Inflammatory bowel disease (IBD) is a chronic intestinal disorder caused by immune dysregulation, leading to persistent inflammation and recruiting a large number of immune cells to the intestinal inflammation sites. When immune cells become aberrantly activated, macrophages, neutrophils, dendritic cells, T cells and B cells infiltrate affected intestinal sites, releasing pro-inflammatory cytokines that amplify tissue damage and perpetuate disease progression. Base on pathological mechanisms, immune cell-targeted nanocarrier systems have emerged as innovative platforms for precise drug delivery to inflamed colonic regions, minimizing off-target effects, regulating immune imbalance and enhancing therapeutic efficacy. This review systematically examines the roles of key immune cells and their associated signaling pathways in IBD pathogenesis, with a particular focus on immune regulatory mechanisms at inflammatory foci. Furthermore, it explores design strategies for nanoparticles functionalized with specific ligands, including mannose, folic acid, lactoferrin, and hyaluronic acid, which facilitate selective targeting of immune cells. These modifications optimize immune cell phenotype modulation, cytokine secretion control, and tissue repair, significantly reducing systemic toxicity and improving drug bioavailability. Finally, challenges and future perspectives, including ligand specificity optimization, clinical translation barriers, and multifunctional nanoparticle development, are discussed to advance IBD treatment paradigms. Collectively, this comprehensive summary of immune cell-targeted nanotherapeutics provides novel insights into precision treatment strategies for IBD, paving the way for more effective and targeted therapeutic interventions.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that various of the western blot data featured in Fig. 2B appeared to have also been included in Figs. 4B and 8A; moreover, western blot data also appeared to have been duplicated comparing Figs. 3A and 8A, Figs. 4B and 5A, Figs. 3A and 5A, and Figs. 6A and 7A. In addition, western blot data featured in various of these figures also reappeared in two papers written by different authors at different research institutes that were submitted for publication at later dates to the journals Experimental and Therapeutic Medicine and Molecular Medicine Reports. In view of the fact that so many instances of the duplication of data within several of the figures in the above paper were identified, the Editor has decided that this paper should be retracted from the Journal on account of a lack of confidence in the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 12: 6591‑6597, 2015; DOI: 10.3892/mmr.2015.4292].

Bioactive triterpenoids present in plant-derived foods are emerging as modulators of metabolic health, although their molecular targets and mechanisms remain unclear. In this study, we characterize Pomolic acid and Hederagenin, two pentacyclic triterpenoids from Rosa canina, as antagonists and selective modulators of peroxisome proliferator-activated receptor gamma (PPARγ). Both compounds reduced lipid accumulation during 3T3-L1 adipocyte differentiation and antagonized rosiglitazone-induced PPARγ transactivation without intrinsic agonist activity. Pomolic acid behaved as a neutral antagonist, repressing adipogenic and lipogenic gene expression and preventing TRAP220 recruitment. In contrast, Hederagenin selectively modulated PPARγ target genes involved in lipid handling while limiting triglyceride accumulation. TR-FRET assays confirmed direct binding to the receptor, and molecular dynamics simulations revealed a betulinic acid─like binding mode that destabilizes helices H11-H12 and disrupts the AF-2 coactivator interface. These findings provide mechanistic insight into how structurally related dietary triterpenoids modulate PPARγ signaling and support them as candidates for metabolic disease strategies.

Group 3 innate lymphoid cells (ILC3s) play an essential role in maintaining intestinal barrier immunity. Dysfunction of ILC3s contributes to the pathogenesis of inflammatory bowel disease (IBD), whereas the mechanisms underlying ILC3 regulation remain incompletely understood. Here, we report that the transcription factor BTB domain and CNC homolog 2 (BACH2) represents an important regulator of intestinal ILC3s. ILC3s from IBD patients exhibited reduced BACH2 expression compared with those from healthy donors. Conditional ablation of BACH2 in ILC3s impaired their function, thereby exacerbating the severity of murine colitis. Mechanistically, BACH2 enhanced mitochondrial oxidative phosphorylation in ILC3s in a peroxisome proliferator-activated receptor γ (PPARγ)-dependent manner. PPARγ was identified as a direct transcriptional target of BACH2 in ILC3s. Notably, pharmacological activation of PPARγ with rosiglitazone restored ILC3 function and ameliorated colitis in BACH2-deficient mice. These observations demonstrate that the presence of BACH2-PPARγ signaling in ILC3s protects against colitis.

Traumatic brain injury (TBI) remains a major global health challenge, characterized by high morbidity and mortality rates. Despite advances in neuroscience, the blood-brain barrier (BBB) limits the effectiveness of potential neuroprotective treatments. Recent nanotechnology breakthroughs have led to smart drug delivery systems that can cross the BBB and target injured brain areas. However, achieving the specificity needed to deliver therapies to affected neurons remains a challenge. In previous work, we developed a mixed-layered dendrimer functionalized with 2-deoxyglucose (2DG-D) for selective neuronal drug delivery. In this study, we explore the therapeutic potential of rosiglitazone (Rosi) for pediatric TBI by creating a 2DG-D-Rosi nanosystem, where Rosi is conjugated to 2DG-D to improve its solubility, bioavailability, and targeted delivery to injured neurons. In vitro, 2DG-D-Rosi demonstrated high neuronal uptake, sustained drug release, and excellent biocompatibility. It significantly reduced neuronal apoptosis, reactive oxygen species formation, pro-inflammatory cytokine expression, and caspase activity, outperforming free Rosi. In vivo, using a pediatric TBI mouse model, 2DG-D-Rosi improved neuronal targeting, reduced neuroinflammation, and enhanced behavioral outcomes. This research highlights 2DG-D-Rosi as a promising nanotherapeutic platform for precise TBI treatment and sets the stage for developing more effective therapies for this challenging condition.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, and tumors harboring p53 mutations have limited therapeutic options. Chronic inflammation and microRNA dysregulation are key drivers of NSCLC progression, yet their coordinated therapeutic targeting remains poorly understood. This study aimed to evaluate whether a novel therapeutic combination of colchicine (Col) and rosiglitazone (Rosi) can modulate hsa-miRNA-26a-5p and hsa-miRNA-21-5p and influence IL-6/STAT3/axis-driven oncogenic signaling in NSCLC, particularly under inflammatory conditions. Given the central role of p53 gene in controlling cellular response to therapy, we investigated the role of mutant p53 vs wild-type in response to the individual and combined treatment of Col/Rosi in two NSCLC cell lines, A549 (p53-wild-type) and NCI-H358 (p53-null, transfected with p53-R273H mutant), using WST-1 viability assays, caspase-3 and PARP1 assays, western blotting, and RT-qPCR analysis of key miRNAs. In silico modeling and transcriptomic data from lung adenocarcinoma patients were used to support mechanistic and clinical relevance. In p53-R273H-mutant NCI-H358 cells, the Col/Rosi treatment synergistically reduced viability and induced apoptosis more effectively than either agent alone. This effect was associated with upregulation of the tumor-suppressor hsa-miRNA-26a-5p, suppression of oncogenic hsa-miRNA-21-5p, restoration of PTEN, PDCD4, and LIN28B, and inhibition of the IL-6/STAT3/NF-κB axis, consistent with patient-derived datasets. In contrast, p53-wild-type A549 cells exhibited an antagonistic response. This study identifies a genotype-dependent therapeutic interaction between Col and Rosi and demonstrates that reprogramming of hsa-miRNA-26a-5p and hsa-miRNA-21-5p constitutes a central mechanism underlying their anti-tumor and anti-inflammatory effects in NSCLC, particularly in p53-R273H-mutant NCI-H358 cells compared with p53-wild-type cells. The findings highlight the need for further investigation into the Col/Rosi combination for inflammation-related lung cancer and p53 expression. In vitro studies and bioinformatics analyses suggest a miRNA-associated regulatory mechanism that could guide future research.

The peroxisome proliferator-activated receptors (PPARs), including PPAR-α, PPAR-β/δ, and PPAR-γ, are nuclear receptors that play critical roles in regulating metabolism and inflammation. While PPARs have been extensively investigated in classical metabolic disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD), type 2 diabetes, and lipid metabolism disorders, their roles in pancreatic metabolic diseases remain underexplored. Given the absence of a systematic review on this topic, the present review provides a comprehensive overview of the mechanisms and therapeutic potential of PPAR subtypes in pancreatic metabolic conditions, including fatty pancreas (FP), hypertriglyceridemic pancreatitis (HTGP), and pancreatogenic diabetes. PPARs contribute to the pathogenesis and progression of these diseases by modulating lipid metabolism, inflammatory responses, and β-cell function. By integrating molecular insights with clinical evidence, this review highlights the lipid-modulating and anti-inflammatory effects of PPAR-targeted therapies and discusses their associated clinical benefits and risks. The aim is to establish a theoretical foundation for novel therapeutic strategies in pancreatic metabolic diseases. Nevertheless, preclinical and clinical studies in this area remain limited, and direct clinical evidence supporting the efficacy of PPAR agonists in pancreatic contexts is currently lacking. Further research is warranted to elucidate the direct therapeutic efficacy of PPAR agonists in pancreatic metabolic diseases.

Heart failure (HF), the advanced stage of diverse cardiac conditions, poses a significant public health challenge. This study analyzes adverse event (AE) signals associated with HF within the FDA Adverse Event Reporting System (FAERS) database, offering critical insights to guide rational medication use in clinical settings. Adverse event reports (AERs) associated with HF in the FAERS database, spanning from the first quarter of 2004 to the fourth quarter of 2024, were analyzed. The potential HF risk of drugs was assessed using the disproportionality analysis, with findings juxtaposed against the American Heart Association (AHA) drug list. Drug-induced HF cases showed equivalent distribution between male and female, and high rates of rehospitalization and mortality. Prominent hypoglycemic drugs associated with HF included rosiglitazone, pioglitazone, and saxagliptin. Combination therapies, such as metformin/saxagliptin and metformin/rosiglitazone, also demonstrated elevated risks. In the context of pulmonary hypertension, drugs like macitentan, selexipag, and epoprostenol were particularly notable. Analysis against the AHA drug list confirmed stronger signal strength and frequency among Class A drugs, validating our results. Furthermore, drugs not flagged as positively signaling in the AHA registry, such as amiodarone, aliskiren, and testosterone, merit closer scrutiny due to their potential for adverse reactions. Our analysis of the FAERS database has identified medications associated with potential HF risks, providing valuable evidence to inform clinical decision-making and promote the safe use of medications.

This article investigates the effects of losartan, metformin, and rosiglitazone on triple-negative breast cancer (TNBC) with an intent to repurpose these drugs for cancer therapy. The cytotoxicity of the compounds was evaluated through the MTT assay, where cells were exposed to each drug, both singularly and in combinations, over 48 h. The median inhibitory concentration (IC50) for each drug was calculated using nonlinear regression via GraphPad Prism, yielding IC50 values of 1231 μM for losartan, 30.37 μM for metformin, and 267.1 μM for rosiglitazone. The study highlights a synergistic effect particularly between losartan and metformin in TNBC, revealing a 1.6-fold increase in potency at a fixed 1:1 combination ratio. This combination facilitated enhanced cell growth inhibition over individual drug treatments, particularly at concentrations below 1280 μM. Furthermore, when losartan was combined with rosiglitazone, there was a notable augmentation in synergistic effects, underscoring improved efficacy, as seen by right-shifted dose-response curves and increased maximal responses at concentrations of 320 μM or higher. In assays with MDA-MB-231 cells, strong synergy was detected at minimal doses when losartan and metformin were combined, leading to significant dose reduction indices (DRIs) of 21.92 for losartan and 17.247 for metformin. In contrast, findings indicated that while losartan moderately inhibited growth within 48 h, the combination treatment did not yield any additional synergism with rosiglitazone at lower doses. The study concludes that although losartan and rosiglitazone exhibit strong synergy in inhibiting TNBC growth, the concurrent administration of these drugs at lower dosages presents limitations in achieving further synergistic or additive effects.

Psoriasis is a chronic, systemic inflammatory disease characterized by combined epidermal and immunological pathology. It is becoming recognized as a metabolic inflammatory disorder caused by interleukin (IL)-23/Th17 axis imbalance and lipid metabolism dysfunction. Peroxisome proliferator-activated receptors (PPARs), including peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor beta/delta (PPARβ/δ), and peroxisome proliferator-activated receptor gamma (PPARγ), regulate metabolic homeostasis and immune tolerance, making them potential targets for treating the psoriatic march of comorbidities such as obesity, insulin resistance, psoriatic arthritis, non-alcoholic fatty liver disease, and accelerated atherosclerosis. This review aims to summarize current evidence on PPAR isoform-specific roles in psoriatic pathogenesis, explore the molecular mechanisms that link PPARs to cutaneous and systemic inflammation, and assess the therapeutic potential and translational challenges of PPAR-directed pharmacotherapy. Peer-reviewed research on PPAR biology in psoriasis, metabolic comorbidities, and the clinical effectiveness of PPAR ligands was identified by a comprehensive literature search of PubMed/MEDLINE, Scopus, and Web of Science (2014-2024, with seminal papers from 2000+). Real-world evidence, randomized controlled trials, and mechanistic studies were given priority in the analysis. In psoriatic lesions, PPARγ is downregulated, leading to nuclear factor-κB and signal transducer and activator of transcription 3 deregulation. This promotes keratinocyte hyperproliferation and Th17 cell differentiation. PPARβ/δ is overexpressed, leading to anaerobic glycolysis and peroxisomal fatty acid β-oxidation. This depletes structural barrier lipids and maintains hyperplasia. Reduced PPARα inhibits lipogenesis at the epidermal barrier. Thiazolidinedione agonists (pioglitazone, rosiglitazone) have modest but clinically significant anti-psoriatic efficacy when combined with traditional systemic medicines, resulting in cardiometabolic benefits. Preclinical studies suggest that PPAR-selective antagonists, such as 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl] sulfonyl} ethyl)benzamide 3 (GSK3787) for PPARδ, outperform broad agonism. Topical PPAR ligand bioavailability remains inadequate, necessitating innovative delivery strategies. Although PPAR modulation offers a dual-benefit treatment approach that simultaneously suppresses metabolic dysregulation and cutaneous inflammation, there are still significant gaps between genetic potential and clinical reality. Future directions include patient biomarker stratification, dual/selective agonists (glitazars), and sensible combination with biologics that target tumor necrosis factor-alpha/IL-17/IL-23. This review reframes PPARs as key players in the relationship between psoriasis and metabolic syndrome by synthesizing molecular understanding and clinical data.

Although hypertension (HYP) consistently predicts cognitive decline, the precise pathogenic cascade within the brain remains elusive. Here we interrogated whether the PPARγ/ACSL3 axis governs HYP-elicited hippocampal ferroptosis and consequent cognitive dysfunction. This study aimed to explore the role of the PPARγ/ACSL3 axis in HYP-induced neuronal ferroptosis and cognitive impairment. In the HYP rat model, behavioral tests (Morris water maze and Y-maze tests) demonstrated that rats in the hypertensive group had a significant decline in learning and memory. Mechanistically, the AngII-AT1R axis was found to be activated in the hippocampus, accompanied by typical ultrastructural features of ferroptosis, increased iron accumulation, elevated oxidative stress, and downregulation of PPARγ, ACSL3, and key ferroptosis defense proteins (GPX4, XCT, and FPN1). In vitro, ACSL3 overexpression alleviated AngII-induced neuronal ferroptosis. Furthermore, the PPARγ agonist rosiglitazone attenuated lipid peroxidation and iron overload by transcriptionally upregulating ACSL3, a direct regulatory relationship confirmed by dual-luciferase reporter assay. In conclusion, under hypertensive conditions, BRAS activation inhibits the PPARγ/ACSL3 axis via the AngII-AT1R pathway, aggravates lipid peroxidation and ferroptosis in hippocampal neurons, and ultimately contributes to cognitive decline. This study provides new experimental evidence for the mechanism research and therapeutic target exploration of HYP-related cognitive impairment.