Following emergence of the tumor stem cell theory, the increasing number of related studies demonstrates the theory's growing importance in cancer research and its potential for clinical applications. Few studies have addressed the in vitro or in vivo properties of glioma stem cells from a Han Chinese population. In the present study, surgically obtained glioblastoma tissue was classified into two subtypes, CD133(+) and CD133(-). The hierarchy, invasiveness, growth tolerance under low nutrient conditions and colony forming abilities of the tissue samples were analyzed. Additionally, the characteristics of tumor cells transplanted subcutaneously or re-transplanted into nude mice were observed. The results demonstrated that CD133(+) glioblastoma cells derived from Han Chinese glioma specimens were more prone to primitive cell differentiation and more invasive than CD133(-) glioblastoma cells, leading to increased tumor malignancy compared with CD133(-) cells. The tumor formation rates of CD133(+) and CD133(-) cells in mice were 26/30 and 2/30, respectively. A comparison of tumor subtypes demonstrated that CD133(+) glioblastoma cells had a lower incidence of cell apoptosis in the tumor tissue and higher protein expression levels of Oct4, Sox2, PCNA, EGFR, Ang2, MMP2 and MMP9 compared with CD133(-) cells. Flow cytometry revealed that in the CD133(+) and CD133(-) glioblastoma cell-induced tumors, the percentage of CD133(+) cells was 2.47±0.67 and 0.44±0.14%, respectively. The tumor formation rates following the re-transplantation of CD133(+) or CD133(-) tumors into nude mice were 10/10 and 4/10, respectively. These findings suggest that the CD133(+) glioblastoma cell subpopulation has a stronger malignant cell phenotype than the CD133(-) subpopulation and that its recurrence rate is increased compared with the primitive tumorigenic rate following in vivo transplantation.

Stem cell transplantation has been considered a promising therapeutic approach for premature ovarian failure (POF). However, to date, no quantitative data analysis of stem cell therapy for POF has been performed. Therefore, the present study performed a meta-analysis to assess the efficacy of stem cell transplantation in improving ovarian function in animal models of POF. In addition, a case report of a patient with POF subjected to stem cell treatment was included to demonstrate that stem cell therapy also contributes to the recovery of ovarian function in patients. Published studies were identified by a systematic review of the PubMed, Embase, and Cochrane's library databases, and references cited in associated reviews were also considered. Data regarding follicle-stimulating hormone (FSH), estradiol (E2), ovarian weight, follicle count, the number of pregnancies and other parameters, including delivery route and cell type, were extracted. Pooled analysis, sensitivity analyses, subgroup analyses and meta-regression were performed. In the case of POF, transvaginal ultrasound (TVS), abdominal ultrasound (TAS) and color Doppler flow imaging (CDFI) were performed to observe the endometrial morphology and blood flow signals in the patient. Overall, pooled results from 16 pre-clinical studies demonstrated that stem cell-based therapy significantly improved FSH levels [standardized mean difference (SMD)=-1.330; 95% confidence interval (CI), -(2.095-0.565); P=0.001], E2 levels (SMD=2.334; 95% CI, 1.350-3.319; P<0.001), ovarian weight (SMD=1.310; 95% CI, 0.157-2.463; P=0.026), follicle count (SMD=1.871; 95% CI, 1.226-2.516; P<0.001), and the number of pregnancies (risk ratio=1.715, 95% CI, 1.213-2.424; P=0.002). The results of TVS and TAS demonstrated improved ovarian size and endometrial thickness in the patient with POF after MSC treatment. Of note, a rich blood flow signal in the endometrium was observed on CDFI. It appeared that stem cell-based therapy may be an effective method for the resumption of ovarian function in a patient and in animal models of POF; however, large-scale and high-quality future studies are required to confirm the present findings due to heterogeneity.

Bacterial infection is a key factor in airway inflammation. The present study describes the time-dependent changes in the leukocyte counts and cytokine levels of the bronchoalveolar lavage fluid (BALF) following subacute airway inflammation induced by lipopolysaccharide (LPS), a major component of the outer membranes of Gram-negative bacteria. LPS (200 μg/rat) or saline was intratracheally administered to rats which were sacrificed 2, 4 or 7 days after LPS treatment. Airway inflammation was evaluated using hematoxylin and eosin staining, cell counts and proinflammatory cytokine levels in the BALF. Rat airways obtained from the LPS group exhibited marked airway wall thickening and infiltration of inflammatory cells compared with the control group, as well as elevated cell counts (neutrophils, macrophages, lymphocytes) and proinflammatory cytokine levels [(tumor necrosis factor (TNF)-α, interleukin (IL)-1β, cytokine-induced neutrophil chemoattractant (CINC)-1)] in the BALF, which peaked on day 2 and subsequently decreased until the experimental endpoint. Notably, IL-1β levels induced by LPS changed in a similar manner to macrophage cell counts, but not neutrophil and lymphocyte counts. Moreover, TNF-α and CINC-1 levels did not decrease as rapidly as neutrophil counts after peaking. These findings suggest that macrophages may play a significant role in maintaining subacute inflammatory responses induced by LPS in rat airways.

Gemcitabine is the first-line chemotherapeutic agent for advanced adenocarcinoma of the pancreas, despite the high risk of chemoresistance as a major disadvantage. In the past few years, significant advances have been made in the field of pancreatic cancer stem-like cells (CSCs) and their critical roles in drug resistance, invasion and metastasis, which are tightly regulated by long non-coding RNAs (lncRNAs). The present study demonstrated that HOX antisense intergenic RNA (HOTAIR) is not different between the pancreatic cancer cell line PANC-1 and its enriched CSC sub-population. However, after gemcitabine treatment, the expression levels of HOTAIR in CSCs were induced, but not in PANC-1 cells. HOTAIR induced by gemcitabine failed to cause chemoresistance, but promoted the clonogenicity, proliferation and migration of the cells. By introducing HOTAIR using lentivirus, chemoresistance was induced and the self-renewal capacity, proliferation and migration were significantly promoted. By contrast, HOTAIR knockdown in PANC-1 CSCs treated with or without gemcitabine decreased the cell proliferation, altered the cell cycle progression and induced apoptosis, demonstrating its critical roles in regulating the malignant character of PANC-1 CSCs. In conclusion, the present study demonstrated that HOTAIR may be induced by gemcitabine and acts as a tumor promoter by inhibiting the chemosensitivity, and promoting the self-renewal capacity, proliferation and migration of PANC-1 CSCs, which supports its potential application as a novel therapeutic approach for pancreatic cancer.

The aim of the present study was to assess the expression status of matrix metalloproteinase (MMP)-28 and to investigate its molecular mechanisms in glioma cells. MicroRNA (miRNA) reverse transcription-quantitative polymerase chain reaction was used to analyze the expression of MMP-28 and transforming growth factor (TGF)-β expression in glioma patients and healthy volunteers. MTT and Transwell assays were conducted to determine cell growth and metastasis, respectively. Annexin V/propidium iodide staining was also employed to measure cell apoptosis. MMP-28 and TGF-β protein expression were measured using western Blot analysis. The results indicated that MMP-28 and TGF-β expression was downregulated in glioma patients, when compared with the normal group. Overall survival and disease-free survival of patients with a low expression of MMP-28 were lower than those with high MMP-28 expression. Overexpression of MMP-28 induced TGF-β protein expression, while downregulation of MMP-28 suppressed TGF-β protein expression in glioma cell. The downregulation of MMP-28 reduced the cell growth and apoptosis of glioma cell via the suppression of TGF-β. By contrast, upregulation of MMP-28 induced cell growth and reduced the apoptosis of glioma cells by activating TGF-β. In addition, the TGF-β inhibitor attenuated the effects of MMP-28 in glioma cells. Collectively, the results indicated that MMP-28 was able to induce TGF-β in human glioma cells.

Long non-coding RNA gastric cancer associated transcript 3 (GACAT3), is a newly identified non-coding RNA, which has been found to be involved in the tumorigenesis of gastric cancer. However, the biological function of GACAT3 in liver cancer remains unclear. The present study aimed to determine the expression level and function of GACAT3 in liver cancer. The authors cultured liver cancer cells in vitro and GACAT3 was silenced in the cells. Cell proliferation, apoptosis and migration were determined by MTT assay, flow cytometric analysis and transwell assay, respectively. It was demonstrated that GACAT3 was upregulated in liver cancer tissues. The inhibition of GACAT3 decreased the ability of hepatoma cells to proliferate and migrate, and increased apoptosis of the cells. These findings provide the first evidence, to the best of our knowledge, of the exact role of GACAT3 in liver cancer, suggesting GACAT3 as a potential target for liver cancer therapy in the future.

Traumatic brain injury (TBI) results in the activation of neurogenesis, but it also triggers multiple cell signaling pathways that may lead to either cell damage or cell survival. In general, the repair processes following TBI are characterized by a failure to replenish the neuronal population entirely. To date, the factors that determine whether neurogenesis will be sufficient for the replacement of lost neurons following brain injury are not fully understood. Decreased activation of Hes1, a transcriptional repressor, is observed as neural differentiation proceeds, and this gene continues to play a role in the quiescence of stem cells into adulthood. Since Hes1 is negatively correlated with neurogenesis in adult rodents, the present study investigated whether this gene inhibits TBI-induced neurogenesis by use of adenovirus-mediated gene transfer to upregulate Hes1 expression in the dentate gyrus (DG) in a mouse model of TBI. Western blot analysis and immunofluorescent staining revealed increased Hes1 protein expression in the subgranular zone (SGZ) of the DG following adenovirus-Hes1 (Ad-Hes1) transfection and a decreased number of bromodeoxyuridine-positive and doublecortin-positive cells in the SGZ in the transfection group following TBI. These data indicated a negative association between the expression of Hes1 and adult neurogenesis following the induction of TBI. Furthermore, the present findings demonstrate the value of downregulating Hes1 expression following TBI to promote the initiation of endogenous neurogenesis, which may be of therapeutic value for patients with brain injuries.

This study investigated the correlation between interleukin (IL)-1β-511C/T gene polymorphism and myocardial infarction (MI) complicated with ischemic stroke (IS). A total of 251 MI patients complicated with IS (observation group) and 200 healthy people (control group) were selected for the case-control study. IL-1β-511C/T gene polymorphism was detected via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype distribution and allele frequency were compared between the two groups, and the correlation between gene polymorphism and MI complicated with IS, was analyzed after traditional risk factors were adjusted by using logistic regression method. The frequencies of CT and TT genotypes in the observation group were higher than those in the control group (P<0.05). The frequency of T allele in the observation group was significantly higher than that in the control group (P<0.05), but the frequency of C allele was obviously lower than that in the control group (P<0.05). According to results of logistic regression analysis, arrhythmia and high-density lipoprotein cholesterol (HDL-C) were associated with MI complicated with IS. In patients with arrhythmia, the risk of disease in carriers with IL-1β-511T gene was 1.7-1.8 times that in non-carriers [odds ratio (OR) = 1.742 and 1.839, P<0.05]. In patients with abnormal HDL-C, the risk of disease in carriers with IL-1β-511T gene was 2.0-2.2 times that in non-carriers (OR = 2.011 and 2.249, P<0.05). Besides, the risk of MI complicated with IS in carriers with CC genotype had no significant difference in patients with arrhythmia and abnormal HDL-C (P>0.05). IL-1β-511C/T gene polymorphism may be related to the risk of MI complicated with IS.

The clinical efficacy of microsurgical neck clipping for the treatment of cerebral aneurysm rupture and its effect on serum nuclear factor κ-light-chain-enhancer of activated β cells (NF-κB), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) levels were investigated. A total of 56 patients with first occurrence of cerebral aneurysm rupture were enrolled from June 2015 to June 2016. These patients were divided into control (25 patients) and observation groups (31 patients) according to treatment received. The patients in the control group were treated with interventional embolization and extraventricular drainage, while the patients in the observation group were treated with microsurgical neck clipping. Serum NF-κB, MCP-1 and MMP-9 levels were measured by ELISA prior to the operation and at 6 h post-operation. Clinical effects were compared at the 6-month follow-up. There was no significant difference in the success rate of the operation between the two groups (p>0.05). The incidence of complications in the observation group was significantly lower than that in the control group (p<0.05). The Glasgow Outcome Scale score was significantly improved in the observation group (p<0.05) compared with the control group. Serum NF-κB, MMP-9 and MCP-1 were significantly decreased in both groups at 6 and 24 h after operation, but the observational group showed significantly lower levels for all three proteins than the control group (p<0.05). The application of early microsurgical neck clipping for the treatment of cerebral aneurysm rupture can reduce complications and improve clinical prognosis, and this may be related to a decrease in serum inflammatory response-related factors (NF-κB and MCP-1) and MMP-9.

Doxorubicin (DOX), a potent and widely used anticancer agent, can give rise to severe cardiotoxicity that limits its clinical use by inducing oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the central regulator of cellular responses to electrophilic/oxidative stress, which serves a critical role in maintenance of normal cardiac function. Tanshinone IIA (Tan IIA) has previously been reported to protect against DOX-induced cardiotoxicity. The aim of the present study was to elucidate whether Nrf2 signaling serves a role in the underlying mechanism. In the animal model, DOX induced acute cardiotoxicity, whereas Tan IIA pretreatment reduced the activity of myocardial enzymes, and increased activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione (GSH). Furthermore, Tan IIA pretreatment (3-10 µM) significantly increased the cell viability and markedly restored morphological changes in DOX-injured H9c2 cells, decreased the generation of reactive oxygen species, and increased the level of intracellular GSH. Additionally, Tan IIA pretreatment also induced the nuclear accumulation of Nrf2 and its downstream genes heme oxygenase-1, NAD(P)H dehydrogenase (quinone) 1, and glutamate-cysteine ligase catalytic subunit in both the mice cardiac tissues and H9c2 cells. Nrf2 knockdown by small interfering RNA downregulated Tan IIA-induced Nrf2 activation and reversed the effect of Tan IIA on the DOX-induced inhibition of cell viability. These results suggest that the Nrf2-dependent antioxidant response mediates the protective effect of Tan IIA on DOX-induced cardiotoxicity.

Radial extracorporeal shock wave therapy (rESWT) has been proven to be effective for nonunion fractures. It was, thus, hypothesized that it may be used as a supplement therapy to promote osteochondral regeneration when combined with a scaffold previously prepared by our research group. In the present study, to verify this hypothesis, New Zealand white adult rabbits were anaesthetized and divided into three groups, as follows: Untreated control group, in which full-thickness cylindrical osteochondral defects were created without repairing; scaffold group, in which rabbits were implanted with the scaffolds; scaffold plus rESWT group, in which rabbits were implanted with scaffolds and then treated with rESWT at 2 weeks post-surgery. At 6 and 12 weeks after surgery, the animals were sacrificed. Nitric oxide (NO) levels in the synovial cavity of the knee joints were measured by the Griess method. In addition, macroscopic observation and the gross score according to the International Cartilage Repair Society (ICRS) histological scoring system were determined. Histological evaluation was also performed by hematoxylin-eosin and Safranin O/fast green staining. The results demonstrated that both the scaffold and scaffold plus rESWT treatments significantly reduced NO levels in the synovial cavity at 6 weeks after surgery (P<0.05), whereas no significant difference was observed at 12 weeks after surgery. The ICRS scores of the scaffold and scaffold plus rESWT groups were significantly higher in comparison with those in the control group (P<0.05), and rESWT further increased these scores at 12 weeks after surgery (P<0.05). Histological results revealed that osteochondral regeneration was improved after treatment with scaffold or scaffold plus rESWT, with the latter displaying better results. These data suggested that rESWT improved the osteochondral regeneration when applied in combination with the scaffold, and that one of the underlying mechanisms may involve the reduction of NO in the synovial fluid. Therefore, rESWT may be a useful treatment for knee osteochondral regeneration.

Osteoarthritis (OA) is the most common type of arthritis, observed mainly in the population aged >65 years. However, the mechanism underlying the development and progression of OA has remained largely elusive. The present study aimed to identify differentially expressed mRNAs and lncRNAs in OA. By analyzing the GSE48556 and GSE82107 datasets, a total of 202 up- and 434 downregulated mRNAs were identified in OA. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that differently expressed genes were mainly involved in regulating antigen processing and presentation, interspecies interaction between organisms, immune response, transcription and signal transduction. In addition, a series of long non-coding (lnc)RNAs were differently expressed in OA. To provide novel data on the molecular mechanisms and functional roles of these lncRNAs in OA, a co-expression analysis was performed, which revealed that the dysregulated lncRNAs were associated with transcription, signal transduction, immune response and cell adhesion. In addition, certain key genes in protein-protein interaction networks were identified. The present study provided useful information for exploring potential candidate biomarkers for the diagnosis and prognosis of OA, as well as novel drug targets.