International journal of molecular medicine最新文献

Following the publication of the above article and an expression of concern statement (doi: 10.3892/ijmm.2025.5680) after it had been drawn to the Editor's attention by an interested reader that, regarding the western blot data shown in Fig. 5 on p. 507, the first set of GAPDH bands for the GH3 cell line were strikingly similar to the EGFR protein bands shown for the GT1‑1 cell line in the adjacent set of gels, the authors have now replied to the Editorial Office to explain the apparently anomalous appearance of this figure. After having examined their original data, the authors have realized that this figure was assembled incorrectly; essentially, the wrong data were included in this figure to portray the GAPDH bands for the GH3 cell line. The revised version of Fig. 5, now showing the correct GAPDH data for the GH3 cell line, is featured on the next page. The authors can confirm that the error made during the assembly of Fig. 5 did not have a significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 47: 500‑510, 2021; DOI: 10.3892/ijmm.2020.4807]

Mangiferin (MGF) is a natural C‑glucosyl xanthone with multitarget activity relevant to metabolic, inflammatory and cancer diseases. Notably, MGF modulates AMP‑activated protein kinase, NF‑κB, PI3K/AKT and MAPK signaling; through these pathways, it affects glucose and lipid metabolism, oxidative stress, apoptosis and inflammatory responses. In metabolic disorders, MGF has been shown to improve insulin sensitivity, support mitochondrial function and reduce diabetic complications. In cancer models, MGF suppresses proliferation, invasion and angiogenesis, and can influence antitumor immunity in the tumor microenvironment. Anti‑inflammatory actions include decreased cytokine release and regulation of the NLR family pyrin domain‑containing 3 inflammasome. Notably, clinical translation remains limited due to its low aqueous solubility, poor oral bioavailability and rapid metabolism. However, benefits of nanocarrier delivery, structural optimization and combination therapy have been reported, which may improve exposure and efficacy in experimental systems. Furthermore, safety signals in animals are favorable at relevant doses, but clinical evidence remains limited. In conclusion, the present review summarizes the pharmacodynamics and mechanisms of MGF across major disease settings and identifies key gaps for translation. Priorities include standardized clinical trials, optimization of delivery strategies, and rigorous assessment of long‑term safety and efficacy.

Musculoskeletal crosstalk is essential for maintaining the balance of bone metabolism, with macrophage‑derived exosomes emerging as key regulators of this process. Exosomes, small extracellular vesicles secreted by cells, carry a variety of bioactive molecules; proteins, lipids, mRNAs and miRNAs and facilitate intercellular communication by transferring these cargos to recipient cells. Specifically, macrophage‑derived exosomes mediate muscle‑bone interactions by transferring key regulators such as insulin‑like growth factor‑1 (IGF‑1) and fibroblast growth factor‑2 (FGF‑2), thereby playing a pivotal role in bone metabolic homeostasis. Macrophages are classified into pro‑inflammatory M1 and anti‑inflammatory M2 phenotypes, each performing distinct functions in immune responses. Exosomes from M1 macrophages typically carry pro‑inflammatory factors that can activate osteoclastic bone resorption, disrupting bone metabolism in pathological conditions. By contrast, exosomes from M2 macrophages often contain anti‑inflammatory factors that promote tissue repair and bone formation. In the context of bone metabolism, exosomes from M1 and M2 macrophages modulate muscle‑bone signaling by delivering regulators that influence the expression of IGF‑1 and FGF‑2, affecting osteoblast proliferation, differentiation, and mineralization. M1 macrophage‑derived exosomes activate signaling pathways such as NF‑κB and MAPK through the transfer of pro‑inflammatory cargo, thereby enhancing bone resorption. By contrast, exosomes from M2 macrophages can suppress pro‑inflammatory signaling while activating pathways like TGF‑β and PI3K/Akt, promoting bone synthesis and repair. As critical myokines, IGF‑1 and FGF‑2 not only support muscle growth, repair, and maintenance but also directly influence bone remodeling through musculoskeletal crosstalk.

Ischemic heart disease remains the leading cause of global disease burden among cardiovascular disorders. In addition to cardiomyocyte injury, ischemia-reperfusion (I/R)-induced microvascular damage plays a crucial role in determining tissue dysfunction and overall prognosis. Mitochondria-associated endoplasmic reticulum membranes (MAMs), specialized contact sites between the ER and mitochondria, are now recognized as key regulators of cardiovascular pathophysiology. The present review summarized current knowledge of the structure of MAMs and their effects on endothelial cells under hypoxia/reoxygenation conditions. Particular attention was given to their role in regulating mitochondrial quality control processes, including fission, fusion, oxidative stress, mitophagy and Ca2+ homeostasis, within the context of cardiac microvascular I/R injury. Targeting MAMs may represent a promising strategy for microvascular protection in ischemic heart disease.

Atherosclerosis constitutes the fundamental pathological basis for cardiovascular diseases, with its pathogenesis intricately associated with dysfunctions in vascular endothelial and smooth muscle cells. Nanomaterials have emerged as a promising research focus within the biomedical field, attributed to their distinctive physicochemical properties. The present review explores the potential of nanomaterials, in conjunction with exercise interventions, to synergistically enhance vascular cell function, thereby presenting innovative therapeutic strategies against atherosclerosis. The present review systematically evaluates the various types of nanomaterials, elucidates their mechanisms of action, examines the synergistic effects of exercise interventions and discusses the challenges encountered in clinical translation, along with prospective directions for future research in this dynamic field.

The present study evaluated the role of microRNA (miR)‑205 as a dual regulator of angiogenesis, exhibiting both pro‑angiogenic and anti‑angiogenic effects depending on the biological context. miRs are small non‑coding sequences that regulate gene expression at the post‑transcriptional level and can be transported in extracellular vesicles (EVs), allowing them to modulate biological processes remotely. miR‑205 is involved in multiple cellular processes, such as proliferation, migration, apoptosis and angiogenesis. In angiogenesis its function is contradictory: On one hand, it can inhibit blood vessel formation by suppressing pro‑angiogenic factors such as VEGF and ANG‑2, as demonstrated in diseases such as psoriasis, thyroid cancer and diabetic retinopathy. However, in other contexts, miR‑205 promotes angiogenesis by inhibiting anti‑angiogenic genes such as PTEN and HITT, facilitating the activation of the PI3K/AKT pathway and cell proliferation in ovarian cancer and thrombosis. Additionally, the present study highlighted the role of EVs in transferring miR‑205 between cells, thereby influencing angiogenesis and disease progression. Studies in myocardial infarction and cancer models have demonstrated that EVs enriched in miR‑205 can affect blood vessel formation and tumor progression. Similarly, in ocular diseases such as macular degeneration and diabetic retinopathy, miR‑205 encapsulated in EVs has shown therapeutic potential by regulating VEGF levels. In conclusion, miR‑205 emerges as a promising therapeutic target for angiogenic diseases. Its application in EV‑based therapy could represent an innovative strategy for treating vascular disorders. However, further studies are needed to fully understand its mechanisms of action and optimize its clinical application.

Following the publication of the above article, a concerned reader drew to the Editor's attention that, in Fig. 1D, the 'SW1990' and 'Bxpc‑3' data panels were overlapping, suggesting that these data were derived from the same original source where experiments showing different experimental conditions were intended to have been portrayed. In addition, further pairings of overlapping data panels were identified with the Ki67 assay data shown in Figs. 7E and the immunohistochemical data shown in Fig. 10C, suggesting that these figures had similarly been assembled incorrectly. Furthermore, four of the centrally placed flow cytometric plots featured in Fig. 5A appeared to be too similar in terms of the distribution of the data to be confident that these were all derived from independently performed experiments, and finally, some of the western blot data shown in Fig. 4B were strikingly similar to data which had already appeared in another paper, also published in International Journal of Molecular Medicine, that featured the same first author (Guanen Qiao). In view of the number of different problems and potential anomalies identified with various of the figures in this paper, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the journal on account of an overall lack of confidence in the presented data. 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 of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 44: 593‑607, 2019; DOI: 10.3892/ijmm.2019.4206].

Hepatocellular carcinoma (HCC) treatment remains challenging due to the prevalence of metastasis and chemotherapy resistance. Mitochondrial stomatin‑like protein 2 (STOML2), which is upregulated in various solid tumors, is associated with a poor prognosis; however, its biological function and molecular mechanism in HCC remain unclear. The present study aimed to elucidate the oncogenic mechanism of STOML2 in HCC and to explore its potential as a therapeutic target. Firstly, STOML2 expression in HCC and matched normal liver tissues was analyzed. In addition, STOML2‑knockdown (HCCLM3‑short hairpin RNA‑STOML2) and ‑overexpression (Huh7‑STOML2) cell models were established. Wound healing, Cell Counting Kit‑8 and Transwell assays, and flow cytometry were performed to assess cell proliferation, invasion, migration and apoptosis in vitro. Furthermore, the biological function of STOML2 was confirmed in vivo. Co‑immunoprecipitation (co‑IP) and immunofluorescence staining were conducted to validate the interaction of STOML2 with prohibitin (PHB) following the prediction of binding partners. Downstream pathways regulated by STOML2 were identified using western blotting and were further investigated using the RAF1 inhibitor sorafenib. The present study revealed that STOML2 expression was significantly upregulated in HCC tissues and metastatic lesions, and was associated with poor patient prognosis. The in vitro experiments showed that STOML2 overexpression promoted proliferation, invasion, migration and autophagy, while inhibiting apoptosis in Huh7 cells. Conversely, STOML2 knockdown reversed these phenotypic changes. Furthermore, co‑IP confirmed the direct interaction between STOML2 and PHB, which activated the RAF/MEK/ERK signaling pathway. The in vivo experiments further confirmed that STOML2 overexpression significantly accelerated tumor growth, whereas STOML2 or PHB knockdown inhibited tumor progression. In addition, sorafenib treatment suppressed STOML2‑mediated cell migration and the expression of autophagy‑related proteins by blocking the MAPK pathway. These findings elucidated the molecular mechanism by which STOML2 promotes the malignant progression of HCC and demonstrated that targeted inhibition of the PHB‑MAPK pathway may reverse the pro‑tumorigenic effects of STOML2. STOML2 may serve as both a prognostic biomarker and a therapeutic target in HCC. The current study provides a theoretical foundation for individualized treatment in patients with HCC and high STOML2 expression.

Fibrosis is a maladaptive response of tissues or organs to adverse stresses, such as chronic inflammation, infection and mechanical injury. It further promotes parenchymal cell loss, abnormal myofibroblast proliferation and excessive extracellular matrix buildup, eventually triggering scar tissue hyperplasia or organ injury. Although a moderate fibrotic response is beneficial for compensatory tissue repair induced by exogenous or endogenous injury, excessive fibrosis is the basis for the promotion of multiorgan pathologies, such as cardiac hypertrophy, idiopathic pulmonary fibrosis, or renal tubulointerstitial fibrosis. In industrialized countries alone, fibrotic diseases account for ~45% of all‑cause mortality. Consequently, the development of medications that regulate the activation of growth factors, proliferation of fibrotic effector cells and deposition and degradation of the extracellular matrix is essential. Botanical compounds derived from Chinese medicine are generally considered natural tonics. Among these compounds, astragaloside IV (AS‑IV) is a bioactive product isolated from the roots of Astragalus membranaceus Bunge. On the basis of the multitarget therapeutic mechanism of Chinese herbal medicine, AS‑IV may have considerable benefits in improving multiorgan fibrosis and complex fibrotic diseases with multisignal cascades. It can effectively alleviate the fibrosis‑induced dysfunction of major tissues or organs, including the heart, lungs, kidneys and liver, by regulating the signal transduction of reactive oxygen species/caspase‑1/gasdermin D, transforming growth factor‑β/Smads, Wnt/β‑catenin and sirtuin 1‑nuclear factor‑κ B. The present review mainly focused on phytomedicine and highlights the potential of AS‑IV as an antifibrotic medication. It aimed to provide a novel reference for the application of AS‑IV in the nutritional intervention of fibrotic diseases.

Branched‑chain amino acids (BCAAs) are biologically active amino acids with branched carbon chains, recognized for their diverse biological functions and therapeutic potential. BCAAs have demonstrated promising effects in the prevention and treatment of various conditions, including muscle growth disorders, cardiovascular diseases and cancer. Despite extensive research confirming their targeted therapeutic effects in multiple domains, the mechanisms of action and therapeutic range of BCAAs remain incompletely understood. Osteoporosis, a metabolic bone disease, is a global public health issue characterized by an imbalance between osteoblast‑mediated bone formation and osteoclast‑induced bone resorption, resulting in fragile bones and an elevated risk of fractures. Given the well‑documented therapeutic roles of BCAAs, their potential link to osteoporosis has been explored, emphasizing the influence of BCAA metabolism on bone metabolism. The present review aims to summarize findings on the relationship between BCAA metabolism and osteoporosis, and to investigate the mechanisms by which BCAA metabolism may exert anti‑osteoporotic effects. The review first outlines the fundamental processes and key factors influencing bone metabolism, BCAA metabolism and osteoporosis. It then examines the interactions between these processes and the effects of BCAA metabolism on bone health. Finally, it explores the potential of targeting BCAA metabolic pathways as a future therapeutic strategy for osteoporosis, highlighting BCAAs as a promising target for treating this condition.