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Purpose: This study aims to evaluate the value of tissue inhibitors of MMPs-2 (TIMP-2) to indicate 5-Fluorouracil (5-Fu) resistance status in colorectal cancer. Methods: The 5-Fu resistance of colorectal cancer cell lines was detected using Cell-Counting Kit-8 (CCK-8) and calculated using IC50. Enzyme-linked immunosorbent assay (ELISA) and real time-quantitative polymerase chain reaction (RT-qPCR) were used to detect TIMP-2 expression level in the culture supernatant and serum. Twenty-two colorectal cancer patients' TIMP-2 levels and clinical characteristics were analyzed before and after chemotherapy. Additionally, the patient-derived xenograft (PDX) model of 5-Fu resistance was used to evaluate the feasibility of TIMP-2 as a predictive biomarker of 5-Fu resistance. Results: Our experimental results display that TIMP-2 expression is elevated in colorectal cancer drug-resistant cell lines, and its expression level is closely related to 5-Fu resistance. Moreover, TIMP-2 in colorectal cancer patient serum undergoing 5-Fu-based chemotherapy could indicate their drug resistance status, and its efficacy is higher than CEA and CA19-9. Finally, PDX model animal experiments reveal that TIMP-2 can detect 5-Fu resistance in colorectal cancer earlier than tumor volume. Conclusion: TIMP-2 is a good indicator of 5-Fu resistance in colorectal cancer. Monitoring the serum TIMP-2 level can help the clinician identify 5-Fu resistance in colorectal cancer patients earlier during chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a chronic infection initiated by oral bacterial and their virulence factors, yet the severity of periodontitis is largely determined by the dysregulated host immuno-inflammatory response. Baicalein is a flavonoid extracted from Scutellaria baicalensis with promising anti-inflammatory properties. This study aims to clarify the anti-inflammatory and osteogenic effects of baicalein in periodontal ligament cells (PDLCs) treated with lipopolysaccharides (LPS). Methods: Human PDLCs were incubated with baicalein (0–100 μM) for 2 h prior to LPS challenge for 24 h. MTT analysis was adopted to assess the cytoxicity of baicalein. The mRNA and protein expression of inflammatory and osteogenic markers were measured by real-time polymerase chain reaction (PCR), western blot and enzyme-linked immunosorbent assay (ELISA) as appropriate. Alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were performed to evaluate the osteogenic differentiation of PDLCs. The expression of Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signaling related proteins was assessed by western blot. Results: MTT results showed that baicalein up to 100 μM had no cytotoxicity on PDLCs. Baicalein significantly attenuated the inflammatory factors induced by LPS, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloprotein-1 (MMP-1), MMP-2 and monocyte chemoattractant protein 1 (MCP-1) at both mRNA and protein level. Moreover, MAPK signaling (ERK, JNK and p38) was significantly inhibited by baicalein, which may account for the mitigated inflammatory response. Next, we found that baicalein effectively restored the osteogenic differentiation of LPS-treated PDLCs, as shown by the increased ALP and ARS staining. Accordingly, the protein and gene expression of osteogenic markers, namely runt-related transcription factor 2 (RUNX2), collagen-I, and osterix were markedly upregulated. Importantly, baicalein could function as the Wnt/β-catenin signaling activator, which may lead to the increased osteoblastic differentiation of PDLCs. Conclusions: With the limitation of the study, we provide in vitro evidence that baicalein ameliorates inflammatory response and restores osteogenesis in PDLCs challenged with LPS, indicating its potential use as the host response modulator for the management of periodontitis. [ABSTRACT FROM AUTHOR]

Amorphophalli Rhizoma (APR) is widely used as an adjuvant treatment for advanced and metastatic triple-negative breast cancer (TNBC), but its effects, potential active ingredients, and mechanism of action on estrogen receptor-positive (ER+) and human epidermal growth factor receptor-positive (HER2+) breast cancer cells were not reported. The present study investigated the effects and mechanism of APR on ER+ and HER2+ breast cancer cells. Rotary evaporation was used to prepare different extracts of APR. Cell activity was assessed using the cell counting kit-8 (CCK-8) method. Wound healing assays were used to assess cell migration, and a cell invasion assay was performed using a Transwell chamber with Matrigel matrix. A xenograft model was used to analyze the inhibitory effects of APR on tumor growth. Bioinformatics analyses were used to explore the potential mechanism of APR in breast cancer. RT–qPCR and Western blotting were performed to reveal the molecular mechanism. The ethyl acetate extract of APR showed the strongest tumor inhibitory effect on ER+ and HER2+ breast cancer cells compared to petroleum ether or N-butanol extracts. APR inhibited ER+ and HER2+ breast cancer cell growth, proliferation, migration, and invasion via the phosphatidylinositol-3 kinase (PI3K)/AKT pathway. APR had a significant inhibitory effect on ER+ and HER2+ breast cancer cells via the PI3K/AKT signaling pathway. Therefore, APR may be useful for preventing ER+ and HER2+ breast tumor growth, proliferation, migration, and invasion. [Display omitted] • APR inhibited cell growth, proliferation, migration, and invasion in ER + breast cancer cells. • APR inhibited cell growth, proliferation, migration, and invasion in HER2+ breast cancer cells. • APR activated the PI3K/AKT signaling pathway. • Different extracts have different cytotoxicity to different types of breast cancer cells. • Different cytotoxicity plays a key role in the accurate treatment of breast cancer. [ABSTRACT FROM AUTHOR]