Poly (ADP-ribose) polymerase (PARP) serves a key role in several neurological disorders, however, the specific role of PARP in delayed cerebral vasospasm (DCVS) following subarachnoid hemorrhage (SAH) remains unclear. The present study was conducted to clarify the possible mechanism of PARP in DCVS with the treatment of 3-aminobenzamide (3-AB), a PARP inhibitor. In the preliminary experiment, an internal carotid artery puncture SAH model, a cisterna magna double injection SAH model and prechiasmatic cistern single injection SAH model were compared with respect to mortality and neurobehavioral test results. The prechiasmatic cistern single injection SAH model was chosen to induce DCVS in the formal experiment. In the formal experiment, a total of 96 Sprague Dawley rats were randomly allocated into the sham group, the SAH group and the SAH+3-AB group and then each group was further subdivided into days 3, 5, 7 and 14 post-SAH subgroups (n=8 for each subgroup). The prechiasmatic cistern single injection SAH model was established to induce DCVS. Neurobehavioral testing and HE staining were conducted to evaluate the degree of cerebral vasospasm. PARP activity was assessed by ELISA and immunohistochemistry. An electrophoretic mobility shift assay was used to detect nuclear factor (NF)-κB DNA-binding activity. The expression of monocyte chemotactic protein 1 (MCP-1) and C-reactive protein (CRP) were measured by western blotting. Cerebral vasospasm occurred following SAH and became most severe on around day 7 post-SAH. NF-κB activity, PARP activity, the expression of MCP-1 and CRP exhibited a similar time course to cerebral vasospasm. Treatment with 3-AB alleviated the degree of cerebral vasospasm. NF-κB activity, PARP activity and the expression of MCP-1 and CRP were also suppressed by 3-AB treatment. In conclusion, PARP may serve an important role in regulating the inflammatory response and ultimately contribute to DCVS. Therefore 3-AB may be a potential therapeutic agent for DCVS.

Oleanolic acid (OA) is a natural compound that can be found in a number of edible and medicinal plants and confers diverse biological actions. However, the direct target of OA in human tumor cells remains poorly understood, preventing its application in clinical and health settings. A previous study revealed that overexpression of caveolin-1 in human leukemia HL-60 cells can increase its sensitivity to OA. The present study aimed to investigate the effects of OA on the doxorubicin-resistant human breast cancer MCF-7 cell line (MCF-7/DOX), harringtonine-resistant human leukemia HL-60 cells (HL-60/HAR) and their corresponding parental cell lines. Western blotting was performed to measure protein expression levels, whilst Cell Counting Kit-8 (CCK-8) assays, cell cycle analysis (by flow cytometry) and apoptosis assays (with Annexin V/PI staining) were used to assess drug sensitivity. CCK-8 assay results suggested that MCF-7/DOX cells, which overexpress the caveolin-1 protein, have similar OA susceptibility to their parent line. In addition, sensitivity of MCF-7/DOX cells to OA was not augmented by knocking down caveolin-1 using RNA interference. HL-60/HAR cells exhibited a four-fold increased sensitivity to OA compared with that in their parental HL-60 cells according to CCK-8 assay. Both of the resistant cell lines exhibited higher numbers of cells at G1 phase arrest compared with those in their parent lines, as measured via flow cytometry. Treatment of both MCF-7 cell lines with 100 µM OA for 48 h induced apoptosis, with increased effects observed in resistant cells. However, no PARP-1 or caspase-3 cleavage was observed, with some positive Annexin V staining found after HL-60/HAR cells were treated with OA, suggesting that cell death occurred via non-classical apoptosis or through other cell death pathways. It was found that OA was not a substrate of ATP-binding cassette subfamily B member 1 (ABCB1) in drug-resistant cells, as indicated by the accumulation of rhodamine 123 assessed using flow cytometry. However, protein expression of ABCB1 in both of the resistant cell lines was significantly decreased after treatment with OA in a concentration-dependent manner. Collectively, these results suggest that OA could reduce ABCB1 protein expression and induce G1 phase arrest in multidrug-resistant cancer cells. These findings highlight the potential of OA for cancer therapy.

Sepsis is a systemic inflammatory response syndrome caused by infection, which has a complex mechanism. The gastrointestinal tract is commonly the first organ affected by sepsis, but intestinal disease itself can also induce sepsis. Roflumilast has been found to exert anti-inflammatory effects and, thus, the present study sought to examine its effect on intestinal damage caused by sepsis. In vivo studies were conducted using cecal ligation and puncture rat models, and in vitro experiments were performed using IEC-6 cells. The intestinal cells were first induced with lipopolysaccharide and the induced cells were then treated with roflumilast to evaluate its effects on phosphodiesterase (PDE)4 expression, intestinal function indices, release of inflammatory factors and cell apoptosis. The expression level of PDE4 in the small intestinal tissue of septic rats was found to be significantly higher compared with that in the normal group, suggesting that PDE4 may play a key role in intestinal injury caused by sepsis. It was found that roflumilast reduced PDE4 expression, as well as the levels of intestinal function indices, including lactate dehydrogenase, diamino oxidase and intestinal fatty acid-binding protein, in intestinal cells. Moreover, roflumilast reduced cellular damage, the release of inflammatory factors and apoptosis. In summary, the findings of the present study indicated that roflumilast can relieve the inflammation and apoptosis of intestinal cells caused by sepsis and can promote their functional recovery. These findings may promote the expansion of the clinical application of roflumilast in the future.

Glioblastoma is the most common malignancy of the central nervous system, and patients typically have a poor prognosis. Previous studies indicate a gender bias in the development of glioblastoma; women are at a lower risk compared with men, suggesting that estrogen may confer protective effects. Icaritin, a prenylflavonoid derivative from a Chinese herb of the Epimedium genus, selectively regulates the estrogen receptor (ER) and possesses anti-cancer properties. The aim of the present study was to investigate the protective effects of icaritin on glioblastoma and its underlying mechanisms, with a particular focus on its association with the ER. The results demonstrated that icaritin inhibited the growth of C6 and U87-MG glioblastoma cells in a dose- and time-dependent manner. At a concentration of 12.5 µM, icaritin induced apoptosis, which was characterized by the increased expression of the cleaved forms of caspases 3, 7, 8 and 9 and poly (ADP-ribose) polymerase, downregulation of BCL2 apoptosis regulator and upregulation of BCL2-associated X, apoptosis regulator expression. Additionally, icaritin inhibited the migration of C6 and U87-MG cells. The protein expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were also downregulated following icaritin treatment. Furthermore, icaritin treatment increased the expression of estrogen receptor (ER)β and the phosphatase and tensin (PTEN) homolog oncoprotein, thus reducing the expression of downstream targets of PTEN; protein kinase B (Akt) and phosphorylated Akt. Subsequent experiments demonstrated that icaritin cooperates with 17β-estradiol to inhibit the growth of glioblastoma cells, and the inhibition of ERβ with the ERβ-specific antagonist ICI 182,780, attenuated the anti-glioblastoma effects of icaritin. In conclusion, the results of the present study demonstrate that the anti-glioblastoma effects of icaritin may be mediated by its modulation of ERβ.

As a global health problem, cardiovascular disease threatens the lives of human beings. It has been reported that microRNAs (miRs) are important in regulating coronary atherosclerosis. In the present study, the expression levels of miR-370 in peripheral blood mononuclear cells of patients with coronary atherosclerosis were significantly increased compared with healthy patients, as demonstrated by reverse transcription-quantitative polymerase chain reaction analysis. Additionally, the target of miR-370 was predicted as Forkhead Box 1 (FOXO1) with bioinformatics, and was confirmed by a dual luciferase assay. The mRNA and protein expression levels of FOXO1 were inhibited by miR-370. Furthermore, the invasion and proliferation of human umbilical vein endothelial cells were promoted by miR-370 via inhibiting the expression of FOXO1. The results obtained in the present study demonstrated that miR-370 served an important role in regulating coronary atherosclerosis via targeting FOXO1. The present data also indicated that miR-370 may be a promising molecular target for treating coronary atherosclerosis.

Colorectal cancer (CRC), the third most common cancer worldwide, poses a threat to human life. However, its underlying mechanism is unclear and no satisfactory treatment is available. The present study aimed to investigate the role of circular RNA argininosuccinate synthase 1 (circASS1) in CRC cells and tissues to identify the potential mechanism underlying the pathogenesis of CRC. The expression of circASS1 in CRC cells and tissues was determined by reverse transcription-quantitative PCR. Following circASS1 overexpression in HT29 cells, cell viability, colony formation and apoptosis were measured using MTT, colony formation and TUNEL assays, respectively. Cell invasion and migration were also assessed. After confirming the associations among circASS1, microRNA (miR)-1269a and vasohibin 1 (VASH1), the characteristics of the HT29 cell line were assessed by performing the aforementioned assays. circASS1 expression was decreased in CRC cells and tissues, and circASS1 overexpression suppressed CRC cell proliferation, invasion and migration. circASS1 adsorbed miR-1269a and regulated its expression, and VASH1 was a target protein of miR-1269a. circASS1 overexpression decreased cell proliferation, invasion and migration, but enhanced cell apoptosis in HT29 cells, which was reversed by co-transfection with miR-1269a mimic or short hairpin RNA-VASH1. In conclusion, circASS1 overexpression inhibited CRC cell proliferation, invasion and migration by regulating miR-1269a/VASH1, which indicated a potential molecular mechanism underlying the pathogenesis of CRC.

Ovarian cancer is one of the most common gynecological diseases with high mortality rates. Previous studies have shown that microRNA (miR)-638 is associated with tumorigenesis. The present study aimed to assess the role and underlying mechanisms of miR-638 in ovarian cancer. miR-638 expression was detected in ovarian cancer tissues and miR-638 was overexpressed or knocked down in ovarian cancer OVCAR-3 and Caov-3 cells. The clinical results revealed that miR-638 expression was downregulated in ovarian cancer tissues compared with in adjacent normal tissues. miR-638 expression was also found to be relatively low in OVCAR-3 cells whilst being relatively high in Caov-3 cells among the five ovarian cancer cell lines tested. miR-638 overexpression inhibited cell viability, arrested the cell cycle at the G1 phase and promoted apoptosis in OVCAR-3 cells. By contrast, miR-638 knockdown increased Caov-3 cell viability, facilitated cell cycle progression and inhibited apoptosis. miR-638 reduced the expression of high mobility group A1 (HMGA1) by directly targeting its 3' untranslated region. HMGA1 overexpression reversed the inhibition of proliferation induced by miR-638 overexpression in OVCAR-3 cells. These results suggest that miR-638 may serve to be a suppressor of ovarian cancer by regulating HMGA1, which may provide a potential therapeutic target for ovarian cancer.

Sperm-associated antigen 5 (SPAG5) is involved in the tumorigenesis of multiple cancer types. However, the role of SPAG5 during lung adenocarcinoma (LUAD) progression remains to be fully elucidated. In the present study, the expression of SPAG5 in tumor tissues of patients with LUAD from public cancer databases was analyzed using the online software Gene Expression Profiling Interactive Analysis and University of Alabama Cancer Database. The association of SPAG5 expression levels with the prognosis of patients with LUAD was analyzed using Kaplan-Meier Plotter. In addition, the role of SPAG5 in the LUAD cell line A549 was determined by knocking down its expression with specific small interfering RNA. The results demonstrated that SPAG5 expression was upregulated in LUAD tissues and its high expression was associated with unfavorable prognosis. Furthermore, in A549 cells, SPAG5 promoted proliferation, migration, invasion and autophagy, but inhibited apoptosis. The present results suggest that SPAG5 has an oncogenic role in LUAD and may be a potential prognostic predictor and therapeutic target for LUAD.