Search

Background. Type 2 diabetes mellitus increases the risk of sarcopenia, which is characterized by decreased muscle mass, strength, and function. However, there are no effective drugs to treat diabetic sarcopenia, and its underlying mechanism remains unknown. Here, we aimed to determine whether the GLP-1 receptor agonist (GLP-1RA) dulaglutide (Dul) affects the progression of diabetic sarcopenia. Methods. db/db mice were injected intraperitoneally with 0.6 mg/kg dulaglutide for 10 weeks. Mouse muscle tissues were then pathologically evaluated and stained with F4/80 or MPO to detect macrophages and neutrophils, respectively. In addition, inflammatory factors and FNDC5 in the muscle tissues were detected using qRT-PCR. Moreover, C2C12 cells were induced to enable their differentiation into skeletal muscle cells, and muscle factor levels were then detected. Furthermore, changes in muscle factor levels were detected at various glucose concentrations (11 mM, 22 mM, and 44 mM). Results. In vivo, dulaglutide alleviated muscle tissue injury; reduced levels of the inflammatory factors, IL-1β, IL-6, CCL2, and CXCL1; and reversed the level of FNDC5 in the muscle tissues of db/db mice. In vitro, a C2C12 cell differentiation model was established through the observation of cell morphology and determination of myokine levels. Upon stimulation with high glucose, the differentiation of C2C12 cells was inhibited. Dulaglutide improved this inhibitory state by upregulating the levels of both FNDC5 mRNA and protein. Conclusions. Treatment with the GLP-1RA dulaglutide protects db/db mice against skeletal muscle injury by inhibiting inflammation and regulating the differentiation of myoblasts. High glucose inhibited the differentiation of C2C12 cells and decreased the mRNA and protein levels of myokines. Dulaglutide could reverse the differentiation state induced in C2C12 cells by high glucose. [ABSTRACT FROM AUTHOR]

We develop a nicking-mediated all-in-one self-consuming molecular beacon bulb lighted by target molecule (the red magic wand) at attomolar level for point mutation and ultra-sensitive detection of cancer-related gene. [Display omitted] • The engineered NAS-MB displays an outstanding single-base mismatch discrimination ability and ultra-sensitivity. • The unique self-consuming behavior shortens the detection time and simplifies the operation. • The excellent target detection capacity in human serum emphasizes its potential applications in disease diagnosis. Molecular beacons (MB) are used to explore as a turn-on probe for the detection of biomarkers of great interest. However, most reported MB-based biosensors suffer from limited sensitivity and poor specificity. Herein, a nicking-mediated all-in-one self-consuming molecular beacon bulb (NAS-MB) of new conception was proposed to identify cancer-related gene. Differing from traditional MB, the engineered NAS-MB, composed of a multifunctional fluorescent hairpin probe (MFHP) and a quenching probe (QP), is utilized not only as a signal reporter but also as a primer and self-extending template during the enzymatic polymerization-cleavage processes (EPCPs). Specifically, several functional regions are integrated into NAS-MB, namely, a target recognition region (TRR), a nicking enzyme recognition site, a primer region (PR) and its complementary sequence (CPR), an intramolecular and an intermolecular stem domain, a four-base complementary domain between PR and QP, resulting in a turn-off state. Once lighted by the target gene, QP is displaced and an intramolecular hybridization between PR and CPR occurs to form a new stem-loop structure with a blunt 3′ terminal in MFHP to activate EPCPs. Meanwhile, a steady stream of nicking fragments (NF) and cyclical target gene flow out, which can in turn tandemly trigger EPCPs, leading to the dramatic accumulation of NF and double-inner-circulation-strengthened self-consuming of NAS-MB. In this way, NAS-MB can be turned on by the target gene with a concentration as low as 10 aM and discriminate single-base mismatched sequences through enzyme-mediated self-consuming behavior. The unique analytical properties reveal its potential promise in the diagnosis of genetic diseases. [ABSTRACT FROM AUTHOR]

Based on the elaboration likelihood model (ELM), this study examined the role of consumers' initial trust in the persuasion process in e-commerce advertising in China. The results of two experiments revealed two significant moderators of the central route for processing of information: the disposition to trust (negative moderator) and institution-based trust (IBT; positive moderator). Specifically, low disposition to trust strengthened the influence of argument quality on consumers' product attitude and purchase intention. The same effect occurred under conditions of high IBT. However, when it came to the peripheral route, the effects of disposition to trust and IBT were not significant. [ABSTRACT FROM AUTHOR]

On the basis of the parasocial interaction and social presence that e-commerce livestream marketing can create，this study used structural equation modeling and the bootstrapping analysis method to explore the impact of consumers' characteristics on their impulsive purchase in livestream marketing. According to an empirical analysis of 400 valid questionnaire data, consumers' empathy ability and real-life social avoidance have a significant positive impact on their perception of parasocial interaction, and their sense of loneliness has a significant negative impact on the same. Parasocial interaction has a significant positive impact on impulsive purchase and mediates the influence mechanism of empathy ability, sense of loneliness, and real-life social avoidance on impulsive purchase. Both consumers' empathy ability and mutual assistance have a significant positive impact on their sense of social presence, but the impact of their social presence on their impulsive purchase is not significant. • Loneliness negatively influence consumer's perception of parasocial interaction in e-commerce live streaming. • The real-life social avoidance positively influence parasocial interaction in e-commerce live streaming. • Consumers' mutual assistance positively effect on their sense of social presence in e-commerce live streaming. • Parasocial interaction mediates the effect of consumer's characteristics on impulsive purchase in e-commerce live streaming. [ABSTRACT FROM AUTHOR]

Sepsis is a dangerous condition with a high mortality rate. In addition to promoting insulin secretion in a glucose-dependent manner, glucagon-like peptide-1 (GLP-1) also exhibits anti-inflammatory properties. Dulaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA). In this study, we investigated the effects and mechanism of action of dulaglutide (Dul) in lipopolysaccharide (LPS) induced lung injury in mice with sepsis. In mice with LPS (15 mg/kg, ip, qd)-induced acute lung injury, the administration of dulaglutide (0.6 mg/kg, ip, qd) improved weight loss, reduced lung injury, reversed the increase in IL-1β, TNF-α, IL-6, CXCL1, CCL2 and CXCL2 expression in the lung, and reduced the infiltration of neutrophils and macrophages in the lung tissues. The decline in caspase-3, cleaved caspase-3, caspase-8, and Bcl-2/Bax expression and the increase in the number of TUNEL positive cells in the lung were reversed, suggesting that GLP-1RA could play a protective role in the lung by inhibiting inflammation and apoptosis. In addition, GLP-1RA could reduce the expression of P-STAT3 and NLRP3, suggesting that P-STAT3 and NLRP3 may be potential targets against lung injury in sepsis. Collectively, our data demonstrated that GLP-1RA exerts a protective effect against sepsis-induced lung injury through mechanisms related to the inhibition of inflammation, apoptosis, and STAT3 signaling. In LPS-induced ALI, dulaglutide treatment down-regulated the phosphorylation of STAT3 and reduced the entry of P-STAT3 into the nucleus, thereby reducing the expression of TNF-α, IL-1β and CCL2, and alleviating the damage caused by inflammation. In addition, dulaglutide treatment also exhibited decreased expression of IL-1β and NLRP3. Moreover, it reduced the expression of apoptotic proteins, inhibited the apoptosis of epithelial cells, and achieved the protective effect of the lung. [Display omitted] [ABSTRACT FROM AUTHOR]

The calculations based on the density functional theory (DFT) have been used to study the structure–activity of resveratrol in the chain reaction of autooxidation. According to the geometry obtained by using a B3LYP/6-31G**, the HOMO, LUMO of resveratrol and the spin density, the single electron distribution of the 4′- and 5-radical of resveratrol were calculated, it was found that resveratrol is a potential antioxidant. The 4′-hydroxyl group of resveratrol is more reactive than 3- and 5-positions because of the resonance effects. The dominant structure of the resveratrol radicals is a semiquinone structure which determines the stability of radicals, and the unpaired electron is mainly distributed to the O-atom and its ortho and para positions. The antioxidant activity of resveratrol is related to the spin density and the unpaired electron distribution of the O-atom. [Copyright &y& Elsevier]