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Folia Biologica 2018Human body reacts to physical, chemical and biological insults with a complex inflammatory reaction. Crucial components and executors of this response are endothelial... (Review)
Review
Human body reacts to physical, chemical and biological insults with a complex inflammatory reaction. Crucial components and executors of this response are endothelial cells, platelets, white blood cells, plasmatic coagulation system, and complement. Endothelial injury and inflammation are associated with elevated blood levels of cell membrane-derived microvesicles. Increased concentrations of microvesicles were found in several inflammatory reactions and diseases including acute coronary syndromes, stroke, vasculitis, venous thromboembolism, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, anti-phospholipid antibody syndrome, inflammatory bowel disease, thrombotic thrombocytopenic purpura, viral myocarditis, sepsis, disseminated intravascular coagulation, polytrauma, and burns. Microvesicles can modulate a variety of cellular processes, thereby having an impact on pathogenesis of diseases associated with inflammation. Microvesicles are important mediators and potential biomarkers of systemic inflammation. Measurement of inflammatory cell-derived microvesicles may be utilized in diagnostic algorithms and used for detection and determination of severity in diseases associated with inflammatory responses, as well as for prediction of their outcome. This review focuses on the mechanisms of release of microvesicles in diseases associated with systemic inflammation and their potential role in the regulation of cellular and humoral interactions.
Topics: Animals; Cell-Derived Microparticles; Humans; Inflammation; Sepsis; Systemic Inflammatory Response Syndrome
PubMed: 30724157
DOI: No ID Found -
Journal of Leukocyte Biology Nov 2021The gastrointestinal (GI) tract is a highly dynamic structure essential for digestion, nutrient absorption, and providing an interface to prevent gut bacterial... (Review)
Review
The gastrointestinal (GI) tract is a highly dynamic structure essential for digestion, nutrient absorption, and providing an interface to prevent gut bacterial translocation. In order to maintain the barrier function, the gut utilizes many defense mechanisms including proliferation, apoptosis, and apical junctional complexes. Disruption of any of these parameters due to injury or disease could negatively impact the intestinal barrier function and homeostasis resulting in increased intestine inflammation, permeability, bacterial dysbiosis, and tissue damage. MicroRNAs are small noncoding RNA sequences that are master regulators of normal cellular homeostasis. These regulatory molecules affect cellular signaling pathways and potentially serve as candidates for providing a mechanism of impaired gut barrier integrity following GI-related pathologic conditions, ethanol exposure, or trauma such as burn injury. MicroRNAs influence cellular apoptosis, proliferation, apical junction complex expression, inflammation, and the microbiome. Due to their widespread functional affiliations, altered expression of microRNAs are associated with many pathologic conditions. This review explores the role of microRNAs in regulation of intestinal barrier integrity. The studies reviewed demonstrate that microRNAs largely impact intestine barrier function and provide insight behind the observed adverse effects following ethanol and burn injury. Furthermore, these studies suggest that microRNAs are excellent candidates for therapeutic intervention or for biomarkers to manage gut barrier integrity following trauma such as burn injury and other GI-related pathologic conditions.
Topics: Animals; Humans; Intestinal Mucosa; Intestines; Permeability; RNA, Messenger; Tight Junctions
PubMed: 33577717
DOI: 10.1002/JLB.3RU0120-090RR -
Journal of Clinical Microbiology May 1996From 1974 to 1994, 2,033 specimens from children were submitted for cultures for anaerobic bacteria. Eighty-three Veillonella spp. were recovered from 83 children (4%).... (Review)
Review
From 1974 to 1994, 2,033 specimens from children were submitted for cultures for anaerobic bacteria. Eighty-three Veillonella spp. were recovered from 83 children (4%). Most Veillonella species were recovered from abscesses, aspiration pneumonias, burns, bites, and sinuses. The infections were polymicrobial in 79 (95%) patients, but in 4 (5%) patients, Veillonella species were recovered in pure culture. The predisposing conditions associated with the recovery of these organisms were previous surgery, malignancy, steroid therapy, foreign body, and immunodeficiency. These data illustrate that Veillonella spp. are found infrequently in children, mostly in association with mixed infections, and are recovered mixed with mouth and bowel flora.
Topics: Abscess; Adolescent; Burns; Child; Child, Preschool; Female; Gram-Negative Bacterial Infections; Humans; Infant; Male; Pneumonia, Aspiration; Pneumonia, Bacterial; Retrospective Studies; Veillonella
PubMed: 8727920
DOI: 10.1128/jcm.34.5.1283-1285.1996 -
Cellular and Molecular Gastroenterology... 2020Defective epithelial barrier function is present in maladies including epidermal burn injury, environmental lung damage, renal tubular disease, and a range of... (Review)
Review
Defective epithelial barrier function is present in maladies including epidermal burn injury, environmental lung damage, renal tubular disease, and a range of immune-mediated and infectious intestinal disorders. When the epithelial surface is intact, the paracellular pathway between cells is sealed by the tight junction. However, permeability of tight junctions varies widely across tissues and can be markedly impacted by disease. For example, tight junctions within the skin and urinary bladder are largely impermeant and their permeability is not regulated. In contrast, tight junctions of the proximal renal tubule and intestine are selectively permeable to water and solutes on the basis of their biophysical characteristics and, in the gut, can be regulated by the immune system with remarkable specificity. Conversely, modulation of tight junction barrier conductance, especially within the gastrointestinal tract, can impact immune homeostasis and diverse pathologies. Thus, tight junctions are both effectors and targets of immune regulation. Using the gastrointestinal tract as an example, this review explores current understanding of this complex interplay between tight junctions and immunity.
Topics: Animals; Homeostasis; Humans; Immunity, Mucosal; Intestinal Mucosa; Mice; Models, Animal; Permeability; Tight Junctions
PubMed: 32304780
DOI: 10.1016/j.jcmgh.2020.04.001 -
BMC Nephrology Nov 2021Gastro-intestinal (GI) intolerance is a frequently reported outcome in patients with kidney failure receiving maintenance dialysis and those who have received kidney...
The CKD bowel health study: understanding the bowel health and gastrointestinal symptom management in patients with chronic kidney disease: a mixed-methods observational longitudinal study (protocol).
BACKGROUND
Gastro-intestinal (GI) intolerance is a frequently reported outcome in patients with kidney failure receiving maintenance dialysis and those who have received kidney transplants. Symptoms of GI intolerance (diarrhoea, constipation, bloating, abdominal pain, heart burn, and reflux) are associated with significant reduction in quality of life, morbidity, and increased used of healthcare resources. Having chronic kidney disease (CKD), together with related changes in diet and medication, may alter the gut microbiota and the microbial-derived uraemic metabolites that accumulate in kidney failure, and contribute to various complications including chronic diarrhoea, opportunistic infections, and drug-related colitis. Despite the high disease burden among patients with kidney replacement therapies, GI symptoms are often under-recognised and, consequently limited resources and strategies are devoted to the management of gastrointestinal complications in patients with CKD.
METHODS
The CKD Bowel Health Study is a multi-centre mixed-methods observational longitudinal study to better understand the bowel health and GI symptom management in patients with CKD. The program comprises of a longitudinal study that will assess the burden and risk factors of GI intolerance in patients treated with maintenance dialysis; a semi-structured interview study that will describe experiences of GI intolerance (including symptoms, treatment, self-management) in transplant candidates and recipients; and a discrete choice experience to elicit patient preferences regarding their experiences and perspectives of various intervention strategies for the management of GI symptoms after kidney transplantation.
DISCUSSION
This proposed program of work aims to define the burden the GI intolerance in patients with kidney failure and generate evidence on the patients' experiences of GI intolerance and their perspectives on their clinical and own management strategies of these symptoms, ensuring a patient-centred approach to guide clinical decision making and to inform the best study design for intervention trials.
TRIAL REGISTRATION
This study is registered on the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000548831 . This study has been approved by the Western Sydney Local Health District Human Research Ethics Committee of New South Wales Health (HREC ETH03007). This study is supported by a National Health and Medical Research Council (NHMRC) Australia Investigator Grant (APP1195414), and an NHMRC Australia Postgraduate Scholarship (APP2005244).
Topics: Humans; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gastrointestinal Tract; Kidney Transplantation; Longitudinal Studies; Renal Insufficiency, Chronic; Renal Replacement Therapy; Risk Factors; Observational Studies as Topic; Multicenter Studies as Topic
PubMed: 34802445
DOI: 10.1186/s12882-021-02600-x -
Journal of Leukocyte Biology Jun 2021The gastrointestinal (GI) tract is a vitally important site for the adsorption of nutrients as well as the education of immune cells. Homeostasis of the gut is... (Review)
Review
The gastrointestinal (GI) tract is a vitally important site for the adsorption of nutrients as well as the education of immune cells. Homeostasis of the gut is maintained by the interplay of the intestinal epithelium, immune cells, luminal Ags, and the intestinal microbiota. The well-being of the gut is intrinsically linked to the overall health of the host, and perturbations to this homeostasis can have severe impacts on local and systemic health. One factor that causes disruptions in gut homeostasis is age, and recent research has elucidated how critical systems within the gut are altered during the aging process. Intestinal stem cell proliferation, epithelial barrier function, the gut microbiota, and the composition of innate and adaptive immune responses are all altered in advanced age. The aging population continues to expand worldwide, a phenomenon referred to as the "Silver Tsunami," and every effort must be made to understand how best to prevent and treat age-related maladies. Here, recent research about changes observed in the intestinal epithelium, the intestinal immune system, the microbiota, and how the aging gut interacts with and influences other organs such as the liver, lung, and brain are reviewed. Better understanding of these age-related changes and their impact on multi-organ interactions will aid the development of therapies to increase the quality of life for all aged individuals.
Topics: Age Factors; Aging; Animals; Gastrointestinal Microbiome; Gastrointestinal Tract; Homeostasis; Humans; Intestinal Mucosa; Organ Specificity
PubMed: 33020981
DOI: 10.1002/JLB.3RI0620-405RR -
Journal of Controlled Release :... Nov 2020Inflammation is intimately related to the pathogenesis of numerous acute and chronic diseases like cardiovascular disease, inflammatory bowel disease, rheumatoid... (Review)
Review
Inflammation is intimately related to the pathogenesis of numerous acute and chronic diseases like cardiovascular disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases. Therefore anti-inflammatory therapy is a very promising strategy for the prevention and treatment of these inflammatory diseases. To overcome the shortcomings of existing anti-inflammatory agents and their traditional formulations, such as nonspecific tissue distribution and uncontrolled drug release, bioresponsive drug delivery systems have received much attention in recent years. In this review, we first provide a brief introduction of the pathogenesis of inflammation, with an emphasis on representative inflammatory cells and mediators in inflammatory microenvironments that serve as pathological fundamentals for rational design of bioresponsive carriers. Then we discuss different materials and delivery systems responsive to inflammation-associated biochemical signals, such as pH, reactive oxygen species, and specific enzymes. Also, applications of various bioresponsive drug delivery systems in the treatment of typical acute and chronic inflammatory diseases are described. Finally, crucial challenges in the future development and clinical translation of bioresponsive anti-inflammatory drug delivery systems are highlighted.
Topics: Drug Delivery Systems; Drug Liberation; Humans; Inflammation; Inflammatory Bowel Diseases; Tissue Distribution
PubMed: 32911014
DOI: 10.1016/j.jconrel.2020.09.008 -
American Journal of Obstetrics and... Nov 2023Endometriosis has been linked to higher rates of a variety of symptoms; however, the findings from longitudinal studies are scarce and inconsistent.
BACKGROUND
Endometriosis has been linked to higher rates of a variety of symptoms; however, the findings from longitudinal studies are scarce and inconsistent.
OBJECTIVE
This study aimed to examine the association between endometriosis and common symptoms in a prospective cohort study.
STUDY DESIGN
This study included 7606 women born from 1973 to 1978 using data from the Australian Longitudinal Study on Women's Health that were collected every 3 years from 2009 to 2018. We identified women with endometriosis based on self-reported incidence from each survey and linked administrative health data. At each survey, women also completed a checklist on the presence of 24 symptoms. Generalized estimating equations for multinomial responses were used for analyses.
RESULTS
Women with endometriosis had significantly more menstrual symptoms than those without endometriosis with an adjusted odds ratio (95% confidence interval) of 3.61 (3.11-4.19) for severe period pain, 2.40 (2.10-2.74) for heavy menstrual bleeding, 1.76 (1.52-2.03) for irregular bleeding, and 1.52 (1.32-1.76) for premenstrual tension. They also had higher odds of mental health problems with adjusted odds ratios of 1.67 (1.39-2.01) for depression and 1.59 (1.24-2.03) for anxiety and higher odds of allergies and nonspecific symptoms with adjusted odds of 1.62 (1.40-1.89) for allergies or hay fever or sinusitis, 1.79 (1.56-2.05) for severe tiredness, 1.56 (1.35-1.81) for sleep difficulty, and 1.77 (1.37-2.18) for palpitations. There was also a strong association with other forms of pain with an adjusted odds ratio of 1.76 (1.53-2.04) for backpain, 1.50 (1.29-1.74) for headaches or migraines, and 1.65 (1.41-1.93) for stiff or painful joints. Women with endometriosis also had increased odds of developing bowel and urinary symptoms with an adjusted odds ratio (95% confidence interval) of 1.67 (1.35-2.08) for constipation, 1.46 (1.12-1.90) for hemorrhoids or piles, 1.25 (1.03-1.52) for indigestion or heartburn, 2.80 (1.71-4.58) for urine burn or stings, and 1.37 (1.03-1.82) for vaginal discharge or irritation. The association between each symptom and endometriosis was similar whether endometriosis was surgically confirmed or clinically suspected. No association was found between endometriosis and the risk for skin problems, leaking urine, or breathing difficulty.
CONCLUSION
This study suggests that women with endometriosis are more likely to report not only menstrual symptoms but are also at an increased risk for mental health problems, other pain symptoms, bowel and urinary symptoms, and nonspecific symptoms, such as severe tiredness and difficulty sleeping.
Topics: Female; Humans; Longitudinal Studies; Endometriosis; Prospective Studies; Australia; Women's Health; Dysmenorrhea; Surveys and Questionnaires; Hypersensitivity
PubMed: 37499990
DOI: 10.1016/j.ajog.2023.07.033 -
ImmunoHorizons Jan 2022Our previous studies have shown that ethanol intoxication combined with burn injury increases intestinal bacterial growth, disrupts the intestinal barrier, and enhances...
Our previous studies have shown that ethanol intoxication combined with burn injury increases intestinal bacterial growth, disrupts the intestinal barrier, and enhances bacterial translocation. Additionally, studies show that Th17 effector cytokines IL-17 and IL-22, which are dependent on IL-23, play important roles in maintaining intestine mucosal barrier integrity. Recent findings suggest neutrophils are a significant source of IL-17 and IL-22. We determined the effect of ethanol and burn injury on neutrophil IL-17 and IL-22 production, as well as their ability to phagocytose and in bacterial clearance, and whether these effects are modulated by IL-23. Mice were given ethanol 4 h prior to receiving ∼12.5% total body surface area burn and were euthanized day 1 after injury. We observed that intoxication combined with burn injury significantly decreases blood neutrophil phagocytosis and bacteria killing, as well as their ability to produce IL-17 and IL-22, compared with sham vehicle mice. The treatment of neutrophils with rIL-23 significantly increases IL-22 and IL-17 release and promotes expression of IL-23R, retinoic acid-related orphan receptor γt, Lipocalin2, and Nod-like receptor 2 following ethanol and burn injury. Furthermore, IL-22- and IL-17-producing neutrophils have enhanced neutrophil extracellular trap formation and bacterial killing ability, which are dependent on IL-23. Finally, although we observed that peritoneal neutrophils harvested after casein treatment are functionally different from blood neutrophils, both blood and peritoneal neutrophils exhibited the same response to rIL-23 treatment. Together these findings suggest that IL-23 promotes neutrophil IL-22 and IL-17 production and their ability to kill bacteria following ethanol and burn injury.
Topics: Alcoholic Intoxication; Animals; Burns; Disease Models, Animal; Escherichia coli Infections; Ethanol; Extracellular Traps; Interleukin-17; Interleukins; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Neutrophils; Phagocytosis; Interleukin-22
PubMed: 35058308
DOI: 10.4049/immunohorizons.2100109 -
Shock (Augusta, Ga.) Oct 2023The Earth's population is aging, and by 2050, one of six people will be 65 years or older. Therefore, proper treatment of injuries that disproportionately impact people...
The Earth's population is aging, and by 2050, one of six people will be 65 years or older. Therefore, proper treatment of injuries that disproportionately impact people of advanced age will be more important. Clinical studies reveal people 65 years or older account for 16.5% of all burn injuries and experience higher morbidity, including neurocognitive decline, and mortality that we and others believe are mediated, in part, by heightened intestinal permeability. Herein, we used our clinically relevant model of scald burn injury in young and aged mice to determine whether age and burn injury cooperate to induce heightened colonic damage, alterations to the fecal microbiome, and whether resultant changes in the microbiome correlate with neuroinflammation. We found that aged, burn-injured mice have an increase in colonic lymphoid aggregates, inflammation, and proinflammatory chemokine expression when compared with young groups and sham-injured aged mice. We then performed fecal microbiota sequencing and found a striking reduction in gut protective bacterial taxa, including Akkermansia , in the aged burn group compared with all other groups. This reduction correlated with an increase in serum fluorescein isothiocyanate-Dextran administered by gavage, indicating heightened intestinal permeability. Furthermore, loss of Akkermansia was highly correlated with increased messenger RNA expression of neuroinflammatory markers in the brain, including chemokine ligand 2, TNF-α, CXC motif ligand 1, and S100 calcium-binding protein A8. Finally, we discovered that postburn alterations in the microbiome correlated with measures of strength in all treatment groups, and those that performed better on the rotarod and hanging wire tests had higher abundance of Akkermansia than those that performed worse. Taken together, these findings indicate that loss of protective bacteria after burn injury in aged mice contributes to alterations in the colon, gut leakiness, neuroinflammation, and strength. Therefore, supplementation of protective bacteria, such as Akkermansia , after burn injury in aged patients may have therapeutic benefit.
Topics: Humans; Aged; Neuroinflammatory Diseases; Dysbiosis; Ligands; Microbiota; Burns; Bacteria; Chemokines; Colon
PubMed: 37548929
DOI: 10.1097/SHK.0000000000002202