Background and aims Defective autophagy has been proposed as an important event in a growing number of autoimmune and inflammatory diseases such as rheumatoid arthritis and lupus. However, the precise role of mechanistic target of rapamycin (mTOR)-dependent autophagy and its underlying regulatory mechanisms in the intestinal epithelium in response to inflammation and oxidative stress remain poorly understood. Methods The levels of p-mTOR, LC3B, p62 and autophagy in mice and LPS-treated cells were examined by immunoblotting, immunohistochemistry, confocal microscopy and transmission electron microscopy (TEM). We evaluated the expression of IL-1β, IL-8, TNF-α, MDA, SOD and T-AOC by quantitative real time-polymerase chain reaction (qRT-PCR) and commercially available kits after silencing of mTOR and ATG5. In vivo modulation of mTOR and autophagy was achieved by using AZD8055, rapamycin and 3-methyladenine. Finally, to verify the involvement of TLR4 signalling and the NF-κB pathway in cells and active ulcerative colitis (UC) patients, immunofluorescence, qRT-PCR, immunoblotting and TEM were performed to determine TLR4 signalling relevance to autophagy and inflammation. Results The mTOR-dependent autophagic flux impairment in a murine model of colitis, human intestinal epithelial cells and active UC patients is probably regulated by TLR4-MyD88-MAPK signalling and the NF-κB pathway. Silencing mTOR remarkably attenuated, whereas inhibiting ATG5 aggravated, LPS-induced inflammation and oxidative injury. Pharmacological administration of mTOR inhibitors and autophagy stimulators markedly ameliorated experimental colitis and oxidative stress in vivo. Conclusions Our findings not only shed light on the regulatory mechanism of mTOR-dependent autophagy, but also provided potential therapeutic targets for intestinal inflammatory diseases such as refractory inflammatory bowel disease.

Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn's disease (CD), is a complicated, uncontrolled, and multifactorial disorder characterized by chronic, relapsing, or progressive inflammatory conditions that may involve the entire gastrointestinal tract. The protracted nature has imposed enormous economic burdens on patients with IBD, and the treatment is far from optimal due to the currently limited comprehension of IBD pathogenesis. In spite of the exact etiology still remaining an enigma, four identified components, including personal genetic susceptibility, external environment, internal gut microbiota, and the host immune response, are responsible for IBD pathogenesis, and compelling evidence has suggested that IBD may be triggered by aberrant and continuing immune responses to gut microbiota in genetically susceptibility individuals. The past decade has witnessed the flourishing of research on genetics, gut microbiota, and immunity in patients with IBD. Therefore, in this review, we will comprehensively exhibit a series of novel findings and update the major advances regarding these three fields. Undoubtedly, these novel findings have opened a new horizon and shed bright light on the causality research of IBD.

Research examining new product development (NPD) practices recognizes the importance of research and development (R&D)-marketing integration to performance. Although a plethora of work has been carried out in the R&D-marketing domain, including Chinese firms, the study of cross-country contexts has relied on country type as the demarcation to explain country differences. No specific cultural elements inherent in the respective countries have been examined. In the case of China, this study introduces the cultural more of guanxi. Seen as an alternative to formal institutionalized interactions, guanxi characterizes the bond between people in Chinese society. To date, the construct of guanxi has received scant attention in NPD literature. The present study examines whether guanxi affects the nature of R&D-marketing integration in Chinese firms. This work is carried out to infer whether specific cultural mores play a role in influencing R&D-marketing integration versus just recognizing a country context. A quantitative survey-based method was adopted to address the research objectives. The sample comprised Chinese high-technology (specifically information technology [IT]) organizations, which were managed by Chinese nationals with headquarters physically located in China. Many Chinese-based IT companies have indigenous R&D departments and are embarking on radical and incremental new-to-the-market product development. Pretest qualitative data were collected through telephone and respondent interviews. The final questionnaire was sent to target senior managers, resulting in a sample comprising 100 marketing and 100 R&D personnel. Study measures were developed, and factor analysis was applied to the NPD integration items. Correlation and logistic regression analyses were employed. The findings identify particular aspects of integration practices between Chinese R&D and marketing managers that differ from the West in light of the significant effect reflected by the guanxi construct. The results show that reliance on informal social systems, through guanxi, can act as a significant support for integration in certain activity areas and that guanxi can influence integration in mid-to late-phase activities. This study's findings suggest that guanxi can act as a unifying force in underdeveloped processes (e.g., NPD) and may, paradoxically, reinforce acceptance of formalized structures. It appears that guanxi is highly utilized to make up for the deficiencies of formal external institutional structures (e.g., regulatory and legal specifications). These findings suggest that where the basis for guanxi exists, traditional and culturally derived interpersonal relationships still impact the way people work together. The results of this research provide new knowledge of how guanxi positively influences the integration of R&D and marketing departments as well as successful NPD performance. Guanxi may underlie how R&D-marketing integration is facilitated in China. The study's findings provide a finer understanding of why Chinese firms...

HuR is a ubiquitously expressed RNA-binding protein that stabilizes the mRNAs of certain genes and regulates the translation to proteins. Elevated cytoplasmic expression of HuR has been suggested to be associated with reduced survival in a wide variety of human carcinomas. However, the clinical significance of HuR expression in lung cancer remains unknown. In this study, we examined HuR expression in 132 patients with non-small cell lung carcinoma (NSCLC) by means of immunohistochemistry and correlated clinicopathologic data, lymphatic microvessel density (LVD), or microvessel density (MVD) with HuR immunostaining. HuR was expressed in 80.3% (106/132) of cases and was predominantly localized in the nucleus. Cytoplasmic HuR expression occurred in 40.9% (54/132) of NSCLC specimens and was associated with high MVD and LVD. In univariate analysis, cytoplasmic HuR, but not nuclear HuR expression was found to significantly influence the relapse-free survival and overall survival. In addition, cytoplasmic expression of HuR was identified as an independent prognostic factor for survival in multivariate analysis. Our data provide evidence for a clinically prognostic role of HuR in NSCLC and demonstrate an association between HuR expression, and angiogenesis and lymphangiogenesis.