Activity

Baicalin is a flavonoid isolated from the root of Scutellaria baicalensis with anti‑inflammatory, antioxidant and antiapoptotic pharmacological properties. however, the therapeutic effect of baicalin on rheumatoid arthritis (RA) is not completely understood. The present study aimed to explore the therapeutic potential and mechanisms underlying baicalin in collagen‑induced arthritis (CIA) model rats. CIA was induced in male SD rats. The hind paw thickness and severity of joint injury were monitored to assess the onset of arthritis. At 28 days after the initial immunization, different doses of baicalin were administered once daily via oral gavage for 40 days. The radiologic and pathological alterations were examined using X‑ray, and hematoxylin and eosin staining, respectively. selleck kinase inhibitor ELISA was employed to measure the serum levels of proinflammatory cytokines. Reverse transcription‑quantitative PCR and western blotting were conducted to determine the expression of toll‑like receptor (TLR)2, myeloid differentiation factor 88 (MYD88) and NF‑κB p65. Baicalin treatment noticeably alleviated radiographic and histologic abnormalities in the hind paw joints of CIA model rats in a dose‑dependent manner. The serum levels of proinflammatory cytokines were significantly decreased in baicalin‑treated CIA model rats compared with vehicle‑treated CIA model rats. The mRNA expression levels of TLR2 and MYD88, as well as the protein expression levels of TLR2, MYD88 and NF‑κB p65 were significantly decreased by baicalin treatment in the synovial tissue of CIA model rats and human RA fibroblast‑like synoviocytes. The results suggested that baicalin may exert a beneficial effect on CIA, which may be mediated by inhibiting the TLR2/MYD88/NF‑κB signaling pathway.N-acetyl cysteine (NAC) has been used to inhibit lipopolysaccharide (LPS)-induced inflammation. However, the molecular mechanism underlying its anti‑inflammatory effects remains to be elucidated. The present study aimed to determine the effect of NAC on the LPS‑induced inflammatory response in bone marrow mesenchymal stem cells (BMSCs) and elucidate the underlying molecular mechanism. First, BMSCs were stimulated by LPS following pretreatment with NAC (0, 0.1, 0.5, 1 or 2 mM). A Cell Counting Kit 8 assay was used to determine the number of viable cells and 1 mM NAC was selected as the experimental concentration. Then, the secretion of inflammatory factors, including interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α was evaluated by enzyme‑linked immunosorbent assay. Finally, the expression levels of mRNA and proteins, including apoptosis‑associated speck‑like protein containing a CARD (ASC), nucleotide‑binding oligomerization domain‑like receptor protein 3 (NLRP3), caspase‑1, thioredoxin‑interacting protein (TXNIP), and thioredoxin (TRX), were evaluated by reverse transcription‑quantitative PCR and western blot analysis, respectively. The results demonstrated that the secretion of inflammatory factors, which was increased by the administration of LPS, was reduced by pretreatment with NAC. Furthermore, NAC reduced the expression of ASC, NLRP3, caspase‑1 and TXNIP, but enhanced that of TRX. To conclude, NAC had anti‑inflammatory effects on LPS‑stimulated BMSCs, which was closely associated with the TXNIP/NLRP3/IL‑1β signaling pathway. Thus, NAC may be a promising treatment to attenuate the inflammatory response in LPS‑induced BMSCs.It has been revealed from microarray data analysis that long intergenic non‑coding RNA 02454 (LINC02454) is highly expressed in papillary thyroid cancer (PTC). The aim of the present study was to explore the potential role of LINC02454 in the tumorigenesis of PTC. The mRNA expression levels of LINC02454 were assessed using data from The Cancer Genome Atlas (TCGA) and the GSE66783 cohort in thyroid cancer, and were validated using reverse transcription‑quantitative PCR in 104 patients with PTC recruited in the present study. The association between the LINC02454 mRNA expression levels and the clinicopathological features of the 104 patients with PTC were also analyzed. Functional enrichment analyses were conducted on the differentially expressed genes in the high and low LINC02454 expression groups that were identified from the TCGA cohort. RNA interference, using short interfering (si)RNA against LINC02454, was used to investigate the role of LINC02454 in the biological functions of PTC cells in vitro. The ex an overall increase in apoptosis, as well as to an unexpected decrease in cell proliferation. LINC02454 may thus potentially function as an oncogene, which inhibits the apoptosis and enhances proliferation of PTC cells. Thus, as suggested by the findings of the present study, LINC02454 may be used as a diagnostic and prognostic biomarker for PTC in the future.Thyroid hormones (TH) are multifunctional mediators that fine‑tune several physiological processes, including metabolic rate, digestive function and tissue development via interactions with type II nuclear thyroid hormone receptors (TR). Upon binding of TH, TRs interact specifically with thyroid hormone response elements of target gene promoter regions to regulate their transcription. Earlier studies suggested a correlation between aberrant TR regulation and hepatocellular carcinoma (HCC). THs are involved in a crosstalk between hepatoma and stromal cells, and disruption of TH signaling is associated with tumorigenesis. Previous cDNA microarray analysis of target gene expression following T3 treatment of wild‑type TR‑expressing hepatoma cells led to the identification of forkhead box M1 (FOXM1) as a factor negatively regulated by T3 and associated with poor prognosis in several cancer types. Increased FOXM1 expression during late stages of HCC was associated with poorer overall and recurrence‑free survival in patients with HCC. However, the specific mechanisms underlying FOXM1 activity in liver cancer progression remain to be elucidated. Experiments from the present study showed that TH/TR signaling suppresses FOXM1 mRNA and protein expression. Depletion of FOXM1 induced inhibition of the cell growth rate and a decline in oncogenic cyclin D1, cyclin E and CDK2 expression. Conversely, overexpression of FOXM1 enhanced cell proliferation and expression of oncogenic factors, which was decreased upon FOXM1 depletion. Re‑expression of FOXM1 partially rescued suppression of cell proliferation induced by T3. Collectively, the present findings suggest that TH/TR participates in HCC progression via modulation of FOXM1 expression.Although primary open‑angle glaucoma (POAG)‑related mutations in the myocilin (MYOC) gene have been reported, the underlying associations remain poorly understood. In the present study, the relationship between a MYOC mutation and POAG was investigated using ophthalmic examination and total exon gene sequencing in a Chinese family comprised of 5 individuals with POAG and 15 unaffected individuals. Pathogenic mutations underlying POAG were identified by whole‑exome sequencing and subsequently validated by Sanger sequencing. Of the family members, nine (45%) harbored heterozygous p.D208Y mutations; among these, five had POAG and four were unaffected. The mean age at diagnosis was 26.2±4.12 years and the mean intraocular pressure (IOP) was 39.7±16.58 mmHg; all affected members complained of vision loss, headaches and eye swelling. Among the five cases of POAG, two presented with blindness. Among 10 members of the family who underwent comprehensive ophthalmologic examination, 3 individuals exhibited severe visual field defects. The mean age at the time of operation was 27.2±3.54 years. In the present study, a novel MYOC mutation (c.G622T p.D208Y) was identified that was associated with severe visual impairment, high IOP and the need for frequent surgical interventions. Some carriers of the mutation were young and did not show signs of glaucoma. These individuals should be followed‑up to firmly establish whether the mutated gene is pathogenic for POAG.Astrotactin 1 (ASTN1) is known to serve a physiological role in neuronal migration; however its role in liver cancer remains to be determined. In the present study, ASTN1 levels were lower in liver cancer tissues compared with those in matching normal tissue. ASTN1 levels were negatively associated with microscopic vascular invasion, advanced clinical stage and a less favorable prognosis in patients with hepatocellular carcinoma (HCC). Furthermore, ASTN1 overexpression in a liver cancer cell line reduced the migratory and invasive capacity of the cells. Based on bioinformatics analysis, ASTN1 levels were negatively associated with the Wnt signaling pathway. In addition, ASTN1 downregulated the protein expression levels of β‑catenin, T‑cell factor (TCF)1, TCF4, Jun proto‑oncogene (C‑jun), Myc proto‑oncogene (C‑myc), cyclooxygenase‑2 (COX2), metalloproteinase (MMP)2, MMP9 and vascular endothelial growth factor (VEGF) protein levels, indicative of suppression of Wnt signaling. Furthermore, XAV939‑induced Wnt signaling suppression reversed the ASTN1‑mediated inhibition of invasion and migration in cells. Overexpression of ASTN1 in xenografts reduced cancer development as well as Wnt signaling. TIMER analysis showed that ASTN1 expression was negatively correlated with B cell, macrophage and neutrophil infiltrating levels in HCC. Together, the results of the present study showed that ASTN1 reduced the migratory and invasive capacity of liver cancer cells, potentially served as a candidate biomarker for diagnosis and prediction of the prognosis of HCC, and was associated with immune infiltration. Understanding the underlying mechanisms of action of ASTN1 may facilitate the development of novel strategies for prevention and treatment of liver cancer.Lower back pain (LBP) is one of the predominant factors contributing to dyskinesia and remains a serious social and economic burden worldwide. Intervertebral disc degeneration (IDD) is the leading cause of LBP; the existing IDD treatments cannot completely prevent IDD. Circular RNAs (circRNAs) are non‑coding RNAs resulting from back‑splicing with unique structural characteristics and functions. Accumulating evidence suggests that circRNAs are involved in the pathological process of IDD and modulate a range of IDD‑related genes or proteins. However, the underlying circRNA‑mediated regulatory mechanisms remain poorly understood. The aim of the present review is to describe the current understanding of circRNA characteristics, classification, biogenesis and function in relation to its specific roles in IDD. Additionally, the limitations on the current knowledge in the field and the future direction of IDD‑related research are also discussed.Chondrocytes in injured cartilage tissue are susceptible to mechanical loading; mechanical overloading can induce cartilage degeneration. The aim of the present study was to investigate whether mechanical loading can regulate chondrocyte degeneration and angiogenesis via the tissue inhibitor of matrix metalloproteinase‑3 (TIMP3)/transforming growth factor (TGF)‑β1 axis. Primary human chondrocytes were obtained from knee articular cartilage of a healthy donor. Then, normal chondrocytes or TIMP3 lentivirus‑transfected (LV‑TIMP3) chondrocytes were subjected to mechanical loading (10 MPa compression). Then, chondrocytes were stimulated with 1 µg/ml lipopolysaccharide (LPS) or treated with LDN‑193189 (inhibitor of TGF‑β1 signaling pathway). In addition, human umbilical vein endothelial cells (HUVECs) were co‑cultured with chondrocytes or LV‑TIMP3 chondrocytes. The expression levels of collagen‑I, proteoglycan, TIMP3, TGF‑β1, Smad2 and Smad3 were detected by reverse transcription‑quantitative PCR and western blotting.