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Mitochondria: The Retina's Achilles' Heel in AMD.

Adv Exp Med Biol 2021 ;1256:237-264

Department of Ophthalmology, University of Florida, Gainesville, FL, USA.

Strong experimental evidence from studies in human donor retinas and animal models supports the idea that the retinal pathology associated with age-related macular degeneration (AMD) involves mitochondrial dysfunction and consequent altered retinal metabolism. This chapter provides a brief overview of mitochondrial structure and function, summarizes evidence for mitochondrial defects in AMD, and highlights the potential ramifications of these defects on retinal health and function. Discussion of mitochondrial haplogroups and their association with AMD brings to light how mitochondrial genetics can influence disease outcome. Read More

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January 2021

Making Biological Sense of Genetic Studies of Age-Related Macular Degeneration.

Adv Exp Med Biol 2021 ;1256:201-219

Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

Age-related macular degeneration (AMD) is a major cause of blindness in older individuals worldwide. The disease is characterized by deposition of drusen between the retinal pigment epithelium (RPE) and Bruch's membrane, RPE atrophy and death of photoreceptors. AMD is a complex disease with multiple genetic and non-genetic risk factors. Read More

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January 2021

Bruch's Membrane and the Choroid in Age-Related Macular Degeneration.

Adv Exp Med Biol 2021 ;1256:89-119

Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.

A healthy choroidal vasculature is necessary to support the retinal pigment epithelium (RPE) and photoreceptors, because there is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch's membrane (BrMb)/choriocapillaris (CC) complex. This relationship is compromised in age-related macular degeneration (AMD) by the dysfunction or death of the choroidal vasculature. This chapter will provide a basic description of the human Bruch's membrane and choroidal anatomy and physiology and how they change in AMD. Read More

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January 2021

Histopathology of Age-Related Macular Degeneration and Implications for Pathogenesis and Therapy.

Adv Exp Med Biol 2021 ;1256:67-88

Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA.

Aging is associated with a number of histological changes in the choroid, Bruch's membrane, RPE, and neuroretina. Outside of the normal physiologic aging spectrum of changes, abnormal deposits such as basal laminar deposits, basal linear deposits, and soft drusen are known to be associated with AMD. Progression of AMD to advanced stages involving geographic atrophy, choroidal neovascularization, and/or disciform scars can result in debilitating vision loss. Read More

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January 2021

Alterations in fecal short chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) in men with benign prostatic hyperplasia (BPH) and metabolic syndrome (MetS).

Aging (Albany NY) 2021 Apr 13;13. Epub 2021 Apr 13.

Department of Histology and Development Biology, Pomeranian Medical University in Szczecin, Szczecin 71-210, Poland.

Gut microbiome-derived short-chain fatty acids (SCFAs) emerge in the process of fermentation of polysaccharides that resist digestion (dietary fiber, resistant starch). SCFAs have a very high immunomodulatory potential and ensure local homeostasis of the intestinal epithelium, which helps maintain the intestinal barrier. We analyzed the association between stool SCFAs levels acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0i), butyric acid (C 4:0n), isovaleric acid (C 5:0i) valeric acid (C 5:0n), isocaproic acid (C 6:0i), and caproic acid (C 6:0n)) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. Read More

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RNA Sequencing and Pathways Analyses of Middle Ear Epithelia From Patients With Otitis Media.

Laryngoscope 2021 Apr 12. Epub 2021 Apr 12.

Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.

Objectives: Otitis media (OM) is the most common pediatric diagnosis in the United States. However, our understanding of the molecular pathogenesis of OM remains relatively poor. Investigation of molecular pathways involved in OM may improve the understanding of this disease process and elucidate novel therapeutic targets. Read More

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IRAK-M knockout promotes allergic airway inflammation, but not airway hyperresponsiveness, in house dust mite-induced experimental asthma model.

J Thorac Dis 2021 Mar;13(3):1413-1426

Departments of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Background: IL-1 receptor associated-kinase (IRAK)-M, expressed by airway epithelium and macrophages, was shown to regulate acute and chronic airway inflammation exhibiting a biphasic response in an OVA-based animal model. House dust mite (HDM) is a common real-life aeroallergen highly relevant to asthma pathogenesis. The role of IRAK-M in HDM-induced asthma remains unknown. Read More

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Combined hamartoma of the retina and retinal pigment epithelium - MRI features of a rare paediatric intraocular tumour.

BJR Case Rep 2021 Apr 17;7(2):20200077. Epub 2020 Nov 17.

Department of Ophthalmology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland.

Combined hamartoma of the retina and retinal pigment epithelium is a rare benign ocular tumour in children, composed of glial cells, vascular tissue, and sheets of pigmented epithelial cells. Although generally thought to be congenital, acquired cases are known to exist. It usually presents with reduced visual acuity and/or strabismus and it can be associated with several syndromes, including Neurofibromatosis Type 2. Read More

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Flagellin From Stimulates ATB Transporter for Arginine and Neutral Amino Acids in Human Airway Epithelial Cells.

Front Immunol 2021 25;12:641563. Epub 2021 Mar 25.

Laboratory of General Pathology, Department of Medicine and Surgery, University of Parma, Parma, Italy.

At present, the central role played by arginine in the modulation of the inflammatory cellular responses is well-recognized, and many pro-inflammatory stimuli are known to modulate the expression and activity of its transmembrane transporters. In this regard, we have addressed the effects of bacterial flagellin from (FLA-PA) on the uptake of the amino acid in human epithelial respiratory cells. Among the arginine transporters, only ATB, yL, and y were operative in bronchial epithelial Calu-3 cells under control conditions; however, only the expression and activity of ATB were stimulated upon incubation with flagellin, whereas those of systems yL and y were not stimulated. Read More

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Family history of esophageal cancer modifies the association of serum lipids and malignant esophageal lesions: a nested case-control study from the "Endoscopic Screening for Esophageal Cancer in China" trial.

Chin Med J (Engl) 2021 Apr 7. Epub 2021 Apr 7.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital and Institute, Beijing 100142, China Hua County People's Hospital, Anyang, Henan 456400, China Anyang Cancer Hospital, Anyang, Henan 455000, China.

Background: The association of lipids and cancer has varied greatly among different cancer types, lipid components and study populations. This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium.

Methods: In the "Endoscopic Screening for Esophageal Cancer in China" (ESECC) trial, serum samples were collected and tested for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol at the time of subject enrollment. Read More

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A comparative analysis of COVID-19 outbreak on age groups and both the sexes of population from India and other countries.

J Infect Dev Ctries 2021 03 31;15(3):333-341. Epub 2021 Mar 31.

Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, India.

Introduction: The study of epidemiological outcomes of COVID-19 in the affected countries needs to be conducted to implement an effective strategy.

Methodology: Our study included age and sex-based analysis of epidemiological data of infected and deceased patients from various countries. The patient data was graphically depicted with the slope's calculation to describe a gradual or steep spread of the disease along with subsequent rise or fall in the death reports. Read More

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A vicious cycle of bisretinoid formation and oxidation relevant to recessive Stargardt disease.

J Biol Chem 2021 Jan 7;296:100259. Epub 2021 Jan 7.

Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. Electronic address:

The ability of iron to transfer electrons enables the contribution of this metal to a variety of cellular activities even as the redox properties of iron are also responsible for the generation of hydroxyl radicals (OH), the most destructive of the reactive oxygen species. We previously showed that iron can promote the oxidation of bisretinoid by generating highly reactive hydroxyl radical (OH). Now we report that preservation of iron regulation in the retina is not sufficient to prevent iron-induced bisretinoid oxidative degradation when blood iron levels are elevated in liver-specific hepcidin knockout mice. Read More

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January 2021

Revealing lineage-related signals in single-cell gene expression using random matrix theory.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.

Gene expression profiles of a cellular population, generated by single-cell RNA sequencing, contains rich information about biological state, including cell type, cell cycle phase, gene regulatory patterns, and location within the tissue of origin. A major challenge is to disentangle information about these different biological states from each other, including distinguishing from cell lineage, since the correlation of cellular expression patterns is necessarily contaminated by ancestry. Here, we use a recent advance in random matrix theory, discovered in the context of protein phylogeny, to identify differentiation or ancestry-related processes in single-cell data. Read More

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Obesity is associated with heavy menstruation that may be due to delayed endometrial repair.

J Endocrinol 2021 May;249(2):71-82

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.

Heavy menstrual bleeding is common and debilitating but the causes remain ill defined. Rates of obesity in women are increasing and its impact on menstrual blood loss (MBL) is unknown. Therefore, we quantified BMI and MBL in women not taking hormones and with regular menstrual cycles and revealed a positive correlation. Read More

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Description of the larval and adult hindgut tract of the common spider crab Maja brachydactyla Balss, 1922 (Brachyura, Decapoda, Malacostraca).

Cell Tissue Res 2021 Apr 9. Epub 2021 Apr 9.

, Barcelona, Spain.

Arthropods are the most diversified animals on Earth. The morphology of the digestive system has been widely studied in insects; however, crustaceans have received comparatively little attention. This study describes the hindgut tract of the common spider crab Maja brachydactyla Balss, 1922, in larvae and adults using dissection, light and electron microscopical analyses. Read More

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Squamous cell carcinoma subverts adjacent histologically normal epithelium to promote lateral invasion.

J Exp Med 2021 Jun;218(6)

Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI.

Recurrent and new tumors, attributed in part to lateral invasion, are frequent in squamous cell carcinomas and lead to poor survival. We identified a mechanism by which cancer subverts adjacent histologically normal epithelium to enable small clusters of cancer cells to burrow undetected under adjacent histologically normal epithelium. We show that suppression of DMBT1 within cancer promotes aggressive invasion and metastasis in vivo and is associated with metastasis in patients. Read More

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Remodeling of an microvessel exposed to cyclic mechanical stretch.

APL Bioeng 2021 Jun 2;5(2):026102. Epub 2021 Apr 2.

Integrative Vascular Biology Laboratory, Max-Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC),13092 Berlin, Germany.

In the lungs, vascular endothelial cells experience cyclic mechanical strain resulting from rhythmic breathing motions and intraluminal blood pressure. Mechanical stress creates evident physiological, morphological, biochemical, and gene expression changes in vascular endothelial cells. However, the exact mechanisms of the mechanical signal transduction into biological responses remain to be clarified. Read More

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Intranasal versus intratracheal exposure to lipopolysaccharides in a murine model of acute respiratory distress syndrome.

Sci Rep 2021 04 8;11(1):7777. Epub 2021 Apr 8.

Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Pavillon Mallet, M2694, 2725, chemin Sainte-Foy, Quebec, QC, G1V 4G5, Canada.

Due to frequent and often severe lung affections caused by COVID-19, murine models of acute respiratory distress syndrome (ARDS) are increasingly used in experimental lung research. The one induced by a single lipopolysaccharide (LPS) exposure is practical. However, whether it is preferable to administer LPS intranasally or intratracheally remains an open question. Read More

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EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden.

Sci Rep 2021 Apr 8;11(1):7696. Epub 2021 Apr 8.

Medical Biosciences/Medical and Clinical Genetics, University of Umeå, 901 87, Umeå, Sweden.

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal degenerations. The ortholog of Drosophila eyes shut/spacemaker, EYS on chromosome 6q12 is a major genetic cause of recessive RP worldwide, with prevalence of 5 to 30%. In this study, by using targeted NGS, MLPA and Sanger sequencing we uncovered the EYS gene as one of the most common genetic cause of autosomal recessive RP in northern Sweden accounting for at least 16%. Read More

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Dysregulation of metallothionein and zinc aggravates periodontal diseases.

J Trace Elem Med Biol 2021 Apr 3;66:126754. Epub 2021 Apr 3.

Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, 50603, Malaysia.

Background: Periodontitis (PD) is a multifaceted inflammatory disease connected to bacterial infection that results in the destruction of tooth supporting structures and eventually tooth loss. Given their involvement in infection and inflammation, both metallothionein (MT) and zinc (Zn) might play vital roles in the development and progression of PD. More specifically, both MT and Zn are heavily involved in regulating immune functions, controlling bacterial infection, balancing inflammatory responses, and reducing oxidative stress, all of which are associated with the pathogenesis of PD. Read More

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Subretinal Rather Than Intravitreal Adeno-Associated Virus-Mediated Delivery of a Complement Alternative Pathway Inhibitor Is Effective in a Mouse Model of RPE Damage.

Invest Ophthalmol Vis Sci 2021 Apr;62(4):11

Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States.

Purpose: The risk for age-related macular degeneration has been tied to an overactive complement system. Despite combined attempts by academia and industry to develop therapeutics that modulate the complement response, particularly in the late geographic atrophy form of advanced AMD, to date, there is no effective treatment. We have previously demonstrated that pathology in the smoke-induced ocular pathology (SIOP) model, a model with similarities to dry AMD, is dependent on activation of the alternative complement pathway and that a novel complement activation site targeted inhibitor of the alternative pathway can be delivered to ocular tissues via an adeno-associated virus (AAV). Read More

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