CD Group Research Articles

Resveratrol protects against cadmium-induced cerebrum toxicity through modifications of the cytochrome P450 enzyme system in microsomes.

Cadmium (Cd), known as a vital contaminant in the environment, penetrates the blood-brain barrier and accumulates in the cerebrum. Acute toxicosis of Cd, which leads to lethal brain cerebral edema, intracellular accumulation and cellular dysfunction, remains to be illuminated with regard to the exact molecular mechanism of cerebral toxicity. Resveratrol (RES) existing in the edible portions of numerous plants is a simply acquirable and correspondingly less toxic natural compound with neuroprotective potential, which provides some theoretical bases for antagonizing Cd-induced cerebral toxicity. This work was executed to research the protective effects of RES against Cd-induced toxicity in chicken cerebrum. Markedly, these lesions were increased in the Cd group, which also exhibited a thinner cortex, reduced granule cells, vacuolar degeneration, and an enlarged medullary space in the cerebrum. Furthermore, Cd induced CYP450 enzyme metabolism disorders by interfering the nuclear xenobiotic receptor response (NXRs), enabling cerebrum to reduce the ability to metabolize exogenous substances, eventually leading to Cd accumulation. Meanwhile, accumulated Cd promotes the oxidative damage, and synergistically promote the damage of the neurons and glial cells. RES initiated the NXRs (especially for AHR and PXR), decreasing the expression of CYP450 genes, changing the content of CYP450, maintaining CYP450 enzyme normal activities, and exerting antagonistic action against the Cd-induced abnormal response of nuclear receptors. These results suggested that the cerebrum toxicity caused by Cd was reduced by pretreatment with RES. This article is protected by copyright. All rights reserved.

Association of mode of delivery with short-term and neurodevelopmental outcomes in periviable singleton infants: A nationwide database study.

To evaluate the association of mode of delivery (MOD) with short-term and neurodevelopmental outcomes at 2 years of corrected age (CA) in periviable singleton infants. This retrospective cohort study of the Taiwan Premature Infant Follow-up Network database between 2010 and 2016 compared non-anomalous singleton deliveries (cesarean delivery [CD] vs vaginal delivery [VD]) between 22 0/7 and 25 6/7 gestational weeks. Major morbidities, mortality, and neurodevelopmental outcomes were evaluated at 2-year CA. The CD and VD groups included 354 and 472 infants, respectively. The intraventricular hemorrhage (IVH) rate was lower in the CD group (54% vs 66%, P = 0.001), but severe IVH differed non-significantly between groups (20% vs 26%, P = 0.057). In the small-for-gestational age subgroup, CD was associated with lower IVH (56% vs 84%, adjusted odds ratio [aOR] 0.17, 95% confidence interval [CI] 0.04-0.69) and better survival without neurodevelopmental impairment (29% vs 8%, aOR, 6.64, 95% CI 1.02-43.29) after controlling for potential confounders. The optimal MOD for periviable singleton birth and its impact are unclear. CD in periviable singleton births is associated with a decreased IVH risk, without improvement in severe IVH, mortality, or neurodevelopment at 2-year CA. The small-for-gestational age subgroup may benefit from CD for better survival without neurodevelopmental impairment.

Assessment of the Hepato-protective Effects of Combined Ethanolic Extract of Psidium guajava and Carica papaya Leaves in Rats Challenged with Cadmium

It has been shown that herbal extracts can protect intoxicated hepatocytes. Therefore, this study examined the hepato-protective effects of pooled ethanolic extract of Psidium guajava and Carica papaya leaves in rats challenged with Cadmium (Cd). Exactly 200g of the grounded leaves were soaked in ethanol for 48hours and was concentrated after filtration using a rotary evaporator. Fifteen adult female rats (150¬-±10g) were randomly assigned into three groups: Group 1 (control: received feed and water alone), Group 2 (Cd group; received single dose of Cd, 30mg/kg b wt, Group 3 (Cd + extract: received Cd as in group 2 and leaf extract 200mg/ kg bwt daily for 2 weeks). Rats were slaughtered and samples were taken for biochemical examination at the conclusion of the study period. When compared to controls, exposure to Cd alone resulted in a significant increase (p<0.05) in the activities of the alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), as well as an increase in the level of total protein (TP). Hepatocytes exposed to cd underwent histological changes as well. As opposed to rats exposed to Cd alone, there was a significant decrease in the values of ALT, AST, ALP, LDH, and TP when Cd-challenged rats were given the combination ethanolic extract of P. guajava and C. papaya. The outcomes suggest that the biherbal combination of P. guajava and C. papaya can shield liver cells against Cd damage.

Heart Rate Change as a Potential Digital Biomarker of Brain Death in Critically Ill Children With Acute Catastrophic Brain Injury.

To determine whether HRC, calculated using numeric HR measurements sampled every 5 seconds, can identify patients with BD among patients with catastrophic brain injury (CBI). Single-center, retrospective study (2008-2020) of critically ill children with acute CBI. Patients with CBI had a neurocritical care consultation, were admitted to an ICU, had acute neurologic injury on presentation or during hospitalization based on clinical and/or imaging findings, and died or survived with Glasgow Coma Scale (GCS) less than 13 at hospital discharge. Patients meeting BD criteria (BD group) were compared with those with cardiopulmonary death (CD group) or those who survived to discharge. HRC was calculated as the interquartile range of HR divided by median HR using 5-minute windows with 50% overlap for up to 5 days before death or end of recording. HRC was compared among the BD, CD, and survivor groups. Of 96 patients with CBI (69% male, median age 4 years), 28 died (8 BD, 20 CD) and 20 survived (median GCS 9 at discharge). Within 24 hours before death, HRC was lower in BD compared with CD patients or survivors (0.01 vs 0.03 vs 0.04, p = 0.001). In BD patients, HRC decreased at least 1 day before death. HRC discriminated BD from CD patients and survivors with 90% sensitivity, 70% specificity, 44% positive predictive value, 96% negative predictive value (area under the receiver operating characteristic curve 0.88, 95% CI, 0.80-0.93). HRC is a novel digital biomarker that, with further validation, may be useful as a classifier for BD in the overall course of patients with CBI.

Toll-like receptor 4 activation contributes to systemic vascular dysfunction in pregnant rats fed a high cholesterol diet during pregnancy

Background: Hypercholesterolemia is a hallmark clinical feature of cardiovascular diseases. Vascular adaptations to pregnancy include withstanding pregnancy-induced hypercholesterolemia, a physiological process required for fetus development. However, excessive (pathological) hypercholesterolemia during pregnancy has been linked to an increased risk of complications (e.g., preeclampsia); still, the underlying mechanisms are unclear. Toll-like receptor 4 (TLR4) is an innate immune receptor modulated by high cholesterol levels (in non-pregnant animals), but whether TLR4 activation also plays a role in vascular dysfunction in pregnancies complicated with hypercholesterolemia is unknown. Hypothesis: Pathological hypercholesterolemia during pregnancy causes maternal vascular dysfunction via activation of TLR4. Methods: Sprague Dawley rats were fed a standard (CD) or high cholesterol diet (HCD; 2% cholesterol and 0.5% cholic acid) from gestational day (GD) 6 to GD20 (term=22 days; n=9-10). Blood pressure was assessed before pregnancy and on GD19, and the results are presented as delta change. On GD20, body weight and pregnancy outcomes were recorded, and mesenteric arteries (systemic resistance arteries) were assessed using wire myography to evaluate vasoconstriction capacity to phenylephrine and endothelial-dependent vasodilation responses to methacholine. Experiments were conducted in the presence or absence of L-NAME (a pan-NOS inhibitor, 100 mmol/l) and/or CLI-095 (a TLR4 inhibitor, 10 mmol/l). Functional data were summarized as Emax (maximum response) or pEC50 (concentration required to produce 50% of Emax). Statistics: Student’s t-test or two-way ANOVA with Sidak post hoc test (significance: p<0.05). Results: The HCD prevented the late gestation systolic (p=0.0004) and diastolic (p=0.0066) blood pressure reduction observed in the CD group, and impaired male (p=0.0062) and female (p=0.0352) fetoplacental efficiency. Total body weight gain during pregnancy was not different between CD and HCD dams (p>0.05). In mesenteric arteries, vasoconstriction responses to phenylephrine (Emax) were increased in HCD dams (p=0.0056), and TLR4 inhibition with CLI-095 reduced the sensitivity (pEC50) of phenylephrine in these vessels (p=0.0147). Additionally, HCD dams presented higher sensitivity (pEC50) to methacholine (p=0.0169), which was not modified by the TLR4 inhibitor (p>0.05). Incubation of arteries with L-NAME abolished the increased sensitivity to methacholine (p>0.05), which was not further altered by CLI-095 (p>0.05). Conclusion: Inhibition of TLR4 ( ex vivo) reduced the enhanced vasoconstriction observed in HCD dams but did not alter endothelial-dependent vasodilation responses. Thus, if inhibiting TLR4 could block the vasoconstrictor effects of excessive hypercholesterolemia during pregnancy, this may be a target for future therapy development. This work was supported by a foundation grant from CIHR (FS154313) and by the generosity of the Stollery Children's Hospital Foundation and the Alberta Women's Health Foundation through the Women and Children's Health Research Institute (WCHRI). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

2 Effects of extra-label bisphosphonate use on growth parameters and endocrine biomarkers of bone health in juvenile horses

Extra-label bisphosphonate use in juvenile horses is widespread despite limited scientific understanding of biological and welfare impacts on skeletally immature, exercising horses. The objective of this study was to determine the effects of bisphosphonate (clodronate disodium; CD) on endocrine regulation of bone growth, hypothesizing there would be no effect. To test this, 32 Quarter Horses were stratified by age (500 ± 13 d of age), BW (336 ± 26 kg), sex (n = 16 males, n = 16 females), and initial bone optical density by aluminum equivalence into 4 treatment groups for a 168-d trial. The experimental period was divided into 2 phases mimicking sales preparation (Phase I: d 0–83) and early performance training (Phase II: d 84–168). Horses were housed in individual stalls (3.6 m × 7.3 m) and fed diets formulated to meet nutrient requirements. Investigators were blinded, and all horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW CD (OSPHOS®) or saline (placebo) on d 0, 42, 84, and 126. Treatments consisted of control (CON; n = 8), single-dose CD (1X; n = 8; d 84), 2-dose CD (2X; n = 8; d 0, 84), and 4-dose CD groups (4X;n = 8; d 0, 42, 84, 126). Physical measurements including BW, wither height (WH), hip height (HH), body length (BL), and heart girth (HG) circumference were recorded every 42 d from d 0. Likewise, serum samples were collected every 42 d before treatment administration to quantify growth hormone (GH), calcitonin (CT), parathyroid hormone (PTH), and ionized calcium. Data were analyzed using PROC MIXED of SAS. All physical growth measurements increased over time (P ≤ 0.01) but were not affected by treatment (P ≥ 0.62). Similarly, there was no effect of treatment (P = 0.44) for GH, but concentrations tended to decrease over time as growth rate slowed (P = 0.09). A treatment ´ time interaction was observed for PTH (P = 0.05) where concentrations increased following 2 clodronate doses. Specifically, concentrations increased on d 84 in 4X and on d 126 in 2X following the second administration of clodronate while 1X and CON remained unchanged. There was no effect of treatment (P = 0.98), time (P = 0.33), nor treatment × time interaction (P = 0.61) for CT despite the increase in PTH. Ionized calcium concentrations decreased over time (P < 0.01) with no effect of treatment (P = 0.26) or treatment × time interaction (P = 0.32). These results suggest that while administration of bisphosphonate has no effect on growth morphometrics, its repetitive use alters PTH concentrations after 2 doses.

Naringenin blocks hepatic cadmium accumulation and suppresses cadmium-induced hepatotoxicity via amelioration of oxidative inflammatory signaling and apoptosis in rats

Liver is one of the targets of cadmium (Cd) bioaccumulation for hepatic damage and pathologies via oxidative inflammation and apoptosis. The current study explored whether the citrus flavonoid naringenin (NAR) could prevent hepatic accumulation of Cd and Cd hepatotoxicity in a rat model. Rats in group 1 received normal saline; group 2 received NAR (50 mg/kg body weight); group 3 received CdCl2 (5 mg/kg body weight); group 4 received NAR + CdCl2, for four consecutive weeks. Assays related to markers of oxidative stress, inflammation, and apoptosis were carried out using liver homogenate. Blood and liver sample analyses revealed significant elevation of blood and hepatic Cd levels coupled with prominent increases in alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities, whereas the albumin and total protein levels were decreased considerably. Hepatic superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx) activities diminished significantly compared to control followed by marked increases in malondialdehyde (MDA) levels, and dysregulation in caspase and cytokine (TNF-α, IL-6, IL-4, IL-10) levels. However, it was found that in the rats administered NAR + Cd, the levels of Cd, hepatic enzymes, MDA, TNF-α, IL-6, and caspases-3/-9 were prominently reduced compared to the Cd group. The hepatic SOD, CAT, GPx, IL-4, IL-10, albumin, and total protein were markedly elevated along with alleviated hepatic histopathological abrasions. Taken together therefore, NAR is a potential flavonoid for blocking hepatic Cd bioaccumulation and consequent inhibition of Cd-induced oxidative inflammation and apoptotic effects on the liver of rats.

Abstract 2055: Prevalent focal amplification of oncogene in lung adenocarcinomas without canonical driver alterations

Abstract Lung adenocarcinoma (LADC) is the most common type of lung cancer and a leading cause of death worldwide. Typical oncogenes that drive LADCs when mutated (referred to as canonical drivers) include EGFR (30-60%), KRAS (10-30%), and fusion oncogenes (~10%) involving ALK, RET, and ROS1. However, approximately 30% of lung adenocarcinomas lack canonical drivers, implying unseen kinds of genomic alterations. Here, we explore alterations beyond the scope of canonical drivers in LADCs (referred to as non-canonical drivers) using large-scale whole-genome sequencing (WGS) of LADCs. We gathered total 183 WGS of LADCs, 138 of which were from our previous study (Lee et al. Cell. 2019) and 45 were newly sequenced from surgically resected LADCs. For raw data processing, we used a standard WGS analysis pipeline from read mapping to variant calling. Variant filtering and downstream analyses were performed using in-house scripts. Genomic variants analyzed in this study include single-base substitution (SBS), indel, structural variation (SV), and copy number variation (CNV). As a result, we found that 53 cases (29%) had no canonical drivers (ND group). Intriguingly, LADCs without canonical drivers had a contrasting genomic landscape compared to LADCs with canonical drivers (CD group). First, the point-mutation burden was ~3-fold higher in the ND group than in the CD group (52,500 vs. 17,900 for SNVs, p&amp;lt;0.001). Mutational signature analysis revealed that these additional mutations are attributable mainly to tobacco smoking (by mutational signature SBS4) and APOBEC-mediated mutagenesis (SBS12 and SBS13) and that they are more enriched in the ND group (4,800 vs 2,600, p=0.03). Second, the ND group harbored more frequent focal amplifications. Recurrently amplified genes include TERT, IL7R, NKX2-1, CCND1, CCND3, CCNE1, and EGFR. The pattern of SVs suggest that the amplifications occurred through the formation of extra-chromosomal DNA involving multiple chromosomes or following chromothripsis. Overall, this study broadens our understanding of non-canonical drivers of LADCs. Similar analyses of thousands of cancers with clinical information of the patient will likely yield the functional impact of these driver mutations and may offer more opportunities for LADC treatment in the future. Citation Format: Seongyeol Park, Joonoh Lim, Kijong Yi, Boram Yi, Ryul Kim, Jaemo Koo, Kwon Joong Na, Samina Park, In Kyu Park, Chang Hyun Kang, Jeong Seok Lee, Young Seok Ju, Young Tae Kim. Prevalent focal amplification of oncogene in lung adenocarcinomas without canonical driver alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2055.

Cadmium exposure induces testicular oxidative damage and histopathological changes in the freshwater leech Limnatis nilotica (Savigny, 1822): the protective role of salicylic acid

The present study examined the histopathological changes and some parameters of oxidative stress in the testes of the freshwater leech Limnatis nilotica, following their exposure to 50 µg l−1 of cadmium (Cd). The protective effects of salicylic acid (SA) in mitigating Cd-induced oxidative and histopathological injury were also investigated. We found that Cd exposure caused several histopathological changes in leech testes, such as vacuolisation of spermatogenic cysts which were strongly destroyed and disorganised. Biochemical study showed oxidative stress damage marked by a substantial increase in malondialdehyde and hydrogen peroxidase levels as well as disturbance in the activity of the leech antioxidant system. Interestingly, the testes from the Cd and SA leech-exposed group exhibited increased enzymatic and nonenzymatic antioxidant mechanism defenses, including superoxide dismutase, catalase, glutathione peroxidase, glutathione, oxidized glutathione, thiols, and ascorbic acid, in comparison with the testes of leeches exposed to Cd alone. Thus, SA supplementation considerably attenuated the histopathological lesions induced by Cd exposure, thereby restoring the normal appearance of the testes. In summary, the findings of this study indicate that SA treatment ameliorated the testicular histopathological and oxidative stress-induced damages caused by exposure to Cd through enhancing the antioxidant defense system.

Crosstalk between Mfn2-mediated mitochondria associated membranes disorder and autophagy induced by molybdenum and cadmium in sheep heart.

To investigate the crosstalk of mitochondria associated membranes (MAMs) disorder and autophagy co-induced by molybdenum (Mo) and cadmium (Cd) in sheep hearts. A total of 48 sheep were randomly divided into 4 groups: control group, Mo group, Cd group and Mo+Cd group. The intragastric administration lasted for 50 days. The results showed that Mo or/and Cd exposure could cause morphological damage, imbalance of trace elements and antioxidant function, Ca2+ concentration decreased markedly, and significantly increase the contents of Mo or/and Cd in myocardium. Additionally, the mRNA and protein levels of endoplasmic reticulum stress (ERS) related factors and mitochondrial biogenesis related factors were altered by Mo or/and Cd, as well as the content of ATP, inducing ERS and mitochondrial dysfunction. Meanwhile, Mo or/and Cd could lead to the alteration of expression level of MAMs-related genes and proteins, and the distance between mitochondria and endoplasmic reticulum (ER), resulting in MAMs disorder. Moreover, Mo or/and Cd exposure upregulated the mRNA and protein levels of autophagy related factors. In conclusion, our results revealed that Mo or/and Cd exposure caused ERS, mitochondrial dysfunction and structural MAMs disruption, ultimately leading to autophagy in sheep hearts, and the effects of Mo and Cd co-exposure were more obvious.

Acetovanillone augmented the cardioprotective effect of carvedilol against cadmium-induced heart injury via suppression of oxidative stress and inflammation signaling pathways

Cardiac toxicity is a public health issue that can be caused by both environmental and occupational exposures. The current study aimed to investigate the effectiveness of carvedilol (CV), Acetovanillone (ACET), and their combination for ameliorating cadmium (Cd)-induced oxidative stress, inflammation, and necroptosis. Rats were assigned to; the normal group, Cd group (2 mg/kg; i.p., single dose), and the other three groups received orally CV (10 mg/kg), ACET (25 mg/kg), and CV plus ACET, respectively and a single dose of Cd. Oral administration of CV, ACET, and their combination significantly dampens cardiac oxidative injury by increasing antioxidants GSH and SOD levels, while it decreases MDA and NADPH oxidase levels mediated by decreasing cardiac abundance of Nrf2, HO-1, and SIRT1 and downregulating KEAP-1 and FOXO-3 levels. Also, they significantly attenuated inflammatory response as indicated by reducing MPO and NOx as well as proinflammatory cytokines TNF-α and IL-6 mediated by downregulating TLR4, iNOS, and NF-κB proteins expression as well as IκB upregulation. Moreover, they potently counteracted cardiac necroptosis by downregulating RIPK1, RIPK3, MLKL, and caspase-8 proteins expression. Of note, the combination of CV and ACET have marked protection that exceeded each drug alone. Conclusively, CV ad ACET potently mitigated Cd-induced cardiac intoxication by regulating NADPH oxidase, KEAP-1/Nrf2/HO-1, SIRT1/FOXO-3, TLR4/NF-κB/iNOS, and RIPK1/RIPK3/MLKL signals.

Ketogenic diets initiated in late mid-life improved measures of spatial memory in male mice

Studies have shown ketogenic diets (KD) started from early middle-age improved health span and longevity in mice. KDs started later in life or administered intermittently may be more feasible and promote compliance. Therefore, this study sought to test if continuous or intermittent KDs started in late-middle-aged mice would improve cognition and motor function at advanced age. Eighteen-month-old male C57BL/6JN mice were assigned to an isocaloric control (CD), KD, or intermittent ketogenic (IKD, 3-day KD/week) diet. A panel of behavior tests were performed to assess cognitive and motor functions with aging. Y-maze alternation rate was higher for both IKD and KD mice at 23 months of age and for KD mice at 26 months indicating an improved spatial working memory. Twenty-six-month-old KD mice also showed better spatial learning memory in Barnes maze when compared to the CD. Improved grid wire hang performance was observed in aged IKD and KD versus CD mice indicating better muscle endurance under isometric contraction. A reduced level of circulating proinflammatory cytokines in aged KD (IL-6 and TNF-α) and IKD (IL-6) mice may contribute to the phenotypic improvements observed with these interventions. This study demonstrates that when initiated at late-middle age, the KD improved measures of spatial memory and grid wire hang performance in aged male mice, with IKD showing results intermediate to the CD and KD groups.

PROTECTIVE ROLE OF ANKAFERD BLOOD STOPPER ON CADMIUM-INDUCED ACUTE NEPHROTOXICITY

Objective&#x0D; Cadmium (Cd) is a very toxic and carcinogenic heavy&#x0D; metal that can cause harmful effects on human health.&#x0D; Toxicity may develop due to Cd exposure, especially in&#x0D; the kidneys. Ankaferd blood stopper (ABS) is a herbal&#x0D; mix that is used for its hemostatic properties in surgery.&#x0D; Also, ABS enhances wound and tissue healing. In this&#x0D; study, we aimed to evaluate the possible ameliorative&#x0D; effects of ABS in Cd-induced renal damage.&#x0D; Material and Method&#x0D; Thirty-two male rats were randomly divided into 4&#x0D; groups: control, Cd (cadmium chloride, 2.5 mg/kg&#x0D; single dose, ip), ABS (ABS, 1.5 ml/kg single dose ip),&#x0D; and Cd+ABS (cadmium chloride, 2.5 mg/kg single dose&#x0D; ip- ABS, 1.5 ml/kg single dose ip). At the end of the&#x0D; experiment, urea and creatinine levels were analyzed&#x0D; from the rats’ serum. In addition, total oxidant status&#x0D; (TOS), total antioxidant status (TAS) levels, superoxide&#x0D; dismutase (SOD), and glutathione peroxidase (GPx)&#x0D; activity were measured spectrophotometrically&#x0D; from renal tissues. The oxidative stress index (OSI)&#x0D; was calculated from TOS and TAS levels. Also, we&#x0D; evaluated alterations in the mRNA expression of Bcl-&#x0D; 2-associated X protein (Bax), B-cell-lymphoma-2 (Bcl-&#x0D; 2), silenced information regulator 1 (SIRT1), and p53&#x0D; in kidney tissue of rats by using the qRT-PCR method.&#x0D; Results&#x0D; In the Cd group, serum urea, creatinine levels, and&#x0D; tissue oxidative stress markers, TOS and OSI were&#x0D; significantly higher while Gpx activity was significantly&#x0D; lower than in the control group (p

Egg white composition, antioxidant capacity, serum and yolk lipids and oxidative damage of the oviduct magnum in laying hens fed diets contaminated with different concentrations of cadmium

Total of 384 healthy 38-week-old hens were randomly divided into four treatments. Layers in four groups were fed a basal diet and a basal diet with Cd at the level of 15, 30 and 60 mg/kg for nine weeks. Results showed that Cd could dose-dependently deposited in magnum and a positive correlation occurred between the accumulation of Cd in magnum and Cd content in egg whites. When compared with control group, 60 mg/kg Cd decreased magnum ovomucin, ovalbumin, lysozyme and ovomucoid gene expressions, but increased avidin gene expression obviously. Hens receiving 60 mg/kg Cd exhibited a significant decrease in egg white ovalbumin content and its proportion in total protein and increase in total cholesterol and LDLC levels in serum and yolk. The level of GSH and activities of T-SOD and CAT in magnum and GSH-Px activity in egg white were decreased significantly, while MDA level in both magnum and egg white was increased obviously in 60 mg/kg Cd group. Besides, Cd induced oxidative stress, inflammation, endoplasmic reticulum stress (ERS) and mitophagy accompanied by a significant up-regulation of the expressions of Keap1, IL1β, TNFα, NF-κB, p65, p-p65, Grp78, CHOP, ATF4, ATF6, IRE1α, Grp94, PINK1, Parkin, Fundc1, GRP75, VDAC1, MCU, MFF, Bnip3 and LC3I/II and a significant down-regulation of the expressions of Nrf2, HO-1, SOD1, SOD2, SOD3, MFN1, MFN2 and PGC1α. These results indicated that Cd can increase serum and yolk cholesterol level and induce magnum oxidative stress, inflammation, ERS and mitophagy through Nrf2/NF-κB and IRE1α/IP3R/GRP75/VDAC1/MCU pathways, thus disrupting egg white composition. Highlights Cd exposure disrupted the synthesis of egg white protein in oviduct magnum and destroyed antioxidant status and protein composition in egg white. Cd exposure significant enhanced serum and yolk total cholesterol and LDL cholesterol levels. Cd exposure induced magnum oxidative stress, inflammation, ERS and mitophagy through Nrf2/NF-κB and IRE1α/IP3R/GRP75/VDAC1/MCU pathways.

Effects of Chronic Alcohol Consumption and Iron Deficiency on Maternal Folate Status and Reproductive Outcome in Mice

The influence of chronic alcohol consumption with or without iron deficiency on reproductive performance and folate status was studied. Female CBA/J mice were fed isocaloric liquid diets prior to and during pregnancy. A 2 × 2 factorial design was employed with ethanol-derived calories (EDC) and iron (Fe) as dietary variables. Groups received 0% EDC and 30 ppm Fe (CA); 0% EDC and 2 ppm Fe (CD); 20% EDC and 30 ppm Fe (EA); and 20% EDC and 2 ppm Fe (ED). Animals were killed on day 18 of gestation. Mean body weights were reduced in CD, EA and ED groups, while daily caloric intakes reduced only in CD and ED groups. Maternal values for hemoglobin, transferrin saturation and red cell folates decreased with iron deficiency and/or 20% EDC; hematocrit, serum iron and serum folates decreased only with iron deficiency. Blood ethanol levels were similar in EA and ED groups. Maternal liver total lipids and alcohol dehydrogenase activity increased only with 20% EDC, while dihydrofolate reductase activity decreased with iron deficiency and/or 20% EDC. Iron deficiency and/or 20% EDC adversely affected gestational performances in mice as indicated by increased resorptions and decreased percentages of live fetuses/litters and live fetal weights. Data indicate that iron deficiency and/or chronic ethanol consumption induce adverse effects on maternal reproductive performance of CBA/J mice possibly via alteration of folate metabolism.

Role of minerals in mushroom residue on its adsorption capability to Cd(II) from aqueous solution

To explore the influence of mineral components in bio-sorbent on its adsorption capability towards heavy metal ions, the physicochemical properties of original mushroom residue (UMR) and that treated by an acid solution to remove its minerals (AMR) were comparatively analyzed using inductively coupled plasma mass spectrometry (ICP-MS), scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and fourier transform infrared spectrometer (FT-IR). Then, the adsorption performance of UMR and AMR for Cd(II) as well as the potential adsorption mechanism were investigated. Results show that UMR contains abundant K, Na, Ca and Mg, with the contents of 245.35, 50.18, 1390.63 and 29.84 mmol kg−1, respectively. Acid treatment (AMR) results in the removal of most of the mineral components, exposing more pore structures and increasing the specific surface area by about 7 times to 20.45 m2 g−1. The adsorption performance of UMR is significantly better than that of AMR when they are employed to purify a Cd(II)-contained aqueous solution. The theoretical maximum adsorption capacity of UMR calculated by Langmuir model is 75.74 mg g−1, which is about 22 times of that of AMR. Moreover, the adsorption of Cd(II) on UMR reaches an equilibrium at about 0.5 h, while the adsorption equilibrium of AMR takes more than 2 h. The mechanism analysis shows that 86.41% of the adsorption of Cd(II) on UMR can be attributed to ion exchange and precipitation caused by mineral components (especially for K, Na, Ca and Mg). The adsorption of Cd(II) on AMR mainly depends on the interactions between Cd(II) and surface functional groups, electrostatic interaction and pore-filling. The study indicates that those bio-solid wastes with abundant mineral components can be potentially developed as low-cost and high-efficient adsorbents for the removal of heavy metal ions from aqueous solution.

Low dosage fluorine ameliorates the bioaccumulation, hepatorenal dysfunction and oxidative stress, and gut microbiota perturbation of cadmium in rats

Many “hot spot” geographic areas around the world with soils and crops co-polluted with cadmium (Cd) and fluorine (F), two of the most representative pollutants in the environment. However, it still exists argumentative on the dose-effect relationship between F and Cd so far. To explore this, a rat model was established to evaluate the effects of F on Cd-mediated bioaccumulation, hepatorenal dysfunction and oxidative stress, and the disorder of intestinal microbiota as well. 30 healthy rats were randomly assigned to Control group (C group), Cd 1 mg/kg (Cd group), Cd 1 mg/kg and F 15 mg/kg (L group), Cd 1 mg/kg and F 45 mg/kg (M group), and Cd 1 mg/kg and F 75 mg/kg (H group) for 12 weeks by gavage. Our results showed that Cd exposure could accumulate in organs, cause hepatorenal function damage and oxidative stress, and disorder of gut microflora. However, different dosages of F showed various effects on Cd-induced damages in liver, kidney, and intestine, and only the low supplement of F showed a consistent trend. After low supplement of F, Cd levels were declined by 31.29% for liver, 18.31% for kidney, and 2.89% for colon, respectively. The serum aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr), and N-acetyl-β-glucosaminidase (NAG) were significantly reduced (p < 0.01); The activity of superoxide dismutase (SOD) was elevated and mRNA expression level of NAD(P)H quinone oxidoreductase 1 (NQO1) was decreased in the liver and kidney (p < 0.05). Moreover, low F dosage up-regulated the abundance of Lactobacillus from 15.56% to 28.73% and the 6.23% of F/B ratio was declined to 3.70%. Collectively, this highlights that low dosage of F might be a potential strategy to ameliorate the hazardous effects by Cd-exposed in the environment.

The Importance of Serum Homocysteine as a Biomarker in Diabetic and Obese COVID-19 Patients.

Homocysteine is a possible risk marker in hematological complications of COVID-19 infection. This study aimed to elucidate the significance of homocysteine as a biomarker for COVID-19 infection, and the relation of homocysteine with COVID-19 severity in obese people and diabetic patients. The study groups were 1- COVID-19 patients + Diabetic + Obese (CDO), 2- COVID-19 patients + Diabetic (CD), 3- COVID-19 patients + Obese (CO), 4- Healthy Group (HG). Serum levels of homocysteine, IL-6, D-dimer, vitamin B12, and folate were measured by a fully automated biochemistry device Cobas 6000 analyzer series.The mean serum concentration of homocysteine in the COD, CD, CO and H groups were 32.0114, 23.604, 19.4154, and 9.3206 umol/l respectively. The mean concentration of homocysteine levels between every two groups was statistically significant differences (P<0.05) except for the CD and the CO group (P=0.957). In the CDO group, the males have higher mean concentrations than females (P<0.05). The means of homocysteine concentrations in the CDO group among different age groups were different (P <0.001). The serum homocysteine level in the CDO group has a strong positive correlation (R=0.748) with D-dimer and a strong negative correlation (R= - 0.788) with serum folate, while its correlation with serum vitamin B12 is moderate negative (-0.499) and its correlation with serum IL-6 is weakly positive (R=0.376). The AUC value for homocysteine in predicting COVID-19 in the CDO group was 0.843, while 0.714 for the CD group, and 0.728 for the CO group. The serum homocysteine concentration test for all study groups was compared to the serum IL-6 test and the sensitivity was equal to 95% and its specificity was 67.5%. Serum homocysteine has potential predictive power in COVID-19 patients, and the severity of COVID-19 infection and the type of comorbidity is associated with higher sensitivity and specificity of homocysteine serological tests.

Dietary Selenium-Rich Lactobacillus plantarum Alleviates Cadmium-Induced Oxidative Stress and Inflammation in Bulatmai barbel Luciobarbus capito

Cadmium (Cd) poses a great threat to the breeding of aquatic economic animals. The present study aimed to explain the antagonistic effects of selenium-enriched Lactobacillus plantarum (SL) on Cd toxicity through the expression of oxidative and inflammatory factors. A total of 225 Bulatmai barbel Luciobarbus capito (L. capito) were divided into 3 groups, namely, the control group, the Cd group (Cd, 0.05 mg·L−1), and the SL + Cd group (Cd, 0.05 mg·L−1; Nano Se, 5 mg·kg−1; L. plantarum, 105 CFU·g−1). The experiment lasted for 28 d, Sampling at 14 and 28 d, respectively. The results showed that Cd exposure caused obvious pathological damage to the liver and kidney, and the serum parameter ALT increased significantly (p &lt; 0.05). In the Cd group, the concentration of Cd in the kidney was significantly increased (p &lt; 0.05), and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the kidney and gill were significantly decreased; malonaldehyde (MDA) increased significantly (p &lt; 0.05) Then the mRNA expression levels in the kidney and liver were measured. Cd exposure significantly decreased the mRNA expressions of SOD, CAT, GSH-Px, HO-1, I-κBα, and Nrf2 (p &lt; 0.05). The Cd-treated group showed significantly increased NF-kBp65, TGF-β, IL-8, IL-1, Keap1, and TNF-α expression levels. SL significantly alleviated the changes in the above indicators. The results of this study suggest that SL can trigger the Nrf2 signalling pathway and NF-kB signalling pathway to alleviate Cd toxicity. SL might be a potential drug for the treatment of Cd poisoning.

Protective Effects of Sodium Para-Aminosalicylic Acid on Lead and Cadmium Co-Exposure in SH-SY5Y Cells.

Combined exposure to lead and cadmium is common in occupational environments. However, the effects of co-exposure to Pb-Cd on neurotoxicity have not been fully clarified. Sodium para-aminosalicylic acid (PAS-Na) has previously been shown to protect neurons from Pb-induced toxicity. This study aimed to investigate the beneficial effect of PAS-Na against co-exposure to Pb-Cd-induced neurodegeneration in SH-SY5Y cells. The MTT assay was used to detect the effects of Pb and Cd alone, or in combination, on SH-SY5Y cell survival. The effects of Pb and Cd alone or in combination on oxidative stress were assessed by reactive oxygen species (ROS) level. Nrf2, the master switch for antioxidant responses, was detected by immunofluorescence. Protein expression levels of PI3K, Akt, p-Akt, Nrf2 and HO-1 were determined by Western blot analysis. MTT assay results established that the survival rate of SH-SY5Y cells was not significantly affected by exposure to 1 μmol/L lead, 0.25 μmol/L cadmium, and 1-fold Pb-Cd mixture (1 μmol/L Pb + 0.25 μmol/L Cd), while 10-fold Pb-Cd combined exposure (10 μmol/L Pb + 2.5 μmol/L Cd) significantly reduced the survival rate of SH-SY5Y cells. Combined Pb-Cd exposure significantly increased intracellular ROS levels, and N-Acetyl-L-cysteine (NAC) treatment in the 10 μmol/L Pb + 2.5 μmol/L Cd group significantly decreased ROS expression levels, attenuating the levels of oxidative stress. Protein expression of PI3K and p-Akt significantly decreased in the 10 μmol/L Pb + 2.5 μmol/L Cd group, while the expression of PI3K and p-Akt protein increased after PAS-Na intervention. Immunofluorescence analysis showed that levels of Nrf2 in the nucleus increased in the 10 μmol/L Pb + 2.5 μmol/L Cd group, along with Nrf2 protein levels, suggesting that Nrf2 was translocated from the cytoplasm into the nucleus upon combined Pb-Cd exposure. In addition, HO-1 protein expression level, a downstream gene product of Nrf2, was increased. In response to NAC intervention, HO-1 protein expression levels significantly decreased. PAS-Na had the same intervention effect as NAC. Combined exposure to Pb-Cd induced oxidative stress and cytotoxicity in SH-SY5Y cells. PAS-Na displayed antagonistic effects on neurodegenerative changes induced by combined Pb-Cd exposure; hence, it may afford a novel treatment modality for exposure to these metals.