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[This retracts the article DOI: 10.1007/s40200-021-00883-3.].
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BACKGROUND: Metabolic syndrome (MS) is becoming a major health risk in the world. Disorders of homeostasis are a trigger for MS and subsequent cardiometabolic diseases (CMDs). Its physiological role can be supported by biological protectors (BP). The purpose of this study is to develop a BP system for managing the MS development. METHODS: Within the framework of the case-control study, 3000 participants aged 20-60 years formed 2 groups: the main group and the control group. RESULTS: The study compared traditional markers of oxidative stress, chronic inflammation, and insulin resistance, which reflect the state of homeostasis. The BP system, proposed based on the concept of maintaining homeostasis, offers the following points for investigating the possibilities of therapeutic intervention: confronting dysregulation of homeostasis, resisting chronic inflammation and oxidative stress, resisting the consequences of disturbed homeostasis. This approach not only contributed to the understanding of general biological processes, but also provided a targeted search and development of BP to maintain the stability of homeostasis with MS. CONCLUSIONS: The study results provided insight into new opportunities in the MS management.
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OBJECTIVE: Changes in the gut microbiota are increasingly recognised to be involved in many diseases. This ecosystem is known to be shaped by many factors, including climate, geography, host nutrition, lifestyle and medication. Thus, knowledge of varying populations with different habits is important for a better understanding of the microbiome. DESIGN: We therefore conducted a metagenomic analysis of intestinal microbiota from Kazakh donors, recruiting 84 subjects, including male and female healthy subjects and metabolic syndrome (MetS) patients aged 25-75 years, from the Kazakh administrative centre, Astana. We characterise and describe these microbiomes, the first deep-sequencing cohort from Central Asia, in comparison with a global dataset (832 individuals from five countries on three continents), and explore correlations between microbiota, clinical and laboratory parameters as well as with nutritional data from Food Frequency Questionnaires. RESULTS: We observe that Kazakh microbiomes are relatively different from both European and East Asian counterparts, though similar to other Central Asian microbiomes, with the most striking difference being significantly more samples falling within the Prevotella-rich enterotype, potentially reflecting regional diet and lifestyle. We show that this enterotype designation remains stable within an individual over time in 82% of cases. We further observe gut microbiome features that distinguish MetS patients from controls (eg, significantly reduced Firmicutes to Bacteroidetes ratio, Bifidobacteria and Subdoligranulum, alongside increased Prevotella), though these overlap little with previously published reports and thus may reflect idiosyncrasies of the present cohort. CONCLUSION: Taken together, this exploratory study describes gut microbiome data from an understudied population, providing a starting point for further comparative work on biogeography and research on widespread diseases. TRIAL REGISTRATION NUMBER: ISRCTN37346212; Post-results.
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Microbioma Gastrointestinal , Probióticos/administração & dosagem , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Fezes/microbiologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cazaquistão , Masculino , Síndrome Metabólica/microbiologia , Metagenômica , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Health authorities of Kazakhstan are seeking for effective measures to interrupt the untoward trend, projected to increase the current number of gastric cancer (GC) cases (n=3,316) by 50% until the year 2030. OBJECTIVE: Use of a non-invasive blood test with four stomach-specific biomarkers [Pepsinogen-I (PG-I) and -II (PG-II), amidated gastrin-17 (G-17), and Helicobacter pylori (HP) IgG antibodies], to assess for the prevalence of stomach conditions: Helicobacter pylori (HP) infection and atrophic gastritis (AG), both known to increase GC risk of in Kazakhstan. MATERIALS AND METHODS: A cohort of 835 (symptomatic and asymptomatic) cases (473 women and 362 men)(median age 46.8 years; range 13.6-74.8) was examined with a panel of biomarkers. Results were assigned in five categories: 1) Healthy stomach, 2) HP infection, 3) atrophic gastritis (AG) of the antrum, 4) AG of the corpus, and 5) AG of both antrum and corpus (pangastritis). RESULTS: The distribution in these five categories was identical in both sexes (p=0.259). Healthy stomach was detected only in 196 (23.5%) subjects, whereas the vast majority, 62.3% (n=519) had HP infection (with no AG). In 118 (14.1%) subjects, results were consistent with AG; in antrum (n=72), corpus (n=42) or pangastritis (n=4). Prevalence of AG increased with patient's age in both sexes. There was no age-related pattern in biomarker levels, and only slight differences between the genders. CONCLUSION: While capable of detecting the subjects at risk for GC (HP or AG), GP seems to be a cost-effective means to intervene the current ominous trend in GC incidence in Kazakhstan.
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Dispepsia/sangue , Gastrite Atrófica/sangue , Infecções por Helicobacter/sangue , Helicobacter pylori/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Dispepsia/epidemiologia , Feminino , Gastrinas/sangue , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/imunologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/imunologia , Humanos , Cazaquistão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Fenótipo , Prevalência , Distribuição por Sexo , Adulto JovemRESUMO
Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive "reporter cells" that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) and young adult controls (YC). AD is characterized by higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed that glycolytic and related enzymes displayed significantly lower activities in AC. However, similar or significantly higher activities were observed in AD and NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were significantly decreased in AD and NA patients. The pattern of changes between groups in the above indices strongly correlates with each other. Collectively, our data suggested that AD and NA patients are associated with chronic disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role in physiological processes, which predispose elderly subjects to AD and NA.
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APP/PS1 double-transgenic mouse models of Alzheimer's disease (AD), which overexpress mutated forms of the gene for human amyloid precursor protein (APP) and presenilin 1 (PS1), have provided robust neuropathological hallmarks of AD-like pattern at early ages. This study characterizes immunocytochemical patterns of AD mouse brain as a model for human AD treated with the EB101 vaccine. In this novel vaccine, a new approach has been taken to circumvent past failures by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol). Our findings showed that administration of amyloid-ß1â42 (Aß) and sphingosine-1-phosphate emulsified in liposome complex (EB101) to APP/PS1 mice before onset of Aß deposition (7 weeks of age) and/or at an older age (35 weeks of age) is effective in halting the progression and clearing the AD-like neuropathological hallmarks. Passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus) in the brain of treated mice was notably reduced. These results demonstrate that immunization with EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.
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Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Peptídeos beta-Amiloides/genética , Presenilina-1/genética , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/antagonistas & inibidores , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/imunologia , Precursor de Proteína beta-Amiloide/uso terapêutico , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/imunologia , Modelos Animais de Doenças , Humanos , Imunoterapia Ativa , Camundongos , Camundongos Transgênicos , Presenilina-1/imunologiaRESUMO
It has been postulated that Alzheimer disease (AD) is a systemic process, which involves multiple pathophysiological factors. A combination of pharmacotherapy and nonpharmacological interventions has been proposed to treat AD and other dementia. The nonpharmacological interventions include but are not limited to increasing sensory input through physical and mental activities, in order to modify cerebral blood flow and implementing nutritional interventions such as diet modification and vitamins and nutraceuticals therapy to vitalize brain functioning. This article highlights the recent research findings regarding novel treatment strategies aimed at modifying natural course of the disease and delaying cognitive decline through simultaneous implementation of pharmacological and nonpharmacological modulators as standardized treatment protocols.
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Doença de Alzheimer/terapia , Transtornos Cognitivos/terapia , Depressão/terapia , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Animais , Transtornos Cognitivos/complicações , Transtornos Cognitivos/metabolismo , Depressão/etiologia , Depressão/metabolismo , Suplementos Nutricionais , Humanos , Vitaminas/metabolismoRESUMO
INTRODUCTION: APP/PS1 double-transgenic mouse models of Alzheimer's disease (AD), which overexpress mutated forms of the gene for the human amyloid precursor protein (APP) and presenilin 1 (PS1), have provided robust neuropathological hallmarks of an AD-like pattern at early ages. This study aimed to characterize immunocytochemical patterns of the AD mouse brain, which is treated with the EB101 vaccine, as a model for human AD. MATERIAL AND METHODS: In this novel vaccine, a new approach has been taken to circumvent past failures with Aß vaccines by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol). RESULTS: Our findings showed that the administration of amyloid-ß1-42 (Aß) and sphingosine-1-phosphate emulsified in liposome complex (EB101) to APP/PS1 mice before the onset of Aß brain deposition (at 7 weeks of age) and/or at an older age (35 weeks of age) can be effective in both halting the progression and clearing the AD-like neuropathological hallmarks. In addition, passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus) in the brain of treated mice was notably reduced. CONCLUSION: These results provide strong evidence that immunization with the EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.