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Background: It has been widely shared that the dysregulation of circular RNA (circRNA) may contribute to the progression of osteoarthritis (OA). OA is characterized by persistent chondrocyte injury. We aimed to clarify the role of circTBX5 in IL-1β-induced chondrocyte injury. Methods: The expression of circTBX5, miR-558 and MyD88 mRNA was measured using quantitative real-time PCR (qPCR). Cell viability, proliferation and apoptosis were assessed by CCK-8, EdU or flow cytometry assay. The protein levels of extracellular matrix (ECM)-associated markers, MyD88, IkBα, p65 and phosphorylated IkBα were measured by western blot. The release of inflammatory factors was assessed by ELISA. The targets of circTBX5 were screened by RIP and pull-down assay. The putative binding between miR-558 and circTBX5 or MyD88 was validated by dual-luciferase reporter assay. Results: CircTBX5 and MyD88 were enhanced, while miR-558 was downregulated in OA cartilage tissues and IL-1β-treated C28/I2 cells. IL-1β induced C28/I2 cell injury by impairing cell viability and proliferation and promoting cell apoptosis, ECM degradation and inflammatory response, while circTBX5 knockdown alleviated IL-1β induced injury. CircTBX5 bound to miR-558 to regulate IL-1β induced cell injury. In addition, MyD88 was a target of miR-558, and circTBX5 targeted miR-558 to positively regulate MyD88 expression. MiR-558 enrichment attenuated IL-1β induced injury by sequestering MyD88 expression. Moreover, circTBX5 knockdown weakened the activity of NF-κB signaling, while miR-558 inhibition or MyD88 overexpression recovered the activity of NF-κB signaling. Conclusion: CircTBX5 knockdown modulated the miR-558/MyD88 axis to alleviate IL-1β induced chondrocyte apoptosis, ECM degradation and inflammation via inactivating the NF-кB signaling pathway. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common malignancies in women, and exhibits high metastasis, recurrence and fatality rates. Novel therapies for breast cancer are constantly emerging, such as targeted therapy, oncolytic virotherapy, and immunotherapy. Despite their potential, these new therapies are still in their infancy, and chemotherapy remains the standard treatment for breast cancer. Therefore, it is of great significance to develop safe and efficient treatment drugs or adjuvants for breast cancer treatment. Traditional Chinese medicine (TCM) has a long clinical history in China, in which Scutellaria baicalensis Georgi exhibits favorable antibreast cancer activities. We therefore conducted a systematic review of the available literature to better understand the molecular mechanisms of S. baicalensis in breast cancer treatment. S. baicalensis and its active components (baicalein, baicalin, wogonin, wogonoside, oroxylin A and scutellarin) exhibited promising antibreast cancer activity through proliferation inhibition, apoptosis induction, invasion and metastasis blockading, and drug-resistance and non-coding RNA regulation. Additionally, senescence, autophagy, angiogenesis, and glycolysis mechanisms were observed to play a role in their antibreast cancer activity. Furthermore, multiple signaling pathways contributed to the antitumor effects of S. baicalensi, such as the NF- κ B, Wnt/ β -catenin, SATB1, Bcl2 family proteins, Caspase, PI3K/Akt, mTOR, ERK, p38-MAPK, TGF- β /Smad, and Hippo/YAP pathways. This review provides valuable insights into the role of S. baicalensis as a breast cancer treatment and acts as a foundation for further investigations in this field. [ABSTRACT FROM AUTHOR]

Zhibai Dihuang Granule (ZDG) is known as traditional Chinese patent medicine with the functions of "Ziyin decrease internal heat" in Traditional Chinses medicine. In clinical, it is also used to treat various kidney diseases. We aimed to provide a basis for the curative effect of ZDG on acute kidney injury induced by cisplatin (CIAKI). The active compounds and protein targets of ZDG, as well as the potential targets of the CIAKI were searched from the database. The protein-protein interaction (PPI) network diagram and the drug-compounds-targets-disease network were constructed. Enrichment analysis was performed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the effect of ZDG on the prevention and treatment of CIAKI was experimentally validated in vivo and in vitro. From the database, we screened 22 active compounds of ZDG and 226 related targets. We obtained 498 gene targets related to CIAKI, among which 40 genes overlapped with ZDG-related targets. Go enrichment and KEGG analysis got 339 terms and 64 pathways, respectively. Based on the above study, we speculated that ZDG has the potential effect on treatment CIAKI, and the mechanism may be related to cell apoptosis and inflammation. The results in vitro experiments showed that ZDG reduced the cytotoxicity of cisplatin to HK-2 and 293T cells, but did not affect the antitumor effect of cisplatin. Moreover, in vivo experiments further proved that ZDG effectively controlled kidney damage caused by cisplatin in SD rats. The results showed that ZDG could regulate the expression of CASP3, p65 and MAPK pathway related proteins, suggesting that ZDG's prevention of CIAKI may be related to apoptosis and inflammatory response. Our study showed that ZDG could prevent and treat CIAKI by inhibiting cell apoptosis and inflammation, which provided a new efficacy and clinical application for ZDG. [Display omitted] [ABSTRACT FROM AUTHOR]