Molecular medicine reports最新文献

Liver diseases have become one of the significant threats to global health. However, there is a lack of effective targeted therapeutic drugs in this field and the existing drugs used for liver disease treatment usually have side‑effects. Traditional Chinese medicine (TCM) has the distinctive advantages of multi‑target and low side‑effects. As a flavonoid with various pharmacological activities such as anti‑tumour, anti‑oxidant, anti‑inflammatory and anti‑bacterial, the TCM myricetin has been widely used in liver disease research. The present work focuses on the role and molecular mechanism of myricetin in liver diseases such as acute liver injury, fatty liver, liver fibrosis and hepatocellular carcinoma. It is a promising reference for further research and application of myricetin in the treatment of liver diseases.

Mitophagy plays significant roles in chronic obstructive pulmonary disease (COPD). The present study aimed to screen and validate mitophagy‑related genes in COPD by using bioinformatic analysis and experimental validation. The original data were downloaded from Gene Expression Omnibus datasets and 29 mitophagy‑related genes sets were acquired from the Molecular Signatures Database. The differentially expressed mitophagy‑related genes (DEMRGs) were screened using the Wilcoxon test. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted for the identification of DEMRGs. In addition, clustering analysis was used to assess the differential expression characteristics of DEMRGs in patients with COPD. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to identify signature genes with COPD diagnostic significance; these genes were validated using the test dataset. In addition, the degree of infiltration of 28 immune cells in COPD and control samples was assessed. Finally, cigarette smoke extract (CSE)‑treated bronchial epithelial cells were employed to verify the role of signature genes in regulating mitophagy in vitro using molecular biology approaches. A total of 14 DEMRGs were identified, which were mainly involved in mitophagy‑related processes and pathways. Clustering analysis indicated the expression levels of 14 DEMRGs except for microtubule‑associated protein 1 light chain‑3β, which was significantly different. Moreover, combination with LASSO, receiver operating characteristic curve and the validation dataset resulted in the identification of the mitochondrial transcription termination factor 3 (MTERF3). The infiltrating abundance of the majority of the immune cells was higher in COPD samples than that noted in the control samples; MTERF3 demonstrated the optimal correlation with macrophages, myeloid‑derived suppressor cells, regulatory T cells and activated cluster of differentiation 8 T cells. Further analysis revealed that MTERF3 expression was increased in CSE‑treated 16HBE cells and knockdown of MTERF3 expression promoted mitophagy. These findings provide novel insights into the role of mitophagy in COPD and identify novel targets for COPD diagnosis and treatment.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell migration and invasion assay data shown in Fig. 2C and D on p. 4 were strikingly similar to data that had already been published in different form in other articles written by different authors from different research institutes, some of which have now been retracted. 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. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply.  The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 23: 460, 2021; DOI: 10.3892/mmr.2021.12099].

Bronchiolitis obliterans (BO) is a destructive fibrotic lung disease, which can be partly induced by 2,3‑butanedione [also known as diacetyl (DA)]; however, the mechanism underlying the effects of DA on BO is not clear. In the present study, a bioinformatics analysis was performed using DA‑treated or untreated lung tissues of rats, and it was observed that cell proliferation regulating inhibitor of protein phosphatase 2A (CIP2A) was significantly increased in samples from the DA group. CIP2A is associated with inflammation and epithelial‑mesenchymal transition (EMT), and facilitates lung injury; however, its effect on DA‑induced BO and the underlying mechanism remain unknown. To solve these issues, DA‑treated models of BO were established in rats and cells, and ethoxysanguinarine (a CIP2A inhibitor) was administered to induce a decrease in CIP2A. The pathological changes were detected by hematoxylin and eosin, Masson and Giemsa staining. Reverse transcription‑quantitative PCR, western blotting, immunohistochemistry, immunofluorescence and enzyme‑linked immunosorbent assay were used to measure CIP2A expression and levels of pathology‑related markers. Notably, inhibition of CIP2A ameliorated the pathological features of BO, including reduced intraluminal occlusion, inflammatory infiltration and fibrosis. The expression of inflammation, fibrosis and EMT markers was also decreased in samples with CIP2A inhibition. Furthermore, CIP2A inhibition was revealed to work through the nuclear factor‑κB (NF‑κB) pathway; phosphorylation of NF‑κB inhibitor α and nuclear translocation of p65 were reduced. In summary, these results demonstrated that CIP2A may promote BO development by increasing inflammation, fibrosis and EMT through activating the NF‑κB signaling pathway. Therefore, inhibition of CIP2A may be considered a potential strategy for BO treatment.

Hydroxychloroquine (HCQ) is an antimalarial drug that has historically been used to treat and prevent malaria. However, its mechanism of action has not yet been fully elucidated. HCQ affects various cellular and molecular pathways through different mechanisms. HCQ has also been shown to be a disease‑improving agent for the treatment of rheumatic diseases, including systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis and primary Sjögren's syndrome. Although generally considered safe, adverse reactions have been reported with the use of HCQ and clinicians should carefully monitor patients with rheumatism when prescribing these drugs. The purpose of the present review is to strengthen the clinical use of HCQ for autoimmune diseases while highlighting the adverse effects that may occur during treatment.

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Fig. 1C and D on p. 2386 were strikingly similar to data appearing in different form in a pair of other articles written by different authors at a different research institute that had already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports. Moreover, some of the data featured in Fig. 6A and C were strikingly similar, also suggesting that the data in this figure had been misassembled. In view of the fact that the abovementioned data 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: 2384‑2392, 2018; DOI: 10.3892/mmr.2017.8152].

The present study aimed to investigate the cardioprotective effects of acteoside (AC) on myocardial ischemia‑reperfusion injury (MIRI). To meet this aim, a network pharmacological analysis was conducted to search for key genes and signaling pathways associated with AC and MIRI. The infarct size of the rat heart was evaluated using 2,3,5‑triphenyltetrazolium chloride staining, and the serum levels of creatine kinase MB isoenzyme, cardiac troponin I, malondialdehyde and superoxide dismutase were subsequently detected in an in vivo experiment. The inhibitory effect of AC on oxidative stress was further confirmed by assessing the intracellular accumulation of reactive oxygen species (ROS). Hematoxylin and eosin staining was subsequently carried out to observe cardiac histopathological damage. The anti‑apoptotic effects of AC were determined using terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay and Hoechst 33342 staining, and the expression levels of apoptosis‑associated proteins in the myocardial tissue were assessed using immunohistochemical analysis. In addition, cell viability was determined using a Cell Counting Kit‑8 assay, and the expression levels of key target proteins associated with AC and MIRI were detected by western blot analysis. The results suggested that pretreatment with AC could mitigate MIRI‑induced myocardial damage, oxidative stress and apoptosis. The anti‑apoptotic effects of AC were associated with elevated Bcl‑2 levels, and reduced caspase‑3 and Bax expression levels in myocardial tissue. In vitro, AC pretreatment both led to an increased rate of cell survival and alleviated oxidative stress, as demonstrated by a decreased level of intracellular ROS accumulation. Moreover, guided by the network pharmacological analysis, heat‑shock protein 90AA1 (HSP90AA1) and the phosphoinositide 3‑kinase (PI3K)/serine‑threonine protein kinase (Akt) signaling pathway emerged as key targets for the action of AC against MIRI. Furthermore, the western blot analysis results showed that pretreatment with AC led to a significant increase in the activity of the PI3K/Akt signaling pathway, in addition to increased expression levels of glycogen synthase kinase‑3β and HSP90AA1. Taken together, the findings of the present study revealed that AC may exert cardioprotective effects on MIRI through suppressing apoptosis and oxidative stress by regulating the expression and activity of key proteins.

Endometriosis (EM) is a chronic inflammatory disease that is one of the most common causes of gynecological systemic lesions in women before menopause. The most representative histological feature of EM is that the endometrium appears outside of the uterine cavity, often in the ovary. Although it is generally accepted that the epithelial and stromal cells of the ectopic endometrium are not malignant, they still have numerous similarities to malignant tumors, including considerable changes to the immune microenvironment (immune monitoring disorder), the creation of a specific hormone environment, high levels of oxidative stress, chronic inflammation and abnormal immune cell regulation. The pathogenesis of EM is not fully understood, which makes it difficult to identify specific biomarkers and potential therapeutic targets for early disease diagnosis and effective treatment. However, considerable progress has been made in this field over the past few decades. The purpose of the present review is to summarize the confirmed and potential biomarkers for EM, and to identify potential therapeutic targets based on changes in immunological factors (including natural killer cells, macrophages, the complement system, miRNA and P‑selectin) in the ectopic endometrial tissue. It is hoped that this work can be used as the basis for identifying accurate diagnostic markers for EM and developing personalized immune‑targeted therapy.

Osteoarthritis (OA) is a common joint disorder involving the cartilage and other joint tissues. Quercetin (QCT) serves a protective role in the development of OA. However, to the best of our knowledge, the regulatory mechanisms of QCT in the progression of OA have not yet been fully elucidated. In order to mimic a model of OA in vitro, IL‑1β was used to stimulate chondrocytes. Furthermore, an in vivo animal model of OA was induced by anterior cruciate ligament transection (ACLT). 5‑Ethynyl‑2'‑deoxyuridine assays, TUNEL assays, ELISAs, western blotting and immunohistochemical assays were conducted to assess the chondroprotective properties of QCT in the development of OA. The results revealed that 100 µM QCT significantly promoted the proliferation, reduced the apoptosis and inflammation, and inhibited the extracellular matrix (ECM) degradation in IL‑1β‑stimulated chondrocytes. Additionally, QCT attenuated the IL‑1β‑induced ferroptosis of chondrocytes, as demonstrated by the reduced lipid reactive oxygen species and Fe²⁺ levels. Conversely, the inhibitory effects of QCT on the apoptosis and inflammatory responses were reversed by the activation of ferroptosis by erastin in IL‑1β‑stimulated chondrocytes. Furthermore, QCT significantly elevated the level of phosphorylated (p‑)5' AMP‑activated protein kinase (AMPK) and the levels of two negative regulators of ferroptosis [nuclear factor erythroid 2‑related factor 2 (Nrf2) and glutathione peroxidase 4 (Gpx4)] in IL‑1β‑stimulated chondrocytes. The AMPK inhibitor compound C notably reversed the promoting effects of QCT on phosphorylated‑AMPK, Nrf2 and Gpx4 expression in IL‑1β‑stimulated chondrocytes. Additionally, QCT markedly ameliorated the destruction and degradation of articular cartilage, and elevated the p‑AMPK, Nrf2 and Gpx4 levels in the mouse model of ACLT‑induced OA. Overall, the present study demonstrated that QCT inhibited the development of OA by suppressing ferroptosis via the activation of the AMPK/Nrf2/Gpx4 signaling pathway. These findings provide novel insights into the regulatory mechanisms of QCT for the treatment of patients with OA.

Among patients with chronic epilepsy, 70‑80% have cognitive impairment. To investigate the relationship between adiponectin (ADPN) and the cognitive level in epilepsy and its mechanism, 20 epileptic patients and 20 healthy controls were included for the assessment of the cognitive level. An ELISA was used to evaluate the serum ADPN level. An epileptic rat model was established and treated with AdipoRon, an ADPN receptor (AdipoR) agonist, which binds to AdipoR1 and AdipoR2. The Morris water maze test was used to assess the cognitive function of rats, and the expression levels of the synapsis‑associated proteins postsynaptic density protein 95 (PSD95), synaptosomal associated protein 25 (SNAP25) and synaptophysin (SYP), as well as AMP‑activated protein kinase (AMPK), mTOR, phosphorylated (p‑)AMPK and p‑mTOR were determined by immunoblotting. Serum ADPN levels were positively correlated with the Montreal cognitive assessment score. AdipoRon improved the cognitive function of epileptic rats, maintained the structural integrity of hippocampal neurons and reduced neuronal damage. It also promoted the mRNA expression of AdipoR1 and AdipoR2 in the hippocampus. Furthermore, AdipoRon increased the expression of the synapsis‑associated proteins PSD95, SNAP25 and SYP by activating the AMPK/mTOR signaling pathway. ADPN improved cognitive impairment in epilepsy by targeting the AMPK/mTOR signaling pathway, providing novel insights for the treatment of epilepsy.