Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease.

Chronic and recurrent inflammatory disorders of the gastrointestinal tract caused by a complex interplay between genetics and intestinal dysbiosis are called inflammatory bowel disease. As a result of the interaction between the liver and the gut microbiota, bile acids are an atypical class of steroids produced in mammals and traditionally known for their function in food absorption. With the development of genomics and metabolomics, more and more data suggest that the pathophysiological mechanisms of inflammatory bowel disease are regulated by bile acids and their receptors. Bile acids operate as signalling molecules by activating a variety of bile acid receptors that impact intestinal flora, epithelial barrier function, and intestinal immunology. Inflammatory bowel disease can be treated in new ways by using these potential molecules. This paper mainly discusses the increasing function of bile acids and their receptors in inflammatory bowel disease and their prospective therapeutic applications. In addition, we explore bile acid metabolism and the interaction of bile acids and the gut microbiota.

miR-3682-3p Activated by c-Myc Aggravates the Migration and Stemness in Hepatocellular Carcinoma Cells by Regulating PTEN/PI3K/AKT/ß-Catenin Signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cancer worldwide. miRNA has been linked to cancer processes. We want to figure out what the underlying mechanism and functions of miR-3682-3p are in HCC. METHODS: Thirty pairs of tumor tissues and adjacent tissues were obtained from HCC patients. mRNA and protein expressions were detected by quantitative real-time PCR and Western blot, respectively. The migration and invasion were measured using transwell or wound-healing assays. Dual luciferase and ChIP assays were utilized to detect gene interactions. RESULTS: miR-3682-3p was highly expressed in HCC tissues and cell lines. Silencing of miR-3682-3p inhibited cell migration and invasion, increased E-cadherin expression, and decreased N-cadherin, vimentin, and snail expressions, as well as the SOX2, OCT4, and Bmi1 expression, thereby restraining EMT and stemness of HCC in vitro. miR-3682-3p was positively activated by c-Myc and could directly target PTEN to activate PI3K/AKT/ß-catenin pathway. In addition, inhibition of PTEN weakened the anti-migration and anti-stemness effects of miR-3682-3p downregulation in HCC cells. CONCLUSION: miR-3682-3p promoted HCC migration and stemness through PTEN/PI3K/AKT/ß-catenin signaling, implying that miR-3682-3p might be a promising target for HCC clinical treatment.

LncRNA SNHG16 promotes colorectal cancer cell proliferation, migration, and epithelial-mesenchymal transition through miR-124-3p/MCP-1.

Colorectal cancer (CRC) has been the third leading cause of cancer-associated deaths. LncRNA SNHG16 is reported to be involved in metastasis of CRC cells. However, the mechanism by which SNHG16 regulates CRC progression is poorly understood. The proliferation of CRC cells was examined by MTT. Wound healing and transwell assay were used to measure migration and invasion ability. RT-qPCR and western blot were used to examine gene expression. Immunofluorescence was conducted to evaluate the EMT of CRC cells. Luciferase reporter assay were used to confirm direct interaction between miR-124-3p and SNHG16 or MCP-1. The interaction between miR-124-3p and SNHG16 was detected by RIP and RNA pull down assay. H&E staining was used to test the histomorphological changes of hepatic metastatic nodules. Finally, xenograft tumor experiment was utilized to determine tumor growth in vivo. SNHG16 and miR-124-3p were dysregulated in human colorectal tumors or cells. Knockdown of SNHG16 led to attenuate cell proliferation, migration, invasion, and EMT of CRC cells. And xenograft tumor experiment showed that SNHG16 might influence tumor growth. In contrast, miR-124-3p exerted the antitumor effects. Knockdown of miR-124-3p can reverse the effect of sh-SNHG16 on CRC cells. miR-124-3p could directly bind to SNHG16 or MCP-1. More importantly, MCP-1 acts as a critical effector mediating the role of SNHG16/ miR-124-3p in CRC cells. In summary, our data suggest that SNHG16 plays a contributory role in proliferation, migration, and EMT of CRC cells via miR-124-3p/MCP-1 axis, which offers a rationale for targeting SNHG16 and developing therapeutic drugs to treat CRC.

Effects of Glycosylation and d-Amino Acid Substitution on the Antitumor and Antibacterial Activities of Bee Venom Peptide HYL.

Glycosylation is a promising strategy for modulating the physicochemical properties of peptides. However, the influence of glycosylation on the biological activities of peptides remains unknown. Here, we chose the bee venom peptide HYL as a model peptide and 12 different monosaccharides as model sugars to study the effects of glycosylation site, number, and monosaccharide structure on the biochemical properties, activities, and cellular selectivities of HYL derivatives. Some analogues of HYL showed improvement not only in cell selectivity and proteolytic stability but also in antitumor and antimicrobial activity. Moreover, we found that the helicity of glycopeptides can affect its antitumor activity and proteolytic stability, and the α-linked d-monosaccharides can effectively improve the antitumor activity of HYL. Therefore, it is possible to design peptides with improved properties by varying the number, structure, and position of monosaccharides. What's more, the glycopeptides HYL-31 and HYL-33 show a promising prospect for antitumor and antimicrobial drugs development, respectively. In addition, we found that the d-lysine substitution strategy can significantly improve the proteolytic stability of HYL. Our new approach provides a reference or guidance for the research of novel antitumor and antimicrobial peptide drugs.

A Pair of CoII Supramolecular Isomers Based on Flexible Bis-Pyridyl-Bis-Amide and Angular Dicarboxylate Ligands.

Thermal reactions of cobalt(II) salts with flexible N,N'-bis(pyrid-3-ylmethyl)adipoamide (L) and angular 4,4'-sulfonyldibenzoic acid (H2SDA) in H2O and CH3OH afforded a pair of supramolecular isomers: [Co2(L)(SDA)2], 1, and [Co2(L)(SDA)2]⋅CH3OH⋅H2O, 2. The structure of complex 1 can be simplified as a one-dimensional (1D) looped chain with L ligands penetrating into the middles of squares, forming a new type of self-catenated net with the (42⋅54)(4)2(5)2 topology, whereas complex 2 displays a 2-fold interpenetrated 2D net with the rare (42⋅68⋅8⋅104)(4)2-2,6L1 topology. While both complexes 1 and 2 display antiferromagnetism with strong spin-orbital coupling, the antiferromagnetism of 2 is accompanied by a cross-over behavior and probably a spin canting phenomenon.

Structural Health Monitoring System Based on FBG Sensing Technique for Chinese Ancient Timber Buildings.

Due to the long-term service, Chinese ancient timber buildings show varying degrees of wear. Thus, structural health monitoring (SHM) for these cultural and historical treasures is desperately needed to evaluate the service status. Although there are some FBG sensing-based SHM systems, they are not suitable for Chinese ancient timber buildings due to the differences in architectural types, structural loads, materials, and environment. Besides, a technical gap in Fiber Bragg grating (FBG) sensing-based column inclination monitoring exists. To overcome these weaknesses, this paper develops an FBG sensing-based structural health monitoring system for Chinese ancient Chuan-dou-type timber buildings that aims at monitoring structural deformation, i.e., beam deflection and column inclination, temperature, humidity, and fire around the building. An in-situ test and simulation analyses were conducted to verify the effectiveness of the developed SHM system. To validate the long-term-operation of the developed SHM system, monitoring data within 15 months were analyzed. The results show good agreement between the developed SHM system in this paper and other methods. In addition, the SHM system operated well in the first year after its deployment. This implies that the developed SHM system is applicable and effective in the health state monitoring of Chinese ancient Chuan-dou-type timber buildings, laying a foundation for damage prognosis of such types of timber buildings.

Salidroside protects PC-12 cells against amyloid ß-induced apoptosis by activation of the ERK1/2 and AKT signaling pathways.

Alzheimer's disease (AD) is one of the most frequent diseases in elderly people and causes high mortality. Its incidence is increasing annually and no effective therapeutic treatment currently exists. In the present study, salidroside, a major active ingredient of Rhodiola rosea, was able to protect PC­12 cells from the toxicity and apoptosis induced by AD inducer amyloid (A)ß1­42. Salidroside significantly protected PC­12 cells by inhibiting Aß1­42­induced cytotoxicity and mitochondria­mediated endogenous caspase apoptotic pathways. Mechanistic studies demonstrated that salidroside significantly activated the extracellular signal regulated kinase (ERK)1/2 and protein kinase B (AKT) signaling pathways. This observation was further confirmed using the ERK1/2 inhibitor PD98059 and the AKT inhibitor LY294002, which demonstrated that salidroside promoted PC­12 cell survival and proliferation by activating the ERK1/2 and AKT signaling pathways. Salidroside is a therapeutic candidate for the treatment of AD and provides a basis for further drug development.

Interhemispheric functional connectivity for Alzheimer's disease and amnestic mild cognitive impairment based on the triple network model.

The purpose of this study was to explore the differences in interhemispheric functional connectivity in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) based on a triple network model consisting of the default mode network (DMN), salience network (SN), and executive control network (ECN). The technique of voxel-mirrored homotopic connectivity (VMHC) analysis was applied to explore the aberrant connectivity of all patients. The results showed that: (1) the statistically significant connections of interhemispheric brain regions included DMN-related brain regions (i.e. precuneus, calcarine, fusiform, cuneus, lingual gyrus, temporal inferior gyrus, and hippocampus), SN-related brain regions (i.e. frontoinsular cortex), and ECN-related brain regions (i.e. frontal middle gyrus and frontal inferior); (2) the precuneus and frontal middle gyrus in the AD group exhibited lower VMHC values than those in the aMCI and healthy control (HC) groups, but no significant difference was observed between the aMCI and HC groups; and (3) significant correlations were found between peak VMHC results from the precuneus and Mini Mental State Examination (MMSE) and Montreal Cognitive Scale (MOCA) scores and their factor scores in the AD, aMCI, and AD plus aMCI groups, and between the results from the frontal middle gyrus and MOCA factor scores in the aMCI group. These findings indicated that impaired interhemispheric functional connectivity was observed in AD and could be a sensitive neuroimaging biomarker for AD. More specifically, the DMN was inhibited, while the SN and ECN were excited. VMHC results were correlated with MMSE and MOCA scores, highlighting that VMHC could be a sensitive neuroimaging biomarker for AD and the progression from aMCI to AD.

Tuning Hierarchical Ferric Nanostructures-Decorated Diatomite for Supercapacitors.

FeOOH nanosheets on porous diatomite have been successfully prepared by a facile two-step hydrothermal approach for supercapacitors, and then α-Fe2O3 and γ-Fe2O3 nanostructures are obtained via calcination under different atmospheres and temperatures. The morphologies and structures of all the samples are investigated in detail to make the hierarchical architecture clear. Besides, systemic tests are carried out in 1 M Na2SO4 electrolyte to characterize the electrochemical properties of these materials. Among the iron-related composite electrodes, diatomite@FeOOH owns the highest specific capacitance (157.9 F g-1 at a current density of 0.5 A g-1) and best cycling performance (98.95% retention after 1000 cycles), which is considered to be a potential material for high-performance supercapacitors. Furthermore, the synthesizing strategy can be extended to the preparation of other metallic oxide-derived functional materials towards energy storage and conversion.

Deformation Monitoring for Chinese Traditional Timber Buildings Using Fiber Bragg Grating Sensors.

The Fiber Bragg Grating (FBG) sensing technique is suitable for a wide variety of measurements, including temperature, pressure, acceleration, liquid level, etc., and has been applied to many bridges and buildings in the past two decades. The fact that the FBG technique can only monitor and measure strain data for most cases when it is used for deformation measurements impedes application of the FBG sensing technique in civil infrastructures. This paper proposes FBG sensing-based deformation monitoring methods that are applicable to monitoring beam deflection, column inclination angle and mortise-tenon joint dislocation for Chinese traditional timber structures. On the basis of improved conjugated beam theory and geometrical trigonometric function relationship, the relationships between the FBG sensing strain values and the deflection of beam, inclination angle of column, as well as the amount of dislocation of mortise-tenon joint are deducted for Chinese traditional buildings. A series of experiments were conducted to verify the applicability and effectiveness of the proposed deformation monitoring methods. The results show that a good agreement is obtained between the values given by the methods proposed in this paper and other methods. This implies that the proposed deformation monitoring methods are applicable and effective in the health monitoring of Chinese traditional timber structures.

One-pot synthesis of substituted tetrahydrocyclobuta[a]naphthalenes by domino aldol condensation/olefin migration/electrocyclization.

A facile one-pot synthetic route for preparing the novel benzofused tricyclic skeleton of 1,2,2a,8b-tetrahydrocyclobuta[a]naphthalenes 5 is developed. The route was realized by a NaH-mediated tandem aldol condensation/olefin migration/electrocyclization of o-allylbenzaldehydes 1 with cinnamyl sulfones 3 in good yields.

NH4OAc promoted cyclocondensation of 3-(o-allylphenyl)pentane-1,5-diones: synthesis of tetracyclic benzofused 1-azahomoisotwistanes.

A facile two-step synthetic route for preparing the novel tetracyclic skeleton of benzofused 2,6-diaryl-1-azahomoisotwistanes 2 had been developed. The route was carried out by a one-pot tandem cross-coupling reaction of o-allylbenzaldehydes 1 with aryl methyl ketones 3, and NH(4)OAc mediated the cascade cyclocondensation reaction of the resulting 1,5-diketones 4 with the 3-o-allylphenyl group in good yield in two steps.

Polyphosphoric acid promoted synthesis of 10,11-dihydrobenzo[j]fluoranthen-12-one.

A straightforward synthesis of 3,8-dimethoxy-10,11-dihydrobenzo[j]fluoranthen-12-ones 1 is reported in a seven-step route from biphenyl-4,4'-diol 2 via the transformation of a double Claisen rearrangement, cross metathesis with ethyl acrylate, and polyphosphoric acid (PPA)-promoted Friedel-Crafts electrophilic benzannulation in good yields.

[A study on the transdifferentiation of adipose mesenchymal stem cells into hepatocytes].

OBJECTIVE: To investigate the possibility of transdifferentiation of adipose mesenchymal stem cells (AMSCs) into hepatocytes. METHODS: Human omentum adipose tissue was dispersed with collagenase I. Cells collected were cultured in a DMEM-F12 medium containing 2% FBS supplemented with 20 ng/ml HGF, 10 ng/ml FGF4, 1xITS and 0.1 micromol/L dexasmison. The cells of the control group were also cultured in the same kind of medium but without any cytokines serving as a control. The expression of hepatic transcriptional factors such as GATA4 and HNF1 were checked by RT-PCR. At the end of the induction, hepatocyte markers were analysed by flow cytometry, and cytokeratin expressions were examined using cyto-immunofluorescence methods. RESULTS: AMSCs grew like fibroblasts and were passaged easily. Most of the third passaged AMSCs were positive against anti-CD29, anti-CD44 antibodies, but negative for the anti-CD34 and anti-CD45 ones. The hepatic transcriptional factor was expressed gradually to higher levels during the induction time. AFP and Alb positive cells were 30.0% and 17.8% of the total cultured cells, and the rate of cells positive to the two markers was 6.9%. The inducted cells were positive for CK18 and CK19 antibodies at the end of the induction. The cells in the control group were negative when checked by these methods. CONCLUSIONS: AMSCs could be directed to differentiate into hepatocytes in vitro by a cytokine cocktail with a low concentration FBS culture system.