46 research outputs found

    9-PAHSA displays a weak anti-inflammatory potential mediated by specific antagonism of chemokine G protein-coupled receptors

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    Introduction: 9-PAHSA belongs to a class of endogenous mammalian bioactive lipids, fatty acid esters of hydroxy fatty acids (FAHFA), that are present in circulation at nanomolar concentrations in mice and humans. Published preclinical data suggest beneficial effects of 9-PAHSA treatment on glucose metabolism as well as modulation of immune function. However, receptor molecules with high affinity towards these lipids have not been identified so far.Methods: In a broad screen of a panel of G protein-coupled receptors (GPCRs) we discovered that 9-PAHSA displays antagonist activity with an IC50 in the micromolar range on selected chemokine receptors, namely, CCR6, CCR7, CXCR4, and CXCR5. The potential immunomodulatory activities in a human cellular model of innate immunity were then investigated.Results and discussion: In our in vitro experiments, a weak anti-inflammatory potential for high concentrations of 9-PAHSA (10–100 µM) could be detected, as treatment reduced the LPS-induced secretion of certain chemokines, such as CXCL10, MIP-1 beta and MCP. Regarding metabolic effects, we re-investigated 9-PAHSA on glucose metabolism and insulin sensitivity in vitro and in mice confirming conclusions from our earlier study that FAHFAs lack glucoregulatory activity following an acute treatment. In conclusion, the specific interactions with a subset of chemokine receptors may contribute to weak anti-inflammatory properties of 9-PAHSA, but further studies are needed to confirm its in anti-inflammatory potential in vivo

    Impact of telehealth interventions on physiological and psychological outcomes in breast cancer survivors: A meta-analysis of randomised controlled trials

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    IntroductionThe use of telehealth interventions has been evaluated in different perspectives in women and also supported with various clinical trials, but its overall efficacy is still ascertained. The objective of the present review is to identify, appraise and analyze randomized controlled trials on breast cancer survivors who have participated in technology-based intervention programs incorporating a wide range of physical and psychological outcome measures.Material and methodsWe conducted electronic search of the literature during last twenty years i.e., from 2001 till August 10, 2021 through four databases. Standardized mean difference with 95% confidence interval was used.ResultsA total of 56 records were included in the qualitative and 28 in quantitative analysis. Pooled results show that telehealth interventions were associated with improved quality of life (SMD 0.48, 95% CI 0.03 to 0.92, p=0.04), reduced depression (SMD -1.27, 95% CI =-2.43 to -0.10 p=0.03), low distress and less perceived stress (SMD -0.40, 95% CI =-0.68 to -0.12, p=0.005). However, no significant differences were observed on weight change (SMD -0.27, 95% CI =-2.39 to 1.86, p=0.81) and anxiety scores (SMD -0.09, 95% CI =-0.20 to 0.02, p=0.10) between the two groups. Improvement in health care competence and fitness among participants was also reported.ConclusionStudy concludes that telehealth care is a quick, convenient and assuring approach to breast cancer care in women that can reduce treatment burden and subsequent disturbance to the lives of breast cancer survivors

    Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses

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    Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system

    COVID-19 Vaccine Hesitancy among the General Population: A Cross-Sectional Study

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    Hesitancy about receiving vaccines has been deemed a global danger to public health by WHO. The sociocultural backgrounds of the people have an impact on vaccine acceptance. The purpose of this study was to examine the effect of sociodemographic factors on COVID-19 vaccination hesitancy as well as to identify the factors that contributed to COVID-19 vaccine hesitancy. Methods: A cross-sectional study was carried out to determine the primary variables causing COVID-19 vaccination hesitancy among residents of Pune. The general population was sampled through simple random sampling. The minimum sample size was determined to be 1246. The questionnaire inquired about the individuals’ sociodemographic information, vaccination status, and reasons for vaccine hesitancy. Results: In total, there were 5381 subjects, 1669 of whom were unvaccinated and 3712 of whom were partially vaccinated. Fear of adverse effects (51.71%), fear of losing a few days of work (43.02%), and inability to secure a vaccine slot online (33.01%) were the most frequently cited reasons. An older population (>60 years, p = 0.004), males (p = 0.032), those who were literate (p = 0.011), those of lower middle socioeconomic status (p = 0.001), and smokers were significantly associated with fear and mistrust of the COVID-19 vaccine, while mistrust of the vaccine was greatest among individuals from the upper and lower middle classes (p = 0.001). Conclusion: Vaccine hesitancy due to concerns about the side effects and long-term complications was prevalent among the elderly, males, those from the lower middle class, and smokers. This study emphasizes the importance of communicating effectively about the vaccine’s efficacy, its distribution, and vaccination sites

    Data from: Evaluation of the innate immunostimulatory potential of originator and non-originator copies of insulin glargine in an in vitro human immune model

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    Background: The manufacture of insulin analogs requires sophisticated production procedures which can lead to differences in the structure, purity, and/or other physiochemical properties of resultant products that can affect their biologic activity. Here, we sought to compare originator and non-originator copies of insulin glargine for innate immune activity and mechanisms leading to differences in these response profiles in an in vitro model of human immunity. Methods: An endothelial/dendritic cell-based innate immune model was used to study antigen-presenting cell activation, cytokine secretion, and insulin receptor signalling pathways induced by originator and non-originator insulin glargine products. Mechanistic studies included signalling pathway blockade with specific inhibitors, analysis of the products in a Toll-like receptor reporter cell line assay, and insulin removal from the products by immunopurification. Findings: All insulin glargine products elicited at least a minor innate immune response comparable to human insulin, but some lots of a non-originator copy product induced the elevated secretion of the cytokines, IL-8 and IL-6. In studies aimed at addressing the mechanisms leading to differential cytokine production by these products, we found (1) the inflammatory response was not mediated by bacterial contaminants, (2) the innate response was driven by the insulin receptor through the MAPK pathway, and (3) the removal of insulin significantly reduced their capacity to induce innate activity. No evidence of product aggregates was detected, though the presence of some high molecular weight proteins argues for the presence of insulin dimers or others contaminants in these products. Conclusion: The data presented here suggests some non-originator insulin glargine product lots drive heightened in vitro human innate activity and provides preliminary evidence that changes in their biochemical composition (dimers, impurities) might be responsible for their greater immunostimulatory potential

    Monkeypox: An Unfamiliar Virus—Clinical and Epidemiological Characteristics, Diagnosis, and Treatment with Special Emphasis on Oral Health

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    With the recent increased prevalence of human outbreaks, monkeypox has been recognized for decades as an infectious disease with substantial pandemic potential. The majority of cases of this virus have been observed in the European region (11,865), with few cases in the Western Pacific (54). Various governing health agencies are striving to restrain the fatal monkeypox virus (MPXV). Health practitioners around the world are learning about the many clinical manifestations of this infection, and its potential therapies. Despite the plethora of new evidence and rising cases, the essential questions remain unsolved. Thus, in this review, we have modernized the outlook for monkeypox, which will be helpful for various medical practitioners. In the light of continuing outbreaks around the world, we have also presented our assessment of the readiness of India against this outbreak, with a special focus on its effects on oral health

    DataSheet1_9-PAHSA displays a weak anti-inflammatory potential mediated by specific antagonism of chemokine G protein-coupled receptors.docx

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    Introduction: 9-PAHSA belongs to a class of endogenous mammalian bioactive lipids, fatty acid esters of hydroxy fatty acids (FAHFA), that are present in circulation at nanomolar concentrations in mice and humans. Published preclinical data suggest beneficial effects of 9-PAHSA treatment on glucose metabolism as well as modulation of immune function. However, receptor molecules with high affinity towards these lipids have not been identified so far.Methods: In a broad screen of a panel of G protein-coupled receptors (GPCRs) we discovered that 9-PAHSA displays antagonist activity with an IC50 in the micromolar range on selected chemokine receptors, namely, CCR6, CCR7, CXCR4, and CXCR5. The potential immunomodulatory activities in a human cellular model of innate immunity were then investigated.Results and discussion: In our in vitro experiments, a weak anti-inflammatory potential for high concentrations of 9-PAHSA (10–100 µM) could be detected, as treatment reduced the LPS-induced secretion of certain chemokines, such as CXCL10, MIP-1 beta and MCP. Regarding metabolic effects, we re-investigated 9-PAHSA on glucose metabolism and insulin sensitivity in vitro and in mice confirming conclusions from our earlier study that FAHFAs lack glucoregulatory activity following an acute treatment. In conclusion, the specific interactions with a subset of chemokine receptors may contribute to weak anti-inflammatory properties of 9-PAHSA, but further studies are needed to confirm its in anti-inflammatory potential in vivo.</p
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