International journal of molecular medicine最新文献

Following the publication of this paper, a concerned reader drew to the Editor's attention that it appeared as if the authors had calculated the apoptotic rates erroneously. The authors were asked to provide an explanation to account for the concerns raised by the interested reader; however, they did not respond to this request submitted by the Editorial Office. Therefore, owing to the lack of responsiveness on the part of the authors, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the journal. The Editor would like to apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 973‑981, 2019; DOI: 10.3892/ijmm.2019.4258].

Cell senescence impedes the self‑renewal and osteogenic capacity of bone marrow mesenchymal stem cells (BMSCs), thus limiting their application in tissue regeneration. The present study aimed to elucidate the role and mechanism of repetitive element (RE) activation in BMSC senescence and osteogenesis, as well as the intervention effect of quercetin. In an H2O2‑induced BMSC senescence model, quercetin treatment alleviated senescence as shown by a decrease in senescence‑associated β‑galactosidase (SA‑β‑gal)‑positive cell ratio, increased colony formation ability and decreased mRNA expression of p21 and senescence‑associated secretory phenotype genes. DNA damage response marker γ‑H2AX increased in senescent BMSCs, while expression of epigenetic markers methylation histone H3 Lys9, heterochromatin protein 1α and heterochromatin‑related nuclear membrane protein lamina‑associated polypeptide 2 decreased. Quercetin rescued these alterations, indicating its ability to ameliorate senescence by stabilizing heterochromatin structure where REs are primarily suppressed. Transcriptional activation of REs accompanied by accumulation of cytoplasmic double‑stranded (ds)RNA, as well as triggering of the RNA sensor retinoic acid‑inducible gene I (RIG‑I) receptor pathway in H2O2‑induced senescent BMSCs were shown. Similarly, quercetin treatment inhibited these responses. Additionally, RIG‑I knockdown led to a decreased number of SA‑β‑gal‑positive cells, confirming its functional impact on senescence. Induction of senescence or administration of dsRNA analogue significantly hindered the osteogenic capacity of BMSCs, while quercetin treatment or RIG‑I knockdown reversed the decline in osteogenic function. The findings of the current study demonstrated that quercetin inhibited the activation of REs and the RIG‑I RNA sensing pathway via epigenetic regulation, thereby alleviating the senescence of BMSCs and promoting osteogenesis.

The present study investigated the anti‑melanogenesis effects of Giant Centella asiatica (GCA), a new cultivator of Centella asiatica (CA) cataloged by the Korea Forest Service in 2022, and compared its efficacy with that of traditional CA. GCA has a high yield per unit area and enhanced antioxidant properties. The anti‑melanogenic effects of GCA were investigated using B16F10 melanoma cells and a 3D human skin‑equivalent model. Key molecular mechanisms were elucidated through western blotting, cAMP assays and molecular docking studies. Focus was addressed on the effect of GCA on skin whitening by comparing the ability of a GCA extract to inhibit melanin production in B16F10 melanoma cells and a 3D human skin‑equivalent model to that of CA. The results showed that the GCA extracts more effectively reduced melanin production, which was attributed to their higher content of two active components, madecassoside and asiaticoside. Further investigation revealed that GCA primarily inhibited melanogenesis through the PKA‑cAMP response element‑binding (CREB)‑microphthalmia‑associated transcription factor (MITF) axis, a key regulatory pathway in melanin synthesis. Notably, the present study, to the best of our knowledge, is the first to demonstrate that madecassoside and asiaticoside, the two principal compounds in GCA, directly bound to MC1R, which contributed to the significant skin‑whitening effects. Moreover, GCA reduced melanin production in a 3D human skin‑equivalent model, showing efficacy within a complex skin environment. These results demonstrated the superior effectiveness of GCA to that of CA for skin anti‑melanogenesis, indicating its potential as a promising natural material for targeting pigmentation disorders.

The tumour suppressor factor p53 plays an essential role in regulating numerous cellular processes, including the cell cycle, DNA repair, apoptosis, autophagy, cell metabolism and immune response. TP53 is the most commonly mutated gene in human cancers. These mutations are primarily non‑synonymous changes that produce mutant p53 proteins characterized by loss of function, a dominant negative effect on p53 tetramerisation and gain of function (GOF). GOF mutations not only disrupt the tumour‑suppressive activities of p53 but also endow the mutant proteins with new oncogenic properties. Recent studies analysing different pathogenic features of mutant p53 in cancer‑derived cell lines have demonstrated that restoring wild‑type p53, rather than removing GOF mutations, reduces cancer cell growth. These findings suggest that therapeutic strategies for reactivating wild‑type p53 function in cancer cells may bring a greater benefit than approaches halting mutant p53. This approach could involve the use of small molecules, gene therapy and other methods to re‑establish wild‑type p53 activity. This review describes the complexity of the biological activities of different p53 mutants and summarizes the current therapeutic approaches to restore p53 function.

Long non‑coding RNA (lncRNA) is a class of non‑coding RNA molecules located in the cytoplasm or nucleus, which can regulate chromosome structure and function by interacting with DNA, RNA, proteins and other molecules; binding to mRNA bases in a complementary manner, affecting the splicing, stabilization, translation and degradation of mRNA; acting as competing endogenous RNA competitively binds to microRNAs to regulate gene expression and participate in the regulation of various vital activities of the body. The PI3K/AKT signalling pathway plays a key role in numerous biological and cellular processes, such as cell proliferation, invasion, migration and angiogenesis. It has been found that the lncRNA/PI3K/AKT axis regulates the expression of cancer‑related genes and thus tumour progression. The abnormal regulation of lncRNA expression in the lncRNA/PI3K/AKT axis is clearly associated with clinicopathological features and plays an important role in regulating biological functions. In the present review, the expression and biological functions of PI3K/AKT‑related lncRNAs both in vitro and in vivo over recent years, were comprehensively summarized and analyzed. Their correlation with clinicopathological features was also evaluated, with the objective of furnishing a solid theoretical foundation for clinical diagnosis and the monitoring of efficacy in digestive system neoplasms. The present review aimed to provide a comprehensive overview of the expression and biological functions of PI3K/AKT‑related lncRNAs in digestive system neoplasms and to assess their correlation with clinicopathological features. This endeavor seeks to establish a solid theoretical foundation for the clinical diagnosis and efficacy monitoring of digestive system tumors.

The pathophysiology of cardiovascular disease (CVD) is complex and presents a serious threat to human health. Cardiomyocyte loss serves a pivotal role in both the onset and progression of CVD. Among various forms of programmed cell death, ferroptosis, along with apoptosis, autophagy and pyroptosis, is closely linked to the advancement of CVD. Ferroptosis, a mechanism of cell death, is driven by the buildup of oxidized lipids and excess iron. This pathway is modulated by lipid, amino acid and iron metabolism. Key characteristics of ferroptosis include disrupted iron homeostasis, increased peroxidation of polyunsaturated fatty acids due to reactive oxygen species, decreased glutathione levels and inactivation of glutathione peroxidase 4. Treatments targeting ferroptosis could potentially prevent or alleviate CVD by inhibiting the ferroptosis pathway. Ferroptosis is integral to the pathogenesis of several types of CVD and inhibiting its occurrence in cardiomyocytes could be a promising therapeutic strategy for the future treatment of CVD. The present review provided an in‑depth analysis of advancements in understanding the mechanisms underlying ferroptosis. The present manuscript summarized the interplay between ferroptosis and CVDs, highlighting its dual roles in these conditions. Additionally, potential therapeutic targets within the ferroptosis pathway were discussed, alongside the current limitations and future directions of these novel treatment strategies. The present review may offer novel insights into preventive and therapeutic approaches for CVDs.

Subsequently to the publication of this article, an interested reader drew to the authors' attention that the Control and Nrf1α data panels in Fig. 1G on p. 2463 contained overlapping data, such that these data, which were intended to show the results from differently performed experiments, had apparently been derived from the same original source. Upon examining their original data, the authors realized that the image for the Control experiment was selected incorrectly for this figure. In rectifying this error, the authors have chosen to show the data from one of their repeated experiments for Fig. 1G, and the revised version of this figure is shown on the next page. They can confirm that the replacement of these data in this corrigendum does not significantly affect the conclusions reported in the study. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this corrigendum, and wish to apologize to readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 2459‑2468, 2018; DOI: 10.3892/ijmm.2018.3816].

In the modern era of medicine, prognosis and treatment, options for a number of cancer types including breast cancer have been improved by the identification of cancer‑specific biomarkers. The availability of high‑throughput sequencing and analysis platforms, the growth of publicly available cancer databases and molecular and histological profiling facilitate the development of new drugs through a precision medicine approach. However, only a fraction of patients with breast cancer with few actionable mutations typically benefit from the precision medicine approach. In the present review, the current development in breast cancer driver gene identification, actionable breast cancer mutations, as well as the available therapeutic options, challenges and applications of breast precision oncology are systematically described. Breast cancer driver mutation‑based precision oncology helps to screen key drivers involved in disease development and progression, drug sensitivity and the genes responsible for drug resistance. Advances in precision oncology will provide more targeted therapeutic options for patients with breast cancer, improving disease‑free survival and potentially leading to significant successes in breast cancer treatment in the near future. Identification of driver mutations has allowed new targeted therapeutic approaches in combination with standard chemo‑ and immunotherapies in breast cancer. Developing new driver mutation identification strategies will help to define new therapeutic targets and improve the overall and disease‑free survival of patients with breast cancer through efficient medicine.

Ginseng may improve the myelosuppression and intestinal microbiota disorder induced by cyclophosphamide (CY); however, the effect of ginseng components on hematopoietic stem cell (HSC) damage remains largely unexplored. The present study aimed to assess the protective effect of ginseng extract (GE), total ginsenosides (TG) and total polysaccharides (TP) from ginseng on the intestinal microflora and HSCs of model mice. In the present study, a mouse model of HSC damage induced by CY was constructed, intestinal microflora of fecal samples were sequenced using the 16S ribosomal RNA (rRNA) sequencing techniques, the differentially expressed genes (DEGs) of HSCs were analyzed using high‑throughput RNA‑sequencing, cell apoptosis and erythroid differentiation were detected using flow cytometry and the blood cell parameters were analyzed using a hematology analyzer. Analysis of the 16S rRNA in fecal samples showed that GE, TG and TP improved an imbalanced intestinal microflora, where the relative abundance of Lactobacillus intestinalis had a positive correlation with ginsenosides content. Specifically, TP significantly increased the expression of low‑abundance microflora. Transcriptomic analysis results revealed 2,250, 3,432 and 261 DEGs in the GE, TG and TP groups compared with those in the Model group, respectively. In the expression analysis of DEGs, both TG and GE were found to markedly increase the expression levels of Klf4, Hhex, Pbx1, Kmt2a, Mecom, Zc3h12a, Zbtb16, Lilr4b, Flt3 and Klf13. Furthermore, TG inhibited the apoptosis of HSCs by increasing the expression levels of Bcl2 and Mcl1, whilst decreasing the expression of Bax. By contrast, GE inhibited the apoptosis of HSCs by reducing the expression of Bax and Bad. Regarding erythroid differentiation and blood cell parameters, GE was found to significantly increase the expression of TER‑119. In addition, GE and TG improved all blood cell parameters, including the count of white blood cells, neutrophils (NEUT), lymphocytes (LYMPH), red blood cells (RBC), hemoglobin (HGB) and reticulocyte and platelets (PLT), whereas TP could only improve the counts of LYMPH, RBC, HGB and PLT. The improvement effect of GE and TG on WBC, NEUT and Ret was superior to TP. In conclusion, TG may protect the hematopoiesis function of HSCs in a CY‑induced mouse model of HSC damage, followed by GE. However, TP did not appear to improve HSC damage. Ginsenosides may therefore be considered essential ingredients in GE when protecting HSCs against damage. GE and TG exerted their protective effects on HSCs by inhibiting the apoptosis of HSCs whilst improving the imbalance of intestinal microflora.

Osteosarcoma malignancy exhibits significant heterogeneity, comprising both osteosarcoma stem cells (OSCs) and non‑OSCs. OSCs demonstrate increased resistance to chemotherapy due to their distinctive cellular and molecular characteristics. Alterations in mitochondrial morphology and homeostasis may enhance chemoresistance by modulating metabolic and regulatory processes. However, the relationship between mitochondrial homeostasis and chemoresistance in OSCs remains to be elucidated. The present study employed high‑resolution microscopy to perform multi‑layered image reconstructions for a quantitative analysis of mitochondrial morphology. The results indicated that OSCs exhibited larger mitochondria in comparison with non‑OSCs. Furthermore, treatment of OSCs with cisplatin (CIS) or doxorubicin (DOX) resulted in preserved mitochondrial morphological stability, which was not observed in non‑OSCs. This finding suggested a potential association between mitochondrial homeostasis and chemoresistance. Further analysis indicated that dynamin‑related protein 1 (DRP1) might play a pivotal role in maintaining the stability of mitochondrial homeostasis in OSCs. Depletion of DRP1 resulted in the disruption of mitochondrial stability when OSCs were treated with CIS or DOX. Additionally, knocking out DRP1 in OSCs led to a reduction in chemoresistance. These findings unveil a novel mechanism underlying chemoresistance in osteosarcoma and suggest that targeting DRP1 could be a promising therapeutic strategy to overcome chemoresistance in OSCs. This provided valuable insights for enhancing treatment outcomes among patients with osteosarcoma.