CHARACTERISTICS OF AGE-DEPENDENT CHANGES IN THE URINE'S PROTEOM COMPOSITION OF THE HEALTHY PERSONS (EXPERIMENTAL AND THEORETICAL STUDY)

2020 ◽  
pp. 735-740
Author(s):  
Л. Х. Пастушкова ◽  
Д. Н. Каширина ◽  
А. Г. Гончарова ◽  
Н. Б. Захарова ◽  
Е. С. Тийс ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Insulin Signaling ◽  
Defense Mechanisms ◽  
Theoretical Study ◽  
Clinical Manifestations ◽  
Age Dependent ◽  
First Time ◽  
Healthy Persons ◽  
Over Time

Впервые описаны белки, достоверно увеличивающиеся и уменьшающиеся в моче с возрастом в интервале 20-60 лет. Охарактеризованы комбинации белков, связанных с изменением иммунных процессов, нарушением реологии крови, в том числе риском коагулопатии, противоопухолевых защитных механизмов, инсулинового сигнального пути, с изменением характеристик клеточного деления и качества новообразованной ткани. Таким образом, возрастная динамика основных процессов запускает каскад реакций, проявляющихся в замыкании «патологических биохимических кругов», которые формируют предпосылки к развитию заболеваний и, с течением времени, клинические проявления. For the first time proteins are described, reliably increasing and decreasing in urine with age in the range of 20 to 60 years. The combinations of proteins associated with changes in immune processes, violation of blood reology, including the risk of coagulopathy, anticancer defense mechanisms, insulin signaling pathway, changes in cell characteristics are characterized division and quality of the newly formed fabric. Thus, the age dynamics of the main processes triggers a cascade of reactions manifested in the closure of «pathological biochemical circles» that form the prerequisites for the development of diseases and, over time, clinical manifestations.

scholarly journals Changes in Plasma Phospholipid Metabolism Are Associated with Clinical Manifestations of Systemic Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2116
Author(s):  
Marija Geroldinger-Simić ◽  
Thomas Bögl ◽  
Markus Himmelsbach ◽  
Norbert Sepp ◽  
Wolfgang Buchberger
Keyword(s):  
Systemic Sclerosis ◽  
High Performance ◽  
Clinical Manifestations ◽  
Plasma Phospholipid ◽  
Phospholipid Metabolism ◽  
Internal Organs ◽  
New Biomarkers ◽  
First Time

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.

scholarly journals Altered Insulin Receptor Substrate 1 Phosphorylation in Blood Neuron-Derived Extracellular Vesicles From Patients With Parkinson’s Disease

2020 ◽  
Vol 8 ◽  
Author(s):  
Szu-Yi Chou ◽  
Lung Chan ◽  
Chen-Chih Chung ◽  
Jing-Yuan Chiu ◽  
Yi-Chen Hsieh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Extracellular Vesicles ◽  
Insulin Signaling ◽  
Clinical Manifestations ◽  
Insulin Signaling Pathway ◽  
Insulin Receptor Substrate ◽  
Neuronal Markers

IntroductionDiabetes increases the risk of Parkinson’s disease (PD). The phosphorylation of type 1 insulin receptor substrate (IRS-1) determines the function of insulin signaling pathway. Extracellular vesicles (EVs) are emerging as biomarkers of human diseases. The present study investigated whether PD patients exert altered phosphorylation IRS-1 (p-IRS-1) inside the blood neuron-derived extracellular vesicles (NDEVs).Research Design and MethodsIn total, there were 94 patients with PD and 63 healthy controls recruited and their clinical manifestations were evaluated. Blood NDEVs were isolated using the immunoprecipitation method, and Western blot analysis was conducted to assess total IRS-1, p-IRS-1, and downstream substrates level in blood NDEVs. Statistical analysis was performed using SPSS 19.0, and p < 0.05 was considered significant.ResultsThe isolated blood EVs were validated according to the presence of CD63 and HSP70, nanoparticle tracking analysis and transmission electron microscopy. NDEVs were positive with neuronal markers. PD patients exerted significantly higher level of p-IRS-1S312 in blood NDEVs than controls. In addition, the p-IRS-1S312 levels in blood NDEVs was positively associated with the severity of tremor in PD patients after adjusting of age, sex, hemoglobin A1c, and body mass index (BMI).ConclusionPD patients exerted altered p-IRS-1S312 in the blood NDEVs, and also correlated with the severity of tremor. These findings suggested the association between dysfunctional insulin signaling pathway with PD. The role of altered p-IRS-1S312 in blood NDEVs as a segregating biomarker of PD required further cohort study to assess the association with the progression of PD.

scholarly journals DAF-16 and SMK-1 Contribute to Innate Immunity During Adulthood in Caenorhabditis elegans

2020 ◽  
Vol 10 (5) ◽  
pp. 1521-1539 ◽  
Author(s):  
Daniel R. McHugh ◽  
Elena Koumis ◽  
Paul Jacob ◽  
Jennifer Goldfarb ◽  
Michelle Schlaubitz-Garcia ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Caenorhabditis Elegans ◽  
Host Defense ◽  
Insulin Signaling ◽  
Bacterial Pathogens ◽  
C Elegans ◽  
Link Type ◽  
Age Dependent ◽  
Over Time

Aging is accompanied by a progressive decline in immune function termed “immunosenescence”. Deficient surveillance coupled with the impaired function of immune cells compromises host defense in older animals. The dynamic activity of regulatory modules that control immunity appears to underlie age-dependent modifications to the immune system. In the roundworm Caenorhabditis elegans levels of PMK-1 p38 MAP kinase diminish over time, reducing the expression of immune effectors that clear bacterial pathogens. Along with the PMK-1 pathway, innate immunity in C. elegans is regulated by the insulin signaling pathway. Here we asked whether DAF-16, a Forkhead box (FOXO) transcription factor whose activity is inhibited by insulin signaling, plays a role in host defense later in life. While in younger C. elegansDAF-16 is inactive unless stimulated by environmental insults, we found that even in the absence of acute stress the transcriptional activity of DAF-16 increases in an age-dependent manner. Beginning in the reproductive phase of adulthood, DAF-16 upregulates a subset of its transcriptional targets, including genes required to kill ingested microbes. Accordingly, DAF-16 has little to no role in larval immunity, but functions specifically during adulthood to confer resistance to bacterial pathogens. We found that DAF-16-mediated immunity in adults requires SMK-1, a regulatory subunit of the PP4 protein phosphatase complex. Our data suggest that as the function of one branch of the innate immune system of C. elegans (PMK-1) declines over time, DAF-16-mediated immunity ramps up to become the predominant means of protecting adults from infection, thus reconfiguring immunity later in life.

Topical Topiramate Improves Wound Healing in an Animal Model of Hyperglycemia

2019 ◽  
Vol 21 (4) ◽  
pp. 420-430
Author(s):  
Carlos Poblete Jara ◽  
Thais Paulino do Prado ◽  
Vanessa Cristina Dias Bóbbo ◽  
Albina de Fátima S. Ramalho ◽  
Maria H. M. Lima ◽  
...  
Keyword(s):  
Wound Healing ◽  
Animal Model ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Inflammatory Marker ◽  
Late Phase ◽  
Skin Lesions ◽  
Insulin Signaling Pathway ◽  
Type I

Wound healing is severely affected in hyperglycemia and other metabolic conditions. Finding new therapeutic approaches that accelerate wound healing and improve the quality of the scar may reduce the morbidity commonly associated with skin lesions in diabetes. This study evaluated the effect of topical topiramate (TPM) on wound healing in C57 mice. Streptozotocin-induced hyperglycemic mice were subjected to a wound on the back and randomly allocated for treatment with either vehicle or topical TPM cream (2%) once a day for 14 days. Polymerase chain reaction, Western blotting, and microscopy were performed for the analysis. TPM improved wound healing (complete resolution at Day 10, 98% ± 5 for TPM vs. 81% ± 28 for vehicle), increased organization and deposition of collagen Type I, and enhanced the quality of the scars as determined by microscopy. In addition, TPM modulated the expression of cytokines and proteins of the insulin-signaling pathway: In early wound-healing stages, expression of interleukin-10, an anti-inflammatory marker, increased, whereas at the late phase, the pro-inflammatory markers tumor necrosis factor-α and monocyte chemoattractant protein-1 increased and there was increased expression of a vascular endothelial growth factor. Proteins of the insulin-signaling pathway were stimulated in the late wound-healing phase. Topical TPM improves the quality of wound healing in an animal model of hyperglycemia. The effect of TPM is accompanied by modulation of inflammatory and growth factors and proteins of the insulin-signaling pathway. Therefore, topical TPM presents as a potential therapeutic agent in skin wounds in patients with hyperglycemia.

scholarly journals Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients

2020 ◽  
Vol 9 (10) ◽  
pp. 3335
Author(s):  
Giulio Tessarin ◽  
Stefano Rossi ◽  
Manuela Baronio ◽  
Luisa Gazzurelli ◽  
Michael Colpani ◽  
...  
Keyword(s):  
Laboratory Data ◽  
Clinical Manifestations ◽  
Lymphoproliferative Disease ◽  
Clinical Feature ◽  
Hematopoietic Stem ◽  
Replacement Treatment ◽  
Phosphoinositide 3 Kinase ◽  
First Time

Activated phosphoinositide 3-kinase delta syndrome 1 (APDS-1) is a recently described inborn error of immunity caused by monoallelic gain-of-function mutations in the PIK3CD gene. We reviewed for the first time medical records and laboratory data of eight Italian APDS-1 patients. Recurrent sinopulmonary infections were the most common clinical feature at onset of disease. Seven patients presented lymphoproliferative disease, at onset or during follow-up, one of which resembled hemophagocytic lymphohistiocytosis (HLH). Genetic analysis of the PIK3CD gene revealed three novel mutations: functional testing confirmed their activating nature. In the remaining patients, the previously reported variants p.E1021K (n = 4) and p.E525A (n = 1) were identified. Six patients were started on immunoglobulin replacement treatment (IgRT). One patient successfully underwent hematopoietic stem cell transplantation (HSCT), with good chimerism and no GVHD at 21 months post-HSCT. APDS-1 is a combined immune deficiency with a wide variety of clinical manifestations and a complex immunological presentation. Besides IgRT, specific therapies targeting the PI3Kδ pathway will most likely become a valid aid for the amelioration of patients’ clinical management and their quality of life.

Cotard's syndrome with glioblastoma multiforme

2012 ◽  
Vol 10 (2) ◽  
pp. 135-139 ◽  
Author(s):  
Michel Reich ◽  
Benedicte Comet ◽  
Emilie Le Rhun ◽  
Carole Ramirez
Keyword(s):  
Glioblastoma Multiforme ◽  
Poor Prognosis ◽  
Clinical Manifestations ◽  
Cognitive Disorders ◽  
Tumor Location ◽  
Psychiatric Symptomatology ◽  
Concomitant Radiochemotherapy ◽  
Personality Changes ◽  
First Time

AbstractObjective:Brain tumors are classically associated with neurological and/or psychiatric symptomatology. Behavioral or cognitive disorders can underlie delirium, personality changes, psychotic reactions, and mood disorders.Method:To illustrate this, we report the case of a 60-year-old male patient confronted with an inoperable glioblastoma multiforme on the splenium of the corpus callosum, of poor prognosis, treated by concomitant radiochemotherapy with temozolomide, who developed psychotic depression with Cotard's syndrome. Clinical manifestations of this syndrome with untoward consequences in terms of prognosis are classically characterized by intense moral suffering, indignity and pessimistic fixations, suicidal ideations, and a nihilistic delusion relating to one's own body.Results:Nevertheless, this association between Cotard's syndrome and glioblastoma has been seldom described. To our knowledge, this is the first time that this has been described as a complication of this particular tumor location. Some neuropsychopathological hypotheses are proposed, which involve medical, iatrogenic, and psychogenesis issues.Significance of results:This case report points to the necessary collaboration between psychiatrists, neuro-oncologists and radiation oncologists in improving the patient's management and quality of life.

scholarly journals Comparative Evaluation of Brandy de Jerez Aged in American Oak Barrels with Different Times of Use

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 288
Author(s):  
Manuel J. Valcárcel-Muñoz ◽  
María Guerrero-Chanivet ◽  
M. Valme García-Moreno ◽  
M. Carmen Rodríguez-Dodero ◽  
Dominico A. Guillén-Sánchez
Keyword(s):  
Life Cycle ◽  
Comparative Evaluation ◽  
Geographical Indication ◽  
Substantial Influence ◽  
Sherry Wine ◽  
Organoleptic Characteristics ◽  
Oak Barrels ◽  
First Time ◽  
Over Time

Brandy de Jerez is a European Geographical Indication for grape-derived spirits aged in oak casks that have previously contained any kind of Sherry wine and, therefore, are known as Sherry Casks®. Wood compounds have a substantial influence in the quality of the brandies that are aged in the barrels. In the cellar, the barrels that have been used for many years to keep Sherry wine or other wine spirits are often used for this purpose. When wooden barrels are used for the first time, they release a large amount of compounds into the liquid contained in them. Such amount decreases over time but casks life cycle has remained unexplored until now. The present work has the aim to study the brandies obtained from the same wine spirit after two years ageing in three differently oak casks: namely new, 7 years of use (4 years containing Oloroso wine and 3 years containing wine spirits) and 32 years of use (8 years containing Oloroso wine and 24 years containing wine spirits). According to the results from our experiments, even after 32 years of use, the wood barrels still contribute to modify the organoleptic characteristics of brandy. Moreover, the brandies aged in used barrels were judged more balanced than those aged in new barrels.

scholarly journals Impact of Lossy Compression Techniques on the Impedance Determination

Energies ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3661
Author(s):  
Maik Plenz ◽  
Marc Florian Meyer ◽  
Florian Grumm ◽  
Daniel Becker ◽  
Detlef Schulz ◽  
...  
Keyword(s):  
High Resolution ◽  
Frequency Characteristic ◽  
Lossy Compression ◽  
Data Output ◽  
Measured Impedance ◽  
The Stability ◽  
Energy Grid ◽  
First Time ◽  
Over Time

One of the essential parameters to measure the stability and power-quality of an energy grid is the network impedance. Including distinct resonances which may also vary over time due to changing load or generation conditions in a network, the frequency characteristic of the impedance is an import part to analyse. The determination and analysis of the impedance go hand in hand with a massive amount of data output. The reduction of this high-resolution voltage and current datasets, while maintaining the fidelity of important information, is the main focus of this paper. The presented approach takes measured impedance datasets and a set of lossy compression procedures, to monitor the performance success with known key metrics. Afterwards, it continually compares the results of various lossy compression techniques. The innovative contribution is the combination of new and existing procedures as well as metrics in one approach, to reduce the size of the impedance datasets for the first time. The approach needs to be efficient, suitable, and exact, otherwise the decompression results are useless.

scholarly journals DAF-16 and SMK-1 contribute to innate immunity during adulthood in Caenorhabditis elegans

2019 ◽  
Author(s):  
Daniel R. McHugh ◽  
Elena Koumis ◽  
Michelle Schlaubitz-Garcia ◽  
Safae Bennani ◽  
Paul Regan ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Caenorhabditis Elegans ◽  
Host Defense ◽  
Insulin Signaling ◽  
Bacterial Pathogens ◽  
Dependent Manner ◽  
C Elegans ◽  
Age Dependent ◽  
Over Time

ABSTRACTAging is accompanied by a progressive decline in immune function termed “immunosenescence”. Deficient surveillance coupled with the impaired function of immune cells compromises host defense in older animals. The dynamic activity of regulatory modules that control immunity appears to underlie age-dependent modifications to the immune system. In the roundworm Caenorhabditis elegans levels of the PMK-1 p38 MAP kinase diminish over time, reducing the expression of immune effectors that clear bacterial pathogens. Along with the PMK-1 pathway, innate immunity in C. elegans is regulated by the insulin signaling pathway. Here we asked whether DAF-16, a Forkhead box (FOXO) transcription factor whose activity is inhibited by insulin signaling, plays a role in host defense later in life. While in younger worms DAF-16 remains in an inactive state unless stimulated by environmental insults, we found that even in the absence of acute stress the transcriptional activity of DAF-16 increases in an age-dependent manner. Beginning in the reproductive phase of adulthood, DAF-16 upregulates a subset of its transcriptional targets, including genes required to kill ingested microbes. Accordingly, DAF-16 has little to no role in larval immunity, but functions specifically during adulthood to confer resistance to bacterial pathogens. We found that DAF-16-mediated immunity in adults requires SMK-1, a regulatory subunit of the PP4 protein phosphatase complex. Our data suggest that as the function of one branch of the innate immune system of C. elegans (PMK-1) declines over time, DAF-16-mediated immunity ramps up to become the predominant means of protecting adults from infection, thus reconfiguring immunity later in life.

scholarly journals Kebijakan Kepemilikan Rumah Susun di Indonesia

Lentera Hukum ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 15
Author(s):  
Ayu Fitria Febriani
Keyword(s):  
Legal Protection ◽  
Land Ownership ◽  
Legal Certainty ◽  
High Rise ◽  
Ownership Status ◽  
Human Need ◽  
The Government ◽  
First Time ◽  
Over Time

In the concept of agrarian law, it is not something new anymore that the land is getting less and less while the human need for land increasingly day increases. This is what makes the government then make a policy in the construction of housing in the form of horizontally building homes to save land called flats. The development of the flats is expected to meet the needs of the community will be a place to live and can improve the quality of life of the community. but over time, in perkembangnnya development of flats is also not free from various problems. This article examines the legal certainty of the ownership status of apartment units, not only from the land ownership aspect in which the high rise is built, but also includes the initial publication of the master certificate issued on behalf of the developer for the first time. Developers as business actors in trust by the government to get the first certificate of a development of flats, this often affects the inhabitants of apartment units. Although each resident of a flats unit may own / hold property certificates of units from separate flats between joint and individual sections, sometimes ownership status with a title certificate also can not protect the inhabitants of various disputes. Therefore, to minimize the occurrence of disputes, legal certainty becomes important to protect the parties concerned so as not to harm each other. Legal protection in such cases can be done by means of preventive law protection and repressive law protection.

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