Gastric cancer is the fifth most common cancer worldwide with a poor survival rate. Therefore, it is important to identify predictive and prognostic biomarkers of gastric cancer. Laminin subunit beta 1 (LAMB1) is involved in attachment, migration, and organization during development, and its elevated expression has been associated with several cancers. However, the role and mechanism of LAMB1 in gastric cancer remains unknown. Here, we determined that LAMB1 is upregulated in gastric cancer tissues and contributes to cell growth and motility. Using a public database, we showed that LAMB1 expression was significantly upregulated in gastric cancer compared to normal tissues. LAMB1 was also found to be associated with poor prognosis in patients with gastric cancer. Overexpression of LAMB1 elevated cell proliferation, invasion, and migration; however, knockdown of LAMB1 decreased these effects in gastric cancer cells. U0126, an extracellular signal-regulated kinase (ERK) inhibitor, regulated the expression of LAMB1 in gastric cancer cells. Additionally, we showed that c-Jun directly binds to the LAMB1 promoter as a transcription factor and regulates its gene expression via the ERK pathway in gastric cancer cells. Therefore, our study indicates that LAMB1 promotes cell growth and motility via the ERK/c-Jun axis and is a potential biomarker and therapeutic target of gastric cancer.

Galectin-1 contains a carbohydrate-recognition domain (CRD) as a member of the lectin family. Here, we investigated whether galectin-1 regulates adipogenesis and lipid accumulation. Galectin-1 mRNA is highly expressed in metabolic tissues such as the muscle and adipose tissues. Higher mRNA expression of galectin-1 was detected in white adipose tissues (WATs) of mice that were fed a high-fat diet (HFD) than in those of mice fed a normal-fat diet (NFD). Protein expression of galectin-1 also increased during adipocyte differentiation. Galectin-1 silencing inhibited the differentiation of 3T3-L1 cells and the expression of lipogenic factors, such as PPARγ, C/EBPα, FABP4, and FASN at both mRNA and protein levels. Lactose, an inhibitor by the binding with CRD of galectin-1 in extracellular matrix, did not affect adipocyte differentiation. Galectin-1 is localized in multiple cellular compartments in 3T3-L1 cells. However, we found that DMI (dexamethasone, methylisobutylxanthine, insulin) treatment increased its nuclear localization. Interestingly, galectin-1 interacted with PPARγ. Galectin-1 overexpression resulted in increased PPARγ expression and transcriptional activity. Furthermore, we prepared galectin-1-knockout (Lgals1^−/−) mice and fed a 60% HFD. After 10 weeks, Lgals1^−/− mice exhibited lower body weight and gonadal WAT (gWAT) mass than wild-type mice. Fasting glucose level was also lower in Lgals1^−/−mice than that in wild-type mice. Moreover, lipogenic genes were significantly downregulated in the gWATs and liver tissues from Lgals1^−/− mice. Pro-inflammatory cytokines, such as CCL2, CCL3, TNFα, and F4/80, as well as macrophage markers, were also drastically downregulated in the gWATs and liver tissues of Lgals1^−/− mice. In addition, Lgals1^−/−mice showed elevated expression of genes involved in thermogenesis in the brown adipose tissue. Collectively, galectin-1 exacerbates obesity of mice fed HFD by increment of PPARγ expression and activation. Our findings suggest that galectin-1 could be a potential therapeutic target for obesity and needed further study for clinical application.

Skin aging is caused by exposure to various external factors. Ultraviolet B (UVB) irradiation induces oxidative stress, photoaging, and inflammation in skin cells. Pinus densiflora Sieb. et Zucc. (red pine) has various antimicrobial and antioxidant activities. However, the anti-inflammatory effects of red pine on skin have rarely been reported. The protective effects of malonic acid (MA) isolated from Pinus densiflora were investigated against UVB-induced damage in an immortalized human keratinocyte cell line (HaCaT). MA increased levels of the antioxidant enzymes superoxide dismutase 1 (SOD-1) and heme oxygenase 1 (HO-1) via activation of nuclear factor-erythroid 2-related factor-2 (Nrf2), resulting in a reduction in UVB-induced reactive oxygen species (ROS) levels. Additionally, the inhibition of ROS increased HaCaT cell survival rate. Thus, MA downregulated the expression of ROS-induced nuclear factor-κB, as well as inflammation-related cytokines (interleukin-6, cyclooxygenase-2, and tumor necrosis factor-α). Furthermore, MA significantly suppressed the mitogen-activated protein kinase/activator protein 1 signaling pathway and reduced the expression of matrix metalloproteinases (MMPs; MMP-1, MMP-3, and MMP-9). In contrast, MA treatment increased the expression of collagen synthesis regulatory genes (COL1A1 and COL3A1) via regulation of Smad2/3 signal induction through transforming growth factor-β. In conclusion, MA protected against UVB-induced photoaging via suppression of skin inflammation and induction of collagen biosynthesis.

Spondin-2 (SPON2) is involved in cancer progression and metastasis of many tumors; however, its role and underlying mechanism in gastric cancer are still obscure. In this study, we investigated the role of SPON2 and related signaling pathway in gastric cancer progression and metastasis. SPON2 expression levels were found to be upregulated in gastric cancer cell lines and patient tissues compared to normal gastric epithelial cells and normal controls. Furthermore, SPON2 silencing was observed to decrease cell proliferation and motility and reduce tumor growth in xenograft mice. Conversely, SPON2 overexpression was found to increase cell proliferation and motility. Subsequently, we focused on regulatory mechanism of SPON2 in gastric cancer. cDNA microarray and in vitro study showed that Notch signaling is significantly correlated to SPON2 expression. Therefore, we confirmed how Notch signaling pathway regulate SPON2 expression using Notch signaling-related transcription factor interaction and reporter gene assay. Additionally, activation of Notch signaling was observed to increase cell proliferation, migration, and invasion through SPON2 expression. Our study demonstrated that Notch signaling-mediated SPON2 upregulation is associated with aggressive progression of gastric cancer. In conclusion, we suggest upregulated SPON2 via Notch signaling as a potential target gene to inhibit gastric cancer progression.

The hyaluronan-mediated motility receptor (HMMR) is overexpressed in gastric cancer; however, the apparent role of HMMR has not been well defined owing to lack of detailed studies on gastric tumorigenesis. Therefore, we elucidated the functional and regulatory mechanisms of HMMR in gastric cancer. Using publicly available data, we confirmed HMMR overexpression in patients with gastric cancer. HMMR silencing decreased proliferation, migration, and invasion of gastric cancer cells, whereas HMMR overexpression reversed these effects. A gastric cancer xenograft mouse model showed statistically significant inhibition of tumor growth upon HMMR depletion. Previous data from cDNA microarray showed reduced HMMR expression upon inhibition of galectin-3. However, overexpression of galectin-3 increased HMMR expression, cell proliferation, and motility in gastric cancer cells, whereas HMMR silencing blocked these effects. Interestingly, galectin-3 interacted directly with C/EBPβ and bound to HMMR promoter to drive its transcription, and gastric cancer cell proliferation and motility. Altogether, high expression of HMMR promoted gastric cancer cell proliferation and motility and could be a prognostic factor in gastric cancer. In addition, HMMR expression was regulated by the interaction between C/EBPβ and galectin-3. Therefore, targeting HMMR along with galectin-3 and C/EBPβ complex could be a potential treatment strategy for inhibiting gastric cancer progression and metastasis. Implications: This study provides evidence that galectin-3 interacts with C/EBPβ in gastric cancer, and galectin-3 and C/EBPβ complex promotes gastric cancer cell progression and motility through upregulating HMMR expression.

An inflammatory reaction caused by the activation of microglia in the brain can lead to neurodegeneration and cause diseases, such as Alzheimer’s and Parkinson’s disease. The regulation of inflammation can aid in preventing the development of neurodegenerative disease. Malonic acid has a variety of biological activity. The effects of malonic acid on microglia are not currently well known. Therefore, in this study, we investigate the effects of inflammation of malonic acid in BV2 microglia cells. As a result, we demonstrated that malonic acid on LPS-treated microglia decreased pro-inflammatory responses and mechanisms of the p38 MAPK/NF-κB pathway. Inflammatory mediators significantly decreased the LPS-induced production of nitric oxide and reactive oxygen species. Pro-inflammatory cytokines of IL-6 suppressed gene expression. In addition, the protein expression of NF-κB decreased at the nucleus, as did the protein expression of activated phosphorylated IκB-α, which is an NF-κB regulator-related protein. The expression of phosphorylated p38, a mediator of inflammatory cytokines, was regulated. Therefore, our results indicate that malonic acid has anti-inflammatory effects and may be a potential therapeutic candidate for neuroinflammatory diseases.