International journal of molecular medicine最新文献

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.

Long interspersed nuclear element‑1 (L1) is highly expressed in the early embryos of humans, rodents and fish. To investigate the molecular mechanisms underlying high expression of L1 during early embryonic development, a C1‑open reading frame (ORF)2 vector was constructed in which ORF2 of human L1 (L1‑ORF2) was inserted into a pEGFP‑C1 plasmid. C1‑ORF2 vector was injected into early zebrafish embryos (EZEs) to observe expression of EGFP reporter protein by fluorescence microscopy. RNA‑seq and RT‑qPCR were used to detect the effects of lipovitellin (LV)  on gene expression in EZEs. The binding ability of LV to L1‑ORF2 DNA was detected by electrophoretic mobility‑shift assay (EMSA). The chromatin recombinant DNase I digestion and ATAC‑seq assay were used to evaluate the accessibility of plasmid DNA. C1‑ORF2 vector induced high expression of enhanced green fluorescent protein (EGFP) reporter gene after it had been injected into 0 h post‑fertilization (hpf) zebrafish embryos, although histone octamer inhibited expression of EGFP in C1‑ORF2. SDS‑PAGE was used to show that LV was the predominant protein binding ORF2 DNA in 0 hpf zebrafish embryo lysate (ZEL). Both ZEL and purified LV from ZEL attenuated the inhibitory effects induced by histone. LV bound histone to interfere with the binding of histone to ORF2 DNA. Both in vitro chromatin reconstitution experiments and assay for transposase‑accessible chromatin with sequencing with HeLa cells were utilized to demonstrate that the interference induced by LV resulted in increased accessibility of C1‑ORF2. Transcription experiments in vitro verified that LV could enhance the mRNA levels of zebrafish early embryo expression genes grainyhead‑like transcription factor 3 (GRHL3), SRY‑box transcription factor 19a (SOX19A) and nanor (NNR) and also of the EGFP gene. LV was found to increase the expression levels of the zebrafish early embryo expression genes in liver tissue after LV had been injected into the abdominal cavity of adult male zebrafish. Taken together, the findings of the present study demonstrated that LV activates the expression of EGFP induced by ORF2 in EZEs by enhancing the accessibility of ORF2 DNA.

A dynamic balance exists between osteogenesis and osteoclastogenesis in bone tissue, which can lead to several bone diseases, such as osteoporosis, osteoarthritis, bone necrosis and bone defects, in cases of insufficient osteogenesis or excessive osteoclastogenesis. NEL‑like molecule‑1 (NELL‑1) was first discovered in 1999 as an osteogenic factor that can prevent or treat bone diseases by increasing osteogenic levels. To date, research has identified multiple signaling pathways involved in improving osteogenic levels. Furthermore, to apply NELL‑1 in clinical practice, researchers have optimized its osteogenic effect by combining it with other molecules, changing its molecular structure and performing bone tissue engineering. Currently, research on NELL‑1 is gaining increasing attention. In the near future, it will definitely be applied in clinical practice to eliminate diseases. Thus, the present study provides a comprehensive review of NELL‑1 in enhancing osteogenic levels from the perspectives of the molecular mechanism, interactions with other molecules/cells, molecular‑level changes, applications in bone tissue engineering and its expression in tumors, providing a solid theoretical basis for its clinical application.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric data shown in Fig. 1D, DCFH‑DA‑stained cellular data in Fig. 2A, and western blotting data in Figs. 2G and 5B were strikingly similar to data that had either already appeared in previously published articles written by different authors at different research institutes (one of which has since been retracted), or were featured in an article that was submitted for publication to a different journal at around the same time. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, 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 reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 50: 89, 2022; DOI: 10.3892/ijmm.2022.5144].

Enocyanin (ENO), an anthocyanin extracted from grapes, has been shown to exert inhibitory effects on acid phosphatase and inflammation; however, its role in osteogenesis and bone formation is currently unknown. The present study aimed to investigate the effects of ENO on osteogenesis in vitro and bone formation in vivo, and to explore the rudimentary mechanisms. KusaO cells were employed to evaluate the osteogenic role of ENO in vitro by Alizarin red S staining, ALP staining, quantitative PCR and western blotting, and an in vivo analysis of the therapeutic effects of ENO on a femoral fracture model was performed using stereo microscope, micro‑CT and histological staining. To further investigate the underlying mechanisms, mRNA sequencing was employed to investigate the changes in gene expression and the downstream pathways after ENO treatment. The results showed that ENO could promote the osteogenic differentiation of KusaO cells in vitro and bone fracture regeneration in vivo. Mechanistically, ENO was highly related to bone formation, including the 'Wnt signalling pathway', 'bone development' and 'bone mineralization'. In addition, matrix metalloproteinase 9 (MMP9) was identified as one of the targets of ENO in its promotional role in osteogenesis. In conclusion, ENO may represent a therapeutic candidate for bone regeneration in bone fractures by regulating osteogenesis and bone formation via MMP9.

Src‑associated in mitosis 68 kDa protein (Sam68) is a protein encoded by the heteronuclear ribonucleoprotein particle K homology (KH) single domain‑containing, RNA‑binding, signal transduction‑associated protein 1 (known as KHDRBS1) gene in humans. This protein contains binding sites for critical components in a variety of cellular processes, including the regulation of gene expression, RNA processing and cell signaling. Thus, Sam68 may play a role in a variety of diseases, including cancer. Sam68 has been widely demonstrated to participate in tumor cell proliferation, progression and metastasis to be involved in the regulation of cancer stem cell self‑renewal. Based on the body of evidence available, Sam68 emerges as a promising target for this disease. The objectives of the present included summarizing the role of Sam68 in cancer murine models and cancer patients, unraveling the molecular mechanisms underlying its oncogenic potential and discussing the effectiveness of antitumor agents in reducing the malignant effects of Sam68 during tumorigenesis.

Coronary heart disease (CHD) remains a leading cause of morbidity and mortality worldwide, posing a substantial public health burden. Despite advancements in treatment, the complex etiology of CHD necessitates ongoing exploration of novel diagnostic markers and therapeutic targets. Circular RNAs (circRNAs), a distinct class of non‑coding RNAs with a covalently closed loop structure, have emerged as significant regulators in various diseases, including CHD. Their high stability, tissue‑specific expression and evolutionary conservation underscore their potential as biomarkers and therapeutic agents in CHD. This review discusses the current knowledge on circRNAs in the context of CHD and explores the molecular mechanisms by which circRNAs influence the pathophysiology of CHD, including cardiomyocyte death, endothelial injury, vascular dysfunction and inflammation. It also summarizes the emerging evidence highlighting the differential expression of circRNAs in patients with CHD and their potential utilities as non‑invasive diagnostic and prognostic biomarkers and therapeutic targets for this disease.