Molecular medicine reports最新文献

Doxorubicin (DOX) is an effective anthracycline agent used to combat a number of neoplastic diseases. However, DOX causes cardiovascular toxicity in juvenile and young adult survivors of cancer that can lead to future cardiomyopathy. Thus, it is important to address the cardiovascular toxicity caused by DOX to improve the long‑term health of patients with cancer. Soluble epoxide hydrolase (sEH) and cyclooxygenase‑2 (COX‑2) are implicated in cardiovascular diseases by impairing vascular health and promoting the transition of endothelial cells to mesenchymal cells. Given the role of sEH and COX‑2 in endothelial‑to‑mesenchymal transition (EndMT)‑derived cardiovascular toxicity, the present study aimed to investigate the effect of a dual sEH/COX‑2 inhibitor, 4‑[5‑phenyl‑3‑[3‑[[[[4‑(trifluoromethyl)phenyl] amino]carbonyl]amino]propyl]‑1H‑pyrazol‑1‑yl]‑benzenesulfonamide (PTUPB), on DOX‑induced EndMT‑derived vascular and cardiac toxicity. The mitigating effect of PTUPB on DOX‑induced cardiovascular toxicity was explored in zebrafish. The cardiovascular parameters were measured using the Viewpoint MicroZebralab software. Additionally, the effect of PTUPB on DOX‑induced EndMT was assessed in human endothelial cells. The data from the present study indicated that the inhibition of sEH and COX‑2 using PTUPB reduced DOX‑induced EndMT and vascular toxicity. The data also demonstrated that PTUPB improved cardiac function and morphology in zebrafish incubated with DOX. The results of the present study showed that PTUPB downregulated inflammation and oxidative stress markers, which contributed to the improvement in DOX‑induced cardiovascular toxicity. In conclusion, the findings of the present study indicated that the suppression of sEH/COX‑2 using PTUPB reduced DOX‑induced EndMT and the resulting vascular and cardiac toxicity.

Allergic rhinitis (AR) is a chronic inflammatory disorder of the nasal mucosa, often a comorbid condition with asthma, posing notable challenges for treatment. Current therapies, including corticosteroids and antihistamines, primarily target nasal symptoms but exhibit limited efficacy against concurrent asthma and systemic inflammation. Saponins, a class of bioactive plant‑derived compounds, have garnered attention for their pleiotropic effects, including immunomodulation, anti‑inflammatory activity and antioxidant properties. Saponins, such as ginsenosides, notoginsenosides, astragalosides, saikosaponins and platycodins, modulate key molecular pathways in AR, including T helper 1/2 cell balance, mast cell stabilization and NF‑κB signaling. Their multi‑target action and low toxicity profile give them advantages such as metabolic compatibility, reduced polypharmacy risks and mucosal protection. The present review highlighted the mechanistic insights into saponin‑mediated alleviation of AR and asthma, focusing on their molecular targets, signaling pathways and potential for clinical translation. The present review also discussed current limitations and future directions for the development of saponin‑based therapeutics, providing a potential foundation for novel strategies in allergic airway diseases in the future.

Sepsis is a systemic inflammatory disorder characterized by multi‑organ dysfunction following infection. Sepsis‑induced cardiomyopathy (SIC) represents a prevalent complication that markedly contributes to in‑hospital mortality. The NOD‑like receptor protein 3 (NLRP3) inflammasome serves as an important regulator in SIC pathogenesis, directly impairing cardiac function through multiple mechanisms: i) Driving cytokine storms; ii) inducing cardiomyocyte pyroptosis and apoptosis; iii) disrupting mitochondrial homeostasis; and iv) suppressing autophagy. Molecularly‑targeted NLRP3 inhibitors have been developed, such as MCC950, curcumin, indole‑3‑propionic acid and carvacrol, which have demonstrated cardioprotective effects in cellular and animal models of SIC. Further exploration of NLRP3 mechanisms and resulting therapeutic targets may yield novel strategies for SIC diagnosis and clinical management. The present review examined NLRP3‑mediated pathways involving inflammation, programmed cell death and mitophagy in SIC pathogenesis, summarized pharmacological interventions targeting these pathways and highlighted previous advances in NLRP3 research to inform future therapeutic development and clinical translation.

Ulcerative colitis (UC) is a chronic autoimmune disease characterized by mucosal inflammation and disruption of the intestinal barrier. Current therapies often produce adverse effects, underscoring the need for novel treatment options. Naringin, a flavonoid from Citrus aurantium L., has shown anti‑inflammatory potential in inflammatory bowel disease. However, its role in UC via the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway remains elusive. The present study investigated the therapeutic effects of naringin on UC, with a focus on JAK2/STAT3 signaling and intestinal barrier restoration. The present study employed a dextran sulfate sodium (DSS)‑induced colitis mouse model and IL‑6‑stimulated Caco‑2 cells. Mice were administered 3% DSS for 10 days along with naringin (40 mg/kg) or mesalazine (0.2 g/kg) treatment. Disease activity index (DAI), histopathology, expression of tight junction proteins zona occludens‑1 (ZO‑1) and occludin and JAK2/STAT3 pathway protein activation were evaluated. In Caco‑2 cells, transepithelial electrical resistance (TEER) and fluorescein isothiocyanate‑dextran 4 kDa (FD‑4) permeability assays assessed barrier function, with STAT3 silencing supporting pathway involvement. Naringin markedly alleviated DSS‑induced colitis, reducing weight loss, colon shortening, DAI and histological scores. Furthermore, naringin restored ZO‑1 and occludin expression while suppressing JAK2/STAT3 phosphorylation in colon tissues. In Caco‑2 cells, naringin reversed IL‑6‑induced reductions in TEER and increases in FD‑4 permeability, while enhancing tight junction fluorescence. Furthermore, STAT3 silencing in combination with naringin led to a further decrease in the p‑JAK2/JAK2 ratio compared with that in the IL‑6 group (though to a lesser extent than naringin alone), consistent with the involvement of the JAK2/STAT3 pathway. Collectively, these findings demonstrate that naringin ameliorates UC by promoting intestinal barrier repair through suppression of JAK2/STAT3 activation, highlighting its therapeutic potential for UC.

Splicing factor 3a subunit 2 (SF3A2) has been implicated in an increasing number of tumor types; however, at present, its role in clear cell renal cell carcinoma (ccRCC) has yet to be fully elucidated. Therefore, the aim of the present study was to preliminarily explore the putative function of SF3A2 in ccRCC. To meet this aim, SF3A2 expression in ccRCC tissues was analyzed using The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset and conducted reverse transcription‑quantitative PCR, western blotting and immunohistochemical staining of ccRCC cell models to validate its functional roles. To evaluate the impact of SF3A2 expression on the proliferation, migration and invasion of ccRCC cells, Cell Counting Kit‑8 assays, colony formation assays, Transwell assays and an in vivo xenograft model were employed. Furthermore, western blot analysis was performed to explore which proteins may be involved in the underlying mechanisms of the effects of SF3A2 in ccRCC progression. SF3A2 was found to be markedly upregulated in ccRCC cells and tissues, and its high expression was associated with poor prognosis. The functional assays and in vivo experiments revealed that SF3A2 knockdown inhibited the proliferation, migration and invasion of the ccRCC cells, whereas its overexpression enhanced these processes. In terms of the underlying mechanism, SF3A2 was shown to promote ccRCC progression via activation of the AKT signaling pathway. In conclusion, the present study identified SF3A2 upregulation as a prognostic marker in ccRCC, which was associated with poor clinical outcomes and accelerated tumor progression. Mechanistically, SF3A2 exerted tumor‑promoting effects through the AKT signaling pathway. Taken together, these findings positioned SF3A2 as a dual‑functional biomarker with translational potential, facilitating prognostic stratification and presenting therapeutic targeting opportunities for ccRCC management.

Ferroptosis is an iron‑dependent form of cell death associated with liver pathologies. However, its role in chronic cholestasis remains to be fully elucidated. The present study therefore investigated the pathological mechanism of ferroptosis in a rat model of α‑naphthyl isothiocyanate (ANIT)‑induced chronic cholestasis and evaluated the therapeutic potential of the iron chelator deferoxamine (DFO). Wistar rats were used to establish a chronic cholestasis model via ANIT administration, with a subset of animals receiving DFO treatment. Wistar rats that were subjected to chronic ANIT exposure were found to develop severe liver injury, characterized by impaired function, inflammation and fibrosis. In addition, pronounced iron deposition and hallmark features of ferroptosis, including elevated lipid peroxidation, depleted glutathione, and aberrant expression of acyl‑CoA synthetase long‑chain family member 4 and cyclooxygenase 2, were observed. Ultrastructural analysis revealed distinctive mitochondrial abnormalities consistent with ferroptosis. Mechanistically, these changes appeared to be mediated by suppression of the Kelch‑like ECH‑associated protein 1/nuclear factor erythroid 2‑related factor 2/heme oxygenase 1 antioxidant pathway and dysregulation of key iron metabolism proteins, including transferrin receptor 1 and ferroportin 1. Intervention with DFO markedly ameliorated the cholestatic injury, reduced iron overload and lipid peroxidation, mitigated mitochondrial damage, and normalized the expression of key proteins involved in ferroptosis, antioxidant defense and iron homeostasis. Taken together, these findings suggested that ferroptosis may be a key pathological mechanism in chronic cholestasis, driven by the concurrent disruption of antioxidant and iron metabolic capacities in hepatocytes. Therefore, targeting iron overload may be a promising therapeutic strategy for cholestasis.

Klebsiella pneumoniae has emerged as a leading cause of pyogenic liver abscess (PLA), driven by hypervirulent and multidrug‑resistant (MDR) strains that pose major diagnostic and therapeutic challenges. This organism exhibits extensive capsular diversity (K1‑K80), with serotypes K1, K2, K5, K20, K54 and K57 being the most associated with invasive infections and severe clinical outcomes. Increasing convergence between hypervirulence and MDR determinants threatens effective management worldwide. Pharmacological and safety limitations of current antibiotics, including nephrotoxicity of colistin, hepatotoxicity of tigecycline and poor drug penetration into abscess cavities, further complicate treatment and encourage exploration of non‑traditional strategies such as anti‑virulence or immunomodulatory approaches. Recent advancements in rapid diagnostic tools such as metagenomic sequencing, MALDI‑TOF and point‑of‑care PCR assays offer promising prospects for early detection and antimicrobial optimization. Pharmacokinetic challenges at the abscess site and the emergence of hybrid hvKp‑MDR strains emphasize the urgency of precision‑guided therapy and robust global surveillance. K. pneumoniae‑associated PLA thus represents an evolving global health threat and understanding serotype diversity, antibiotic limitations and diagnostic innovations is essential for developing more effective preventive and therapeutic strategies. The present review provides current insights into the epidemiology, pathogenesis and therapeutic challenges of K. pneumoniae‑associated PLA, while highlighting translational opportunities and research priorities to counter the escalating dual threat of hypervirulence and resistance.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the cell invasion and migration assay data shown in Fig. 5B were strikingly similar to data appearing in different form in another article written by different authors at different research institutes that had already been published in the journal PLoS One, albeit the brightness and contrast of the images appeared to have been altered. Owing to the fact that the contentious data mentioned above had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. 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 17: 6526-6532, 2018; DOI: 10.3892/mmr.2018.8663].

In 2022, the World Health Organization estimated that globally, ~2.5 billion adults were overweight, including 890 million individuals with obesity. Adipose tissue dysfunction in obese individuals is a key contributor to the pathogenesis of insulin resistance. Within the present study, the association between serum levels of C1q/TNF‑related protein 4 (CTRP4) and insulin resistance (IR) in overweight/obese patients was investigated and the effects and mechanisms of CTRP4 on IR in dexamethasone‑induced 3T3‑L1 adipocytes were evaluated. A total of 98 overweight/obese patients were enrolled in the present study. Serum CTRP4 concentration levels were measured with ELISA kits. Correlations between CTRP4 and the homeostatic model assessment of IR (HOMA‑IR) were evaluated using Spearman's correlation analysis. Recombinant CTRP4 protein was administered to fully differentiated 3T3‑L1 adipocytes to explore the impact of CTRP4 on lipid accumulation. In addition, the effects of CTRP4 on restoring impaired glucose uptake were examined through the glucose oxidase‑peroxidase method. Molecular marker expression levels in the insulin signaling pathway, in 3T3‑L1 adipocytes with IR induced by 1 µM dexamethasone, were also examined, through western blotting. The expression levels of CTRP4 exhibited a negative association with body mass index (r=‑0.35; P<0.001), HOMA‑IR (r=‑0.24; P=0.048), waist circumference (r=‑0.38; P<0.001) and abdomen circumference (r=‑0.39; P<0.001). Following treatment of cells with recombinant CTRP4, a significant reduction in lipid accumulation was observed in 3T3‑L1 adipocytes, alongside with an increase in the glucose uptake rate in dexamethasone‑induced 3T3‑L1 adipocytes (all, P<0.05). Furthermore, a marked elevation in the expression levels of insulin receptor substrate 1 (IRS‑1), PI3K and AKT phosphorylation and GLUT4 was observed in the IR model of 3T3‑L1 adipocytes. Serum CTRP4 concentration levels were negatively correlated with IR in overweight/obese patients. CTRP4 suppressed lipid accumulation and promoted glucose uptake through the IRS‑1/PI3K/AKT signaling pathway and caused increased GLUT4 expression in 3T3‑L1 adipocytes.8.

Overactive bladder (OAB) is a common condition that affects lower urinary tract symptoms and markedly affects the physical and mental health of individuals. While the cause of OAB is unclear, some studies suggest a possible link to psychological factors, particularly anxiety. Despite this, research on the connection between anxiety and OAB is limited. The present study aimed to explore anxiety‑induced OAB by analyzing clinical data and identifying key genes and pathways in vivo, ultimately providing new insights for diagnosing and treating OAB. Clinical data were analyzed to explore the relationship between anxiety and OAB. A chronic restraint stress model was used to induce anxiety, with histological scoring and cystometry assessing bladder function. Bladder transcriptomics identified key genes and pathways in OAB development. Differences in oxidative stress and NF‑κB pathway activity were validated using immunohistochemistry, enzyme‑linked immunosorbent assay and quantitative PCR. Clinical data showed a positive link between overactive bladder symptom scores and general anxiety disorder scale‑7, with higher urination urgency scores in OAB patients with anxiety. Analysis confirmed anxiety as an independent risk factor for OAB. In vivo experiments showed that anxiety induced OAB‑like symptoms in mice through oxidative stress and NF‑κB pathway activation, with RNA sequencing revealing key hub genes included heat shock protein 90 (Hsp90) aa1, Hsp90ab1 and Hsp90b1. The present study demonstrated that anxiety may precipitate the onset of OAB by activating oxidative stress and the NF‑κB signaling pathway. Hsp90 may serve as a potential biomarker for diagnosing anxiety‑induced OAB. Retrospectively registered on 1 April 2025, The present study received the identifier ChiCTR2500100548 from the Chinese Clinical Trial Registry.