1,408 results match your criteria leaky blood

Molecular cancer cell responses to solid compressive stress and interstitial fluid pressure.

Cytoskeleton (Hoboken) 2021 Jul 22. Epub 2021 Jul 22.

Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas, USA.

Alterations to the mechanical properties of the microenvironment are a hallmark of cancer. Elevated mechanical stresses exist in many solid tumors and elicit responses from cancer cells. Uncontrolled growth in confined environments gives rise to elevated solid compressive stress on cancer cells. Read More

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The Neuroinflammatory Role of Pericytes in Epilepsy.

Biomedicines 2021 Jun 30;9(7). Epub 2021 Jun 30.

Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo 160-8402, Japan.

Pericytes are a component of the blood-brain barrier (BBB) neurovascular unit, in which they play a crucial role in BBB integrity and are also implicated in neuroinflammation. The association between pericytes, BBB dysfunction, and the pathophysiology of epilepsy has been investigated, and links between epilepsy and pericytes have been identified. Here, we review current knowledge about the role of pericytes in epilepsy. Read More

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LPS Primes Brain Responsiveness to High Mobility Group Box-1 Protein.

Pharmaceuticals (Basel) 2021 Jun 11;14(6). Epub 2021 Jun 11.

Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany.

High mobility group box (HMGB)1 action contributes to late phases of sepsis, but the effects of increased endogenous plasma HMGB1 levels on brain cells during inflammation are unclear. Here, we aimed to further investigate the role of HMGB1 in the brain during septic-like lipopolysaccharide-induced inflammation in rats (LPS, 10 mg/kg, i.p. Read More

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Influence of HII01 Supplementation on Glycemia and Inflammatory Biomarkers in Type 2 Diabetes: A Randomized Clinical Trial.

Foods 2021 Jun 23;10(7). Epub 2021 Jun 23.

Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

It has been shown that gut dysbiosis can be associated with the development of type 2 diabetes mellitus (T2DM). Consequently, intervention with probiotics may be a useful approach to improve metabolic variables in diabetes. The present study aimed to evaluate the efficacy of HII01 on glycemia in T2DM patients. Read More

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Intestinal permeability in type 1 diabetes: An updated comprehensive overview.

J Autoimmun 2021 Aug 25;122:102674. Epub 2021 Jun 25.

The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen N, Denmark.

The etiopathogenesis of the autoimmune disease type 1 diabetes (T1D) is still largely unknown, however, both genetic and environmental factors contribute to the development of the disease. A major contact surface for environmental factors is the gastrointestinal (GI) tract, where barrier defects in T1D likely cause diabetogenic antigens to enter the body tissues, contributing to beta-cell autoimmunity. Human and animal research imply that increased intestinal permeability is an important disease determinant, although the underlying methodologies, interpretations and conclusions are diverse. Read More

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The Emerging Roles of Pericytes in Modulating Tumor Microenvironment.

Front Cell Dev Biol 2021 11;9:676342. Epub 2021 Jun 11.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Pericytes (PCs), known as mural cells, play an important blood vessel (BV) supporting role in regulating vascular stabilization, permeability and blood flow in microcirculation as well as blood brain barrier. In carcinogenesis, defective interaction between PCs and endothelial cells (ECs) contributes to the formation of leaky, chaotic and dysfunctional vasculature in tumors. However, recent works from other laboratories and our own demonstrate that the direct interaction between PCs and other stromal cells/cancer cells can modulate tumor microenvironment (TME) to favor cancer growth and progression, independent of its BV supporting role. Read More

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Ultrasound-mediated disruption of the blood tumor barrier for improved therapeutic delivery.

Neoplasia 2021 Jul 14;23(7):676-691. Epub 2021 Jun 14.

Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, HSC, Morgantown, WV. Electronic address:

The blood-brain barrier (BBB) is a major anatomical and physiological barrier limiting the passage of drugs into brain. Central nervous system tumors can impair the BBB by changing the tumor microenvironment leading to the formation of a leaky barrier, known as the blood-tumor barrier (BTB). Despite the change in integrity, the BTB remains effective in preventing delivery of chemotherapy into brain tumors. Read More

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Centrally administered butyrate improves gut barrier function, visceral sensation and septic lethality in rats.

J Pharmacol Sci 2021 Aug 28;146(4):183-191. Epub 2021 Apr 28.

Department of General Medicine, Asahikawa Medical University, Japan.

Short chain fatty acids readily crosses the gut-blood and blood-brain barrier and acts centrally to influence neuronal signaling. We hypothesized that butyrate, a short-chain fatty acid produced by bacterial fermentation, in the central nervous system may play a role in the regulation of intestinal functions. Colonic permeability and visceral sensation was evaluated in rats. Read More

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Altered vascular permeability but not angiogenesis may play a role in the epileptogenesis of human hippocampal sclerosis.

Epileptic Disord 2021 Jun;23(3):490-499

Department of Neurology, NIMHANS, Bangalore, India.

Objective: We investigated the role of angiogenesis and vascular permeability in the pathogenesis of human drug-resistant epilepsy due to hippocampal sclerosis.

Methods: Resected hippocampi from 30 histologically confirmed cases of hippocampal sclerosis and 30 age-matched post-mortem controls were examined by immunohistochemical quantitation of vascular endothelial markers, CD31 and CD105 (markers of newly formed vessels), and data were analysed relative to MR volumetry. The blood-brain barrier was evaluated based on immunohistochemistry for IgG, albumin, VEGF and AQP4. Read More

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In silico investigations of intratumoral heterogeneous interstitial fluid pressure.

J Theor Biol 2021 Oct 1;526:110787. Epub 2021 Jun 1.

University of Stavanger, Faculty of Science and Technology, NO-4068 Stavanger, Norway. Electronic address:

Recent preclinical studies have shown that interstitial fluid pressure (IFP) within tumors can be heterogeneous Andersen et al. (2019). In that study tumors of two xenograft models, respectively, HL-16 cervical carcinoma and Panc-1 pancreatic carcinoma, were investigated. Read More

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October 2021

Identification of leaky gut-related markers as indicators of metabolic health in Dutch adults: The Nutrition Questionnaires plus (NQplus) study.

PLoS One 2021 4;16(6):e0252936. Epub 2021 Jun 4.

Wageningen Food and Biobased Research, Wageningen University & Research, Wageningen, The Netherlands.

Background And Aim: Chronic inflammation is a primary risk factor for chronic metabolic disease and may be triggered by a "leaky gut." Several biomarkers have been recognized to indicate intestinal permeability (i.e. Read More

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Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review.

Brain Sci 2021 May 19;11(5). Epub 2021 May 19.

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 St. Petersburg, Russia.

Epilepsy is a chronic neurological disorder characterized by recurring spontaneous seizures. Drug resistance appears in 30% of patients and it can lead to premature death, brain damage or a reduced quality of life. The purpose of the study was to analyze the drug resistance mechanisms, especially neuroinflammation, in the epileptogenesis. Read More

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Natural Endotoxemia in Dogs-A Hidden Condition That Can Be Treated with a Potential Probiotic Containing and : A Study Model.

Animals (Basel) 2021 May 11;11(5). Epub 2021 May 11.

Department of Animal Physiology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Calea Manastur No. 3-5, 400372 Cluj-Napoca, Romania.

Spore-based spp. products are considered to have a higher probiotic potential compared to products containing only lactic acid bacteria because their viability in the gastrointestinal (GI) tract is higher, even when GI environmental conditions are unfavorable. The aim of this study was to assess the effect of a , and spore-based potential probiotic on the natural levels of postprandial endotoxemia. Read More

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Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy.

J Mol Med (Berl) 2021 May 21. Epub 2021 May 21.

Center for Interdisciplinary Pain Medicine, Department of Anesthesiology, University Hospital of Würzburg, 97080, Würzburg, Germany.

Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN. Read More

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High-resolution, depth-resolved vascular leakage measurements using contrast-enhanced, correlation-gated optical coherence tomography in mice.

Biomed Opt Express 2021 Apr 2;12(4):1774-1791. Epub 2021 Mar 2.

Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.

Vascular leakage plays a key role in vision-threatening retinal diseases such as diabetic retinopathy and age-related macular degeneration. Fluorescence angiography is the current gold standard for identification of leaky vasculature however it lacks depth resolution, providing only 2D images that complicate precise identification and localization of pathological vessels. Optical coherence tomography (OCT) has been widely adopted for clinical ophthalmology due to its high, micron-scale resolution and rapid volumetric scanning capabilities. Read More

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Liver Damage and Exposure to Toxic Concentrations of Endogenous Retinoids in the Pathogenesis of COVID-19 Disease: Hypothesis.

Viral Immunol 2021 May 13. Epub 2021 May 13.

Department of Ophthalmology and Pathology, University of Mississippi Medical Center, Jackson, Mississippi, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a marked tropism for the biliary tract; it damages the bile ducts and hepatocytes and can lead to liver decompensation, cirrhosis, and sepsis. The pathogenesis of liver damage and its association with damage to the lung, heart, and brain and to the other protean manifestations of COVID-19 disease are not fully understood. In particular, tissue damage from thinning and leaky blood vessels appears to result from an inflammatory response to the virus rather than the virus itself. Read More

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Systemic manifestation and contribution of peripheral tissues to Huntington's disease pathogenesis.

Ageing Res Rev 2021 08 9;69:101358. Epub 2021 May 9.

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA. Electronic address:

Huntington disease (HD) is an autosomal dominant neurodegenerative disease that is caused by expansion of cytosine/adenosine/guanine repeats in the huntingtin (HTT) gene, which leads to a toxic, aggregation-prone, mutant HTT-polyQ protein. Beyond the well-established mechanisms of HD progression in the central nervous system, growing evidence indicates that also peripheral tissues are affected in HD and that systemic signaling originating from peripheral tissues can influence the progression of HD in the brain. Herein, we review the systemic manifestation of HD in peripheral tissues, and the impact of systemic signaling on HD pathogenesis. Read More

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Nanomedicine for acute respiratory distress syndrome: The latest application, targeting strategy, and rational design.

Acta Pharm Sin B 2021 May 7. Epub 2021 May 7.

Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. Read More

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Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment.

Front Cell Dev Biol 2021 16;9:674553. Epub 2021 Apr 16.

Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.

Although platelets and the coagulation factors are components of the blood system, they become part of and contribute to the tumor microenvironment (TME) not only within a solid tumor mass, but also within a hematogenous micrometastasis on its way through the blood stream to the metastatic niche. The latter basically consists of blood-borne cancer cells which are in close association with platelets. At the site of the primary tumor, the blood components reach the TME via leaky blood vessels, whose permeability is increased by tumor-secreted growth factors, by incomplete angiogenic sprouts or by vasculogenic mimicry (VM) vessels. Read More

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Mycobacterium tuberculosis causes a leaky blood-brain barrier and neuroinflammation in the prefrontal cortex and cerebellum regions of infected mice offspring.

Int J Dev Neurosci 2021 May 1. Epub 2021 May 1.

Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of Kwazulu Natal, Durban, South Africa.

The maternal system's exposure to pathogens influences foetal brain development through the influx of maternal cytokines and activation of the foetal immune status to a persistent inflammatory state characterised by glia cell activation. Neuroinflammation influences the blood-brain barrier's (BBB) permeability allowing peripheral immune cell trafficking into the brain. Mycobacterium tuberculosis (Mtb) is a pathogen that causes Tuberculosis (TB), a global pandemic responsible for health and economic burdens. Read More

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Mathematical modeling of intraplaque neovascularization and hemorrhage in a carotid atherosclerotic plaque.

Biomed Eng Online 2021 Apr 29;20(1):42. Epub 2021 Apr 29.

School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, China.

Background: Growing experimental evidence has identified neovascularization from the adventitial vasa vasorum and induced intraplaque hemorrhage (IPH) as critical indicators during the development of vulnerable atherosclerotic plaques. In this study, we propose a mathematical model incorporating intraplaque angiogenesis and hemodynamic calculation of the microcirculation, to obtain the quantitative evaluation of the influences of intraplaque neovascularization and hemorrhage on vulnerable plaque development. A two-dimensional nine-point model of angiogenic microvasculature is generated based on the histology of a patient's carotid plaque. Read More

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Gastrointestinal dysfunction in Parkinson's disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation.

J Neurol 2021 Apr 21. Epub 2021 Apr 21.

Department of Neurosciences, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK.

Gastrointestinal symptoms and gut dysbiosis may occur before the onset of motor symptoms in Parkinson's disease (PD). Prediagnostic and prodromal features, such as constipation and α-synuclein pathology, can be detected several years before the clinical diagnosis of PD and have the potential to develop as early PD biomarkers. Environmental toxins and gut dysbiosis may trigger oxidative stress and mucosal inflammation, and initiate α-synuclein accumulation in the enteric nervous system, early in PD. Read More

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Methods and Techniques to Facilitate the Development of NT as an Effective, Therapeutic Oncolytic Bacteria.

Front Microbiol 2021 29;12:624618. Epub 2021 Mar 29.

Cell and Molecular Biology Program, North Dakota State University, Fargo, ND, United States.

The tumor microenvironment is characterized by anomalous vascularization, hypoxia, and acidity at the core of solid tumors that culminates in concentrated necrosis and immune system dysregulation among other effects. While this environment presents several challenges for the development of oncotherapeutics that deliver their activity via the enhanced permeability and retention (EPR) effect of the leaky blood vessels around a tumor, oncolytic bacteria, or a class of bacteria with a noted capacity to lyse solid tumors, are attracted to the very environment found at the center of solid tumors that confounds other therapeutics. It is this capacity that allows for a potent, active penetration from the tumor margins into the core, and subsequent colonization to facilitate lysis and immune reactivation. Read More

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Estrogen-related receptor α is involved in angiogenesis and skeletal muscle revascularization in hindlimb ischemia.

FASEB J 2021 05;35(5):e21480

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, UTHealth, Houston, TX, USA.

Skeletal muscle ischemia is a major consequence of peripheral arterial disease (PAD) or critical limb ischemia (CLI). Although therapeutic options for resolving muscle ischemia in PAD/CLI are limited, the issue is compounded by poor understanding of the mechanisms driving muscle vascularization. We found that nuclear receptor estrogen-related receptor alpha (ERRα) expression is induced in murine skeletal muscle by hindlimb ischemia (HLI), and in cultured myotubes by hypoxia, suggesting a potential role for ERRα in ischemic response. Read More

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Interstitial Fluid in Lipedema and Control Skin.

Womens Health Rep (New Rochelle) 2020 14;1(1):480-487. Epub 2020 Oct 14.

Department of Medicine, TREAT Program, University of Arizona, Tucson, Arizona, USA.

Fluid in lymphedema tissue appears histologically as spaces around vessels and between dermal skin fibers. Lipedema is a painful disease of excess loose connective tissue (fat) in limbs, almost exclusively of women, that worsens by stage, increasing lymphedema risk. Many women with lipedema have hypermobile joints suggesting a connective tissue disorder that may affect vessel structure and compliance of tissue resulting in excess fluid entering the interstitial space. Read More

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October 2020

Chromogranin A regulates gut permeability via the antagonistic actions of its proteolytic peptides.

Acta Physiol (Oxf) 2021 06 6;232(2):e13655. Epub 2021 May 6.

VA San Diego Healthcare System, San Diego, CA, USA.

Aim: A "leaky" gut barrier has been implicated in the initiation and progression of a multitude of diseases, for example, inflammatory bowel disease (IBD), irritable bowel syndrome and celiac disease. Here we show how pro-hormone Chromogranin A (CgA), produced by the enteroendocrine cells, and Catestatin (CST: hCgA ), the most abundant CgA-derived proteolytic peptide, affect the gut barrier.

Methods: Colon tissues from region-specific CST-knockout (CST-KO) mice, CgA-knockout (CgA-KO) and WT mice were analysed by immunohistochemistry, western blot, ultrastructural and flowcytometry studies. Read More

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Linking cortical astrocytic neogenin deficiency to the development of Moyamoya disease-like vasculopathy.

Neurobiol Dis 2021 Jul 26;154:105339. Epub 2021 Mar 26.

Department of Neurosciences, Case Western Reserve University, Cleveland, OH, USA. Electronic address:

Moyamoya-like vasculopathy, the "puff of smoke"-like small vessels in the brain, is initially identified in patients with Moyamoya disease (MMD), a rare cerebrovascular disease, and later found in patients with various types of neurological conditions, including Down syndrome, Stroke, and vascular dementia. It is thus of interest to understand how this vasculopathy is developed. Here, we provided evidence for cortical astrocytic neogenin (NEO1) deficiency to be a risk factor for its development. Read More

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Detection of Alterations in the Gut Microbiota and Intestinal Permeability in Patients With Hashimoto Thyroiditis.

Front Immunol 2021 5;12:579140. Epub 2021 Mar 5.

Microbiome Study Group, School of Health Sciences Dr. Paulo Prata, São Paulo, Brazil.

Hashimoto thyroiditis (HT) is the most common autoimmune disease worldwide, characterized by chronic inflammation and circulating autoantibodies against thyroid peroxidase and thyroglobulin. Patients require hormone replacement with oral levothyroxine, and if untreated, they can develop serious adverse health effects and ultimately death. There is a lot of evidence that the intestinal dysbiosis, bacterial overgrowth, and increased intestinal permeability favor the HT development, and a thyroid-gut axis has been proposed, which seems to impact our entire metabolism. Read More

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Dysregulation of IL-17/IL-22 Effector Functions in Blood and Gut Mucosal Gamma Delta T Cells Correlates With Increase in Circulating Leaky Gut and Inflammatory Markers During cART-Treated Chronic SIV Infection in Macaques.

Front Immunol 2021 25;12:647398. Epub 2021 Feb 25.

Division of Microbiology, Tulane National Primate Research Center, Covington, LA, United States.

HIV-associated inflammation has been implicated in the premature aging and increased risk of age-associated comorbidities in cART-treated individuals. However, the immune mechanisms underlying the chronic inflammatory state of cART-suppressed HIV infection remain unclear. Here, we investigated the role of γδT cells, a group of innate IL-17 producing T lymphocytes, in the development of systemic inflammation and leaky gut phenotype during cART-suppressed SIV infection of macaques. Read More

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February 2021

Targeting receptor-ligand chemistry for drug delivery across blood-brain barrier in brain diseases.

Life Sci 2021 Jun 9;274:119326. Epub 2021 Mar 9.

Department of Radiation Biology & Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India. Electronic address:

The blood-brain barrier (BBB) is composed of a layer of endothelial cells that is interspersed with a series of tight junctions and characterized by the absence of fenestrations. The permeability of this barrier is controlled by junctions such as tight junctions and adherent junctions as well as several cells such as astrocytes, pericytes, vascular endothelial cells, neurons, microglia, and efflux transporters with relatively enhanced expression. It plays a major role in maintaining homeostasis in the brain and exerts a protective regulatory control on the influx and efflux of molecules. Read More

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