Abnormal hyperplasia of fibroblast-like synoviocytes (FLS) leads to the progression of rheumatoid arthritis (RA). This study aimed to investigate the role of miR-124a in the pathogenesis of RA. The viability and cell cycle of FLS in rheumatoid arthritis (RAFLS) were evaluated by Cell Counting Kit 8 and flow cytometry assay. The expression of PIK3CA, Akt, and NF-κB in RAFLS was examined by real-time PCR and Western blot analysis. The production of tumour necrosis factor (TNF)-α and interleukin (IL)-6 was detected by ELISA. The joint swelling and inflammation in collagen-induced arthritis (CIA) mice were examined by histological and immunohistochemical analysis. We found that miR-124a suppressed the viability and proliferation of RAFLS and increased the percentage of cells in the G1 phase. miR-124a suppressed PIK3CA 3'UTR luciferase reporter activity and decreased the expression of PIK3CA at mRNA and protein levels. Furthermore, miR-124a inhibited the expression of the key components of the PIK3/Akt/NF-κB signal pathway and inhibited the expression of pro-inflammatory factors TNF-α and IL-6. Local overexpression of miR-124a in the joints of CIA mice inhibited inflammation and promoted apoptosis in FLS by decreasing PIK3CA expression. In conclusion, miR-124a inhibits the proliferation and inflammation in RAFLS via targeting PIK3/NF-κB pathway. miR-124a is a promising therapeutic target for RA.

Signal transducer and activator of transcription 3 (STAT3), a transcriptional factor involved in tumorigenesis and cancer stemness formation, contributes to drug resistance in cancer therapies. STAT3 not only mediates gene transcription but also participates in microRNA suppression. This study identified a STAT3-downstream micro RNA (miRNA) involved in drug resistance against regorafenib in colorectal cancer stem-like tumorspheres. Small RNAseq was used to investigate differential microRNAs in colorectal cancer cell-derived tumorspheres and in a STAT3-knockdown strain. The miRNA-mediated genes were identified by comparing RNAseq data with gene targets predicted using TargetScan. Assays for detecting cell viability and apoptosis were used to validate findings. The formation of colorectal cancer stem-like tumorspheres was inhibited by BBI608, a STAT3 inhibitor, but not by regorafenib. Additional investigations for microRNA expression demonstrated an increase in 10 miRNAs and a decrease in 13 miRNAs in HT29-derived tumorspheres. A comparison of small RNAseq results between tumorspheres and HT29shSTAT3 cells revealed the presence of four STAT3-mediated miRNAs in HT29-derived tumorspheres: hsa-miR-215-5p, hsa-miR-4521, and hsa-miR-215-3p were upregulated, whereas miR-30a-5p was downregulated. Furthermore, hsa-miR-4521 was associated with poor overall survival probability, and miR-30a-5p was associated with better overall survival probability in patients with rectum cancer. Comparisons of RNAseq findings between HCT116- and HT29-derived tumorspheres revealed that HSPA5 were mediated by the STAT3-miR-30a-5p axis, which is overexpressed in colorectal tumorspheres associating to anti-apoptosis. In addition, the transfection of miR-30a-5p and inhibition of HSPA5 by HA15 significantly reduced cell viability and increased apoptosis in HT29 cells. In conclusion, a STAT3-miR-30a-5p-HSPA5 axis was observed against regorafenib-mediated apoptosis in colorectal cancer tumorspheres. The expression of miR-30a-5p was repressed by STAT3; in addition, HSPA5 was identified as the target gene of miR-30a-5p and contributed to both tumorsphere formation and anti-apoptosis.

The one-step HPS test exhibited a high sensitivity and low specificity compared with the other tests, indicating that it is not sufficiently accurate for use in a clinical setting for diagnosing H. pylori infection. However, the test is simple to use (requiring only a saliva sample), inexpensive, and noninvasive in its application, and thus appealing for use in population-based prevalence surveys of the epidemiology of H. pylori infection.

Benign pancreatic hyperenzymemia, or Gullo's syndrome, is an uncommon syndrome characterized by a long-term increase of serum pancreatic enzyme in the absence of pancreatic diseases. It is primarily discovered incidentally and occurs in either sporadic or familial form. Herein, we report the first case of benign pancreatic hyperenzymemia in Taiwan. A 57-year-old Chinese male was incidentally noted with elevated serum amylase and lipase levels during a health check-up and was diagnosed with benign pancreatic hyperenzymemia using a series of image and serological tests. Although this is the first case of benign pancreatic hyperenzymemia in Taiwan, its prevalence may be underestimated due to the diagnostic difficulties. Correct diagnosis of this disease is important to avoid costly test duplication, unfounded anxieties, and multiple consultations.

STAT3 is a transcriptional factor involved in tumorigenesis and the initiation of cancer stemness property. However, the STAT3-downstream regulatory gene expressions in the formation of colorectal cancer (CRC)-derived tumorsphere is obscure.In this study, RNAseq was used to uncover the potential genes involved in the formation of colorectal HCT116-and HT29-derived stem-like tumorspheres, whereas HCT116 and HT29 overexpressed CD133. Furthermore, STAT3 was knockdowned and analyzed consequently by RNAseq for picking up the STAT3-mediated genes associated with tumorspheres formation. Then, quantitative polymerase chain reaction was used for validating the expressions of selected driver genes in epidermal growth factor (EGF) treated-and in STAT3-knockdowned HT29 cells. We found that 654 genes and 646 genes were upregulated in HCT116-and HT29-derived tumorspheres, respectively. There were 103 genes simultaneously increased in both CRC tumorspheres, including, STAT3 selected as a driver gene by NetworkAnalyst (https://www.networkanalyst.ca/). Moreover, there were 139 genes downregulated in HT29shSTAT3 cells compared to HT29shLuc cells, 12 of the genes were overlapped with the overexpressed 103 genes from tumorspheres, including, NDRG1,

No abstract

No abstract

No abstract