Search Results (193)

This literature review provides an overview of the food safety and toxicological characteristics of various heavy metals and metalloids and the public health significance of their occurrence in food. Metals also occur as natural components of the environment, but they can enter food of animal origin and the human body primarily due to anthropogenic (industrial, agricultural, transport-related) activities. The persistent heavy metals (e.g., Hg, Pb, Cd) found in the environment are not biodegradable, can accumulate, and can enter the bodies of higher animals and subsequently, humans, where they are metabolized into various compounds with differing toxicity. Thus, due to their environmental contamination, they can accumulate in living organisms and their presence in the food chain is of great concern for human health. Regulations of the European Community in force lay down maximum levels for a limited number of metals, and the types of regulated foodstuffs of animal origin are also narrower than in the past, e.g., wild game animals and eggs are not included. The regulation of game meat (including offal) deserves consideration, given that it is in close interaction with the environmental condition of a given area and serves as indicator of it. Full article

Excessive levels of Pb²⁺ and Cd²⁺ in seawater pose significant combined toxicity to marine organisms, resulting in harmful effects and further threatening human health through biomagnification in the food chain. Traditional methods for detecting marine Pb²⁺ and Cd²⁺ rely on laboratory analyses, which are hindered by limitations such as sample degradation during transport and complex operational procedures. In this study, we present an electrochemical sensor based on intelligent mobile detection devices. By combining G-COOH-MWCNTs/ZnO with differential pulse voltammetry, the sensor enables the efficient, simultaneous detection of Pb²⁺ and Cd²⁺ in seawater. The G-COOH-MWCNTs/ZnO composite film is prepared via drop-coating and is applied to a glassy carbon electrode. The film is characterized using cyclic voltammetry, electrochemical impedance spectroscopy, and scanning electron microscopy, while Pb²⁺ and Cd²⁺ are quantified using differential pulse voltammetry. Using a 0.1 mol/L sodium acetate buffer (pH 5.5), a deposition potential of −1.1 V, and an accumulation time of 300 s, a strong linear correlation was observed between the peak response currents of Pb²⁺ and Cd²⁺ and their concentrations in the range of 25–450 µg/L. The detection limits were 0.535 µg/L for Pb²⁺ and 0.354 µg/L for Cd²⁺. The sensor was applied for the analysis of seawater samples from Maowei Sea, achieving recovery rates for Pb²⁺ ranging from 97.7% to 103%, and for Cd²⁺ from 97% to 106.1%. These results demonstrate that the sensor exhibits high sensitivity and stability, offering a reliable solution for the on-site monitoring of heavy metal contamination in marine environments. Full article

Potentially toxic elements such as cadmium (Cd) in agricultural soils represent a global concern due to their toxicity and potential accumulation in the food chain. However, our understanding of cadmium’s complex sources and the mechanisms controlling its spatial distribution across diverse edaphic and geological contexts remains limited, particularly in underexplored agricultural regions. Our study aimed to assess the total accumulated Cd content in soils under avocado cultivation and its association with edaphic, geochemical, and geomorphological variables. To this end, we considered the total concentrations of other metals and explored their associations to gain a better understanding of Cd’s spatial distribution. We analyzed 26 physicochemical properties, the total concentrations of 22 elements (including heavy and trace metals such as As, Ba, Cr, Cu, Hg, Ni, Pb, Sb, Se, Sr, Tl, V, and Zn and major elements such as Al, Ca, Fe, K, Mg, and Na), and six geospatial variables in 410 soil samples collected from various avocado-growing regions in Peru in order to identity potential associations that could help explain the spatial patterns of Cd. For data analysis, we applied (1) univariate statistics (skewness, kurtosis); (2) multivariate methods such as Spearman correlations and principal component analysis (PCA); (3) spatial modeling using the Geodetector tool; and (4) non-parametric testing (Kruskal–Wallis test with Dunn’s post hoc test). Our results indicated (1) the presence of hotspots with Cd concentrations exceeding 3 mg·kg⁻¹, displaying a leptokurtic distribution (skewness = 7.3); (2) dominant accumulation mechanisms involving co-adsorption and cation competition (Na⁺, Ca²⁺), as well as geogenic co-accumulation with Zn and Pb; and (3) significantly higher Cd concentrations in Leptosols derived from Cretaceous intermediate igneous rocks (diorites/tonalites), averaging 1.33 mg kg⁻¹ compared to 0.20 mg·kg⁻¹ in alluvial soils (p < 0.0001). The factors with the greatest explanatory power (q > 15%, Geodetector) were the Zn content, parent material, geological age, and soil taxonomic classification. These findings provide edaphogenetic insights that can inform soil cadmium (Cd) management strategies, including recommendations to avoid establishing new plantations in areas with a high risk of Cd accumulation. Such approaches can enhance the efficiency of mitigation programs and reduce the risks to export markets. Full article

Background/Objectives: Esophageal squamous cell carcinoma (ESCC) is a common form of esophageal cancer with a poor prognosis and limited treatment options. Epidermal growth factor receptor (EGFR), an overexpressed oncogenic gene in all ESCC patients, is an attractive target for developing therapies against ESCC. There is an extremely urgent need to develop immunotherapy tools targeting EGFR for the treatment of ESCC. Methods: In this study, we developed human Interleukin-21 (hIL-21)-armed, chimeric-antigen-receptor-modified T (CAR-T) cells targeting EGFR as a new therapeutic approach. The CAR contains a variable domain of the llama heavy chain of heavy-chain antibodies (VHHs), also known as nanobodies (Nbs), as a promising substitute for the commonly used single-chain variable fragment (ScFv) for CAR-T development. Results: We show that nanobody-derived, EGFR-targeting CAR-T cells specifically kill EGFR-positive esophageal cancer cells in vitro and in animal models. Human IL-21 expression in CAR-T cells further improved their expansion and antitumor ability and were observed to secrete more interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and Interleukin-2 (IL-2) when co-cultured with ESCC cell lines in vitro. More CD8⁺ CAR-T cells and CD3⁺CD8⁺CD45RO⁺CD62L⁺ central memory T cells were detected in CAR-T cells expressing hIL-21 cells. Notably, hIL-21-expressing CAR-T cells showed superior antitumor activity in vivo in a KYSE-150 xenograft mouse model. Conclusions: Our results show that hIL-21-armed, nanobody-derived, EGFR-specific CAR-T cell therapy is a highly promising option for treating ESCC patients. Full article

Recombinantly produced monoclonal antibodies (mabs) belong to the fastest growing class of biotherapeutics. In humans, antibodies are classified into five different classes: IgA, IgD, IgE, IgG and IgM. Most of the therapeutic mabs used in the clinic belong to the IgG class, albeit other antibody classes, e.g., IgM, have been evaluated in clinical stages. Antibodies are composed of heavy chains paired with a light chain. In IgM and IgA, an additional chain, the J-chain, is present. Two types of light chains exist in humans: the κ-light chain and the λ-light chain. The κ-light chain predominates in humans and is used in the vast majority of therapeutic IgG. The reason for the preference of the κ-light chain in humans is not known. Our study investigates whether light-chain selection influences the productivity of the clinically validated mabs adalimumab and trastuzumab. Both mabs were expressed as IgG and IgM with a κ- or a λ-light chain in HEK293 cells. Besides comparing the expression levels of the different mabs, we also evaluated whether the passage number of the cell line has an impact on product yield. In addition, the expressions of adalimumab, trastuzumab, an anti-CD38 and an anti-PD-L1-antibody were analyzed in HEK293 and CHO cells when both the κ- and λ-light chains are present. In summary, IgG outperformed IgM variants in expression efficacy, while light-chain selection had minimal impact on the overall expression levels. The yields of all mab variants were higher in fresh cells, despite cell cultures with a high cell passage number having higher cell densities and cell numbers at the time of harvest. The incorporation of a particular light chain occurred at similar rates in HEK293 and CHO cells. Full article

Cadmium (Cd) accumulation in plants hinders their growth and development while posing significant risks to human health through food chain transmission. Glycyrrhiza uralensis Fisch. (G. uralensis) is a medicinal plant valued for its roots and plays a crucial role in harmonizing various herbs in traditional Chinese medicine prescriptions. However, widespread Cd contamination in soil limits safe cultivation and application. Selenium (Se), a beneficial element in plants, can regulate plant growth by enhancing carbon metabolism and reducing heavy metal uptake. This study aimed to elucidate the protective mechanisms of Se application in licorice plants exposed to 20 μM Cd. Experiments with 1 and 5 μM of Se revealed that 1 μM of Se provided the best protective effects. This concentration reduced the Cd²⁺ content in the roots of G. uralensis, while significantly increasing plant biomass, root length, SPAD value, and contents of K⁺, Ca²⁺, and S²⁻. Additionally, the treatment reduced the malondialdehyde (MDA) content by 30.71% and 58.91% at 12 h and 30 d, respectively. The transcriptome analysis results suggest that Se mitigated Cd toxicity by enhancing carbon metabolism, regulating the AsA-GSH cycle, reducing Cd absorption, promoting Cd transport and compartmentalization, and modulating Cd resistance-associated transcription factors. These findings clarify the mechanisms by which Se alleviates Cd toxicity in G. uralensis and offer a promising strategy for the safe cultivation and quality control of medicinal herbs in Cd-contaminated soils. Full article

Immune checkpoint inhibitors like programmed cell death 1 (PD-1) antibodies have revolutionized cancer treatment, but patient response rates remain limited. Sialic acid-binding Ig-like lectin 15 (Siglec-15) has emerged as a promising new immune checkpoint target. Through phage display technology using a Bactrian camel immunized with recombinant human Siglec-15, we generated six anti-Siglec-15 camelid nanobodies and constructed chimeric heavy-chain antibodies by fusing the VHH domains with human IgG-Fc. Following expression in HEK293-F cells and purification, three antibodies (S1, S5, S6) demonstrated specific binding to both human and murine Siglec-15 in ELISA and biolayer interferometry assays. In a xenograft model established by subcutaneous inoculation of NCI-H157-S15 cells into BALB/c nude mice, these antibodies showed distinct tumor targeting and significant blockade of Siglec-15 interactions with CD44, MAG, sialyl-Tn, and LRR4C ligands. All three antibodies exhibited anti-tumor effects, with S1 showing the most potent activity. S1-treated mice had significantly smaller tumor volumes and weights compared to controls. The S1, S5, and S6 treatment groups showed enhanced anti-tumor immunity, with reduced TGF-β, IL-6, and IL-10 levels. Notably, S1 treatment significantly increased tumor-associated macrophages in tumor tissues (p < 0.05). In conclusion, S1 exhibits remarkable anti-tumor activity and has the potential to be developed as a cancer immunotherapy targeting Siglec-15. Full article

Heavy metal pollution, particularly cadmium (Cd) contamination in water and farmland, might accumulate in natural insect enemies through the food chain. In response to this heavy metal stress, natural enemy insects adapt by altering their metabolism and behaviors. As a result, this investigation aimed to elucidate how the development, reproduction, and feeding of Harmonia axyridis Pallas (Coleoptera: Coccinellidae) are affected under Cd contamination. Compared to the control group, the developmental period of H. axyridis was prolonged, with decreased survival, predation, and body weights. Notably, adult insects exhibited deformation, including molting difficulties and wing deformities, which indicated reduced fitness. The ovarian development of female insects was delayed with reduced size, and the pre-oviposition period was prolonged under Cd contamination. Additionally, the hatching rate of offspring was significantly reduced. The Vitellogenin 1 (Vg1) and Vitellogenin 2 (Vg2) exhibited considerable changes throughout their developmental stages. Our results confirmed that the accumulation of Cd has a significant impact on the growth, development, and normal molting of H. axyridis, affecting the reproduction of H. axyridis. The aforementioned results provide valuable insights into the potential ecological effects of Cd accumulation on the food chain, which can inform strategies for pest control, ecosystem stabilization in rice fields, and potentially novel bioremediation approaches. Thereby establishing a theoretical foundation for pest control and ecosystem stabilization in rice fields under Cd contamination while simultaneously providing novel insights for bioremediation strategies. Full article

At the present stage, heavy metal pollution, led by environmental exposure to cadmium (Cd), has caused incalculable losses in animal husbandry. The potential value of caprylic acid as a medium- and long-chain fatty acid with a unique role in regulating lipid metabolism has attracted much attention. Our previous study found that octanoic acid levels were significantly reduced under Cd-exposed conditions in Hu Sheep, on the basis of which we investigated the protective effect of sodium octanoate, a derivative of octanoic acid, against Cd exposure in Hu Sheep in the present study. In this study, an animal model of Cd exposure in Hu Sheep was established. Comprehensive assessment of Cd-induced intestinal injury using hematoxylin and eosin (H&E) staining, immunostaining and carried out in-depth analyses combined with lipid metabolomics and transcriptomics. The results showed that Cd exposure triggered intestinal inflammation, barrier function damage and oxidative stress imbalance. Lipid metabolomics analysis showed that Cd exposure severely disrupted lipid metabolic processes, especially the glycerophospholipid metabolic pathway, suggesting that lipid metabolic disorders are closely related to intestinal injury. Notably, sodium octanoate could partially reverse the lipid metabolism abnormality by regulating the Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, effectively alleviating the Cd toxicity, which provides a brand-new prevention and control strategy for Cd-induced intestinal injury in the livestock industry pollution-mediated disease. Full article

Cadmium (Cd) is an extremely toxic heavy metal that can move from the soil to plants and enter the human body via the food chain, causing severe health issues for humans. Phytoremediation uses hyperaccumulators to extract heavy metals from polluted soil. Phytohormones, wildly used plant growth regulators, have been explored to improve phytoremediation efficiency. Abscisic acid (ABA) is also an essential regulator of plant tolerance to biotic and abiotic stresses, including heavy metal-induced toxicity. Previous research has revealed that Phytolacca acinosa Roxb. (P. acinosa) has a strong ability to enrich Cd and can be used as a Cd hyperaccumulator. In this study, physiological and biochemical analysis revealed that under Cd stress, exogenous ABA application alleviated oxidative stress, increased the Cd²⁺ concentration in P. acinosa, especially in the roots, and changed the phytohormone concentration in P. acinosa. Transcriptome analysis was conducted to explore the molecular mechanisms by which ABA regulates Cd uptake and accumulation in P. acinosa, and to further understand the regulatory role of ABA. The results show that ABA treatment affected gene expression in P. acinosa roots under Cd stress. This study identified 5788 differentially expressed genes (DEGs) (2541 up-regulated and 3247 down-regulated). Moreover, 96 metal transport-related DEGs, 54 phytohormone-related DEGs, 89 cell wall-related DEGs, 113 metal chelation-related DEGs, and 102 defense system-related DEGs cooperated more closely under exogenous ABA application to regulate Cd uptake and accumulation in P. acinosa under Cd stress. These results may help to elucidate the mechanisms by which ABA regulates Cd uptake and accumulation in plants, and provide a reference for developing a phytohormone-based strengthening strategy to improve the phytoremediation ability of other hyperaccumulators or accumulator species. The key genes involved in ABA’s regulation of Cd uptake and accumulation in P. acinosa need to be further analyzed and functionally verified. This may expand our understanding of the molecular regulatory mechanisms underlying heavy metal uptake and accumulation in hyperaccumulators. Full article

Ensuring food security is essential for achieving sustainable global development, requiring a balance between sufficient food production and maintaining its safety and nutritional value. However, this objective faces considerable challenges due to the infiltration of toxic metal species into the food supply. Heavy metals and metalloids, depending on their molecular form and daily dose, exhibit varying degrees of toxicity, making the precise identification of their species essential for assessing their impact on human health and the environment. This study focuses on identifying the primary anthropogenic sources and dissemination pathways of heavy metal pollutants, with an emphasis on their speciation and bioavailability. It examines how toxic metal species, such as Pb²⁺, Cd²⁺, Hg²⁺, and various arsenic species (AsIII and AsV), infiltrate ecosystems, bioaccumulate within the food chain, and ultimately compromise food safety and nutritional value. Furthermore, the research explores the physiological and biochemical disruptions caused by these toxic metal species, including the displacement of essential ions from enzymatic active sites and transport proteins due to competitive binding by pollutants, oxidative stress induced by reactive oxygen species generation, and cellular dysfunction affecting metabolic pathways and signaling cascades, all of which contribute to both chronic and acute health conditions. By providing a detailed analysis of exposure routes and toxicological processes, this paper highlights the far-reaching consequences of heavy metal contamination on public health and agricultural sustainability. Special attention is given to the need for precise terminology, as the toxicity of metals is inherently linked to their daily dose and chemical species rather than their elemental form. Finally, this study advocates for integrated, multidisciplinary strategies aimed at mitigating these risks, enhancing ecosystem stability, and ensuring long-term food security in the face of environmental challenges. Full article

IgE may lead to life-threatening anaphylaxis. Currently, no satisfactory treatment to inhibit IgE production exists. This study aims to explore the anti-IgE effect of berberine (BBR) and possible mechanisms using human tonsil cells. Tonsil cells were treated with BBR at different doses following stimulation with anti-CD40/IL4 alone or in combination with poly I:C and Pam3CSK4 for 10 or 4 days. IgE and IgG levels were determined by ELISA and cell viability by trypan blue exclusion. Gene expression was analyzed by qRT-PCR and affinity binding assay was performed by chromatin immunoprecipitation assay (ChIP). BBR showed dose-dependent inhibition of IgE production following anti-CD40/IL4 stimulation without affecting cell viability and IgG levels. BBR (10 µg/mL) completely inhibited IgE production by B cells stimulated with anti-CD40/IL4 in combination with vaccine adjuvants—poly I:C and Pam3CSK4 without affecting IgG levels and cell viability. BBR inhibited IgE heavy chain (IgEh), epsilon germline-transcript (εGLT), STAT6, and NFκB1 and enhanced IFN-γ, NFκB1A, and BCL6 gene expression. ChIP assay showed that BBR inhibited STAT6 binding in the IgEh promoter region by enhancing BCL6 binding. This study shows BBR regulates IgE in human tonsil cells by inhibiting STAT6 binding through BCL6 at the IgEh promoter showing its potential for treating IgE-mediated allergies. Full article

Severe acute pancreatitis (SAP) is mainly triggered by the abnormal activation of pancreatic enzymes. Obesity acts as an independent risk factor for SAP; however, the underlying mechanism has not been fully elucidated. In this study, SAP models were established in mice with normal and high-fat diets. Subsequently, this study examined ferroptosis and inflammatory markers in pancreas and epididymal adipose tissues. To mimic obesity-related SAP in adipose tissue macrophages (ATMs), lipopolysaccharide (LPS) and palmitic acid (PA) were introduced, and alterations in ferroptosis and inflammation were assessed. To elucidate the regulatory role of cluster of differentiation 36 (CD36) in ferroptosis, liproxstatin-1 (Lip-1) and sulfosuccinimidyl oleate sodium (SSO) were utilized for in-depth analysis in the pancreas, epididymal adipose tissues, and ATMs. Our findings suggest that obesity aggravates ferroptosis in pancreas tissue, epididymal adipose tissues, and ATMs during SAP, as evidenced by increased lipid peroxidation, elevated Fe²⁺ levels, and alterations in ferroptosis markers, while these alterations were regained by Lip-1. Notably, CD36 levels were significantly increased in pancreatic tissue, epididymal adipose tissue, and ATMs, indicating that CD36 promotes ferroptosis and induces inflammation. SSO treatment alleviated changes in ferroptosis markers and reduced inflammation. Western blot results showed that CD36 promoted ferroptosis through the acyl-CoA synthetase long-chain family member 4 (ACSL4)/glutathione peroxidase 4 (GPX4) axis in pancreatic tissue, while a similar regulatory role was mediated by the ferritin heavy chain 1 (FTH1)/GPX4 axis and ATMs. These findings demonstrate that CD36 induces inflammation by facilitating ferroptosis in pancreas tissue, epididymal adipose tissue, and ATMs in obesity-related SAP. The inhibition of CD36 could provide novel viewpoints for the prevention and treatment of obesity-related SAP. Full article

Background: Fibroblast activation protein (FAP) is a cell surface glycoprotein expressed by myofibroblastic cells in areas of active tissue remodeling, such as wound healing, fibrosis, and certain chronic inflammatory lesions. As FAP is uniquely present in chronic inflammatory lesions and has an important role in extracellular matrix (ECM) turnover, it appears to have all the characteristics necessary for involvement in atherosclerosis and atherosclerotic plaque rupture and has become a potential target in the treatment of myocardial infarction. Methods: To further understand the role of FAP, its expression in atherosclerotic plaques was examined in a genetically modified mouse model of accelerated atherosclerosis (Apobec1 −/− Ldlr −/− double-knockout mice). The immunohistochemical Fap staining of atherosclerotic plaques in a mouse model of atherosclerosis was correlated with quantification of Fap mRNA obtained from the atherosclerotic plaques of the aortic arch. Fap distribution was characterized in mouse atherosclerotic plaques relative to other markers of activated smooth muscle cells, such as alpha smooth muscle actin and myosin heavy chain (Acta2 and Myh2), ECM turnover (Ki-67, procollagen III and Mmp-9), and inflammation in atherosclerosis (Cd-44, Il-12 and Tgf beta) using immunohistochemistry (IH) and RT-PCR analysis. Results: The mouse model of accelerated atherosclerosis showed an increasing presence of Fap with the progression of atherosclerosis and a high expression level in advanced atherosclerotic lesions compared with other markers of ECM turnover and inflammation in atherosclerosis. Conclusions: FAP exhibits a distinct pattern of expression in a mouse model of atherosclerosis as compared to other markers of activated vascular smooth muscle cells, ECM degeneration, and inflammatory cytokines. Full article

Heavy metals represent a class of pollutants detected at concentrations lower than 10 ppm in different matrices that are intensively monitored due to having a major impact on human health. Industrial activities including mining, agriculture, and transport, determine their presence in different environments. Corrosion phenomena of various installations, volcanic eruptions, or atmospheric deposition on the soil surface and in water can contaminate the respective environments. Atmospheric pollutants in the form of suspended dust particles with diameters below 10 microns are predominantly composed of different metallic species from Cd, Cr, Cu, Ni, etc. This paper presents a review of the main sources and types of heavy metals present in the atmosphere in the composition of particulate matter (PM), highlighting the main mechanisms of occurrence and detection techniques, including the impact on bio-geo-chemical processes in the soil and food chain, in close correlation with their impact on environment and human health. The purpose of this review is to highlight the current level of knowledge regarding the global situation of heavy metals in PM and to identify gaps as targets for future research. Full article