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Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria

Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria
science.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from science.org Daily Mail and Mail on Sunday newspapers.

Discoverx-pathhunter , Tocris-bioscience , Norbinaltorphimine-nor , Harlan-sprague-dawley , Association-for-assessment , Associates-inc , Scripps-research-institute-jupiter , Accreditation-of-laboratory-animal-care , Analysis-software , Perkinelmer , Wake-forest-school-of-medicine-winston-salem

Microglial cell response to experimental periodontal disease | Journal of Neuroinflammation

Microglial activation is critical for modulating the neuroinflammatory process and the pathological progression of neurodegenerative diseases, such as Alzheimer's disease (AD). Microglia are involved in forming barriers around extracellular neuritic plaques and the phagocytosis of β-amyloid peptide (Aβ). In this study, we tested the hypothesis that periodontal disease (PD) as a source of infection alters inflammatory activation and Aβ phagocytosis by the microglial cells. Experimental PD was induced using ligatures in C57BL/6 mice for 1, 10, 20, and 30 days to assess the progression of PD. Animals without ligatures were used as controls. Maxillary bone loss and local periodontal tissue inflammation associated with the development of PD were confirmed by morphometric bone analysis and cytokine expression, respectively. The frequency and the total number of activated microglia (CD45+ CD11b+ MHCII+) in the brain were analyzed by flow cytometry. Mouse microglial cells (1 × 105) were incubated with heat-inactivated bacterial biofilm isolated from the ligatures retrieved from the teeth or with Klebsiella variicola, a relevant PD-associated bacteria in mice. Expression of pro-inflammatory cytokines, toll-like receptors (TLR), and receptors for phagocytosis was measured by quantitative PCR. The phagocytic capacity of microglia to uptake β-amyloid was analyzed by flow cytometry. Ligature placement caused progressive periodontal disease and bone resorption that was already significant on day 1 post-ligation (p < 0.05) and continued to increase until day 30 (p < 0.0001). The severity of periodontal disease increased the frequency of activated microglia in the brains on day 30 by 36%. In parallel, heat-inactivated PD-associated total bacteria and Klebsiella variicola increased the expression of TNFα, IL-1β, IL-6, TLR2, and TLR9 in microglial cells (1.6-, 83-, 3.2-, 1.5-, 1.5-fold, respectively p < 0.01). Incubation of microglia with Klebsiella variicola increased the Aβ-phagocytosis by 394% and the expression of the phagocytic receptor MSR1 by 33-fold compared to the non-activated cells (p < 0.0001). We showed that inducing PD in mice results in microglia activation in vivo and that PD-associated bacteria directly promote a pro-inflammatory and phagocytic phenotype in microglia. These results support a direct role of PD-associated pathogens in neuroinflammation.

Fiji , United-states , Italy , La-jolla , California , Fremont , San-diego , Canada , Miltenyi-biotec , Dnasei-zymo-research , Hbss-rd-systems-inc , Sigma-aldrich

mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent

mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent
science.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from science.org Daily Mail and Mail on Sunday newspapers.

Guinea , Kyoto , Japan , Canada , Powassan , Ontario , United-states , America , Supermix-bio-rad , Qiagen-rneasy , Cleancap-trilink , Mann-whitney-welch

Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity

Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity
elifesciences.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from elifesciences.org Daily Mail and Mail on Sunday newspapers.

France , Hamburg , Germany , Paris , France-general- , Burlington , California , United-states , Cambridge , Cambridgeshire , United-kingdom , Vienna

Identification of immune-related candidate biomarkers in plasma of patients with sporadic vestibular schwannoma

Identification of immune-related candidate biomarkers in plasma of patients with sporadic vestibular schwannoma
science.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from science.org Daily Mail and Mail on Sunday newspapers.

Massachusetts , United-states , Vienna , Wien , Austria , Burlington , Rockville , Waltham , Ostend , Region-flamande , Belgium , Boston

Six-hour time-restricted feeding inhibits lung cancer progression and reshapes circadian metabolism | BMC Medicine

Accumulating evidence has suggested an oncogenic effect of diurnal disruption on cancer progression. To test whether targeting circadian rhythm by dietary strategy suppressed lung cancer progression, we adopted 6-h time-restricted feeding (TRF) paradigm to elucidate whether and how TRF impacts lung cancer progression. This study used multiple lung cancer cell lines, two xenograft mouse models, and a chemical-treated mouse lung cancer model. Stable TIM-knockdown and TIM-overexpressing A549 cells were constructed. Cancer behaviors in vitro were determined by colony formation, EdU proliferation, wound healing, transwell migration, flow cytometer, and CCK8 assays. Immunofluorescence, pathology examinations, and targeted metabolomics were also used in tumor cells and tissues. mCherry-GFP-LC3 plasmid was used to detect autophagic flux. We found for the first time that compared to normal ad libitum feeding, 6-h TRF inhibited lung cancer progression and reprogrammed the rhythms of metabolites or genes involved in glycolysis and the circadian rhythm in tumors. After TRF intervention, only timeless (TIM) gene among five lung cancer-associated clock genes was found to consistently align rhythm of tumor cells to that of tumor tissues. Further, we demonstrated that the anti-tumor effect upon TRF was partially mediated by the rhythmic downregulation of the TIM and the subsequent activation of autophagy. Combining TRF with TIM inhibition further enhanced the anti-tumor effect, comparable to treatment efficacy of chemotherapy in xenograft model. Six-hour TRF inhibits lung cancer progression and reshapes circadian metabolism, which is partially mediated by the rhythmic downregulation of the TIM and the subsequent upregulation of autophagy.

Chicago , Illinois , United-states , Wuhan , Hubei , China , Lipo , Hainan , Tokyo , Japan , Wuxi , Jiangsu

Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies

Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies
elifesciences.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from elifesciences.org Daily Mail and Mail on Sunday newspapers.

Turkey , Japan , Wuhan , Hubei , China , Osaka , Beckton-dickinson , Cryopreserved-pbmcs , Osaka-university-institutional-review-board , Cell-signaling-technology , Ge-healthcare , Department-of-health-development

Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation

Immunoglobulin M regulates airway hyperresponsiveness independent of T helper 2 allergic inflammation
elifesciences.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from elifesciences.org Daily Mail and Mail on Sunday newspapers.

United-states , Texas , Germany , Randburg , Gauteng , South-africa , University-of-cape-town , Western-cape , Waltham , Massachusetts , Johannesburg , United-kingdom

SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood | Infectious Diseases | JAMA

This longitudinal study of young children in 5 European countries investigates whether there is a temporal association between SARS-CoV-2 infection and islet au

Warsaw , L67- , Poland , Sweden , Dresden , Sachsen , Germany , United-states , Belgium , United-kingdom , Munich , Bayern

A blood-based marker of mitochondrial DNA damage in Parkinson's disease | Science Translational Medicine

A blood-based marker of mitochondrial DNA damage in Parkinson's disease | Science Translational Medicine
science.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from science.org Daily Mail and Mail on Sunday newspapers.

Italy , Oregon , United-states , Australia , Blue-rock , Vanqua-bio , Resolight-roche , Genzyme-sanofi , Science-center , Scientist-office-senior-clinical-academic-fellowship , Critical-path-for-parkinson-consortium , Ethical-committee