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Sporothrix schenckii (S. schenckii) induces sporotrichosis, which has gained attention in recent years due to its worldwide prevalence. The dimorphic switching process is essential for the pathogenesis of S. schenckii. Previously, overexpression of several signal transduction genes, including SsDRK1 and SsSte20, was observed during the mycelium‑to‑yeast transition; these were necessary for asexual development, yeast‑phase cell formation, cell wall integrity and melanin synthesis. However, the mechanisms of the signaling pathways during dimorphic switching of S. schenckii remain unclear. In the present study, transcriptome sequencing of the 48‑h induced yeast forms and mycelium of S. schenckii was performed. In total, 24,904,510 high‑quality clean reads were obtained from mycelium samples and 22,814,406 from 48‑h induced yeast form samples. Following assembly, 31,779 unigene sequences were obtained with 52.98% GC content (The proportion of guanine G and cytosine C to all bases in nucleic acid). The results demonstrated that 12,217 genes, including genes involved in signal transduction and chitin synthesis, were expressed differentially between the two stages. According to these results, a map of the signaling pathways, including two‑component and heterotrimeric G‑protein signaling systems, Ras and MAPK cascades associated with the dimorphic switch, was drawn. Taken together, the transcriptome data and analysis performed in the present study lay the foundation for further research into the molecular mechanisms controlling the dimorphic switch of S. schenckii and support the development of anti‑S. schenckii strategies targeting genes associated with signaling pathways.

Bone marrow mesenchymal stem cells (BM-MSCs) regulate the balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells. However, the role of different factors on BM-MSCs-mediated regulation of the Treg/Th17 balance is unknown. BM-MSCs and CD4+ T lymphocytes were co-cultured with various treatments. The ratio of Treg/Th17 cells was calculated and the expression of different cytokines was measured. BM-MSCs were found to have a proliferative effect on Th17 cells at a basal concentration and at a 2-fold increase in the number of BM-MSCs. However, when the number of BM-MSCs used was increased 4-fold, they had an inhibitory effect on the Th17 cells. The effect of BM-MSCs on Tregs was inhibited by the addition of tacrolimus but not rapamycin. The effect of BM-MSCs on Th17 cells was inhibited by rapamycin. Additionally, the effect of BM-MSCs on Tregs were inhibited by the addition of a transforming growth factor-β (TGF-β) blocker, whereas these TGF-β-blockers had no effect on Th17 cells. Addition of an interleukin (IL)-2 blocker reduced the proportion of Th17 cells when co-cultured with a high number of MSCs compared with the low concentration group and the proportion of Treg cells was significantly decreased when cells were treated with an IL-2 blocker compared with the control group. Together, these results showed the varying effects of MSCs on the ratio of Treg/Th17, its dependence on the number of MSCs and the effects of cytokines in inducing these changes in the balance.

Activation of endothelial cells is the first step of atherosclerosis. The current authors have previously reported that exosomes from mature dendritic cells (mDC‑exo) participate in endothelial inflammation and atherosclerosis through membrane tumor necrosis factor‑α mediated the nuclear factor (NF)‑κB signaling pathway. However, whether mDC‑exo shuttled microRNAs (miRNAs/miRs) play a role in endothelial inflammation remains unknown. In this study, mDC‑exo were co‑cultured with human umbilical vein endothelial cells (HUVECs) and the expression of adhesion molecules, such as vascular cell adhesion molecule‑1, intercellular adhesion molecule‑1 and E‑Selectin was investigated. Then the expression of miRNAs in DC‑exo was explored and the role of miR‑146a in endothelial inflammation was investigated. mDC‑exos were first demonstrated to increase endothelial expression of adhesion molecules through a quick activation of the NF‑κB signaling pathway. Then it was demonstrated that HUVECs resistant to a second stimulation after the first stimulation by mDC‑exo. A set of miRNAs were targeted and their expression in HUVECs stimulated with mDC‑exo was measured. Finally, it was confirmed that mDC‑exo shuttles miR‑146a into HUVECs and the shuttled miR‑146a contributes to protect HUVECs from a second stimulation through inhibiting interleukin‑1 receptor‑associated kinase. These data suggest a negative feedback loop of inflammation regulation by DC‑exo.

Paeonol (Pae) is an herbal extract that has attracted extensive attention for its anti‑cancer effects demonstrated by a number of studies, which have predominantly demonstrated inhibition of cell proliferation and induction of apoptosis. The influence of Pae on cancer cell metastasis has been less widely reported. The present study aimed to investigate the under‑reported effects of Pae on the growth, invasion and migration of poorly differentiated BGC823 gastric cancer cells with strong invasive and metastatic abilities. The anti‑proliferative and pro‑apoptotic effects of Pae on BGC823 cells were verified by Cell Counting kit‑8 and Annexin V‑fluorescein isothiocyanate/propidium iodide assays. Cell scratch‑wound healing and Transwell methods were applied, and it was demonstrated that Pae could exert inhibitory activities on the invasion and migration of BGC823 cells. Furthermore, it was indicated by western blot analysis that Pae could downregulate the protein expression levels of matrix metalloproteinase (MMP)‑2 and ‑9 in a concentration‑dependent manner, which may support a novel potential mechanism accounting for its anti‑cancer effects on gastric cancer.

Adipose‑derived mesenchymal stromal cells (ADSCs) possess a multilineage potential and immunoregulatory properties, and may have great potential in autologous cell‑based technologies. The aim of the present study was to investigate how the age of patients with benign end‑stage liver disease affected the biological and functional characteristics of ADSCs, which is important for increasing the potential effectiveness of autologous cell therapy. ADSCs were obtained and cultured from three distinct age groups: Infant, adult and elderly. Cell immunophenotypic characteristics and antiapoptotic capacity were determined by flow cytometry, and cell proliferation and migration were monitored with a Real‑Time Cell Analyzer. Multilineage differentiation potential was investigated by evaluating the induction response and by reverse transcription‑quantitative polymerase chain reaction. Suppression of T cell proliferation was assessed in a co‑culture system by MTT assay. The regulatory T cells (Tregs) were analyzed by flow cytometry, and ELISAs were performed to detect the cytokine profile in culture supernatants. All ADSC sample phenotypes were characterized as CD90+/CD73+/CD105+/CD45‑/CD34‑, and the apoptotic rate was not statistically different among all ages. However, the proliferation and migratory capacity were significantly increased in infant‑derived ADSCs. In addition, ADSCs derived from infant patients demonstrated a relatively high proclivity for osteogenic differentiation compared with cells derived from either adult or elderly patients. Furthermore, ADSCs co‑cultured with mitogen‑activated T cells significantly suppressed T‑cell proliferation, downregulated the secretion of interferon‑γ and increased the percentage of Tregs, with infant‑derived ADSCs being most effective. Results from the present study indicated that ADSCs derived from infant patients may have biological advantages compared with older cell sources, and may provide an effective reference for the clinical application of ADSCs.

Podoplanin and fibroblast growth factor (FGF) 1 have been detected more frequently in lung squamous cell carcinoma (SQCC) compared with lung adenocarcinoma. Furthermore, it has been previous demonstrated that FGF1 is located on the edge of tumor nests in certain lung SQCC sections, which resembles the characteristic expression pattern of podoplanin. Podoplanin and FGF1 have roles in lymphangiogenesis and angiogenesis. Based on their consistently specific expression in lung SQCC and similar localization patterns, the present study aimed to investigate whether the expression of podoplanin in tumor cells is correlated with FGF1 expression in lung SQCC and whether their co-expression has clinicopathological significance, particularly for lymphangiogenesis/angiogenesis. The correlation between podoplanin and FGF1 expression in tumor cells of 82 lung SQCC cases was investigated by immunohistochemical staining and the association between the co-expression of podoplanin and FGF1, and clinicopathological factors such as microvessel density (MVD), was examined in these samples. In addition, the prognostic value of co-expression of podoplanin and FGF1 in tumor cells was determined, and the regulation of FGF1 expression and angiogenesis by podoplanin was examined in vitro in a human lung SQCC cell line. Immunohistochemical analysis demonstrated that there was a significant correlation between podoplanin and FGF1 expression in lung SQCC tumor cells (R=0.591; P

NORAD (non-coding RNA activated by DNA damage) is a long non-coding RNA (lncRNA) that is upregulated and promotes cell progression in various human types of cancer; however, its function in non-small cell lung cancer (NSCLC) remains unclear. The present study investigated the regulatory function and underlying mechanisms of NORAD in NSCLC. NORAD and miR-136-5p expression were assessed by reverse transcription-quantitative polymerase chain reaction, and proliferation and glycolysis-associated markers were also assessed. Direct miR-136-5p regulation by NORAD was detected using luciferase reporter assay and RNA immunoprecipitation. NORAD was highly expressed in NSCLC tissues and cell lines. NORAD overexpression increased NSCLC proliferation and glycolysis. Further investigation revealed that NORAD serves as a competing endogenous RNA for miR-136-5p. Gain- and loss-of-function experiments confirmed that miR-136-5p reversed the promoting effects of NORAD in NSCLC. Results of the present study indicate that NORAD serves as a growth-promoting lncRNA in NSCLC by suppressing the function of miR-136-5p. NORAD and miR-136-5p interaction may provide a potential target for NSCLC treatment.

Ankylosing spondylitis (AS) is an autoimmune condition characterized by chronic inflammation and abnormal ossification as the primary features of the disease. The aim of the present study was to investigate the role of C‑X‑C chemokine receptor type 4 (CXCR4) in ossification from patients with AS. CXCR4 expression was assessed by western blot analysis and immunohistochemistry analysis of tissues obtained from patients with AS and controls. Fibroblasts were isolated, cultured and incubated with AMD 3100 and stromal cell‑derived factor‑1 to inhibit and promote CXCR4 levels, respectively. CXCR4 was upregulated in hip synovial tissues from patients with AS compared with that observed in controls. AS fibroblasts exhibited increased proliferation and growth rates. Inhibition of CXCR4 increased the phosphorylation of β‑catenin and downregulated the expression of β‑catenin, v‑myc avian myelocytomatosis viral oncogene homolog, cyclin D1 and osteocalcin. Alizarin red staining demonstrated a decrease in biomineralization activity following the inhibition of CXCR4. These data support the hypothesis that inhibiting CXCR4 in patients with AS may suppress the ossification of fibroblasts.

Lung cancer is the most prevalent and observed type of cancer in Xuanwei County, Yunnan, South China. Lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microRNA (miR)‑218 functions as a tumor suppressor in multiple types of cancer. However, the role of miR‑218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR‑218 in XWLC‑05 cells were markedly lower compared with those in immortalized lung epithelial BEAS‑2B cells. The present study also demonstrated that overexpression of miR‑218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC‑05 and NSCLC cell line NCI‑H157. Additionally, the results revealed that overexpression of miR‑218 could induce XWLC‑05 and NCI‑H157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR‑218 could lead to a significant increase in phosphatase and tensin homolog (emPTEN/em) and YY1 transcription factor (emYY1/em), and a decrease in B‑cell lymphoma 2 (emBCL‑2/em) and BMI1 proto‑oncogene, polycomb ring finger (emBMI‑1/em) at the mRNA and protein level in XWLC‑05 and NCI‑H157 cell lines. However, we did not observe any remarkable difference in the roles of miR‑218 and miR‑218‑mediated regulation ofemBCL‑2/em,emBMI‑1/em,emPTEN/emandemYY1/emexpression in the progression of Xuanwei lung cancer. In conclusion, miR‑218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasingemPTEN/emandemYY1/emexpression, while decreasingemBCL‑2/emandemBMI‑1/emin Xuanwei lung cancer. The results demonstrated that miR‑218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR‑218 may be a novel approach for the treatment of Xuanwei lung cancer.

The percentage rate of Epstein-Barr virus (EBV)-positive cases of Hodgkin's lymphoma (HL) ranges between 20 and 70% in various studies worldwide. To further explore the definite rate in China, three methods, including immunohistochemistry for EBV latent membrane protein 1 (LMP1), in situ hybridization (ISH) for EBV-encoded RNA (EBER)-1 and polymerase chain reaction (PCR) for EBV BamHI‑W fragment, were employed to detect EBV in 59 cases of HL in China using paraffin-embedded tissue samples. Our results revealed that the PCR method presented the highest (44/59, 74.6%) detection rate among the three methods. The other two methods identified 66.1% (39/59, LMP1) and 67.8% (40/59, EBER1 ISH) EBV-positive results, respectively. Three samples were positive for LMP1 but negative when using EBER1 ISH, while another four samples were EBER1-positive but LMP1-negative. Of the four major histopathological subtypes of HL, the lymphocyte predominant (LR) subtype is the one most frequently associated with EBV, followed by the mixed cellularity (MC), nodular sclerosis (NS) and lymphocyte depletion (LD) subtypes. Our results also indicated the seldomly reported fact that EBV-positive cases in children were more numerous than those of adults with HL.

Long non-coding RNAs (lncRNAs) have emerged recently as important factors in regulating fundamental biological processes. Alterations in the expression and function of lncRNAs have been observed to promote tumor formation, progression and metastasis. Although downregulation of the expression levels of LET lncRNA in several tumors has been reported, its role in gastric cancer remains unknown. The aim of the present study was to investigate the expression and function of LET in gastric cancer development. The expression levels of LET in 37 pairs of gastric cancer and adjacent non‑tumor tissues were detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). In addition, LET expression in gastric cancer cell lines was analyzed by RT‑qPCR assay analysis. Furthermore, the impact of LET on cell proliferation, migration and apoptosis were detected using the cell counting kit‑8, wound scratch and ELISA assays, respectively. The results demonstrated that the expression level of LET was downregulated in gastric cancer tissues and cell lines (SGC‑7901 and MGC‑803) compared with normal tissues and a normal human gastric epithelial cell line (GES‑1). Restoration of LET expression using a synthesized recombinant overexpression vector transfected into SGC‑7901 and MGC‑803 cells, significantly inhibited cell proliferation and migration, and promoted cell apoptosis in vitro. The present study is the first to demonstrate that LET may function as a tumor suppressor in gastric cancer. The results indicate that LET may be a promising biomarker and/or a therapeutic target for gastric cancer.

Previous studies have reported that triple-negative breast cancer is more sensitive to cytotoxic treatment, compared with estrogen receptor (ER)‑positive cancer. However, the underlying molecular mechanisms remain to be fully elucidated. In the present study, we employed reverse transcription‑quantitative polymerase chain reaction, western blot and in vivo assays to investigate the underlying mechanisms. The sensitivities of cells to cisplatin were examined in ER-positive and ER‑negative breast cancer cells, and it was found that the ER‑negative cells were more sensitive to cisplatin, compared with the ER‑positive cells. In addition, it was found that mitochondrial transcription factor A (TFAM), which functions in mitochondrial DNA replication and repair, was expressed at a high level in ER‑positive cell lines and patient tissues, compared with ER‑negative cell lines and tissues. It was also found that the sensitivity to cisplatin was decreased when TFAM was knocked down in the breast cancer cells, and these effects were reversed when TFAM was reintroduced to the cells. Similar results were observed in xenograft tumors. The results of the present study provided evidence that resistance to cisplatin chemotherapy in ER‑positive breast cancer may be through TFAM and indicated that TFAM may be a target for chemoresistance in patients with breast cancer. These findings offer potential guidance for chemotherapy in patients with breast cancer.

Rhomboid domain containing 1 (RHBDD1), is a member of the rhomboid protease family, which has a pivotal role in the progression of numerous severe malignancies. However, its role in colorectal carcinoma (CRC) remains to be elucidated. In the present study, RHBDD1 was shown to be widely expressed in CRC cell lines. Lentivirus-mediated RNA interference was employed to knockdown RHBDD1 expression in RKO CRC cells. Functional analyses indicated that depletion of RHBDD1 expression resulted in significantly reduced CRC cell proliferation and colony formation, and induced a G0/G1 phase cell cycle arrest. The findings of the present study suggest that RHBDD1 may contribute to CRC tumorigenesis and serve as a potential therapeutic target in human CRC.

Previous experimental studies have demonstrated that hepatocyte growth factor (HGF) and its receptor c‑Met serve an important function in lymphangiogenesis, but their biological functions in malignant tumors have remained elusive. The present study aimed to investigate the expression patterns of HGF‑α and c‑Met and their association with vascular endothelial growth factor (VEGF)‑C, lymphatic vessel density and lymph node metastasis in non‑small‑cell lung cancer (NSCLC). In the present study, the lymphatic microvessel density (LMVD) and the expression levels of HGF‑α, its receptor c‑Met and VEGF‑C were determined in 113 human NSCLC tissues and 113 normal lung tissue samples, using immunohistochemical staining. As a result, it was determined that the expression levels of HGF‑α, c‑Met and VEGF‑C were significantly higher in NSCLC tissues than those in normal lung tissues (HGF‑α, 67.3 vs. 20.4%, P

Heat shock protein 70 (Hsp70), a chaperone involved in tumor progression, is overexpressed in various human tumors. However, its role in colon cancer progression is not completely understood. In the present study, two shRNA plasmid vectors against Hsp70 were constructed and stably transfected into the colon cancer cell line HT29 to determine the effect of Hsp70 on cell proliferation, cell cycle distribution and cell apoptosis in HT29 cells in vitro, and its effect on xenograft tumor growth and apoptosis in vivo. Cell proliferation was determined using MTT assay. The results revealed that Hsp70 silencing efficiently inhibited the growth of HT29 cells in culture, induced cell cycle arrest at the G1 phase, and significantly increased apoptosis. Moreover, stable clones from the Hsp70 shRNA-2 vector suppressed xenograft tumor growth and enhanced apoptosis in vivo compared with a mock and vector control group. In conclusion, specific Hsp70 shRNA silencing may inhibit colon cancer growth, indicating that Hsp70 silencing is a potential therapeutic strategy for the treatment of colon cancer.