Digital technologies have changed firms' innovation logic and value creation mode, how organizations leverage the digital platform to promote value cocreation to promote digital transformation has ...become increasingly prominent. Based on the perspective of platform participants and the theory of resource orchestration, this article integrates resource and capability view to build a chain mediating model to explore the mechanism of value cocreation influencing participating enterprises' business process digitization in the context of digital platforms. Then, we use multiple regression and bootstrapping methods with survey data from 247 Chinese manufacturing SMEs to empirically test the proposed model. Our analysis results indicate that 1) value cocreation has a significant positive impact on business process digitization; 2) resource patchwork and digital platform capability play a partial mediating role between value cocreation and business process digitization; 3) there is a chain mediating path of "value cocreation-resource patchwork-digital platform capability-business process digitization." This study could provide a theoretical basis and practical guidance for organizations to achieve digitization by leveraging the digital platform to facilitate value cocreation.
Apigenin is a non-toxic natural flavonoid that is abundantly present in common fruits and vegetables. It has been reported that apigenin has various beneficial health effects such as ...anti-inflammation and chemoprevention. Multiple studies have shown that inflammation is an important risk factor for atherosclerosis, diabetes, sepsis, various liver diseases, and other metabolic diseases. Although it has been long realized that apigenin has anti-inflammatory activities, the underlying functional mechanisms are still not fully understood.
In the present study, we examined the effect of apigenin on LPS-induced inflammatory response and further elucidated the potential underlying mechanisms in human THP-1-induced macrophages and mouse J774A.1 macrophages. By using the PrimePCR array, we were able to identify the major target genes regulated by apigenin in LPS-mediated immune response. The results indicated that apigenin significantly inhibited LPS-induced production of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α through modulating multiple intracellular signaling pathways in macrophages. Apigenin inhibited LPS-induced IL-1β production by inhibiting caspase-1 activation through the disruption of the NLRP3 inflammasome assembly. Apigenin also prevented LPS-induced IL-6 and IL-1β production by reducing the mRNA stability via inhibiting ERK1/2 activation. In addition, apigenin significantly inhibited TNF-α and IL-1β-induced activation of NF-κB.
Apigenin Inhibits LPS-induced Inflammatory Response through multiple mechanisms in macrophages. These results provided important scientific evidences for the potential application of apigenin as a therapeutic agent for inflammatory diseases.
PurposeThe purpose of this paper is to build a System Dynamics model to reveal the structure and dynamics of knowledge coupling affecting firms' innovation results in the digital ...context.Design/methodology/approachDrawing on the recombined view of innovation, this paper divides knowledge coupling into two dimensions: component knowledge coupling and architectural knowledge coupling. Then, the authors build a system dynamics model to identify the interaction of knowledge coupling factors and use the professional Vensim PLE to conduct simulation analysis to capture the dynamic interaction of motivation factors in knowledge coupling system.FindingsThe results show that both technology resources and digital dynamic capability play positive effects in the mechanism of knowledge coupling influencing firms' innovation results, while organizational inertia negatively affects the process of knowledge coupling to achieve innovation outcomes.Originality/valueThis study develops a holistic system dynamics model to reveal and elaborate on the complex dynamic mechanism of knowledge coupling impacting firms' innovation results in the context of digitization and provides a theoretical reference for companies to effectively adopt digital technology to carry out knowledge coupling strategy.
Background and Aims
Hepatic macrophages can be activated by many factors such as gut‐derived bacterial components and factors released from damaged hepatocytes. Macrophage polarization toward a ...proinflammatory phenotype (M1) represents an important event in the disease progression of nonalcoholic fatty liver disease (NAFLD). However, the underlying molecular mechanisms remain incompletely understood. Exosomes have been identified as important mediators for cell–cell communication by transferring various biological components such as microRNAs (miRs), proteins, and lipids. The role of exosomes in crosstalk between hepatocytes and macrophages in disease progression of NAFLD is yet to be explored.
Approach and Results
In the present study, we reported that lipotoxic injury–induced release of hepatocyte exosomes enriched with miR‐192‐5p played a critical role in the activation of M1 macrophages and hepatic inflammation. Serum miR‐192‐5p levels in patients with NAFLD positively correlated with hepatic inflammatory activity score and disease progression. Similarly, the serum miR‐192‐5p level and the number of M1 macrophages, as well as the expression levels of the hepatic proinflammatory mediators, were correlated with disease progression in high‐fat high‐cholesterol diet–fed rat models. Lipotoxic hepatocytes released more miR‐192‐5p‐enriched exosomes than controls, which induced M1 macrophage (cluster of differentiation 11b–positive CD11b+/CD86+) activation and increase of inducible nitric oxide synthase, interleukin 6, and tumor necrosis factor alpha expression. Furthermore, hepatocyte‐derived exosomal miR‐192‐5p inhibited the protein expression of the rapamycin‐insensitive companion of mammalian target of rapamycin (Rictor), which further inhibited the phosphorylation levels of Akt and forkhead box transcription factor O1 (FoxO1) and resulted in activation of FoxO1 and subsequent induction of the inflammatory response.
Conclusions
Hepatocyte‐derived exosomal miR‐192‐5p plays a critical role in the activation of proinflammatory macrophages and disease progression of NAFLD through modulating Rictor/Akt/FoxO1 signaling. Serum exosomal miR‐192‐5p represents a potential noninvasive biomarker and therapeutic target for nonalcoholic steatohepatitis.
Chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are associated with bile stasis and gradually progress to fibrosis, cirrhosis, ...and liver failure, which requires liver transplantation. Although ursodeoxycholic acid is effective in slowing the disease progression of PBC, it has limited efficacy in PSC patients. It is challenging to develop effective therapeutic agents due to the limited understanding of disease pathogenesis. During the last decade, numerous studies have demonstrated that disruption of bile acid (BA) metabolism and intrahepatic circulation promotes the progression of cholestatic liver diseases. BAs not only play an essential role in nutrition absorption as detergents but also play an important role in regulating hepatic metabolism and modulating immune responses as key signaling molecules. Several excellent papers have recently reviewed the role of BAs in metabolic liver diseases. This review focuses on BA-mediated signaling in cholestatic liver disease.
Acquiring and combining different knowledge elements across organizational boundaries has become an important strategy for firms’ innovation outcomes. Based on the theory of resource orchestration, ...this paper divides knowledge coupling into two dimensions: complementary knowledge coupling and substitutable knowledge coupling. Then, this study aims to explore the different impacts of knowledge coupling types on firm’s incremental innovation and verify the moderating role of government support policies in this relationship. Based on the survey of 279 high-tech enterprises from China, our analysis results indicate the following. (1) Complementary knowledge coupling has an inverted U-shaped impact on firm’s incremental innovation, while substitutable knowledge coupling has a positive influence on incremental innovation. (2) The fitness between government support policies and knowledge coupling types can promote the result of firm’s incremental innovation: when firms adopt complementary knowledge coupling strategies, finance and taxation support policies are more conducive to firm’s incremental innovation; when enterprises use substitutable knowledge coupling strategies, innovative environment support policies are better for the promotion of firm’s incremental innovation. The research results provide a theoretical basis for firms to select appropriate government support strategies to exert the effects of innovation based on characteristics of internal and external knowledge resources.
Inflammation plays an essential role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Berberine (BBR), an isoquinoline alkaloid isolated from Chinese medicinal herbs, has been widely ...used to treat various diseases, including liver diseases for hundreds of years. The previous studies have shown that BBR inhibits high fat-diet-induced steatosis and inflammation in rodent models of NAFLD. However, the underlying molecular mechanisms remain unclear. This study is aimed to identify the potential mechanisms by which BBR inhibits free fatty acid (FFA) and LPS-induced inflammatory response in mouse macrophages and hepatocytes. Mouse RAW264.7 macrophages and primary mouse hepatocytes were treated with palmitic acid (PA) or LPS or both with or without BBR (0-10 μM) for different periods (0-24 h). The mRNA and protein levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β, MCP-1) and ER stress genes (CHOP, ATF4, XBP-1) were detected by real-time RT-PCR, Western blot and ELISA, respectively. The results indicated that BBR significantly inhibited PA and LPS-induced activation of ER stress and expression of proinflammatory cytokines in macrophages and hepatocytes. PA/LPS-mediated activation of ERK1/2 was inhibited by BBR in a dose-dependent manner. In summary, BBR inhibits PA/LPS-induced inflammatory responses through modulating ER stress-mediated ERK1/2 activation in macrophages and hepatocytes.
Bile acids as regulatory molecules Hylemon, Phillip B.; Zhou, Huiping; Pandak, William M. ...
Journal of lipid research,
08/2009, Volume:
50, Issue:
8
Journal Article
Peer reviewed
Open access
In the past, bile acids were considered to be just detergent molecules derived from cholesterol in the liver. They were known to be important for the solubilization of cholesterol in the gallbladder ...and for stimulating the absorption of cholesterol, fat-soluble vitamins, and lipids from the intestines. However, during the last two decades, it has been discovered that bile acids are regulatory molecules. Bile acids have been discovered to activate specific nuclear receptors (farnesoid X receptor, preganane X receptor, and vitamin D receptor), G protein coupled receptor TGR5 (TGR5), and cell signaling pathways (c-jun N-terminal kinase 1/2, AKT, and ERK 1/2) in cells in the liver and gastrointestinal tract. Activation of nuclear receptors and cell signaling pathways alter the expression of numerous genes encoding enzyme/proteins involved in the regulation of bile acid, glucose, fatty acid, lipoprotein synthesis, metabolism, transport, and energy metabolism. They also play a role in the regulation of serum triglyceride levels in humans and rodents. Bile acids appear to function as nutrient signaling molecules primarily during the feed/fast cycle as there is a flux of these molecules returning from the intestines to the liver following a meal. In this review, we will summarize the current knowledge of how bile acids regulate hepatic lipid and glucose metabolism through the activation of specific nuclear receptors and cell signaling pathways.—Hylemon, P. B., H. Zhou, W. M. Pandak, S. Ren, G. Gil, and P. Dent. Bile acids as regulatory molecules.
Cholestatic liver injury is an important clinical problem with limited understanding of disease pathologies. Exosomes are small extracellular vesicles released by a variety of cells, including ...cholangiocytes. Exosome‐mediated cell‐cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies indicate that the long noncoding RNA (lncRNA), H19, is mainly expressed in cholangiocytes, and its aberrant expression is associated with significant down‐regulation of small heterodimer partner (SHP) in hepatocytes and cholestatic liver injury in multidrug resistance 2 knockout (Mdr2−/−) mice. However, how cholangiocyte‐derived H19 suppresses SHP in hepatocytes remains unknown. Here, we report that cholangiocyte‐derived exosomes mediate transfer of H19 into hepatocytes and promote cholestatic injury. Hepatic H19 level is correlated with severity of cholestatic injury in both fibrotic mouse models, including Mdr2−/− mice, a well‐characterized model of primary sclerosing cholangitis (PSC), or CCl4‐induced cholestatic liver injury mouse models, and human PSC patients. Moreover, serum exosomal‐H19 level is gradually up‐regulated during disease progression in Mdr2−/− mice and patients with cirrhosis. H19‐carrying exosomes from the primary cholangiocytes of wild‐type (WT) mice suppress SHP expression in hepatocytes, but not the exosomes from the cholangiocytes of H19−/− mice. Furthermore, overexpression of H19 significantly suppressed SHP expression at both transcriptional and posttranscriptional levels. Importantly, transplant of H19‐carrying serum exosomes of old fibrotic Mdr2−/− mice significantly promoted liver fibrosis (LF) in young Mdr2−/− mice. Conclusion: Cholangiocyte‐derived exosomal‐H19 plays a critical role in cholestatic liver injury. Serum exosomal H19 represents a noninvasive biomarker and potential therapeutic target for cholestatic diseases. (Hepatology 2018).
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