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Since 2005, GLP-1 receptor (GLP-1R) agonists (GLP-1RAs) have been developed as therapeutic agents for type 2 diabetes (T2D). GLP-1R is not only expressed in pancreatic islets but also other organs, especially the lung. However, controversy on extra-pancreatic GLP-1R expression still needs to be further resolved, utilizing different tools including the use of more reliable GLP-1R antibodies in immune-staining and co-immune-staining. Extra-pancreatic expression of GLP-1R has triggered extensive investigations on extra-pancreatic functions of GLP-1RAs, aiming to repurpose them into therapeutic agents for other disorders. Extensive studies have demonstrated promising anti-inflammatory features of GLP-1RAs. Whether those features are directly mediated by GLP-1R expressed in immune cells also remains controversial. Following a brief review on GLP-1 as an incretin hormone and the development of GLP-1RAs as therapeutic agents for T2D, we have summarized our current understanding of the anti-inflammatory features of GLP-1RAs and commented on the controversy on extra-pancreatic GLP-1R expression. The main part of this review is a literature discussion on GLP-1RA utilization in animal models with chronic airway diseases and acute lung injuries, including studies on the combined use of mesenchymal stem cell (MSC) based therapy. This is followed by a brief summary. T2D drugs known as GLP-1RAs can target GLP-1R which is abundantly expressed in the lung, making them strong candidates as repurposed drugs for chronic airway disorders and acute lung injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Indole-3-propionic acid (IPA), a microbiota-produced tryptophan metabolite, has been shown to exhibit cardioprotective effects in animal models. However, the relation of IPA with cardiovascular risk in humans is currently unknown. Objectives This prospective study aimed to investigate whether plasma tryptophan and IPA levels are associated with decreased risks of mortality. Methods Ultra-HPLC-MS/MS was used to measure plasma tryptophan and IPA levels in 1829 patients with coronary artery disease (CAD). Cox proportional hazards regression models were used to estimate the associations between tryptophan and IPA levels and the risks of cardiovascular and all-cause mortality. Results During the median 9.2-year follow-up, 424 all-cause deaths occurred, of which 272 were cardiovascular deaths. Plasma tryptophan and IPA levels were significantly associated with reduced risks of cardiovascular and all-cause mortality. Patients with CAD with the highest quartiles of tryptophan and IPA levels had multivariable-adjusted HRs of 0.62 (95% CI, 0.43–0.89) and 0.71 (95% CI, 0.50–0.99), respectively, for cardiovascular mortality and 0.67 (95% CI, 0.50–0.90) and 0.75 (95% CI, 0.57–0.99), respectively, for all-cause mortality compared with those in patients with CAD in the lowest quartile. After multivariable adjustments, 1-SD increases in the continuous plasma tryptophan and IPA levels were associated with 16% and 14% decreases, respectively, in the risks of cardiovascular mortality and with 13% and 14% decreases, respectively, in the risks of all-cause mortality. Restricted cubic splines displayed linear associations between plasma tryptophan and IPA levels and cardiovascular and all-cause mortality among patients with CAD. Conclusions Our findings suggest that plasma tryptophan and IPA levels are significantly associated with decreased risks of cardiovascular and all-cause mortality in patients with CAD. Further studies are needed to determine the clinical diagnostic and therapeutic values of tryptophan and IPA levels on the risks of mortality among patients with CAD. [ABSTRACT FROM AUTHOR]

Most azobenzene derivatives require the use of ultraviolet light for photoisomerization, this limits the utilization of them in biological systems, energy-storing material fields and so on. It’s useful to develop azo-based photo-switches triggered with visible light. Three synthesized azobenzene derivatives (tetra-o-methoxyl-4,4′-diacetamidoazobenzene, 5,6-dihydrodibenzo[c,g][1,2]diazocine and 3,5-dimethyl-bisazo) who can be driven by visible light were studied by DFT calculations in this article. We found that they all have the same structural features of the twisted azobenzene trans geometries. The planarity of azobenzene, which can be reflected by ϕ C N N C (the dihedral angle connecting the azo moiety and two phenyl rings) and θ C C N N (the dihedral angle connecting the azo moiety and one of the phenyl rings). To better understand the relationship between structure and optical properties, absorption spectra of azobenzene in vacuum as the function of ϕ C N N C and θ C C N N rotation were investigated by using DFT and TDDFT methods. Calculations demonstrated that distorting ϕ C N N C and θ C C N N can both result in the red shift of the absorption bands to the visible light wavelength, and ϕ C N N C has a greater impact than θ C C N N . Furthermore, the influence of twisted structure on the absorption band of 4-(4-aminophenylazo) nitrobenzene (a D-π-A type azobenzene derivative) in DMSO solution was also studied. Our results indicated that both ϕ C N N C and θ C C N N ( NH 2 ) rotation decreased the HOMO–LUMO gap, causing a red shift of the S 0 → S 1 absorption band. However, the θ C C N N ( NO 2 ) rotation increased the HOMO–LUMO gap slightly, resulting in a little blue shift of the whole bands. This work may provide useful theoretical foundation for fabricating of new visible light driven azobenzene-based photo-switches. [ABSTRACT FROM AUTHOR]

It is desirable to research the photoswitchable supramolecular catalysts by theoretical methods. The azobis-(benzo-18-crown-6) ether (butterfly-AZO for short) combined with the alkaline earth metal cations (Mg 2+ , Ca 2+ , Sr 2+ and Ba 2+ ) investigated by using both density functional theory (DFT) and reactive molecular dynamics (reactive MD) simulations in this article. DFT calculations demonstrated that butterfly-AZO⋯Ba 2+ is a suitable photocontrol catalytic candidate and its isomerization is mainly controlled by the N N rotational mechanism. Furthermore, 100 independent reactive MD simulations demonstrated that 100% trans isomers of butterfly-AZO⋯Ba 2+ translated to the cis forms, in good agreement with the experimental data of ∼95%. [ABSTRACT FROM AUTHOR]

The preparation of switchable azobenzene derivatives driven by visible light is desirable for applications in biomolecular systems. o -R-substituted 4,4′-diacetamidoazobenzene derivatives (R H, CH 3 , OCH 3 or OH) were investigated by using both density functional theory (DFT) and reactive molecular dynamics simulations. DFT calculations demonstrated that the nonplanar azo trans geometric structure, which caused by bulky groups tetra substituted in the ortho-position, is the key factor to enable the trans → cis transition with visible light. Furthermore, 100 independent reactive MD simulations demonstrated that 71% trans isomers of tetra o -OCH 3 -substituted 4,4′-diacetamidoazobenzene translated to cis , in good agreement with the experimental data. [ABSTRACT FROM AUTHOR]

[Display omitted] Resveratrol (RSV) is a dietary polyphenol with well-documented cardio-protective activity, but its effects on blood cholesterol levels remain to be established. Due to its poor bioavailability, tissue accumulation of RSV is extremely low except for that in the small intestine. In the present study, we aimed to investigate the dose-dependent effects of RSV on blood cholesterol levels and the involvement of small intestine in the cholesterol-lowering impacts of RSV. Mice were administrated with RSV at various doses with high-fat diet (HFD) or high-fat and high-cholesterol diet (HCD) for 12 weeks. The fecal neutral sterol contents were analyzed, and intestinal perfusion test was performed. An enteric barrier model using Caco-2 cells was established. We observed that RSV reduced blood cholesterol levels in a dose-dependent manner in mice fed with HFD or HCD. Further investigation revealed that RSV administration increased the bile acid pool size but did not affect cholesterol consumption or de novo cholesterol synthesis. Interestingly, RSV promoted trans -intestinal cholesterol excretion (TICE) by 2-fold in the intestinal perfusion test. In addition, RSV upregulated the expressions of ATP-binding cassette sub-family G member 5 or 8 (Abcg5/8) and ATP-binding cassette sub-family B member 1a or 1b (Abcb1a/b) by up to 8 times in the duodenum mucosa but not in the liver. RSV also significantly downregulated the expression of intestinal Niemann-Pick C1-Like 1 (Npc1l1). Knock-down of liver X receptor alpha (LXRα) but not Sirt1 by siRNA significantly blocked RSV-induced cholesterol excretion in Caco-2 cells. In conclusion, RSV could decrease circulating cholesterol levels through enhancing TICE and limiting cholesterol absorption via selective activation of intestinal LXRα. [ABSTRACT FROM AUTHOR]

• DFT studies were carried out for the novel derivatives of the azobenzene photoswitch. • Possible design rules were given for future synthesis of photoswitches in the visible. • The rotational pathway was demonstrated as the main method for the isomerization of bridged azobenzene. To reduce the damage from UV light and develop biocompatible visible light driven azobenzene-based photo-switches for biomedical applications, bridged azobenzene derivatives were designed and systematically studied by density functional theory (DFT). The influence of bridge length on geometric structures, absorption spectra and photoisomerization mechanism were investigated. DFT calculations demonstrated that bridged azobenzene derivative with one carbon atom (C1) and two carbon atoms (C2) were optimal candidate for visible light driven photo-switches in this work. Furthermore, the bridge has not changed the main isomerization of azobenzene, i.e. the torsion path. [ABSTRACT FROM AUTHOR]

China is dealing with a serious aging issue. Social participation is essential for active aging. The health status of spouses is intertwined with the trajectory of the social function of the elderly. This study examined the association between spouse health and social participation among older Chinese adults. The study also explored the mediating role of loneliness and anxiety between spousal health and social participation. The analytic sample included 6125 adults aged 60 years and above. Prospective data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). First, we described basic socio-demographic information about the sample. Secondly, Spearman's correlation analysis was used to determine whether correlations existed between spousal health, loneliness, anxiety, and social participation. Finally, mediation analysis was run using the SPSS macro PROCESS program. Spousal health, loneliness, anxiety, and social participation were significantly correlated (P < 0.01). Spousal health could not only have a direct positive impact on social participation in older adults (β = 0.239, 95 % CI: 0.120, 0.359), but also indirectly on social participation through three pathways: an independent mediating effect of loneliness (β = 0.020, 95 % CI: 0.009, 0.034), an independent mediating effect of anxiety (β = 0.018, 95%CI: 0.009, 0.032), and a chain mediating effect of loneliness and anxiety (β = 0.004, 95%CI: 0.002, 0.007). This study suggests paying more attention to elderly couples and decreasing the negative consequences of changes in spousal health. • The social participation of elders is linked to their spouse's health. • The effects of social participation are mediated by loneliness and anxiety. • Promote family-centred programs as a means of responding to active aging. [ABSTRACT FROM AUTHOR]

In this study, a synthetic steroidal glycoside SBF-1 had strong and preferential antitumor effects on the human chronic myeloid leukemia (CML) cell line K562 and its imatinib-resistant form K562/G. SBF-1 induced apoptosis in both cell lines without any effect on cell cycle arrest. It also inhibited the activation of PI3K/Akt pathway members, such as PI3K and Akt, as well as downstream targets mTOR and Bcl-2. Moreover, the degradation of the Bcr-Abl protein was induced by SBF-1 in a concentration- and time-dependent manner. Using a pull-down assay, SBF-1 was found to bind to both Bcr-Abl and PTP1B and disrupted the interaction between them. SBF-1 triggered the degradation of Bcr-Abl through ubiquitination via the lysosome pathway. Taking together these findings, this study, for the first time, suggests that the blockade of the interaction between Bcr-Abl and PTP1B may be a feasible strategy for the treatment of CML, especially CML with resistance to Bcr-Abl kinase inhibitor imatinib. Our study also indicates that SBF-1 may serve as a leading compound for novel anti-CML therapeutic agents. [ABSTRACT FROM AUTHOR]

Adropin has been reported to be involved in metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). However, the clinical relevance of adropin expression to the histological severity of NAFLD is unclear. This study aimed to investigate adropin expression in biopsy-proven NAFLD patients. This case-control study enrolled a total of 109 participants, including 15 normal histological controls, 26 nonalcoholic fatty liver (NAFL), 21 nonalcoholic steatohepatitis (NASH) subjects and B-ultrasound NAFLD-free normal controls matched to the cases based on age and sex (the case:control ratio was 1:1). Liver biopsies were obtained and histological characteristics were assessed. Primary murine hepatocytes were isolated from C57BL/6J mice and incubated with doses of palmitate to induce oxidative stress. The serum adropin level in NASH patients was 9.99 ± 5.51 ng/ml, significantly lower than that in B-ultrasound normal controls (22.70 ± 6.32 ng/ml), histological normal controls (21.93 ± 6.63 ng/ml) and NAFL patients (17.82 ± 6.90 ng/ml). Serum adropin levels were negatively correlated with the histological severity of NAFLD. The lower serum adropin level predicted NASH (area under the ROC curve: 87.1%). Adropin expression in serum and liver was also negatively associated with hepatic MDA and serum 8-iso-PGF2α levels. Furthermore, palmitate rather than oleate induced oxidative stress in a dose-dependent manner with a gradient decrease in adropin expression in primary murine hepatocytes. Adropin overexpression or treatment ameliorated palmitate-induced oxidative stress in hepatocytes. Circulating adropin was inversely associated with the oxidative stress and histological severity of NAFLD. It may play an important role in the development of NAFLD. Image 1 • Serum adropin levels were lowered in NASH patients and might be able to predict NASH. • Circulating adropin was inversely correlated with oxidative stress and histological severity of NAFLD. • Oxidative stress induced by palmitate decreased adropin expression in hepatocytes. • Adropin overexpression or treatment alleviated the oxidative stress caused by palmitate in hepatocytes. [ABSTRACT FROM AUTHOR]

Background Understanding the function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancers. Here, we studied the contribution of basal autophagy in human liposarcoma. Methods The levels of basal autophagy were analyzed by measuring autophagy-related protein expression and autophagosome formation. TP53INP2 expression was determined by real-time PCR, western blot and tissue microarray. Genetic inhibition or overexpression of TP53INP2 was performed to examine its effects on autophagic activity and cell growth. Results Compared with human liposarcoma cell line SW872, low level of basal autophagy were present in SW872-S cells with high malignancy. Moreover, a decrease of TP53INP2 expression was found accompanying liposarcoma malignant progression in cell lines and primary tissues. TP53INP2 expression was required for autophagic activity in liposarcoma cells. Autophagy inhibition with chloroquine suppressed the growth of liposarcoma cells. TP53INP2-related basal autophagy rendered liposarcoma cells to be more resistant to bortezomib-induced inhibition of cell growth. Conclusions The results reveal the association of TP53INP2-related basal autophagy with cell growth and malignant progression of human liposarcoma, which helps re-evaluate targeting autophagy for cancer therapy, and suggest that TP53INP2 expression might be used as a prognostic marker to predict human liposarcoma malignancies. [ABSTRACT FROM AUTHOR]

• Non-toxic acellular design of a dual crosslinked hyaluronic acid (HA) hydrogel • Hydrogen phosphate ions form physical crosslinks with cystamine-crosslinked HA • Salt treatment is non-toxic and generates cell-migrating aggregated structures • Physical crosslinks act as a nucleation site for hydroxyapatite mineralisation • Hydroxyapatite crystals were accomplished across the hydrogel in simulated body fluid The creation of hyaluronic acid (HA)-based materials as biomineralisation scaffolds for cost-effective hard tissue regenerative therapies remains a key biomedical challenge. A non-toxic and simple acellular method to generate specific hydrogen phosphate (HPO 4 2−) interactions within the polymer network of cystamine-crosslinked HA hydrogels is reported. Reinforced dual crosslinked hydrogel networks were accomplished after 4-week incubation in disodium phosphate-supplemented solutions that notably enabled the mineralisation of hydroxyapatite (HAp) crystals across the entire hydrogel structure. HPO 4 2−–cystamine-crosslinked HA hydrogen bond interactions were confirmed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and density functional theory (DFT) calculations. HPO 4 2−-mediated physical crosslinks proved to serve as a first nucleation step for acellular hydrogel mineralisation in simulated body fluid allowing HAp crystals to be detected by X-ray powder diffraction (2θ = 27°, 33° and 35°) and visualised with density gradient across the entire hydrogel network. On a cellular level, the presence of aggregated structures proved key to inducing ATDC 5 cell migration whilst no toxic response was observed after 3-week culture. This mild and facile ion-mediated stabilisation of HA-based hydrogels has significant potential for accelerated hard tissue repair in vivo and provides a new perspective in the design of dual crosslinked mechanically competent hydrogels. [ABSTRACT FROM AUTHOR]

Organic-inorganic perovskite solar cell materials have attracted considerable attention in recent years. Ag and Au are commonly employed as the counter electrode in such cells. In this study, molecular dynamics simulation were used to investigate the diffusion properties of Ag ions in α-CsPbI 3. Ag ions have the highest diffusion coefficient at temperatures between 318 K and 358 K. Density functional theory calculations were performed to study the effects of Ag diffusion on the band structures, crystal structures and optical absorption spectra of α-CsPbI 3 materials. The results suggest that, Ag ions have diffusion coefficients ranging from 0.6 × 10−6 cm2 × s−1 to 1.1 × 10−6 cm2 × s−1 in α-CsPbI 3 at temperatures between 278 K and 398 K. Ag doping can insert a Ag dopant level in α-CsPbI 3 and reduce the band gap of α-CsPbI 3. Furthermore, increasing the Ag content could reduce the energy gap between the Ag dopant level and the valence band or conduction band. • Treat Ag as a dopant to study the Ag diffusion effect in α-CsPbI3. • Using both DFT and MD simulation to discuss the Ag diffusion effect in α-CsPbI3. [ABSTRACT FROM AUTHOR]