Breast cancer (BC) is one of the most common types of cancer with the highest morbidity rate amongst all cancers in women worldwide. Arctigenin is isolated from the seeds of Asteraceae lappa and exhibits anti-inflammatory and anti-viral effects. The present study aimed to investigate the effect of arctigenin on BC cells and to explore the regulation of arctigenin on eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) expression. To do so, MDA-MB-231 and BT549 cells were treated with arctigenin at various concentrations (0, 5, 10, 20 and 40 µM). Cells treated with 40 µM arctigenin were transfected with pcDNA3.1-4EBP1 or NC control. Cell Counting Kit-8 assay was used to determine cell proliferation, reverse transcription quantitative PCR was used to evaluate the transfection efficiency, western blotting was used to detect relative protein expression and Transwell assays were performed to evaluate the migratory and invasive abilities of BC cells. The results demonstrated that arctigenin could inhibit the proliferation, migratory and invasive abilities, and epithelial to mesenchymal transition (EMT) of MDA-MB-231 and BT549 cells. Furthermore, arctigenin downregulated the expression of 4EBP1 in MDA-MB-231 and BT549 cells, whereas 4EBP1 overexpression could reverse the inhibiting effect of arctigenin on proliferation, migratory and invasive abilities, and EMT in MDA-MB-231 and BT549 cells. The findings suggested that arctigenin may inhibit human BC cell proliferation, migratory and invasive abilities, and EMT by targeting 4EBP1.

Acute respiratory distress syndrome (ARDS) is a multifactorial syndrome that leads to increased morbidity and mortality in infants and children. The identification of novel biomarkers is critical for the treatment of ARDS. The present study aimed to investigate the effects of chitinase-3-like-1 protein (CHI3L1 or YKL-40) in an in vitro model of ARDS and to explore the potential underlying mechanisms. The in vitro model of ARDS was established in A549 alveolar epithelial type II cells, which were treated by lipopolysaccharide (LPS) to induce inflammation. Transfection was performed to alter YKL-40 expression. The mRNA and protein expression of YKL-40 was determined using reverse transcription-quantitative PCR and western blotting, respectively. Cell Counting Kit-8 and TUNEL assays were used to evaluate the cell viability and apoptosis, respectively. The production of cytokines was evaluated using specific ELISA kits. The relationship between YKL-40 and Fos-related antigen 1 (Fra-1) was verified using luciferase reporter and chromatin immunoprecipitation assays. The expression of the apoptotic proteins was detected using western blotting. The expression levels of YKL-40 and Fra-1 were increased in LPS-treated A549 cells. Higher levels of pro-inflammatory cytokines and induction of cell apoptosis were observed in LPS-treated A549 cells compared with the control. YKL-40 knockdown in LPS-treated A549 cells significantly decreased the production of pro-inflammatory cytokines and reduced cell apoptosis, whereas it concomitantly caused upregulation of Bax and downregulation of Bcl-2, cleaved caspase-3 and cleaved caspase-9. In addition, Fra-1 could directly bind to YKL-40 promoter and regulate its expression level. Overexpression of YKL-40 partly decreased the inhibitory effects of Fra-1 knockdown on the inflammatory response and induction of apoptosis. In summary, the findings from the present study indicated that Fra-1 could bind to YKL-40 and regulate its expression, whereas YKL-40 knockdown could further suppress LPS-induced inflammatory response and apoptosis in A549 cells. These data may provide novel evidence on the diagnosis and therapy of ARDS.

Ischemic stroke is one of the most common causes of disability and death globally; therefore, the repair and reconstruction of the central nervous system (CNS) after stroke is very important. Neural stem/progenitor cells (NSPCs) may be the key to cell replacement therapy to treat CNS damage. It has previously been reported that artesunate (ART) is involved in the regulation of the biological functions of NSPCs; however, the mechanism of action of ART remains unclear. In the present study, different concentrations of ART were used to treat NSPCs following oxygen-glucose deprivation (OGD). Cell viability and apoptosis were analyzed using Cell Counting Kit-8 assay and flow cytometry, respectively, whereas immunofluorescence analysis was used to measure the expression levels of the differentiation-related molecule doublecortin (DCX) and proliferating cell nuclear antigen (PCNA). Western blotting was performed to analyze the expression levels of molecules related to the JAK-2/STAT-3 signaling pathway. The present results indicated that treatment with ART following OGD significantly promoted the viability of NSPCs, inhibited the apoptosis of NSPCs, and promoted the expression of PCNA and DCX. Moreover, ART significantly downregulated the protein expression levels of phosphorylated (p)-JAK-2 and p-STAT-3. Furthermore, activation of the JAK-2/STAT-3 signaling pathway and treatment with ART reversed the effects of ART on the proliferation, apoptosis and differentiation of NSPCs. In conclusion, the present data suggested that ART may promote the proliferation and differentiation of NSPCs, and reduce the apoptosis of NSPCs, by inhibiting the JAK-2/STAT-3 signaling pathway. ART may potentially be used for the treatment of ischemic stroke.

An effective treatment for hepatic fibrosis is not available clinically. Nuclear factor (NF)-κB plays a central role in inflammation and fibrosis. The aim of the present study was to investigate the effect of an NF-κB inhibitor, BAY-11-7082 (BAY), on mouse liver fibrosis. The effects of BAY on hepatic stellate cell (HSC) activation were measured in the lipopolysaccharide-activated rat HSC-T6 cell line. In addition, the therapeutic effect of BAY was studied in vivo using a model of hepatic fibrosis induced by carbon tetrachloride (CCl4) in mice. BAY effectively decreased the cell viability of activated HSC-T6 cells and suppressed HSC-T6 activation by downregulating the expression of collagen I and α-smooth muscle actin. BAY significantly inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase-protein kinase B (Akt) in activated HSC-T6 cells. In addition, administration of BAY attenuated mouse liver fibrosis induced by CCl4, as shown by histology and the expression of profibrogenic markers. BAY also significantly decreased the levels of serum alanine aminotransferase in this model of hepatic fibrosis. Therefore, the results of the present study demonstrate that BAY attenuates liver fibrosis by blocking PI3K and Akt phosphorylation in activated HSCs. Thus, BAY demonstrates therapeutic potential as a treatment for hepatic fibrosis.

Atrial interstitial fibrosis plays a dual role in inducing and maintaining atrial fibrillation (AF). Hypoxia-inducible factor-1α (HIF-1α) has been reported as closely associated with renal, liver and pulmonary fibrosis diseases. However, whether HIF-1α is involved in myocardial fibrosis, and the associations between HIF-1α, transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) remain unknown. Therefore, this area warrants studying for the significance of AF diagnosis and treatment. The present study investigated the expression of HIF-1α in atrial fibrosis and its possible mechanism in isoproterenol (ISO)-induced rats. The three groups of rats; control, ISO and ISO plus sirolimus [also known as rapamycin (Rapa)], were treated for 15 days and sacrificed to remove the myocardial tissues. The expression levels of HIF-1α, TGF-β1 and MMP-9 and their associations with atrial fibrosis were examined through histomorphology and protein and mRNA levels. The protein and mRNA levels of HIF-1α, TGF-β1 and MMP-9 in the ISO group were increased markedly (P<0.01) compared with the control group, while those in the Rapa group were clearly decreased (P<0.01) compared with the ISO group. The protein and mRNA levels of HIF-1α, TGF-β1 and MMP-9 were positively correlated (P<0.01) with atrial fibrosis (collagen volume fraction index), as were the HIF-1α, TGF-β1 and MMP-9 mRNA levels (P<0.01) and the mRNA levels between MMP-9 and TGF-β1 (P<0.01). During the process of atrial fibrosis in ISO-induced rats, HIF-1α promotes the expression of TGF-β1 and MMP-9 protein, and thus is involved in in atrial fibrosis.

Caffeoylxanthiazonoside (CYT) is an active constituent isolated from the fruit of the Xanthium strumarium L plant. The aim of the present study was to investigate the cardioprotective effects of oral administration of CYT on chronic heart failure (CHF) and its underlying mechanisms. A rat model of CHF was first established, and cardiac function indices, including the heart/body weight index, left heart/body weight index, fractional shortening (FS), ejection fraction (EF), cardiac output (CO) and heart rate (HR), were subsequently determined by cardiac ultrasound. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and the levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in heart tissues and cardiac microvascular endothelial cells (CMECs) were determined using ELISA. In addition, the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway members were determined by western blotting in CMECs. The results demonstrated that oral administration of 10, 20, 40 mg/kg CYT significantly reduced cardiac hypertrophy and reversed FS, EF, CO and HR when compared with CHF model rats. In addition, CYT administration significantly decreased the levels of TNF-α, IL-6 and IL-1β in heart tissues, as well as serum LDH and CK levels. Furthermore, exposure of CMECs to 20, 40 and 80 µg/ml CYT significantly decreased the production of TNF-α, IL-1β and IL-6. The protein expression levels of cytoplasmic NF-κB p65 and IκB were upregulated, while nuclear NF-κB p65 was downregulated following treatment of CMECs with 20, 40 and 80 µg/ml CYT when compared with untreated CHF model controls. In conclusion, the results of the current study suggest that CYT demonstrates cardioprotective effects in CHF model rats by suppressing the expression of pro-inflammatory cytokines and the NF-κB signaling pathway.

Compared with traditional imaging techniques, multimodal imaging obtains more accurate images that may increase disease detection rates. The present study prepared stromal cell-derived factor 1 (SDF-1)-loaded, targeted nanoparticles coated with iron (II,III) oxide and perfluorohexane (PFH) to be used as polymer-shelled contrast agents with multimodal imaging functions, with the aim of improving tongue cancer and lymph node metastasis diagnosis. The multifunctional, targeted, polymeric nanoparticles were prepared using a double emulsion method and chemokine SDF-1 was conjugated to nanoparticles by a sulfide bond. The nanoparticles were spherical, uniform size and well dispersed. The results of the in vitro photoacoustic and ultrasonic imaging experiments demonstrated that the multifunctional nanoparticles displayed excellent multimodal imaging functions, as even small concentrations of nanoparticles presented clear ultrasound and photoacoustic imaging. When the temperature reached the boiling point of PFH (56˚C), a liquid-gas phase change occurred and the microsphere volume and acoustic impedance increased, leading to enhanced ultrasonic development. The nanoparticles were automatically targeted to tongue squamous carcinoma cells in vitro via SDF-1-CXC chemokine receptor 4 interactions. The targeted experiment and flow cytometry results indicated that the nanoparticles underwent strong targeted binding to human tongue squamous cell carcinoma (SCC-15) cells. In summary, the nanoparticles were automatically targeted to SCC-15 cells and displayed promising characteristics for ultrasound and photoacoustic imaging. Higher concentrations of nanoparticles was associated with clearer imaged and greater echo intensity value and photoacoustic value. The present study established a foundation for the development of procedures for primary tongue cancer and lymph node metastasis diagnosis.

Sepsis increases the risk of developing liver injury. Previous studies have demonstrated that thymoquinone (TQ) exhibits hepatoprotective properties in vivo as well as in vitro. The present study aimed to investigate the underlying mechanisms of the protective effects of TQ against liver injury in septic BALB/c mice. Male BALB/c mice (age, 8 weeks) were randomly divided into four groups, namely, the control, TQ (50 mg/kg/day) treatment, cecal ligation and puncture (CLP), and TQ + CLP groups. CLP was performed following gavage of TQ for 2 weeks. At 48 h post-CLP, the histopathological alterations in the liver tissue (LT) and plasma levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were assessed. The present study evaluated microtubule-associated protein light chain 3 (LC3), sequestosome-1 (p62) and beclin 1 protein expression by western blotting and immunostaining, as well as interleukin (IL)-6, IL-1β, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) mRNA expression by RT-qPCR. The results of the present study indicated that administration of TQ to mice reduced the histological alterations caused by CLP in LT. TQ inhibited the plasma levels of ALT, AST and ALP in the CLP group. TQ significantly inhibited the elevation of p62, IL-1β, IL-6, MCP-1 and TNF-α levels as well as increased the LC3, beclin 1 and IL-10 levels in LT. PI3K expression in the TQ + CLP group was significantly decreased compared with that in the CLP group. TQ treatment effectively modulated the expression levels of p62, LC3, beclin 1, PI3K and proinflammatory cytokines, and may be an important agent for the treatment of sepsis-induced liver injury.

The protective effects of gastrodin on myocardial ischemia-reperfusion injury in rats and the underlying mechanism were investigated. Sprague Dawley (SD) rats were randomly divided into three groups, of which the gastrodin group was treated with gastrodin, and the other two groups were treated with normal saline. In the myocardial ischemia-reperfusion model group, myocardial ischemia was induced by ligation of the left anterior descending coronary artery, and myocardial reperfusion was performed by ligature removal. Only thread without ligation for the sham operation group was conducted. The rats were euthanized 8 days after surgery. Heart tissues were harvested and used for measurement of apoptotic rate and expression levels of apoptosis-related proteins. Serum levels of cytokines were measured also using blood samples. Compared with the myocardial ischemia-reperfusion model group, significant reduction of cardiomyocyte apoptosis was observed in the gastrodin group (P<0.05). In the gastrodin group, the protein and mRNA expression levels for Bax and activated caspase-3 decreased, while for Bcl-2 increased (P<0.05). Gastrodin can downregulate inflammatory cytokines (P<0.05) and upregulate anti-inflammatory cytokines such as IL-10 (P<0.05) in serum of SD rats. Therefore, gastrodin played a protective role in myocardial ischemia-reperfusion injury by regulating the expression levels of apoptosis-related signaling proteins and inflammatory cytokines.