Neutrophil extracellular traps (NETs) are web-like structures composed of DNA, histones, and antimicrobial proteins that extend the defensive repertoire of neutrophils beyond classical phagocytosis and degranulation. Initially considered solely antimicrobial, NETs are now recognized as dynamic regulators of immunity, inflammation, and tissue remodeling. Their formation is orchestrated by the generation of reactive oxygen species, neutrophil elastase-mediated chromatin remodeling, and peptidyl arginine deiminase 4-driven histone citrullination. At the same time, clearance involves DNase activity and macrophage-mediated phagocytosis. In physiological contexts, NETs immobilize and kill pathogens, restrict biofilm formation, and coordinate immune cell crosstalk, thereby supporting host defense and repair. However, when NET formation or clearance becomes dysregulated, these structures drive a broad spectrum of pathologies. Aberrant NET activity has been implicated in infectious diseases (bacterial, viral, fungal), autoimmune disorders such as systemic lupus erythematosus, ANCA-associated vasculitis, rheumatoid arthritis, Gout, and psoriasis, cardiovascular disorders including atherosclerosis, thrombosis, acute coronary syndrome, Myocardial ischemia/reperfusion injury, hypertension, atrial fibrillation, heart failure, and viral myocarditis, as well as cancer progression, metastasis, and other inflammation-associated disorders such as asthma, Alzheimer’s disease, diabetes, and pregnancy-related complications. Advances in imaging, proteomics, and single-cell sequencing have expanded our ability to characterize NETs across contexts, revealing stimulus- and disease-specific heterogeneity. At the translational levels, therapies that inhibit NETs formation, promote their degradation, or regulate their release, including PAD4 and elastase inhibitors, DNase-based approaches, and antibody strategies, are under active investigation. By integrating these advances, this review provides a framework for translating NET biology into clinically relevant applications.

The regulatory relationship between silent information regulator 2 (SIRT2) and glucose 6-phosphate dehydrogenase (G6PD) in clear cell renal cell carcinoma (ccRCC) is still unclear. The present study aimed to explore the function of SIRT2 and its regulatory effect on G6PD in ccRCC. The Cancer Genome Atlas data mining of SIRT2 was first analyzed. RT-qPCR and western blotting analyses were used to assess the mRNAs and proteins expressions levels respectively. The cell viability assay, colony formation assay, EdU staining, cell cycle assay, cell apoptosis assay, and TUNEL assay were used to investigate the roles of SIRT2 in ccRCC proliferation and apoptosis. The co-immunoprecipitation (Co-IP) assay was performed to analyze the association of SIRT2 with G6PD in ccRCC cells. Quantitative Co-IP assay was used to detect the levels of G6PD ubiquitination and small ubiquitin-related modifier 1 (SUMO1). A in vivo experiment was also performed to confirm in vitro findings. The results indicated that SIRT2 promoted ccRCC proliferation and inhibited apoptosis by regulating cell cycle and apoptosis related proteins. SIRT2 interacted with G6PD, facilitated its activity through deacetylation and increased its stability by reducing its ubiquitination and enhancing its SUMO1 modification. SIRT2 also promoted ccRCC tumor development in vivo. Taken together, the present study demonstrated that SIRT2 promoted ccRCC progression by increasing G6PD activity and stability, and it could be a potential new diagnostic and therapeutic target for ccRCC.

Diabetes mellitus is a group of metabolic disorders that can lead to severe health problems, and the current treatments often have harmful side effects. Therefore, there is a growing interest in discovering new antidiabetic drugs with fewer adverse effects, and natural products are a promising source for this purpose. Cicer arietinum and Hordeum vulgare are plants with high levels of phytochemicals that have been shown to have therapeutic properties. This study investigates the anti-diabetic potential of C. arietinum and H. vulgare seeds and their secondary metabolites. We employed a comprehensive approach combining in vitro, in silico, and in vivo methods to evaluate the efficacy of the compounds. Our findings reveal that the extracts of C. arietinum (IC₅₀ 55.08 μg/mL) and H. vulgare (IC₅₀ 115.8 ± 5 μg/mL) demonstrated a stronger inhibitory effect on α-amylase compared to acarbose (standard drug) (IC₅₀ 196.3 ± 10 μg/mL). Similarly, both C. arietinum and H. vulgare exhibited significant inhibitory activity against α-glucosidase (IC₅₀ 100.2 ± 5 μg/mL and IC₅₀ 216.2 ± 5 μg/mL, respectively) compared to acarbose (IC₅₀ 246.5 ± 10 μg/mL). To further investigate their mechanism of action, a computational screening of 194 phytochemicals from these plants was conducted, followed by molecular docking with α-amylase (PDB ID#1B2Y) and α-Glucosidase (PDB ID# 5NN8) receptors. According to the binding affinities and molecular dynamics (MD) simulations, Medicagol, Euphol, Stigmasterol, and Beta-Sitosterol emerged as promising candidates for diabetes treatment. Molecular dynamics showed that Medicagol was a strong inhibitor against selected receptor proteins because the ligand–protein complexes remained stabilized during the entire simulation time of 100 ns. In vitro analysis also confirmed that Medicagol, stigmasterol, and Euphol have significant potential for type 2 diabetes prevention via inhibition of carbohydrates hydrolyzing enzymes. In vivo study demonstrated significant therapeutic effects in STZ-induced diabetes mice. Including reductions in hyperlipidemia, hyperglycemia, and insulin resistance. Histopathological analysis revealed that plant extracts mitigated STZ-induced pancreatic and liver damage. Additionally, extracts enhanced antioxidant defenses by increasing SOD, CAT, and GSH levels, while decreasing MDA levels in the liver, kidneys, and pancreas, highlighting their protective role against oxidative stress. These results support the potential of Cicer arietinum and Hordeum vulgare as natural sources for developing antidiabetic agents.

Background: Long intergenic non-coding RNA 00511 (LINC00511) is highly expressed in diverse cancers and has a correlation with poor clinical outcomes for cancer patients. In view of contradictory data among published data, we aim to evaluate the prognostic role of LINC00511 for cancer patients. Methods: In the present study, a meta-analysis of related studies has been performed to investigate the prognostic significance of LINC00511 in cancer patients. Relevant studies published before December 22, 2019 were systematically searched online in PubMed, EMBASE, Web of Science, and the Cochrane Library databases. The relationship between LINC00511 expression and cancer patients’ survival, including overall survival (OS), disease-free survival (DFS)/relapse-free survival (RFS) and progression-free survival (PFS), was evaluated using pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). The association between LINC00511 expression and clinicopathological features was assessed using odd ratios (ORs) and their corresponding 95% CIs. Results: A total of 14 eligible studies with 1883 patients were enrolled in the present meta-analysis. The results demonstrated that elevated expression of LINC00511 was significantly associated with poor OS (HR = 2.62; 95% CI: 2.00–3.45; p < 0.001), PFS (HR = 1.80; 95% CI: 1.29–2.51; p = 0.001) and DFS/RFS (HR = 2.90; 95% CI: 1.04–8.12; p = 0.04). Additionally, High LINC00511 expression was associated with large tumor size (OR = 3.10; 95% CI: 1.97–4.86; p < 0.00001), lymph node metastasis (OR = 3.11; 95% CI: 2.30–4.21; p < 0.00001), advanced clinical stage (OR = 3.95; 95% CI: 2.68–5.81; p < 0.00001), distant metastasis (OR = 2.39; 95% CI: 1.16–4.93; p = 0.02), and disease recurrence (OR = 4.62; 95% CI: 2.47–8.65; p < 0.00001). Meanwhile, no correlation was found between LINC00511 expression and age, gender, and histological grade. These findings were consolidated by the results of bioinformatics analysis. Conclusions: Based on our findings, LINC00511 may serve as a novel prognostic biomarker for cancer patients.

Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, is essential for the heart, motor neuron and pancreas development. Recently, ISL-1 has been found in some types of human cancers. However, how ISL-1 exerts the role in tumor development is not clear. The expression of ISL-1 was assessed in 211 human lymphoma samples and 23 normal lymph node samples. Immunohistochemistry results demonstrated a markedly higher expression of ISL-1 in 75% of non-Hodgkin lymphoma (NHL) samples compared with that in normal lymph nodes or Hodgkin lymphoma (HL) samples. CCK-8 analysis, cell cycle assay and xenograft model were performed to characterize the association between ISL-1 expression level and biological functions in NHL. The results showed that ISL-1 overexpression obviously promoted NHL cells proliferation, changed the cell cycle distribution in vitro and significantly enhanced xenografted lymphoma development in vivo. Real-time PCR, Western blot, luciferase assay and ChIP assay were used to explore the potential regulatory targets of ISL-1 and the results demonstrated that ISL-1 activated the c-Myc expression in NHL by direct binding to a conserved binding site on the c-Myc enhancer. Further results revealed that ISL-1 could be positively regulated by the c-Jun N-terminal kinase (JNK) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. Both the JNK and JAK/STAT signaling inhibitors could significantly suppressed the growth of NHL cells through the down-regulation of ISL-1 as demonstrated by CCK-8 and Western blot assays. Bioinformatic analysis and luciferase assay exhibited that ISL-1 was a novel target of p-STAT3 and p-c-jun. ChIP, Co-IP and ChIP-re-IP analysis revealed that ISL-1 could participate with p-STAT3 and p-c-Jun to form a p-STAT3/p-c-Jun/ISL-1 transcriptional complex that binds directly on the ISL-1 promoter, demonstrating a positive feedback regulatory mechanism for ISL-1 expression in NHL. Our results provide the first evidence that ISL-1 is tightly linked to NHL proliferation and development by promoting c-Myc transcription, and its aberrant expression was regulated by p-STAT3/p-c-Jun/ISL-1 complex activation.

A high-fat diet plays an important role in aggravating cancers. Palmitic acid (PA) is one of the components of saturated fatty acids; it has been reported to promote tumor proliferation in melanomas, but the signal transduction pathway mediated by palmitic acid remains unclear. This study showed that palmitic acid can promote the lung metastasis of melanomas. Moreover, the interaction between palmitic acid and toll-like receptor 4 (TLR4) was predicted by molecular docking. The experimental results proved that palmitic acid could promote the TLR4 and Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF) expression. The expression of Pellino1 (Peli1) and the phosphorylation of NF-kappa B (pNF-κB) were downregulated after the suppression of TLR4 and the silencing of Peli1 also inhibited the phosphorylation of NF-κB. Therefore, we concluded that palmitic acid promoted the lung metastasis of melanomas through the TLR4/TRIF-Peli1-pNF-κB pathway.