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Muscarinic acetylcholine receptors (MRs) play important roles in the regulation of hepatic fibrosis and the receptor agonists and antagonists can affect hepatocyte proliferation. However, little is known about the impact of M 3R subtypes and associated signaling pathways on liver injury. The aim of this study is to explore the function and mechanism of M 3R in the regulation of liver injury. We evaluate liver injury and detect the changes in related indexes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), and transforming growth factor-β1 (TGF-β1), after administration of an M 3R agonist. Western blot analysis and qRT-PCR show that the transcription factor Sp1 and long noncoding RNA (lncRNA) Gm2199 are also changed significantly. Rescue assay is performed to further confirm that M 3R contributes to the progression of hepatocyte proliferation through regulating Sp1 and Gm2199. The activated M 3R can specifically regulate Gm2199 by inhibiting the expression of Sp1. Meanwhile, Gm2199 directly regulates miR-212, and ERK is a potential target of miR-212. Collectively, these findings define a novel mechanism for activating M 3R to reverse liver injury, which affects hepatocyte proliferation through the Sp1/Gm 2199/miR-212/ERK axis.

This study focuses on mitigating the decrease in the quality of mulberry after harvest and increasing the value of mulberry products through microwave vacuum drying. The effects of mulberry moisture content on texture properties were investigated, and the test method was optimized through the membership function model and the central composite technique. The influences of the material surface temperature, vacuum degree, and microwave power on the quality of instant mulberry were analyzed comprehensively. A regression model was established to analyze the relationship between each test factor and quality index. The results show that, with increases in the moisture content, both the hardness and chewiness of mulberry present a decreasing trend; when elasticity increases gradually, adhesivity is presented in an inverted V-shaped variation trend, and the cohesiveness remains basically constant. Moreover, the moisture content of mulberry had significant correlations with elasticity, glueyness, chewiness, and hardness (R2 > 0.9). When the moisture content of the samples reached ≤44.07%, the total plate count reached a minimum and changed gradually; thus, the moisture content (44.07%) of mulberry was determined for the technological optimization test. The combination of optimal technological parameters was as follows: material surface temperature = 51.0 °C, vacuum degree = 0.07 MPa, and microwave power = 370 W. Under these optimal technological parameters, the soluble solid content was 42.37%, chewiness was 9.08, and the Vc content was 0.725 mg·(100 g)−1. The average error between the test results and software optimization parameters was 5.88%. The optimized microwave vacuum drying technological parameters improved the drying quality of mulberry significantly. The results can provide theoretical support for the microwave vacuum drying of berries. [ABSTRACT FROM AUTHOR]

Implementing combination medication through crystal engineering technology receives increasing attention from researchers due to improvements in the clinical treatment effects as well as the physicochemical properties of the drug. Berberine (BER) is commonly used to treat gastroenteritis and bacterial diarrhea, with the problems of poor solubility and low oral bioavailability. Recently, it is found that gallic acid (GA) also has anti‐inflammatory and anti‐bacterial activities. Therefore, if the above‐mentioned two ingredients can be combined, it is possible to enhance the therapeutic effects and physicochemical properties of BER. Inspired by this, 8‐hydroxy‐7,8‐dihydroberberine (8H‐HBER) in this study is employed to react with gallic acid to yield BER gallate dihydrate (2BER‐2GA‐2 W). Furthermore, dissolution experiments demonstrate that the maximum apparent solubility (MAS) of 2BER‐2GA‐2 W in dilute hydrochloric acid solution medium (pH 1.2) has increased by 7 times compared to the commercial form of BER, because of avoiding the common‐ion effect. Moreover, 2BER‐2GA‐2 W has also obviously enhanced stability relative to the commercial form of BER. In addition, 2BER‐2GA‐2 W has a better inhibitory effect on Staphylococcus aureus (S. aureus) relative to the commercial form of BER. Hence, 2BER‐2GA‐2 W will be a promising solid‐state form of BER for its further development. [ABSTRACT FROM AUTHOR]

In a stimulus with multiple moving elements, an observer may perceive that the whole stimulus moves in unison if (a) one can associate an element in one frame with one in the next (correspondence) and (b) a sufficient proportion of correspondences signal a similar motion direction (coherence). We tested the necessity of these two conditions by asking the participants to rate the perceived intensity of linear, concentric, and radial motions for three types of stimuli: (a) random walk motion, in which the direction of each dot was randomly determined for each frame, (b) random image sequence, which was a set of uncorrelated random dot images presented in sequence, and (c) global motion, in which 35% of dots moved coherently. The participants perceived global motion not only in the global motion conditions but also in the random image sequences, though not in random walk motion. The type of perceived motion in the random image sequences depends on the spatial context of the stimuli. Thus, although there is neither a fixed correspondence across different frames nor a coherent motion direction, observers can still perceive global motion in the random image sequence. This result cannot be explained by motion energy or local aperture border effects. [ABSTRACT FROM AUTHOR]

Background/Aims: Interleukin-1 (IL-1) is known to be involved in cartilage degeneration following joint injury or due to osteoarthritis. In the present study, we explored the effects of miR-150 on IL-1-stimulated human chondrogenic cells ATDC5. Methods: ATDC5 cells were transfected with the mimic, inhibitor or negative controls specific for miR-150, and subsequently treated by IL-1. CCK8 assay, PI and FITC-conjugated Annexin V double-staining, Western blot, qRT-PCR and ELISA assay were performed to determine the changes of cell viability, apoptosis, and the release of pro-inflammatory cytokines. Targeting relationship between miR-150 and KLF2 was detected by dual luciferase activity assay. Results: IL-1 reduced cell viability, induced apoptosis, and enhanced the expression and release of pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) in ATDC5 cells. IL-1 also increased the expression of miR-150. Suppression of miR-150 alleviated IL-1-induced cell damage in ATDC5 cells, while overexpression of miR-150 resulted in an opposite impact. KLF2 was negatively regulated by miR-150, and it was proved as a target gene of miR-150. KLF2 overexpression exhibited protective actions in IL-1-injured ATDC5 cells, even if miR-150 was suppressed in cell. Moreover, IL-1-induced activation of NF-kB and Notch pathways was alleviated by KLF2 overexpression. Conclusions: Suppression of miR-150 led to up-regulation of KLF2, which in turn protected ATDC5 cells against IL-1-induced injury. [ABSTRACT FROM AUTHOR]

Guests' evaluation of indoor environmental quality (IEQ) is important for identifying environment quality problems in hotels and improving service quality. This paper aims to identify IEQ problems in budget hotels in China and improve them. Specifically, 2.06 million online reviews of budget hotels were used to assess IEQ issues in China's budget hotels in four areas: acoustic environment, luminous environment, indoor air quality (IAQ) and thermal environment. The influences of the season, region and type of customers on the IEQ evaluation were also explored, and the main causes of IEQ problems were also identified. The research results show that the IEQ complaint rates of budget hotels are relatively high. In particular, complaints about the acoustic environment are more common. Differences in seasons and climate zones have significant effects on complaints about the acoustic environment, thermal environment and IAQ. Different types of customers have different concerns about hotel IEQ, among which solo travelers and traveling couples have higher requirements for IEQ. The occurrence of IEQ problems significantly reduces a hotel's online rating, with IAQ and the thermal environment having the greatest impacts, but the causal factors that trigger IEQ problems are relatively concentrated. The findings of this paper can provide a reference for assessing IEQ problems in hotel buildings and guide hotel managers to adopt targeted IEQ improvement programs to promote sustainable development in the hotel industry. [ABSTRACT FROM AUTHOR]

Notoginsenoside R1 (NG-R1) exhibits a pharmacological activity against excessive inflammation. Here, we aimed to ascertain the anti-inflammatory role of NG-R1 in ankylosing spondylitis (AS) as well as the possible mechanism which is still under to be elucidated. In this study, lipopolysaccharide (LPS) was applied to evoke extreme inflammation in ATDC5 cells. To investigate the anti-inflammatory property of NG-R1, ATDC5 cells were exposed to NG-R1 prior to LPS stimulation. microRNA-301a (miR-301a)-overexpressed ATDC5 cells were established which confirmed by qRT-PCR. Then, inflammatory lesions were indicated by cell viability, apoptosis and inflammatory factors, including interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α). Nuclear factor-kappa B (NF-κB) pathway was determined by Western blotting assay. We found NG-R1 dramatically dampened the decrease of cell viability, facilitation of apoptosis and abundance of inflammatory factors induced by LPS. Additionally, NG-R1 pre-incubation impeded LPS-induced accumulation of miR-301a. However, the protective capacity of NG-R1 was impaired by miR-301a overexpression. Of note, LPS-caused phosphorylation of p65 and inhibitor of nuclear factor kappa-B alpha (IκBα) was repressed by NG-R1, while further enhanced in miR-301-transfected ATDC5 cells. NG-R1 relived LPS-elicited inflammatory damages via blocking NF-κB in a miR-301a-silenced manner. • Notoginsenoside R1 protects ATDC5 cells from inflammation-caused lesions; • Lipopolysaccharide-induced miR-301a is eliminated by notoginsenoside R1; • miR-301a-mediated blockade of NF-κB pathway is triggered by notoginsenoside R1. [ABSTRACT FROM AUTHOR]

Background Astragalus membranaceus has been clinically used in cerebral ischemia treatment in China and its main component, Astragaloside IV (Ast IV) shows anti-hypoxia activity, but the underlying mechanism has not been clearly clarified. This study was aimed to investigate the effects of Ast IV on hypoxia-induced injury in PC-12 cells as well as the underlying mechanism. Methods Relative miR-124 expression was detected by qRT-PCR. Hic-5 expression was analyzed by qRT-PCR and Western blot. To alter miR-124 and Hic-5 expressions, cells were respectively transfected with miR-124 mimic and pEX-Hic-5. Cell proliferation and apoptosis were measured by BrdU assay and Annexin V-fluorescein isothiocynate (FITC)/propidium iodide (PI) double staining method, respectively. Besides, apoptotic proteins and cell proliferation-associated factors were analyzed by Western blot. Results Ast IV alleviated hypoxia-induced injury in PC-12 cells by decreasing apoptosis ( P  <  0.01). Ast IV inhibited up-regulation of miR-124 induced by hypoxia ( P  <  0.01). miR-124 mimic impaired the anti-apoptotic effect of Ast IV on PC-12 cells ( P  <  0.01). Hic-5 expression was significantly down-regulated in miR-124 overexpressed cells ( P  <  0.001) and Hic-5 overexpression activated Sp1/Survivin signaling pathway ( P  <  0.001). Conclusion Ast IV could ameliorate hypoxia-induced injury in PC-12 cells by decreasing miR-124 expression and then up-regulating Hic-5 expression. [ABSTRACT FROM AUTHOR]

Myriocin is an inhibitor of de novo synthesis of sphingolipids and ceramides. In this research, we showed myriocin could significantly reduce Mtb burden and histopathological inflammation in mice. However, the underlying mechanism remains unclear. RNA-seq analysis revealed a significant increase in gene expression of PLIN2/CD36/CERT1 after myriocin treatment. The reduced bactericidal burden was only reversed after silencing the lipid droplets (LDs) surface protein PLIN2. This suggests that myriocin enhances the ability of macrophages to clear Mtb depending on the PLIN2 gene, which is part of the PPARγ pathway. Indeed, we observed a significant increase in the number of LDs following myriocin treatment.IMPORTANCE Mycobacterium tuberculosis has the ability to reprogram host cell lipid metabolism and alter the antimicrobial functions of infected macrophages. The sphingolipids, such as ceramides, are the primary host lipids utilized by the bacteria, making the sphingomyelinase/ceramide system critical in Mtb infections. Surprisingly, the antimicrobial effect of myriocin was found to be independent of its role in reducing ceramides, but instead, it depends on the lipid droplets surface protein PLIN2. Our findings provide a novel mechanism for how myriocin enhances Mtb clearance in macrophages.

As an extremely popular natural product, berberine (BER) is mainly used for gastroenteritis and diarrhoea caused by bacteria. Research has also revealed the potent and extensive pharmacological properties of BER including its anti-arrhythmic, anti-tumour, anti-inflammatory and hypoglycemic activities and so on; therefore, BER is a promising drug for further development. However, its commercial form with hydrochloride exhibits poor stability and solubility, which are detrimental to its clinical therapeutic effects. For these purposes, the salt form was regulated via the reactive crystallization of 8-hydroxy-7,8-dihydroberberine (8H-HBER) with five pharmaceutically suitable organic acids including malonic acid (MA), L-tartaric acid (LTA), D-tartaric acid (DTA), DL-tartaric acid (DLTA) and citric acid (CA), resulting in the six novel solid forms 1BER-1LTA-1W, 1BER-1DTA-1W, 1BER-1DLTA and 2BER-2CA as well as two rare multi-stoichiometric solid forms 1BER-1MA and 1BER-2MA-2W. The preparation of the multi-stoichiometric products was greatly influenced by both the crystallization solvent type and the molar ratio of reactants. The structures of these multi-component solid forms were determined using single-crystal X-ray diffraction and further characterized by powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy. Stability experiments showed that all samples prepared had superior physical stability under high temperature and high humidity. Furthermore, dissolution experiments demonstrated that the maximum apparent solubilities (MAS) of all the products were significantly improved compared with the commercial form of BER in dilute hydrochloric solution (pH = 1.2). In particular, the MAS of 1BER-1MA in dilute hydrochloric solution is as high as 34 times that of the commercial form. In addition, it is preliminarily confirmed that the MAS of the samples prepared in pure water and dilute hydrochloric solution is primarily influenced by a combination of factors including the packing index, intermolecular interactions, affinity of the counter-ion to the solvent, the molar ratio of the drug to counter-ion in the product and the common ion effect. These novel solids are potential candidates for BER solid forms with improved oral dosage design and may prompt further development., (open access.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article “… the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated”, the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)