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Abstract Background The global demographic shift towards an aging population is generating a rise in neurodegenerative conditions, with Alzheimer’s disease (AD) as the most prominent problem. In this landscape, the use of natural supplements has garnered attention for their potential in dementia prevention. Curcumin (Cur), derived from Curcuma longa, has demonstrated promising pharmacological effects against AD by reducing the levels of inflammatory mediators. However, its clinical efficacy is hindered by poor solubility and bioavailability. Our study introduces the use of H-Ferritin nanocages (HFn) as a nanoformulation vehicle for Cur, aiming to enhance its therapeutic potential for AD. In this work, we characterized a nanoformulation of Cur in HFn (HFn-CUR) by evaluating its safety, stability, and its transport across the blood-brain barrier (BBB) in vitro. Moreover, we evaluated the efficacy of HFn-CUR by transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from both AD patients and healthy controls (HC), and by using the well-established 5xFAD mouse model of AD. Results Our data show that HFn-CUR exhibits improved water dispersibility, is non-toxic, and can traverse the BBB. Regarding its activity on PBMCs from AD patients, HFn-CUR enhances cellular responses to inflammation and reduces RAGE-mediated stress. Studies on an AD mouse model demonstrate that HFn-CUR exhibits mild beneficial effects on cognitive performance. Moreover, it effectively reduces microgliosis and astrogliosis and in vivo in mouse, suggesting potential neuroprotective benefits. Conclusions Our data suggest that HFn-CUR is safe and effective in reducing inflammation in both in vitro and in vivo models of AD, supporting the need for further experiments to define its optimal use. Graphical abstract

Psoriasis is a chronic, immune-mediated skin condition with significant metabolic complications. Although lipid metabolism is linked to its pathogenesis, reliable biomarkers and the impact of modifiable factors remain underexplored. The aim of the present study was to identify potential biomarkers, study the affected metabolic networks, and assess the role of dietary and lifestyle factors in psoriasis. Plasma samples from 56 patients with psoriasis and 49 healthy controls were analyzed, as part of the Metabolic Biomarkers in Hashimoto’s Thyroiditis and Psoriasis (METHAP) clinical trial. Using Gas Chromatography-Mass Spectrometry 23 fatty acids and their ratios were quantified, revealing significant changes in psoriasis. Specifically, lower levels of α-linoleic acid (C18:3n3), linoleic acid (C18:2n6), and gamma-linolenic acid (C18:3n6) were observed along with higher levels of eicosatrienoic acid (C20:3n3), eicosapentaenoic acid (C20:5n3), and erucic acid (C22:1n9). Total polyunsaturated fatty acids (PUFA) were significantly decreased, and the ratio of saturated to total fatty acids (SFA/Total) was increased in psoriasis (p-values < 0.0001). Linear regression identified α-linoleic acid, linoleic acid, eicosatrienoic acid, and eicosapentaenoic acid as potential biomarkers for psoriasis, adjusting for demographic, dietary, and lifestyle confounders. Network analysis revealed key contributors in the metabolic reprogramming of psoriasis. These findings highlight the association between psoriasis and fatty acid biomarkers of inflammation, insulin resistance and micronutrients deficiency, suggesting their potency in disease management.

Telomeres, the protective chromosomal ends, progressively shorten and potentially are implicated in the pathogenesis of age-related diseases. In type 2 diabetes (T2DM), telomere shortening may play an important role, but the whole ‘picture’ remains limited. From a therapeutic perspective, the phytonutrient quercetin appears to be clinically effective and safe for patients with T2DM. Considering the above, we aimed to examine whether quercetin could interfere with telomere length (TL) dynamics. One hundred patients with T2DM on non-insulin medications registered within a primary healthcare facility were stratified by age and sex and randomly assigned to either standard care or standard care plus quercetin (500 mg/day) for 12 weeks, succeeded by an 8-week washout period and another 12 weeks of supplementation. Of the 88 patients completing the trial, 82 consented to blood sampling for TL measurements. Health assessments and whole blood absolute TL measurements using quantitative polymerase chain reaction (qPCR) were conducted at baseline and study end, and the findings of this subcohort are presented. Quercetin supplementation was associated with a significant increase in mean TL (odds ratio ≥ 2.44; p < 0.05) with a strengthened association after full adjustment for potential confounders through multiple logistic regression analysis (odds ratio = 3.48; p = 0.026), suggesting it as a potentially promising supplementation option. Further studies are needed to confirm this finding, elucidating the underlying molecular mechanisms of quercetin.

In modern athlete assessment, the integration of conventional biochemical and ergophysiologic monitoring with innovative methods like telomere analysis, genotyping/phenotypic profiling, and metabolomics has the potential to offer a comprehensive understanding of athletes' performance and potential longevity. Telomeres provide insights into cellular functioning, aging, and adaptation and elucidate the effects of training on cellular health. Genotype/phenotype analysis explores genetic variations associated with athletic performance, injury predisposition, and recovery needs, enabling personalization of training plans and interventions. Metabolomics especially focusing on low-molecular weight metabolites, reveal metabolic pathways and responses to exercise. Biochemical tests assess key biomarkers related to energy metabolism, inflammation, and recovery. Essential elements depict the micronutrient status of the individual, which is critical for optimal performance. Echocardiography provides detailed monitoring of cardiac structure and function, while burnout testing evaluates psychological stress, fatigue, and readiness for optimal performance. By integrating this scientific testing battery, a multidimensional understanding of athlete health status can be achieved, leading to personalized interventions in training, nutrition, supplementation, injury prevention, and mental wellness support. This scientifically rigorous approach hereby presented holds significant potential for improving athletic performance and longevity through evidence-based, individualized interventions, contributing to advances in the field of sports performance optimization.

Hashimoto’s thyroiditis and psoriasis are inflammatory disorders that significantly impact patients’ quality of life, stressing the need for novel biomarkers of early diagnosis. This randomized clinical trial (NCT04693936) aims to identify Hashimoto’s thyroiditis’ and psoriasis’ metabolic biomarkers and to investigate the effect of environmental factors on the disease-related metabolic imprint and quality of life. Patients with Hashimoto’s thyroiditis, patients with psoriasis, and healthy individuals aged 18–60 will be recruited, enrolled according to eligibility criteria (medical history, clinical thyroid markers and the PASI score) and randomized to two groups. The intervention group will receive a combination of nutraceuticals for 6 months as part of a Mediterranean diet, and the control group will follow their usual diet. Data will be collected at baseline and the end of the study, including metabolite levels, lifestyle and anthropometric measurements, adherence to the Mediterranean diet (through the Mediterranean Diet Score) and disease-specific quality of life (through the Thyroid Patient Report Outcome for Hashimoto’s group, and the Dermatology Life Quality Index for the psoriasis group). This study will investigate metabolic biomarkers and related changes in Hashimoto’s thyroiditis and psoriasis and evaluate the association of metabolic changes with dietary factors and quality of life.

COVID-19 pandemic mitigation strategies are mainly based on social distancing measures and healthcare system reinforcement. However, many countries in Europe and elsewhere implemented strict, horizontal lockdowns because of extensive viral spread in the community which challenges the capacity of the healthcare systems. However, strict lockdowns have various untintended adverse social, economic and health effects, which have yet to be fully elucidated, and have not been considered in models examining the effects of various mitigation measures. Unlike commonly suggested, the dilemma is not about health vs wealth because the economic devastation of long-lasting lockdowns will definitely have adverse health effects in the population. Furthermore, they cannot provide a lasting solution in pandemic containment, potentially resulting in a vicious cycle of consecutive lockdowns with in-between breaks. Hospital preparedness has been the main strategy used by governments. However, a major characteristic of the COVID-19 pandemic is the rapid viral transmission in populations with no immunity. Thus, even the best hospital system could not cope with the demand. Primary, community and home care are the only viable strategies that could achieve the goal of pandemic mitigation. We present the case example of Greece, a country which followed a strategy focused on hospital preparedness but failed to reinforce primary and community care. This, along with strategic mistakes in epidemiological surveillance, resulted in Greece implementing a second strict, horizontal lockdown and having one of the highest COVID-19 death rates in Europe during the second wave. We provide recommendations for measures that will reinstate primary and community care at the forefront in managing the current public health crisis by protecting hospitals from unnecessary admissions, providing primary and secondary prevention services in relation to COVID-19 and maintaining population health through treatment of non−COVID-19 conditions. This, together with more selective social distancing measures (instead of horizontal lockdowns), represents the only viable and realistic long-term strategy for COVID-19 pandemic mitigation.

Mycotoxins are secondary fungi metabolites that induce acute and chronic toxic effects in humans and animals. In the present study, nine mycotoxins including aflatoxins (AFB1, AFB2, AFG1 and AFG2), fumonisins (FB1 and FB2), Ochratoxin A (OTA), deoxynivalenol (DON), and zearalenone (ZEN) were determined in one hundred rice samples collected from Tehran using high performance liquid chromatography (HPLC) with fluorescence or photodiode array detector. In addition, possible risk to public health was investigated by assessing dietary exposure through rice consumption, the margin of exposure (MOE), respective risk of cancer and hazard index (HI) of the monitored mycotoxins in children and adults. The higher mean levels were determined for DON (102.22 μg.Kg−1), followed by FB1 (85.00 μg.Kg−1). For the rests of mycotoxins the levels did not exceed 20 μg.Kg−1. The estimated AFB1 intake for the adults and children through rice consumption exceeds the safe levels established for both carriers and non-carriers of hepatitis B virus. The mean and median determined exposure levels of OTA, DON ZEN and FB1, were found lower than the Provisional Maximum Tolerable Daily Intake (PMTDI) value for both adults and children of Tehran that consuming domestic and imported rice. The mean HI for adults and median HI for adults and children were below one, and mean HI for children was close to one. All the mean, median and maximum MoE values were

The potential health-promoting effects of probiotics against intoxication by pesticides is a topic of increasing commercial interest with limited scientific evidence. In this study, we aimed to investigate the positive effects of probiotic Saccharomyces boulardii on the male reproductive system under low dose neonicotinoid pesticide exposure conditions. We observed that acetamiprid and imidacloprid caused a degeneration and necrosis of the spermatocytes in the tubular wall, a severe edema of the intertubular region and a hyperemia. This was concomittant to increased levels of 8-hydroxy-2′-deoxyguanosine reflecting oxidative stress, and an increase in caspase 3 expression, reflecting apoptosis. According to our results, Saccharomyces boulardii supplementation mitigates these toxic effects. Further in vivo and clinical studies are needed to clarify the molecular mechanisms of protection. Altogether, our study reinforces the burden of evidence from emerging studies linking the composition of the gut microbiome to the function of the reproductive system.

Carbon monoxide (CO) is the leading cause of poisoning deaths in many countries, including Japan. Annually, CO poisoning claims about 2000–5000 lives in Japan, which is over half of the total number of poisoning deaths. This paper discusses the physicochemical properties of CO and the toxicological evaluation of CO poisoning.

Dramatic changes in the environment in recent decades have resulted in low-nutrient food and excessive intake of heavy metals and toxins through air, drinking water, and dietary habits. Non-communicable diseases (NCD), which are responsible for almost 70% of global deaths, are mainly caused by modifiable risk factors. These include behavioral and metabolic risk factors such as unhealthy diet, tobacco smoke and alcohol. Epigenetic factors have high attributable risks of 80% for most NCDs. Xenobiotics such as persistent organic pollutants, food additives and occupational toxicants, together with nutritional deficiencies, contribute to the development of chronic diseases. Precision medicine integrates the individual variability in genes, environment, and lifestyle of each person for the prevention and treatment of disease. Metabolomics, the quantitative and comprehensive evaluation of metabolites, has emerged as a novel and powerful tool in precision medicine. Analysis of metabolites gives precise data on nutritional deficiencies, metabolic imbalances, environmental toxins, and microbiome conditions and uncovers underlying genetic predispositions that can be modified through diet, lifestyle, supplements or medications. Critical signs of systemic dysfunction at the molecular level can be revealed years before clinical symptoms appear. Thus, through the assessment of the overall health status, early detection of diseases and intervention to restore these deficiencies is feasible. Lifestyle interventions to improve longevity and metabolic balance are being discussed

Identification of novel biomarkers of contrast-induced nephropathy (CIN) that may more accurately detect renal function changes; reflect kidney damage; assist monitoring; and elucidate pathophysiology attract considerable scientific attention nowadays. To evaluate novel biomarkers of nephrotoxicity in blood/tissue samples of a CIN model, 10 New Zealand white rabbits were divided into group 1 (n = 5; iopromide) and group 2 (n = 5; control). Blood was drawn at 0 h (immediately), 24 h and 48 h after contrast medium (CM) administration. Animals were euthanized at 48 h and kidneys were removed. Serum creatinine (sCr)/symmetric-asymmetric dimethylarginine (SDMA-ADMA) levels were measured. CM genotoxic/cytotoxic effect was investigated 48 h post-CM exposure using micronucleus assay in lymphocytes. Cytological examination was conducted using touch preparation technique (TPT). All animals in group 1 developed CIN: mean sCr levels increased by 68.2% within 48 h. Significant SDMA-ADMA level elevation was observed at 0 h and 24 h with insignificant drop at 48 h in group 1, remaining normal in group 2 at all time-points. Significant increase in bi-nucleated cells with micronuclei and micronuclei frequency was detected in group 1. Cytokinesis block proliferation index was reduced insignificantly in group 1. TPT revealed degenerative lesions/inflammation, cell degeneration, abnormal uterine tubular casts and rubella in kidneys of all animals in group 1. Group 2 presented normal cells. Keywords: Asymmetric dimethylarginine, Contrast media, Kidney, Models, Animal, Iopromide, Nephropathy, Nephrotoxicity, Symmetric dimethylarginine

Glufosinate is a common herbicide with neurotoxic effects, leading to seizures, convulsions and memory loss. Glufosinate indirectly induces glutamate toxicity by inhibiting glutamine synthesis in astrocytes. Here, we studied the acute toxic effects of a glufosinate-based herbicide in rat optic nerve at three doses (40, 80 or 120 μM, equal to 714 or 21 mg/kg bw/day). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, calcium, as well as creatinine concentrations were analyzed after 24, 48 and 72 h treatment. Intraocular pressure (IOP) (expressed as the average of both eyes) was measured with a rebound tonometer. Interleukin-1β (IL-1β) and c-Fos expression were determined by immunohistochemistry. The results established that the glufosinate-based herbicide significantly increased IL-1β and c-Fos immunopositivity in the optic nerve (p

Probiotics have been shown to have positive effects when it comes to combating various health issues when consumed, preventing even the absorption of environmental toxins. One of the main environmental toxins encountered today is pesticide residues. Neonicotinoids, widely applied today in countries that have approved of them, are a known class of insecticides with an excellent and effective potency. Neonicotinoids have been shown to cause various toxic effects, either acutely or chronically, on human health and on beneficial insects when exposed. To clarify the assumption that probiotics could counteract these toxic effects, especially on vital organs, the probiotic yeast “Saccharomyces boulardii” (S. boulardii) was tested against the neonicotinoids, acetamiprid (ACE) and imidacloprid (IMI), as it has outstanding physiological and metabolic properties. The results obtained from the studies indicated that although ACE and IMI induced liver, kidney, brain and bowel damage, there was a considerable level of protection by the dietary supplementation of S. boulardii, as it reduced the absorption of these insecticides.

The objective of the present study was to evaluate of serum metal levels in COVID-19 patients with different disease severity, and to investigate the independent association between serum metal profile and markers of lung damage. The cohort of COVID-19 patients consisted of groups of subjects with mild, moderate, and severe illness, 50 examinees each. Forty-four healthy subjects of the respective age were involved in the current study as the control group. Serum metal levels were evaluated using inductively-coupled plasma mass-spectrometry. Examination of COVID-19 patients demonstrated that heart rate, respiratory rate, body temperature, C-reactive protein levels, as well as lung damage increased significantly with COVID-19 severity, whereas SpO2 decreased gradually. Increasing COVID-19 severity was also associated with a significant gradual decrease in serum Ca, Fe, Se, Zn levels as compared to controls, whereas serum Cu and especially Cu/Zn ratio were elevated. No significant group differences in serum Mg and Mn levels were observed. Serum Ca, Fe, Se, Zn correlated positively with SpO2, being inversely associated with fever, lung damage, and C-reactive protein concentrations. Opposite correlations were observed for Cu and Cu/Zn ratio. In regression models, serum Se levels were inversely associated with lung damage independently of other markers of disease severity, anthropometric, biochemical, and hemostatic parameters. Cu/Zn ratio was also considered as a significant predictor of lower SpO2 in adjusted regression models. Taken together, these findings demonstrated that metal metabolism significantly interferes with COVID-19 pathogenesis, although the causal relations as well as precise mechanisms are yet to be characterized.

Sunscreen application is the main strategy used to prevent the maladies inflicted by ultraviolet (UV) radiation. Despite the continuously increasing frequency of sunscreen use worldwide, the prevalence of certain sun exposure-related pathologies, mainly malignant melanoma, is also on the rise. In the past century, a variety of protective agents against UV exposure have been developed. Physical filters scatter and reflect UV rays and chemical filters absorb those rays. Alongside the evidence for increasing levels of these agents in the environment, which leads to indirect exposure of wildlife and humans, recent studies suggest a toxicological nature for some of these agents. Reviews on the role of these agents in developmental and endocrine impairments (both pathology and related mechanisms) are based on both animal and human studies, yet information regarding the potential neurotoxicity of these agents is scant. In this review, data regarding the neurotoxicity of several organic filters: octyl methoxycinnamate, benzophenone-3 and â4, 4-methylbenzylidene camphor, 3-benzylidene camphor and octocrylene, and two allowed inorganic filters: zinc oxide and titanium dioxide, is presented and discussed. Taken together, this review advocates revisiting the current safety and regulation of specific sunscreens and investing in alternative UV protection technologies. Keywords: Neurotoxicity, Sunscreen, Zinc oxide, Titanium dioxide, Octyl methoxycinnamate, Benzophenone-3, 4-Methylbenzylidene camphor, Octocrylene

Curcumin’s pharmacological properties and its possible benefits for neurological diseases and dementia have been much debated. In vitro experiments show that curcumin modulates several key physiological pathways of importance for neurology. However, in vivo studies have not always matched expectations. Thus, improved formulations of curcumin are emerging as powerful tools in overcoming the bioavailability and stability limitations of curcumin. New studies in animal models and recent double-blinded, placebo-controlled clinical trials using some of these new formulations are finally beginning to show that curcumin could be used for the treatment of cognitive decline. Ultimately, this work could ease the burden caused by a group of diseases that are becoming a global emergency because of the unprecedented growth in the number of people aged 65 and over worldwide. In this review, we discuss curcumin’s main mechanisms of action and also data from in vivo experiments on the effects of curcumin on cognitive decline.

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients’ prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients’ samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA. Hence, to highlight the relevant achievements obtained so far in this field, a clearer description of the current methodologies used, as well as the obtained results, are strongly needed. On these bases, this review discusses the most relevant studies on ctDNA analysis in cancer, as well as the future directions and applications of liquid biopsy. In particular, special attention was paid to the early diagnosis of primary cancer, to the diagnosis of tumors with an unknown primary location, and finally to the prognosis of cancer patients. Furthermore, the current limitations of ctDNA-based approaches and possible strategies to overcome these limitations are presented.

Glioblastoma multiforme is the most aggressive malignant tumor of the central nervous system. Due to the absence of effective pharmacological and surgical treatments, the identification of early diagnostic and prognostic biomarkers is of key importance to improve the survival rate of patients and to develop new personalized treatments. On these bases, the aim of this review article is to summarize the current knowledge regarding the application of molecular biology and proteomics techniques for the identification of novel biomarkers through the analysis of different biological samples obtained from glioblastoma patients, including DNA, microRNAs, proteins, small molecules, circulating tumor cells, extracellular vesicles, etc. Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.

Silica is deposited extra- and intracellularly in plants in solid form, as phytoliths. Phytoliths have emerged as accepted taxonomic tools and proxies for reconstructing ancient flora, agricultural economies, environment, and climate. The discovery of silicon transporter genes has aided in the understanding of the mechanism of silicon transport and deposition within the plant body and reconstructing plant phylogeny that is based on the ability of plants to accumulate silica. However, a precise understanding of the process of silica deposition and the formation of phytoliths is still an enigma and the information regarding the proteins that are involved in plant biosilicification is still scarce. With the observation of various shapes and morphologies of phytoliths, it is essential to understand which factors control this mechanism. During the last two decades, significant research has been done in this regard and silicon research has expanded as an Earth-life science superdiscipline. We review and integrate the recent knowledge and concepts on the uptake and transport of silica and its deposition as phytoliths in plants. We also discuss how different factors define the shape, size, and chemistry of the phytoliths and how biosilicification evolved in plants. The role of channel-type and efflux silicon transporters, proline-rich proteins, and siliplant1 protein in transport and deposition of silica is presented. The role of phytoliths against biotic and abiotic stress, as mechanical barriers, and their use as taxonomic tools and proxies, is highlighted.

Measuring the antioxidant capacity of foods is essential, as a means of quality control to ensure that the final product reaching the consumer will be of high standards. Despite the already existing assays with which the antioxidant activity is estimated, new, faster and low cost methods are always sought. Therefore, we have developed a novel colorimeter and combined it with a slightly modified DPPH assay, thus creating a kit that can assess the antioxidant capacity of liquids (e.g., different types of coffee, beer, wine, juices) in a quite fast and low cost manner. The accuracy of the colorimeter was ensured by comparing it to a fully validated Hitachi U-1900 spectrophotometer, and a coefficient was calculated to eliminate the observed differences. In addition, a new, user friendly software was developed, in order to render the procedure as easy as possible, while allowing a central monitoring of the obtained results. Overall, a novel kit was developed, with which the antioxidant activity of liquids can be measured, firstly to ensure their quality and secondly to assess the amount of antioxidants consumed with the respective food.