Programmed death 1 ligand 1 (PD‑L1) is a negative co‑stimulatory molecule in immune responses. Previous reports have indicated that inflammatory cytokines can upregulate the expression of PD‑L1 in tumor cells, which in turn suppresses host immune responses. Periodontitis is characterized by persistent inflammation of the periodontium, which is initiated by infection with oral bacteria and results in damage to cells and the matrices of the periodontal connective tissues. In the present study, the expression and function of PD‑L1 in periodontal tissue destruction were examined. Periodontal ligament cells (PDLCs) were stimulated by inflammatory cytokines and periodontal pathogens. The expression and function of PD‑L1 on the surface of PDLCs was investigated using flow cytometry in vitro. Periodontal disease was induced by the injection of Porphyromonas gingivalis in mouse models. The expression levels of PD‑L1 in the periodontal tissues of the mice were analyzed using flow cytometry and immunohistochemistry. PD‑L1 was inducibly expressed on the PDLCs by the inflammatory cytokines and periodontal pathogens. The inflammation‑induced expression of PD‑L1 was shown to cause the apoptosis of activated T lymphocytes and improve the survival of PDLCs. Furthermore, in the mouse model of experimental periodontitis, the expression of PD‑L1 in severe cases of periodontitis was significantly lower, compared with that in mild cases. By contrast, no significant differences were observed between the healthy control and severe periodontitis groups. The results of the present study showed that the expression of PD‑L1 may inhibit the destruction of periodontal tissues, indicating the involvement of a possible protective feedback mechanism against periodontal infection.

Aberrant hedgehog signaling contributes to the development of various malignancies, including glioblastoma (GBM). However, the potential mechanism of hedgehog signaling in GBM migration and invasion has remained to be elucidated. The present study showed that enhanced hedgehog signaling by recombinant human sonic hedgehog N‑terminal peptide (rhSHH) promoted the adhesion, invasion and migration of GBM cells, accompanied by increases in mRNA and protein levels of matrix metalloproteinase‑2 (MMP‑2) and MMP‑9. However, inhibition of hedgehog signaling with cyclopamine suppressed the adhesion, invasion and migration of GBM cells, accompanied by decreases in mRNA and protein levels of MMP‑2 and ‑9. Furthermore, it was found that MMP‑2- and MMP‑9-neutralizing antibodies or GAM6001 reversed the inductive effects of rhSHH on cell migration and invasion. In addition, enhanced hedgehog signaling by rhSHH increased AKT phosphorylation, whereas blockade of hedgehog signaling decreased AKT phosphorylations. Further experiments showed that LY294002, an inhibitor of phosphoinositide-3 kinase (PI3K), decreased rhSHH‑induced upregulation of MMP‑2 and ‑9. Finally, the protein expression of glioblastoma-associated oncogene 1 was positively correlated with levels of phosphorylated AKT as well as protein expressions of MMP‑2 and ‑9 in GBM tissue samples. In conclusion, the present study indicated that the hedgehog pathway regulates GBM-cell migration and invasion by increasing MMP-2 and MMP-9 production via the PI3K/AKT pathway.

Non‑small cell lung cancer (NSCLC) remains the leading cause of cancer‑related mortality despite the fact that great advances have been made in therapeutic treatment methods. Therefore, in the present study, the role of adenovirus-mediated retinoblastoma 94 (Ad‑RB94) gene therapy in NSCLC was investigated. Following treatment with Ad‑RB94, the proportion of A549 cells in the G2/M phase was increased. In the mouse xenograft model, the overexpression of RB94 inhibited the tumor growth compared with the control group and the Ad-‑LacZ-treated group. In the transplanted tumors, the overexpression of RB94 induced the apoptosis of tumors as well as an increase in the mRNA levels of cyclinB1. In conclusion, the results of the present study suggested that RB94 may effectively inhibit NSCLC tumor cell growth by inducing G2/M cell cycle arrest and apoptosis, indicating that RB94 may be a promising candidate for adjuvant therapy with radiation or chemotherapy in NSCLC.

The present study aimed to examine the changes in mesenteric lymph during the development of sepsis and to identify the distinct proteins involved, as targets for further study. The sepsis animal model was constructed by cecal ligation and puncture (CLP). The mesenteric lymph was collected from 28 adult male Sprague‑Dawley rats, which were randomly divided into the following four groups (n=7 per group): CLP‑6 h, CLP‑24 h, sham‑6 h and sham‑24 h groups. Capillary high performance liquid chromatography‑tandem mass spectrometry was performed to analyze the proteome in mesenteric lymph. A comprehensive bioinformatic analysis was then conducted to investigate the distinct proteins. Compared with the sham group, 158 distinct proteins were identified in the lymph samples from the CLP group. Five of these proteins associated with the same lipid metabolism pathway were selected, apolipoprotein E (ApoE), annexin A1 (Anxa1), neutrophil gelatinase‑associated lipocalin (NGAL), S100a8 and S100a9. The expression of ApoE, Anxa1, NGAL, S100a8 and S100a9 were all elevated in the progression of sepsis. The five proteins were reported to be closely associated with disease development and may be a potential target for the diagnosis and treatment of sepsis. In conclusion, identifying proteome changes in mesenteric lymph provides a novel perspective to understand the pathological mechanisms underlying sepsis.

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.

FGD5 antisense RNA 1 (FGD5‑AS1) is a long non‑coding RNA in acute myocardial infarction (AMI), which is primarily caused by myocardial ischemia‑hypoxia. Retinoid acid receptor‑related orphan receptor α (RORA) is a key protector in maintaining heart function. However, the roles of FGD5‑AS1 and RORA in AMI have not previously been elucidated. The present study investigated the effect and mechanism of FGD5‑AS1 and RORA in human cardiomyocyte AC16 cells under hypoxia. Reverse transcription‑quantitative PCR and western blotting demonstrated that FGD5‑AS1 and RORA were downregulated in the serum of patients with AMI and hypoxia‑challenged AC16 cells. Functional experiments were performed via assays, flow cytometry and western blotting. In response to hypoxia, superoxide dismutase (SOD) activity was inhibited, but apoptosis rate and levels of reactive oxygen species and malondialdehyde were promoted in AC16 cells, accompanied by increased Bax and cleaved caspase‑3 expression levels, and decreased SOD2 and glutathione peroxidase 1 expression levels. However, hypoxia‑induced oxidative stress and apoptosis in AC16 cells were attenuated by ectopic expression of FGD5‑AS1 or RORA. Moreover, silencing RORA counteracted the suppressive role of FGD5‑AS1 overexpression in hypoxic injury. FGD5‑AS1 controlled RORA expression levels via microRNA‑195‑5p (miR‑195), as confirmed by dual‑luciferase reporter and RNA pull‑down assays. Consistently, miR‑195 knockdown suppressed hypoxia‑induced oxidative stress and apoptosis in AC16 cells, which was abrogated by downregulating FGD5‑AS1 or RORA. In conclusion, FGD5‑AS1 modulated hypoxic injury in human cardiomyocytes partially via the miR‑195/RORA axis, suggesting FGD5‑AS1 as a potential target in interfering with the progression of AMI.

Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB‑222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB‑222 was more effective than a 5 µg dose of the antibody. In addition, RB‑222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB‑222 significantly repressed VEGF expression as well as decreased MMP‑2 and MMP‑9 expression. However, it enhanced occludin and collagen‑IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.

In this study, six compounds were isolated and purified from dandelion, and only sample I exhibited notable antifungal effect on Candida albicans (CA). high‑performance liquid chromatography‑diode‑array detector‑electrospray ionization‑tandem mass spectrometry analysis showed that sample I comprised 4‑coumaric acid, ferulic acid, quercetin pentoside, 3,5‑di‑O‑caffeoylquinic acid, 4,5‑di‑O‑caffeoylquinic acid, luteolin, and two unknown compounds, at a relative percent composition of 11.45, 3.96, 10.48, 34.24, 3.91, 11.80, 3.65 and 4.21%, respectively. Further antimicrobial experiments showed that the minimum inhibitory concentration of sample I was 32.0 mg/ml, and sample I mainly acts on bacterial growth in the exponential phase of CA growth. Optical density and infrared analyses conclusively suggested that sample I damages the structure of CA cells, particularly the cell wall and cell membrane, resulting in macromolecule leakage of intracellular nucleic acids and cell metabolism disruption. In conclusion, dandelion sample I was reported to increase CA cell membrane permeability by affecting the glycosidic bond in β‑(1‑3)‑D glucan and destroying the cell wall, ultimately leading CA to death.