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Ulcerative colitis (UC) is a significant burden on human health, and the elucidation of the mechanism by which it develops has potential for the prevention and treatment of UC. It has been reported that acteoside (ACT) exhibits strong anti‑inflammatory activity. In the present study, it was hypothesized that ACT may exert a protective effect against UC. The effects of ACT on inflammation, oxidative stress and apoptosis were evaluated using dextran sulphate sodium (DSS)‑treated mice and DSS‑treated human colorectal adenocarcinoma Caco‑2 cells, which have an epithelial morphology. The results demonstrated that the ACT‑treated mice with DSS‑induced UC exhibited significantly reduced colon inflammation, as demonstrated by a reversal in body weight loss, colon shortening, disease activity index score, inflammation, oxidative stress and colonic barrier dysfunction. Further

Phosphoinositide 3-kinase catalytic subunit δ isoform (P110δ) is mainly expressed in white blood cells. It is involved in T and B lymphocyte differentiation, maturation and the neutrophil chemotaxis process. Apolipoprotein E (ApoE) is an arginine-rich alkaline protein, which is present in plasma chylomicron, low-density lipoprotein and very low-density lipoprotein. The present study aimed to determine the effects of P110δ deletion on myocarditis in ApoE−/− mice. A mouse model of ApoE and P110δ double deletion was initially constructed; hematoxylin and eosin (H&E) staining was performed to detect the histological alterations in the mouse myocardium. Systolic and diastolic alterations, and alterations in the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were examined by electrocardiogram. Blood cell of ApoE and P110δ double mice was used to detect changes in white blood cells and monocytes. Western blotting was used to detect the expression levels of apoptosis-associated proteins, whereas flow cytometry was used to detect the percentage of apoptosis. Morphological alterations in myocardial cells were observed under a microscope. The results of polymerase chain reaction demonstrated that double deletion mice were successfully constructed. H&E staining revealed that cells in the ApoE−/− mice were spindle-shaped; however, the nuclei were smaller in the double deletion mice. There was no change in cardiac contraction in normal mice; however, in double deletion mice, the systolic and diastolic contractions were markedly reduced. LVFS and LVEF were decreased compared with in the control group. Blood cell analysis indicated that the content of white blood cells and monocytes in the experimental group was significantly higher than that in the control group. Western blotting demonstrated that the expression levels of apoptotic proteins in double deletion mice were significantly higher compared with in the control group. Flow cytometry revealed that the apoptotic ratio was increased in double deletion mice compared with in the control group (42 vs. 21%). These findings suggested that deletion of P110δ may induce monocyte peritoneal infiltration and increase apoptosis, thus promoting the development of myocarditis.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M. tuberculosis) infection and has the highest mortality rate of any single infectious disease worldwide. The aim of the present study was to investigate the function of microRNA (miR)‑502‑3p in M. tuberculosis‑infected macrophages. The Gene Expression Omnibus database was used to analyze miR‑502‑3p expression in patients with TB and healthy individuals. THP‑1 and RAW 264.7 cells were transfected with miR‑502‑3p mimic, miR‑502‑3p inhibitor, pcDNA3.1‑ROCK1 or their negative controls. The expression levels of miR‑502‑3p and inflammatory cytokines were evaluated using reverse transcription‑quantitative PCR. The colony‑forming unit assay was performed to assess the survival of M. tuberculosis in macrophages, and Toll‑like receptor (TLR)4/NF‑κB signaling pathway‑associated protein expression levels were detected by western blotting. The nuclear translocation of NF‑κB p65 was detected via immunocytochemistry. TargetScan was used to predict the binding sites between miR‑502‑3p and ROCK1. The interaction between miR‑502‑3p and Rho‑associated coiled‑coil‑forming protein kinase 1 (ROCK1) was confirmed using a dual‑luciferase reporter assay; ROCK1 was demonstrated to be a direct target gene of miR‑502‑3p. Results from the present study demonstrated that miR‑502‑3p expression was significantly increased during M. tuberculosis infection in macrophages. Upregulation of miR‑502‑3p expression levels significantly enhanced the survival of intracellular M. tuberculosis. IL‑6, TNF‑α, and IL‑1β mRNA expression levels were significantly upregulated during M. tuberculosis infection but were downregulated by miR‑502‑3p overexpression. Moreover, miR‑502‑3p mimics transfection significantly downregulated TLR4/NF‑κB signaling pathway‑associated protein expression and significantly reduced nuclear transcription of NF‑κB in M. tuberculosis‑infected macrophages. ROCK1 overexpression reversed the miR‑502‑3p inhibitory effect on cytokine production in M. tuberculosis‑infected macrophages. In conclusion, miR‑502‑3p/ROCK1 may serve an anti‑inflammatory role and may improve the survival of M. tuberculosis within macrophages, which may provide a promising therapeutic target for TB.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M. tuberculosis) infection and has the highest mortality rate of any single infectious disease worldwide. The aim of the present study was to investigate the function of microRNA (miR)-502-3p in M. tuberculosis-infected macrophages. The Gene Expression Omnibus database was used to analyze miR-502-3p expression in patients with TB and healthy individuals. THP-1 and RAW 264.7 cells were transfected with miR-502-3p mimic, miR-502-3p inhibitor, pcDNA3.1-ROCK1 or their negative controls. The expression levels of miR-502-3p and inflammatory cytokines were evaluated using reverse transcription-quantitative PCR. The colony-forming unit assay was performed to assess the survival of M. tuberculosis in macrophages, and Toll-like receptor (TLR)4/NF-κB signaling pathway-associated protein expression levels were detected by western blotting. The nuclear translocation of NF-κB p65 was detected via immunocytochemistry. TargetScan was used to predict the binding sites between miR-502-3p and ROCK1. The interaction between miR-502-3p and Rho-associated coiled-coil-forming protein kinase 1 (ROCK1) was confirmed using a dual-luciferase reporter assay; ROCK1 was demonstrated to be a direct target gene of miR-502-3p. Results from the present study demonstrated that miR-502-3p expression was significantly increased during M. tuberculosis infection in macrophages. Upregulation of miR-502-3p expression levels significantly enhanced the survival of intracellular M. tuberculosis. IL-6, TNF-α, and IL-1β mRNA expression levels were significantly upregulated during M. tuberculosis infection but were downregulated by miR-502-3p overexpression. Moreover, miR-502-3p mimics transfection significantly downregulated TLR4/NF-κB signaling pathway-associated protein expression and significantly reduced nuclear transcription of NF-κB in M. tuberculosis-infected macrophages. ROCK1 overexpression reversed the miR-502-3p inhibitory effect on cytokine production in M. tuberculosis-infected macrophages. In conclusion, miR-502-3p/ROCK1 may serve an anti-inflammatory role and may improve the survival of M. tuberculosis within macrophages, which may provide a promising therapeutic target for TB.

Osteosarcoma is the most common primary bone tumor that occurs in children and adolescents. Osteosarcoma has a poor prognosis and is often unresponsive to chemotherapy. Therefore, it remains a challenge to identify a novel strategy to effectively treat osteosarcoma. The present study demonstrated a novel opportunity in osteosarcoma treatment using the natural compound plumbagin. Plumbagin reduced cell viability in osteosarcoma cells but not normal bone cells, as determined by MTT assay and colony formation assay. Plumbagin induced cell apoptosis by mitochondrial dysfunction, which in turn promoted Ca2+ release and endoplasmic reticulum (ER)‑stress, as determined by DAPI staining assay, DNA fragmentation assay, flow cytometry and western blotting analysis. In addition, plumbagin improved reactive oxygen species (ROS) generation, as determined by flow cytometry. Finally, these apoptotic cascades activated caspase‑3 and caspase‑9 to elicit apoptosis response. Our results demonstrated the anticancer effect of plumbagin by inducing cell apoptosis in osteosarcoma cells. In conclusion, plumbagin activated the apoptosis signaling pathway through eliciting ROS, ER stress, mitochondria dysfunction, and finally causing caspase activation. These results indicated that plumbagin may serve as potential antitumor drug by its multifunctional effects in osteosarcoma.

Bone marrow‑derived mesenchymal stem cells (BMSCs) and adipose tissue‑derived mesenchymal stem cells (ADSCs) are able to differentiate into neuron‑like cells when exposed to small molecule compounds, however the specific differences in their neuronal differentiation abilities remain to be fully elucidated. The present study aimed to compare the neuronal differentiation abilities of BMSCs and ADSCs. BMSCs and ADSCs from the same Sprague Dawley rats were isolated and cultured for use. The proliferation capacity was revealed using a cell counting method. Following BMSCs and ADSCs induction by four types of small‑molecular compounds, the expression of various neuronal markers and the secretion of several neurotrophic factors were detected by immunofluorescence, western blotting, reverse transcription‑quantitative polymerase chain reaction and ELISA. It was demonstrated that the ADSCs exhibited an increased proliferation capacity compared with BMSCs, according to cumulative population doubling analyses. Following a 7‑day neuronal induction period, BMSCs and ADSCs exhibited a neuron‑like morphology, and were termed neuronal induced (NI)‑BMSCs and NI‑ADSCs. They expressed neuronal markers including β‑tubulin III, microtubule associated protein 2 and choline acetyltransferase. The number of NI‑BMSCs that positively expressed the neuronal markers was significantly decreased compared with NI‑ADSCs, and the expression and secretion of the neurotrophic factors nerve growth factor and 3'‑nucleotidase in NI‑BMSCs were additionally decreased compared with NI‑ADSCs. The findings of the present study indicated that the neuronal differentiation abilities and neurotrophic factor secretion abilities of ADSCs were increased compared with BMSCs. ADSCs may therefore act as efficient candidates in cell transplantation therapy for diseases and injuries of the nervous system.

The cytochrome P450 (CYP) 1A2 gene is involved in the metabolism of several carcinogens and clinically important drugs, generating a high potential for pharmacokinetic interactions. Since no data are available for Tibetan aborigines, the present study aimed to investigate the distribution of variant CYP1A2 alleles in a population living in Tibetan region of China. Genotyping analyses of CYP1A2 were conducted in 96 unrelated, healthy volunteers of Tibetan ancestry using direct sequencing assays. A total of 14 different CYP1A2 polymorphisms, including two novel variants (1690G>A and 2896C>T) in the intron region and a novel non-synonymous one (795G>C, Gln265His) were detected. CYP1A2*1A (6.77%), CYP1A2*1B (58.33%) and CYP1A2*1F (14.58%) were the most frequent defective alleles identified in the sample. The frequencies of the prevalent genotypes CYP1A2*1A/*1B, *1B/*1B, *1B/*1F were 13.54%, 16.67% and 29.17%, respectively. In addition, the novel non-synonymous variant 795G>C (Gln265His) was predicted to be benign by PolyPhen-2 and SIFT tools. The present study provides useful information on the pattern of CYP1A2 polymorphisms in Chinese Tibetan population. The current results may have potential benefits for the development of personalized medicine in the Tibetan population.

The present study aimed to prepare cisplatin (CDDP)-loaded magnetic nanoparticles (MNPs), which target folate receptors via a pH-sensitive release system (FA‑PEG‑NH‑N=MNPs‑CDDP). This is of interest for the development of intelligent drug delivery systems that target tumors of the head and neck. The chemical coprecipitation method was used to prepare ferroferric oxide MNPs. These were modified with aldehyde sodium alginate complexed with the chemotherapeutic agent, CDDP on the surface of the nanoparticles. Double hydrazine‑poly(ethylene glycol; PEG) was also prepared by attaching the carboxyl group of hydrazine‑folate on one side of the double hydrazine‑PEG, obtaining folate‑hydrazine‑PEG‑diazenyl. This binds the aldehyde group of sodium alginic acid on the MNP to enclose CDDP, in order that it is sequestered within the carrier. This method obtained a pH‑sensitive, FA‑modified CDDP‑loaded MNP (FA‑PEG‑NH‑N=MNPs‑CDDP), which acts as an intelligent tumor targeting drug delivery system. The mean size of the MNPs was ~10.2±1.5 nm, the mean hydrodynamic diameter detected by laser particle sizing instruments was 176.6±1.1 nm, and the ζ‑potential was ‑20.91±1.76 mV. The CDDP content was 0.773 mg/ml, the iron content was ~1.908 mg/ml and the maximum saturation magnetization was 16.3±0.2 emu/g. The current study produced a pH‑sensitive FA‑modified CDDP‑loaded MNP that is stable and exhibits magnetic responsiveness, which releases CDDP in a low pH environment.

The present study aimed to investigate the virulence diversity of Helicobacter pylori (H. pylori) in major ethnic groups residing in Guizhou province, China, and its association with clinical outcomes. Gastric mucosal biopsies were collected from the pylorus of patients with gastrointestinal disorders. H. pylori was identified by colonial morphology, Gram staining, a urease test and H. pylori‑specific 16S rRNA gene fragment PCR amplification. DNA was extracted from pure culture and used for virulence gene analysis. The cytotoxin associated gene A (cagA), vacuolating cytotoxin A (vacA) and induced by contact with epithelium gene A (iceA) genes were analyzed by polymerase chain reaction analysis. The cagA gene was further analyzed through sequencing of the C‑terminal region containing EPIYA motifs, and phylogenetic analysis of the cagA C‑terminal variable region was performed using MEGA 6.0 software. In the present study, 73 H. pylori strains were isolated from clinical samples. cagA genotypes were detected in all strains, namely cagA‑AB, ‑ABC, ‑ABD and ‑BD genotypes were found in five (6.85%), three (4.11%), 63 (86.30%) and two (2.74%) isolates, respectively. Phylogenetic analysis showed that there was a clustering association between the cagA‑AB and cagA‑ABC genotypes, and between the cagA‑ABD and cagA‑BD genotypes. In terms of the frequency of the four EPIYA or EPIYA‑like motifs, the most predominant was EPIYA (92.92%), followed by EPIYT (3.77%), ESIYA (2.83%) and ESIYT (0.47%). The predominant vacA genotype was s1c/m2 (65.75%), and the predominant iceA genotype was iceA1 (79.45%). There were no associations between the H. pylori cagA, vacA or iceA genotypes and clinical outcomes. No significant difference was found in the distribution of these genotypes according to the age, ethnicity or location of residence of patients. In conclusion, H. pylori isolated from patients in Guizhou region, China, showed a unique genotype, which was mainly East Asia‑type cagA (ABD), vacA s1c/m2 genotype or iceA1‑postiive. These results provide important information on the distribution of H. pylori virulence genotypes in Guizhou province, China.

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 adeno- virus-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 investigate the effects of the phosphoinositide 3‑kinase (PI3K)/Akt signaling pathway on the Wnt/β‑catenin signaling pathway in rats with focal cerebral ischemia‑reperfusion injury. A total of 96 rat focal cerebral ischemia‑reperfusion models, established according to a modified version of Longa's method, were randomly divided into four groups: Sham‑operated (S), cerebral ischemia‑reperfusion injury (I), cerebral ischemia‑reperfusion + basic fibroblast growth factor (bFGF) post‑processing and, finally, cerebral ischemia‑reperfusion + bFGF post‑processing + PI3K inhibitor LY294002 (LY). Each group consisted of 24 rats and each group was divided into four subgroups according to the indicated reperfusion times of 12, 24, 48 and 72 h. The morphological changes of the cortical tissue and the cellular apoptosis were determined using hematoxylin and eosin staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling method, respectively. The expression levels of phosphorylated (p‑)Akt, glycogen synthase kinase‑3β (GSK‑3β) mRNA and β‑catenin in the cortical tissue were detected at different time‑points. The number of apoptotic cells and the expression levels of p‑Akt, GSK‑3β mRNA and β‑catenin in the I and LY groups were significantly higher compared with those in the S group (P

The development of targeted tyrosine kinase inhibitors (TKIs) has succeeded in altering the course of chronic myeloid leukemia (CML). However, a number of patients have failed to respond or experienced disease relapse following TKI treatment. Proviral integration site for moloney murine leukemia virus-1 (PIM-1) is a serine/threonine kinase that participates in regulating apoptosis, cell cycle, signal transduction and transcriptional pathways, which are associated with tumor progression, and poor prognosis. SMI-4a is a selective PIM-1 kinase inhibitor that inhibits PIM-1 kinase activity in vivo and in vitro. The present study aimed to explore the mechanism underlying the antitumor effect of SMI-4a in K562 and imatinib-resistant K562 (K562/G) cell lines. It was demonstrated that SMI-4a inhibited the proliferation of K562 and K562/G cells using a WST-8 assay. The Annexin V-propidium iodide assay demonstrated that SMI-4a induced apoptosis of K562 and K562/G cells in a dose-, and time-dependent manner. Furthermore, Hoechst 33342 staining was used to verify the apoptosis rate. The clone formation assay revealed that SMI-4a significantly inhibited the colony formation capacity of K562 and K562/G cells. Western blot analysis demonstrated that SMI-4a decreased phosphorylated (p)-Ser9-glycogen synthase kinase (GSK) 3β/pGSK3β and inhibited the translocation of β-catenin. In addition, the downstream gene expression of apoptosis regulator Bax and poly(ADP-ribose) polymerase-1 was upregulated, and apoptosis regulator Bcl-2 and Myc proto-oncogene protein expression levels were downregulated. Immunofluorescence results demonstrated changes in the expression level of β-catenin in the plasma and nucleus. The results of the present study suggest that SMI-4a is an effective drug to use in combination with current chemotherapeutics for the treatment of imatinib-resistant CML.

Hippocampal neurogenesis in temporal lobe epilepsy (TLE) may result in alteration of the excitability of neurons, which contributes to spontaneous recurrent seizures. Axon initial segment (AIS) structural and functional plasticity is important in the control of neuronal excitability. It remains to be elucidated whether the plasticity of AIS occurs in hippocampal newly‑generated neurons that are involved in recurrent seizures following pilocarpine‑induced status epilepticus (SE). The present study first established a pilocarpine‑induced TLE rat model to assess the features of newborn neurons and AIS plasticity alterations using double immunofluorescence staining of Ankyrin G and doublecortin (DCX). AIS plasticity alterations include length and distance from soma in the hippocampal newly‑generated neurons post‑SE. The results of the present study demonstrated that pilocarpine‑induced epileptic rats exhibited aberrant hippocampal neurogenesis and longer DCX‑labeled cell dendrites in the dentate gyrus. Pilocarpine‑induced epileptic rats demonstrated shortened lengths of AIS and an increased distance from the soma in hippocampal newborn neurons. Mibefradil, a T/L‑type calcium blocker, reversed the alterations in length and position of AIS in hippocampal newborn neurons post‑SE, accompanied by decreased long‑term seizure activity without increased aberrant neurogenesis. These findings indicate that the plasticity of AIS in hippocampal neurogenesis may have profound consequences in epilepsy, at least in animals.

Puerarin, a predominant isoflavonoid compound extracted from the Chinese medicinal herb Radix Puerariae, is considered to exhibit an antitumor effect. In the present study, the effects of puerarin on SMMC-7721 human hepatocellular carcinoma cells were investigated. Cell viability was assessed by MTT assay. Apoptosis was detected by flow cytometry with Annexin V-fluorescein isothiocyante staining and morphological observation of nuclear changes by Hoechst staining. The mitochondrial membrane potential (MMP) was monitored using rhodamine 123. The generation of reactive oxygen species (ROS) was quantified using dichloro‑dihydro‑fluorescein diacetate. Polymerase chain reaction and western blot analysis were used to detect the expression levels of apoptosis‑associated genes. The results revealed that high concentrations of puerarin (500, 1,000 and 1,500 µg/ml) significantly inhibited the proliferation of SMMC-7721 cells in a time- and dose-dependent manner. Simultaneously, apoptotic rates were increased and cell morphology was changed following puerarin treatment. Furthermore, puerarin‑induced apoptosis of SMMC-7721 cells was associated with loss of MMP and generation of ROS. Puerarin treatment increased caspase‑3,8,9 and apoptosis‑inducing factor (AIF) mRNA expression levels in SMMC‑7721 cells, while the phosphorylation levels of P38, extracellular signal‑regulated kinase (ERK1) and c-Jun N‑terminal kinase were also increased. Furthermore, caspase-9 and AIF protein expression was upregulated. In conclusion, puerarin inhibited proliferation and induced apoptosis in SMMC‑7721 cells via the mitochondria‑dependent pathway; however, the specific mechanisms require further investigation.

High-density lipoprotein (HDL) is a key mediator in reverse cholesterol transport and is involved in a mechanism known as 'selective lipid uptake', a process mediated by scavenger receptor B type I (SR‑BI), which is a HDL receptor. The aim of the present study was to investigate the therapeutic effect of the SR‑BI gene when delivered by combining cationic liposomal microbubbles (CLMs) and ultrasound (US) in hypercholesterolemic rats. Hypercholesterolemia was induced by administration of excessive doses of vitamin D3 and cholesterol in rats. The CLMs consisted of perfluoropropane gas encapsulated in a phospholipid shell using the sonication‑lyophilization method. The SR‑BI gene, mixed with the self‑made microbubbles, was transfected into hypercholesterolemic rat arteries using therapeutic US. SR‑BI protein expression was determined by western blot analysis 2 days post-transfection. Two weeks after transfection, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and HDL serum concentrations were measured. Transfection efficiency of the SR‑BI gene in the SR‑BI + US/CLM group increased 6‑7‑fold compared with the SR‑BI group. Two weeks after transfection, plasma lipid levels in treated hypercholesterolemic rats were observed to be significantly reduced compared with rats that did not receive treatment. However, no significant change was observed in the SR‑BI group compared with that in the SR‑BI + US/CLM group. Results of the present study indicate that the combination of US and CLMs loaded with the SR‑BI gene may exert a protective role in hypercholesterolemia.

Protein phosphatase 2, regulatory subunit A, α (PPP2R1A) and β (PPP2R1B) are paralogous subunits of the heterotrimeric protein phosphatase 2 (PP2A) holoenzyme that catalyzes the dephosphorylation of target substrate proteins. Subtype‑specific PPP2R1A mutations have been frequently observed in ovarian and endometrial cancer. Mutations in the paralogous genes were frequently observed in human malignancies. Thus, the present study aimed to analyze the mutation frequencies of the paralogous PPP2R1A and PPP2R1B genes in patients with primary and secondary ovarian cancer. A total of 251 patients with primary (n=234) and secondary (n=17) ovarian cancer were analyzed for the presence of PPP2R1A and PPP2R1B mutations by direct sequencing. For PPP2R1A, a heterozygous, somatic mutation (c.771G>T, p.W257C) was identified in 1 out of 37 patients (2.7%) with primary ovarian endometrioid carcinoma. The mutant sample was that of a 46‑year‑old female, who was also diagnosed with ectopic endometriosis in the benign ovary. No PPP2R1A mutations were detected in the remaining 250 patients with ovarian cancer. For PPP2R1B, no mutations were detected in our samples. The results of this study suggested that PPP2R1A mutations are less common in Chinese patients with ovarian cancer when compared with European and American patients. Furthermore, our study also supported previous observations that PPP2R1B mutations were absent in ovarian cancer, suggesting that PPP2R1B mutations are not actively involved in the pathogenesis of ovarian cancer.

The aim of the present study was to explore the effect of silencing wild‑type p53‑induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells. SKOV3 cells cultured in vitro were divided into three groups: untreated cells, cells transfected with control small interfering RNA (siRNA) and cells transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect cell apoptosis. Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase‑3, caspase‑3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl‑2), p38 mitogen‑activated protein kinase (p38 MAPK) and phosphorylated (p)‑p38 MAPK. Reverse transcription‑quantitative polymerase chain reaction was used to detect expression of p53, Bax, Bcl‑2 and caspase‑3 mRNAs. Compared with control, apoptosis of SKOV3 cell was significantly increased following Wip1 siRNA silencing. Wip1 silencing also resulted in a significant increase of p53 and p‑p38 MAPK expression, as well as increased cleaved caspase‑3/caspase‑3 and Bax/Bcl‑2 protein ratios. No significant differences were observed in apoptosis and apoptosis‑related protein expression in the control siRNA transfected cells. The present study demonstrated that Wip1 silencing promotes apoptosis of human ovarian cancer SKOV3 cells by activation of the p38 MAPK signaling pathways and through subsequent upregulation of p53, and cleaved caspase‑3/caspase‑3 and Bax/Bcl‑2 protein ratios. Overall, the findings of the present study suggest that targeting Wip1 may be a potential therapeutic avenue for the treatment of human ovarian cancer in the future.

Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC). Kinesin family member 4A (KIF4A) is a microtubule‑based motor protein, which is upregulated in cervical and lung cancer. However, the expression of KIF4A in HBV‑associated HCC, and the effect of HBV on the expression of KIF4A remain to be elucidated. In the present study, the expression profiles of KIF4A were examined in cancerous tissues and paracancerous tissues from patients with HCC, who presented with histories of chronic HBV infection, and the role of HBV in the induction of the expression of KIF4A was investigated. HepG2 cells were transfected with the pHBV1.3, HBV infectious clone and a construct, which contained the luciferase gene under the control of the KIF4A gene promoter. The results demonstrated that the expression of KIF4A was significantly higher in the HCC tissues than in the paracancerous tissues. HBV activated the KIF4A gene promoter and upregulated the mRNA and protein expression of KIF4A. Furthermore, activation of the gene expression of KIF4A increased in a pHBV1.3 concentration‑dependent manner. These results provide novel insights into the understanding of HCC oncogenesis caused by HBV.

The toxicities of conventional chemotherapeutic agents to normal cells restrict their dosage and clinical efficacy in acute leukemia; therefore, it is important to develop novel chemotherapeutics, including natural products, which selectively target cancer-specific pathways. The present study aimed to explore the effect of the chemopreventive agent asiatic acid (AA) on the proliferation and apoptotic rate of the leukemia cell line HL-60 and investigated the mechanisms underlying its anti-tumor activity. The effect of AA on the proliferation of HL-60 cells was evaluated using the MTT assay. Annexin V-fluorescein isothiocyanate/propidium iodide double staining followed by flow cytometric analysis as well as Hoechst 33258 staining were used to analyze the apoptotic rate of the cells. Furthermore, changes of survivin, B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 expressions were detected by western blot analysis. AA blocked the growth of HL-60 cells in a dose- and time-dependent manner. The IC50-value of AA on HL-60 cells was 46.67 ± 5.08 µmol/l for 24 h. AA induced apoptosis in a dose-dependent manner, which was inhibited in the presence of Z-DEVD-FMK, a specific inhibitor of caspase. The anti-apoptotic proteins Bcl-2, Mcl-1 and survivin were downregulated by AA in a dose-dependent manner. Concurrently, AA inhibited ERK and p38 phosphorylation in a dose-dependent manner, while JNK phosphorylation was not affected. In conclusion, the present study indicated that the p38 and ERK pathways, as well as modulation of Bcl-2 family and survivin proteins were key regulators of apoptosis induced in HL-60 cells in response to AA.

Hepatitis C virus (HCV) infection is one of the major causes of hepatocellular carcinoma (HCC). It has been demonstrated that the overexpression of angiogenic factors are associated with the maintenance of liver neoplasia. Hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) are important regulators of angiogenesis and are important in wound healing, the regeneration of new vessels and reproductive functions. The present study investigated the role of the HCV core protein in the induction of HIF-1α and VEGF expression. The HCV core gene and HIF-1α siRNA were transfected into Huh7.5.1 cells. The results demonstrated that the induction of HCV core gene expression in Huh7.5.1 cells leads to the overexpression and stabilization of HIF-1α, and the activation of HIF-1α leads, in turn, to the stimulation of VEGF, which is one of the most important angiogenic factors. These results provide new information to facilitate the understanding of HCC oncogenesis.