Molecular medicine reports最新文献

Oxidative stress and macrophage migration contribute to chronic inflammation and resultant tissue damage. The nuclear factor erythroid 2‑related factor 2 (Nrf2) antioxidant pathway plays a key role in maintaining redox balance and modulating immune cell behavior. Lipoteichoic acid (LTA), a component of Gram‑positive bacterial membranes, activates macrophages and overproduces reactive oxygen species (ROS), causing oxidative stress and aberrant macrophage migration. In the present study, the effects of glabridin (GBD), a flavonoid from licorice with antioxidant potential, on LTA‑mediated oxidative stress and alveolar macrophage migration were investigated. GBD pretreatment reduced intracellular ROS levels, as measured through 2',7'‑dichlorofluorescin diacetate and dihydroethidium staining. Immunofluorescence microscopy revealed increased nuclear translocation of Nrf2 following GBD treatment. Western blotting demonstrated elevated expression of Nrf2 and its downstream target, heme oxygenase‑1 (HO‑1). Cotreatment with the Nrf2 inhibitor ML385 attenuated GBD‑mediated Nrf2 activation and HO‑1 expression, suggesting involvement of the Nrf2/HO‑1 pathway. Functionally, GBD inhibited LTA‑induced macrophage migration, and this effect was attenuated by ML385 cotreatment. These findings demonstrate that GBD suppresses LTA‑induced macrophage migration, at least in part, through the Nrf2/HO‑1 signaling pathway, suggesting potential therapeutic relevance in inflammatory lung diseases.

Tuberculosis (TB) is an infectious disease caused by infection with Mycobacterium tuberculosis (MTB). The morbidity of TB in the Xinjiang region of China is higher than that in other provinces. Macrophage apoptosis after infection with MTB is considered to serve a key role in killing the bacteria. However, the biological process of apoptosis and the underlying molecular mechanisms triggered by the infection of macrophages with clinical isolates of MTB from Xinjiang (XJMTB) are not clear. The present study aimed to investigate the unique characteristics of XJMTB. Briefly, western blotting and flow cytometry were employed in the present study, and it was demonstrated that macrophages infected with MTB H37Rv or XJMTB underwent G2/M cell cycle arrest and apoptosis. The transcriptome sequencing analysis showed that cyclin‑dependent kinase 1 (CDK1) was a key regulatory gene in regulating the G2/M cell cycle arrest and apoptosis in MTB‑infected macrophages, and the p53 gene was most likely involved in the regulation of this. Moreover, the phosphorylation of p53 (Ser315) was elevated with the upregulation of CDK1 activation, leading to a higher proportion of MTB‑infected macrophages exhibiting G2/M cell cycle block and apoptosis. The current study also revealed that enhanced activation of CDK1 reversed the attenuation of the G2/M cell cycle block and the reduction in the percentage of apoptosis caused by inhibition of p53 (Ser315) phosphorylation. Furthermore, the co‑immunoprecipitation experiment demonstrated an interaction between CDK1 and p53. The present study indicated that, in an in vitro model of macrophage infection with XJMTB, enhanced activation of CDK1 may regulate the phosphorylation of p53 (Ser315), promote the secretion of TNF‑α, IL‑6, IL‑10, IL‑1β and IL‑12, promote G2/M cell cycle arrest and apoptosis of macrophages, and enhance the survival of XJMTB in macrophages. These results provide CDK1 and phosphorylated‑p53 as two new potential therapeutic targets for TB in Xinjiang, and lay a foundation for the development of novel TB treatment strategies.

Spinal cord injury (SCI) represents a notable global health challenge, with neuropathic pain (NP) being a common complication that intensifies patient suffering. Existing research tends to overlook the temporal aspects of NP and fails to offer targeted treatment options. To tackle this issue, the present study initially examined genome‑wide association study summaries related to NP, incorporating expression quantitative trait locus (eQTL) from blood samples through summary‑based Mendelian randomization. This allowed the investigation of the association between NP and eQTL, facilitating the identification of genes linked to the risk of NP. Following this, weighted gene co‑expression network analysis of a Gene Expression Omnibus dataset was utilized to identify SCI‑related module genes, resulting in the detection of 218 shared genes across these analyses. Subsequent functional enrichment assessments, protein‑protein interaction evaluations and machine learning technique analyses, including least absolute shrinkage and selection operator regression, random forest and support vector machine recursive feature elimination analyses, highlighted three central genes: Glycerol‑3‑phosphate dehydrogenase 1‑like, epoxide hydrolase 2 and cytochrome P450 family 1 subfamily B member 1 (CYP1B1). Additionally, network pharmacology and molecular docking analyses confirmed CYP1B1 as a viable therapeutic target. A analysis of single‑cell RNA sequencing datasets demonstrated an increase in CYP1B1 expression within spinal cord fibroblasts following SCI. Furthermore, quercetin (Que) was shown to inhibit CYP1B1 expression and reduce NP (based on mechanical paw withdrawal threshold and thermal paw withdrawal latency) in murine models. The results of the present study highlight the important role of spinal cord fibroblast CYP1B1 as a notable contributor to NP following SCI and suggest that Que may serve as a promising mechanism‑based therapeutic option.

The combination of knee osteoarthritis (KOA) and atherosclerosis (AS) is a common multimorbidity. Epidemiological studies have demonstrated the existence of common risk factors, with metabolic syndrome possibly considered the most critical. In the present study, metabolism‑related clinical information was analyzed and metabolic profiles were assessed in healthy controls, patients with KOA, patients with AS and patients with both conditions using untargeted serum metabolomics assays. Potential KOA‑AS multimorbidity hub genes were identified using transcriptomics datasets from the Gene Expression Omnibus database and were validated using clinical samples and animal experiments. Finally, the clinical applications of the analyzed biomolecules were predicted. The results showed that the caffeine metabolic pathway was markedly associated with KOA‑AS multimorbidity and caffeine interacted with two potential hub genes (EGR1 and GSK3B). In the validation experiment using clinical samples, early growth response 1 (Egr1) protein was only associated with AS. In the mouse disease model, Egr1 protein in the serum and cartilage was associated with KOA‑AS multimorbidity, with consistent expression trends. Receiver operating characteristic (ROC) analysis showed three metabolites with an area under the ROC curve of >0.7; drug prediction yielded two drugs that interacted with EGR1. In conclusion, KOA‑AS multimorbidity may be associated with metabolic abnormalities in the early stages and could develop into chronic inflammation in the later stages. Through multi‑omics analysis, three caffeine‑related metabolites with diagnostic value were obtained and EGR1 was identified as the key gene for KOA‑AS multimorbidity.

Glaucoma is a notable public health concern as it can lead to irreversible vision loss; however, it remains challenging to treat effectively. Current options focus solely on managing intraocular pressure (IOP) to delay the progression of vision loss. The present review describes the multifaceted mechanisms of glaucoma and concludes by describing future promising treatment options that target specific mechanisms. Gene editing therapy is a promising option for patients with mutations known to cause glaucoma. Modulating the expression of genes involved in IOP regulation or neurodegeneration is another potential approach. Additionally, therapies targeting relevant molecular and metabolic pathways are also currently under investigation. The present review aims to highlight the most promising avenues for molecular intervention in glaucoma and guide future research efforts toward effective, long‑term solutions for preserving vision.

Osteoarthritis (OA) is a prevalent chronic joint disorder with a notable global health burden, characterized by articular cartilage degeneration, abnormal bone remodeling and synovial inflammation. Traditional treatments mainly focus on symptom management rather than addressing the underlying disease mechanisms. The gut microbiome serves a potential role in OA through the gut‑bone‑cartilage axis. Notably, the gut microbiome and its metabolites can influence bone and cartilage homeostasis, and the Wnt/β‑catenin signaling pathway has been implicated in OA pathogenesis. The present study comprehensively reviews the emerging evidence supporting the gut‑bone‑cartilage axis in OA and the role of microbial regulation of Wnt/β‑catenin signaling in joint remodeling. The current understanding of the influence of the gut microbiome on OA pathogenesis is summarized, discussing the mechanisms underlying the gut‑bone‑cartilage axis and exploring the therapeutic potential of targeting this axis. Future research should focus on developing targeted therapies that modulate the gut microbiome and the Wnt/β‑catenin pathway, as well as exploring the potential of gene editing and carrier technologies for OA treatment.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the control GAPDH western blotting data shown in Fig. 2B on p. 1385 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 Biomedicine & Pharmacotherapy. Certain of the other western blot data featured in Figs. 2 and 4 were likewise very similar to data which subsequently appeared in other articles that were unrelated to this one. In view of the fact that the abovementioned data in Fig. 2C 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 22: 1382‑1390, 2020; DOI: 10.3892/mmr.2020.11188].

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the flow cytometric data shown in Fig. 2A on p. 4085 were strikingly similar to data that had either already been published previously in articles that were written by different authors at different research institutes, or were featured in articles that were submitted for publication to different journals at around the same time. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After contacting with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 4081‑4090, 2019; DOI: 10.3892/mmr.2019.10064].

Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, primarily resulting from placental abnormalities and endothelial dysfunction. The present review explores the role of ubiquitination and deubiquitination (key post‑translational modifications), in the pathogenesis of PE. Ubiquitination, catalyzed by E1, E2 and E3 enzymes, and reversed by deubiquitinating enzymes, regulates protein stability and function, thereby influencing key cellular processes in trophoblasts. Dysregulation of these pathways impairs trophoblast functions and contributes to PE development. In addition, the present review discusses emerging therapeutic strategies targeting the ubiquitin‑proteasome system, including deubiquitinase‑targeting chimera and proteolysis‑targeting chimeras. Targeting ubiquitination and deubiquitination mechanisms presents a promising avenue for the treatment of PE. Further research into these pathways may lead to novel interventions aimed at improving maternal and fetal outcomes.

The present study investigated the effects of Notoginsenoside R1 (NG‑R1) on human non‑small cell lung cancer (NSCLC) A549 cells and explored its potential mechanisms. Cell viability was assessed using the MTT assay after 72 h of treatment with varying concentrations of NG‑R1 (0.1, 0.2, 0.4, 0.8, 1.6 and 2 mg/ml), which inhibited A549 cell viability in a dose‑dependent manner. Cell proliferation, migration and invasion were evaluated using the BeyoClick™ EdU‑594 proliferation assay, wound healing assay and Matrigel®‑coated Transwell invasion assay, respectively. NG‑R1 at concentrations of 0.4, 0.8 and 1.6 mg/ml significantly suppressed proliferation, migration and invasion of A549 cells compared with the control. In addition, these doses of NG‑R1 increased intracellular reactive oxygen species (ROS) levels as measured using the fluorescent probe 2',7'‑dichlorofluorescein diacetate. Western blot analysis revealed that treatment with NG‑R1 (0.4, 0.8 and 1.6 mg/ml) upregulated the expression of the ferroptosis‑related protein transferrin receptor 1, and downregulated solute carrier family 7 member 11, glutathione peroxidase 4 and ferritin heavy chain 1. Collectively, these findings indicate that NG‑R1 inhibited the proliferation of NSCLC A549 cells, likely through the induction of ROS accumulation and ferroptosis.