Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with a complex pathological mechanism involving autoimmune response, local inflammation and bone destruction. Metabolic pathways play an important role in immune-related diseases and their immune responses. The pathogenesis of rheumatoid arthritis may be related to its metabolic dysregulation. Moreover, histological techniques, including genomics, transcriptomics, proteomics and metabolomics, provide powerful tools for comprehensive analysis of molecular changes in biological systems. The present study explores the molecular and metabolic mechanisms of RA, emphasizing the central role of metabolic dysregulation in the RA disease process and highlighting the complexity of metabolic pathways, particularly metabolic remodeling in synovial tissues and its association with cytokine-mediated inflammation. This paper reveals the potential of histological techniques in identifying metabolically relevant therapeutic targets in RA; specifically, we summarize the genetic basis of RA and the dysregulated metabolic pathways, and explore their functional significance in the context of immune cell activation and differentiation. This study demonstrates the critical role of histological techniques in decoding the complex metabolic network of RA and discusses the integration of histological data with other types of biological data.

B cells are crucial to the humoral immune response, originating in the bone marrow and maturing in the spleen and lymph nodes. They primarily function to protect against a wide range of infections through the secretion of antibodies. The role of B cells in primary membranous nephropathy (PMN) has gained significant attention, especially following the discovery of various autoantibodies that target podocyte antigens and the observed positive outcomes from B cell depletion therapy. Increasing evidence points to the presence of abnormal B cell subsets and functions in MN. B cells have varied roles during the different stages of disease onset, progression, and relapse. Initially, B cells facilitate self-antigen presentation, activate effector T cells, and initiate cellular immunity. Subsequently, the disruption of both central and peripheral immune tolerance results in the emergence of autoreactive B cells, with strong germinal center responses as a major source of MN autoantibodies. Additionally, critical B cell subsets, including Bregs, memory B cells, and plasma cells, play roles in the immune dysregulation observed in MN, assisting in predicting disease recurrence and guiding management strategies for MN. This review offers a detailed overview of research advancements on B cells and elucidates their pathological roles in MN.

Iron metabolism plays a crucial role in various physiological functions of the human body, as it is essential for the growth and development of almost all organisms. Dysregulated iron metabolism-manifested either as iron deficiency or overload-is a significant risk factor for the development of cardiovascular disease (CVD). Moreover, emerging evidence suggests that ferroptosis, a form of iron-dependent programed cell death, may also contribute to CVD development. Understanding the regulatory mechanisms of iron metabolism and ferroptosis in CVD is important for improving disease management. By integrating different perspectives and expertise in the field of CVD-related iron metabolism, this overview provides insights into iron metabolism and CVD, along with approaches for diagnosing, treating, and preventing CVD associated with iron dysregulation.

Transfer RNA-derived small RNAs (tsRNAs), a recently identified subclass of small non-coding RNAs (sncRNAs), emerge through the cleavage of mature transfer RNA (tRNA) or tRNA precursors mediated by specific enzymes. The tumor necrosis factor (TNF) protein, a signaling molecule produced by activated macrophages, plays a pivotal role in systemic inflammation. Its multifaceted functions include the capacity to eliminate or hinder tumor cells, enhance the phagocytic capabilities of neutrophils, confer resistance against infections, induce fever, and prompt the production of acute phase proteins. Notably, four TNF-related tsRNAs have been conclusively linked to distinct diseases. Examples include 5\'tiRNA-Gly in skeletal muscle injury, tsRNA-21109 in systemic lupus erythematosus (SLE), tRF-Leu-AAG-001 in endometriosis (EMs), and tsRNA-04002 in intervertebral disk degeneration (IDD). These tsRNAs exhibit the ability to suppress the expression of TNF-α. Additionally, KEGG analysis has identified seven tsRNAs potentially involved in modulating the TNF pathway, exerting their influence across a spectrum of non-cancerous diseases. Noteworthy instances include aberrant tiRNA-Ser-TGA-001 and tRF-Val-AAC-034 in intrauterine growth restriction (IUGR), irregular tRF-Ala-AGC-052 and tRF-Ala-TGC-027 in obesity, and deviant tiRNA-His-GTG-001, tRF-Ser-GCT-113, and tRF-Gln-TTG-035 in irritable bowel syndrome with diarrhea (IBS-D). This comprehensive review explores the biological functions and mechanisms of tsRNAs associated with the TNF signaling pathway in both cancer and other diseases, offering novel insights for future translational medical research.

Protein methylation, similar to DNA methylation, primarily involves post-translational modification (PTM) targeting residues of nitrogen-containing side-chains and other residues. Protein arginine methylation, occurred on arginine residue, is mainly mediated by protein arginine methyltransferases (PRMTs), which are ubiquitously present in a multitude of organisms and are intricately involved in the regulation of numerous biological processes. Specifically, PRMTs are pivotal in the process of gene transcription regulation, and protein function modulation. Abnormal arginine methylation, particularly in histones, can induce dysregulation of gene expression, thereby leading to the development of cancer. The recent advancements in modification mediated by PRMTs and cancer research have had a profound impact on our understanding of the abnormal modification involved in carcinogenesis and progression. This review will provide a defined overview of these recent progression, with the aim of augmenting our knowledge on the role of PRMTs in progression and their potential application in cancer therapy.

As a novel post-translational modification of proteins, succinylation is widely present in both prokaryotes and eukaryotes. By regulating protein translocation and activity, particularly involved in regulation of gene expression, succinylation actively participates in diverse biological processes such as cell proliferation, differentiation and metabolism. Dysregulation of succinylation is closely related to many diseases. Consequently, it has increasingly attracted attention from basic and clinical researchers. For a thorough understanding of succinylation dysregulation and its implications for disease development, such as inflammation, tumors, cardiovascular and neurological diseases, this paper provides a comprehensive review of the research progress on abnormal succinylation. This understanding of association of dysregulation of succinylation with pathological processes will provide valuable directions for disease prevention/treatment strategies as well as drug development.

Biomechanical factors are strongly linked with the emergence and development of intervertebral disc degeneration (IVDD). The intervertebral disc (IVD), as a unique enclosed biomechanical structure, exhibits distinct mechanical properties within its substructures. Damage to the mechanical performance of any substructure can disrupt the overall mechanical function of the IVD. Endplate degeneration serves as a significant precursor to IVDD. The endplate (EP) structure, especially the cartilaginous endplate (CEP), serves as a conduit for nutrient and metabolite transport in the IVD. It is inevitably influenced by its nutritional environment, mechanical loading, cytokines and extracellular components. Currently, reports on strategies targeting the CEP for the prevention and treatment of IVDD are scarce. This is due to two primary reasons: first, limited knowledge of the biomechanical microenvironment surrounding the degenerated CEP cells; and second, innovative biological treatment strategies, such as implanting active cells (disc or mesenchymal stem cells) or modulating natural cell activity through the addition of therapeutic factors or genes to treat IVDD often overlook a critical aspect-the restoration of the nutrient supply function and mechanical microenvironment of the endplate. Therefore, restoring the healthy structure of the CEP and maintaining a stable mechanical microenvironment within the EP are crucial for the prevention of IVDD and the repair of degenerated IVDs. We present a comprehensive literature review on the mechanical microenvironment characteristics of cartilage endplates and their associated mechanical signaling pathways. Our aim is to provide valuable insights into the development and implementation of strategies to prevent IVDD by delaying or reversing CEP degeneration.

Chronic obstructive pulmonary disease (COPD) is a disease whose incidence increase with age and is characterised by chronic inflammation and significant immune dysregulation. Inhalation of toxic substances cause oxidative stress in the lung tissue as well as airway inflammation, under the recruitment of chemokines, immune cells gathered and are activated to play a defensive role. However, persistent inflammation damages the immune system and leads to immune dysregulation, which is mainly manifested in the reduction of the body\'s immune response to antigens, and immune cells function are impaired, further destroy the respiratory defensive system, leading to recurrent lower respiratory infections and progressive exacerbation of the disease, thus immune dysregulation play an important role in the pathogenesis of COPD. This review summarizes the changes of innate and adaptive immune-related cells during the pathogenesis of COPD, aiming to control COPD airway inflammation and improve lung tissue remodelling by regulating immune dysregulation, for further reducing the risk of COPD progression and opening new avenues of therapeutic intervention in COPD.

Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification, thereby contributing significantly to the maintenance of cellular functions related to protein synthesis. SnoRNAs have been discovered to possess the ability to influence cell fate and alter disease progression, holding immense potential in controlling human diseases. It is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types, stages, metastasis, treatment response and/or prognosis in patients. On the other hand, colorectal cancer (CRC), a prevalent malignancy of the digestive system, is characterized by high incidence and mortality rates, ranking as the third most common cancer type. Recent research indicates that snoRNA dysregulation is associated with CRC, as snoRNA expression significantly differs between normal and cancerous conditions. Consequently, assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of CRC. Nevertheless, current comprehension of the potential roles of snoRNAs in CRC remains limited. This review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC, providing valuable insights into the discovery of novel biomarkers, therapeutic targets, and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.

CD4+ T-cell counts are increased and activated in patients with chronic heart failure (CHF), whereas regulatory T-cell (Treg) expansion is inhibited, probably due to aberrant T-cell receptor (TCR) signaling. TCR signaling is affected by protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in autoimmune disorders, but whether PTPN22 influences TCR signaling in CHF remains unclear. This observational case-control study included 45 patients with CHF [18 patients with ischemic heart failure versus 27 patients with nonischemic heart failure (NIHF)] and 16 non-CHF controls. We used flow cytometry to detect PTPN22 expression, tyrosine phosphorylation levels, zeta-chain-associated protein kinase, 70 kDa (ZAP-70) inhibitory residue tyrosine 292 and 319 phosphorylation levels, and CD4+ T cell and Treg proportions. We conducted lentivirus-mediated PTPN22 RNA silencing in isolated CD4+ T cells. PTPN22 expression increased in the CD4+ T cells of patients with CHF compared with that in controls. PTPN22 expression was positively correlated with left ventricular end-diastolic diameter and type B natriuretic peptide but negatively correlated with left ventricular ejection fraction in the NIHF group. ZAP-70 tyrosine 292 phosphorylation was decreased, which correlated positively with PTPN22 overexpression in patients with NIHF and promoted early TCR signaling. PTPN22 silencing induced Treg differentiation in CD4+ T cells from patients with CHF, which might account for the reduced frequency of peripheral Tregs in these patients. PTPN22 is a potent immunomodulator in CHF and might play an essential role in the development of CHF by promoting early TCR signaling and impairing Treg differentiation from CD4+ T cells.