding protein 5 (FABP5), and affects its ubiquitination through the K48R pathway to increase its stability, thereby activating protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling axis to weaken the RFA-mediated antitumor effect. In addition, the synthesis of arginylglycylaspartic acid (RGD)-lipid nanoparticles (LNPs) targeting tumor cell-intrinsic MELK enhanced RFA efficacy in HCC.

Conclusion: MELK is a therapeutic target by regulating RFA efficacy in HCC, and targeting MELK via RGD-LNPs provides new insight into improving RFA efficacy in HCC clinical treatment and combating the malignant progression of liver cancer.

Background: With the increasing risk of nuclear exposure, more attention has been paid to the prevention and treatment of acute radiation syndrome (ARS). Although amino acids are key nutrients involved in hematopoietic regulation, the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mechanisms have not been fully elucidated. Hence, it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms.

Methods: The content of serum amino acids was analyzed using metabolomic sequencing. The survival rate and body weight of the irradiated mice were detected after altering the methionine content in the diet. Extracellular matrix (ECM) protein analysis was performed via proteomics analysis. Inflammatory factors were examined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry, Western blotting, and immunofluorescence were employed to determine the mechanism by which S100 calcium-binding protein A4 (S100A4) regulates macrophage polarization.

Results: The survival time of irradiated mice was significantly associated with alterations in multiple amino acids, particularly methionine. A high methionine diet promoted irradiation tolerance, especially in the recovery of bone marrow hematopoiesis, yet with dose limitations. Folate metabolism could partially alleviate the dose bottleneck by reducing the accumulation of homocysteine. Mechanistically, high methionine levels maintained the abundance of ECM components, including collagens and glycoproteins, in the bone marrow post-irradiation, among which the level of S100A4 was significantly changed. S100A4 regulated macrophage polarization via the STAT3 pathway, inhibited bone marrow inflammation and facilitated the proliferation and differentiation of hematopoietic stem/progenitor cells.

Conclusions: We have demonstrated that an appropriate elevation in dietary methionine enhances irradiation tolerance in mice and explains the mechanism by which methionine regulates bone marrow hematopoiesis after irradiation.