Potential safety concerns of volatile constituents released from coffee-ground-blended single-use biodegradable drinking straws: A chemical space perspective.

Incorporating spent coffee grounds into single-use drinking straws for enhanced biodegradability also raises safety concerns due to increased chemical complexity. Here, volatile organic compounds (VOCs) present in coffee ground straws (CGS), polylactic acid straws (PLAS), and polypropylene straws (PPS) were characterized using headspace - solid-phase microextraction and migration assays, by which 430 and 153 VOCs of 10 chemical categories were identified by gas chromatography - mass spectrometry, respectively. Further, the VOCs were assessed for potential genetic toxicity by quantitative structure-activity relationship profiling and estimated daily intake (EDI) calculation, revealing that the VOCs identified in the CGS generally triggered the most structural alerts of genetic toxicity, and the EDIs of 37.9% of which exceeded the threshold of 0.15 µg person-1 d-1, also outnumbering that of the PLAS and PPS. Finally, 14 VOCs were prioritized due to their definite hazards, and generally higher EDIs or detection frequencies in the CGS. Meanwhile, the probability of producing safer CGS was also illustrated. Moreover, it was uncovered by chemical space that the VOCs with higher risk potentials tended to gather in the region defined by the molecular descriptor related to electronegativity or octanol/water partition coefficient. Our results provided valuable references to improve the chemical safety of the CGS, to promote consumer health, and to advance the sustainable development of food contact materials.

Huangqi Decoction, a compound Chinese herbal medicine, inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-ß axis.

OBJECTIVE: Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-ß/small mothers against decapentaplegic (TGF-ß/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-ß/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis. METHODS: The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-ß/Smad signaling pathway-related proteins were determined using Western blotting. RESULTS: Lnc-C18orf26-1 was upregulated in TGF-ß1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-ß1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-ß1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-ß1, TGF-ß type I receptor (TGF-ßRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment. CONCLUSION: Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-ß1/TGF-ßRI/p-Smad2 axis.

Intermittent pressure imitating rolling manipulation ameliorates injury in skeletal muscle cells through oxidative stress and lipid metabolism signalling pathways.

BACKGROUND: Traditional Chinese medicine manipulation (TCMM) is often used to treat human skeletal muscle injury, but its mechanism remains unclear due to difficulty standardizing and quantifying manipulation parameters. METHODS: Here, dexamethasone sodium phosphate (DSP) was utilized to induce human skeletal muscle cell (HSkMC) impairments. Cells in a three-dimensional environment were divided into the control normal group (CNG), control injured group (CIG) and rolling manipulation group (RMG). The RMG was exposed to intermittent pressure imitating rolling manipulation (IPIRM) of TCMM via the FX­5000™ compression system. Skeletal muscle damage was assessed via the cell proliferation rate, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and creatine kinase (CK) activity. Isobaric tagging for relative and absolute protein quantification (iTRAQ) and bioinformatic analysis were used to evaluate differentially expressed proteins (DEPs). RESULTS: Higher-pressure IPIRM ameliorated the skeletal muscle cell injury induced by 1.2 mM DSP. Thirteen common DEPs after IPIRM were selected. Key biological processes, molecular functions, cellular components, and pathways were identified as mechanisms underlying the protective effect of TCMM against skeletal muscle damage. Some processes (response to oxidative stress, response to wounding, response to stress and lipid metabolism signalling pathways) were related to skeletal muscle cell injury. Western blotting for 4 DEPs confirmed the reliability of iTRAQ. CONCLUSIONS: Higher-pressure IPIRM downregulated the CD36, Hsp27 and FABP4 proteins in oxidative stress and lipid metabolism pathways, alleviating excessive oxidative stress and lipid metabolism disorder in injured HSkMCs. The techniques used in this study might provide novel insights into the mechanism of TCMM.

Glycyrrhetinic Acid-Induced MiR-663a Alleviates Hepatic Stellate Cell Activation by Attenuating the TGF-ß/Smad Signaling Pathway.

Glycyrrhetinic acid (GA), a hydrolysate of glycyrrhizic acid from licorice root extract, has been used to treat liver fibrotic diseases. However, the molecular mechanism involved in the antifibrotic effects of GA remains unclear. The involvement of miR-663a and its roles in TGF-ß-1-induced hepatic stellate cell (HSC) activation remains unclear. In this study, we investigated the roles of miR-663a in the activation of HSCs and the antifibrosis mechanism of GA. MiR-663a expression was downregulated in TGF-ß-treated HSCs. The overexpression of miR-663a inhibited HSC proliferation. TGF-ß-1was confirmed as a direct target gene of miR-663a. MiR-663a alleviated HSC activation, concomitant with decreased expression of α-smooth muscle actin (α-SMA), human α2 (I) collagen (COL1A2), TGF-ß1, TGF-ßRI, Smad4, p-Smad2, and p-Smad3. GA upregulated miR-663a expression and inhibited the TGF-ß/Smad pathway in HSCs. Further studies showed that miR-663a inhibitor treatment reversed GA-mediated downregulation of TGF-ß1, TGF-ßRI, Smad4, p-Smad2, p-Smad3, α-SMA, and CoL1A2 in TGF-ß1-treated HSCs. These results show that miR-663a suppresses HSC proliferation and activation and the TGF-ß/Smad signaling pathway, highlighting that miR-663a can be utilized as a therapeutic target for hepatic fibrosis. GA inhibits, at least in part, HSC proliferation and activation via targeting the miR-663a/TGF-ß/Smad signaling pathway.

A network pharmacology approach to investigating the mechanism of Tanshinone IIA for the treatment of liver fibrosis.

ETHNOPHARMACOLOGICAL REVELVANCE: Tanshinone IIA (TIIA) is a major component extracted from the traditional herbal medicine salvia miltiorrhiza (Danshen), which activates blood circulation and treats chronic hepatitis and liver fibrosis. However, the underlying molecular mechanism of TIIA against hepatic fibrosis is still largely unknown. AIM OF THE STUDY: The present study aimed to evaluate the antifibrotic effects of TIIA in liver fibrosis and investigate its underlying mechanism through network pharmacology-based prediction and experimental verification. MATERIALS AND METHODS: In this study, a "TIIA-targets-liver fibrosis" network was constructed by combining the TIIA-specific and hepatic fibrosis-specific targets with protein-protein interactions (PPIS), and network pharmacology was applied to identify the potential targets and mechanisms of TIIA in the treatment of hepatic fibrosis. The antifibrotic effect of TIIA was investigated in CCl4-induced liver fibrosis in rats in vivo and in the human HSC line LX2 in vitro. RESULTS: We identified 75 potential targets of TIIA and 1382 targets of liver fibrosis. Subsequently, the 29 target proteins that overlapped between the potential TIIA targets and the liver fibrosis targets indicated that TIIA has potential antifibrotic effects through regulating multiple targets, including c-Jun, c-Myc, CCND1, MMP9 and P65. Pathway and functional enrichment analysis of these putative targets showed that TIIA could regulate the MAPK, PI3K/Akt and Wnt signaling pathways. Consistently, in vivo and in vitro experiments indicated that TIIA attenuated CCl4-induced liver injury and fibrosis and inhibited hepatic stellate cell (HSC) proliferation and activation; these findings were concomitant with the decreased expression of α-smooth muscle actin (α-SMA) and human α2 (I) collagen (COL1A2). Moreover, TIIA remarkably downregulated the expression of c-Jun, c-Myc, MMP9, PI3K and P38 proteins, which were upregulated in CCl4-induced hepatic fibrosis in vivo. TIIA significantly downregulated the expression of c-Jun, p-c-Jun, c-Myc, CCND1, MMP9, P65, P-P65, PI3K and P38 proteins, which were upregulated during HSC activation in vitro. CONCLUSION: Our study demonstrated that TIIA could significantly improve liver function, decrease liver injury, alleviate ECM accumulation, and attenuate HSC proliferation and activation, thus exerting an antifibrotic effect. The possible molecular mechanism involved MAPK, Wnt and PI3K/Akt signaling pathways via inhibiting c-Jun, p-c-Jun, c-Myc, CCND1, MMP9, P65, P-P65, PI3K and P38. Overall, our results suggest that TIIA could alleviate liver fibrosis through multiple targets and multiple signaling pathways and provide deep insight into the pharmacological mechanisms of TIIA in the treatment of hepatic fibrosis.

Preventive and therapeutic role of Tanshinone â ¡A in hepatology.

Liver diseases cause serious public health problems because of their high global prevalence and poor long-term clinical outcomes. With its mild and broad therapeutic efficacy, traditional Chinese medicine (TCM) has played an important role in the prevention and treatment of liver diseases in China for hundreds of years. Tanshinone IIA (TIIA), a major component extracted from the traditional herbal medicine Salvia miltiorrhiza Bunge, has been broadly studied for its multiple biological activities, including antiangiogenic, antioxidant, anti-inflammatory and anticancer properties. In this article, we focus on the effects of TIIA on the development of liver diseases, including hepatic injury, fatty liver, hepatic fibrosis and hepatocellular carcinoma (HCC), as well as the mechanism underlying TIIA and its new formulations and carriers in order to provide a reference for its further study and clinical therapeutic use in liver diseases.