Lung cancer is one of the leading causes of tumor‑associated mortality, and >75% of patients with lung cancer have non‑small cell lung cancer (NSCLC). Pemetrexed, a folate antagonist, is a first‑line chemotherapy drug for NSCLC that is administered alone or in combination with cisplatin. The present study established in vitro cell models of PTEN inhibition and overexpression, and the effects of the treatment with pemetrexed were investigated in these cell models. Result from the present study demonstrated that treatment with pemetrexed suppressed lung cancer cell proliferation, inhibited mRNA and protein expression levels of anti‑apoptotic Bcl2, and increased the mRNA and the protein expression levels of pro‑apoptotic p53 and apoptosis regulator BAX. The present study suggested that pemetrexed regulated apoptosis via the inhibition of the mTOR/PI3K/AKT signaling pathway. Additionally, cellular processes associated with the aerobic oxidation of carbohydrates were identified to be significantly inhibited. The present findings suggested that treatment with pemetrexed may exhibit synergistic effects with PTEN on lung cancer cells via the inhibition of the PI3K/AKT/mTOR signaling pathway and through carbohydrate metabolism, and treatment with pemetrexed combined with PTEN overexpression may represent a novel therapeutic strategy for the treatment of NSCLC.

Cytotoxic T lymphocyte dysfunction is frequently associated with PD‑L1/PD‑1 pathway activation, and is a principal obstacle in cancer therapy. In the present study, the mechanisms underlying the human papillomavirus (HPV)‑induced evasion of cervical cancer cells to the host immune system via the programmed death ligand  1/programmed death 1 (PD‑L1/PD‑1) signaling pathway was investigated. A significant increase in the expression of the HPV16E7 viral protein and PD‑L1 in cervical tissues was observed when compared with normal cervical tissues. In addition, a positive correlation between HPV16E7 and PD‑L1 expression was observed by immunohistochemical staining and reverse transcription‑polymerase chain reaction. Overexpressing HPV16E7 oncoprotein in the epithelial carcinoma of PC3 cells increased the expression level of the PD‑L1 protein and inhibited peripheral blood mononuclear cell (PBMC) proliferation and cytotoxic T lymphocyte (CTL) activity. Upon knockdown of HPV16E7 in HPV16‑associated CaSki cervical cancer cells with a relevant siRNA, a reduction in PD‑L1 protein expression was observed, as well as a significant increase in PBMC proliferation and CTL activity. A recombinant plasmid, MSCVPIG‑soluble PD‑1, was constructed and transfected into the CaSki cell line, and was co‑cultured with PBMCs. PBMC proliferation and CTL activity were observed to increase significantly. In conclusion, the results presented in the current study suggest that overexpression of PD‑L1, induced by HPV16E7, may be responsible for lymphocyte dysfunction. In addition, soluble PD‑1 may restore the function of tumor‑infiltrating lymphocytes by inhibiting the PD‑L1/PD‑1 signaling pathway. These results may provide a novel insight for immunotherapeutic approaches in the treatment of cervical cancer.

Ulcerative colitis (UC) is a global disease, characterized by periods of relapse that seriously affects the quality of life of patients. Oligosaccharides are considered to be a prospective strategy to alleviate the symptoms of UC. The present study aimed to evaluate the effect of weilan gum oligosaccharide (WLGO) on a mouse UC model induced by dextran sulfate sodium (DSS). WLGO structural physical properties were characterized by electrospray mass spectrometry and fourier tansform infrared spectroscopy. MTT assays were performed to evaluate the non‑toxic concentration of WLGO. RT‑qPCR and ELISAs were conducted to determine the levels of inflammatory factors. The clinical symptoms and mucosal integrity of the DSS‑induced UC model were assessed by DAI and histological assessment. LPS‑induced Caco‑2 cells and DSS‑induced UC mice were used to explore the effects of WLGO on UC. Treatment of the mice with 4.48 g/kg/day WLGO via gavage for 7 days significantly relieved the symptoms of DSS‑induced UC model mice, whereas significant effects were not observed for all symptoms of DSS‑induced UC in the WLGO‑low group. The disease activity index score was decreased and the loss of body weight was reduced in DSS‑induced UC model mice treated with WLGO. Moreover, colonic damage and abnormally short colon length shortenings were relieved following WLGO treatment. WLGO treatment also reduced the concentration and mRNA expression levels of proinflammatory cytokines, including interleukin‑1β, interleukin‑6 and tumor necrosis factor α, in DSS‑induced UC model mice and lipopolysaccharide‑treated Caco‑2 cells. These results indicated that WLGO may be an effective strategy for UC treatment.

It has been established that dental pulp stem cells (DPSCs) serve an important role in the restoration and regeneration of dental tissues. DPSCs are present in blood vessels and also exist in the vessel microenvironment in vivo and have a close association with endothelial cells (ECs). The present study aimed to evaluate the influence of ECs and their secretory product endothelin‑1 (ET‑1) on the differentiation of DPSCs. In the present study, cells were divided into four groups: i) a DPSC‑only control group; ii) a DPSC with ET‑1 administration group; iii) a DPSC and human umbilical vein endothelial cell (HUVEC) direct co‑culture group; and iv) a DPSC and HUVEC indirect co‑culture group using a Transwell system. Reverse transcription‑quantitative polymerase chain reaction was used to detect the expression of the odontoblastic differentiation‑associated genes, including dentin sialoprotein (DSP) and dentin matrix acidic phosphoprotein 1 (DMP‑1) at days 4, 7, 14 and 21. Alizarin Red S staining, immunofluorescence and western blot analyses were also conducted to assess the differentiation of the DPSCs in each group. The highest expression levels of odontoblastic differentiation‑associated genes were observed on day 7 and in the two co‑culture groups were increased compared with the DPSC‑only and DPSC + ET‑1 culture groups at all four time points. However, expression levels in the DPSC + ET‑1 group were not downregulated as notably as in the co‑culture groups on days 14 and 21. The Transwell group exhibited the greatest ability for odontoblastic differentiation compared with the other groups according to staining with Alizarin Red S, immunofluorescence and western blot analysis results. According to the results of the present study, the culture solution with HUVECs affected the differentiation of DPSCs. In addition, ET‑1 may promote the odontoblastic differentiation of DPSCs.

3,3'‑Diindolylmethane (DIM) is a naturally derived indole compound found in the Brassica family of vegetables. DIM has several beneficial effects, including anti‑cancer, anti‑inflammatory and anti‑angiogenic functions. However, the effects of DIM on acute kidney injury (AKI) stimulated by lipopolysaccharide (LPS) are poorly studied. In this present study, male BALB/c mouse models of AKI were established using intraperitoneal injections of 10 mg/kg LPS. DIM (40 mg/kg) was administered intraperitoneally 24 and 2 h before LPS exposure. The results indicated that DIM significantly mitigated histopathological changes in the kidneys and improved the levels of blood urea nitrogen and serum creatinine. DIM also suppressed the LPS‑induced production of reactive oxygen species and cell apoptosis. Furthermore, DIM treatment significantly decreased the expression of NADPH oxidase 2 (NOX2) and NOX4 in LPS‑treated mice. Therefore, DIM may exert its renoprotective actions by inhibiting NOX‑mediated oxidative stress and the apoptosis of renal tubular epithelial cells.

Posterior capsular opacification (PCO) is the main complication following cataract surgery. The proliferation of the residual lens epithelial cells (LECs) serves an important role in PCO formation. The authors' previous study revealed that vitamin C inhibited the proliferation of human LECs by increasing the rapid degradation of hypoxia‑inducible factor‑1 (HIF‑1α), and hence inhibited the expression of vascular endothelial growth factor (VEGF). The present study aimed to further investigate the mechanisms underlying the effects of vitamin C on the expression levels of VEGF. The present study demonstrated that the HIF‑1 inhibitor BAY 87‑2243 significantly inhibited the cell proliferation and the expression levels of VEGF in LECs through the use of colony formation, western blotting and ELISA assays. Moreover, it was revealed that vitamin C could further inhibit the cell proliferation and the expression levels of VEGF in LECs following the cotreatment with the HIF‑1 inhibitor. The proline hydroxylation of HIF‑1α by prolyl hydroxylases (PHDs) was previously discovered to be responsible for the rapid degradation of HIF‑1α. Thus, the present study subsequently used three PHD inhibitors to investigate their effects on the expression levels of VEGF; it was found that the PHD2 specific inhibitor increased the expression levels of VEGF to the greatest extent. Moreover, the genetic knockdown of PHD2 by lentiviral transfection also significantly increased the expression levels of VEGF, whereas the PHD2 specific inhibitor did not alter the expression levels of VEGF in the PHD2 knockdown LECs. AKT kinase activity is an important mediator known to upregulate VEGF expression. Using an immunoprecipitation assay to isolate endogenous AKT, it was demonstrated that AKT was prolyl hydroxylated by PHD2, which inhibited its activity. It was also revealed that vitamin C enhanced the proline‑hydroxylation and inhibited the activity of AKT. Furthermore, an AKT inhibitor increased the effects of vitamin C on the expression levels of VEGF. However, the AKT inhibitor did not affect the expression levels of glucose transporter 1, which is a HIF‑1α target gene. In conclusion, the findings of the present study suggested that vitamin C may inhibit the expression levels of VEGF via HIF‑1α‑dependent and AKT‑dependent pathways in LECs.