Iffet Ipek Bosgelmez

According to WHO data, approximately 57 million people worldwide were affected by dementia in 2021, with prevalence projected to rise. Alzheimer’s disease (AD), responsible for 60%–80% of dementia cases, continues to be a leading cause of mortality, with current treatments offering limited efficacy and disease-modifying therapies lacking widespread adoption or conclusive safety evidence, shifting the focus toward prevention and risk modification. Risk factors for AD include both non-modifiable elements, such as age, genetics, and gender, and modifiable factors, like environmental pollution, health status, and diet. While age remains the primary non-modifiable risk factor, early-onset dementia represents only up to 9% of cases. Addressing modifiable factors is essential, as it could prevent or delay almost half of dementia cases, with interventions—such as increased physical activity, smoking cessation, alcohol limitation, and overall health management—being significantly associated with a reduced risk. In this context, the exposome approach offers a comprehensive, integrative framework in which both modifiable and non-modifiable risk factors interact to influence individual susceptibility. Within the neural exposome, chronic low-dose exposure to xenobiotics—such as industrial chemicals, pesticides, metals, pharmaceuticals and personal care products (PPCPs), and air pollutants—may induce neurodegeneration via mechanisms including oxidative stress, neuroinflammation, proteinopathies, and epigenetic modifications, although establishing causality remains challenging. Integration of genomics, transcriptomics, proteomics, metabolomics, and lipidomics, combined with artificial intelligence (AI) techniques such as machine learning (ML) and deep learning (DL), provides promising avenues for biomarker discovery, enhanced preventive strategies, early non-invasive diagnosis, and therapeutic target identification by integrating multi-layered biological data with exposure profiles. This review highlights emerging AD risk factors—including PPCPs—underscoring complex, multifactorial nature of AD and exposome, and the requirement for an interdisciplinary research approach, while also addressing several critical research gaps and methodological limitations.

According to the latest data from WHO, about 57 million individuals worldwide were living with dementia in 2021, with 10 million new cases diagnosed each year. Alzheimer’s disease (AD) accounts for approximately 60–80% of dementia cases and ranks as the seventh leading cause of death globally. Currently, the therapeutic options available for AD have limited effectiveness, and potential disease-modifying therapies are not widely adopted or reliably deemed safe. Therefore, implementing preventive strategies and raising public awareness about the relevant AD risk factors are crucial. Existing data delineate various risk factors for AD, encompassing non-modifiable factors such as age, genetic predisposition, and gender, alongside modifiable factors including environmental pollution and diet. This chapter aims to explore emerging environmental risk factors that contribute to AD, including air pollution, toxic elements, pesticides, microplastics, nanoplastics, endocrine disruptors, pharmaceuticals and personal care products, environmental disasters, and global climate change. The intricate and multifaceted nature of neurodegenerative disorders such as AD necessitates an interdisciplinary approach to unravel the underlying mechanisms. This involves the effective application of various omics techniques—such as genomics, transcriptomics, proteomics, metabolomics, and lipidomics—paired with advanced artificial intelligence (AI) methods, including machine learning and deep learning.

Alcohol Use Disorder (AUD) poses global health challenges, and causes hematological alterations such as macrocytosis and oxidative stress. Disruption of protein structures by alcohol and/or its metabolites may exacerbate AUDs; proteomics can elucidate the underlying biological mechanisms. This study examined the proteins differentially expressed in the cytosol and membrane fractions of erythrocytes obtained from 30 male patients with AUD, comparing them to samples from 15 age- and BMI-matched social drinkers (SDs) and 15 non-drinkers (control). The analysis aimed to identify the molecular differences related to alcohol consumption. The AUD patient subgrouping was based on mean corpuscular volume (MCV), with 16 individuals classified as having a normal MCV and 14 having a high MCV. Proteins were separated via two-dimensional(2D)-gel electrophoresis, digested with trypsin, and identified via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (TOF) mass spectrometry (MALDI-TOF/TOF). Additionally, levels of malondialdehyde and 4-hydroxyalkenals (MDA + HAE), reduced glutathione (GSH), oxidized glutathione (GSSG), serum carbohydrate-deficient transferrin (%CDT), disialotransferrin (%DST), and sialic acid (SA) were analyzed. The results showed increased MDA + HAE and decreased total thiols in AUD patients, with GSSG elevated and the GSH/GSSG ratio reduced in the AUD MCV-high subgroup. Serum %CDT, %DST, and SA were significantly higher in AUD. Compared to the control profiles, the AUD group exhibited differential protein expression. Few proteins, such as bisphosphoglycerate mutase, were downregulated in AUD versus control and SD, as well as in the MCV-high AUD subgroup. Conversely, endoplasmin and gelsolin were upregulated in AUD relative to control. Cytoskeletal proteins, including spectrin-alpha chain, actin cytoplasmic 2, were overexpressed in the AUD group and MCV-high AUD subgroup. Several proteins, such as 14-3-3 isoforms, alpha-synuclein, translation initiation factors, heat shock proteins, and others, were upregulated in the MCV-high AUD subgroup. Under-expressed proteins in this subgroup include band 3 anion transport protein, bisphosphoglycerate mutase, tropomyosin alpha-3 chain, uroporphyrinogen decarboxylase, and WD repeat-containing protein 1. Our findings highlight the specific changes in protein expression associated with oxidative stress, cytoskeletal alterations, and metabolic dysregulation, specifically in AUD patients with an elevated MCV. Understanding these mechanisms is crucial for developing targeted interventions and identifying biomarkers of alcohol-induced cellular damage. The complex interplay between oxidative stress, membrane composition, and cellular function illustrates how chronic alcohol exposure affects cellular physiology.

Alzheimer’s disease (AD) is one of the most common and severe forms of dementia and neurodegenerative disease. As life expectancy increases in line with developments in medicine, the elderly population is projected to increase in the next few decades; therefore, an increase in the prevalence of some diseases, such as AD, is also expected. As a result, until a radical treatment becomes available, AD is expected to be more frequently recorded as one of the top causes of death worldwide. Given the current lack of a cure for AD, and the only treatments available being ones that alleviate major symptoms, the identification of contributing factors that influence disease incidence is crucial. In this context, genetic and/or epigenetic factors, mainly environmental, disease-related, dietary, or combinations/interactions of these factors, are assessed. In this review, we conducted a literature search focusing on environmental factors such as air pollution, toxic elements, pesticides, and infectious agents, as well as dietary factors including various diets, vitamin D deficiency, social factors (e.g., tobacco and alcohol use), and variables that are affected by both environmental and genetic factors, such as dietary behavior and gut microbiota. We also evaluated studies on the beneficial effects of antibiotics and diets, such as the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) and Mediterranean diets.

Bitkisel ürünler, binlerce yıldır tüm dünyada yaygın olarak kullanılmaktadır. Tamamlayıcı ve alternatif tedaviye ilgi artışı ile bağlantılı olarak, bitkisel çayların tüketimi de artmaktadır. Bununla birlikte, bu ürünlerin özellikle özel popülasyonlarda sık veya fazla miktarda kullanımı, bazı elementlere potansiyel maruziyet nedeniyle toksisiteye sebep olabilir. Bitkisel ürünlerde olası bir kontaminasyon kaynağı, hava, toprak ve su yoluyla bitkilere ulaşan çevre kirliliği olabilir. Ayrıca, ürün işleme basamakları da metal kontaminasyonu kaynağı haline gelebilir. Ihlamur özellikle kış aylarında, soğuk algınlığı ve öksürüğe karşı sıklıkla tüketilen bitkisel çaylardan biridir. Ihlamur ağaçları, oluşturdukları güzel görüntüden dolayı yol kenarlarına dikilebildiği için, ıhlamur bitki çayı örneklerinde element düzeyleri bir endişe kaynağı olabilir. Ağır metaller ve diğer toksik elementler insan ve hayvan sağlığı için tehlike oluşturabilmektedir; bu nedenle düzenleyici çerçevede ele alınması gerekir. Bu derlemede, ıhlamur bitki çaylarının element düzeyleri ve bu elementlerin toksikolojisi ile ilgili güncel makaleler değerlendirilmiştir. Mevcut bulgulara dayanarak, ıhlamur bitki çaylarının Cd, Pb ve Hg limitlerini aşma olasılığının düşük olduğu sonucuna varılmakla birlikte, sınır değerlerin aşıldığı örneklerin varlığı dikkate alındığında, daha kapsamlı değerlendirmeler gerektiği düşünülmektedir.

Aquaporins are unique water channel proteins located at cell membranes that possess high water permeability and high solute rejection. Their primary function is to maintain the osmotic balance of the cells via regulating the water transport. However, their discovery had also provided the scientists to understand the pathophysiology of some diseases. In fact, aquaporins are shown to be strongly related to cancer by taking part in several tumor-related processes such as cell migration, cell proliferation and cell adhesion. Other than their functions in human body, recently, aquaporins have started to be used in engineering biomimetic membranes, for different applications such as desalination. This review investigates the properties and functions of the aquaporins in a multidisciplinary point of view and demonstrates the recent developments in aquaporin-based research.

In recent years, great emphasis has been placed on non-animal toxicological methods (e.g.in vitro models,in silico or −omics data) as alternative strategies to reduce animal-testing, in line with the 3R principle. These methods help in the rapid and accurate estimation of preclinical efficacy and safety associated with discovery of new drugs, and reduction of failure rates in clinical trials. Currently, the in vitro studies have been in a transformation or replacement from two-dimensional cell cultures to three-dimensional cell cultures that can mimic the physiology of tissues, organs, and organism. In this context, organ-on-a-chip systems have been developed by integration of three-dimensional culture models with emerging microfluidic technologies. The organ-on-a-chip systems provide a good understanding of dose-response and toxicity mechanisms in drug development process, since impact of xenobiotics on human body can be predicted in a satisfactory level. Besides, these systems may support assessment of pharmacokinetic-pharmacodynamic parameters as well as detection of drug resistance. Models can be generated as “disease-models-on-a-chip” or with healthy cells to evaluate response to xenobiotic under test. In this study, we will focus on microfluidic systems being used in organ-on-a-chip systems and emphasize their potential for toxicity studies in which micro-environments of examples including liver,kidney,brain,lung,heart,and intestines and their physiological properties as reflected to organ-on-a-chip models.

Sickle cell disease (SCD) is a group of disorders that affects hemoglobin due to a mutation of the hemoglobin beta gene (HBB) on chromosome 11. Patients with SCD have atypical hemoglobin molecules called hemoglobinS (HbS), which distort erythrocytes into a “sickle-shape”. Typical symptoms of SCD include periodic episodes of pain, repeated infections, and anemia. This disorder is abundant in sub-Saharan African countries, the Mediterranean region, and also appears in some southern provinces in Turkey. Because of the high concentration of HbS in patients, a high risk of chronic anemia and vaso-occlusive events, such as stroke may deteriorate suddenly. In these conditions, transfusion of blood, especially erythrocytes, can be life-saving. However, chronic blood transfusions may lead to iron overload in SCD patients. Erythrocyte transfusion is associated with a higher risk in most patients with SCD than in the general population. Therefore, chelation therapy has become an important component of the transfusion program to prevent complications of iron accumulation in organs such as liver and heart. In this study, we sought to conduct a systematic review to assess the safety of iron chelating agents used by SCD patients with iron overload mainly due to necessary blood transfusion regime. Our evaluation revealed that in general iron chelation therapy, either deferasirox, deferoxamine or deferiprone, remains the most effective and safest available method to treat iron overload in SCD. Furthermore, current reports do not reflect any significant safety concerns against the use of available chelators.

Hexavalent chromium[Cr(VI)] compounds may induce toxic effects, possibly via reactive intermediates and radicals formed during Cr(VI) reduction. In this study, we probed the possible effects of N-acetyl-L-cysteine (NAC) and taurine pre- or post-treatments on Cr(VI)-induced changes in lipid peroxidation and nonprotein thiols (NPSH) in mice heart, lung, spleen, and testis tissues. The mice were randomly assigned to six groups, consisting of control, Cr(VI)-exposed (20 mg Cr/kg, intraperitoneal ,ip), NAC (200 mg/kg, ip) as pre-treatment and post-treatment, and taurine (1 g/kg, ip) pre-treatment and post-treatment groups. Lipid peroxidation and NPSH levels were determined and the results were compared with regard to tissue- and antioxidant-specific basis. Exposure to Cr(VI) significantly increased lipid peroxidation in all tissues as compared to the control (p < 0.05); and consistent with this data, NPSH levels were significantly decreased (p < 0.05). Notably, administration of NAC and taurine, either before or after Cr(VI) exposure, was able to ameliorate the lipid peroxidation (p < 0.05) in all tissues. In the case of NPSH content, while the decline could be alleviated by both NAC and taurine pre- and post-treatments in the spleen, diverging results were obtained in other tissues. The effects of Cr(VI) on the lung thiols were abolished by pre-treatment with NAC and taurine; however, post-treatments could not exert significant effect. While thiol depletion in the heart was totally replenished by NAC and taurine administrations, NAC pre-treatment was partially more effective than post-treatment. In contrast with lipid peroxidation data, NAC treatment could not provide a statistically significant beneficial effect on NPSH content of the testis, whereas the effect in this tissue by taurine was profound. Thus, these data highlight the importance of tissue-specific factors and the critical role of administration time. Overall, our data suggest that NAC and taurine may have potential in prevention of Cr(VI)-induced toxicity in the heart, lung, spleen, and testis tissues.