Advances in mechanism and regulation of PANoptosis: Prospects in disease treatment.

PANoptosis, a new research hotspot at the moment, is a cell death pattern in which pyroptosis, apoptosis, and necroptosis all occur in the same cell population. In essence, PANoptosis is a highly coordinated and dynamically balanced programmed inflammatory cell death pathway that combines the main features of pyroptosis, apoptosis, and necroptosis. Many variables, such as infection, injury, or self-defect, may be involved in the occurrence of PANoptosis, with the assembly and activation of the PANoptosome being the most critical. PANoptosis has been linked to the development of multiple systemic diseases in the human body, including infectious diseases, cancer, neurodegenerative diseases, and inflammatory diseases. Therefore, it is necessary to clarify the process of occurrence, the regulatory mechanism of PANoptosis, and its relation to diseases. In this paper, we summarized the differences and relations between PANoptosis and the three types of programmed cell death, and emphatically expounded molecular mechanism and regulatory patterns of PANoptosis, with the expectation of facilitating the application of PANoptosis regulation in disease treatment.

Targeting regulation of stem cell exosomes: Exploring novel strategies for aseptic loosening of joint prosthesis.

Periprosthetic osteolysis is a major long-term complication of total joint replacement. A series of biological reactions caused by the interaction of wear particles at the prosthesis bone interface and surrounding bone tissue cells after artificial joint replacement are vital reasons for aseptic loosening. Disorder of bone metabolism and aseptic inflammation induced by wear particles are involved in the occurrence and development of aseptic loosening of the prosthesis. Promoting osteogenesis and angiogenesis and mediating osteoclasts and inflammation may be beneficial in preventing the aseptic loosening of the prosthesis. Current research about the prevention and treatment of aseptic loosening of the prosthesis focuses on drug, gene, and stem cell therapy and has not yet achieved satisfactory clinical efficacy or has not been used in clinical practice. Exosomes are a kind of typical extracellular vehicle. In recent years, stem cell exosomes (Exos) have been widely used to regulate bone metabolism, block inflammation, and have broad application prospects in tissue repair and cell therapy.

Focus on ferroptosis regulation: Exploring novel mechanisms and applications of ferroptosis regulator.

Ferroptosis is a kind of iron-dependent regulatory necrosis characterized by the fatal accumulation of iron-dependent lipid peroxides in the plasma membrane and the final oxidative damage of the cell membrane. Morphologically, ferroptosis features high membrane density, decreased or disappeared cristae, rupture of the mitochondrial outer membrane, plasma membrane integrity loss, cytoplasmic swelling, and organelle swelling. Under physiological conditions, ferroptosis occurs through two major pathways, the extrinsic or transporter-dependent pathway and the intrinsic or enzyme-regulated pathway, triggered by a series of small molecules inside and outside the cell. At present, it is assumed that ferroptosis is mainly related to abnormal toxicity of iron, lipid peroxidation, and mitochondrial dysfunction. With more detailed studies, ferroptosis plays potential pathogenic roles in multisystem diseases as a pathological response, and targeted regulation of ferroptosis in treating ferroptosis-related diseases has broad prospects. In conclusion, it is of great clinical significance to further clarify the specific mechanism of ferroptosis and explore new strategies for ferroptosis regulation. The present review emphatically summarizes the latest mechanism of ferroptosis, focusing on the regulation mechanism and clinical application of ferroptosis inducers and inhibitors. We are devoted to providing new ideas for the further study of ferroptosis and the diagnosis and treatment of ferroptosis-related multisystem diseases.

Focusing on OB-OC-MΦ Axis and miR-23a to Explore the Pathogenesis and Treatment Strategy of Osteoporosis.

Osteoporosis is a bone metabolic disorder characterized by decreased bone density and deteriorated microstructure, which increases the risk of fractures. The imbalance between bone formation and bone resorption results in the occurrence and progression of osteoporosis. Osteoblast-mediated bone formation, osteoclast-mediated bone resorption and macrophage-regulated inflammatory response play a central role in the process of bone remodeling, which together maintain the balance of the osteoblast-osteoclast-macrophage (OB-OC-MΦ) axis under physiological conditions. Bone formation and bone resorption disorders caused by the imbalance of OB-OC-MΦ axis contribute to osteoporosis. Many microRNAs are involved in the regulation of OB-OC-MΦ axis homeostasis, with microRNA-23a (miR-23a) being particularly crucial. MiR-23a is highly expressed in the pathological process of osteoporosis, which eventually leads to the occurrence and further progression of osteoporosis by inhibiting osteogenesis, promoting bone resorption and inflammatory polarization of macrophages. This review focuses on the role and mechanism of miR-23a in regulating the OB-OC-MΦ axis to provide new clinical strategies for the prevention and treatment of osteoporosis.

SIX3 function in cancer: progression and comprehensive analysis.

The homeobox gene family encodes transcription factors that are essential for cell growth, proliferation, and differentiation, and its dysfunction is linked to tumor initiation and progression. Sine oculis homeobox (SIX) belongs to the homeobox gene family, with SIX3 being a core member. Recent studies indicate that SXI3 functions as a cancer suppressor or promoter, which is mainly dependent on SIX3's influence on the signal pathways that promote or inhibit cancer in cells. The low expression of SIX3 in most malignant tumors was confirmed by detailed studies, which could promote the cell cycle, proliferation, migration, and angiogenesis. The recovery or upregulation of SIX3 expression to suppress cancer is closely related to the direct or indirect inhibition of the Wnt pathway. However, in some malignancies, such as esophageal cancer and gastric cancer, SIX3 is a tumor-promoting factor, and repressing SIX3 improves patients' prognosis. This review introduces the research progress of SIX3 in tumors and gives a comprehensive analysis, intending to explain why SIX3 plays different roles in different cancers and provide new cancer therapy strategies.

Megakaryocytes in pulmonary diseases.

Megakaryocytes (MKs) are typical cellular components in the circulating blood flowing from the heart into the lungs. Physiologically, MKs function as an important regulator of platelet production and immunoregulation. However, dysfunction in MKs is considered a trigger in various diseases. It has been described that the lung is an important site of platelet biogenesis from extramedullary MKs, which may play an essential role in various pulmonary diseases. With detailed studies, there are different degrees of numerical changes of MKs in coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis (PF), and other pulmonary diseases. Also, MKs inhibit or promote the development of pulmonary diseases through various pathways. Here, we summarize the current knowledge of MKs in pulmonary diseases, highlighting the physiological functions and integrated molecular mechanisms. We aim to shine new light on not only the subsequent study of MKs but also the diagnosis and treatment of pulmonary diseases.

Targeting Ferroptosis for Lung Diseases: Exploring Novel Strategies in Ferroptosis-Associated Mechanisms.

Ferroptosis is an iron-dependent regulated necrosis characterized by the peroxidation damage of lipid molecular containing unsaturated fatty acid long chain on the cell membrane or organelle membrane after cellular deactivation restitution system, resulting in the cell membrane rupture. Ferroptosis is biochemically and morphologically distinct and disparate from other forms of regulated cell death. Recently, mounting studies have investigated the mechanism of ferroptosis, and numerous proteins play vital roles in regulating ferroptosis. With detailed studies, emerging evidence indicates that ferroptosis is found in multiple lung diseases, demonstrating that ferroptosis appears to be particularly important for lung diseases. The mounting interest in ferroptosis drugs specifically targeting the ferroptosis mechanism holds substantial therapeutic promise in lung diseases. The present review emphatically summarizes the functions and integrated molecular mechanisms of ferroptosis in various lung diseases, proposing that multiangle regulation of ferroptosis might be a promising strategy for the clinical treatment of lung diseases.

The role and mechanism of ß-arrestin2 in signal transduction.

ß-arrestin2 is a ubiquitously expressed scaffold protein localized on the cytoplasm and plasma membrane. It was originally found to bind to GPCRs, uncoupling G proteins and receptors' binding and inhibiting the signal transduction of the GPCRs. Further investigations have revealed that ß-arrestin2 not only mediates the desensitization of GPCRs but also serves as a multifunctional scaffold to mediate receptor internalization, kinase activation, and regulation of various signaling pathways, such as TLR4/NF-κB, MAPK, Wnt, TGF-ß, and AMPK/mTOR pathways. ß-arrestin2 regulates cell invasion, migration, autophagy, angiogenesis, and anti-inflammatory effects by regulating various signaling pathways, which play a vital role in many physiological and pathological processes. This paper reviews the structure and function of ß-arrestin2, the regulation of ß-arrestin2 based signaling pathways. The role and mechanism of ß-arrestin2 signaling have been delineated in sufficient detail. The prospect of regulating the expression and activity of ß-arrestin2 in multisystem diseases holds substantial therapeutic promise.