International journal of molecular medicine最新文献

The ubiquitin (Ub)‑proteasome system (UPS) plays a pivotal role in maintaining protein homeostasis and function to modulate various cellular processes including skeletal cell differentiation and bone homeostasis. The Ub ligase E3 promotes the transfer of Ub to the target protein, especially transcription factors, to regulate the proliferation, differentiation and survival of bone cells, as well as bone formation. In turn, the deubiquitinating enzyme removes Ub from modified substrate proteins to orchestrate bone remodeling. As a result of abnormal regulation of ubiquitination, bone cell differentiation exhibits disorder and then bone homeostasis is affected, consequently leading to osteoporosis. The present review discussed the role and mechanism of UPS in bone remodeling. However, the specific mechanism of UPS in the process of bone remodeling is still not fully understood and further research is required. The study of the mechanism of action of UPS can provide new ideas and methods for the prevention and treatment of osteoporosis. In addition, the most commonly used osteoporosis drugs that target ubiquitination processes in the clinic are discussed in the current review.

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post‑translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism‑related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non‑alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

Osteoporosis is a common bone metabolic disease that causes a heavy social burden and seriously threatens life. Improving osteogenic capacity is necessary to correct bone mass loss in the treatment of osteoporosis. Osteoblasts are derived from the differentiation of bone marrow mesenchymal stem cells, a process that opposes adipogenic differentiation. The peroxisome proliferator‑activated receptor γ and Wnt/β‑catenin signaling pathways mediate the mutual regulation of osteogenesis and adipogenesis. Lipid substances play an important role in the occurrence and development of osteoporosis. The content and proportion of lipids modulate the activity of immunocytes, mainly macrophages, and the secretion of inflammatory factors, such as IL‑1, IL‑6 and TNF‑α. These inflammatory effectors increase the activity and promote the differentiation of osteoclasts, which leads to bone imbalance and stronger bone resorption. Obesity also decreases the activity of antioxidases and leads to oxidative stress, thereby inhibiting osteogenesis. The present review starts by examining the bidirectional differentiation of BM‑MSCs, describes in detail the mechanism by which lipids affect bone metabolism, and discusses the regulatory role of inflammation and oxidative stress in this process. The review concludes that a reasonable adjustment of the content and proportion of lipids, and the alleviation of inflammatory storms and oxidative damage induced by lipid imbalances, will improve bone mass and treat osteoporosis.

Following the publication of the above paper, it has been drawn to the Editors' attention by a concerned reader that certain of the lumen formation assay data shown in Fig. 5A on p. 112 were strikingly similar to data appearing in different form in another article written by different authors at different research institute, which had already been published in the journal Biomedicine & Pharmacotherapy prior to the submission of this paper to International Journal of Molecular Medicine, and which has also subsequently been retracted. In view of the fact that the contentious data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 103‑114, 2019; DOI: 10.3892/ijmm.2019.4183].

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the colony formation assay data shown in Fig. 7A on p. 1183 were strikingly similar to data appearing in different form in the following article written by different authors at different research institutes that had already been published prior to its date of submission: Lou L, Chen G, Zhong B and Liu F: Lycium barbarum polysaccharide induced apoptosis and inhibited proliferation in infantile hemangioma endothelial cells via down‑regulation of PI3K/AKT signaling pathway. Biosci Rep 39: BSR20191182, 2019. In addition, possible anomalies were noted regarding the appearance of the western blots in the paper. 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 46: 1175‑1185, 2020; DOI: 10.3892/ijmm.2020.4671].

Ovarian cancer (OC) is one of the most common gynecological malignancies. Currently, chemoradiotherapy is the primary clinical treatment approach for OC; however, it has severe side effects and a high rate of recurrence. Thus, there is an urgent need to develop innovative therapeutic options. Paeoniflorigenone (PFG) is a monoterpene compound isolated from the traditional Chinese medicine Paeoniae Radix Rubra. PFG can inhibit the proliferation of tumor cells; however, its anticancer activity against OC has yet to be elucidated. Mucin 1 (MUC1) is highly expressed in various malignant tumors, and is associated with tumor proliferation, metastasis and epithelial‑mesenchymal transition (EMT). In addition, MUC1 affects numerous signaling pathways in tumor cells. In order to develop a possible treatment approach for metastatic OC, the antitumor activity of PFG in OC cells was investigated using Cell Counting Kit‑8 assay, Edu assay, flow cytometry, Transwell assay and western blot analysis. In addition, it was assessed how PFG affects MUC1 expression and function. The experiments revealed that PFG significantly inhibited OC cell proliferation, migration, invasion and EMT. PFG also induced S‑phase cell cycle arrest in OC cells. Furthermore, PFG inhibited MUC1 promoter activity, which led to a decrease in MUC1 protein expression. By contrast, MUC1 promoted OC progression, including cell proliferation, cell cycle progression and cell migration. Stable knockdown of MUC1 in OC cells improved the ability of PFG to block the Wnt/β‑catenin pathway, and to limit tumor cell invasion and migration, whereas MUC1 overexpression partially counteracted the antitumor effects of PFG. In conclusion, the present study demonstrated that PFG may inhibit the MUC1/Wnt/β‑catenin pathway to induce anti‑metastatic, anti‑invasive and anti‑EMT effects on OC. Notably, MUC1 may be a direct target of PFG. Thus, PFG holds promise as a specific antitumor agent for the treatment of OC.

In paraquat (PQ)‑induced acute lung injury (ALI)/ acute respiratory distress syndrome, PQ disrupts endothelial cell function and vascular integrity, which leads to increased pulmonary leakage. Anthrahydroquinone‑2,6‑disulfonate (AH2QDS) is a reducing agent that attenuates the extent of renal injury and improves survival in PQ‑intoxicated Sprague‑Dawley (SD) rats. The present study aimed to explore the beneficial role of AH2QDS in PQ‑induced ALI and its related mechanisms. A PQ‑intoxicated ALI model was established using PQ gavage in SD rats. Human pulmonary microvascular endothelial cells (HPMECs) were challenged with PQ. Superoxide dismutase, malondialdehyde, reactive oxygen species and nitric oxide (NO) fluorescence were examined to detect the level of oxidative stress in HPMECs. The levels of TNF‑α, IL‑1β and IL‑6 were assessed using an ELISA. Transwell and Cell Counting Kit‑8 assays were performed to detect the migration and proliferation of the cells. The pathological changes in lung tissues and blood vessels were examined by haematoxylin and eosin staining. Evans blue staining was used to detect pulmonary microvascular permeability. Western blotting was performed to detect target protein levels. Immunofluorescence and immunohistochemical staining were used to detect the expression levels of target proteins in HPMECs and lung tissues. AH2QDS inhibited inflammatory responses in lung tissues and HPMECs, and promoted the proliferation and migration of HPMECs. In addition, AH2QDS reduced pulmonary microvascular permeability by upregulating the levels of vascular endothelial‑cadherin, zonula occludens‑1 and CD31, thereby attenuating pathological changes in the lungs in rats. Finally, these effects may be related to the suppression of the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (AKT)/endothelial‑type NO synthase (eNOS) signalling pathway in endothelial cells. In conclusion, AH2QDS ameliorated PQ‑induced ALI by improving alveolar endothelial barrier disruption via modulation of the PI3K/AKT/eNOS signalling pathway, which may be an effective candidate for the treatment of PQ‑induced ALI.

Among women globally, breast cancer is the most prevalent cancer and the leading cause of cancer‑related death. Interestingly, though genetic mutations contribute to the disease, <15% of women diagnosed with breast cancer have a family history of the disease, suggesting a prevalence of sporadic genetic mutations in breast cancer development. In the rapidly rising field of cancer genomics, neoantigen‑based immunotherapy has come to the fore. The investigation of novel proteins arising from unique somatic mutations or neoantigens have opened a new pathway for both individualized and public cancer treatments. Because they are shared among individuals with similar genetic changes, public neoantigens provide an opportunity for 'off‑the‑shelf' anticancer therapies, potentially extending the benefits to a wider patient group. The present review aimed to highlight the role of shared or public neoantigens as therapeutic targets for patients with breast cancer, emphasizing common hotspot mutations of certain genes identified in breast cancer. The clinical utilization of public neoantigen‑based therapies for breast cancer treatment were also discussed.

Inflammatory bowel disease (IBD) is marked by persistent inflammation, and its development and progression are linked to environmental, genetic, immune system and gut microbial factors. DNA methylation (DNAm), as one of the protein modifications, is a crucial epigenetic process used by cells to control gene transcription. DNAm is one of the most common areas that has drawn increasing attention recently, with studies revealing that the interleukin (IL)‑23/IL‑12, wingless‑related integration site, IL‑6‑associated signal transducer and activator of transcription 3, suppressor of cytokine signaling 3 and apoptosis signaling pathways are involved in DNAm and in the pathogenesis of IBD. It has emerged that DNAm‑associated genes are involved in perpetuating the persistent inflammation that characterizes a number of diseases, including IBD, providing a novel therapeutic strategy for exploring their treatment. The present review discusses DNAm‑associated genes in the pathogenesis of IBD and summarizes their application as possible diagnostic, prognostic and therapeutic biomarkers in IBD. This may provide a reference for the particular form of IBD and its related methylation genes, aiding in clinical decision‑making and encouraging therapeutic alternatives.

Numerous studies have attempted to develop biological markers for the response to radiation for broad and straightforward application in the field of radiation. Based on a public database, the present study selected several molecules involved in the DNA damage repair response, cell cycle regulation and cytokine signaling as promising candidates for low‑dose radiation‑sensitive markers. The HuT 78 and IM‑9 cell lines were irradiated in a concentration‑dependent manner, and the expression of these molecules was analyzed using western blot analysis. Notably, the activation of ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHK2), p53 and H2A histone family member X (H2AX) significantly increased in a concentration‑dependent manner, which was also observed in human peripheral blood mononuclear cells. To determine the radioprotective effects of cinobufagin, as an ATM and CHK2 activator, an in vivo model was employed using sub‑lethal and lethal doses in irradiated mice. Treatment with cinobufagin increased the number of bone marrow cells in sub‑lethal irradiated mice, and slightly elongated the survival of lethally irradiated mice, although the difference was not statistically significant. Therefore, KU60019, BML‑277, pifithrin‑α, and nutlin‑3a were evaluated for their ability to modulate radiation‑induced cell death. The use of BML‑277 led to a decrease in radiation‑induced p‑CHK2 and γH2AX levels and mitigated radiation‑induced apoptosis. On the whole, the present study provides a novel approach for developing drug candidates based on the profiling of biological radiation‑sensitive markers. These markers hold promise for predicting radiation exposure and assessing the associated human risk.