Metastasis is a crucial hallmark of cancer progression, which involves numerous factors including the degradation of the extracellular matrix (ECM), the epithelial-to-mesenchymal transition (EMT), tumor angiogenesis, the development of an inflammatory tumor microenvironment, and defects in programmed cell death. Programmed cell death, such as apoptosis, autophagy, and necroptosis, plays crucial roles in metastatic processes. Malignant tumor cells must overcome these various forms of cell death to metastasize. This review summarizes the recent advances in the understanding of the mechanisms by which key regulators of apoptosis, autophagy, and necroptosis participate in cancer metastasis and discusses the crosstalk between apoptosis, autophagy, and necroptosis involved in the regulation of cancer metastasis.
25 August 2023 in Experimental and Therapeutic Medicine
Knee osteoarthritis (KOA) is a common chronic articular disease worldwide. It is also the most common form of OA and is characterized by high morbidity and disability rates. With the gradual increase in life expectancy and ageing population, KOA not only affects the quality of life of patients, but also poses a burden on global public health. OA is a disease of unknown etiology and complex pathogenesis. It commonly affects joints subjected to greater loads and higher levels of activity. The knee joint, which is the most complex joint of the human body and bears the greatest load among all joints, is therefore most susceptible to development of OA. KOA lesions may involve articular cartilage, synovium, joint capsule and periarticular muscles, causing irreversible articular damage. Factors such as mechanical overload, inflammation, metabolism, hormonal changes and ageing serve key roles in the acceleration of KOA progression. The clinical diagnosis of KOA is primarily based on combined analysis of symptoms, signs, imaging and laboratory examination results. At present, there is no cure for KOA and the currently available therapies primarily focus on symptomatic treatment and delay of disease progression. Knee replacement surgery is typically performed in patients with advanced disease. The current study presents a review of epidemiological characteristics, risk factors, histopathological manifestations, pathogenesis, diagnosis, treatment modalities and progress in KOA research.
Osteomyelitis remains a global challenge in the field of orthopedics. Even after standard debridement and antibiotic-assisted treatment, the long-term recurrence rate remains at 20%-30%. Given the dynamic changes in immune responses and defense mechanisms during bone infection, as well as the complex “race for the surface” involving bacterial adhesion and host cells (macrophages and tissue cells) on implant surfaces, biomaterials with immunomodulatory functions have attracted considerable attention. Macrophages, as crucial components of the immune system, participate in the inflammatory regulation and tissue remodeling of bone infections through highly plastic polarization mechanisms after bacterial invasion. The different microenvironmental characteristics and therapeutic needs at different stages of bone infection highlight the promising applications of biomaterials capable of macrophage polarization remodeling and sequential regulation. In this review, we provide a detailed discussion of the complex immune regulatory patterns in the bone infection microenvironment and the critical functions of macrophage polarization. We then explore how implant surface properties influence bacterial adhesion and macrophage function, highlighting the importance of achieving precise and dynamic regulation of macrophage polarization based on the Race for the Surface theory. Furthermore, we focus on recent advances, potential challenges, and opportunities in biomaterial-mediated macrophage polarization remodeling and sequential modulation strategies across different stages of osteomyelitis, aiming to offer insights that may accelerate the clinical translation of novel biomaterial-based macrophage immunotherapies.
Background: Osteosarcoma is the most common primary bone cancer occurring in young adults and the 5-year survival rate of patients with metastatic osteosarcoma is less than 30% due to high metastatic recurrence and drug resistance. Notch is a highly conserved cell to cell signaling pathway in evolution, and Jagged1 is an important ligand of Notch. Although some studies have found that Notch receptors and ligands including Jagged1 were highly expressed in osteosarcoma tissues and osteosarcoma cells, the role of Jagged1 in osteosarcoma progression and metastasis are still not clear. Methods: Tumor tissues were collected from 68 patients and immunohistochemical staining was employed to group these patients by expression of Jagged1. Real-time quantitative PCR and Western blotting were used to detect the expression of Jagged1. We used siRNA to knockdown the expression of Jagged1 in F5M2 cells. Colony formation assay and MTT were employed to detect and analyze the proliferation of F5M2 cells with or without knockdown of Jagged1. Transwell assay were used to detect the migration and invasion of F5M2 cells. Results: In this study, we found that the high expression of Jagged1 is closely related to the metastasis and recurrence of osteosarcoma in 68 clinical specimens. The expression of Jagged1 in F5M2 cells with high metastasis was significantly higher than that in F4 cells with low metastasis. Knockdown of Jagged1 led to lower ability of proliferation, migration, and invasion in F5M2 cells. Conclusion: The high expression of Jagged1 is closely related to the metastasis and recurrence of osteosarcoma. Knockdown of Jagged1 significantly reduced the proliferation, migration, and invasion of osteosarcoma cells. Our results suggested that knockdown of Jagged1 may be a potentially effective treatment for metastatic osteosarcoma.
Background: Exposure of the anterior or lateral lumbar via the retroperitoneal approach easily causes injuries to the lumbar plexus. Lumbar plexus injuries which occur during anterior or transpsoas lumbar spine exposure and placement of instruments have been reported. This study aims is to provide more anatomical data and surgical landmarks in operations concerning the lumbar plexus in order to prevent lumbar plexus injuries and to increase the possibility of safety in anterior approach lumbar surgery. Methods: To study the applied anatomy related to the lumbar plexus of fifteen formaldehyde-preserved cadavers, Five sets of Virtual Human (VH) data set were prepared and used in the study. Three-dimensional (3D) computerized reconstructions of the lumbar plexus and their adjacent structures were conducted from the VH female data set. Results: The order of lumbar nerves is regular. From the anterior view, lumbar plexus nerves are arranged from medial at L5 to lateral at L2. From the lateral view, lumbar nerves are arranged from ventral at L2 to dorsal at L5. The angle of each nerve root exiting outward to the corresponding intervertebral foramen increases from L1 to L5. The lumbar plexus nerves are observed to be in close contact with transverse processes (TP). All parts of the lumbar plexus were located by sectional anatomy in the dorsal third of the psoas muscle. Thus, access to the psoas major muscle at the ventral 2/3 region can safely prevent nerve injuries. 3D reconstruction of the lumbar plexus based on VCH data can clearly show the relationships between the lumbar plexus and the blood vessels, vertebral body, kidney, and psoas muscle. Conclusion: The psoas muscle can be considered as a surgical landmark since incision at the ventral 2/3 of the region can prevent lumbar plexus injuries for procedures requiring exposure of the lateral anterior of the lumbar. The transverse process can be considered as a landmark and reference in surgical operations by its relative position to the lumbar plexus. 3D reconstructions of the lumbar plexus based on VCH data provide a virtual morphological basis for anterior lumbar surgery.