Molecular medicine reports最新文献

Cisplatin (DDP) is a key chemotherapeutic agent in the treatment of gastric cancer; however, its efficacy is often limited by chemoresistance, a notable challenge in clinical oncology. The present study aimed to investigate the influence of exosomes derived from M2‑polarized macrophages, which promote this resistance, on the response of gastric cancer cells to DDP, examining both the effects and the underlying mechanisms. M2 macrophages, differentiated from mouse bone marrow cells with interleukin (IL)‑13 and IL‑4, were identified using immunofluorescence staining for CD206 and CD163. Exosomes derived from these macrophages were characterized using transmission electron microscopy and protein markers, including calnexin, tumor susceptibility gene 101 and CD9. The role of exosomal microRNA (miR)‑3681‑3p in DDP resistance was assessed using Cell Counting Kit‑8 and apoptosis assays, while a luciferase reporter assay was used to elucidate the interaction between miR‑3681‑3p and MutL protein homolog 1 (MLH1). Co‑culturing gastric cancer cells with M2 macrophages enhanced DDP resistance, an effect amplified by exosomes from M2 macrophages enriched with miR‑3681‑3p. This microRNA directly targeted and reduced MLH1 protein expression. Overexpression of miR‑3681‑3p through mimic transfection, along with MLH1 silencing by small interfering RNA transfection, significantly increased DDP resistance, as evidenced by elevated IC50 values in AGS cells. By contrast, the overexpression of MLH1 effectively reversed the drug resistance of AGS cells to DDP caused by miR‑3681‑3p mimic transfection, as evidenced by a decrease in the IC50 value. In conclusion, exosomal miR‑3681‑3p from M2 macrophages may have a key role in conferring DDP resistance to gastric cancer by suppressing MLH1, offering a new therapeutic target for overcoming chemoresistance.

α‑1 Antitrypsin (AAT) is an acute phase protein encoded by the serine protease inhibitor family A member 1 gene. This multifunctional protein serves several roles, including anti‑inflammatory, antibacterial, antiapoptotic and immune regulatory functions. The primary role of AAT is to protect tissues and organs from protease‑induced damage due to its function as a serine protease inhibitor. AAT is associated with the development of lung inflammation, liver inflammation and immune‑mediated inflammatory diseases, which are influenced by environmental and genetic factors. For instance, AAT acts as an anti‑inflammatory protein to prevent and reverse type I diabetes. The present study briefly reviewed the molecular properties and mechanisms of AAT, as well as advances in the study of lung, liver and inflammatory diseases associated with AAT. The potential of AAT as a diagnostic and therapeutic target for inflammatory and immune‑mediated inflammatory diseases was reviewed. In addition, the damaging and protective effects of AAT, and its effects on organ function were discussed.

Tumor tissues generally exist in a relatively hypovascular state, and cancer cells must adapt to severe tissue conditions with a limited molecular oxygen and nutrient supply for their survival. Lipid metabolism serves a role in this adaptation. Lipids are supplied not only through the bloodstream but also through autonomous synthesis by cancer cells, and they function as sources of adenosine triphosphate and cell components. Although cancer‑associated lipid metabolism has been widely reviewed, how this metabolism responds to the tumor environment with poor molecular oxygen and nutrient supply remains to be fully discussed. The main aim of the present review was to summarize the findings on this issue and to provide insights into how cancer cells adapt to better cope with metabolic stresses within tumors. It may be suggested that diverse types of lipid metabolism have a role in enabling cancer cells to adapt to both hypoxia and nutrient‑poor conditions. Gaining a deeper understanding of these molecular mechanisms may reveal novel possibilities of exploration for cancer treatment.

Malignant melanoma (MM) is a highly aggressive subtype of skin cancer characterized by a poor prognosis, particularly in the advanced stages. Despite advancements in targeted therapy and immunotherapy, the survival rates for MM remain low, underscoring the need for new therapeutic targets. Pleckstrin homology domain‑containing family A member 4 (PLEKHA4), which has regulatory functions in pivotal cellular processes, has emerged as a potential target in melanoma. The present study aimed to investigate the role of PLEKHA4 in melanoma progression, focusing on its influence on the MAPK and Wnt/β‑catenin signaling pathways. Bioinformatics analysis revealed that PLEKHA4 was upregulated in melanoma tissues, whereas PLEKHA4 knockdown in melanoma cell lines (A375 and A2058) significantly inhibited cell proliferation and migration, enhanced apoptosis and inhibited tumor growth in vivo. Mechanistic studies demonstrated that PLEKHA4 may exert its effects by modulating the MAPK signaling pathway through interactions with key proteins, including ERK, JNK and MEK. Additionally, PLEKHA4 was shown to impact apoptosis by regulating caspase‑3, COX2 and p65. Additionally, β‑catenin nuclear translocation was affected via the Wnt pathway. Moreover, PLEKHA4 knockdown reduced cMyc ubiquitination, consequently promoting its degradation. The present findings suggested that PLEKHA4 could promote melanoma cell proliferation by regulating both the MAPK and Wnt/β‑catenin pathways, thereby proposing PLEKHA4 as a promising therapeutic target for MM. Further studies are warranted to elucidate the mechanisms underlying PLEKHA4‑mediated modulation of cMyc ubiquitination.

Cytoplasmic phospholipase A2 (cPLA2) is a vital member of the PLA2 family. Studies have demonstrated that cPLA2 plays a key role in various inflammatory‑related diseases and cancers. However, limited research has focused on cPLA2 in cardiovascular diseases. The present review discussed and summarized the research progress on cPLA2 in atherosclerosis, cardiomyopathy, myocardial ischemia‑reperfusion injury and other related conditions. It also highlighted the critical molecular mechanisms by which cPLA2 regulates the pathophysiological processes of vascular endothelial cells, platelets and myocardial cells in cardiovascular diseases. Current studies confirm that cPLA2 plays an important role in cardiovascular diseases and has the potential to become a therapeutic target for the diagnosis, treatment evaluation and prognosis of these conditions. The present review systematically explored the significant role of cPLA2 in cardiovascular diseases and elaborated on its underlying molecular mechanisms. The findings aimed to refine the theoretical understanding of cardiovascular disease pathogenesis and provide a foundation for developing novel treatment strategies.

MicroRNAs (miRNAs/miRs) are endogenous, small non‑coding RNAs conserved across species that post‑transcriptionally regulate gene expression by both suppressing translation and inducing mRNA degradation. miRNAs are found in various tissues, exhibit variable expression and their dysregulation is implicated in numerous disease processes. Furthermore, miRNA expression levels have a key role in the normal development of kidney tissue and are key regulators of kidney function, modulating diverse biological processes across renal cell lineages. miR‑378 participates in pathological processes associated with kidney diseases, including kidney cancer, kidney transplantation and diabetic nephropathy. Despite its considerable effects on these conditions, a comprehensive summary of the roles of miR‑378 is unavailable. In the present review, the existing literature on miR‑378 in kidney diseases is consolidated, and its validated gene targets and biological effects in both malignant and non‑malignant conditions are highlighted, thereby providing a foundation for future research.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the migration assay data shown in Fig. 2D on p. 4904 were strikingly similar to data that had already been published in another article in the journal Oncotarget written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, 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. [Molecular Medicine Reports 17: 4899‑4908, 2018; DOI: 10.3892/mmr.2018.8535].

Post‑translational modifications (PTMs) of proteins influence their functionality by altering the structure of precursor proteins. These modifications are closely linked to tumor progression through the regulation of processes such as cell proliferation, apoptosis, angiogenesis and invasion. Tumors produce large amounts of lactic acid through aerobic glycolysis. Lactic acid not only serves an important role in cell metabolism, but also serves an important role in cell communication. Lactylation, a PTM involving lactate and lysine residues as substrates, serves as an epigenetic regulator that modulates intracellular signaling, gene expression and protein function, thereby serving a crucial role in tumorigenesis and progression. The identification of lactylation provides a key breakthrough in elucidating the interaction between tumor metabolic reprogramming and epigenetic modification. The present review primarily summarizes the occurrence of lactylation, its effect on tumor progression, drug resistance, the tumor microenvironment and gut microbiota, and its potential as a therapeutic target for cancer. The aim of the present review was to provide novel strategies for potential cancer therapies.

Radiation‑induced lung injury (RILI) is a prevalent complication following thoracic radiation, and currently there is a lack of effective intervention options. The present study investigated the potential of Compound Kushen Injection (CKI), a botanical drug, to mitigate inflammatory responses in mice with RILI, along with its underlying mechanisms of action. C3H mice underwent total lung irradiation (TLI) and intraperitoneal injection of CKI (2, 4 or 8 ml/kg) once daily for 8 weeks. Pre‑radiation treatment with 4 or 8 ml/kg CKI starting 2 weeks before TLI or concurrent treatment of 8 ml/kg CKI with TLI led to a significantly longer overall survival compared with the TLI vehicle‑treated group. Micro‑computed tomography evaluations showed that concurrent treatment with 8 ml/kg CKI was associated with a significantly lower incidence of RILI. Histological evaluations revealed that concurrent CKI (4 and 8 ml/kg) treatment significantly reduced grades of lung inflammation. Following radiation at 72 h, TLI plus vehicle‑treated mice had significantly elevated serum IL6, IL17A, and transforming growth factor β (TGF‑β) levels compared with non‑irradiated normal mice. Conversely, mice that received TLI plus CKI displayed lower cytokine levels than those in the TLI plus vehicle‑treated mice. Immunohistochemistry staining showed a reduction of TGF‑β positive cells in the lung tissues of TLI mice after CKI treatment. The concurrent TLI CKI‑treated mice had a significantly reduced cyclooxygenase 2 (COX‑2) activity and COX‑2 metabolites compared with TLI vehicle‑treated mice. These data highlight that CKI substantially reduced radiation‑induced lung inflammation, mitigated RILI incidence, and prolonged overall survival.

The present study aimed to investigate whether soluble protein hydrolysate (SPH) protects against intestinal oxidative stress injury. An in vitro lactate dehydrogenase assay was used to assess the cytotoxicity and protective effect of SPH. For in vivo assessment, friend virus B NIH Jackson mouse pups aged 21 days were administered with 5% w/v soluble protein hydrolysate (SPH) through drinking water for 14 days and then luminally injected with 0.3% or 0.6% H₂O₂. Thereafter, the fecal samples of mice were collected, and the mice were sacrificed. Intestinal epithelial injury was assessed, and the expressions of 84 oxidative stress‑related genes in intestinal tissues was determined. SPH prophylactically protected against H₂O₂‑induced oxidative stress injury in human intestinal epithelial cells. An animal model of oxidative stress‑induced intestinal injury was established using 0.3 and 0.6% H₂O₂. SPH treatment reduced oxidative stress (0.3% H₂O₂)‑induced gut injury in mice. As no accelerated body growth was observed in SPH‑treated mice, it was hypothesized that the underlying protective mechanism of SPH is not related to nutrient oversupply. Treatment with SPH upregulated five oxidative protective genes that were not consistent between the sexes. Some antioxidative genes, including ferritin heavy polypeptide‑1 (Fth1), heme oxygenase‑1 (Hmox1), NAD(P)H dehydrogenase quinone 1 (Nqo1) and superoxide dismutase 1 (Sod1), were commonly upregulated in both male and female mice. Overall, an antioxidative protective effect was observed following SPH treatment, which may be attributed to the upregulation of genes that protect against oxidative damage. The findings of the present study highlight the promising potential of SPH as a functional food for alleviating intestinal oxidative stress injury.