233 results match your criteria bloodstream leaky


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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Research Note: Modified serum fluorescein isothiocyanate dextran (FITC-d) assay procedure to determine intestinal permeability in poultry fed diets high in natural or synthetic pigments.

Poult Sci 2021 Jun 21;100(6):101138. Epub 2021 Mar 21.

Department of Poultry Science, University of Arkansas: Division of Agriculture, Fayetteville, AR, USA.

Oral administration of fluorescein isothiocyanate dextran (FITC-d) has been used as an indicator for intestinal permeability in poultry research for several years. Under healthy conditions, tight junctions in the intestinal wall will not allow the 4-6kDa FITC-d to enter the bloodstream. Detection of FITC-d in serum (1-hour post-oral administration of FITC-d) has proven to be a reliable indicator of leaky gut syndrome (increased intestinal inflammation and disruption of tight junctions). Read More

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Effect of endothelial glycocalyx on water and LDL transport through the rat abdominal aorta.

Am J Physiol Heart Circ Physiol 2021 04 12;320(4):H1724-H1737. Epub 2021 Mar 12.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

The surface of vascular endothelial cells (ECs) is covered by a protective negatively charged layer known as the endothelial glycocalyx. Herein, we hypothesized its transport barrier and mechanosensory role in transmural water flux and low-density lipoprotein (LDL) transport in an isolated rat abdominal aorta perfused under 85 mmHg and 20 dyn/cm ex vivo. The endothelial glycocalyx was digested by hyaluronidase (HAase) from bovine tests. Read More

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Bacterial infections in lupus: Roles in promoting immune activation and in pathogenesis of the disease.

J Transl Autoimmun 2021 23;4:100078. Epub 2020 Dec 23.

Department of Biochemistry, State University of New York at Buffalo, Buffalo, NY, 14203, USA.

Background: Bacterial infections of the lung, skin, bloodstream and other tissues are common in patients with systemic lupus erythematosus (lupus) and are often more severe and invasive than similar infections in control populations. A variety of studies have explored the changes in bacterial abundance in lupus patients, the rates of infection and the influence of particular bacterial species on disease progression, using both human patient samples and mouse models of lupus.

Objective: The aim of this review is to summarize human and mouse studies that describe changes in the bacterial microbiome in lupus, the role of a leaky gut in stimulating inflammation, identification of specific bacterial species associated with lupus, and the potential roles of certain common bacterial infections in promoting lupus progression. Read More

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December 2020

The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors.

Chem Rev 2021 02 14;121(3):1746-1803. Epub 2021 Jan 14.

NanoHealth and Optical Imaging Group, Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Herestraat 49, B3000 Leuven, Belgium.

Nanomaterial (NM) delivery to solid tumors has been the focus of intense research for over a decade. Classically, scientists have tried to improve NM delivery by employing passive or active targeting strategies, making use of the so-called enhanced permeability and retention (EPR) effect. This phenomenon is made possible due to the leaky tumor vasculature through which NMs can leave the bloodstream, traverse through the gaps in the endothelial lining of the vessels, and enter the tumor. Read More

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February 2021

The Pathogenesis of Fever-Induced Febrile Seizures and Its Current State.

Neurosci Insights 2020 2;15:2633105520956973. Epub 2020 Nov 2.

University of KwaZulu-Natal College of Health Sciences, Durban, KwaZulu-Natal, South Africa.

Febrile seizures, commonly in children between the ages of 3 months to 5 years, are a neurological abnormality characterized by neuronal hyper-excitability, that occur as a result of an increased core body temperature during a fever, which was caused by an underlying systemic infection. Such infections cause the immune system to elicit an inflammatory response resulting in the release of cytokines from macrophages. The cytokines such as interleukin (IL)- 1β, IL-6, and tumour necrosis factor-α (TNF-α) combat the infection in the localized area ultimately spilling over into circulation resulting in elevated cytokine levels. Read More

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November 2020

Leaky Gut and Gut-Liver Axis in Liver Cirrhosis: Clinical Studies Update.

Authors:
Hiroshi Fukui

Gut Liver 2020 Oct 21. Epub 2020 Oct 21.

Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan.

Portal blood flows into the liver containing the gut microbiome and its products such as endotoxin and bacterial DNA. The cirrhotic liver acts and detoxifies as the initial site of microbial products. In so-called "leaky gut," the increased intestinal permeability for bacteria and their products constitutes an important pathogenetic factor for major complications in patients with liver cirrhosis. Read More

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October 2020

Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease Progression.

Crit Rev Oncog 2020 ;25(1):57-70

Asian Healthcare Foundation, AIG Hospitals, Gachibowli, Hyderabad-500032, India.

The gut microbiome (GM) is a multifaceted environment wherein nearly 1014 microorganisms play various roles in host immune regulation, intestinal cell proliferation, bone mineralization, xenobiotics metabolism, and protection against pathogens. GM is also strongly coupled with the development and progression of nutrition-related diseases such as nonalcoholic fatty liver disease (NAFLD), wherein the gut-liver axis plays a major role as the gut and liver are functionally and anatomically associated through the portal vein. Dysbiosis causes leaky gut, resulting in the activation of inflammatory processes in the liver. Read More

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Overcoming the Blood-Brain Barrier: Successes and Challenges in Developing Nanoparticle-Mediated Drug Delivery Systems for the Treatment of Brain Tumours.

Int J Nanomedicine 2020 30;15:2999-3022. Epub 2020 Apr 30.

Department of Drug Science and Technology, University of Turin, Turin, Italy.

High-grade gliomas are still characterized by a poor prognosis, despite recent advances in surgical treatment. Chemotherapy is currently practiced after surgery, but its efficacy is limited by aspecific toxicity on healthy cells, tumour cell chemoresistance, poor selectivity, and especially by the blood-brain barrier (BBB). Thus, despite the large number of potential drug candidates, the choice of effective chemotherapeutics is still limited to few compounds. Read More

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Vascular permeability in retinopathy is regulated by VEGFR2 Y949 signaling to VE-cadherin.

Elife 2020 04 21;9. Epub 2020 Apr 21.

Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Science for Life Laboratory Uppsala University, Uppsala, Sweden.

Edema stemming from leaky blood vessels is common in eye diseases such as age-related macular degeneration and diabetic retinopathy. Whereas therapies targeting vascular endothelial growth factor A (VEGFA) can suppress leakage, side-effects include vascular rarefaction and geographic atrophy. By challenging mouse models representing different steps in VEGFA/VEGF receptor 2 (VEGFR2)-induced vascular permeability, we show that targeting signaling downstream of VEGFR2 pY949 limits vascular permeability in retinopathy induced by high oxygen or by laser-wounding. Read More

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Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins-Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain.

Authors:
Walter J Lukiw

Front Cell Infect Microbiol 2020 12;10:22. Epub 2020 Feb 12.

LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA, United States.

The microbiome of the human gastrointestinal (GI)-tract is a rich and dynamic source of microorganisms that together possess a staggering complexity and diversity. Collectively these microbes are capable of secreting what are amongst the most neurotoxic and pro-inflammatory biopolymers known. These include lipopolysaccharide (LPS), enterotoxins, microbial-derived amyloids and small non-coding RNA (sncRNA). Read More

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Effect of a polyphenol-rich dietary pattern on intestinal permeability and gut and blood microbiomics in older subjects: study protocol of the MaPLE randomised controlled trial.

BMC Geriatr 2020 02 26;20(1):77. Epub 2020 Feb 26.

Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, 20133, Milan, Italy.

Background: During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of a diet-microbiota-IP axis in older subjects, food bioactives such as polyphenols may play a beneficial modulatory role.

Methods: MaPLE is a project centered on a randomized, controlled cross-over dietary intervention trial [polyphenol-rich diet (PR-diet) versus control diet (C-diet)] targeted to older people (≥ 60 y) living in a well-controlled setting (i. Read More

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February 2020

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain.

Folia Neuropathol 2019 ;57(3):211-219

LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Read More

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February 2020

Alcohol or Gut Microbiota: Who Is the Guilty?

Int J Mol Sci 2019 Sep 14;20(18). Epub 2019 Sep 14.

General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i. Read More

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September 2019

Additional administration enhances the severity of dextran sulfate solution induced colitis mouse model through leaky gut-enhanced systemic inflammation and gut-dysbiosis but attenuated by L34.

Gut Microbes 2020 05 18;11(3):465-480. Epub 2019 Sep 18.

Department of Microbiology, Faculty of Medicine, Chulalongkorn University , Bangkok, Thailand.

Candida Albicans: is abundant in the human gut mycobiota but this species does not colonize the mouse gastrointestinal tract. administration in dextran-sulfate solution (DSS) induced-colitis mouse model (DSS+) might resemble more to human condition, therefore, a DSS colitis model with administration was studied; first, to test the influence of fungi in DSS model and second, to test the efficacy of L34. We demonstrated serum (1→3)-β-D-glucan (BG) elevation in patients with IBD and endoscopic moderate colitis in clinical remission, supporting the possible influence of gut fungi toward IBD in human. Read More

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Role of Delayed Neuroglial Activation in Impaired Cerebral Blood Flow Restoration Following Comorbid Injury.

Cell Mol Neurobiol 2020 Apr 14;40(3):369-380. Epub 2019 Sep 14.

Department of Pathology and Laboratory Medicine, University of Western Ontario, London, N6A 5C1, Canada.

Besides other causes, ischemia and Alzheimer's disease pathology is also linked to decreased cerebral blood flow (CBF). There is little or no consensus about the role of neuroglial cells in maintaining CBF in various neuropathologies. This consensus becomes scarcer when it comes to clinical and experimental cases of comorbid Abeta-amyloid (Aβ) toxicity and ischemia. Read More

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Symptomatic Carotid Plaques Demonstrate Less Leaky Plaque Microvasculature Compared With the Contralateral Side: A Dynamic Contrast-Enhanced Magnetic Resonance Imaging Study.

J Am Heart Assoc 2019 04;8(8):e011832

1 Department of Radiology and Nuclear Medicine Maastricht University Medical Centre Maastricht The Netherlands.

Background Rupture of a vulnerable carotid atherosclerotic plaque is an important underlying cause of ischemic stroke. Increased leaky plaque microvasculature may contribute to plaque vulnerability. These immature microvessels may facilitate entrance of inflammatory cells into the plaque. Read More

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Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice.

Elife 2019 04 1;8. Epub 2019 Apr 1.

Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

The circumventricular organs (CVOs) in the central nervous system (CNS) lack a vascular blood-brain barrier (BBB), creating communication sites for sensory or secretory neurons, involved in body homeostasis. Wnt/β-catenin signaling is essential for BBB development and maintenance in endothelial cells (ECs) in most CNS vessels. Here we show that in mouse development, as well as in adult mouse and zebrafish, CVO ECs rendered Wnt-reporter negative, suggesting low level pathway activity. Read More

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Beneficial effects of CNCM I-745 on clinical disorders associated with intestinal barrier disruption.

Clin Exp Gastroenterol 2019 11;12:67-82. Epub 2019 Feb 11.

Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc scientifique et technologique de Luminy, Marseille, France.

Intestinal barrier defects lead to "leaky gut syndrome", defined as an increase in intestinal permeability that allows the passage of luminal content into intestinal tissue and the bloodstream. Such a compromised intestinal barrier is the main factor underlying the pathogenesis of inflammatory bowel disease, but also commonly occurs in various systemic diseases such as viral infections and metabolic syndrome. The non-pathogenic yeast CNCM I-745 has demonstrated its effectiveness as a probiotic in the prevention and treatment of antibiotic-associated, infectious and functional diarrhea. Read More

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February 2019

R-Ras regulates vascular permeability, but not overall healing in skin wounds.

Exp Dermatol 2019 02 21;28(2):202-206. Epub 2018 Dec 21.

Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Wounds close by keratinocytes migrating from the edge of the wound and re-epithelializing the epidermis. It has been proposed that the major stimuli for wound closure are blood-derived growth factors, chemokines and cytokines. The small GTPase R-Ras, a known integrin activator, also regulates vascular permeability during angiogenesis, and blood vessels lacking R-Ras leak plasma proteins constantly. Read More

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February 2019

Collateral vessels on optical coherence tomography angiography in eyes with branch retinal vein occlusion.

Br J Ophthalmol 2019 10 22;103(10):1373-1379. Epub 2018 Nov 22.

Department of Ophthalmology & Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Aims: To detect collateral vessels using optical coherence tomography angiography (OCTA) in eyes with branch retinal vein occlusion (BRVO) and to investigate the associations with visual outcomes and macular oedema.

Methods: Eyes with macular oedema secondary to BRVO that underwent OCTA at baseline and were followed up for more than 6 months were enrolled. The presence of collaterals, whether the collaterals were leaky or not, and the associations with visual outcomes and macular oedema were investigated. Read More

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October 2019

Leaky Gut, Leaky Brain?

Microorganisms 2018 Oct 18;6(4). Epub 2018 Oct 18.

Research Service, Louis Stokes Cleveland Department of Veteran's Affairs Medical Center, Cleveland, OH 44106, USA.

'Leaky gut' syndrome, long-associated with celiac disease, has attracted much attention in recent years and for decades, was widely known in complementary/alternative medicine circles. It is often described as an increase in the permeability of the intestinal mucosa, which could allow bacteria, toxic digestive metabolites, bacterial toxins, and small molecules to 'leak' into the bloodstream. Nervous system involvement with celiac disease is know to occur even at subclinical levels. Read More

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October 2018

PAMAM dendrimers: blood-brain barrier transport and neuronal uptake after focal brain ischemia.

J Control Release 2018 12 9;291:65-79. Epub 2018 Oct 9.

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; FEUP - Faculdade de Engenharia da Universidade do Porto, R. Dr. Roberto Frias s/n, 4200-465 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, R. de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. Electronic address:

Drug delivery to the central nervous system is restricted by the blood-brain barrier (BBB). However, with the onset of stroke, the BBB becomes leaky, providing a window of opportunity to passively target the brain. Here, cationic poly(amido amine) (PAMAM) dendrimers of different generations were functionalized with poly(ethylene glycol) (PEG) to reduce cytotoxicity and prolong blood circulation half-life, aiming for a safe in vivo drug delivery system in a stroke scenario. Read More

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December 2018

Blood-brain and blood-cerebrospinal fluid barrier permeability in spontaneously hypertensive rats.

Fluids Barriers CNS 2018 Sep 24;15(1):26. Epub 2018 Sep 24.

Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Background: Hypertension is an important risk factor for cerebrovascular disease, including stroke and dementia. Both in humans and animal models of hypertension, neuropathological features such as brain atrophy and oedema have been reported. We hypothesised that cerebrovascular damage resulting from chronic hypertension would manifest itself in a more permeable blood-brain barrier and blood-cerebrospinal fluid barrier. Read More

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September 2018

Facile marriage of Gd to polymer-coated carbon nanodots with enhanced biocompatibility for targeted MR/fluorescence imaging of glioma.

Int J Pharm 2018 Dec 14;552(1-2):84-90. Epub 2018 Sep 14.

Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai 201203, China. Electronic address:

Overcoming blood-brain barrier (BBB) for precise glioma diagnosis remains an urgent challenge due to its peculiar location in central nervous system (CNS). Herein, polymer-coated carbon nanodots with high hydrophilicity were facilely married with Gd-DTPA to construct a dual-modal imaging system (NCDDG). This system was demonstrated with obviously decreased toxicity and enhanced magnetic resonance imaging (MRI) ability compared to traditional Gd-DTPA. Read More

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December 2018

Marital distress, depression, and a leaky gut: Translocation of bacterial endotoxin as a pathway to inflammation.

Psychoneuroendocrinology 2018 12 4;98:52-60. Epub 2018 Aug 4.

Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, OH, USA; Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH, USA.

Background: Marital distress and depression work in tandem to escalate risks for inflammation-related disorders. Translocation of bacterial endotoxin (lipopolysaccharide, LPS) from the gut microbiota to blood circulation stimulates systemic inflammatory responses.

Methods: To investigate increased gut permeability (a "leaky gut") as one potential mechanistic pathway from marital distress and depression to heightened inflammation, this secondary analysis of a double-blind, randomized crossover study examined serial assessments of two endotoxin biomarkers, LPS-binding protein (LBP) and soluble CD14 (sCD14), as well as C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) during two separate 9. Read More

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December 2018

Block copolymer crystalsomes with an ultrathin shell to extend blood circulation time.

Nat Commun 2018 08 1;9(1):3005. Epub 2018 Aug 1.

Department of Materials Science and Engineering, Drexel University, Philadelphia, PA, 19104, USA.

In water, amphiphilic block copolymers (BCPs) can self-assemble into various micelle structures depicting curved liquid/liquid interface. Crystallization, which is incommensurate with this curved space, often leads to defect accumulation and renders the structures leaky, undermining their potential biomedical applications. Herein we report using an emulsion-solution crystallization method to control the crystallization of an amphiphilic BCP, poly (L-lactide acid)-b-poly (ethylene glycol) (PLLA-b-PEG), at curved liquid/liquid interface. Read More

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Reduced blood volume decreases cerebral blood flow in preterm piglets.

J Physiol 2018 12 2;596(23):6033-6041. Epub 2018 Jul 2.

UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

Key Points: Preterm infants often have poor cardiovascular function that is associated with adverse neurodevelopmental outcomes. Preterm infants may be vulnerable to hypovolaemia due to excessive vasodilatation and leaky capillaries. Following reduction in blood volume, cardiac output and mean arterial pressure were reduced to the same extent in term and preterm piglets. Read More

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December 2018

Composition and richness of the serum microbiome differ by age and link to systemic inflammation.

Geroscience 2018 06 5;40(3):257-268. Epub 2018 Jun 5.

Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.

Advanced age has been associated with alterations to the microbiome within the intestinal tract as well as intestinal permeability (i.e., "leaky gut"). Read More

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