International journal of molecular medicine最新文献

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.

Glioblastoma (GBM) is the most aggressive primary malignant brain tumor type in adults, and is characterized by high invasiveness, therapeutic resistance and recurrence. Current treatments, primarily surgery combined with radiotherapy and chemotherapy, offer limited efficacy, thus necessitating more effective interventions. Matrix metalloproteinases (MMPs) crucially contribute to GBM progression through extracellular matrix degradation, epithelial‑mesenchymal transition and angiogenesis. MMP expression is intricately regulated by signaling pathways, non‑coding RNAs and the tumor microenvironment. Recently, strategies targeting MMPs have gained attention, including natural active substances and small‑molecule compounds with promising therapeutic potential. Nano‑delivery systems have notably improved drug delivery efficiency to the brain by overcoming the blood‑brain barrier, and combination therapies have demonstrated enhanced efficacy. However, chemotherapy resistance and functional heterogeneity remain critical challenges. The present review summarizes recent advances in understanding MMP regulatory mechanisms in GBM, highlighting the roles of signaling pathways and non‑coding RNAs. Additionally, the therapeutic potential of natural products, small‑molecule inhibitors, smart nanocarriers and combination treatments are discussed. Future research should focus on identifying novel inhibitors, and leveraging interdisciplinary approaches to facilitate precision‑targeted drug development, thereby addressing current treatment bottlenecks in GBM.

Ferroptosis, an iron‑catalyzed form of regulated cell death driven by lipid peroxidation‑induced membrane rupture, has emerged as a critical determinant of cellular fate across diverse physiological and pathological contexts. Simultaneously, lactate has undergone a notable conceptual transformation, evolving from being regarded as merely a glycolytic waste product to being recognized as a key signaling metabolite that modulates iron homeostasis, lipid dynamics, cellular redox balance and the immune response. This metabolic renaissance has revealed an intricate lactate‑ferroptosis regulatory network with implications for human disease. Notably, lactate exhibits diametrically contrasting effects on ferroptosis susceptibility: Promoting cell death in certain contexts while conferring protection in others. This apparent paradox, particularly evident when contrasting tumor and normal cell responses, suggests sophisticated context‑dependent regulatory mechanisms that are yet to be fully elucidated. The present review explores the molecular basis of both ferroptosis execution and lactate signaling, synthesizing recent advances that illuminate their dynamic interplay. Crucially, the present review discusses putative key contextual determinants, including the metabolic state, pH tolerance and antioxidant capacity, which may govern divergent roles of lactate in ferroptosis regulation. Furthermore, understanding these context‑specific mechanisms promises to unlock new therapeutic strategies for diseases ranging from cancer to neurodegeneration, where the lactate‑ferroptosis axis represents both a vulnerability and an opportunity.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the 'Normal ctrl' and 'mimic ctrl' data panels shown for the flow cytometry experiments in Fig. 3B on p. 1743 were strikingly similar to data panels that had already been published in an article in the journal Molecular and Cellular Biochemistry which had been written by different authors at different research institutes. Owing to the fact that the contentious data in the above article were found to be strikingly similar to data that had already been published elsewhere, the Editor of International Journal of Molecular Medicine 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. [International Journal of Molecular Medicine 41: 1740‑1748, 2018; DOI: 10.3892/ijmm.2018.3358].

Macrophages, an essential component of the innate immune system, exhibit remarkable plasticity and functional heterogeneity governed by the intricate transcriptional regulatory networks. Activating transcription factors (ATFs) have recently been recognized to modulate multiple signaling pathways, including the MAPK cascades, endoplasmic reticulum stress response and NF‑κB signaling, thereby regulating macrophage biological processes such as inflammatory response, glucose‑lipid metabolism, cellular stress adaptation, autophagy‑apoptosis balance and senescence. By integrating stress signals and metabolic cues, ATF family members construct a sophisticated regulatory network implicated in the pathogenesis of infectious and inflammatory diseases, metabolic disorders, malignancies and neurodegenerative diseases. Therefore, targeted modulations of ATFs or their associated pathways are considered to be capable of precisely regulating macrophage anti‑inflammatory function, metabolic activity and tissue repair capacity in disease settings. Recent technological advances, such as specific targeted delivery systems and gene‑editing strategies, offer promising avenues for the spatiotemporal ATF‑targeting interventions in macrophages, which is critical for improving therapeutic efficacy and safety. The present review systematically summarized recent advances in the understanding of ATF‑mediated regulation of macrophage development, survival, migration, phagocytosis, activation/cytokine secretion, along with polarization and metabolic reprogramming. It also elucidated the pathophysiological implications of these regulatory mechanisms and critically evaluated the clinical feasibility of ATF‑targeted therapeutic interventions.

Long‑term hyperglycemia can damage the capillaries and neural regulation of the lungs, leading to pulmonary microvascular disease and neural regulation disorders, causing abnormalities in lung structure and function. The present study explored the effect of fibroblast growth factor (FGF)4 as a potential therapeutic growth factor on the effect of hyperglycemia on the lungs in vitro and in vivo models. The effect of FGF4 on the damage of lung cells caused by high glucose was evaluated in vitro and in vivo by a series of biochemical experiments (indirect immunofluorescence, western blotting, immunohistochemistry and siRNA). The results showed that FGF4 could effectively alleviate the inhibition of lung cell proliferation caused by high glucose. Further experiments found that high glucose caused inflammation, oxidative stress and fibrosis of lung cells, while the above pathological reactions were alleviated after treatment with FGF4. Further mechanism research showed that FGF4 treatment could markedly improve the survival rate of lung cells, reduce cell death and inflammatory responses and enhance the antioxidant stress resistance of cells. These effects are achieved by activating the adenosine monophosphate (AMP)‑activated protein kinase (AMPK)‑peroxisome proliferator‑activated receptor coactivator 1 (PGC‑1) signaling axis, which plays an important role in regulating cellular metabolism, antioxidant stress and anti‑inflammatory responses. In vivo experiments further confirmed the mitigating effect of FGF4 on lung tissue damage caused by high glucose. FGF4 treatment to diabetic model animals, lung function can be markedly improved and the degree of lung inflammation and fibrosis can be reduced. In summary, FGF4 exhibits a significant mitigating effect on high‑glucose‑induced lung cell damage through the AMPK‑PGC‑1 signaling axis, providing a new strategy for the treatment of diabetes and its pulmonary complications.