TIPE2 regulates periodontal inflammation by inhibiting NF-κB p65 phosphorylation

The roles and molecular mechanisms of tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) in periodontitis remain largely unknown. Objective: This study aimed to determine the expression of TIPE2 and NF-κB p65 in rat Porphyromonas gingivalis-induced periodontics in vivo. Methodology: Periodontal inflammation and alveolar bone resorption were analyzed using western blotting, micro-computed tomography, TRAP staining, immunohistochemistry, and immunofluorescence. THP-1 monocytes were stimulated using 1 μg/ml Pg. lipopolysaccharide (Pg.LPS) to determine the expression of TIPE2 in vitro. TIPE2 mRNA was suppressed by siRNA transfection, and the transfection efficiency was proven using western blotting and real-time PCR. The NF-κB pathway was activated by treating the cells with 1 μg/ml Pg.LPS to explore related mechanisms. Results: The expression of both TIPE2 and NF-κB p65 was increased in the gingival tissues of rat periodontitis compared with normal tissues. Positive expression of TIPE2 was distributed in inflammatory infiltrating cells and osteoclasts in the marginal lacunae of the alveolar bone. However, strong positive expression of TIPE2 in THP-1 was downregulated after Pg.LPS stimulation. TIPE2 levels negatively correlated with TNF-α and IL-1β. Decreased TIPE2 in THP-1 further promoted NF-κB p65 phosphorylation. Mechanistically, TIPE2 knockdown upregulated NF-κB signaling pathway activity. Conclusions: Taken together, these findings demonstrate that TIPE2 knockdown aggravates periodontal inflammatory infiltration via NF-κB pathway. Interventions aimed at increasing TIPE2 may help in the therapeutic applications for periodontitis

Sustainable–Smart–Resilient–Low Carbon–Eco–Knowledge Cities; Making sense of a multitude of concepts promoting sustainable urbanization

Over the last couple of decades, metropolitan areas around the world have been engaged in a multitude of initiatives aimed at upgrading urban infrastructure and services, with a view to creating better environmental, social and economic conditions and enhancing cities' attractiveness and competitiveness. Reflecting these developments, many new categories of 'cities' have entered the policy discourse: 'sustainable cities'; 'green cities'; 'digital cities'; 'smart cities'; intelligent cities'; 'information cities'; 'knowledge cities'; 'resilient cities'; 'eco-cities'; 'low carbon cities'; 'liveable cities'; and even combinations, such as 'low carbon eco-cities' and 'ubiquitous eco-cities’. In practice, these terms often appear to be used interchangeably by policy makers, planners and developers. However, the question arises whether these categories nevertheless each embody distinct conceptual perspectives, which would have implications for how they are understood theoretically and applied in policy. In response, this article investigates, through a comprehensive bibliometric analysis, how the twelve most frequent city categories are conceptualised individually and in relation to one another in the academic literature. We hypothesize that, notwithstanding some degree of overlap and cross-fertilization, in their essence the observed categories each harbour particular conceptual perspectives that render them distinctive. This is borne out by the findings, which demonstrate robustly for the first time the conceptual differences and interrelationships among twelve dominant city categories. The 'sustainable city' is the most frequently occurring category and, in a map of keyword co-occurrences, by far the largest and most interconnected node, linked closely to the 'eco-city' and 'green city' concepts. Recently, the more narrow concepts of 'low carbon city' and 'smart city' have been on the rise, judging by their frequency of occurrence in academic journals; the latter in particular appears to have become an increasingly dominant category of urban modernization policy. On their part, ‘resilient city’ and ‘knowledge city’ represent distinct concepts, albeit with comparatively low frequency. Overall, the findings point to the need for rigor and nuance in the use of these terms, not least if one wishes to comprehend their implications for urban development and regeneration policy and practice

Metabolic engineering to simultaneously activate anthocyanin and proanthocyanidin biosynthetic pathways in Nicotiana spp

[EN] Proanthocyanidins (PAs), or condensed tannins, are powerful antioxidants that remove harmful free oxygen radicals from cells. To engineer the anthocyanin and proanthocyanidin biosynthetic pathways to de novo produce PAs in two Nicotiana species, we incorporated four transgenes to the plant chassis. We opted to perform a simultaneous transformation of the genes linked in a multigenic construct rather than classical breeding or retransformation approaches. We generated a GoldenBraid 2.0 multigenic construct containing two Antirrhinum majus transcription factors (AmRosea1 and AmDelila) to upregulate the anthocyanin pathway in combination with two Medicago truncatula genes (MtLAR and MtANR) to produce the enzymes that will derivate the biosynthetic pathway to PAs production. Transient and stable transformation of Nicotiana benthamiana and Nicotiana tabacum with the multigenic construct were respectively performed. Transient expression experiments in N. benthamiana showed the activation of the anthocyanin pathway producing a purple color in the agroinfiltrated leaves and also the effective production of 208.5 nmol (-) catechin/g FW and 228.5 nmol (-) epicatechin/g FW measured by the p-dimethylaminocinnamaldehyde (DMACA) method. The integration capacity of the four transgenes, their respective expression levels and their heritability in the second generation were analyzed in stably transformed N. tabacum plants. DMACA and phoroglucinolysis/HPLC-MS analyses corroborated the activation of both pathways and the effective production of PAs in T0 and T1 transgenic tobacco plants up to a maximum of 3.48 mg/g DW. The possible biotechnological applications of the GB2.0 multigenic approach in forage legumes to produce "bloatsafe" plants and to improve the efficiency of conversion of plant protein into animal protein (ruminal protein bypass) are discussed.This work was supported by grants BIO2012-39849-C02-01 and BIO2016-75485-R from the Spanish Ministry of Economy and Competitiveness (MINECO) (http://www.idi.mineco.gob.es/portal/site/MICINN) to LAC and a fellowship of the JAE-CSIC program to SF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Fresquet-Corrales, S.; Roque Mesa, EM.; Sarrión-Perdigones, A.; Rochina, M.; López-Gresa, MP.; Díaz-Mula, HM.; Belles Albert, JM.... (2017). Metabolic engineering to simultaneously activate anthocyanin and proanthocyanidin biosynthetic pathways in Nicotiana spp. PLoS ONE. 12(9). https://doi.org/10.1371/journal.pone.0184839Se018483912

Amelioration of Experimental Autoimmune Encephalomyelitis in Alzheimer’s Disease Mouse Models: A Potential Role for Aβ

Emerging data have highlighted the coexistence of multiple sclerosis (MS) and Alzheimer’s disease (AD), both of which are common central nervous system degenerative diseases with a heavy burden on patients, their families, and society. However, it is unclear how MS progresses under an AD pathological background. We aimed to address the question of how MS progresses under an AD pathological background. We induced the experimental autoimmune encephalomyelitis (EAE) model of MS in two types of AD mouse models, Tg6799 and APP/PS1 mice. We found that, compared with wild-type mice, the clinical symptoms of EAE were significantly ameliorated in APP/PS1 mice but not in Tg6799 mice. Moreover, a much lower level of serum Aβ was observed in Tg6799 mice. EAE clinical symptoms in Tg6799 and C57BL/6J mice were ameliorated by intraperitoneal injection of Aβ42. Peripheral administration of Aβ42 peptides was able to inhibit Th17 development in vivo, which is likely to occur through the inhibition of IL-6 production in dendritic cells. Our findings revealed that AD and EAE could coexist in the same mouse, and Aβ residing in peripheral circulation likely plays an anti-inflammatory role in preventing EAE progression. These findings reveal the potential benefit of Aβ, one of the supervillains of AD, at least in certain contexts

CXCR1 drives the pathogenesis of EAE and ARDS via boosting dendritic cells-dependent inflammation

Abstract Chemokines secreted by dendritic cells (DCs) play a key role in the regulation of inflammation and autoimmunity through chemokine receptors. However, the role of chemokine receptor CXCR1 in inflammation-inducing experimental autoimmune encephalomyelitis (EAE) and acute respiratory distress syndrome (ARDS) remains largely enigmatic. Here we reported that compared with healthy controls, the level of CXCR1 was aberrantly increased in multiple sclerosis (MS) patients. Knockout of CXCR1 not only ameliorated disease severity in EAE mice but also suppressed the secretion of inflammatory factors (IL-6/IL-12p70) production. We observed the same results in EAE mice with DCs-specific deletion of CXCR1 and antibody neutralization of the ligand CXCL5. Mechanically, we demonstrated a positive feedback loop composed of CXCL5/CXCR1/HIF-1α direct regulating of IL-6/IL-12p70 production in DCs. Meanwhile, we found CXCR1 deficiency in DCs limited IL-6/IL-12p70 production and lung injury in LPS-induced ARDS, a disease model caused by inflammation. Overall, our study reveals CXCR1 governs DCs-mediated inflammation and autoimmune disorders and its potential as a therapeutic target for related diseases

Prevalence and risk factors of disability and anxiety in a retrospective cohort of 432 survivors of Coronavirus Disease-2019 (Covid-19) from China.

ObjectiveTo estimate the prevalence of disability and anxiety in Covid-19 survivors at discharge from hospital and analyze relative risk by exposures.DesignMulti-center retrospective cohort study.SettingTwenty-eight hospitals located in eight provinces of China.MethodsA total of 432 survivors with laboratory-confirmed SARS CoV-2 infection participated in this study. At discharge, we assessed instrumental activities of daily living (IADL) with Lawton's IADL scale, dependence in activities of daily living (ADL) with the Barthel Index, and anxiety with Zung's self-reported anxiety scale. Exposures included comorbidity, smoking, setting (Hubei vs. others), disease severity, symptoms, and length of hospital stay. Other risk factors considered were age, gender, and ethnicity (Han vs. Tibetan).ResultsPrevalence of at least one IADL problem was 36.81% (95% CI: 32.39-41.46). ADL dependence was present in 16.44% (95% CI: 13.23-20.23) and 28.70% (95% CI: 24.63-33.15) were screened positive for clinical anxiety. Adjusted risk ratio (RR) of IADL limitations (RR 2.48, 95% CI: 1.80-3.40), ADL dependence (RR 2.07, 95% CI 1.15-3.76), and probable clinical anxiety (RR 2.53, 95% CI 1.69-3.79) were consistently elevated in survivors with severe Covid-19. Age was an additional independent risk factor for IADL limitations and ADL dependence; and setting (Hubei) for IADL limitations and anxiety. Tibetan ethnicity was a protective factor for anxiety but a risk factor for IADL limitations.ConclusionA significant proportion of Covid-19 survivors had disability and anxiety at discharge from hospital. Health systems need to be prepared for an additional burden resulting from rehabilitation needs of Covid-19 survivors