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1.
Giuseppe Murdaca Alessandra Gerosa Francesca Paladin Lorena Petrocchi Sara Banchero Sebastiano Gangemi 《International journal of molecular sciences》2021,22(8)
There is increasing recognition of the importance of both the microbiome and vitamin D in states of health and disease. Microbiome studies have already demonstrated unique microbial patterns in systemic autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus. Dysbiosis also seems to be associated with allergies, in particular asthma, atopic dermatitis, and food allergy. Even though the effect of vitamin D supplementation on these pathologies is still unknown, vitamin D deficiency deeply influences the microbiome by altering the microbiome composition and the integrity of the gut epithelial barrier. It also influences the immune system mainly through the vitamin D receptor (VDR). In this review, we summarize the influence of the microbiome and vitamin D on the immune system with a particular focus on allergic diseases and we discuss the necessity of further studies on the use of probiotics and of a correct intake of vitamin D. 相似文献
2.
Aleksandra Dondalska Sandra Axberg Plsson Anna-Lena Spetz 《International journal of molecular sciences》2022,23(23)
Here, we link approved and emerging nucleic acid-based therapies with the expanding universe of small non-coding RNAs (sncRNAs) and the innate immune responses that sense oligonucleotides taken up into endosomes. The Toll-like receptors (TLRs) 3, 7, 8, and 9 are located in endosomes and can detect nucleic acids taken up through endocytic routes. These receptors are key triggers in the defense against viruses and/or bacterial infections, yet they also constitute an Achilles heel towards the discrimination between self- and pathogenic nucleic acids. The compartmentalization of nucleic acids and the activity of nucleases are key components in avoiding autoimmune reactions against nucleic acids, but we still lack knowledge on the plethora of nucleic acids that might be released into the extracellular space upon infections, inflammation, and other stress responses involving increased cell death. We review recent findings that a set of single-stranded oligonucleotides (length of 25–40 nucleotides (nt)) can temporarily block ligands destined for endosomes expressing TLRs in human monocyte-derived dendritic cells. We discuss knowledge gaps and highlight the existence of a pool of RNA with an approximate length of 30–40 nt that may still have unappreciated regulatory functions in physiology and in the defense against viruses as gatekeepers of endosomal uptake through certain routes. 相似文献
3.
Carlotta Lassandro Giuseppe Banderali Giovanni Radaelli Elisa Borghi Francesca Moretti Elvira Verduci 《International journal of molecular sciences》2015,16(8):19989-20000
Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure) and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome. 相似文献
4.
Pauline Chabosseau Guy A. Rutter Steven J. Millership 《International journal of molecular sciences》2021,22(3)
Diabetes mellitus now affects more than 400 million individuals worldwide, with significant impacts on the lives of those affected and associated socio-economic costs. Although defects in insulin secretion underlie all forms of the disease, the molecular mechanisms which drive them are still poorly understood. Subsets of specialised beta cells have, in recent years, been suggested to play critical roles in “pacing” overall islet activity. The molecular nature of these cells, the means through which their identity is established and the changes which may contribute to their functional demise and “loss of influence” in both type 1 and type 2 diabetes are largely unknown. Genomic imprinting involves the selective silencing of one of the two parental alleles through DNA methylation and modified imprinted gene expression is involved in a number of diseases. Loss of expression, or loss of imprinting, can be shown in mouse models to lead to defects in beta cell function and abnormal insulin secretion. In the present review we survey the evidence that altered expression of imprinted genes contribute to loss of beta cell function, the importance of beta cell heterogeneity in normal and disease states, and hypothesise whether there is a direct link between the two. 相似文献
5.
6.
Yoshifumi Saisho 《International journal of molecular sciences》2014,15(10):18381-18406
Diabetes is associated with a two to three-fold increase in risk of cardiovascular disease. However, intensive glucose-lowering therapy aiming at reducing HbA1c to a near-normal level failed to suppress cardiovascular events in recent randomized controlled trials. HbA1c reflects average glucose level rather than glycemic variability. In in vivo and in vitro studies, glycemic variability has been shown to be associated with greater reactive oxygen species production and vascular damage, compared to chronic hyperglycemia. These findings suggest that management of glycemic variability may reduce cardiovascular disease in patients with diabetes; however, clinical studies have shown conflicting results. This review summarizes the current knowledge on glycemic variability and oxidative stress, and discusses the clinical implications. 相似文献
7.
Monodisperse iron oxide particles were deposited on a planar silica transmission electron microscope (TEM) grid and from TEM and Energy Filtered TEM analyses it is confirmed that the particles are involved in a series of re-arrangements during the pretreatment and initial carbon nanotube (CNT) growth. It is also shown that CNT growth occurs in two stages; an initial disordered growth, followed by a more aligned growth underneath. The planar silica TEM grid serves the dual purpose of being the catalytic support, and the tool which facilitates TEM analysis on a planar model system. The particle re-arrangements and the two modes of CNT growth may offer an explanation as to why we find no correlation between primary particle size and final CNT diameter. 相似文献
8.
Brigita Urbanc 《Israel journal of chemistry》2017,57(7-8):651-664
Revised amyloid cascade hypothesis of Alzheimer′s disease (AD) states that amyloid β-protein (Aβ) triggers the disease through formation of soluble low molecular weight (LMW) assemblies, called oligomers, which are challenging to characterize experimentally as well as computationally due to their heterogeneous and polymorphic nature, lack of ordered structure, and short lifetimes. Recent findings challenge the view of Aβ oligomers as exclusively toxic entities by revealing their dual, protective and disruptive nature in the context of immune response and AD, respectively. In this review, the understanding of Aβ oligomer formation and structure is discussed from the AD perspective. The structure-activity relationship (SAR) that implicates flexible, solvent exposed N-termini of Aβ oligomers, observed in computer simulations, in mediating their toxic as well as protective activity is proposed. 相似文献
9.
Roxana Mihaela Chiorescu Mihaela Mocan Andreea Ioana Inceu Andreea Paula Buda Dan Blendea Sonia Irina Vlaicu 《International journal of molecular sciences》2022,23(21)
Atherosclerosis and its clinical manifestations, coronary and cerebral artery diseases, are the most common cause of death worldwide. The main pathophysiological mechanism for these complications is the rupture of vulnerable atherosclerotic plaques and subsequent thrombosis. Pathological studies of the vulnerable lesions showed that more frequently, plaques rich in lipids and with a high level of inflammation, responsible for mild or moderate stenosis, are more prone to rupture, leading to acute events. Identifying the vulnerable plaques helps to stratify patients at risk of developing acute vascular events. Traditional imaging methods based on plaque appearance and size are not reliable in prediction the risk of rupture. Intravascular imaging is a novel technique able to identify vulnerable lesions, but it is invasive and an operator-dependent technique. This review aims to summarize the current data from literature regarding the main biomarkers involved in the attempt to diagnose vulnerable atherosclerotic lesions. These biomarkers could be the base for risk stratification and development of the new therapeutic drugs in the treatment of patients with vulnerable atherosclerotic plaques. 相似文献
10.
Laura Caliogna Viviana Guerrieri Salvatore Annunziata Valentina Bina Alice Maria Brancato Alberto Castelli Eugenio Jannelli Alessandro Ivone Federico Alberto Grassi Mario Mosconi Gianluigi Pasta 《International journal of molecular sciences》2021,22(18)
Ehlers-Danlos syndromes (EDS) are an inherited heterogeneous group of connective tissue disorders characterized by an abnormal collagen synthesis affecting skin, ligaments, joints, blood vessels, and other organs. It is one of the oldest known causes of bruising and bleeding, and it was described first by Hippocrates in 400 BC. In the last years, multiple gene variants involved in the pathogenesis of specific EDS subtypes have been identified; moreover, new clinical diagnostic criteria have been established. New classification models have also been studied in order to differentiate overlapping conditions. Moreover, EDS shares many characteristics with other similar disorders. Although distinguishing between these seemingly identical conditions is difficult, it is essential in ensuring proper patient care. Currently, there are many genetic and molecular studies underway to clarify the etiology of some variants of EDS. However, the genetic basis of the hypermobile type of EDS (hEDS) is still unknown. In this review, we focused on the study of two of the most common forms of EDS—classic and hypermobile—by trying to identify possible biomarkers that could be of great help to confirm patients’ diagnosis and their follow up. 相似文献
11.
Alice Chaplin Ramon Maria Rodriguez Juan Jos Segura-Sampedro Aina Ochogavía-Seguí Dora Romaguera Gwendolyn Barcel-Coblijn 《International journal of molecular sciences》2022,23(21)
Colorectal cancer (CRC) is a major health problem worldwide, with an estimated 1.9 million new cases and 915,880 deaths in 2020 alone. The etiology of CRC is complex and involves both genetic and lifestyle factors. Obesity is a major risk factor for CRC, and the mechanisms underlying this link are still unclear. However, the generalized inflammatory state of adipose tissue in obesity is thought to play a role in the association between CRC risk and development. Visceral adipose tissue (VAT) is a major source of proinflammatory cytokines and other factors that contribute to the characteristic systemic low-grade inflammation associated with obesity. VAT is also closely associated with the tumor microenvironment (TME), and recent evidence suggests that adipocytes within the TME undergo phenotypic changes that contribute to tumor progression. In this review, we aim to summarize the current evidence linking obesity and CRC, with a focus on the role of VAT in tumor etiology and progression. 相似文献
12.
Flávia Galv?o Candido Josefina Bressan 《International journal of molecular sciences》2014,15(4):6569-6591
Vitamin D (1,25(OH)2D3) is a steroid hormone that has a range of physiological functions in skeletal and nonskeletal tissues, and can contribute to prevent and/or treat osteoporosis, obesity, and Type 2 diabetes mellitus (T2DM). In bone metabolism, vitamin D increases the plasma levels of calcium and phosphorus, regulates osteoblast and osteoclast the activity, and combats PTH hypersecretion, promoting bone formation and preventing/treating osteoporosis. This evidence is supported by most clinical studies, especially those that have included calcium and assessed the effects of vitamin D doses (≥800 IU/day) on bone mineral density. However, annual megadoses should be avoided as they impair bone health. Recent findings suggest that low serum vitamin D is the consequence (not the cause) of obesity and the results from randomized double-blind clinical trials are still scarce and inconclusive to establish the relationship between vitamin D, obesity, and T2DM. Nevertheless, there is evidence that vitamin D inhibits fat accumulation, increases insulin synthesis and preserves pancreatic islet cells, decreases insulin resistance and reduces hunger, favoring obesity and T2DM control. To date, there is not enough scientific evidence to support the use of vitamin D as a pathway to prevent and/or treat obesity and T2DM. 相似文献
13.
Ahmed Abdelhak Andreas Junker Johannes Brettschneider Jan Kassubek Albert C. Ludolph Markus Otto Hayrettin Tumani 《International journal of molecular sciences》2015,16(8):17565-17588
Many neurodegenerative disorders share a common pathophysiological pathway involving axonal degeneration despite different etiological triggers. Analysis of cytoskeletal markers such as neurofilaments, protein tau and tubulin in cerebrospinal fluid (CSF) may be a useful approach to detect the process of axonal damage and its severity during disease course. In this article, we review the published literature regarding brain-specific CSF markers for cytoskeletal damage in primary progressive multiple sclerosis and amyotrophic lateral sclerosis in order to evaluate their utility as a biomarker for disease progression in conjunction with imaging and histological markers which might also be useful in other neurodegenerative diseases associated with affection of the upper motor neurons. A long-term benefit of such an approach could be facilitating early diagnostic and prognostic tools and assessment of treatment efficacy of disease modifying drugs. 相似文献
14.
Vladimira Vuleti Valentino Ra
ki Elia Papi Borut Peterlin 《International journal of molecular sciences》2021,22(13)
Background: Parkinson’s disease (PD) is the second most frequent neurodegenerative disease, which creates a significant public health burden. There is a challenge for the optimization of therapies since patients not only respond differently to current treatment options but also develop different side effects to the treatment. Genetic variability in the human genome can serve as a biomarker for the metabolism, availability of drugs and stratification of patients for suitable therapies. The goal of this systematic review is to assess the current evidence for the clinical translation of pharmacogenomics in the personalization of treatment for Parkinson’s disease. Methods: We performed a systematic search of Medline database for publications covering the topic of pharmacogenomics and genotype specific mutations in Parkinson’s disease treatment, along with a manual search, and finally included a total of 116 publications in the review. Results: We analyzed 75 studies and 41 reviews published up to December of 2020. Most research is focused on levodopa pharmacogenomic properties and catechol-O-methyltransferase (COMT) enzymatic pathway polymorphisms, which have potential for clinical implementation due to changes in treatment response and side-effects. Likewise, there is some consistent evidence in the heritability of impulse control disorder via Opioid Receptor Kappa 1 (OPRK1), 5-Hydroxytryptamine Receptor 2A (HTR2a) and Dopa decarboxylase (DDC) genotypes, and hyperhomocysteinemia via the Methylenetetrahydrofolate reductase (MTHFR) gene. On the other hand, many available studies vary in design and methodology and lack in sample size, leading to inconsistent findings. Conclusions: This systematic review demonstrated that the evidence for implementation of pharmacogenomics in clinical practice is still lacking and that further research needs to be done to enable a more personalized approach to therapy for each patient. 相似文献
15.
Patrycja Rzepka-Wrona Szymon Skoczyski Adam Barczyk 《International journal of molecular sciences》2022,23(23)
In this pilot study, we aim to determine differences in pathogenetic pathways between interstitial pneumonia with autoimmune features (IPAF), connective-tissue-disease-associated interstitial lung diseases (CTD-ILDs), and idiopathic interstitial pneumonias (IIPs). Forty participants were recruited: 9 with IPAF, 15 with CTD-ILDs, and 16 with IIPs. Concentration of transforming growth factor beta (TGF-β1), surfactant proteins A and D (SP-A, SP-D), interleukin 8 (IL-8), and chemokine 1 (CXCL1) were assessed with ELISA assay in bronchoalveolar lavage (BAL) fluid. We revealed that IL-8 and TGF-β1 concentrations were significantly lower in the IPAF group than in the CTD-ILD group (p = 0.008 and p = 0.019, respectively), but similar to the concentrations in the IIP group. There were significant correlations of IL-8 (rs = 0.46; p = 0.003) and CXCL1 (rs = 0.52; p = 0.001) and BAL total cell count (TCC). A multivariate regression model revealed that IL-8 (β = 0.32; p = 0.037) and CXCL1 (β = 0.45; p = 0.004) are significant predictors of BAL TCC. We revealed that IL-8 and TGF-β1 BAL concentrations vary in patients with different ILDs and found that IL-8 is a predictor of BAL TCC in IPAF. However, this needs to be confirmed in a multicenter cooperative study (ClinicalTrials.gov Identifier: ). NCT03870828相似文献
16.
Franck Paganelli Giovanna Mottola Julien Fromonot Marion Marlinge Pierre Deharo Rgis Guieu Jean Ruf 《International journal of molecular sciences》2021,22(4)
The influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H2S) is a cardioprotector. Previous research proposed a positive role of H2S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H2S, which decreases the expression of adenosine A2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively. 相似文献
17.
Edna Soares Julie Reis Mariana Rodrigues Carlos Fontes Ribeiro Frederico C. Pereira 《International journal of molecular sciences》2021,22(2)
Depression is associated with an increased risk of aging-related diseases. It is also seemingly a common psychological reaction to pandemic outbreaks with forced quarantines and lockdowns. Thus, depression represents, now more than ever, a major global health burden with therapeutic management challenges. Clinical data highlights that physical exercise is gaining momentum as a non-pharmacological intervention in depressive disorders. Although it may contribute to the reduction of systemic inflammation associated with depression, the mechanisms underlying the beneficial physical exercise effects in emotional behavior remain to be elucidated. Current investigations indicate that a rapid release of extracellular vesicles into the circulation might be the signaling mediators of systemic adaptations to physical exercise. These biological entities are now well-established intercellular communicators, playing a major role in relevant physiological and pathophysiological functions, including brain cell–cell communication. We also reviewed emerging evidence correlating depression with modified circulating extracellular vesicle surfaces and cargo signatures (e.g., microRNAs and proteins), envisioned as potential biomarkers for diagnosis, efficient disease stratification and appropriate therapeutic management. Accordingly, the clinical data summarized in the present review prompted us to hypothesize that physical exercise-related circulating extracellular vesicles contribute to its antidepressant effects, particularly through the modulation of inflammation. This review sheds light on the triad “physical exercise–extracellular vesicles–depression” and suggests new avenues in this novel emerging field. 相似文献
18.
Yuri Utkin Andrei Siniavin Igor Kasheverov Victor Tsetlin 《International journal of molecular sciences》2022,23(7)
Viruses infect all types of organisms, causing viral diseases, which are very common in humans. Since viruses use the metabolic pathways of their host cells to replicate, they are difficult to eradicate without affecting the cells. The most effective measures against viral infections are vaccinations and antiviral drugs, which selectively inhibit the viral replication cycle. Both methods have disadvantages, which requires the development of new approaches to the treatment of viral diseases. In the study of animal venoms, it was found that, in addition to toxicity, venoms exhibit other types of biological activity, including an antiviral one, the first mention of which dates back to middle of the last century, but detailed studies of their antiviral activity have been conducted over the past 15 years. The COVID-19 pandemic has reinforced these studies and several compounds with antiviral activity have been identified in venoms. Some of them are very active and can be considered as the basis for antiviral drugs. This review discusses recent antiviral studies, the found compounds with high antiviral activity, and the possible mechanisms of their action. The prospects for using the animal venom components to create antiviral drugs, and the expected problems and possible solutions are also considered. 相似文献
19.
Alessandro Conforti Salvatore Longobardi Luigi Carbone Giuseppe Gabriele Iorio Federica Cariati Maria Rosaria Campitiello Ida Strina Michela Palese Thomas DHooghe Carlo Alviggi 《International journal of molecular sciences》2022,23(20)
Various interventions have been proposed to improve embryo implantation in IVF. Among these, intrauterine injections of human chorionic gonadotropin seem to have promising results. Consequently, we conducted a review and meta-analysis to assess IVF outcomes by comparing couples who underwent intrauterine hCG injection transfer versus those who underwent embryo transfer with intrauterine injection of placebo, or without any additional intervention. The primary outcome was the clinical pregnancy rate. Secondary outcomes were the implantation rate, miscarriage rate, and live birth rate. A meta-analysis was conducted using the random effects model, while bias within studies was detected using the Cochrane risk of bias tool. Ectopic pregnancies and stillbirths were also assessed. The clinical pregnancy (RR 1.38, 95% CI 1.17–1.62, p < 0.0001) and implantation rate (RR 1.40, 95% CI 1.12–1.75, p = 0.003) were significantly higher in women who underwent hCG injection than in the control group. These significant effects persisted only in women who underwent cleavage-stage embryo transfer. No significant differences between groups were observed in the other secondary outcomes. In conclusion, our systematic review and meta-analysis demonstrate that intrauterine injection of hCG could be a valuable approach in women who undergo cleavage-stage embryo transfer. Given the lack of data about the live birth rate, caution should be exercised in interpreting these data. 相似文献
20.
Fbio Cunha Coelho Giselle Cerchiaro Sheila Espírito Santo Araújo Joo Paulo Lima Daher Silvia Almeida Cardoso Gustavo Fialho Coelho Arthur Giraldi Guimares 《International journal of molecular sciences》2022,23(14)
Alzheimer’s disease (AD) and other forms of dementia was ranked 3rd in both the Americas and Europe in 2019 in a World Health Organization (WHO) publication listing the leading causes of death and disability worldwide. Copper (Cu) imbalance has been reported in AD and increasing evidence suggests metal imbalance, including molybdenum (Mo), as a potential link with AD occurrence.We conducted an extensive literature review of the last 60 years of research on AD and its relationship with Cu, sulfur (S), and Mo at out of range levels.Weanalyzed the interactions among metallic elements’ metabolisms;Cu and Mo are biological antagonists, Mo is a sulfite oxidase and xanthine oxidase co-factor, and their low activities impair S metabolism and reduce uric acid, respectively. We found significant evidence in the literature of a new potential mechanism linking Cu imbalance to Mo and S abnormalities in AD etiology: under certain circumstances, the accumulation of Cu not bound to ceruloplasmin might affect the transport of Mo outside the blood vessels, causing a mild Mo deficiency that might lowerthe activity of Mo and S enzymes essential for neuronal activity. The current review provides an updated discussion of the plausible mechanisms combining Cu, S, and Mo alterations in AD. 相似文献