Role Of Cd Research Articles

Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health.

Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca2+ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd2+ at the cellular and tissue levels. The role of Cd in inducing oxidative stress-a pivotal mechanism behind its toxicity-is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd's impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications.

Rapidly reducing cadmium from contaminated farmland soil by novel magnetic recyclable Fe3O4/mercapto-functionalized attapulgite beads

Reducing cadmium (Cd) content from contaminated farmland soils remains a major challenge due to the difficulty in separating commonly used adsorbents from soils. This study synthesized novel millimeter-sized magnetic Fe3O4/mercapto-functionalized attapulgite beads (MFBs) through a facile one-step gelation process incorporating alginate. The MFBs inherit the environmental stability of alginate and enhance its mechanical strength by hybridizing Fe3O4 and clay mineral components. MFBs can be easily separated from flooded soils by magnets. When applied to 12 Cd-polluted paddy soils and 14 Cd-polluted upland soils, MFBs achieved Cd(II) removal rates ranging from 16.9% to 62.2% and 9.8%–54.6%, respectively, within a 12-h period. The MFBs predominantly targeted the exchangeable and acid soluble, and reducible fractions of Cd, with significantly enhanced removal efficiencies in paddy soils compared to upland soils. Notably, MFBs exhibited superior adsorption performance in soils with lower pH and organic matter (OM) content, where the bioavailability and mobility of Cd are heightened. The reduction of Cd content by MFBs is a sustainable and safe method, as it permanently removes the bioavailable Cd from soil, rather than temporarily reducing its bioavailability. The functional groups such as –SH, –OH, present in attapulgite and alginate of MFBs, played a crucial role in Cd(II) adsorption. Additionally, attapulgite and zeolite provided a porous matrix structure that further enhanced Cd(II) adsorption. The results of X-ray photoelectron spectroscopy suggested that both chemical precipitation and surface complexation contributed to Cd(II) removal. The MFBs maintained 87.6% Cd removal efficiency after 5 regeneration cycles. The surface of the MFBs exposed new adsorption sites and increased the specific surface area during multiple cycles with Cd-contaminated soil. This suggests that MFBs treatment with magnetic retrieval is a potentially effective pathway for the rapid removal of Cd from contaminated farmland soils.

A196 CSF2 AUTOANTIBODIES AS A SEROLOGICAL MARKER FOR CROHN'S DISEASE

Abstract Background Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that severely affects quality of life. Despite technological advances, CD diagnoses remain difficult and invasive, with delayed diagnoses correlated with worse prognosis and complications. CD is multifactorial, involving complex interactions between genetic and environmental risk factors, which leads to difficulty in identifying a cause and cure. However, research alludes to an underlying dysregulation of immune activity that leads to chronic intestinal inflammation. Mononuclear phagocytes (MNP) are essential immune cells that promote intestinal homeostasis through supporting immune tolerance, antimicrobial activity, and barrier integrity. A crucial cytokine that promotes the survival and function of intestinal MNP is Colony Stimulating Factor 2 (CSF2). Intriguingly, previous work in our lab demonstrated that CSF2 autoantibodies (CSF2-Ab) can be detected in the serum of every third CD patient and antedate the onset of CD by up to 6 years. In contrast, these titers are not seen in healthy donors or ulcerative colitis. Moreover, CSF2-Ab were predictive of disease location and severity, and are able to neutralize CSF2 by binding to glycosylations, impacting downstream signaling in MNP. These data suggest a role for CSF2-Ab in promoting intestinal immune dysregulation in CD. Aims Our work aims to characterize CSF2-Ab and their role in CD. Methods We developed a bead-based flow cytometric assay to screen CD patient serum for CSF2-Ab in several cohorts that contain samples at time points prior to, at, and after diagnosis. Results Our preliminary data demonstrate that our assay is rapid and specific for detecting CSF2-Ab of various isotypes in human serum and can be validated using ELISA. Furthermore, we show that this assay can be used to determine the epitope specificity of CSF2-Ab in CD patients in just one single sample. Conclusions We have developed a rapid and accessible assay to predict CD development years before diagnosis using minimal serum samples. Moreover, this screen will enable subclassification of patients based on their autoantibody reactivity to glycovariants of CSF2. Glycovariants that escape recognition by CD-specific CSF2-Ab could potentially be used as a therapeutic to ameliorate disease. Beyond treatment, understanding how CSF2-Ab epitope specificity and isotypes may change over the course of disease development will serve as a roadmap for elucidating the role of CSF2-Ab in CD. Funding Agencies CAG, CIHR

Effects of selenium on structure of the essential oil isolated from Satureja hortensis L. (Lamiaceae) under the cadmium stress

One of the heavy metals which cause severe environmental pollution and biochemical changes in plants is Cadmium (Cd) while Selenium (Se) acts as an important anti-stress agent in plants. In the present research, the glasshouse experiment was conducted to examine the effect of Cd and Se on structure of the essential oil isolated from the savory plant, Satureja hortensis L. To do so, the plants were polluted with different Cd levels including 0 (the control), 75, 100, and 150 µM. Moreover, Se was used in the form of sodium selenite salt in concentrations of 0 (control), 10, 20, and 40 µM. The results show that carvacrol was the main constituent in most of the essential oil analyses, except for one of them (0 µM of Cd×10 µM of Se). Furthermore, differences among minor constituents in most of treatments were not significant. Therefore, these results indicate the role of Cd and Se in the compositional changes of S. hortensis essential oil.

RACIAL AND GENDER DISPARITIES IN THE DEVELOPMENT OF CROHN’S DISEASE COMPLICATIONS: A RETROSPECTIVE ANALYSIS

Abstract BACKGROUND Crohn’s disease (CD) is a chronic systemic inflammatory disease that most commonly affects the gastrointestinal tract (GI) and is characterized by transmural inflammation. Complications of CD include fistulization, abscess formation, and GI bleed. CD predominantly affects patients with European ancestry, however Black and Hispanic patients have been noted to have phenotypic differences in disease presentation. Gender may also play a role in CD, with some studies suggesting that men develop more severe disease. METHODS Patients with a diagnosis of CD were identified using the 2020 Nationwide Inpatient Sample (NIS). Patients were stratified based on the presence of CD complications which included fistula, abscess, and bleed. Patients with complications were further stratified based on the specific complication. Data were collected regarding age, gender, race, primary insurance, median income, hospital region, hospital bed size, and comorbidities. The relationship between gender, race, and the development of fistula, abscess, or bleed among patients hospitalized with CD was analyzed using multivariate regression analysis. RESULTS A total of 178,279 patients with a diagnosis of CD were included in the study. Of these, 23,889 (13.4%) developed a complication of CD including fistula, abscess, or bleed. Female patients with CD had a statistically significant lower odds of developing a CD complication (aOR 0.79, P < 0.001). Higher odds of developing a complication of CD were seen in Black patients (aOR 1.47, P < 0.001) and Hispanic patients (aOR 1.29, P < 0.001). Black patients with CD had increased odds of developing fistula (aOR 1.35, P < 0.001), abscess (aOR 1.26, P = 0.004), and bleed (aOR 1.60, P < 0.001). Hispanic patients with CD had higher odds of developing a bleed (1.46, P < 0.001). CONCLUSION CD is a complex inflammatory process that is influenced by both genetic and environmental factors. Complications of CD such as fistulization, abscesses, and GI bleed are commonly seen. Our study found that women are at lower risk of developing these complications compared to men. Despite CD being primarily seen in White patients, our study found that Black and Hispanic patients are more likely to develop complications of CD. Further studies are needed to elucidate the socioeconomic and genetic factors that are responsible for these findings. Inclusion process for the study.

Potential role of SNP rs2071475 in rheumatoid arthritis and inflammatory bowel disease in the East Asian population: a Mendelian randomization study

BackgroundPrevious observational studies have identified an association between rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, the causal relationship between RA and IBD in the East Asian population remains uncertain.MethodsThe two-sample Mendelian randomization (MR) analysis was conducted to elucidate the potential causal relationship between RA and IBD. Summary-level data from genome-wide association studies (GWAS) in the East Asian population were utilized, including RA (n = 19,190) and IBD (n = 6543), including Crohn's disease (CD, n = 5409) and ulcerative colitis (UC, n = 4853). The inverse variance weighted (IVW) method was employed as the primary analysis, supplemented by weighted median, weighted mode, simple median, MR-Egger, and MR-PRESSO analyses. Sensitivity analyses were conducted to assess the robustness of the results. Genetic data for RA (n = 22,515) were utilized to validate the findings in the East Asian population.ResultsThe IVW method showed no significant association between genetically predicted RA and overall IBD in the East Asian population (OR = 1.028; 95% CI: 0.935–1.129; P = 0.567). The subgroup analysis revealed a positive association between RA and CD (OR = 1.268; 95% CI: 1.108–1.451; P < 0.001), while a negative association was observed with UC (OR = 0.839; 95% CI: 0.710–0.993; P = 0.041). These findings were supported by another set of RA data. Additionally, an SNP rs2071475 was identified to play an important role in CD and UC.ConclusionThis study revealed a potential increased susceptibility to CD and a decreased susceptibility to UC in the East Asian population with RA. Furthermore, a key SNP rs2071475 was discovered along with its opposite effects in CD and UC. These findings provide new evidence for research on the corresponding molecular mechanisms and offer insights for clinical management of RA-associated IBD.

Liposomal silymarin anti-oxidative and anti-apoptotic features in lung cells: An implication in cadmium toxicity

BackgroundSeveral metallic elements with high atomic weight and density are serious systemic toxicants, and their wide environmental distribution increase the risk of their exposure to human. Silymarin (SL), a polyphenol from milk thistle (Silybum marianum) plant has shown protective role against heavy metal toxicity. However, its low aqueous solubility and rapid metabolism limits its therapeutic potential in clinic. MethodsWe compared the role of silymarin nanoliposomes (SL-L) against cadmium (Cd) toxicity in normal MRC-5 and A 549 cancer cells. MRC-5 and A 549 cells exposed to Cd at 25 and 0.25 µM respectively, were treated with various non-toxic SL-L concentrations (2.5, 5, 10 µM) and cells viability, reactive oxygen species (ROS) generation, apoptosis and levels of cleaved PARP and caspase-3 proteins were determined following incubation. ResultsResults indicated that Cd exposure significantly increased apoptosis due to ROS generation, and showed greater toxicity on cancer cells compared to normal cells. While SL-L at higher concentrations (25 µM and higher) exhibits pro-apoptotic features, lower concentrations (10 and 2.5 µM for MRC-5 and A 549 cancer cells, respectively) played a protective and anti-oxidant role in Cd induced toxicity in both cells. Further, lower SL-L was required to protect cancer cells against Cd toxicity. In general, treatment with SL-L significantly improved cell survival by decreasing ROS levels, cleaved PARP and caspase-3 in both MRC-5 and A 549 cells compared to free silymarin. ConclusionResults demonstrated that SL-L potential in protecting against Cd-induced toxicity depends on concentration-dependent antioxidant and anti-apoptotic balance.

Exclusive Enteral Nutrition Alleviates Th17-Mediated Inflammation via Eliminating Mechanical Stress-Induced Th17-Polarizing Cytokines in Crohn's-like Colitis.

Exclusive enteral nutrition (EEN) with a liquid diet is the only established dietary treatment for Crohn's' disease (CD). However, the mechanism of action of EEN in CD is unclear. T helper 17 (Th17) immune response plays a critical role in CD. We hypothesized that EEN alleviates Th17 response by eliminating mechanical stress-induced expression of Th17-polarizing cytokines. A rat model of Crohn's-like colitis was established by intracolonic instillation of TNBS (65 mg/kg in 250 µL of 40% ethanol). Control rats were treated with saline. We characterized immunophenotypes and molecular changes of the colon in control and colitis rats with and without EEN treatment. Th17 differentiation was determined using coculture assays. TNBS instillation induced transmural inflammation with stenosis in the inflammation site and a marked increase of Th17-polarizing cytokines interleukin (IL)-6 and osteopontin and the Th17 cell population in the mechanically distended preinflammation site (P-site). EEN treatment eliminated mechanical distention and the increase of IL-6, osteopontin, and Th17 response in the P-site. IL-6 and osteopontin expression was found mainly in the muscularis externa. Mechanical stretch of colonic smooth muscle cells in vitro induced a robust increase of IL-6 and osteopontin. When naïve T cells were cultured with conditioned media from the P-site tissue or stretched cells, Th17 differentiation was significantly increased. Inhibition of IL-6, but not deletion of osteopontin, blocked the increase of Th17 differentiation. Mechanical stress induces Th17-polarizing cytokines in the colon. EEN attenuates Th17 immune response by eliminating mechanical stress-induced IL-6 in Crohn's-like colitis.

The spatial distribution, health risk, and cytotoxicity of metal(loid)s in contaminated field soils: The role of Cd in human gastric cells damage

The spatial distribution and pollution level of heavy metal(loid)s in soil (0–6 m) from a typical industrial region in Jiangmen City, Southeast China was investigated. Their bioaccessibility, health risk, and human gastric cytotoxicity in topsoil were also evaluated using an in vitro digestion/human cell model. The average concentrations of Cd (87.52 mg/kg), Co (106.9 mg/kg), and Ni (1007 mg/kg) exceeded the risk screening values. The distribution profiles of metal(loid)s showed a downward migration trend to reach a depth of 2 m. The highest contamination was found in topsoil (0–0.5 m), with the concentrations of As, Cd, Co, and Ni being 46.98, 348.28, 317.44, and 2395.60 mg/kg, respectively, while Cd showed the highest bioaccessibility in the gastric phase (72.80 %), followed by Co (21.08 %), Ni (18.27 %), and As (5.26 %) and unacceptable carcinogenic risk. Moreover, the gastric digesta of topsoil suppressed the cell viability and triggered cell apoptosis, evidenced by disruption of mitochondrial transmembrane potential and increase of Cytochrome c (Cyt c) and Caspases 3/9 mRNA expression. Bioaccessible Cd in topsoil was responsible for those adverse effects. Our data suggest the importance to reduce Cd in the soil to decrease its adverse impacts on the human stomach.

Browning of Mesenteric White Adipose Tissue in Crohn's Disease: A New Pathological Change and Therapeutic Target.

Hypertrophic mesenteric adipose tissue [htMAT] is a distinctive hallmark of Crohn's disease [CD], and it affects enteritis via inflammatory adipokine secretion by dysfunctional white adipocytes. White adipocytes can become beige adipocytes, which are characterized by active lipid consumption and favourable endocrine function, via white adipocyte browning. Our study aimed to determine whether white adipocyte browning occurs in htMAT and its role in CD. White adipocyte browning was examined in MAT samples from CD patients and controls. Human MAT explants and primary mesenteric adipocytes were cultured for in vitro experiments. Mice with 2,4,6-trinitrobenzenesulphonic acid solution [TNBS]-induced colitis were used for in vivo studies. A β3-adrenergic receptor agonist [CL316,243] was used to induce white adipocyte browning, and IL-4/STAT6 signalling was analysed to explore the mechanism underlying the anti-inflammatory activity of beige adipocytes. White adipocyte browning was observed in htMAT from CD patients, as shown by the appearance of uncoupling protein 1 [UCP1]-positive multilocular [beige] adipocytes with lipid-depleting activity and anti-inflammatory endocrine profiles. Both human MAT and primary mesenteric adipocytes from CD patients and controls could be induced to undergo browning, which increased their lipid-depleting and anti-inflammatory activities in vitro. Inducing MAT browning ameliorated mesenteric hypertrophy and inflammation as well as colitis in TNBS-treated mice in vivo. The anti-inflammatory activity of beige adipocytes was at least partially related to STAT6 signalling activation via the autocrine and paracrine effects of IL-4. White adipocyte browning is a newly identified pathological change in htMAT of CD patients and a possible therapeutic target.

SaMT3 in Sedum alfredii drives Cd detoxification by chelation and ROS-scavenging via Cys residues

Metallothioneins (MTs), a group of cysteine-rich proteins, are effective chelators of cadmium (Cd) and play a key role in plant Cd detoxification. However, little is known about the role of single cysteine (Cys) residues in the MTs involved in the adaptation of plants to Cd stress, especially, in hyperaccumulators. In the present study, we functionally characterised SaMT3 in S. alfredii, a Cd/Zn hyperaccumulator native to China. Our results showed that the C- and N- terminal regions of SaMT3 had differential functional natures in S. alfredii and determined its Cd hypertolerance and detoxification. Two CXC motifs within the C-terminal region were revealed to play a crucial role in Cd sensing and binding, whereas the four Cys-residues within the N-terminal region were involved in scavenging reactive oxygen species (ROS). An S. alfredii transgenic system based on callus transformation was developed to further investigate the in-planta gene function. The SaMT3-overexpressing transgenic plant roots were more tolerant to Cd than those of wild-type plants. Knockout of SaMT3 resulted in significantly decreased Cd concentrations and increased ROS levels after exposure to Cd stress. We demonstrated the SaMT3-mediated adaptation strategy in S. alfredii, which uses metal chelation and ROS scavenging in response to Cd stress. Our results further reveal the molecular mechanisms underlying Cd detoxification in hyperaccumulating plants, as well as the relation between Cys-related motifs and the metal binding properties of MTs. This research provides valuable insights into the functions of SaMT3 in S. alfredii, and improves our understanding of Cd hyperaccumulation in plants.

Cadmium contributes to heat tolerance of a hyperaccumulator plant species Sedum alfredii

Hyperaccumulators are plant species that tolerate and accumulate very high concentrations of toxic metals, including Cd. Hyperaccumulation of heavy metals is reported to benefit plant biotic resistance; however, no prior study has examined the possible role of toxic metals on abiotic stress resistance in hyperaccumulators. A preliminary experiment found that Cd significantly improved plant growth of a hyperaccumulator, Sedum alfredii Hance, under heat stress. This study investigated the possible role of Cd in S. alfredii’s heat resistance, using infrared thermography, transmission electron microscopy (TEM), real-time quantitative polymerase chain reaction (RTqPCR), and high-throughput sequencing. The results showed that high temperatures irreversibly damaged stomatal function, chloroplast structure, photosynthesis in S. alfredii, and lowered survival rates to 25%. However, Cd application significantly decreased the leaf temperature of S. alfredii and increased the survival rate to 75%. Cd penetrated the guard cells, restored stomatal function, and mitigated excessive water loss from S. alfredii under heat stress. Moreover, it activated antioxidant enzymes, promoted phytohormone biosynthesis, and upregulated a series of unigenes, thereby augmenting heat resistance in S. alfredii. These results indicate that Cd effectively improved thermotolerance in S. alfredii by regulating stomatal movement and antioxidant systems via upregulation of phytohormones and heat shock proteins.

Chronic exposure to low-dose cadmium facilitated nonalcoholic steatohepatitis in mice by suppressing fatty acid desaturation

Exposure to cadmium (Cd), a toxic metal, is epidemiologically linked to nonalcoholic steatohepatitis (NASH) in humans. However, the role of Cd in NASH remains to be fully elucidated. This study employed a novel murine NASH model to investigate the effects of chronic low-dose Cd on hepatic pathology and its underlying mechanisms. NASH is characterized by lipid accumulation, extensive cell death, and persistent inflammation in the liver. We found that treatment with Cd in drinking water (10 mg/L) for 6 or 12 weeks significantly boosted hepatic fat deposition, increased hepatocyte destruction, and amplified inflammatory responses in mice, confirming that low-dose Cd can facilitate NASH development in vivo. Mechanistically, chronic Cd exposure reshaped the hepatic transcriptional landscape, with PPAR-mediated fatty acid metabolic pathways being the most significantly altered. In particular, Cd repressed fatty acid desaturation, leading to the accumulation of saturated fatty acids whose lipotoxicity exacerbated cell death and, consequently, inflammatory activation. In summary, we validated the causal effects of chronic low-dose Cd on NASH in vivo and identified the fatty acid desaturation program as a novel target for Cd to instigate hepatopathological alterations.

Comparison of properties, adsorption performance and mechanisms to Cd(II) on lignin-derived biochars under different pyrolysis temperatures by microwave heating

The application of biochar derived from various biomass to treat heavy metal pollution has received particular attention in recent years. Lignin is an abundant, highly aromatic byproduct from the paper-making industry with a low utilization rate, which is a potential feedstock for biochar preparation. In this study, lignin was carbonized at different temperatures by microwave heating to obtain biochars (LBx), and the effect of pyrolysis temperature on biochar properties, Cd(II) adsorption behavior, and mechanisms was comprehensively investigated. It was found that the biochar-inherent minerals gradually enriched, the surface functional groups decomposed, and more structural defects formed at the edges of graphite-like structures with the increasing pyrolysis temperature. Adsorption experiments demonstrated that the adsorption capacity of lignin improved significantly after carbonization. And as the temperature increased from 200 °C to 500 o C, the q m of LBx increased from 573.27 to 635.44 mg ⋅ g −1 , which were vastly superior to common reported biochars. The adsorption mechanisms of Cd(II) on the LBx can be classified into the interaction with dissolved fractions (biochar-inherent minerals co-precipitation and DOM interaction) and bulk biochar (surface complexation and ionic exchange). The quantitative mechanisms indicated that the dissolved matters contribute more to Cd(II) adsorption than bulk biochar, but the contribution decreased from 89.48% to 77.38% with increasing temperature. Surface complexation and ionic exchange are two dominant mechanisms on bulk biochar, and the former has a more significant advantage for higher-temperature prepared biochar. Taken together, lignin was an efficient and promising feedstock to prepare biochar used for Cd(II) removal. • A low-cost biochar was directly prepared with industrial lignin by microwave heating. • LBs showed excellent adsorption performance to Cd(II) than common reported biochars. • Dissolved matters and bulk biochar on LBs both play important role in Cd(II) removal. • Surface complexation dominated the adsorption of higher-temperature bulk biochars.

Role of microRNAs in response to cadmium chloride in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal and aggressive malignancies with a 5-year survival rate less than 9%. Early detection is particularly difficult due to the lack of symptoms even in advanced stages. microRNAs (miRs/miRNAs) are small (~ 18–24 nucleotides), endogenous, non-coding RNAs, which are involved in the pathogenesis of several malignancies including PDAC. Alterations of miR expressions can lead to apoptosis, angiogenesis, and metastasis. The role of environmental pollutants such as cadmium (Cd) in PDAC has been suggested but not fully understood. This study underlines the role of miRs (miR-221, miR-155, miR-126) in response to cadmium chloride (CdCl2) in vitro. Lethal concentration (LC50) values for CdCl2 resulted in a toxicity series of AsPC-1 > HPNE > BxPC-3 > Panc-1 = Panc-10.5. Following the treatment with CdCl2, miR-221 and miR-155 were significantly overexpressed, whereas miR-126 was downregulated. An increase in epithelial–mesenchymal transition (EMT) via the dysregulation of mesenchymal markers such as Wnt-11, E-cadherin, Snail, and Zeb1 was also observed. Hence, this study has provided evidence to suggest that the environmental pollutant Cd can have a significant role in the development of PDAC, suggesting a significant correlation between miRs and Cd exposure during PDAC progression. Further studies are needed to investigate the precise role of miRs in PDAC progression as well as the role of Cd and other environmental pollutants.

Role of Autophagy in Cadmium-Induced Hepatotoxicity and Liver Diseases.

Cadmium (Cd) is a toxic pollutant that is associated with several severe human diseases. Cd can be easily absorbed in significant quantities from air contamination/industrial pollution, cigarette smoke, food, and water and primarily affects the liver, kidney, and lungs. Toxic effects of Cd include hepatotoxicity, nephrotoxicity, pulmonary toxicity, and the development of various human cancers. Cd is also involved in the development and progression of fatty liver diseases and hepatocellular carcinoma. Cd affects liver function via modulation of cell survival/proliferation, differentiation, and apoptosis. Moreover, Cd dysregulates hepatic autophagy, an endogenous catabolic process that detoxifies damaged cell organelles or dysfunctional cytosolic proteins through vacuole-mediated sequestration and lysosomal degradation. In this article, we review recent developments and findings regarding the role of Cd in the modulation of hepatotoxicity, autophagic function, and liver diseases at the molecular level.

Cadmium Water Pollution Associated with Motor Vehicle Brake Parts

With increasing industrial growth, there is a greater need to understand factory production processes, the resulting products, and the pollution caused by the fabrication processes leading to these products. Cadmium (Cd) is used in the electro-less Nickel-Cadmium bath phase of the brake manufacturing process, which provides the brake coating that produces corrosion-resistant brake parts. During the operation, the friction created during braking corrodes the Cd layer and releases Cd particles into the environment. Cd particles can enter water bodies and drinking water supplies through stormwater runoff. This research will first examine Cd pollution associated with motor vehicle brake discs from cradle to grave. Following this comprehensive look into the role of Cd in the brake manufacturing process as well as Cd speciation in natural waters, three interventions are proposed to prevent Cd pollution associated with brake parts: (i) Carbon-reinforced silicon carbide as an alternative for metal based brake parts; (ii) bacteria “coating” instead of Cd coating; (iii) permeable roads that can effectively remove Cd from runoff with nearly 98% reduction. A discussion into the advantages and disadvantages of each proposition are provided with this presentation.

The endocrine disruptor cadmium: a new player in the pathophysiology of metabolic diseases.

Cadmium (Cd), a highly toxic heavy metal, is found in soil, environment and contaminated water and food. Moreover, Cd is used in various industrial activities, such as electroplating, batteries production, fertilizers, while an important non-occupational source is represented by cigarette smoking, as Cd deposits in tobacco leaves. Since many years it is clear a strong correlation between Cd body accumulation and incidence of many diseases. Indeed, acute exposure to Cd can cause inflammation and affect many organs such as kidneys and liver. Furthermore, the attention has focused on its activity as environmental pollutant and endocrine disruptor able to interfere with metabolic and energy balance of living beings. Both in vitro and in vivo experiments have demonstrated that the Cd-exposure is related to metabolic diseases such as obesity, diabetes and osteoporosis even if human studies are still controversial. Recent data show that Cd-exposure is associated with atherosclerosis, hypertension and endothelial damage that are responsible for cardiovascular diseases. Due to the large environmental diffusion of Cd, in this review, we summarize the current knowledge concerning the role of Cd in the incidence of metabolic and cardiovascular diseases.

Mechanisms of Cd and Cu induced toxicity in human gastric epithelial cells: Oxidative stress, cell cycle arrest and apoptosis

Cadmium (Cd) and copper (Cu) are widely present in foods. However, their adverse effects on human gastric epithelium are not fully understood. Here, human gastric epithelial cells (SGC-7901) were employed to study the toxicity and associated mechanisms of Cd + Cu co-exposure. Their effects on cell viability, morphology, oxidative damage, cell cycle, apoptosis, and the mRNA levels of antioxidases and cell cycle regulatory genes were investigated. Co-exposure to Cd (5 μM)/Cu (10 μM) induced >40% cell viability loss, whereas little effect on cell viability at <10 μM Cd or 40 μM Cu. Compared to individual exposure, co-exposure induced greater oxidative damage by elevating ROS (3.5 folds), malondialdehyde (2.3 folds) and expression of SOD1 and HO-1 besides inhibiting CAT, GPX1 and Nrf2. A marked S cell-cycle arrest was observed in co-exposure, evidenced by more cells staying in the S phase (36%), up-regulation of cyclins-dependent kinase (CDK4) and CDKs inhibitor (p21) and down-regulation of CDK2, CDK6 and p27. Furthermore, higher apoptosis (22%) with floated and round cells occurred in co-exposure group. Our data implicate the cytotoxicity of Cd + Cu co-exposure was higher than individual exposure, and individual assessment would underestimate their potential health risk. Oxidative stress and cell cycle arrest possibly played a role in Cd + Cu induced toxicity and apoptosis in SGC-7901 cells. Our data suggest the importance to reduce Cd in foods to decrease its adverse impacts on human digestive system.

AML-126: Prognostic Value of Serum CD 155 in Adult Acute Myeloid Leukemia Patients: Relation to Clinical Outcome

Context CD155 is called polio virus receptor (PVR) due to its function as the receptor for poliovirus; the role of CD 155 in hematological malignancies are limited. Objective The aim of the study is to measure CD 155 levels in serum of adult acute myeloid leukemia (AML) patients using (ELISA) and correlate the level with clinical outcome. Design Prospective study and follow-up for 6 months. Setting Clinical Hematology and Bone Marrow Transplantation Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Patients The study conducted on 30 randomly selected, newly diagnosed adult AML patients and 15 healthy controls of matched age and sex. Intervention Measurement of CD 155 levels in serum of adult AML patients and healthy controls using ELISA. Main outcome measures Measurement of CD 155 levels in serum of adult AML patients in comparison to healthy controls and correlate its level with clinical outcome. Results Serum CD 155 was significantly higher in AML patients in comparison to controls (mean=66.067 ± 30.172 ng/L vs 11.067 ± 5.021 ng/L, P Conclusion Adult AML patients have elevated CD 155 levels, which were associated with an inferior OS, DFS, and poor prognosis.