Background Depression shows significant clinical and biological heterogeneity, largely driven by individual differences in stress responsivity. The nucleus accumbens (NAc), a key integrator of motivational and affective processing, undergoes molecular remodeling under chronic stress, contributing to anhedonia and variable antidepressant efficacy. Defining how stress reshapes the NAc’s molecular architecture across biological backgrounds may reveal molecular networks underlying treatment outcomes. This study aimed to characterize NAc proteomic signatures associated with stress vulnerability and antidepressant response in two rat strains with distinct stress-related phenotypes. Methods Male Wistar and Kyoto rats were exposed to chronic mild stress (CMS) and subsequently received chronic venlafaxine or vehicle administration. Anhedonia-like behavior, behavioral reactivity, social behavior, and serum corticosterone levels were assessed. High-resolution data-independent acquisition mass spectrometry was used to identify NAc proteomic signatures. Results Across-strain comparisons revealed baseline increases in reward sensitivity, reduced social investigation, and heightened defensive and aggressive behaviors in Kyoto rats, associated with NAc cellular metabolic pathway enrichment, including alterations in Ogdhl and Nit2. Under CMS, Kyoto rats displayed early-onset anhedonia, social withdrawal, and blunted glucocorticoid output. Moreover, they showed increased NAc proteomic enrichment in mitochondrial protein degradation and oxidative stress pathways, and decreased enrichment in synaptic signaling pathways, including Ppp1r1b/DARPP-32, compared to Wistar rats.Venlafaxine reversed stress-induced behavioral and proteomic alterations in Wistar rats. In Kyoto rats, it failed to improve anhedonia, exacerbated aggressive behavior, and induced enrichment of the NAc pathway related to bioenergetics and transmembrane transport, as well as astrocyte activation-related proteins. Conclusion Strain-specific NAc proteomic signatures characterize distinct trajectories of stress vulnerability, antidepressant non-response, and adverse behavioral activation. Although these male-only proteomic signatures require functional validation across sexes and antidepressant classes, they identify molecular candidates for precision pharmacology in depression.
Background Diabetic wounds exhibit persistent inflammation and impaired tissue repair. Excessive M1 macrophage polarization contributes to delayed healing. Exosomes derived from adipose-derived mesenchymal stem cells (ADSCs) are promising cell-free therapies, and resveratrol (RES) enhances stem cell functions. This study investigated whether exosomes from RES-pretreated ADSCs (RES-exo) promote diabetic wound healing by regulating macrophage polarization through the PI3K/AKT pathway. Methods Human ADSCs were pretreated with RES for exosome isolation. The effects of ADSC-derived exosomes (ADSC-exo) and RES-exo on lipopolysaccharide-induced M1 macrophage polarization were assessed by immunofluorescence staining, quantitative real-time PCR, enzyme-linked immunosorbent assay, and Western blotting. The PI3K agonist 740 Y-P was used for pathway validation. Therapeutic effects were evaluated in db/db diabetic mice. Results Both ADSC-exo and RES-exo inhibited M1 macrophage polarization and reduced pro-inflammatory mediator expression, with RES-exo showing stronger effects. RES-exo regulated PI3K/AKT phosphorylation and suppressed excessive M1 activation. In diabetic mice, RES-exo accelerated wound closure, enhanced collagen deposition and angiogenesis, and reduced inflammation compared with ADSC-exo and controls. Conclusion RES pretreatment enhances ADSC-exo therapeutic efficacy. RES-exo promotes diabetic wound healing by modulating macrophage polarization through PI3K/AKT signaling regulation, indicating its potential as a cell-free therapy. However, the responsible exosomal cargos and long-term efficacy and safety require further investigation.
Background Marburg virus (MARV) ranks among the most detrimental zoonotic viruses, exhibiting lethal impacts on nonhuman and human primates. Owing to recurring MARV outbreaks marked by a high mortality rate, the WHO classified it as a risk group 4 pathogen and underscored the imperative demand for developing viable medications. Among the potential viral targets, the polymerase cofactor (VP35) serves as a promising target due to its central function in the replication process. The purpose of this study was to identify potential VP35 inhibitors from toxicological sources using computational approaches. Methods In-silico computations were performed to identify VP35 inhibitors derived from toxicological sources. The T3DB database was screened to identify potent inhibitors against VP35 through docking estimations. The top-scoring toxins were further characterized using molecular dynamics simulations (MDS) and MM/GBSA binding energy computations. Results Following 300ns MDS with MM/GBSA analysis, two toxins —namely T3D4864 and T3D3233— demonstrated more favorable binding affinities toward VP35 with ΔGbinding values of −42.0 and −37.9kcal/mol, respectively, in comparison with galidesivir (ΔGbinding = −16.3kcal/mol). Their superior binding was attributed to multiple H-bonds, hydrophobic, and vdW interactions with the key residues of VP35. Post-MD structural and energetic analyses, including radius of gyration and root-mean-square deviation analyses, confirmed the stability of the identified toxins bound to VP35 over 300ns MDS. Subsequently, DFT computations were performed to evaluate the electronic features of the identified toxins, revealing their favorable chemical reactivities. Conclusion These computational findings suggest that T3D4864 and T3D3233 may represent putative VP35 inhibitors for further investigation. However, this study is limited to in-silico predictions and necessitates further experimental validation of antiviral activity, cytotoxicity, selectivity, and pharmacological safety. Funding This work was funded by Ongoing Research Funding Program (ORF-2026-759), King Saud University, Riyadh, Saudi Arabia.
Background Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor with limited therapeutic options. Galectin−1 (Gal−1) has been implicated in tumor progression in several cancers; however, its roles in ICC remain unclear. This study examined the role of Gal−1 in ICC progression and characterized its molecular mechanisms. Methods The expression of Gal−1 in ICC was evaluated by Western blot analysis and immunohistochemistry, and its functional effects on ICC cell proliferation and migration were assessed through Western blot analysis, wound healing assays, CCK8 assays, and in vivo knockdown models. Transcriptome sequencing was performed on Gal-1-deficient cells to identify downstream effectors. Fructose−1,6−bisphosphatase 1 (FBP1) was identified as a key candidate and further validated in clinical samples and functional assays. The involvement of the RAS/ERK signaling pathway was investigated, and mechanistic causality was confirmed through FBP1 overexpression and rescue experiments. Results Gal−1 was significantly overexpressed in ICC and correlated with poor prognosis. Gal−1 knockdown markedly inhibited ICC cell proliferation and migration both in vitro and in vivo. Mechanistically, suppression of Gal−1 resulted in upregulation of FBP1 and inhibition of the RAS/ERK signaling pathway. Conclusion Our findings identify a previously unrecognized Gal−1/FBP1/RAS-ERK regulatory axis driving ICC progression, highlighting Gal−1 as a possible therapeutic target and prognosis indicator. However, further investigation is required to elucidate Gal−1 detailed regulatory mechanisms in ICC.
Background Prostate cancer is the fourth most common cancer worldwide. Despite the high incidence rate, in vitro research of prostate cancer has been limited to fewer than ten commonly available cell lines. The limited availability of disease-representative model cell lines is a widely acknowledged challenge in translational prostate cancer research. Establishment of novel prostate cancer cell lines is therefore of critical importance to facilitate functional target discovery and drug development for prostate cancer. Methods In this study, we report the establishment of the first large cell neuroendocrine prostate cancer cell line, MISB114, from a liver metastasis of an aggressive castration resistant neuroendocrine prostate cancer. Comparative transcriptomic, DNA sequencing and high-throughput drug screening against the currently available prostate cancer cell lines and molecular profiling of prostate cancers are used for characterization of the MISB114 cell line. Results MISB114 cells are characterized by aggressive large cell neuroendocrine prostate cancer associated molecular features including high neuronatin and somatostatin expression, androgen independency and complete inactivation of TP53 and RB1. High-throughput drug screening studies indicate a drug sensitivity profile reflecting the dual TP53/RB1 loss associated with elevated replication stress and sensitivity to DNA repair targeting and novel therapeutic targets such as RNA N6-methyladenosine regulator METTL3. Conclusion Large cell neuroendocrine prostate cancer is a rare entity of castration resistant prostate cancer. Due to a lack of validated markers for diagnosis, large cell neuroendocrine prostate cancer is generally under-recognized, and the therapeutic implications remain poorly understood. While stable patient derived cell lines best represent the individual tumor of origin, MISB114 cell line provides an invaluable novel model for the study of pathogenesis, molecular characteristics and drug sensitivity of this aggressive neuroendocrine differentiated prostate cancer subtype.Data is available through EMBL-EBI European Nucleotide Archive under accession no. ERP181257.This study has not received any external funding.
Background Rivaroxaban is primarily utilized in patients with atrial fibrillation (AF) to decrease the risk of thrombosis. Drug repositioning strategies have been regarded as beneficial in identifying the potential effects of clinical drugs, and the current study was conducted to explore the potential blood pressure reduction effect of rivaroxaban. Methods A combination of machine learning models was employed to screen 3285 non-antihypertensive drugs in the FDA database for potential antihypertensive effects. A comprehensive approach was adopted, encompassing retrospective clinical data analysis, animal experiments, and cell-based studies. This multifaceted strategy was employed to systematically assess the concordance between the outcomes of predictive models and the observed data. Results The machine learning predicted eight top non-antihypertensive drugs with pressure reduction effects. Next, the retrospective clinical data showed that the patients treated with Rivaroxaban were associated with greatly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP). Meanwhile, it demonstrated that rivaroxaban inhibited Ang II-induced Vimentin and Col 1a mRNA levels in human umbilical vein endothelial cells (HUVECs), and reduced the migration of human vascular smooth muscle cell (HUVSCs) after Ang II stimulation in vitro. In vivo, Rivaroxaban also exhibited an obvious effect on pressure reduction in hypertensive mice. The molecular docking revealed that rivaroxaban primarily exhibited strong binding affinity for glucose-dependent insulinotropic receptor (GIR, −10.6 kcal/mol). Conclusions This approach provides a potential new option for patients with AF with hypertension, to ameliorate cardiovascular remodeling when selecting rivaroxaban as the oral anticoagulant. While further validation should be conducted to explore the detailed mechanism by which rivaroxaban regulates GIR in hypertension.
Background The continuous emergence of SARS-CoV-2 variants highlights the need for antiviral agents targeting conserved viral proteins. The N-terminal domain of the SARS-CoV-2 nucleocapsid protein plays a critical role in RNA binding and genome packaging but remains relatively underexplored as a therapeutic target. Therefore, this study aimed to identify and optimize thiazolide derivatives as potential inhibitors of the SARS-CoV-2 nucleocapsid N-terminal domain using an integrated computational approach. Methods Comprehensive in silico screening and AI-assisted optimization of thiazolide derivatives were performed using ADMET analysis, molecular docking, density functional theory calculations, fragment-based optimization, and molecular dynamics simulations. Results Comp7 was identified as a lead compound with a docking affinity of −7.7 kcal/mol, a predicted inhibition constant of 2.23 µM, and favorable electronic properties. Fragment optimization generated an optimized lead compound with a comparable docking affinity of −7.8 kcal/mol, together with improved predicted pharmacokinetic and toxicity profiles. Molecular dynamics simulations over 200 ns demonstrated favorable protein–ligand interactions, with root mean square deviation stabilization around 0.25 nm and a consistent radius of gyration of approximately 2.46 nm, indicating structural compactness of the complex. Root mean square fluctuation analysis showed limited residue fluctuations, supporting consistent binding stability. Binding free energy calculations further supported favorable interaction energetics, with a calculated binding free energy of −24.5327 kcal/mol. Conclusion The findings suggest that the optimized thiazolide derivative may serve as a promising lead compound targeting the conserved SARS-CoV-2 nucleocapsid protein. However, further experimental validation through in vitro and in vivo studies is required.
Background Esophageal squamous cell carcinoma (ESCC) remains a leading cause of cancer-related deaths in East Asia, and its molecular mechanisms are not fully understood. Two-hybrid-associated protein 1 (TWA1/GID8), a scaffold protein involved in cell-cycle regulation and stress responses, has been implicated in tumor progression; however, its role in ESCC remains unclear. This study aimed to investigate the expression, biological function, and underlying molecular mechanisms of TWA1 in ESCC. Methods TWA1 expression was evaluated using proteomic analysis, public datasets, and two independent ESCC cohorts. Functional roles of TWA1 were examined through gain- and loss-of-function assays in vitro and in vivo. RNA sequencing, pathway enrichment analysis, biochemical assays, and pharmacological interventions were performed to identify downstream signaling mechanisms. Results TWA1 was significantly overexpressed in ESCC tissues and associated with advanced stage and poor overall survival. TWA1 promoted ESCC cell proliferation, cell-cycle progression, migration, invasion, and tumor growth while inhibiting apoptosis. Mechanistically, TWA1 activated p38 signaling to enhance CXCL2 expression. Increased CXCL2 subsequently stimulated ERK1/2 activation, contributing to malignant phenotypes. Inhibition of p38 or CXCL2/CXCR2 signaling attenuated TWA1-driven ESCC progression. Conclusion This study elucidates TWA1 as an upstream regulator of the p38–CXCL2–CXCR2–ERK1/2 signaling cascade in ESCC and provides mechanistic evidence connecting TWA1 to crosstalk between MAPK and chemokines during tumor progression. Furthermore, it underscores the potential of TWA1 as a prognostic biomarker and candidate target in ESCC. However, the study is limited by the retrospective nature of clinical cohorts, the limited size of the initial discovery cohort, and the use of subcutaneous xenograft models that may not fully recapitulate the tumor microenvironment.
Background The ECM-receptor interaction signaling pathway is essential for the progression of various tumors. Histamine N-methyltransferase (HNMT), a histamine metabolic enzyme, is significantly upregulated in hepatocellular carcinoma (HCC). However, the impact of HNMT on tumor progression through regulation of the ECM-receptor interaction signaling pathway within the tumor microenvironment remains unclear. This study explores HNMT as a potential candidate target gene for HCC treatment and investigates its mechanism of action. Methods The HNMT target gene was overexpressed in the liver cancer cell line MHCC97L, while the HNMT gene was knocked down in HepG2 cells. Differentially expressed genes were identified using a combination of transcriptomic and proteomic analyses. Validation of differentially expressed proteins was performed through q-PCR and Western blotting. Results HNMT consumption of the intracellular methyl pool leads to the suppression of histone H3K9 trimethylation (H3K9me3), resulting in elevated expression of VTN and activation of the ECM-receptor interaction signaling pathway. This biological process enhances the proliferation, vascular adhesion, and invasion capabilities of HCC cells. However, whether the changes in VTN gene expression are directly governed by H3K9me3 modification remains to be further verified experimentally. Conclusion HNMT facilitates HCC progression via modulating histone methylation. The HNMT-VTN axis offers new insights for HCC targeted therapy.
Background Cholestatic liver fibrosis is a common pathological manifestation of various biliary tract diseases. Given the limited efficacy of current pharmacotherapies, there is a clear need to develop novel and effective treatment strategies. This study aims to evaluate the protective effects of puerarin against cholestatic liver fibrosis. Methods The therapeutic efficacy of puerarin was assessed in a bile duct ligation rat model. Collagen deposition was evaluated using picrosirius red staining and Masson’s trichrome staining. Immunohistochemistry for cytokeratin 7 (CK7) and CK19 was performed to assess bile duct proliferation. Hepatic mRNA expression profiles and metabolic profiles were analyzed by transcriptome sequencing and untargeted metabolomics, respectively. In parallel, in vitro experiments were conducted using HepaRG hepatocyte cultures exposed to a bile acid mixture, with cell proliferative capacity assessed via EdU assays. Results Puerarin treatment ameliorated serum biochemical abnormalities, histological injury, and bile duct proliferation in the cholestatic liver fibrosis rat model. Mechanistically, puerarin modulated extracellular matrix deposition and regulated the PI3K-Akt signaling pathway. Furthermore, metabolomic analysis indicated that puerarin altered the hepatic bile acid profile, promoting the conjugation of hydrophobic bile acids. In vitro studies demonstrated that puerarin attenuated bile acid mixture-induced hepatotoxicity in hepatocytes. Conclusion The present study suggests that puerarin may alleviate cholestatic liver fibrosis, potentially by reducing bile duct proliferation, modulating extracellular matrix deposition, and promoting the conjugation of toxic bile acids. These findings indicate that puerarin could be a candidate therapeutic agent for cholestatic liver fibrosis. Further studies are required to fully elucidate its net protective effect on bile acid homeostasis.
Tumor drug resistance remains a major obstacle in cancer therapy, leading to the failure of chemotherapy, targeted therapy, and immunotherapy. This review explores how artificial intelligence (AI), particularly machine and deep learning models, integrates multi-omics data, including genomics, transcriptomics, and proteomics, with large-scale tumor databases such as TCGA and GDSC to enhance the prediction of drug resistance mechanisms. These approaches help identify key biomarkers and molecular pathways underlying resistance, such as DNA repair defects in chemotherapy, secondary mutations in targeted therapy, immunosuppressive microenvironments in immunotherapy, and other complications that alter the tumor-resistance microenvironment, such as thrombosis. Despite challenges like data heterogeneity, model interpretability, and clinical applicability, emerging strategies, such as multimodal data fusion, real-time monitoring via liquid biopsy, and explainable AI (XAI), are paving the way for more accurate and translatable predictive tools. These advances not only facilitate the development of personalized treatment regimens but also hold great potential to substantially improve prognostic outcomes and therapeutic efficacy in precision oncology.
Pancreatic ductal adenocarcinoma is a highly aggressive gastrointestinal malignancy with an extremely poor prognosis. Metabolic reprogramming serves as a key driver of its growth and invasion. Substantial evidence indicates that lactate, a product of glucose metabolic reprogramming, plays a crucial role in tumorigenesis and progression. Beyond its traditional view as a waste product, lactate functions as a metabolic fuel, signaling molecule, and epigenetic modification substrate, exhibiting pleiotropic roles in tumor proliferation, invasion, and immune suppression. Notably, lactate-mediated histone and non-histone lactylation exerts crucial regulatory effects across tumor cells, immune cells, and stromal cells within the cancer microenvironment. Inhibitors targeting key lactate-metabolizing enzymes and transporters, along with combinatorial therapeutic strategies, represent potential avenues for the future precision treatment of pancreatic ductal adenocarcinoma. This systematic review summarizes research advances on lactate metabolism and lactylation modification in pancreatic ductal adenocarcinoma, aiming to provide insights for the future exploration of lactate regulatory networks and the development of precision targeted therapies.
Background Tumor metastasis is the primary cause of poor survival in gastric cancer (GC) patients. PVT1 and EIF4A1 have been shown to synergistically promote GC metastasis and invasion. However, the underlying mechanism remains unclear. Methods The binding site between PVT1 and EIF4A1 was identified by RNA-binding protein immunoprecipitation (RIP). 4D-DIA proteomics combined with mass spectrometry was used to identify downstream proteins regulated by PVT1 and EIF4A1. From the differentially expressed proteins, Stanniocalcin-1 ( STC1) expression was validated in GC tissues, cell lines, and animal metastatic tumor samples. Following STC1 knockdown, cell proliferation and migration were assessed using MTT, colony formation, wound healing, and Transwell assays. Epithelial-mesenchymal transition (EMT) and Notch1 signaling were also evaluated. Results PVT1 bound to EIF4A1 through its N-terminal domain (NTD). Proteomic analysis revealed that PVT1 and EIF4A1 jointly upregulate STC1 expression. Immunohistochemistry (IHC) on a tissue microarray containing 183 GC samples, 128 adjacent normal tissues, and animal metastatic lesions demonstrated that STC1 was significantly upregulated in GC and correlated with metastasis, histological type, and tumor stage. Inhibition of EIF4A1 reduced STC1 expression, suggesting that STC1 is a key downstream target of the PVT1/EIF4A1 axis. Knockdown of STC1 attenuated GC cell migration and proliferation, and suppressed both EMT and the Notch1 signaling pathway. Conclusion STC1 acts as a critical downstream effector of PVT1 and EIF4A1, promoting GC cell metastasis and proliferation, thereby driving malignant progression. This mechanism involves the regulation of the Notch1 signaling pathway and the EMT process.
Cancer is one of the foremost causes of mortality worldwide and is characterized by uninterrupted cell growth, metastasis, and resistance to therapy. The present approach in molecular biology has emphasised the pivotal role of microRNAs (miRNAs) in regulating various cancer hallmarks. Among these, miR-29a has emerged as a pivotal regulator in the advancement of cancer, exhibiting as either an oncogene or a tumour suppressor depending on the cellular context. miRNA synthesis is biphasic-firstly, primary miRNA forms in the nucleus, then it is processed by Drosha (nucleus) and Dicer (cytoplasm) into mature miRNA. The miR-29 family (miR-29a, miR-29b, miR-29c) is linked to tumour aggressiveness and patient prognosis, making it a potential biomarker for predicting cancer development and recurrence. MiR-29a influences the tumour microenvironment and prevents invasion by selectively targeting collagen substrates. Research studies have demonstrated the impact of natural bioactive compounds in modulating the expression of miR-29a, which is known for its tumour-suppressive functions. Several natural products, including polyphenols, flavonoids, alkaloids, and terpenoids, have shown promising results in preclinical investigations by targeting key signalling pathways regulated by miR-29a. Further studies are imperative to elucidate the precise mechanisms through which miRNA-29a interacts with natural bioactive compounds in order to facilitate the development of novel therapeutic strategies in cancer treatment. This review comprehensively explores how natural bioactive compounds regulate miR-29a expression and their potential implication in cancer prevention, emphasising the integration of traditional knowledge with modern therapeutic approaches.
Background: Lactobacillus rhamnosus CMU-pb-7, one of the normal intestinal floras, can regulate intestinal micro-ecology and improve the body's anti-oxidative stress function, yet its protective role in diabetic nephropathy (DN) remains unclear. Methods: 24 male rats were divided into a normal control, a DN model, and a CMU-pb-7 treatment group. The DN model was induced by a high-fat diet plus streptozotocin. After CMU-pb-7 administration, biochemical and oxidative stress indicators and renal histopathology was detected. Renal Keap1, Nrf2, HO-1, and Gpx4 expression was determined by IHC, RT-PCR, and Western Blot. In vitro, AGEs-stimulated HK-2 cells were treated with butyrate, and cell viability, ROS level, and the related protein expression were determined. Results: Compared with the DN model group, CMU-pb-7 treatment significantly improved the general condition and serum biochemical profiles of DN rats, with reductions in serum TC, TG, UA, SCr and BUN (36.30%, 55.10%, 36.00%, 39.70%, 60.60%). CMU-pb-7 also effectively reversed DN-related renal interstitial fibrosis, restored renal antioxidant capacity by increasing GSH and SOD levels (58.30%, 99.80%), and reduced MDA and Fee+ levels (38.10%, 24.30%). IHC, qPCR, and Western blot analyses showed a suppressed expression of Nrf2, HO-1, and Gpx4, concomitantly with an elevation in Keap1 in DN rat kidney tissues. These alterations were effectively reversed by CMU-pb-7 administration. In HK-2 cells, butyrate treatment significantly attenuated AGEs-induced increased ROS levels and the downregulation of Nrf2/HO-1/Gpx4 pathway. Conclusion: CMU-pb-7 alleviates renal dysfunction in DN rats, possibly by reducing oxidative stress, an effect associated with activation of the renal Nrf2/HO-1/Gpx4 pathway.
Background: Aging impairs the resolution of bleomycin-induced pulmonary fibrosis (PF) in mice. As extracellular matrix degradation is crucial for PF reversal, we investigated whether aging compromises collagen I phagocytosis and explored the underlying mechanisms. Methods: Primary lung fibroblasts were isolated from young (6-week-old) and middle-aged (8-month-old) mice. Collagen I phagocytosis, lysosomal pH, and mitochondrial reactive oxygen species (mitoROS) were assessed. The role of full-length PRD-BF1 and RIZ homology (PR) domain-containing 16 (fPRDM16) was evaluated via overexpression and knockdown. In vivo fibrosis resolution and fPRDM16 expression were analyzed in bleomycin-treated mice. Results: Fibroblasts from aged mice exhibited reduced collagen I phagocytosis, elevated lysosomal pH, and increased mitoROS. Enhancing lysosomal function with rapamycin or scavenging mitoROS with mitoquinone restored phagocytosis. fPRDM16 expression was downregulated with age and upon transforming growth factor-j3 (TGF-j3) stimulation. Its overexpression rescued phagocytic defects, improved lysosomal acidification, and reduced mitoROS, thereby disrupting a pathogenic mitochondria-lysosome feedback loop. In vivo, aged mice showed impaired fibrosis resolution and reduced lung fPRDM16 levels. Conclusions: fPRDM16 downregulation in aging impairs fibroblast-mediated collagen clearance via a mitochondria-lysosome dysfunction loop. Targeting fPRDM16 may represent a novel therapeutic strategy to promote fibrosis resolution.
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell-surface receptor primarily expressed on myeloid cells, including macrophages, monocytes, and neutrophils, where it functions as a potent amplifier of innate immune responses. Dysregulated TREM-1 activation has been increasingly implicated in the pathogenesis of both acute and chronic inflammatory conditions, including sepsis, inflammatory arthritis, and neurodegenerative diseases. Despite advances in supportive care, effective targeted therapies that modulate excessive inflammation remain limited, particularly in sepsis and neuroinflammatory disorders. Recent preclinical and emerging clinical evidence highlight TREM-1 as a promising therapeutic target and soluble TREM-1 as a potential biomarker for disease severity and prognosis. This review provides an updated overview of TREM-1 biology, its signalling pathways, and its pathogenic role in sepsis, arthritis, and neurodegenerative diseases, with a particular focus on recent advances in TREM-1-targeted therapeutic strategies and their translational relevance.
Lactylation is a newly identified post-translational modification of proteins that occurs in both histones and non-histones. Studies have shown that lactylation plays a key role in the progression of lung cancer (LC) and is associated with poor clinical outcomes. Aberrant histone lactylation can alter gene expression in tumor and immune cells, thereby affecting LC progression and immune suppression. Lactylation of non-histones also plays a role in regulating proliferation and drug resistance in LC. This article provides a brief introduction to lactylation modification, reviews its role and mechanism in the progression and drug resistance of LC, shares the latest research results of lactylation modification in LC, and discusses its potential application in tumor targeted therapy and combined immunotherapy.
