Inflammation bowl disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the worldwide COVID-19 pandemic. Animal models are extremely helpful for testing vaccines and therapeutics and for dissecting the viral and host factors that contribute to disease severity and transmissibility. Here, we report the assessment and comparison of intranasal and small particle (~3 µm) aerosol SARS-CoV-2 exposure in ferrets. The primary endpoints for analysis were clinical signs of disease, recovery of the virus in the upper respiratory tract, and the severity of damage within the respiratory tract...

Due to the importance of 4R tau in the pathogenicity of primary tauopathies, it has been challenging to model these diseases in iPSC-derived neurons, which express very low levels of 4R tau. To address this problem we have developed a panel of isogenic iPSC lines carrying the MAPT splice-site mutations S305S, S305I or S305N, derived from four different donors. All three mutations significantly increased the proportion of 4R tau expression in iPSC-neurons and astrocytes, with up to 80% 4R transcripts in S305N neurons from as early as 4 weeks of differentiation...

Temporomandibular joint (TMJ) osteoarthritis is a common osteochondral degenerative disease which can severely affect patient's mouth opening and mastication. Meloxicam (MLX), one of the most widely used non-steroidal anti-inflammatory drugs, is the main clinical therapy for the treatment of TMJ osteoarthritis. However, the clinical effect is greatly compromised because of its poor water solubility and high lipophilicity. In the present study, we developed an actively-loaded liposomal formulation, namely MLX-Ca(AC)2 Lipo, using meglumine to enhance aqueous solubility and divalent metal (Ca2+ ) solution to improve encapsulation efficiency...

BACKGROUND: Cardiac involvement is an important determinant of mortality among sarcoidosis patients. Although granulomatous inflammation is a hallmark finding in cardiac sarcoidosis, the precise immune cell populations that comprise the granuloma remain unresolved. Furthermore, it is unclear how the cellular and transcriptomic landscape of cardiac sarcoidosis differs from other inflammatory heart diseases. METHODS: We leveraged spatial transcriptomics (GeoMx digital spatial profiler) and single-nucleus RNA sequencing to elucidate the cellular and transcriptional landscape of cardiac sarcoidosis...

BACKGROUND: Parkinson's disease (PD) is genetically associated with the H1 haplotype of the MAPT 17q.21.31 locus, although the causal gene and variants underlying this association have not been identified. METHODS: To better understand the genetic contribution of this region to PD and to identify novel mechanisms conferring risk for the disease, we fine-mapped the 17q21.31 locus by constructing discrete haplotype blocks from genetic data. We used digital PCR to assess copy number variation associated with PD-associated blocks, and used human brain postmortem RNA-seq data to identify candidate genes that were then further investigated using in vitro models and human brain tissue...

INTRODUCTION: We experienced a rare case of right-sided large bowl obstruction (LBO) of the colon caused by chronic diverticulitis, which was challenging to diagnose. PRESENTATION OF CASE: A young male was admitted to our department with a fever, diarrhea, and right-sided lateral abdominal pain for several days. CT showed a thickened ascending colon wall with stenosis and adjacent retroperitoneal inflammation without marked diverticula. The next day, he developed severe abdominal pain, and perforation was suspected...

The incidence of inflammatory bowel diseases (IBD), including Crohn's diseases and ulcerative colitis, is increasing by time and showing a trend of younger age. Precise diagnosis and effective treatments for IBD have attracted growing attention in recent years. However, diagnosing and locating inflammatory lesions remain a great challenge for IBD. In this study, assisted by a kind of aggregation-induced emission (AIE) nanoprobes (BPN-BBTD nanoparticles [NPs]), the second near-infrared (NIR-II) fluorescence imaging is first utilized to accurately trace inflammatory lesions, monitor inflammation severity and detect the response to the drug intervention in IBD mouse models...

Purpose: We report two patients who presented initially to ophthalmology clinics with symptoms and signs of orbital inflammation that led to a diagnosis of Erdheim-Chester Disease (ECD). Observations: ECD is a rare form of non-Langerhans cell histiocytosis (LCH) which is characterised by multi-system organ involvement and poor prognosis with standard therapies. Both patients were positive for the BRAF V600E mutation on genetic testing and were treated with the BRAF inhibitors Vemurafenib and Dabrafenib respectively...

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Cell therapies are an up and coming technology in orthopedic medicine that have the potential to provide regenerative treatments for musculoskeletal disease. Despite numerous cell therapies showing preclinical success for common musculoskeletal indications of disc degeneration and osteoarthritis, there have been mixed results when testing these therapies in humans during clinical trials. A theory behind the mixed success of these cell therapies is that the harsh microenvironments of the disc and knee they are entering inhibits their anabolism and survival...

The infrapatellar fat pad (IFP) serves as a reservoir of Mesenchymal Stem Cells (MSC), and with adjacent synovium plays key roles in joint disease including the production of Substance P (SP) affecting local inflammatory responses and transmitting nociceptive signals. Here, we interrogate human IFP-derived MSC (IFP-MSC) reaction to inflammatory and pro-fibrotic environments (cell priming by TNFα/IFNγ and TNFα/IFNγ/CTGF exposure respectively), compared with bone marrow-derived MSC (BM-MSC). Naïve IFP-MSC exhibit increased clonogenicity and chondrogenic potential compared with BM-MSC...

Adipose stem cells (ASCs) have gained attention in the fields of stem cells regenerative medicine due to their multifaceted therapeutic capabilities. Promising preclinical evidence of ASCs has supported the substantial interest in the use of these cells as therapy for human disease. ASCs are an adult stem cell resident in adipose tissue with the potential to differentiation along mesenchymal lineages. They also are known to be recruited to sites of inflammation where they exhibit strong immunomodulatory capabilities to promote wound healing and regeneration...

Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11...

The pathogenesis of many diseases is driven by the interactions between helper T (TH ) cells and macrophages. The phenotypes of these cells are functional dichotomies that are persuaded according to the surrounding milieu. In both multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, TH 1 and TH 17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this proinflammatory repertoire promotes the classical activation, formerly the M1-type, macrophages...

BACKGROUND: Patients are at increased risk of disease recurrence after surgical treatment of Crohn's disease. Endoscopic detection of postoperative, ileo-colonic inflammation is well established, but the potential of pan-intestinal endoscopy is yet unknown. METHODS: This prospective multicenter pilot study assessed the value of pan-intestinal capsule endoscopy using a colon capsule endoscope for the detection of inflammatory recurrence of Crohn´s disease. Patients who had been operatively treated for Crohn´s disease were included...

Carbon nanomaterials have been used to treat neurodegenerative diseases and neural disorders due to their diverse molecular structures. Corannulene is a three-dimensional π-bowl carbon nanomaterial that is different from planar PAHs, fullerenes and carbon nanotubes, but little is known about its biological functions. Herein, corannulene was functionalized with mPEG-DESP to prepare PEGylation corannulene nanoparticles (PEGylation CoNps). The synthesized PEGylation CoNps shows enhanced solubility and reduced aggregation when compared corannulene...

Musculoskeletal diseases have been associated with inflammatory cytokine action, particularly action by TNF-α and IL-1β. These inflammatory cytokines promote apoptosis and senescence of cells in diseased tissue and extracellular matrix breakdown. Stem cell-based therapies are being considered for the treatment of musculoskeletal diseases, but the presence of these inflammatory cytokines will have similar deleterious action on therapeutic cells delivered to these environments. Methods that prevent inflammatory-induced apoptosis and proinflammatory signaling, in cell and pathway-specific manners are needed...

Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease...

Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes...

Tolerance to environmental antigens that encounter the organism at interfaces like skin or gut prevents deleterious systemic immune responses. The aim of this study was to analyze whether and how low doses of haptens, by entry through the skin or gastrointestinal tract, affect the outcome of the predominantly Th1/Th17-mediated 2,4,6-trinitro-benzenesulfonic acid-induced colitis, which mimics an autoimmune bowl disease in man. Epicutaneous and oral applications of low doses of the allergen resulted in the induction of low-zone tolerance (LZT) and protected from colitis development, demonstrated by a significantly reduced inflammatory response of the gut in vivo...