scholarly journals Current Trends in IBD—Development of Mucosal-Based Biomarkers and a Novel Minimally Invasive Recoverable Sampling System

2021 ◽  
Vol 27 (Supplement_2) ◽  
pp. S17-S24 ◽  
Author(s):  
Yunki Y Yau ◽  
Valerie C Wasinger ◽  
Robert P Hirten ◽  
Emil Chuang ◽  
Merodean Huntsman ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Mucosal Healing ◽  
Diagnostic Tools ◽  
Disease Monitoring ◽  
Gut Health ◽  
Sampling System ◽  
Bowel Diseases ◽  
Recent Developments ◽  
Host Microbe Interactions ◽  
New Treatment

Abstract Despite recent developments in therapy for inflammatory bowel diseases (IBDs), there have been limited advances in diagnostic tools available to aid in disease management. A growing body of evidence suggests that there are important host-microbe interactions at the mucosal interface that modulate the inflammatory response in patients with IBD. Additionally, the importance of mucosal integrity and its disruption appears to be important in the pathophysiology and perpetuation of the disease. The ability to characterize this interface may provide valuable information for both disease monitoring and identification of new treatment targets. Endoscopy remains the primary tool for disease monitoring, and mucosal healing is the primary therapeutic target in IBD treatment. However, establishing mucosal healing requires repetitive endoscopic procedures, and endoscopy is limited by factors such as invasiveness, cost, and risk of adverse events. Moreover, the use of a bowel preparation for colonoscopies alters the mucus layer and thus perturbs evaluation of the host-microbe interaction. Stool sampling may also be inaccurate because it reflects the end state of metabolites and proteins, failing to take into account the degradation or alteration of substrates of interest by bacterial proteases and other enzymes during passage through the colon. A novel sampling capsule, called the Recoverable Sampling System (RSS), is being developed as a complementary tool to colonoscopy. The RSS is intended to be a platform for noninvasive autonomous sampling, preservation, handling, and storage of analytes of interest found in the gastrointestinal fluids. A proprietary preservative contained within the chambers of the capsule has been developed to stabilize DNA and proteins for ex vivo microbiome and metabolomics analyses. Surrogate markers such as SPP24 and GUCA2a have been identified to correlate with gut health, intestinal permeability, and inflammation and could be locally sampled by the RSS. The potential clinical utility of an RSS device is broad and would likely be able to guide therapy by allowing for more frequent disease monitoring, aiding in disease characterization, and facilitating in the identification of novel therapeutic targets.

scholarly journals The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Camille Kropp ◽  
Katy Le Corf ◽  
Karima Relizani ◽  
Kevin Tambosco ◽  
Ccori Martinez ◽  
...  
Keyword(s):  
Mucosal Healing ◽  
Intestinal Cell ◽  
Intestinal Damage ◽  
Intestinal Epithelial ◽  
Gut Health ◽  
Bowel Diseases ◽  
Anti Inflammatory ◽  
Microbial Symbiosis

AbstractChristensenellaceae is a family of subdominant commensal bacteria found in humans. It is thought to play an important role in gut health by maintaining microbial symbiosis. Indeed, these bacteria occur at significantly lower levels or are absent in individuals suffering from inflammatory bowel diseases (IBDs). Here, we explored if type species Christensenella minuta (strain: DSM 22607) could have the potential to help treat IBDs. We assessed key properties displayed by the bacterium using a combination of in vitro and in vivo assays. We found that while C. minuta is a strict anaerobe, it is also oxygen tolerant. Additionally, we observed that the species produces high levels of acetate and moderate levels of butyrate. We performed deep phenotyping using Biolog microarrays. Using human intestinal cell lines, we discovered that C. minuta demonstrated strong anti-inflammatory activity, resulting in reduced levels of proinflammatory IL-8 cytokines via the inhibition of the NF-κB signaling pathway. Furthermore, C. minuta protected intestinal epithelial integrity in vitro. Finally, in two distinct animal models of acute colitis, C. minuta prevented intestinal damage, reduced colonic inflammation, and promoted mucosal healing. Together, these results indicate that C. minuta has potent immunomodulatory properties, underscoring its potential use in innovative microbiome-based IBD biotherapies.

Application of Nanomaterials in Regulating the Fate of Adipose-derived Stem Cells

2021 ◽  
Vol 16 (1) ◽  
pp. 3-13
Author(s):  
Lang Wang ◽  
Yong Li ◽  
Maorui Zhang ◽  
Kui Huang ◽  
Shuanglin Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Research ◽  
Adult Stem Cells ◽  
Adipose Derived Stem Cells ◽  
Proliferation And Differentiation ◽  
Recent Developments ◽  
Good Biocompatibility ◽  
Regulatory Effects ◽  
New Treatment

Adipose-derived stem cells are adult stem cells which are easy to obtain and multi-potent. Stem-cell therapy has become a promising new treatment for many diseases, and plays an increasingly important role in the field of tissue repair, regeneration and reconstruction. The physicochemical properties of the extracellular microenvironment contribute to the regulation of the fate of stem cells. Nanomaterials have stable particle size, large specific surface area and good biocompatibility, which has led them being recognized as having broad application prospects in the field of biomedicine. In this paper, we review recent developments of nanomaterials in adipose-derived stem cell research. Taken together, the current literature indicates that nanomaterials can regulate the proliferation and differentiation of adipose-derived stem cells. However, the properties and regulatory effects of nanomaterials can vary widely depending on their composition. This review aims to provide a comprehensive guide for future stem-cell research on the use of nanomaterials.

Recent developments and opportunities in fighting COVID-19

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Vikram Rao ◽  
Subrat Kumar Bhattamisra
Keyword(s):  
World Health ◽  
Diagnostic Tools ◽  
Extensive Literature ◽  
Angiotensin Converting Enzyme 2 ◽  
Recent Developments ◽  
Therapeutic Molecules ◽  
Discharged Patients ◽  
Extensive Literature Search ◽  
Repurposed Drugs ◽  
Health Organization

Background: COVID-19, a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) was first diagnosed in the patients from Wuhan, China in December 2019. Within couple of months of infection, it was declared as pandemic by World health organization. COVID-19 has become the most contagious infection with a serious threat to global health. In this review, we aimed to discuss the pathogenesis, diagnostics, current treatments and potential vaccines for COVID-19. Methods: An extensive literature search was conducted using keywords “COVID-19”; “Coronavirus”; “SARS-Cov-2”; “SARS” in public domains of Google, Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Results: SARS-Cov-2 uses the Spike (S) protein on its surface to recognize the receptor on angiotensin-converting enzyme 2 (ACE2) and bind with 10-folds greater affinity than SARS-Cov-1. Molecular assays and immunoassays are the most frequently used tests whereas computed tomography (CT) scans, Artificial intelligence enabled diagnostic tools were also used in patients. In therapeutic treatment, few drugs were repurposed and there are 23 therapeutic molecules including the repurposed drugs are in different stages of clinical trial. Similarly, development of vaccines is also in the pipeline. Few countries have managed well to contain the spread by rapid testing and identifying the clusters. Conclusion: Till now, the acute complications and mortality of COVID-19 has been linked to the pre-existing comorbid conditions or age. Besides the development of therapeutic strategies that includes drugs and vaccine, the long term implication of COVID-19 infection in terms of the disorder/disability in the cured/discharged patients is a new area to investigate.

scholarly journals A31 COMPLEX ROLE OF DIETARY FIBERS IN IBD: MICROBES MEDIATE FIBER-INDUCED INFLAMMATION

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 148-150
Author(s):  
H Armstrong ◽  
R Valcheva ◽  
D Santer ◽  
Z Zhang ◽  
A Rieger ◽  
...  
Keyword(s):  
Immune Responses ◽  
Anaerobic Fermentation ◽  
Ex Vivo ◽  
Severe Disease ◽  
Cytokine Secretion ◽  
Dietary Fibers ◽  
Gut Health ◽  
T84 Cells ◽  
Microbial Composition ◽  
Barrier Integrity

Abstract Background Dietary fibers pass through the bowel undigested and are fermented within the intestine by microbes, typically promoting gut health. However, many IBD patients describe experiencing sensitivity to fibers. β-glucan, found on the surface of fungal cells during fungal infection, has been shown to bind to fiber receptors, such as Dectin-1, on host immune cells, resulting in a pro-inflammatory response. These fungal fibres share properties with dietary fibers. Aims As an altered gut microbial composition has been associated with IBD, we hypothesized that the loss of fiber-fermenting microbes populating the gut in IBD could lead to dietary fibers not being efficiently broken down into their beneficial biproducts (e.g. short chain fatty acids; SCFA), resulting in binding of intact fibers to pro-inflammatory host cell receptors. Methods Immune and epithelial cell lines and colonic biopsies cultured ex vivo were incubated with oligofructose or inulin (5g/L), or pre-fermented fibers (24hr anaerobic fermentation). Immune responses were measured by cytokine secretion (ELISA), and expression (qPCR). Barrier integrity was measured by transepithelial resistance (TEER). Food frequency questionnaire (FFQ) data of patient fiber consumption were correlated with gut microbes (shotgun sequencing) and immune responses to fiber in patient biopsies. Results Unfermented oligofructose induced IL-1β secretion in leukocytes (macrophage, T cell, neutrophil) and in colon biopsies from pediatric Crohn disease (CD; n=38) and ulcerative colitis (UC; n=20) patients cultured ex vivo, but not in non-IBD patients (n=21). IL-1β secretion was greater in patients with more severe disease. Pre-fermentation of oligofructose by whole-microbe intestinal washes from non-IBD patients or remission patients reduced secretion of IL-1β, while whole microbe intestinal washes from severe IBD patients were unable to ferment oligofructose or reduce cytokine secretion. Fiber effects on IL-1β secretion in biopsies positively correlated with effects on barrier integrity in T84 cells. Fiber-associated immune responses in patient biopsies cultured ex vivo (ELISA) correlated with fiber avoidance (FFQ) and gut microbiome (sequencing) in matching patient samples. Conclusions Our findings demonstrate that intolerance and avoidance of prebiotic fibers in select IBD patients is associated with the inability to ferment these fibers, leading to pro-inflammatory immune responses and intestinal barrier disruption. This highlights select disease state scenarios, in which administration of fermentable fibers should be avoided and tailored dietary interventions should be considered in IBD patients. Funding Agencies CIHRWeston Foundation

scholarly journals A pilot study to establish non-invasive biomarkers for higher-grade meningioma

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv6-iv6
Author(s):  
Daniele Baiz ◽  
Caterina Negroni ◽  
Emanuela Ercolano ◽  
Claire L Adams ◽  
Kathreena M Kurian ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Regulation Of Gene Expression ◽  
Diagnostic Tools ◽  
Malignant Tumours ◽  
Liquid Biopsies ◽  
Benign Meningioma ◽  
Non Invasive ◽  
Serum Exosomes

Abstract Introduction Meningioma brain tumours are the most common primary tumour in adults. Despite surgery and/or radiation therapy, meningioma may recur. The 5-year recurrence rate in benign meningioma is estimated in about 10% while much greater in atypical and malignant tumours. MicroRNAs (miRNAs) represent a large class of small RNAs driving regulation of gene expression and playing a role in tumour progression and therefore proposed as diagnostic tools. Moreover, miRNAs can be released from tumour cells into the blood stream via exosomes, showing potential to be used as liquid biopsies. Methods Identification of novel circulating biomarkers was conducted by performing an unbiased Cancer MicroRNA qPCR Array, followed by bioinformatics analysis. In parallel, we conducted a biased in silico analysis of the miRNAs targeting Cyclin D1 and E1, recently proposed as immunohistochemical meningioma biomarkers. Validation studies performed using TaqMan® reagents. Results Stringent unbiased (p<0.01) miRNA profiling followed by validation in ex vivo samples revealed that the miR-9-1 is upregulated in higher-grade meningioma tissues and serum exosomes, controlled by the EGFR/AP-1 axis and correlated with lower levels of E-Cadherin, a proposed biomarker for malignant meningioma. On the contrary, biased analysis, followed by validation in vitro and ex vivo, showed that the miR-497~195 cluster is downregulated in higher-grade meningioma tissues and serum exosomes, correlating with the overexpression of GATA-4, a novel meningioma tissue biomarker. Conclusion Our data demonstrated that both miR-497~195 and miR-9-1 show potential to become promising non-invasive biomarkers for higher-grade meningioma, reflecting their expression status in tissues. (DB and CN contributed equally).

Ex Vivo Phenotypic Screening of Two Small Repurposing Drug Collections Identifies Nifuratel as a Potential New Treatment against Visceral and Cutaneous Leishmaniasis

2021 ◽  
Author(s):  
Bárbara Domínguez-Asenjo ◽  
Camino Gutiérrez-Corbo ◽  
María Álvarez-Bardón ◽  
Yolanda Pérez-Pertejo ◽  
Rafael Balaña-Fouce ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Ex Vivo ◽  
Phenotypic Screening ◽  
New Treatment

scholarly journals Cell-Based Regeneration and Treatment of Liver Diseases

2021 ◽  
Vol 22 (19) ◽  
pp. 10276
Author(s):  
Julia Hofmann ◽  
Verena Hackl ◽  
Hannah Esser ◽  
Andras T. Meszaros ◽  
Margot Fodor ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Ex Vivo ◽  
Organ Shortage ◽  
Clinical Implementation ◽  
Organ Function ◽  
Novel Technologies ◽  
Recent Developments ◽  
Underlying Mechanisms ◽  
The Moment ◽  
End Stage

The liver, in combination with a functional biliary system, is responsible for maintaining a great number of vital body functions. However, acute and chronic liver diseases may lead to irreversible liver damage and, ultimately, liver failure. At the moment, the best curative option for patients suffering from end-stage liver disease is liver transplantation. However, the number of donor livers required by far surpasses the supply, leading to a significant organ shortage. Cellular therapies play an increasing role in the restoration of organ function and can be integrated into organ transplantation protocols. Different types and sources of stem cells are considered for this purpose, but highly specific immune cells are also the focus of attention when developing individualized therapies. In-depth knowledge of the underlying mechanisms governing cell differentiation and engraftment is crucial for clinical implementation. Additionally, novel technologies such as ex vivo machine perfusion and recent developments in tissue engineering may hold promising potential for the implementation of cell-based therapies to restore proper organ function.

scholarly journals Haemoglobin scavenger receptor: function in relation to disease.

2006 ◽  
Vol 53 (2) ◽  
pp. 257-268 ◽  
Author(s):  
Jolanta Zuwała-Jagiełło
Keyword(s):  
Transplant Rejection ◽  
Scavenger Receptor ◽  
Interleukin 10 ◽  
Diagnostic Tools ◽  
Soluble Cd163 ◽  
Disease States ◽  
Promising Target ◽  
Inflammatory Processes ◽  
Haem Oxygenase ◽  
New Treatment

Highly efficient systems remove the toxic and proinflammatory haemoglobin from the circulation and local sites of tissue damage. Macrophages are major haemoglobin-clearing cells; CD163 was recently recognized as the specific haemoglobin scavenger receptor (HbSR). It is tightly involved in both physiological as well as pathophysiological processes, such as cytoprotection and inflammation. Haemoglobin functions as a double-edged sword. In moderate quantities and bound to haptoglobin, it forms a ligand for haemoglobin scavenger receptor CD163/HbSR, but when unleashed in large amounts, it can become toxic by mediating oxidative stress and inflammation. CD163/HbSR plays a crucial role in the control of inflammatory processes, probably in part through its effects on both ferritin induction and subsequent induction of antiinflammatory pathways through interleukin-10 and haem oxygenase. Besides the observation that the haemoglobin scavenger receptor provides a promising target for new treatment possibilities, it offers a novel view on the aetiology of diverse physiological as well as pathophysiological processes. In addition, monocyte CD163/HbSR and soluble CD163/HbSR are potential diagnostic tools in a variety of disease states, such as inflammation, atherosclerosis, transplant rejection, and carcinoma.

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