Role and mechanism of COL3A1 in regulating the growth, metastasis, and drug sensitivity in cisplatin-resistant non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is among the most difficult malignancies to treat. Type III collagen (COL3A1) can affect the progression and chemoresistance development of NSCLC. We herein explored the mechanism that drives COL3A1 dysregulation in NSCLC. Potential RNA-binding proteins (RBPs) and transcription factors (TFs) that could bind to COL3A1 were searched by bioinformatics. mRNA expression was detected by quantitative PCR. Protein expression was evaluated using immunoblotting and immunohistochemistry. The effects of the variables were assessed by gauging cell growth, invasiveness, migratory capacity, apoptosis, and cisplatin (DDP) sensitivity. The direct YY1/COL3A1 relationship was confirmed by ChIP and luciferase reporter experiments. Xenograft experiments were done to examine COL3A1's function in DDP efficacy. COL3A1 showed enhanced expression in DDP-resistant NSCLC. In H460/DDP and A549/DDP cells, downregulation of COL3A1 exerted inhibitory functions in cell growth, invasiveness, and migration, as well as promoting effects on cell DDP sensitivity and apoptosis. Mechanistically, ELAV-like RNA binding protein 1 (ELAVL1) enhanced the mRNA stability and expression of COL3A1, and Yin Yang 1 (YY1) promoted the transcription and expression of COL3A1. Furthermore, upregulation of COL3A1 reversed ELAVL1 inhibition- or YY1 deficiency-mediated functions in DDP-resistant NSCLC cells. Additionally, COL3A1 downregulation enhanced the anti-tumor efficacy of DDP in vivo. Our investigation demonstrates that COL3A1 upregulation, induced by both RBP ELAVL1 and TF YY1, exerts important functions in phenotypes of NSCLC cells with DDP resistance, offering an innovative opportunity in the treatment of drug-resistant NSCLC.

Triptolide restrains the growth, invasion, stemness, and glycolysis of non-small cell lung cancer cells by PFKFB2-mediated PI3K/AKT pathway.

Triptolide (TP) has been found to have anti-tumor effects. However, more potential molecular mechanisms of TP in the progression of non-small cell lung cancer (NSCLC) deserve further investigation. Cell proliferation, apoptosis, invasion, and stemness were detected by cell counting kit 8 assay, EdU assay, flow cytometry, transwell assay, and sphere formation assay. Cell glycolysis was evaluated by corresponding assay kits. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) expression was measured by western blot (WB), qRT-PCR and immunohistochemical staining. PI3K/AKT pathway-related markers were determined by WB. Besides, xenograft tumor model was conducted to evaluate the anti-tumor effect of TP in NSCLC. Our results revealed that TP treatment suppressed NSCLC cell proliferation, invasion, stemness, glycolysis, and enhanced apoptosis. PFKFB2 was upregulated in NSCLC tissues and cells, and its expression was decreased by TP. PFKFB2 knockdown restrained NSCLC cell functions, and its overexpression also eliminated TP-mediated NSCLC cell functions inhibition. TP decreased PFKFB2 expression to inactivate PI3K/AKT pathway. Moreover, PI3K/AKT pathway inhibitor LY294002 also could reverse the promoting effect of PFKFB2 on NSCLC cell functions. In addition, TP suppressed NSCLC tumorigenesis by inhibiting PFKFB2/PI3K/AKT pathway. In conclusion, TP exerted anti-tumor role in NSCLC, which was achieved by reducing PFKFB2 expression to inactivate PI3K/AKT pathway.

The redox requirement and regulation during cell proliferation.

The intracellular metabolic network comprises a variety of reduction-oxidation (redox) reactions that occur in a temporally and spatially distinct manner. In order to coordinate these redox processes, mammalian cells utilize a collection of electron-carrying molecules common to many redox reactions, including NAD, NADP, coenzyme Q (CoQ), and glutathione (GSH). This review considers the metabolic basis of redox regulation in the context of cell proliferation by analyzing how cells acquire and utilize electron carriers to maintain directional carbon flux, sustain reductive biosynthesis, and support antioxidant defense. Elucidating the redox requirement during cell proliferation can advance the understanding of human diseases such as cancer, and reveal effective therapeutic opportunities in the clinic.

Effectiveness and safety of traditional Chinese medicines for non-alcoholic fatty liver disease: Protocol for systematic review and meta-analysis.

BACKGROUND: Previous reviews indicate that the effect of Traditional Chinese medicines (TCM) on non-alcoholic fatty liver disease (NAFLD) remains uncertainty. The study results published in the past 8 years may change this situation, but there is no updated systematic review. Therefore, we designed this study to systematically evaluate the effectiveness and safety of TCM in the treatment of NAFLD. METHODS AND ANALYSIS: We will search nine online databases from inception to October 01 2019, and the language will not be restricted on included trials. Randomized controlled trials that included patients with NAFLD receiving TCM therapy versus a control group will be included. Two researcher will perform independently the selection of studies, risk of bias assessment and data extraction. We will use the RevMan V.5.2 software with fixed effects model or random effects model according to the heterogeneity test to conduct the data synthesis. We will present the dichotomous data and the continuous data with risk ratios with 95% CIs and weighted mean differences or standardized mean differences with 95% CIs. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system will be used to evaluate the evidence quality with low risk, unclear risk, and high risk. RESULTS: This study will demonstrate an evidence-based review of TCM for NAFLD. CONCLUSION: The study will provide clear evidence to assess the effectiveness and side effects of TCM for NAFLD.

Patterned FeNi soft magnetic strips film with tunable resonance frequency from 1 to 10.6 GHz.

Soft magnetic films with a wide-range tunable ferromagnetic resonance frequency are suitable for miniaturization and multifunctionalization of microwave integrated circuits. Fabrication of these films for high-frequency applications is usually complicated and difficult. We demonstrate a simple method to fabricate patterned FeNi soft magnetic strip films by magnetron sputtering and photolithography. Films prepared by this method exhibits a tunable in-plane uniaxial magnetic anisotropy (IPUMA) for different strip widths and gaps. As the strip widths changing from 500 to 2 µm, the IPUMA field increases monotonically from 2.2 to 576 Oe and resonance frequency from 1 to 10.6 GHz(which covers four microwave bands, including the L,S,C and X bands) respectively. This ultra-wide-range adjustability of resonance frequency can be attributed to shape anisotropy of strips. Considering that FeNi alloy has relatively low magnetocrystalline anisotropy, so a wider adjustable range of resonance frequency could be obtained using materials with stronger magnetocrystalline anisotropy.