While >200 types of etiologies have been shown to be involved in the pathogenesis of infantile spasms, the pathophysiology of infantile spasms remains largely elusive. Pre-natal stress and hypothalamic-pituitary-adrenal axis dysfunction were shown to be involved in the development of infantile spasms. To test the genetic association between the CRHR1 gene, which encodes the corticotrophin-releasing hormone (CRH) receptor, and infantile spasms, five single nucleotide polymorphisms (SNPs) in the CRHR1 gene were genotyped in a sample set of 128 cases with infantile spasms and 131 healthy controls. Correlation analysis was performed on the genotyped data. Under the assumption of the dominant model, the selected five SNPs, rs4458044, rs171440, rs17689966, rs28364026 and rs242948, showed no association with the risk of infantile spasms and the effectiveness of adrenocorticotropic hormone treatment. In addition, subsequent haplotype analysis suggested none of them was associated with infantile spasms. In conclusion, the experimental results of the present study suggested no association between the CRHR1 gene and infantile spasms in a Chinese population.

The aim of the present study was to evaluate the effects of the B7/cluster of differentiation (CD)28 signaling pathway on experimental lupus nephritis and examine the molecular mechanism involved by inhibiting the B7/CD28 signaling pathway. A lupus nephritis model in C57BL/6 J mice was induced via intraperitoneal injection of pristane. A recombinant B7‑1 short hairpin RNA (shRNA) lentivirus vector was constructed by synthesis and splicing. A neutralizing mouse anti‑human B7‑1 antibody termed 4E5 was also prepared. The mouse model of lupus nephritis was treated with B7‑1 shRNA and 4E5 via injection through the tail vein. The silencing effects of B7‑1 shRNA lentiviral infection on target molecules were evaluated using immunofluorescence and flow cytometry. The levels of protein in the urine were detected using Albustix test paper each month over 10 months. The concentration of interleukin (IL)‑4 and interferon‑γ in the serum was determined using an ELISA. The immune complex (IC) deposits in the kidney were analyzed using direct immunofluorescence. The results demonstrated that the C57BL/6 J mouse lupus nephritis model was successfully constructed with immune cells activated in the spleen of the mice, increases in the concentration of anti‑nuclear antibody (ANA) and anti‑double stranded DNA antibodies as well as positive IC formation. Following B7‑1 shRNA lentivirus or 4E5 treatment, CD11b+B7‑1+, CD11c+B7‑1+ and CD21+B7‑1+ cells in the spleen of the mice were significantly reduced. The concentration of ANA and IL‑4 in the serum was also decreased. The concentration of urine protein was reduced and it was at its lowest level in the 4E5 early intervention group. It was also revealed that the immunofluorescence intensity of the IC deposits was weak in the 4E5 early intervention group. In conclusion, inhibiting the B7‑1/CD28 signaling pathway is able to alleviate experimental lupus nephritis and provides an experimental basis for the therapeutic use of blocking the B7‑1/CD28 signaling pathway in human lupus nephritis and other autoimmune disorders.

The aim of the present study was to explore the function and interaction of differentially expressed genes (DEGs) in pulmonary embolism (PE). The gene expression profile GSE13535, was downloaded from the Gene Expression Omnibus database. The DEGs 2 and 18 h post‑PE initiation were identified using the affy package in R software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the DEGs were analyzed using Database for Annotation Visualization and Integrated Discovery (DAVID) online analytical tools. In addition, protein‑protein interaction (PPI) networks of the DEGs were constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins. The PPI network at 18 h was modularized using Clusterone, and a functional enrichment analysis of the DEGs in the top three modules was performed with DAVID. Overall, 80 and 346 DEGs were identified 2 and 18 h after PE initiation, respectively. The KEGG pathways, including chemokine signaling and toll‑like receptor signaling, were shown to be significantly enriched. The five highest degree nodes in the PPI networks at 2 or 18 h were screened. The module analysis of the PPI network at 18 h revealed 11 hub nodes. A Gene Ontology terms analysis demonstrated that the DEGs in the top three modules were associated with the inflammatory, defense and immune responses. The results of the present study suggest that the DEGs identified, including chemokine‑related genes TFPI2 and TNF, may be potential target genes for the treatment of PE. The chemokine signaling pathway, inflammatory response and immune response were explored, and it may be suggested that these pathways have important roles in PE.

Novel therapeutic strategies to improve clinical efficacy in patients with renal cell carcinoma (RCC) are required. The possibility of combination therapy with Lycium barbarum polysaccharides (LBP) and recombinant interferon (IFN)‑α2b remains to be elucidated in RCC. The present study investigated the putative synergistic immunotherapeutic roles of LBP and IFN‑α2b against RCC in vitro and in vivo. The mouse RCC cell line, Renca, was used for in vitro experiments. Treatment of the cells with a combination of LBP and IFN‑α2b markedly inhibited cell proliferation, retarded cell cycle growth and promoted apoptosis in the Renca cells. Western blot analysis revealed that LBP and IFN‑α2b synergistically downregulated the expression levels of cyclin D1, c‑Myc and Bcl‑2, and upregulated the expression of the antiapoptotic protein, Bax. Myeloid‑derived suppressor cells (MDSCs) were markedly upregulated during tumour progression and promoted tumour growth by inhibiting the T‑cell‑mediated immune response. In vivo, a marked reduction in the MDSC ratio and tumour volume was observed in a group receiving combined treatment with LBP and IFN‑α2b in a xenograft tumour model. In conclusion, the present study suggested that the combination of LBP and IFN‑α2b is likely to be more effective in treating murine RCC compared with the less pronounced immunotherapeutic effects of administering LBP or IFN-α2b alone.

The aim of the present was to evaluate the effects of DNA methylation and histone acetylation on 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD)‑induced cleft palate in fetal mice. Pregnant mice (n=10) were randomly divided into two groups: i) TCDD group, mice were treated with 28 µg/kg TCDD on gestation day (GD) 10 by oral gavage; ii) control group, mice were treated with an equal volume of corn oil. On GD 16.5, the fetal mice were evaluated for the presence of a cleft palate. An additional 36 pregnant mice were divided into the control and TCDD groups, and palate samples were collected on GD 13.5, GD 14.5 and GD 15.5, respectively. Transforming growth factor‑β3 (TGF‑β3) mRNA expression, TGF‑β3 promoter methylation, histone acetyltransferase (HAT) activity and histone H3 (H3) acetylation in the palates were evaluated in the two groups. The incidence of a cleft palate in the TCDD group was 93.55%, and no cases of cleft palate were identified in the control group. On GD 13.5 and GD 14.5, TGF‑β3 mRNA expression, HAT activity and acetylated H3 levels were significantly increased in the TCDD group compared with the control. Methylated bands were not observed in the TCDD or control groups. In conclusion, at the critical period of palate fusion (GD 13.5‑14.5), TCDD significantly increased TGF‑β3 gene expression, HAT activity and H3 acetylation. Therefore, histone acetylation may be involved in TCDD‑induced cleft palate formation in fetal mice.

During development of disease, complex intracellular signaling pathways regulate an intricate series of events, including resistance to external toxins, the secretion of cytokines and the production of pathological phenomena. Adenosine 3',5'-cyclic monophosphate (cAMP) is a nucleotide that acts as a key second messenger in numerous signal transduction pathways. cAMP regulates various cellular functions, including cell growth and differentiation, gene transcription and protein expression. This review aimed to provide an understanding of the effects of the cAMP signaling pathway and the associated factors on disease occurrence and development by examining the information from a new perspective. These novel insights aimed to promote the development of novel therapeutic approaches and aid in the development of new drugs.

Bone morphogenetic protein 9 (BMP9) belongs to the transforming growth factor‑β (TGF‑β) superfamily, and has been reported to promote cancer cell proliferation and epithelial‑mesenchymal transition (EMT). Cisplatin (DDP) is the first line treatment for ovarian cancer. However, initiation of EMT confers insensitivity to chemotherapy. The present study aimed to verify and examine the mechanisms underlying the effects of BMP9 on treatment with DDP for ovarian cancer. Prior to treatment with DDP, ovarian cancer cells were exposed to BMP9 for 3 days. Following this, cell viability, apoptosis rate and the extent of DNA damage were evaluated to compare the effects of DDP on BMP9‑pretreated and non‑pretreated ovarian cancer cells. In addition, EMT marker expression was evaluated by western blotting and immunofluorescence. The results demonstrated that BMP9 pretreatment inhibited the cytotoxicity of DDP on ovarian cancer cells. Additionally, BMP9‑pretreated ovarian cancer cells had downregulated expression of the epithelial marker E‑cadherin, which was accompanied by an upregulation of the mesenchymal markers N‑cadherin, Snail, Slug, and Twist. Taken together, the findings of the present study indicated that BMP9 conferred resistance to DDP in ovarian cancer cells by inducing EMT. The present study provided valuable insight into the mechanisms of chemotherapy in ovarian cancer and highlighted the potential of BMP9 as a novel therapeutic target for improving cisplatin chemosensitivity.

Numerous microRNAs (miRs) have been implicated in breast cancer; however, the molecular mechanism is not fully understood. The present study examined the function and regulatory mechanism of miR‑181 in breast cancer. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to examine the RNA and protein expression. MTT assay, wound healing assay and transwell assay were conducted to study cell proliferation, migration and invasion. Luciferase reporter gene assay was used to confirm targeting relationship. The results suggested that the miR‑181 expression levels were significantly higher in breast cancer cell lines and clinical tissue samples. The increased expression of miR‑181 was markedly associated with higher clinical stage and lymph node metastasis. The patients with high miR‑181 expression demonstrated worse prognosis compared with those with a low expression of miR‑181. Small interfering RNA‑induced miR‑181 downregulation significantly inhibited breast cancer cell proliferation, migration and invasion in vitro, and tumor growth in vivo. Protein sprouty homolog 4 (SPRY4), downregulated in breast cancer tissues and cell lines, was observed to be a novel target gene of miR‑181. Downregulation of SPRY4 was significantly associated with breast cancer progression in addition to poor prognosis. Knockdown of SPRY4 rescued the inhibitory effects of miR‑181 downregulation on the malignant phenotypes of breast cancer cells. Thus, the present study demonstrated that miR‑181 serves a promoting role in breast cancer at least in part through the inhibition of SPRY4 expression. The present results expand the understanding of the miR‑181/SPRY4 axis' function during for the malignant progression of breast cancer.

IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein, which is aberrantly expressed in several tumor types and is closely associated with the development, metastasis and prognosis of cancer. Several studies have demonstrated that IQGAP1 has broad prospects in the basic and clinical research of tumors. The present study aimed to explore the effects of IQGAP1‑small interfering (si) NA on the proliferation and metastasis of U251 and U373 glioma cell lines, which markedly expressed IQGAP1. The human glioma cell lines (U251 and U373) were transfected with siRNA and transfection efficacy was confirmed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. Cell proliferation was detected using the Cell Counting kit‑8, and cell metastasis capabilities were detected using cell adhesion, migration and invasion assays. In addition, the expression levels of several tumor‑associated genes were determined by RT‑qPCR and western blotting. The results indicated that IQGAP1 was expressed at higher levels in glioma tissues compared with in normal brain tissues. IQGAP1‑siRNA significantly inhibited cell proliferation, and cell adhesion, migration and invasion. Furthermore, the expression levels of matrix metalloproteinase (MMP)2, Snail, MMP9, fibronectin 1 and Twist were suppressed, and E‑cadherin was upregulated in response to siRNA‑IQGAP1. The present study identified the function of IQGAP1 in glioma cell biology, and indicated that it may be considered a novel target for glioma treatment.

N‑acetyl‑seryl‑aspartyl‑lysyl‑proline (Ac‑SDKP) is a natural tetrapeptide that is released from thymosin β4 by prolyl oligopeptides. It is hydrolyzed by the key enzyme of the renin‑angiotensin system, angiotensin‑converting enzyme (ACE). The aim of the present study was to investigate the alterations in Ac‑SDKP and the ACE/angiotensin II (Ang II)/angiotensin II type 1 (AT1) receptor axis and its impact on the pathogenesis and development of silicotic fibrosis. For in vivo studies, a HOPE MED 8050 exposure control apparatus was used to establish different stages of silicosis in a rat model treated with Ac‑SDKP. For in vitro studies, cultured primary lung fibroblasts were induced to differentiate into myofibroblasts by Ang II, and were pretreated with Ac‑SDKP and valsartan. The results of the present study revealed that, during silicosis development, ACE/Ang II/AT1 expression in local lung tissues increased, whereas that of Ac‑SDKP decreased. Ac‑SDKP and the ACE/AT1/Ang II axis were inversely altered in the development of silicotic fibrosis. Ac‑SDKP treatment had an anti‑fibrotic effect in vivo. Compared with the silicosis group, the expression of α‑smooth muscle actin (α‑SMA), Collagen (Col) I, Fibronectin (Fn) and AT1 were significantly downregulated, whereas matrix metalloproteinase‑1 (MMP‑1) expression and the MMP‑1/tissue inhibitor of metalloproteinases‑1 (TIMP‑1) ratio was increased in the Ac‑SDKP treatment group. In vitro, pre‑treatment with Ac‑SDKP or valsartan attenuated the expression of α‑SMA, Col I, Fn and AT1 in Ang II‑induced fibroblasts. In addition, MMP‑1 expression and the MMP‑1/TIMP‑1 ratio were significantly higher in Ac‑SDKP and valsartan pre‑treatment groups compared with the Ang II group. In conclusion, the results of the present study suggest that an imbalance between Ac‑SDKP and ACE/Ang II/AT1 molecules promotes the development of silicosis and that Ac‑SDKP protects against silicotic fibrosis by inhibiting Ang II‑induced myofibroblast differentiation and extracellular matrix production.

Hypoxemia and hypercarbia resulting from a lack of surfactant is considered to be the primary mechanism underlying neonatal respiratory distress syndrome (NRDS). Surfactant replacement therapy may mitigate the symptoms of the disease by decreasing the surface tension of alveoli and facilitating inflation. However, surfactant serves an additional role in immunological processes. Therefore, it may be hypothesized that mechanisms of NRDS involving surfactant exert additional functions to promoting alveolar inflation. Using peripheral blood obtained from mature infants with and without NRDS, in tandem with mRNA sequencing (mRNA‑seq) analysis, the present study identified that, while cell cycle regulation and alveolar surfactants serve a role in deterring the further onset of NRDS, innate and pathogen‑induced responses of the immune system are among the most important factors in the pathology. The present study illustrated the regulatory importance of these immune pathways in response to alterations in the expression of gene families, particularly in perpetual lung injury leading to NRDS. Notably, data collected from the mRNA‑seq analysis revealed similar mechanisms between NRDS and acute respiratory distress syndrome, a clinical phenotype precipitated by the manifestation of a severe form of lung injury due to numerous lung insults, implying that similar therapies may be applied to treat these two diseases.

Dioscin, an extract from traditional Chinese herbal plants, displays various biological and pharmacological effects on tumors, including inhibition of cell proliferation and induction of DNA damage. However, the effects of dioscin on oral squamous cell carcinoma (OSCC) cells are not completely understood. The present study aimed to evaluate the impact of dioscin on OSCC cell proliferation. Cell Counting Kit‑8 and 5‑ethynyl‑2'‑deoxyuridine incorporation assays were performed to assess cell proliferation. Flow cytometry was conducted to detect alterations in the cell cycle and cell apoptosis. Western blotting and coimmunoprecipitation were performed to determine protein expression levels. In SCC15 cells, dioscin treatment significantly induced cell cycle arrest, increased apoptosis and inhibited proliferation compared with the control group. Mechanistically, the tumor suppressor protein Ras association domain‑containing protein 1A (RASSF1A) was activated and oncoprotein yes‑associated protein (YAP) was phosphorylated by dioscin. Furthermore, YAP overexpression and knockdown reduced and enhanced the inhibitory effects of dioscin on SCC15 cells, respectively. In summary, the results demonstrated that, compared with the control group, dioscin upregulated RASSF1A expression in OSCC cells, which resulted in YAP phosphorylation, thus weakening its transcriptional coactivation function, enhancing cell cycle arrest and apoptosis, and inhibiting cell proliferation. The present study indicated that dioscin may serve as a therapeutic agent for OSCC.

Ginkgolide B (GB), the diterpenoid lactone compound isolated from the extracts of Ginkgo biloba leaves, significantly improves cognitive impairment, but its potential pharmacological effect on astrocytes induced by β‑amyloid (Aβ)1‑42 remains to be elucidated. The present study aimed to investigate the protective effect and mechanism of GB on astrocytes with Aβ1‑42‑induced apoptosis in Alzheimer's disease (AD). Astrocytes obtained from Sprague Dawley rats were randomly divided into control, Aβ, GB and GB + compound C groups. Cell viability and apoptosis were analyzed using Cell Counting Kit‑8 and flow cytometry assays, respectively. Protein and mRNA expression levels were analyzed using western blotting and reverse transcription‑quantitative PCR, respectively. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH‑Px), reactive oxygen species (ROS) and ATP were determined using the corresponding commercial kits. The findings revealed that GB attenuated Aβ1‑42‑induced apoptosis and the 5' adenosine monophosphate‑ activated protein kinase (AMPK) inhibitor compound C reversed the protective effects of GB. In addition, GB reversed Aβ1‑42‑induced oxidative damage and energy metabolism disorders, including decreases in the levels of SOD, GSH‑Px and ATP and increased the levels of MDA and ROS in astrocytes, while compound C reversed the anti‑oxidative effect and the involvement of GB in maintaining energy metabolism in astrocytes. Finally, GB decreased the expression levels of the endoplasmic reticulum stress (ERS) proteins and the apoptotic protein CHOP and increased both mRNA and protein expression of the components of the energy metabolism‑related AMPK/peroxisome proliferator‑activated receptor γ coactivator 1α/peroxisome proliferator‑activated receptor α and anti‑oxidation‑related nuclear respiratory factor 2/heme oxygenase 1/NAD(P)H dehydrogenase (quinone 1) pathways and downregulated the expression of β‑secretase 1. However, compound C could antagonize these effects. In conclusion, the findings demonstrated that GB protected against Aβ1‑42‑induced apoptosis by inhibiting ERS, oxidative stress, energy metabolism disorders and Aβ1‑42 production probably by activating AMPK signaling pathways. The findings provided an innovative insight into the treatment using GB as a therapeutic in Aβ1‑42‑related AD.

Sepsis is a life‑threatening organ dysfunction caused by a dysregulated host response to infection, and is a leading cause of mortality worldwide. Myocardial dysfunction is associated with poor prognosis in patients with sepsis and contributes to a high risk of mortality. However, the pathophysiological mechanisms underlying sepsis‑induced myocardial dysfunction are not completely understood. The aim of the present study was to investigate the role of toll‑like receptor 4 (TLR4)/c‑Jun N‑terminal kinase (JNK) signaling in pro‑inflammatory cytokine expression and cardiac dysfunction during lipopolysaccharide (LPS)‑induced sepsis in mice. C57BL/6 mice were pretreated with TAK‑242 or saline for 1 h and then subjected to LPS (12 mg/kg, intraperitoneal) treatment. Cardiac function was assessed using an echocardiogram. The morphological changes of the myocardium were examined by hematoxylin and eosin staining and transmission electron microscopy. The serum protein levels of cardiac troponin I (cTnI) and tumor necrosis factor‑α (TNF‑α) were determined by an enzyme‑linked immunosorbent assay (ELISA). The TLR4 and JNK mRNA levels were analyzed via reverse transcription‑quantitative PCR. TLR4, JNK and phosphorylated‑JNK protein levels were measured by western blotting. In response to LPS, the activation of TLR4 and JNK in the myocardium was upregulated. There were significant increases in the serum levels of TNF‑α and cTnI, as well as histopathological changes in the myocardium and suppressed cardiac function, following LPS stimulation. Inhibition of TLR4 activation using TAK‑242 led to a decrease in the activation of JNK and reduced the protein expression of TNF‑α in plasma, and alleviated histological myocardial injury and improved cardiac function during sepsis in mice. The present data suggested that the TLR4/JNK signaling pathway played a critical role in regulating the production of pro‑inflammatory cytokines and myocardial dysfunction induced by LPS.

Diabetic nephropathy (DN) is a predominant cause of end‑stage renal disease. The impairment of the autophagy of human renal tubular epithelial cells (HK‑2 cells) is involved in the pathogenic mechanisms of DN. Sirtuin (Sirt)3 regulates the scavenging of damaged organelles and maintains energy balance. The present study aimed to examine the protective effects of Sirt3 on HK‑2 cells stimulated by high glucose (HG). HK‑2 cells were cultured in normal glucose (NG), HG or hyperosmotic medium. The viability of the HK‑2 cells was detected using a Cell Counting Kit‑8 assay. The expression and localization of Sirt3 were detected via immunofluorescence. Following transfection with an overexpression plasmid, the expression levels of key components in the Notch homolog 1 (Notch‑1)/hairy and enhancer of split‑1 (Hes‑1) pathway and those of the autophagy‑related proteins, Beclin‑1, LC‑3II and p62, were measured by western blot analysis and reverse transcription‑quantitative PCR (RT‑qPCR). As the Notch‑1/Hes‑1 pathway was inhibited, the expression levels of Beclin‑1, LC‑3II and p62 were also examined at transcriptional and translational level. It was found that prolonged culture in HG medium markedly reduced cell viability compared with the cells cultured in NG or in NG + mannitol, an effect that was aggravated with the increasing duration of culture. HG was capable of inhibiting the expression levels of Beclin‑1, LC‑3II and Sirt3, and upregulating p62 and the Notch‑1/Hes‑1 pathway, as verified by western blot analysis and RT‑qPCR. The results of immunofluorescence staining revealed that HG decreased Sirt3 expression. Sirt3 reversed the HG‑induced inhibition of the expression of Beclin‑1 and LC‑3II and the upregulation of p62. Moreover, Sirt3 reversed the HG‑induced inhibition of the Notch‑1/Hes‑1 signaling pathway. However, this autophagy‑promoting effect of Sirt3 was counteracted by the Notch‑1/Hes‑1 pathway activator. On the whole, the present study demonstrated that Sirt3 promoted the autophagy of HK‑2 cells, at least partly, via the downregulation of Notch‑1/Hes‑1.

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.

Primary nephrotic syndrome (PNS) is the commonest glomerular disease affecting children. Previous studies have confirmed that CXC motif chemokine ligand 16 (CXCL16) is involved in the pathogenesis of PNS. However, the exact mechanisms underlying the pathogenesis of PNS remain to be elucidated. Thus, the present study aimed to elucidate the role of CXCL16 in PNS. It was found that the expression of CXCL16 and extracellular signal‑regulated kinases 1 and 2 (ERK1/2) were significantly increased in clinical PNS renal tissues using reverse transcription‑quantitative PCR, western blot analysis and immunohistochemistry. Lentivirus overexpression or short hairpin RNA vector was used to induce the overexpression or knockdown of CXCL16 in podocytes, respectively. Overexpression of CXCL16 in podocytes could decrease the cell proliferation and increase the migration and apoptosis, whereas CXCL16 knockdown increased cell proliferation and decreased cell migration and apoptosis. Results of the present study further demonstrated that ERK2 protein expression was regulated by CXCL16. The knockdown of ERK2 expression reversed the effects of CXCL16 on the proliferation, apoptosis, migration and epithelial mesenchymal transition (EMT) of podocytes. Collectively, the findings of the present study highlighted that the CXCL16/ERK1/2 pathway regulates the growth, migration, apoptosis and EMT of human podocytes.

1,4‑Naphthoquinone derivatives have superior anticancer effects, but their use has been severely limited in clinical practice due to adverse side effects. To reduce the side effects and extend the anticancer effects of 1,4‑naphthoquinone derivatives, 2‑(butane‑1‑sulfinyl)‑1,4‑naphthoquinone (BQ) and 2‑(octane‑1‑sulfinyl)‑1,4‑naphthoquinone (OQ) were synthesized, and their anticancer activities were investigated. The anti‑proliferation effects, determined by MTT assays, showed that BQ and OQ significantly inhibited the viability of gastric cancer cells and had no significant cytotoxic effect on normal cell lines. The apoptotic effect was determined by flow cytometry, and the results showed that BQ and OQ induced cell apoptosis by regulating the mitochondrial pathway and cell cycle arrest at the G2/M phase via inhibition of the Akt signaling pathway in AGS cells. Furthermore, BQ and OQ significantly increased the levels of reactive oxygen species (ROS) and this effect was blocked by the ROS scavenger NAC in AGS cells. BQ and OQ induced apoptosis by upregulating the protein expression of p38 and JNK and downregulating the levels of ERK and STAT3. Furthermore, expression levels of these proteins were also blocked after NAC treatment. These results demonstrated that BQ and OQ induced apoptosis and cell cycle arrest at the G2/M phase in AGS cells by stimulating ROS generation, which caused subsequent activation of MAPK, Akt and STAT3 signaling pathways. Thus, BQ and OQ may serve as potential therapeutic agents for the treatment of human gastric cancer.

The safety of anesthetics on the developing brain has caused concern. Ketamine, an N‑methyl‑D‑aspartate receptor antagonist, is widely used as a general pediatric anesthetic. Recent studies suggested that ketamine alters the plasticity of dendritic spines in the developing brain and may be an important contributing factor to learning and cognitive impairment. However, the underlying molecular mechanism remains poorly understood. Therefore, the aim of the present study was to investigate the effect of ketamine on the plasticity of dendritic spines in cultured hippocampal neurons and the potential underlying mechanisms. After 5 days in vitro, rat hippocampal neurons were exposed to different concentrations (100, 300 and 500 µM) of ketamine for 6 h. Ketamine decreased the number and length of dendritic spines in a dose‑dependent manner. Ketamine at a concentration of 300 µM caused an upregulation of transforming protein RhoA (RhoA) and Rho‑associated kinase (ROCK) protein. These effects were inhibited by the ROCK inhibitor Y27632. These results suggested that ketamine induces loss and shortening of dendritic spines in hippocampal neurons via activation of the RhoA/ROCK signaling pathway.

Derivatives of 1,4‑naphthoquinone have excellent anti‑cancer effects, but their use has been greatly limited due to their serious side effects. To develop compounds with decreased side effects and improved anti‑cancer activity, two novel types of 1,4‑naphthoquinone derivatives, 2,3‑dihydro‑2,3‑epoxy‑2‑propylsulfonyl‑5,8‑dimethoxy‑1,4‑naphthoquinone (EPDMNQ) and 2,3‑dihydro‑2,3‑epoxy‑2‑nonylsulfonyl‑5,8‑dimethoxy‑1,4‑naphthoquinone (ENDMNQ) were synthesized and their anti‑tumor activities were investigated. The effects of EPDMNQ and ENDMNQ on cell viability, apoptosis and accumulation of reactive oxygen species (ROS) in liver cancer cells were determined by MTT cell viability assay and flow cytometry. The expression levels of mitochondrial, mitogen activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathway‑associated proteins in Hep3B liver cancer cells were analyzed by western blot analysis. The results demonstrated that EPDMNQ and ENDMNQ inhibited the proliferation of liver cancer Hep3B, HepG2, and Huh7 cell lines but not that of normal liver L‑02, normal lung IMR‑90 and stomach GES‑1 cell lines. The number of apoptotic cells and ROS levels were significantly increased following treatment with EPDMNQ and ENDMNQ, and these effects were blocked by the ROS inhibitor N‑acetyl‑L‑cysteine (NAC) in Hep3B cells. EPDMNQ and ENDMNQ induced apoptosis by upregulating the protein expression of p38 MAPK and c‑Jun N‑terminal kinase and downregulating extracellular signal‑regulated kinase and STAT3; these effects were inhibited by NAC. The results of the present study demonstrated that EPDMNQ and ENDMNQ induced apoptosis through ROS‑modulated MAPK and STAT3 signaling pathways in Hep3B cells. Therefore, these novel 1,4‑naphthoquinone derivatives may be useful as anticancer agents for the treatment of liver cancer.