Stretchable structural colors with polarization dependence using lithium niobate metasurfaces.

Independently tunable biaxial color pixels, composed of isolated nanosquare dimers, are demonstrated in this study. These pixels are capable of displaying a full range of colors under a linear-polarization dependent reflection mode. The metasurface is constructed by arranging LiNbO3 nanodimers on a PDMS substrate. By exciting a strong magnetic dipole (MD) resonance and effectively suppressing other multipolar resonances using surface lattice resonances, the researchers achieved a single reflection peak with a bandwidth of less than 9 nm and a reflective efficiency of up to 99%. Additionally, the stretchability of the PDMS substrate allows for active and continuous tuning of the metasurface by up to 40% strain, covering almost 150 nm of the visible light spectrum and enabling changes in reflection color. This metasurface holds potential applications in various fields, such as color displays, data storage, and anti-counterfeiting technologies.

A quality-comprehensive-evaluation-index-based model for evaluating traditional Chinese medicine quality.

BACKGROUND: Evaluating traditional Chinese medicine (TCM) quality is a powerful method to ensure TCM safety. TCM quality evaluation methods primarily include characterization evaluations and separate physical, chemical, and biological evaluations; however, these approaches have limitations. Nevertheless, researchers have recently integrated evaluation methods, advancing the emergence of frontier research tools, such as TCM quality markers (Q-markers). These studies are largely based on biological activity, with weak correlations between the quality indices and quality. However, these TCM quality indices focus on the individual efficacies of single bioactive components and, therefore, do not accurately represent the TCM quality. Conventionally, provenance, place of origin, preparation, and processing are the key attributes influencing TCM quality. In this study, we identified TCM-attribute-based quality indices and developed a comprehensive multiweighted multi-index-based TCM quality composite evaluation index (QCEI) for grading TCM quality. METHODS: The area of origin, number of growth years, and harvest season are considered key TCM quality attributes. In this study, licorice was the model TCM to investigate the quality indicators associated with key factors that are considered to influence TCM quality using multivariate statistical analysis, identify biological-evaluation-based pharmacological activity indicators by network pharmacology, establish real quality indicators, and develop a QCEI-based model for grading TCM quality using a machine learning model. Finally, to determine whether different licorice quality grades differently reduced the inflammatory response, TNF-α and IL-1ß levels were measured in RAW 264.7 cells using ELISA analysis. RESULTS: The 21 quality indices are suitable candidates for establishing a method for grading licorice quality. A computer model was established using SVM analysis to predict the TCM quality composite evaluation index (TCM QCEI). The tenfold cross validation accuracy was 90.26%. Licorice diameter; total flavonoid content; similarities of HPLC chromatogram fingerprints recorded at 250 and 330 nm; contents of liquiritin apioside, liquiritin, glycyrrhizic acid, and liquiritigenin; and pharmacological activity quality index were identified as the key indices for constructing the model for evaluating licorice quality and determining which model contribution rates were proportionally weighted in the model. The ELISA analysis results preliminarily suggest that the inflammatory responses were likely better reduced by premium-grade than by first-class licorice. CONCLUSIONS: In the present study, traditional sensory characterization and modern standardized processes based on production process and pharmacological efficacy evaluation were integrated for use in the assessment of TCM quality. Multidimensional quality evaluation indices were integrated with a machine learning model to identify key quality indices and their corresponding weight coefficients, to establish a multiweighted multi-index and comprehensive quality index, and to construct a QCEI-based model for grading TCM quality. Our results could facilitate and guide the development of TCM quality control research.

Study on the material basis and action mechanisms of sophora davidii (Franch.) skeels flower extract in the treatment of non-small cell lung cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora davidii (Franch.) Skeels Flower (SDF) is a characteristic folk medicine in Yunnan and Guizhou, which can be used to prevent the occurrence of tumors. The extract of SDF (SDFE) is confirmed to be antitumor by pre-experiment. However, effective components and anticancer mechanisms of SDFE are still unclear. AIM OF THE STUDY: The purpose of this study was to explore the material basis and action mechanisms of SDFE in the treatment of non-small cell carcinoma (NSCLC). MATERIALS AND METHODS: UHPLC-Q-Exactive-Orbitrap-MS/MS was used to identify the chemical components of SDFE. The network pharmacology was applied to screen out the main active components, core genes and related signaling pathways of SDFE in treatment of NSCLC. Molecular docking was used to predict the affinity of major components and core targets. The database was applied to predict the mRNA and protein expression levels of core targets in NSCLC. Finally, the experiments in vitro were performed by CCK-8, flow cytometry and western blot (WB). RESULTS: In this study, 98 chemical components were identified by UHPLC-Q-Exactive- Orbitrap-MS/MS. 5 main active components (namely quercetin, genistein, luteolin, kaempferol, isorhamnetin), 10 core genes (namely TP53, AKT1, STAT3, SRC, MAPK3, EGFR, JUN, EP300, TNF, PIK3R1) and 20 pathways were screened out through network pharmacology. The 5 active ingredients were molecularly docked with the core genes, and most the LibDockScore values were higher than 100. The data collected from the database indicated that TP53, AKT1 and PIK3R1 were closely related to the occurrence of NSCLC. The results of experiment in vitro showed that SDFE promoted NSCLC cells apoptosis by down-regulating the phosphorylation of PI3K, AKT and MDM2, up-regulating the phosphorylation of P53, inhibiting the expression of Bcl-2 and up-regulating the expression of Bax. CONCLUSION: The combination of network pharmacology, molecular docking, database validation, and in vitro experimental validation effectively demonstrates that SDFE can promote cell apoptosis by regulating PI3K-AKT/MDM2-P53 signaling pathway, so as to treat NSCLC.

Correction: Zheng et al. Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis. Cells 2021, 10, 3424.

The authors wish to make the following changes to their paper [...].

7-Ketocholesterol Induces Oxiapoptophagy and Inhibits Osteogenic Differentiation in MC3T3-E1 Cells.

7-Ketocholesterol (7KC) is one of the oxysterols produced by the auto-oxidation of cholesterol during the dysregulation of cholesterol metabolism which has been implicated in the pathological development of osteoporosis (OP). Oxiapoptophagy involving oxidative stress, autophagy, and apoptosis can be induced by 7KC. However, whether 7KC produces negative effects on MC3T3-E1 cells by stimulating oxiapoptophagy is still unclear. In the current study, 7KC was found to significantly decrease the cell viability of MC3T3-E1 cells in a concentration-dependent manner. In addition, 7KC decreased ALP staining and mineralization and down-regulated the protein expression of OPN and RUNX2, inhibiting osteogenic differentiation. 7KC significantly stimulated oxidation and induced autophagy and apoptosis in the cultured MC3T3-E1 cells. Pretreatment with the anti-oxidant acetylcysteine (NAC) could effectively decrease NOX4 and MDA production, enhance SOD activity, ameliorate the expression of autophagy-related factors, decrease apoptotic protein expression, and increase ALP, OPN, and RUNX2 expression, compromising 7KC-induced oxiapoptophagy and osteogenic differentiation inhibition in MC3T3-E1 cells. In summary, 7KC may induce oxiapoptophagy and inhibit osteogenic differentiation in the pathological development of OP.

Integration of UPLC-QE-MS/MS and network pharmacology to investigate the active components and action mechanisms of tea cake extract for treating cough.

The active components and mechanisms of tea cake extract (TCE) were investigated for treating cough. The components of TCE were tentatively identified by ultrahigh-performance liquid chromatography coupled with Q-Exactive MS/MS (UPLC-QE-MS/MS), whose targets were obtained from the Swiss Target Prediction database and the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. Cough-related targets were retrieved from the Gene Cards and Online Mendelian Inheritance in Man database. After the intersection targets had been obtained, enrichment analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined, and the protein-protein interaction network and active compound-intersection target-KEGG pathway network were constructed. Core active compounds and their targets were validated with molecular docking. A total of 78 compounds were identified from TCE, including 24 flavonoids, 17 phenolic acids, 10 alkaloids, seven organic acids, five triterpenes, five amino acids, five coumarins, three carbohydrates, one anthraquinone and one other. A total of 347 intersection targets were obtained. The top five GO terms with the most significant P-values were responses to oxygen-containing compounds and organic substances, chemical and cellular responses to chemical stimulus, and regulation of biological quality. The top five KEGG pathways with the most significant P-values were: the PI3K-Akt signaling pathway, lipids and atherosclerosis, human cytomegalovirus infection, fluid shear stress and atherosclerosis, and proteoglycans in cancer. The top five core active compounds were quercetin, genistein, luteolin, kaempferol and emodin. The top five core targets were protein kinase B (Akt1), prostaglandin-endoperoxide synthase 2 (PTGS2), mitogen-activated protein kinase 1/3 (MAPK1/3) and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). The top five core active compounds could stably bind to their targets with LibDockScores higher than 100. Tea cake extract plays the antitussive role via multiple components and targets. Core targets (AKT1, MAPK1, MAPK3 and PIK3R1) and core components (quercetin, genistein, luteolin and kaempferol) involved in the PI3K-Akt signaling pathway are worth more attention in subsequent validation experiments.

Continuous preparation of a nontoxic magnetic fluid as a dual-mode contrast agent for MRI.

Ultrasmall nanoparticle contrast agents provide dual-mode MRI. However, the application of ultrasmall nanoparticle contrast agents is limited by low manufacturing outputs and cumbersome preparation processes. Herein, we report a novel continuous-flow coprecipitation method for the preparation of the Fe3O4 nanoparticles magnetic fluid (CFCPFe) coated with ultrasmall cysteine-terminated polymethacrylic acid (Cys-PMAA). The preparation process is more coherent, simpler, and less expensive. Compared with magnetic fluids prepared by the conventional method (Cys-PMAA@Fe3O4), CFCPFe has smaller particle sizes (3.27 ± 0.93 nm). Moreover, CFCPFe demonstrates excellent stability for >180 days with different pH values (pH = 2-12) and salt concentrations (up to 2 mol/L). In addition, HEK293T cytotoxicity tests, hemolysis tests, and H&E tissue sections show excellent in vitro and in vivo biocompatibility. In vitro magnetic resonance imaging (MRI) at 1.5 T shows that the r2 value (50.51 mM-1·s-1) of CFCPFe is slightly lower than that of Combidex (r2 = 65 mM-1·s-1) and that the r1 value (9.54 mM-1·s-1) is 2.7 times higher than that of Gd-DTPA (r1 = 3.5 mM-1·s-1). Finally, in vivo imaging shows that CFCPFe reaches the tumor region of the mouse liver cancer model, and a small tumor can be observed in dual-mode imaging. This work offers an effective method for the preparation of a low-cost, stable, and biocompatible ultrasmall contrast agent exhibiting a strong magnetic-imaging effect for dual-mode imaging.

Geniposide ameliorated dexamethasone-induced endoplasmic reticulum stress and mitochondrial apoptosis in osteoblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliver has been traditionally used for treatment of various diseases, including osteoporosis, knee pain, and paralysis. The extract of Eucommia ulmoides has been reported to stimulate the bone formation and suppress the bone resorption, leading to protection against osteoporosis (OP). Geniposide (GEN) has been considered as one of the effective compounds responsible for the therapeutic efficacy of Eucommia ulmoides against OP. AIM OF THE STUDY: To explore whether GEN protected against dexamethasone (DEX)-induced osteoporosis (OP) by activating NRF2 expression and inhibiting endoplasmic reticulum (ER) stress. MATERIALS AND METHODS: The DEX-induced rat OP models were duplicated. The pathological changes were examined by histological/immunohistochemical evaluation and micro-computed tomography (micro-CT) assessment. Apoptosis was detected by a flow cytometer. Mitochondrial Ca2+ concentrations and mitochondrial membrane potential were detected. Western blot assays were used to detect the protein expression. RESULTS: GEN effectively reversed DEX-induced pathological changes of trabecular bone in rats. In addition, the DEX-increased expression of ATF4/CHOP was also ameliorated. In MC3T3-E1 cells, DEX promoted endoplasmic reticulum (ER) stress and mitochondrial apoptosis. Inhibition of ER stress abolished the induction of apoptosis by DEX. Similarly, GEN significantly ameliorated DEX-induced mitochondrial apoptosis. The possible underlying mechanism might be associated with the pharmacological effects of GEN on activating the expression of NRF2 and alleviating ER stress in DEX-treated MC3T3-E1 cells. CONCLUSION: GEN ameliorated DEX-induced ER stress and mitochondrial apoptosis in osteoblasts.

A general procedure for establishing composite quality evaluation indices based on key quality attributes of traditional Chinese medicine.

Licorice, a medicinal herb and food flavor ingredient, has been widely used in traditional Chinese medicine (TCM) for the past 4000 years. In this study, we propose a new quality evaluation approach for licorice quality control based on the key quality attributes commonly used in TCM. The high quality of TCM formulations is ensured by verifying the genuine origin and implementing good agricultural and collection practices for each medicinal herb. In our study, the genuine production area, the harvest season, and the number of growth years were considered the key quality attributes of TCM. To ensure the representativeness of our analysis, we obtained a total of 158 licorice sample batches that differed in the number of growth years, the location of the production areas, and the season for harvesting. Initially, the 158 sample batches were subjected to ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS). A preliminary screen identified 11 licorice compounds related to the three key quality attributes of TCM . An analysis by ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-TQ-MS/MS) verified the presence of 34 compounds in all licorice samples. These 34 compounds included the 11 compounds related to the three key quality attributes of the samples, along with other bioactive components identified in previous studies. After using UHPLC-TQ-MS/MS to assess the signal peak intensities of the 34 compounds, we selected 17 licorice compounds to establish sample content evaluation indices, which were determined by high-performance liquid chromatography at four different wavelengths in all 158 licorice sample batches. Finally, the screen identified nine compounds that were closely associated with the quality attributes of licorice based on principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Our results suggested that liquiritin and eight other compounds could be used as quality control indicators of licorice, which provided a foundation to establish the TCM quality composite evaluation index (TCM QCEI). In summary, this research concept can serve as a reference for research on quality markers and the evaluation of TCM.

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis.

BACKGROUND: Overexposure to glucocorticoid (GC) produces various clinical complications, including osteoporosis (OP), dyslipidemia, and hypercholesterolemia. Geniposide (GEN) is a natural iridoid compound isolated from Eucommia ulmoides. Our previous study found that GEN could alleviate dexamethasone (DEX)-induced differentiation inhibition of MC3T3-E1 cells. However, whether GEN protected against Dex-induced cholesterol accumulation in osteoblasts was still unclear. METHODS: DEX was used to induce rat OP. Micro-CT data was obtained. The ALP activity and mineralization were determined by the staining assays, and the total intracellular cholesterol was determined by the ELISA kits. The protein expression was detected by western blot. RESULTS: GEN ameliorated Dex-induced micro-structure damages and cell differentiation inhibition in the bone trabecula in rats. In MC3T3-E1 cells, Dex enhanced the total intracellular cholesterol, which reduced the activity of cell proliferation and differentiation. Effectively, GEN decreased DEX-induced cholesterol accumulation, enhanced cell differentiation, and upregulated the expression of the GLP-1R/ABCA1 axis. In addition, inhibition of ABAC1 expression reversed the actions of GEN. Treatment with Exendin9-39, a GLP-1R inhibitor, could abrogate the protective activity of GEN. CONCLUSIONS: GEN ameliorated Dex-induced accumulation of cholesterol and inhibition of cell differentiation by mediating the GLP-1R/ABCA1 axis in MC3T3-E1 cells.

5,7,3',4'-tetramethoxyflavone ameliorates cholesterol dysregulation by mediating SIRT1/FOXO3a/ABCA1 signaling in osteoarthritis chondrocytes.

Dyslipidemia has been associated with the development of osteoarthritis. Our previous study found that 5,7,3',4'-tetramethoxyflavone (TMF) exhibited protective activities against the pathological changes of osteoarthritis. Aim: To investigate the roles of TMF in regulating ABCA1-mediated cholesterol metabolism. Methods: Knockdown and overexpression were employed to study gene functions. Protein-protein interaction was investigated by co-immunoprecipitation, and the subcellular locations of proteins were studied by immunofluorescence. Results: IL-1ß decreased ABCA1 expression and induced apoptosis. Therapeutically, TMF ameliorated the effects of IL-1ß. FOXO3a knockdown expression abrogated the effects of TMF, and FOXO3a overexpression increased ABCA1 expression by interacting with LXRα. TMF promoted FOXO3a nuclear translocation by activating SIRT1 expression. Conclusions: TMF ameliorates cholesterol dysregulation by increasing the expression of FOXO3a/LXRα/ABCA1 signaling through SIRT1 in C28/I2 cells.

Nab-paclitaxel promotes the cancer-immunity cycle as a potential immunomodulator.

Paclitaxel is a widely used anti-tumor chemotherapeutic drug. Solvent-based paclitaxel causes bone marrow suppression, allergic reactions, neurotoxicity and systemic toxicity, which are associated with non-specific cytotoxicity and side effects of fat-soluble solvents. Studies have explored various new nano-drug strategies of paclitaxel, including nanoparticle albumin-bound paclitaxel (nab-paclitaxel) to improve the water solubility and safety of paclitaxel. Nab-paclitaxel is a targeted solvent-free formulation that inhibits microtubule depolymerization to anticancer. It is easily taken up by tumor and immune cells owing to the nano-scaled size and superior biocompatibility. The internalized nab-paclitaxel exhibits significant immunostimulatory activities to promote cancer-immunity cycle. The aim of this study was to explore the synergistic effect of nab-paclitaxel in tumor antigen presentation, T cell activation, reversing the immunosuppressive pattern of tumor microenvironment (TME), and the synergistic effect with cytotoxic lymphocytes (CTLs) in clearance of tumor cells. The effects of nab-paclitaxel on modulation of cancer-immunity cycle, provides potential avenues for combined therapeutic rationale to improve efficacy of immunotherapy.

Evolution of time-delay signature of polarized chaos in a unidirectional-coupling VCSEL system with variable-polarization optical injection.

The evolution characteristics of the time-delay signature (TDS) of polarized chaos is systematically investigated in a unidirectional-coupling vertical-cavity surface-emitting (VCSEL) scheme with variable-polarization optical injection (VPOI), by means of the time series, optical spectra, power spectra, and autocorrelation function. In this scheme, the polarized chaos with TDS from a master VCSEL (M-VCSEL) with the external cavity is unidirectionally injected into another solitary slave VCSEL (S-VCSEL) through VPOI. The numerical results show that the VPOI can exert significant influence on the TDS characteristics of polarized chaos in the S-VCSEL. Under special injection parameters, as the polarization injection angle (θp) of VPOI varies, the TDS evolution for the X polarization component can exhibit almost an opposite evolutionary pattern to that for the Y polarization component in the S-VCSEL. A series of TDSs is mapped in the θp plane, and the injection strength and frequency detuning have been simulated to thoroughly elaborate the TDS evolution of polarization-resolved chaos in the S-VCSEL. Moreover, the optimal parameter spaces with effectively suppressed TDS are also determined for each polarization component in those maps.

Network Pharmacology-Based Strategy for Elucidating the Molecular Basis Forthe Pharmacologic Effects of Licorice (Glycyrrhiza spp.).

Licorice (Glycyrrhiza spp.) is used widely in traditional Chinese medicine (TCM) due to its numerous pharmacologic effects. However, the mechanisms of action of the chemical constituents of licorice and their structure-function relationships are not fully understood. To address these points, we analyzed the chemical compounds in licorice listed in the TCM Systems Pharmacology database and TCM Integrated database. Target proteins of the compounds were predicted using Integrative Pharmacology-based Research Platform of TCM v2.0. Information on the pharmacologic effects of licorice was obtained from the 2020 Chinese Pharmacopoeia, and disease-related genes that have been linked to these effects were identified from the Encyclopedia of TCM database. Pathway analyses using the Kyoto Encyclopedia of Genes and Genomes database were carried out for target proteins, and pharmacologic networks were constructed based on drug target-disease-related gene and protein-protein interactions. A total of 451 compounds were analyzed, of which 211 were from the medicinal parts of the licorice plant. The 241 putative targets of 106 bioactive compounds in licorice comprised 52 flavonoids, 47 triterpenoids, and seven coumarins. Four distinct pharmacologic effects of licorice were defined: 61 major hubs were the putative targets of 23 compounds in heat-clearing and detoxifying effects; 68 were targets of six compounds in spleen-invigorating and qi-replenishing effects; 28 were targets of six compounds in phlegm-expulsion and cough-suppressant effects; 25 compounds were targets of six compounds in spasm-relieving and analgesic effects. The major bioactive compounds of licorice were identified by ultra-high-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry. The anti-inflammatory properties of liquiritin apioside, liquiritigenin, glycyrrhizic acid and isoliquiritin apioside were demonstrated by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Liquiritin apioside, liquiritigenin, isoliquiritin, isoliquiritin apioside, kaempferol, and kumatakenin were the main active flavonoids, and 18α- and 18ß-glycyrrhetinic acid were the main active triterpenoids of licorice. The former were associated with heat-clearing and detoxifying effects, whereas the latter were implicated in the other three pharmacologic effects. Thus, the compounds in licorice have distinct pharmacologic effects according to their chemical structure. These results provide a reference for investigating the potential of licorice in treatment of various diseases.

Metabolism and pharmacological activities of the natural health-benefiting compound diosmin.

Diosmin is a famous natural flavonoid for treating chronic venous insufficiency and varicose veins. Recently, extensive study has indicated that diosmin possesses diverse pharmacological activities, including anti-inflammation, anti-oxidation, anti-diabetes, anti-cancer, anti-microorganism, liver protection, neuro-protection, cardiovascular protection, renoprotection, and retinal protection activities. Due to its low water solubility, diosmin is dramatically limited in clinical application. Expectedly, many potential strategies have been developed for improving its pharmacokinetic values and bioavailability. This health-benefiting compound has been explored as the major component of Daflon and micronized purified flavonoid fraction (MPFF), which have been used in clinics to improve micro-circulation. However, no specific drug targets for diosmin are reported, although some potential factors have been involved in screening, such as P-glycoprotein (P-gp), IKKß, acetylcholinesterase (AChE), and aldose reductase (AR). More investigations on the underlying mechanisms of diosmin in mediating cellular processes with high specificity is still needed.

Time-delay signature suppression of polarization-resolved wideband chaos in VCSELs with dual-path chaotic optical injections.

The combining investigation on the time-delay signature (TDS) and chaos bandwidth have been theoretically investigated in a vertical-cavity surface-emitting laser (VCSEL) system with dual-path chaotic optical injections. In this scheme, the polarized chaos with the TDS from an external-cavity master VCSEL is routed into two different paths and then unidirectionally injected into another solitary slave VCSEL. With the aid of the autocorrelation function and the effective bandwidth calculation, the TDS and bandwidth of polarized chaos from the chaotic system are quantitatively evaluated. The results show that, in such a dual-path chaotic optical-injection system, the high-quality polarized chaos with the successful TDS suppression and chaotic bandwidth enhancement can be achieved in wider parameter regions in contrast with the case for the single-path chaotic optical injection. Further research also finds that the injected time-delay difference between two injection paths is desired to mismatch the feedback time delay, which is conducive to suppressing TDS and expanding bandwidth of polarized chaos. Besides, the better chaotic quality with low TDS and wide bandwidth can be expected by choosing the appropriate injection strengths of two injection paths.

The roles of post-translational modifications and coactivators of STAT6 signaling in tumor growth and progression.

Signal transducers and activators of transcription 6 (STAT6) are highly expressed in various tumors and associated with tumorigenesis, immunosuppression, proliferation, metastasis and poor prognosis in human cancers. In response to IL-4/13, STAT6 is phosphorylated, dimerizes and triggers transcriptional regulation after recruitment of coactivators to transcriptosome, such as CBP/p300, SRC-1, PARP-14 and PSF. Post-translational modifications, including phosphorylation, ubiquitination, ADP-ribosylation and acetylation, have been explored for molecular mechanisms of STAT6 in tumor development and management. STAT6 has been developed as a specific biomarker for distinguishing and diagnosing tumor phenotypes, although it is observed to be frequently mutated in metastatic tumors. In this article, we focus mainly on the structural characteristics of STAT6 and its role in tumor growth and progression.

Oxysophocarpine protects airway epithelial cells against inflammation and apoptosis by inhibiting miR-155 expression.

Oxysophocarpine (OSC) has been documented for anti-inflammatory activity. However, the mechanisms of OSC in anti-inflammation are unclear. Aim: To investigate the protective effects of OSC on inflammation and apoptosis induced by lipopolysaccharide in NCI-H292 and human primary airway epithelial cells. Materials & methods: MTT and Annexin V-FITC/PI staining were used to detect cells viability. Inflammatory responses were determined by ELISA. The quantitative real-time PCR (qRT-PCR) and western blot were used to detect mRNA/miRNA and protein expressions respectively. Co-immunoprecipitation was investigated for protein interactions. Results & conclusion: miR-155 mimics significantly induced cell apoptosis, inflammatory responses and MAPK and NF-κB pathways. NDFIP1 was identified as the target of miR-155. OSC protected cells against apoptosis and inflammatory responses and compromised miR-155 activity by attenuating MAPK and NF-κB pathways.

Review on the Structures and Activities of Transthyretin Amyloidogenesis Inhibitors.

Transthyretin (TTR) is a tetrameric protein, and its dissociation, aggregation, deposition, and misfolding are linked to several human amyloid diseases. As the main transporter for thyroxine (T4) in plasma and cerebrospinal fluid, TTR contains two T4-binding sites, which are docked with T4 and subsequently maintain the structural stability of TTR homotetramer. Affected by genetic disorders and detrimental environmental factors, TTR degrades to monomer and/or form amyloid fibrils. Reasonably, stabilization of TTR might be an efficient strategy for the treatment of TTR-related amyloidosis. However, only 10-25% of T4 in the plasma is bound to TTR under physiological conditions. Expectedly, T4 analogs with different structures aiming to bind to T4 pockets may displace the functions of T4. So far, a number of compounds including both natural and synthetic origin have been reported. In this paper, we summarized the potent inhibitors, including bisaryl structure-based compounds, flavonoids, crown ethers, and carboranes, for treating TTR-related amyloid diseases and the combination modes of some compounds binding to TTR protein.