364 research outputs found
Key role of dysregulated airway epithelium in response to respiratory viral infections in asthma
A differentiated air–liquid interface model shows that the airway epithelium plays a key role in response to respiratory viral infections in people with asthma https://bit.ly/3yDgiX
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Group 2 Innate Lymphoid Cells Are Redundant in Experimental Renal Ischemia-Reperfusion Injury.
Acute kidney injury (AKI) can be fatal and is a well-defined risk factor for the development of chronic kidney disease. Group 2 innate lymphoid cells (ILC2s) are innate producers of type-2 cytokines and are critical regulators of homeostasis in peripheral organs. However, our knowledge of their function in the kidney is relatively limited. Recent evidence suggests that increasing ILC2 numbers by systemic administration of recombinant interleukin (IL)-25 or IL-33 protects against renal injury. Whilst ILC2s can be induced to protect against ischemic- or chemical-induced AKI, the impact of ILC2 deficiency or depletion on the severity of renal injury is unknown. Firstly, the phenotype and location of ILC2s in the kidney was assessed under homeostatic conditions. Kidney ILC2s constitutively expressed high levels of IL-5 and were located in close proximity to the renal vasculature. To test the functional role of ILC2s in the kidney, an experimental model of renal ischemia-reperfusion injury (IRI) was used and the severity of injury was assessed in wild-type, ILC2-reduced, ILC2-deficient, and ILC2-depleted mice. Surprisingly, there were no differences in histopathology, collagen deposition or mRNA expression of injury-associated (Lcn2), inflammatory (Cxcl1, Cxcl2, and Tnf) or extracellular matrix (Col1a1, Fn1) factors following IRI in the absence of ILC2s. These data suggest the absence of ILC2s does not alter the severity of renal injury, suggesting possible redundancy. Therefore, other mechanisms of type 2-mediated immune cell activation likely compensate in the absence of ILC2s. Hence, a loss of ILC2s is unlikely to increase susceptibility to, or severity of AKI
Plants derived therapeutic strategies targeting chronic respiratory diseases: Chemical and immunological perspective
The apparent predicament of the representative chemotherapy for managing respiratory distress calls for an obligatory deliberation for identifying the pharmaceuticals that effectively counter the contemporary intricacies associated with target disease. Multiple, complex regulatory pathways manifest chronic pulmonary disorders, which require chemotherapeutics that produce composite inhibitory effect. The cost effective natural product based molecules hold a high fervor to meet the prospects posed by current respiratory-distress therapy by sparing the tedious drug design and development archetypes, present a robust standing for the possible replacement of the fading practice of poly-pharmacology, and ensure the subversion of a potential disease relapse. This study summarizes the experimental evidences on natural products moieties and their components that illustrates therapeutic efficacy on respiratory disorders
The diagnostic potential of oxidative stress biomarkers for preeclampsia : systematic review and meta-analysis
Background: Preeclampsia is a multifactorial cardiovascular disorder of pregnancy. If left untreated, it can lead to severe maternal and fetal outcomes. Hence, timely diagnosis and management of preeclampsia are extremely important. Biomarkers of oxidative stress are associated with the pathogenesis of preeclampsia and therefore could be indicative of evolving preeclampsia and utilized for timely diagnosis. In this study, we conducted a systematic review and meta-analysis to determine the most reliable oxidative stress biomarkers in preeclampsia, based on their diagnostic sensitivities and specificities as well as their positive and negative predictive values. Methods: A systematic search using PubMed, ScienceDirect, ResearchGate, and PLOS databases (1900 to March 2021) identified nine relevant studies including a total of 343 women with preeclampsia and 354 normotensive controls. Results: Ischemia-modified albumin (IMA), uric acid (UA), and malondialdehyde (MDA) were associated with 3.38 (95% CI 2.23, 4.53), 3.05 (95% CI 2.39, 3.71), and 2.37 (95% CI 1.03, 3.70) odds ratios for preeclampsia diagnosis, respectively. The IMA showed the most promising diagnostic potential with the positive predictive ratio (PPV) of 0.852 (95% CI 0.728, 0.929) and negative predictive ratio (NPV) of 0.811 (95% CI 0.683, 0.890) for preeclampsia. Minor between-study heterogeneity was reported for these biomarkers (Higgins’ I2 = 0–15.879%). Conclusions: This systematic review and meta-analysis identified IMA, UA, and MDA as the most promising oxidative stress biomarkers associated with established preeclampsia. IMA as a biomarker of tissue damage exhibited the best diagnostic test accuracy. Thus, these oxidative stress biomarkers should be further explored in larger cohorts for preeclampsia diagnosis
A unique role for IL-13 in inducing esophageal eosinophilia through MID-1 and STAT6
IntroductionEosinophilic esophagitis (EoE) is associated with allergen-driven inflammation of the esophagus and an upregulated Th2 cytokine signature. Recombinant interleukin (IL)-13 (rIL-13) administration to mice induces some of the hallmark features of EoE, including increased eotaxin expression and eosinophil recruitment. Inflammation in EoE has previously been shown to depend on the expression of TRAIL and MID-1, which reduced protein phosphatase 2A (PP2A) activity. The relationship between IL-13 and TRAIL signalling in esophageal eosinophilia is currently unknown.ObjectiveTo investigate the interaction between IL-13-driven eosinophil infiltration and TRAIL or MID-1 in the esophagus.MethodWe administered rIL-13 to wild type (WT), TRAIL-deficient (Tnsf10−/−) or STAT6-deficient (STAT6−/−) mice and targeted MID-1 with small interfering RNA.ResultsrIL-13 administration to mice increased TRAIL and MID-1 expression in the esophagus while reducing PP2A activity. TRAIL deficient, but not STAT6 deficient mice demonstrated increased MID-1 expression and PP2A reduction upon IL-13 challenge which correlated with eosinophil infiltration into the esophagus. Silencing MID-1 expression with siRNA completely ablated IL-13 induced eosinophil infiltration of the esophagus, restored PP2A activity, and reduced eotaxin-1 expression.ConclusionIL-13-driven eosinophil infiltration of the esophagus induced eosinophilia and eotaxin-1 expression in a STAT6-dependent and MID-1-dependent manner. This study highlights a novel mechanism employed by IL-13 to perpetuate eosinophil infiltration
Group 2 Innate Lymphoid Cells Are Redundant in Experimental Renal Ischemia-Reperfusion Injury
Acute kidney injury (AKI) can be fatal and is a well-defined risk factor for the development of chronic kidney disease. Group 2 innate lymphoid cells (ILC2s) are innate producers of type-2 cytokines and are critical regulators of homeostasis in peripheral organs. However, our knowledge of their function in the kidney is relatively limited. Recent evidence suggests that increasing ILC2 numbers by systemic administration of recombinant interleukin (IL)-25 or IL-33 protects against renal injury. Whilst ILC2s can be induced to protect against ischemic- or chemical-induced AKI, the impact of ILC2 deficiency or depletion on the severity of renal injury is unknown. Firstly, the phenotype and location of ILC2s in the kidney was assessed under homeostatic conditions. Kidney ILC2s constitutively expressed high levels of IL-5 and were located in close proximity to the renal vasculature. To test the functional role of ILC2s in the kidney, an experimental model of renal ischemia-reperfusion injury (IRI) was used and the severity of injury was assessed in wild-type, ILC2-reduced, ILC2-deficient, and ILC2-depleted mice. Surprisingly, there were no differences in histopathology, collagen deposition or mRNA expression of injury-associated (Lcn2), inflammatory (Cxcl1, Cxcl2, and Tnf) or extracellular matrix (Col1a1, Fn1) factors following IRI in the absence of ILC2s. These data suggest the absence of ILC2s does not alter the severity of renal injury, suggesting possible redundancy. Therefore, other mechanisms of type 2-mediated immune cell activation likely compensate in the absence of ILC2s. Hence, a loss of ILC2s is unlikely to increase susceptibility to, or severity of AKI
Inhibition of beta-Catenin/CREB Binding Protein Signaling Attenuates House Dust Mite-Induced Goblet Cell Metaplasia in Mice
Excessive mucus production is a major feature of allergic asthma. Disruption of epithelial junctions by allergens such as house dust mite (HDM) results in the activation of β-catenin signaling, which has been reported to stimulate goblet cell differentiation. β-catenin interacts with various co-activators including CREB binding protein (CBP) and p300, thereby regulating the expression of genes involved in cell proliferation and differentiation, respectively. We specifically investigated the role of the β-catenin/CBP signaling pathway in goblet cell metaplasia in a HDM-induced allergic airway disease model in mice using ICG-001, a small molecule inhibitor that blocks the binding of CBP to β-catenin. Female 6- 8-week-old BALB/c mice were sensitized to HDM/saline on days 0, 1, and 2, followed by intranasal challenge with HDM/saline with or without subcutaneous ICG-001/vehicle treatment from days 14 to 17, and samples harvested 24 h after the last challenge/treatment. Differential inflammatory cells in bronchoalveolar lavage (BAL) fluid were enumerated. Alcian blue (AB)/Periodic acid–Schiff (PAS) staining was used to identify goblet cells/mucus production, and airway hyperresponsiveness (AHR) was assessed using invasive plethysmography. Exposure to HDM induced airway inflammation, goblet cell metaplasia and increased AHR, with increased airway resistance in response to the non-specific spasmogen methacholine. Inhibition of the β-catenin/CBP pathway using treatment with ICG-001 significantly attenuated the HDM-induced goblet cell metaplasia and infiltration of macrophages, but had no effect on eosinophils, neutrophils, lymphocytes or AHR. Increased β-catenin/CBP signaling may promote HDM-induced goblet cell metaplasia in mice
Host-microbe cross-talk in the lung microenvironment:implications for understanding and treating chronic lung disease
Chronic respiratory diseases are highly prevalent worldwide and will continue to rise in the foreseeable future. Despite intensive efforts over recent decades, the development of novel and effective therapeutic approaches has been slow. However, there is new and increasing evidence that communities of micro-organisms in our body, the human microbiome, are crucially involved in the development and progression of chronic respiratory diseases. Understanding the detailed mechanisms underlying this cross-talk between host and microbiota is critical for development of microbiome- or host-targeted therapeutics and prevention strategies. Here we review and discuss the most recent knowledge on the continuous reciprocal interaction between the host and microbes in health and respiratory disease. Furthermore, we highlight promising developments in microbiome-based therapies and discuss the need to employ more holistic approaches of restoring both the pulmonary niche and the microbial community
A large-scale automated radio telemetry network for monitoring movements of terrestrial wildlife in Australia
Technologies for remotely observing animal movements have advanced rapidly in the past decade. In recent years, Australia has invested in an Integrated Marine Ocean Tracking (IMOS) system, a land ecosystem observatory (TERN), and an Australian Acoustic Observatory (A2O), but has not established movement tracking systems for individual terrestrial animals across land and along coastlines. Here, we make the case that the Motus Wildlife Tracking System, an open-source, rapidly expanding cooperative automated radio-tracking global network (Motus, https://motus.org) provides an unprecedented opportunity to build an affordable and proven infrastructure that will boost wildlife biology research and connect Australian researchers domestically and with international wildlife research. We briefly describe the system conceptually and technologically, then present the unique strengths of Motus, how Motus can complement and expand existing and emerging animal tracking systems, and how the Motus framework provides a much-needed central repository and impetus for archiving and sharing animal telemetry data. We propose ways to overcome the unique challenges posed by Australia’s ecological attributes and the size of its scientific community. Open source, inherently cooperative and flexible, Motus provides a unique opportunity to leverage individual research effort into a larger collaborative achievement, thereby expanding the scale and scope of individual projects, while maximising the outcomes of scant research and conservation funding
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