Pioglitazone may have potential benefits as an alternative therapeutic treatment for patients with Alzheimer's disease (AD), particularly in individuals that also have comorbid diabetes; however, the mechanisms of action remain unclear. The present study aimed to explore the effects of pioglitazone on amyloid β, isoform 42 (Aβ42) deposition in rats with diet‑induced insulin resistance (IR). Diet‑induced IR model rats were established in the presence or absence of pioglitazone. Plasma glucose and insulin levels, and cerebrospinal fluid insulin levels were measured; in addition, hippocampal tissues were collected for immunohistochemical analysis of Aβ42 expression. The levels of insulin‑degrading enzyme (IDE) and peroxisome proliferator‑activated receptor γ (PPARγ) mRNA and protein expression were analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, the activation of glycogen synthase kinase 3β (GSK3β) induced by phosphatidylinositol 3‑kinase (PI3K) /protein kinase B (AKT) signaling was detected by western blotting. Results from the present study demonstrated that pioglitazone may enhance peripheral and brain insulin sensitivity in diet‑induced IR model rats. Treatment with pioglitazone ameliorated Aβ42 deposition in the hippocampus by increasing IDE and PPARγ expression. Notably, activation of the PI3K/AKT/GSK3β pathway was also demonstrated to serve a role in pioglitazone‑induced Aβ42 degradation, which was abrogated by the PPARγ antagonist GW9662. Results from the present study indicated that pioglitazone may improve insulin sensitivity and ameliorate Aβ42 accumulation in rats with diet‑induced IR by regulating AKT/GSK3β activation, suggesting that pioglitazone may be a promising drug for AD treatment.

Objective Interleukin 34 (IL-34) and microRNA 21 (miR-21) were found to be involved in the pathological process of rheumatoid arthritis (RA), but the details were unclear. In this study, we aimed to clarify the relationship between IL-34 and miR-21 in RA. Methods IL-34 concentrations in serum and synovial fluid (SF) of patients with RA were measured by ELISA. Fibroblast-like synovial cells (FLS) were cultured for evaluation of STAT3 activation, miR-21, and Bax/Bcl-2 expression by Western blot and real-time PCR. Correlations were analyzed between clinical features and detectable variables including SF IL-34 levels and miR-21 expression. Results SF IL-34 levels were significantly higher in patients with RA who had a high 28-joint Disease Activity Score (DAS28 ≥ 3.2) than in those with a lower DAS28 (DAS28 < 3.2). DAS28 scores and miR-21 expression in FLS had a significant positive correlation with the SF IL-34 levels. In addition, IL-34 stimulation strengthened the activation of p-STAT3, resulting in the increment of miR-21 expression. Inhibiting of miR-21 expression contributed to decreased Bcl-2/Bax ratio, suggesting that miR-21 was involved in the resistance to apoptosis. With the blocking of the colony-stimulating factor-1 receptor (CSF1R), decreased protein expressions including CSF1R, p-STAT3/STAT3, and Bcl-2/Bax were shown, suggesting that CSF1R participated in the biological functions of IL-34 in RA. Conclusion The IL-34/STAT3/miR-21 pathway is crucial for the survival of synovial fibroblasts in RA, which might be candidate therapeutic targets for RA treatment.

Colon carcinoma is one of the most common cancers worldwide. Epidemiological studies have revealed that colon cancer is the third leading cause of cancer‑related deaths, which is due to the increased incidence and mortality rates. However, the treatment strategies for colon cancer remain unsatisfactory for patients, especially for those with advanced or recurrent colon cancer. Dysregulated microRNAs (miRNAs) are considered to influence tumor development and metastasis. However, the molecular mechanism through which miRNAs affect cancer progression is not yet completely understood. The aim of the present study was to investigate the expression levels of has‑miR‑15a‑5p and its molecular mechanism in colon cell carcinoma. In the present study, the expression levels of hsa‑miR‑15a‑5p were found to be decreased in colon tumor tissues and cancer cell lines. Hsa‑miR‑15a‑5p overexpression inhibited colon cell proliferation and migration. Mechanistically, the G1/S‑specific cyclin‑D1 (CCND1) gene was predicted as a target of hsa‑miR‑15a‑5p, as evidenced by bioinformatics and dual‑luciferase reporter assay analyses. CCND1 overexpression significantly increased the progression of colon cancer. Furthermore, CCND1 was demonstrated to mediate the effects of hsa‑miR‑15a‑5p on colon cancer cells. The present study demonstrated that hsa‑miR‑15a‑5p alleviated the proliferation, migration and invasion of colon cancer by targeting the CCND1 gene, which represents a potential molecular target for the diagnosis and treatment of colon cancer.

Objective: Sinomenine (SIN), an alkaloid isolated from sinomenium acutum plant, possesses many pharmacological properties, such as anti-inflammation, anti-hyperalgesia, anti-allergy, anti-apoptosis, and anti-angiogenesis. In this study, we aimed to investigate the detailed molecular mechanisms associated with the anti-inflammatory activity of SIN in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Methods: RAW264.7 cells were treated with LPS and/or indicated concentrations of SIN. Inflammatory cytokine production, such as TNF-α, IL-1β, and IL-6, was detected by ELISA. Expression of microRNA-155 (miR-155), SOCS1 and NF-κB was assessed by qRT-PCR and Western blot, separately. Simultaneously, miR-155 inhibitor and SOCS1 SiRNA were transfected to observe the regulative effects of SIN on the expression of miR-155, SOCS1, and NF-κB. Results: Our result showed that SIN treatment significantly reduced LPS-induced inflammatory cytokine release, suppressed the expression of miR-155, enhanced SOCS1 expression at mRNA and protein levels, and prevented NF-ĸB transcription. Furthermore, transfection of miR-155 inhibitor and SOCS1 SiRNA emphasized that the regulation of miR-155, SOCS1, and NF-ĸB was associated with the anti-inflammatory activation of SIN in LPS-treated macrophages. Conclusions: This study indicated that SIN alleviated LPS-induced inflammatory responses in RAW264.7 macrophages by downregulating miR-155 and upregulating SOCS1, at least partly, leading to the suppression of NF-ĸB transcription. These findings suggest that SIN might be developed as an alternative and promising drug for the treatment of inflammatory diseases.