Molecular medicine reports最新文献

The advancement of tumor cell metastasis is significantly influenced by epithelial‑to‑mesenchymal transition (EMT), and metastasis is a prominent contributor to the mortality of patients diagnosed with colorectal cancer (CRC). AT‑rich interactive domain‑containing protein 1A (ARID1A), which acts as a tumor suppressor, frequently exhibits a loss‑of‑function mutation in metastatic CRC tissues. However, the underlying molecular mechanisms of ARID1A relating to EMT remain poorly understood. The present study aimed to clarify the association between ARID1A and EMT regulation in human CRC cells. The investigation into the loss of ARID1A expression in tissues from patients with CRC was performed using immunohistochemistry. Furthermore, ARID1A‑overexpressing SW48 cells were established using lentiviruses carrying human full‑length ARID1A. The results revealed that overexpression of ARID1A induced cellular morphological changes by promoting the tight junction molecule zonula occludens 1 (ZO‑1) and the adherens junction molecule E‑cadherin, whereas it decreased the intermediate filament protein vimentin. The results of reverse transcription‑quantitative PCR also confirmed that ARID1A overexpression upregulated the mRNA expression levels of TJP1/ZO‑1 and CDH1/E‑cadherin, and downregulated VIM/vimentin and zinc finger E‑box binding homeobox 1 expression, which are considered epithelial and mesenchymal markers, respectively. In addition, the overexpression of ARID1A in CRC cells resulted in a suppression of cell motility and migratory capabilities. The present study also demonstrated that the tumor suppressor ARID1A was commonly absent in CRC tissues. Notably, ARID1A overexpression could reverse the EMT‑like phenotype and inhibit cell migration through alterations in EMT‑related markers, leading to the inhibition of malignant progression. In conclusion, ARID1A may serve as a biomarker and therapeutic target in the clinical management of metastatic CRC.

Copper, a vital trace element, is indispensable for the maintenance of physiological functioning, particularly in the cardiac system. Unlike other forms of cell death such as iron death and apoptosis, copper‑induced cell death has gained increasing recognition as a significant process influencing the development of cardiovascular diseases. The present review highlights the significance of maintaining copper homeostasis in addressing cardiovascular diseases. This review delves into the crucial roles of copper in physiology, including the metabolic pathways and its absorption, transport and excretion. It provides detailed insights into the mechanisms underlying cardiovascular diseases resulting from both excess and deficient copper levels. Additionally, it summarizes strategies for treating copper imbalances through approaches such as copper chelators and ion carriers while discussing their limitations and future prospects.

Lung cancer has the highest incidence and mortality rates of all cancer types in China and therefore represents a serious threat to human health. In the present study, the mechanism of rabdoternin E against the proliferation of the lung cancer cell line A549 was explored. It was found that rabdoternin E caused the accumulation of large amounts of reactive oxygen species (ROS), promoted cell S phase arrest by reducing the expression of CDK2 and cyclin A2, induced apoptosis by increasing the Bax/Bcl‑2 ratio and promoted the phosphorylation of proteins in the ROS/p38 MAPK/JNK signaling pathway, which is associated with apoptosis and ferroptosis. In addition, it was also found that Z‑VAD‑FMK (an apoptosis inhibitor), ferrostatin‑1 (ferroptosis inhibitor) and N‑acetylcysteine (a ROS inhibitor) could partially or greatly reverse the cytotoxicity of rabdoternin E to A549 cells. Similarly, NAC (N‑acetylcysteine) treatment notably inhibited the rabdoternin E‑stimulated p38 MAPK and JNK activation. Furthermore, in vivo experiments in mice revealed that Rabdoternin E markedly reduced tumor volume and weight and regulated the expression levels of apoptosis and ferroptosis‑related proteins (including Ki67, Bcl‑2, Bax, glutathione peroxidase 4, solute carrier family 7 member 11 and transferrin) in the tumor tissues of mice. Histopathological observation confirmed that the number of tumor cells decreased markedly after administration of rabdoternin E. Taken together, rabdoternin E induced apoptosis and ferroptosis of A549 cells by activating the ROS/p38 MAPK/JNK signaling pathway. Therefore, the results of the present study showed that rabdoternin E is not toxic to MCF‑7 cells (normal lung cells), had no significant effect on body weight and was effective and therefore may be a novel therapeutic treatment for lung cancer.

The present study aimed to validate the association between core cuproptosis genes (CRGs) and Alzheimer's disease (AD) from both bioinformatics and experimental perspectives and also to develop a risk prediction model. To this end, 78 human‑derived temporal back samples were analyzed from GSE109887, and the biological functions of the resulting CRGs were explored by cluster analysis, weighted gene co‑expression network analysis and similar methods to identify the best machine model. Moreover, an external dataset GSE33000 and a nomogram were used to validate the model. The mRNA and protein expression of CRGs were validated using the SH‑SY5Y cell model and the Sprague‑Dawley rat animal model. The RT‑qPCR and western blotting results showed that the mRNA and protein expression content of dihydrolipoamide dehydrogenase, ferredoxin 1, glutaminase and pyruvate dehydrogenase E1 subunit β decreased, and the expression of dihydrolipoamide branched chain transacylase E2 increased in AD, which supported the bioinformatic analysis results. The CRG expression alterations affected the aggregation and infiltration of certain immune cells. The present study also confirmed the accuracy and validity of AD diagnostic models and nomograms, and validated the association between five CRGs and AD, indicating a significant difference between patients with AD and healthy individuals. Therefore, CRGs are expected to serve as relevant biomarkers for the diagnosis and prognostic monitoring of AD.

The tetraspanin family of membrane proteins is essential for controlling different biological processes such as cell migration, penetration, adhesion, growth, apoptosis, angiogenesis and metastasis. The present review summarized the current knowledge regarding the expression and roles of tetraspanins in different types of cancer of the digestive system, including gastric, liver, colorectal, pancreatic, esophageal and oral cancer. Depending on the type and context of cancer, tetraspanins can act as either tumor promoters or suppressors. In the present review, the importance of tetraspanins in serving as biomarkers and targets for different types of digestive system‑related cancer was emphasized. Additionally, the molecular mechanisms underlying the involvement of tetraspanins in cancer progression and metastasis were explored. Furthermore, the current challenges are addressed and future research directions for advancing investigations related to tetraspanins in the context of digestive system malignancies are proposed.

Following acute myocardial infarction, the recovery of blood flow leads to myocardial ischemia‑reperfusion (MI/R) injury, which is primarily characterized by the activation of inflammatory signals, microvascular obstruction, increased oxidative stress and excessive Ca²⁺ overload. It has also been demonstrated that platelets can exacerbate MI/R injury by releasing reactive oxygen species, inflammatory factors and chemokines, while also obstructing microvessels through thrombus formation. As a bioactive molecule with proinflammatory and chemotactic properties, lipocalin 2 (LCN2) exhibits a positive correlation with obesity, hyperglycemia, hypertriglyceridemia and insulin resistance index, which are all significant risk factors for ischemic cardiomyopathy. Notably, the potential role of LCN2 in promoting atherosclerosis may be related to its influence on the function of macrophages, smooth muscle cells and endothelial cells, but its effect on platelet function has not yet been reported. In the present study, the effect of a high‑fat diet (HFD) on LCN2 expression was determined by detecting LCN2 expression levels in the liver and serum samples of mice through reverse transcription‑quantitative PCR and enzyme linked immunosorbent assay, respectively. The effect of LCN2 on platelet function was evaluated by examining whether LCN2 affected platelet activation, aggregation, adhesion, clot retraction and P‑selectin expression. To determine whether LCN2 aggravated MI/R injury in HFD‑fed mice by affecting platelet and inflammatory cell recruitment, wild‑type and LCN2 knockout mice fed a HFD were subjected to MI/R injury, then hearts were collected for hematoxylin and eosin staining and 2,3,5‑triphenyltetrazolium chloride staining, and immunohistochemistry was employed to detect the expression of CD42b, Ly6G, CD3 and B220. Based on observing the upregulation of LCN2 expression in mice fed a HFD, the present study further confirmed that LCN2 could accelerate platelet activation, aggregation and adhesion. Moreover, in vivo studies validated that knockout of LCN2 not only mitigated MI/R injury, but also inhibited the recruitment of platelets and inflammatory cells in myocardial tissue following ischemia‑reperfusion. In conclusion, the current findings suggested that the effect of HFD‑induced LCN2 on aggravating MI/R injury may totally or partially dependent on its promotion of platelet function.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell invasion assay data shown in Figs. 2E, 3E, 4E and 5E, and the Transwell migration assay data shown in Fig. 2D, were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time (some of which have already been retracted). Moreover, data were also found to be duplicated comparing the data panels in Figs. 3D and 4D, such that data which were intended to have shown the results from differently performed experiments had been derived from the same original source. In view of the fact that certain of 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 22: 4163‑4172, 2020; DOI: 10.3892/mmr.2020.11498].

Pancreatic β‑cells are the only cells that synthesize insulin to regulate blood glucose levels. Various conditions can affect the mass of pancreatic β‑cells and decrease insulin levels. Diabetes mellitus is a disease characterized by insulin resistance and chronic hyperglycemia, mainly due to the loss of pancreatic β‑cells caused by an increase in the rate of apoptosis. Additionally, hyperglycemia has a toxic effect on β‑cells. Although the precise mechanism of glucotoxicity is not fully understood, several mechanisms have been proposed. The most prominent changes are increases in reactive oxygen species, the loss of mitochondrial membrane potential and the activation of the intrinsic pathway of apoptosis due to p53. The present review analyzed the location of p53 in the cytoplasm, mitochondria and nucleus in terms of post‑translational modifications, including phosphorylation, O‑GlcNAcylation and poly‑ADP‑ribosylation, under hyperglycemic conditions. These modifications protect p53 from degradation by the proteasome and, in turn, enable it to regulate the intrinsic pathway of apoptosis through the regulation of anti‑apoptotic and pro‑apoptotic elements. Degradation of p53 occurs in the proteasome and depends on its ubiquitination by Mdm2. Understanding the mechanisms that activate the death of pancreatic β‑cells will allow the proposal of treatment alternatives to prevent the decrease in pancreatic β‑cells.

Diabetic cardiomyopathy (DCM), a significant complication of diabetes mellitus, is marked by myocardial structural and functional alterations due to chronic hyperglycemia. Despite its clinical significance, optimal treatment strategies are still elusive. Bariatric surgery via sleeve gastrectomy and Roux-en-Y gastric bypass have shown promise in treating morbid obesity and associated metabolic disorders including improvements in diabetes mellitus and DCM. The present study reviews the molecular mechanisms by which bariatric surgery improves DCM, offering insights into potential therapeutic targets. Future research should further investigate the mechanistic links between bariatric surgery and DCM, to evaluate the benefits and limitations of these surgical interventions for DCM treatment. The present study aims to provide a foundation for more effective DCM therapies, contributing to the advancement of patient care.

Fibrosis is the basis of structural remodeling in atrial fibrillation (AF), during which inflammation is crucial. Programmed cell death factor 4 (PDCD4) is a newly identified inflammatory gene, with unknown mechanisms of action in AF. The present study aimed to elucidate the effects of PDCD4 on the inflammation and structural remodeling of atrial myocytes. For this purpose, a PDCD4 overexpression plasmid (oePDCD4) and PDCD4 small interfering (si)RNA (siPDCD4) were used to modulate PDCD4 expression in mouse atrial myocytes (HL‑1 cells). The expression of PDCD4 was detected using reverse transcription‑quantitative PCR and western blot analysis. The optimal drug concentrations of peroxisome proliferator‑activated receptor γ (PPARγ) agonist (pioglitazone hydrochloride), NF‑κB inhibitor (CBL0137), PPARγ inhibitor (GW9962) and NF‑κB agonist (betulinic acid) were screened using a Cell Counting Kit‑8 assay. The levels of inflammatory factors were detected using enzyme‑linked immunosorbent assays, the expression levels of fibrosis‑related proteins and NF‑κB subunits were detected using western blot analysis, and the expression of phosphorylated (p‑)p65/p65 was detected using immunofluorescence staining. The results revealed that PDCD4 overexpression increased the levels of fibrotic factors (collagen I, collagen III, fibronectin, α‑smooth muscle actin and matrix metalloproteinase 2), pro‑inflammatory cytokines (IFN‑γ, IL‑6, IL‑17A and TNF‑α) and p‑p65, whereas it reduced the levels of anti‑inflammatory cytokines (IL‑4) in HL‑1 cells. Additionally, treatment with the PPARγ agonist and NF‑κB inhibitor reversed the levels of fibrotic‑, pro‑inflammatory and anti‑inflammatory factors in oePDCD4‑HL‑1 cells. By contrast, PDCD4 silencing exerted the opposite effects on fibrotic factors, pro‑inflammatory cytokines, anti‑inflammatory cytokines and p‑p65. In addition, treatment with the PPARγ inhibitor and NF‑κB agonist reversed the levels of fibrotic‑, pro‑inflammatory and anti‑inflammatory factors in siPDCD4‑HL‑1 cells. In conclusion, the present study demonstrated that PDCD4 may induce inflammation and fibrosis by activating the PPARγ/NF‑κB signaling pathway, thereby promoting the structural remodeling of atrial myocytes in AF.