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Introduction: Transcriptional regulation of autophagy depends on the transcription factors coordinated inflammatory feedback mechanism. Here, we provide a comprehensive functional characterization of periodontal ligament fibroblasts (PDLFs) treated with Porphyromonas gingivalis lipopolysaccharide (LPS), aiming to reveal previously unappreciated biological changes and to investigate how a transcription factor differentiated embryonic chondrocytes 2 (Dec2)‐deficient environment influences the function of autophagy in nflamed human PDLFs. Methods: A Dec2‐deficient (Dec2KO) experimental periodontal inflammation mouse model and treatment with P. gingivalis LPS were employed to examine the role of autophagy in PDLFs using hematoxylin and eosin staining and immunohistochemistry in vivo. A Dec2 small interfering RNA (siRNA) was used to modulate autophagy, and the effect of autophagy on the Dec2 pathway was explored using real‐time polymerase chain reaction and western blot analysis in vitro. Results: LPS‐treated human PDLFs (HPDLFs) induced autophagy, as demonstrated by the enhanced levels of microtubule‐associated protein 1 light chain 3‐II (LC3‐II) and the induction of ATG5, Beclin1, and Dec2. Compared with a scrambled siRNA, a Dec2 siRNA triggered the detrimental influences of LPS and markedly enhanced autophagy expression in inflamed HPDLFs. The expression of phosphorylated ERK was increased and levels of phosphorylated mammalian target of rapamycin (mTOR) were decreased after exposure to LPS in Dec2 siRNA transfected HPDLFs. The Dec2KO model exhibited that P. gingivalis in Dec2 deficient conditions increases the inflammation of PDLFs by regulating autophagy. Conclusions: These results demonstrate that a Dec2 deficiency can alleviate LPS‐induced inflammation via the ERK/mTOR signaling pathway by regulating autophagy, conceivably delivering a novel approach for the detection of periodontal treatments. [ABSTRACT FROM AUTHOR]

This narrative review aimed to clarify the characteristics of international government support for sepsis research, trends in published literature on sepsis, and potential contributions of government-source grants to progress in sepsis research between fiscal years 2010 and 2019. The data in this study were collected from the National Institutes of Health (NIH, https://projectreporter.nih.gov/reporter.cfm/) of the United States of America (USA), National Natural Science Foundation of China (NSFC, https://isisn.nsfc.gov.cn/egrantweb/), and Japan Society for the Promotion of Science (JSPS, https://kaken.nii.ac.jp/). All sepsis-related projects approved by the NIH, NSFC, and JSPS were retrieved by searching the project titles, abstracts, and key words for "sepsis," "septic shock," or "sepsis inflammatory response syndrome" between 2010 and 2019. Representative sepsis-related studies published between Jan 2010 and Aug 2020 by the first/corresponding authors from these countries were obtained by searching the PubMed database using Medical Subject Heading terms for "sepsis" in representative journals, including Nature , Cell, Science, The Lancet, New England Journal of medicine (New Engl J Med), The Journal of American Medical Association (JAMA), Critical Care Medicine (CCM), Intensive Care Medicine (ICM), Chest, Annals of Emergency Medicine (Ann Emerg Med), and American Thoracic Society journals (ATS). The total/annual institutional budgets, major funding mechanisms and schemes, superior institutions and individual principal investigators, and published original research articles in the field of sepsis in the USA, China, and Japan during the past decade were investigated. The national supporting schemes of the NIH, NSFC, and JSPS were similar. Support from these institutions is quite important for the development of the field of "sepsis" which was acknowledged in 57-64% of original research articles published in CCM. For the future development of precision medicine in sepsis, more government funding support is necessary.

MicroRNAs are emerging as critical post-transcriptional modulators in bone remodeling, regulating the functions of osteoblasts and osteoclasts. Intercellular crosstalk between osteoblasts and osteoclasts is mediated by miR-21 that controls the bone homeostasis response, providing potential targets for the maintenance of osteoblast function. The aim of this study was to investigate the effects of miR-21 on osteoblast function, and to explore the underlying mechanism. Increased alkaline phosphatase (ALP) activity and accelerated matrix mineralization was observed in mouse pre-osteoblast MC3T3-E1 cells compared with the non-induction (control) group. MiR-21 positively regulates osteogenic differentiation and mineralization by facilitating the expression of key osteogenic factors (ALP, Runx2, Osteopontin (OPN), Osterix (OSX) and Mef2c) in MC3T3-E1 cells. Furthermore, a deficiency of miR-21 suppresses the expression of those factors at both the mRNA and protein levels, indicating that miR-21 is a positive regulator of osteoblastic differentiation. H-E staining, Azan staining, Masson's Trichrome staining and Toluidine blue staining were performed in jaw and femur tissues of miR-21 knockout (miR-21KO) and wild-type (WT) mice. Immunohistochemical staining revealed substantially lower levels of ALP, Runx2 and OSX expression in jaw and femur tissues of miR-21KO mice. A similar trend was observed in femur tissues using quantitative real-time (RT) PCR. A total of 17 osteogenesis-related mRNAs were found to be differentially expressed in miR-21KO femur tissues using Mouse Gene Expression Microarray analysis. GeneSpring and Ingenuity Pathway Analysis revealed several potential target genes that are involved in bone remodeling, such as IL-1β and HIF-1α. Several important pathways were determined to be facilitators of miR-21, which provides a reliable reference for future studies to elucidate the biological mechanisms of osteoblast function. Taken together, these results lead us to hypothesize a potential role for miR-21 in regulating osteoblast function, thus representing a potential biomarker of osteogenesis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)