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LINC01272 is a long non-coding RNA (lncRNA) that has been considered as a biomarker for many diseases including lung squamous cell carcinoma. Here, we investigated the function and mechanism of LINC01272 on lung cancer (LC). The differential expression of LINC01272 in LC and normal samples was analyzed by GEPIA based on the data from TCGA-LUAD database, as survival prognosis was analyzed through Kaplan-Meier Plotter. LINC01272 overexpression plasmid and miR-7-5p mimic were transfected into A549 and PC-9 cells. LINC01272, miR-7-5p and cardiolipin synthase 1 (CRLS1) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction. Cell viability was detected through MTT assay. Cell multiplication was evaluated by cell formation assay. Cell apoptosis was assessed through flow cytometry assay. Through bioinformatics, the target miRNA of LINC01272 and downstream genes of miR-7-5p were predicted. The targeting relationship was tested by dual luciferase reporter analysis. CRLS1, B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax) and cleaved caspase-3 protein levels were detected through western blot. LINC01272 was downregulated in LC and low LINC01272 expression had poor prognosis. In A549 and PC-9 cells, LINC01272 inhibited cell viability and multiplication and induced apoptosis. LINC01272 negatively regulated miR-7-5p and CRLS1 was a target of miR-7-5p. MiR-7-5p reversed the effect of LINC01272 on viability, multiplication, apoptosis and expression of miR-7-5p and CRLS1 as well as apoptosis-related factors (Bcl-2, Bax and cleaved caspase-3). LINC01272 suppressed cell multiplication and induced apoptosis via regulating the miR-7-5p/CRLS1 axis in LC.

Aims: Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression-induced damage in rat nucleus pulposus (NP) cells., Materials and Methods: Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca 2+ ] i ) were determined by fluorescent probes DCFH-DA, JC-1 and Fluo-3/AM, respectively. Apoptosis-related proteins (cleaved caspase-3, cytosolic cytochrome c, Bax and Bcl-2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot., Key Findings: Edaravone attenuated the compression-induced decrease in viability of NP cells in a dose-dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression-induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression-induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca 2+ ] i . In addition, edaravone promoted the expression of aggrecan and collagen II in compression-treated NP cells., Significance: These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Hepatic ischemia–reperfusion injury (HIRI) is the main reason for organ failure following liver surgery; however, its underlying causes are complex, and include oxidative stress, sterile inflammatory, and mitochondrial damage. Unfortunately, treatments for HIRI are based on supportive therapy, and no specific drugs or methods are currently available. Chlorogenic acid (CGA) is a dietary polyphenol with a wide range of pharmacological effects and it has a protective effect on HIRI; however, its specific mechanism remains unclear. In this study, we investigated that CGA pretreatment exerts protective effects against HIRI and the potential underlying mechanisms. We found that CGA pretreatment reduced ALT, AST, MDA, TNF-α, and IL-1β levels following HIRI, improved SOD and GSH levels, and alleviated pathological liver tissue damage, with the highest CGA dose (100 mg/kg.d) exerted the strongest effect. In addition, we showed that CGA pretreatment significantly decreased the levels of reactive oxygen species following HIRI, inhibited HMGB1 release by decreasing IRF-1 expression, inhibited the expression of HMGB1, TLR-4, MyD88, P-IκB-α, NF-κB P65, and P-P65, and promoted IκB-α degradation. Thus, CGA appears to inhibit oxidative stress and inflammatory responses during HIRI. Furthermore, we found that CGA pretreatment reduced hepatocyte apoptosis following HIRI, alleviated mitochondrial damage, promoted BCL-2 expression, inhibited Bax upregulation, and inhibited cytochrome C release to prevent caspase activation, thereby reducing the expression of the caspase-independent pathway components, ENDOG and AIF. Together, our findings suggest that CGA can protect against HIRI by inhibiting oxidative stress, the HMGB1/TLR-4/NF-κB signaling pathway–mediated inflammatory responses, and mitochondria-mediated apoptosis. Thus, CGA appears to be a promising therapeutic approach for treating HIRI. [ABSTRACT FROM AUTHOR]

Background: Many circular RNAs (circRNAs) have been identified as potential targets for cancer therapy. However, the role of circ_0002476 in non–small cell lung cancer (NSCLC) progression has not been explored. Methods: The expression levels of circ_0002476, microRNA (miR)‐1182, and mitochondrial transcription factor A (TFAM) were detected by quantitative real‐time polymerase chain reaction. Cell functions were measured by cell counting kit 8 assay, EdU assay, colony formation assay, flow cytometry and transwell assay. Mitochondrial DNA (mtDNA) damage was assessed by measuring mtDNA copy number and transcript levels of ND1 and ATP6. Protein expression was examined by western blot. The interaction between miR‐1182 and circ_0002476 or TFAM was detected by dual‐luciferase reporter assay and RNA pull‐down assay. Animal experiments were performed to explore circ_0002476 role in vivo. Exosomes (Exs) were extracted and identified by transmission electron microscopy and nanoparticle tracking analysis. Results: Circ_0002476 was overexpressed in NSCLC tissues and cells. Circ_0002476 knockdown suppressed NSCLC cell proliferation and invasion, while promoted apoptosis and mtDNA damage. Circ_0002476 could sponge miR‐1182, and miR‐1182 inhibitor reversed the influence induced by circ_0002476 knockdown. Moreover, TFAM was targeted by miR‐1182, and miR‐1182 hindered NSCLC cell progression by regulating TFAM. Additionally, circ_0002476 silencing could reduce NSCLC tumor growth by miR‐1182/TFAM. Further analyzed showed that Exs were involved in the transport of circ_0002476 between cells. Conclusion: Taken together, our findings suggested that circ_0002476 might be a potential molecular target for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Background: Compound Turkish gall ointment (CTGO) has a long history of being widely used as a folk medicine in Xinjiang for the treatment of eczema. CTGO is currently in the pre-investigational new drug application stage, but its pharmacological mechanisms of action have not yet been clarified. Methods: First, a sensitive and reliable ultra-high performance liquid chromatography-Q exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) technique was established. Second, an integrative strategy of network analysis and molecular docking based on identified and retrieved ingredients was implemented to investigate the potential targets and pathways involved in the treatment of eczema with CTGO. Finally, Sprague–Dawley (SD) rats with eczema were prepared to verify the predicted results. The skin conditions of the rats were observed, evaluated, and scored. Skin tissues were observed by hematoxylin–eosin (HE) staining, and the levels of serum interferon-γ (IFN-γ) and interleukin-4 (IL-4) were determined by enzyme-linked immunosorbent assay (ELISA). The expression levels of toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Results: A total of 29 compounds were identified. We found 38 active components and 58 targets for the treatment of eczema, which included 118 signaling pathways related to inflammation, immunity, and apoptosis. CTGO significantly improved the skin surface and histopathological characteristics of eczema-affected rats, downregulated the expression of IL-4, TLR4, NF-κB (p65), IL-1β, and TNF-α, and upregulated the expression level of IFN-γ. Conclusion: We predicted and validated our prediction that CTGO may be used to treat eczema by affecting the TLR4/NF-κB signaling pathway, which provides guidance for future experimental studies. [ABSTRACT FROM AUTHOR]

Significance: Ample evidence has demonstrated an important role for autophagy as either a protective mechanism or a cause for hepatotoxicity, denoting the likely potentials for targeting autophagy in the prevention or treatment of hepatotoxicity. Recent Advances: The functional role of autophagy in the pathogenesis of hepatotoxicity has been gradually recognized. Mechanistically, the autophagy-mediated protective or promoting effect on hepatotoxicity is attributed to its functions in regulation of oxidative stress, endoplasmic reticulum (ER) stress, lipid metabolism, iron homeostasis, inflammatory response, and programmed cell death. Targeting autophagy as a novel strategy for fighting against hepatotoxicity has demonstrated encouraging efficacy in a number of models. Critical Issues: Clarifying the precise functional role of autophagy in different types of hepatotoxicity is essential for developing a type-specific autophagy-based intervention. Identification of molecular targets and novel agents for effectively and accurately manipulating autophagy is needed for better utilization of an autophagy-based approach to exert beneficial effects on hepatotoxicity. Future Directions: Well-designed clinical trials are needed to validate the efficacy of an autophagy-targeting intervention strategy for hepatotoxicity. Further studies should be also focused on developing novel autophagy-targeting agents that can accurately regulate autophagy based on the characteristics of each type of hepatotoxicity. Antioxid. Redox Signal. 38, 1082–1100. [ABSTRACT FROM AUTHOR]

RBBP6 (retinoblastoma binding protein 6, also known as PACT or P2P-R in humans) is a multi-domain protein that functions in multiple processes, such as mitosis, cell differentiation, and cell apoptosis. RBBP6 is evolutionarily conserved and is present in unicellular organisms to mammals. Studies of RBBP6 have mostly focused on its RB- and p53-binding domains, which are found exclusively in mammals. Here, we investigated the C. elegans homolog of RBBP6 to explore the functional roles of its other domains. We found that RBPL-1, the homolog of RBBP6 in C. elegans, is indispensable for worm development. RNAi silencing of rbpl-1 led to embryonic lethality, as well as defects in oocyte production and intestine development. rbpl-1 RNAi worms showed defects in germ cell proliferation, suggesting that RBPL-1 regulates mitosis. Moreover, RNAi silencing of rbpl-1 inhibited nutrient synthesis in the worm intestine. RBPL-1, as a nucleolus protein, was found to be expressed in diverse tissues and necessary for both germline and soma development. Using microarray analysis, we identified ≈700 genes whose expression levels were changed at least 10-fold in rbpl-1 worms. We propose that RBPL-1, like its yeast homolog, may regulate gene expression as an mRNA cleavage and polyadenylation factor. Taken together, the findings from this study reveal that RBPL-1 plays a pivotal role in C. elegans germline and soma development, suggesting that the functions of RBBP6 are conserved in diverse eukaryotic species. [ABSTRACT FROM AUTHOR]

A homogenous polysaccharide (APP), with a molecular weight of 120 kDa, was isolated from the dried aerial parts of Agrimonia pilosa . Gas chromatography (GC) and GC–MS analysis revealed that APP has a backbone of 1,3-linked Glcp and 1,3, 6-linked Glc p , and branched with 1-linked Glc p terminal along the main chain in a relative ratio of 2:1:1. We investigated the response of human osteosarcoma U-2 OS cells to APP treatment. MTT result showed that APP significantly inhibited cell viability in a concentration dependent manner via induction of apoptotic death in U-2 OS cells, as determined by annexin V/propidium iodide (PI) staining. Western blot analysis also indicated that APP CRA increased in Bax/Bcl-2 ratios by up-regulating Bax expression and triggered the release of cytochrome c from mitochondria into the cytoplasm. Moreover, APP supplement induced the activation of caspase-3, and −9, but not caspase-8 in U-2 OS cells. Likewise, APP administration significantly suppressed tumor growth in BALB/C nude mice bearing U-2 OS xenograft tumors. All these results indicate that APP-induced apoptosis is associated with the activation of a caspase-3-mediated mitochondrial pathway. [ABSTRACT FROM AUTHOR]