He Zhang’s research while affiliated with Shanghai University of Traditional Chinese Medicine and other places

B7 homolog 3 (B7-H3, also known as CD276) is a novel member of the B7 immune protein family. There is a marked difference in the expression and distribution of B7-H3 protein and mRNA between normal and tumor tissues, with widespread expression in tumor tissues and a close relationship with tumor progression. B7-H3 activates or inhibits tumor immune responses by binding to receptors on the surface of immune cells. Apart from participating in tumor immune activities, it has regulatory effects on non-immunological functions, such as tumor migration and invasion, angiogenesis, glycometabolism, and drug resistance. Thus, it has important biological functions in regulating the progression of malignant tumors. Current research on the structure, function, and therapeutic methods of B7-H3 is continuously breaking new ground, deepening our understanding of B7-H3, and promoting the development of therapeutic drugs targeting this new protein. This review briefly discusses the structure and distribution of B7-H3, as well as its immune and non-immune functions in the progression of cancer. It also summarizes the research progress on drugs targeting B7-H3 and the latest developments in clinical trials, highlighting their significant potential for the treatment of malignant tumors.

Preoperative neoadjuvant therapy is crucial for large malignant tumors or tumors that are challenging to resect. Consequently, an objective assessment of its therapeutic efficacy is important. Currently, the conventional evaluation methods for neoadjuvant therapy of tumors are mainly divided into two categories: imaging-based and pathological evaluations. In imaging-based evaluation, the World Health Organization criteria are straightforward; however, they exhibit some issues such as unclear criteria for minimum lesions and measurement errors. Moreover, although the Response Evaluation Criteria In Solid Tumors criteria have been improved, they remain insensitive to internal tumor changes and are prone to measurement errors. The Modified Response Evaluation Criteria In Solid Tumors criteria are specifically designed for hepatocellular carcinoma, yet they have limitations, such as difficulty defining complex tumor boundaries. The Positron Emission Tomography Response Criteria in Solid Tumors criteria, which integrate positron emission tomography/computed tomography, offer high accuracy but are influenced by factors related to the patient’s body condition and equipment. The Choi criteria, which comprehensively consider tumor size and density, can be used to evaluate the efficacy of targeted therapy; however, they are characterized by cumbersome measurement procedures and strong subjectivity. In terms of pathological evaluation, the Huvos score determines the therapeutic effect based on the degree of tumor necrosis, which can guide subsequent treatment and prognosis. However, the evaluation time is fixed and subject to interference from pathological procedures. The Miller–Payne criteria focus on changes in the number and density of tumor cells and provide a reference for surgical decision-making. Nevertheless, it does not consider lymph node metastasis. The Residual Cancer Burden assessment criteria comprehensively quantify residual tumors by integrating multiple factors. Moreover, these offer a precise assessment of breast cancer and have a high value in predicting prognosis. However, their parameter calculation is complex and highly subjective. In summary, each method has its own advantages and disadvantages. With the advancement of scientific research, evaluation methods for neoadjuvant therapy are constantly evolving. In-depth research into these methods can help identify more accurate and effective evaluation strategies, providing a more scientific basis for tumor treatment and propelling the field of tumor therapy toward greater precision.

Osteoarthritis (OA) is a degenerative joint disease characterized by the metabolic dysfunction of chondrocytes. A promising therapeutic strategy for OA involves suppressing the catabolism of the chondrocyte and promoting its anabolism to restore joint homeostasis. Here, it is demonstrated that Catalpol, a natural compound, can promote chondrocyte anabolic and proliferation, while inhibiting the catabolic activities and oxidative stress, thereby maintaining the dynamic balance of the extracellular matrix and alleviating inflammation‐induced cartilage damage. Mechanistically, it has been discovered that Catalpol acts as a direct inhibitor of heat shock protein 90β (Hsp90β), and the amino acids ASP88, THR179, ASP49, and ASN46 of N‐terminal domain‐Hsp90β are confirmed as the binding sites for Catalpol. Knockdown of Hsp90β in primary chondrocytes demonstrates a similar biological effect as Catalpol treatment. Moreover, to develop a nanoparticle‐based interventional platform for OA management, biodegradable mesoporous silica nanoparticles (bMSN) are prepared to load Catalpol (Ca‐bMSN). The engineered Ca‐bMSN is able to penetrate into the chondrocytes, prolong retention in the joint space, and mitigate OA progression. These findings shed light on a potential mechanism by which Catalpol modulates chondrocyte metabolism, offering a promising therapeutic strategy for OA treatment.

Introduction Osteoarthritis (OA) is a prevalent chronic degenerative disease, marked by a complex interplay of mechanical stress, inflammation, and metabolic imbalances. Recent studies have highlighted the potential of spermidine (SPD), a naturally occurring polyamine known for its anti-inflammatory and antioxidant properties, as a promising therapeutic agent for OA. This study delves into the therapeutic efficacy and mechanistic pathways of SPD in mitigating OA symptoms. Methods Forty Sprague-Dawley rats were randomly assigned to four groups, including the CG (sham operation), model (anterior cruciate ligament transection [ACLT], and treatment (ACLT + two different doses of SPD) groups. In vivo, correlations between OA severity and different interventions were assessed by ELISA, X-rays, CT imaging, histological staining, and immunohistochemistry. In vitro, IL-1β was used to trigger chondrocyte inflammation, and SPD’s cytotoxicity was assessed in primary rat chondrocytes. Next, inflammatory markers, extracellular matrix (ECM) proteins, and pathway marker proteins were detected in chondrocytes administered IL-1β alone, SPD, or aryl hydrocarbon receptor (AhR) silencing, by qRT-PCR, Griess reaction, ELISA, Western blot, and immunofluorescence. Morphological alterations and pyroptosis in chondrocytes were examined by transmission electron microscopy (TEM) and flow cytometry. Results Our research reveals that SPD exerts significant anti-inflammatory and antipyroptotic effects on IL-1β-treated chondrocytes and in anterior cruciate ligament transection (ACLT) rat models of OA, primarily through interaction with the Aryl hydrocarbon receptor (AhR). Specifically, SPD’s binding to AhR plays a crucial role in modulating the inflammatory response and cellular pyroptosis by inhibiting both the AhR/NF-κB and NLRP3/caspase-1/GSDMD signaling pathways. Furthermore, the knockdown of AhR was found to negate the beneficial effects of SPD, underscoring the centrality of the AhR pathway in SPD’s action mechanism. Additionally, SPD was observed to promote the preservation of cartilage integrity and suppress ECM degradation, further supporting its potential as an effective intervention for OA. Discussion Collectively, our findings propose SPD as a novel therapeutic approach for OA treatment, targeting the AhR pathway to counteract the disease’s progression and highlighting the need for further clinical evaluation to fully establish its therapeutic utility.

Introduction Osteosarcoma is a common type of bone cancer characterized by a poor prognosis due to its metastatic nature. The tumor microenvironment (TME) plays a critical role in tumor metastasis and therapy response. Therefore, our study aims to explore the metastatic mechanism of osteosarcoma, potentially opening new avenues for cancer treatment. Methods In this study, we collected data from the GSE152048, GSE14359, and GSE49003 datasets. Differentially expressed genes (DEGs) were identified in osteosarcoma cases with primary and metastatic features using R software and the limma package. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate metastasis-related genes. A protein–protein interaction (PPI) network was established using the STRING database to further analyze these metastasis-associated genes. The abundances of different cell types with a mixed cell population were estimated using the CIBERSORT approach. The scRNA-seq data were analyzed by the Seurat package in R software, and intercellular communications were elucidated using the CellChat R package. Results In this study, 92 DEGs related to metastasis were identified, including 41 upregulated and 51 downregulated genes in both the GSE14359 and GSE49003 datasets. Metastasis-associated pathways were identified, including those involving the cyclin-dependent protein kinase holoenzyme complex, transferase complex, transferring phosphorus-containing groups, SCF ubiquitin ligase complex, and the serine/threonine protein kinase complex. KEGG and PPI network analyses revealed 15 hub genes, including Skp2, KIF20A, CCNF, TROAP, PHB, CKS1B, MCM3, CCNA2, TRIP13, CENPM, Hsp90AB1, JUN, CKS2, TK1, and KIF4A. Skp2 has been known as an E3 ubiquitin ligase involved in osteosarcoma progression. The proportion of CD8+ T cells was found to be higher in metastatic osteosarcoma tissues, and high expression of PHB was associated with a favorable prognosis in osteosarcoma patients. Additionally, 23 cell clusters were classified into eight cell types, including chondrocytes, MSC, T cells, monocytes, tissue stem cells, neurons, endothelial cells, and macrophages. The 15 hub genes were expressed across various cell types, and interactions between different cell types were observed. Conclusion Our study reveals the intricate communication between tumor microenvironment components and tumor metastasis in osteosarcoma.

Accumulating evidence has demonstrated that F‐box protein 22 (FBXO22) participates in tumour development and progression in various types of human malignancies. However, the functions and detailed molecular mechanisms of FBXO22 in osteosarcoma tumorigenesis and progression remain elusive. In this study, we aimed to determine the effects of FBXO22 on the cell proliferation, migration and invasion of osteosarcoma cells using cell counting kit‐8 and Matrigel Transwell approaches. Moreover, we explored the molecular mechanisms by which FBXO22 mediated oncogenesis and progression in osteosarcoma via Western blotting, immunoprecipitation and ubiquitination. We found that FBXO22 depletion inhibited the proliferation, migration and invasion of osteosarcoma cells, whereas FBXO22 overexpression increased the proliferation and motility of osteosarcoma cells. Mechanistically, FBXO22 promoted the ubiquitination and degradation of FoxO1 in osteosarcoma cells. FBXO22 depletion reduced cell proliferation and motility via regulation of FoxO1. Taken together, our findings provide new insight into FBXO22‐induced osteosarcoma tumorigenesis. The inhibition of FBXO22 could be a promising strategy for the treatment of osteosarcoma.

Background Chondrosarcomas are common primary malignant bone tumors; however, comprehensive bibliometric analysis in this field has not yet been conducted. Therefore, this study aimed to explore the research hotspots and trends in the field of chondrosarcoma through bibliometric analysis to help researchers understand the current status and direction of research in the field. Methods Articles and reviews related to chondrosarcoma published between 2003 and 2022 were retrieved from the Web of Science. Countries, institutions, authors, journals, references, and keywords in this field were visualized and analyzed using CtieSpace and VOSviewer software. Results Between 2003 and 2022, 4,149 relevant articles were found. The number of articles published on chondrosarcoma has increased significantly annually, mainly from 569 institutions in China and the United States, and 81 in other countries. In total, 904 authors participated in the publication of studies related to chondrosarcomas. Over the past 20 years, articles on chondrosarcoma have been published in 958 academic journals, with Skeletal Radiology having the highest number of publications. Furthermore, keywords such as “gene expression,” “radiotherapy,” “experience,” and “apoptosis” have been popular in recent years. Conclusion Over the past 20 years, the global trend in chondrosarcoma research has primarily been clinical research, with basic research as a supplement. In the future, communication and exchange between countries and institutions should be strengthened. Further, the future main research hotspots in the field of chondrosarcoma include mutated genes and signaling pathways, precision surgical treatment, proton therapy, radiation therapy, chemotherapy, immunotherapy, and other aspects.