BACKGROUND: As research progresses, there is a growing body of evidence indicating that urinary metallothionein (MT) levels may be elevated in individuals exposed to cadmium (Cd). This study aimed to investigate the potential association between urinary MT levels and causes of mortality among residents of the Kakehashi River Basin who have been exposed to Cd. METHOD: The study involved a total of 1,398 men and 1,731 women were conducted between 1981 and 1982, with follow-up until November 2016. The study employed the Cox proportional-hazards model to examine the association between higher urinary MT concentrations and the risk of all-cause or cause-specific mortality within the population. Furthermore, the Fine and Gray competing risks regression model was used to evaluate the links between specific causes of death. RESULTS: The findings revealed that elevated urinary MT concentrations were linked to increased all-cause mortality and higher mortality rates from renal and urinary tract diseases across all participants. Specifically, in men, higher urinary MT levels were associated with elevated all-cause mortality, while in women, increased concentrations were linked to higher mortality from endocrine, nutritional, and metabolic diseases, as well as cardiovascular diseases. Even after adjusting for competing risks, higher urinary MT concentrations were associated with tumor-related mortality in men and continued to be associated with cardiovascular disease mortality in women. CONCLUSIONS In conclusion, the results suggest that women may face a greater risk of adverse health effects due to prolonged exposure to Cd. Urinary MT levels could potentially serve as a biomarker for mortality from these diseases in populations chronically exposed to Cd.
Humans ; Male ; Female ; Cadmium/urine* ; Japan/epidemiology* ; Metallothionein/metabolism* ; Middle Aged ; Cause of Death ; Adult ; Follow-Up Studies ; Aged ; Environmental Exposure/analysis* ; Proportional Hazards Models

OBJECTIVES: Previous studies have demonstrated that the metals cadmium and arsenic exhibit estrogen-like effects and may influence the occurrence and development of gynecological tumors. This study aims to explore the association between urinary cadmium and arsenic levels and the prevalence of gynecologic cancers using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: Data from female participants in NHANES 2003-2018 were analyzed. Using R software, datasets (DEMO, BMX, etc.) were merged, and complete cases were retained by intersecting row names, yielding a total of 2 999 participants. After applying strict exclusion criteria, 2 802 participants were included: 83 with gynecologic cancer (cancer group) and 2 719 without (control group). Demographic, reproductive health, and urinary cadmium and arsenic data were collected. Binary Logistic regression models were employed to assess associations between urinary cadmium and arsenic levels and gynecologic cancer risk. RESULTS: High urinary cadmium and arsenic levels were risk factors for gynecologic cancers, with odds ratios (ORs) of 1.623 (95% CI 1.217 to 2.166) and 1.003 (95% CI 1.001 to 1.005), respectively. After propensity score matching (PSM), the trend remained; cadmium was still a statistically significant risk factor with an OR of 2.182 (95% CI 1.343 to 3.545), while arsenic's association, though not statistically significant, still trended toward risk (OR=1.004, 95% CI 0.999 to 1.009). Subgroup analyses showed that both cadmium and arsenic were risk factors for ovarian cancer (OR=1.745, 95% CI 1.178 to 2.586 and OR=1.005, 95% CI 1.002 to 1.008, respectively); these associations persisted after PSM. Additionally, cadmium increased the risk of endometrial cancer (OR=1.617, 95% CI 1.109 to 2.356). CONCLUSIONS Exposure to cadmium and arsenic is associated with an increased risk of ovarian and endometrial cancers. These findings suggest that reducing environmental exposure to heavy metals such as cadmium and arsenic may help prevent certain gynecologic cancers.
Humans ; Female ; Cadmium/urine* ; Arsenic/urine* ; Genital Neoplasms, Female/urine* ; Middle Aged ; Nutrition Surveys ; Adult ; Risk Factors ; Environmental Exposure/adverse effects* ; Aged

Ophiopogon japonicus, a precious medicinal plant endemic to Zhejiang Province. Its tuberous roots are rich in bioactive components such as flavonoids, possessing anti-inflammatory, antioxidant, and immunomodulatory properties. To elucidate the impact of cadmium (Cd) stress on the accumulation and biosynthetic pathway of flavonoids in O. japonicus, this study exposed O. japonicus to different concentrations of Cd stress and explored the changes through integrated transcriptomics and metabolomics analysis. The results demonstrated that Cd stress (1 mg/L and 10 mg/L) significantly increased the content of flavonoids in O. japonicus in a concentration-dependent manner. The metabolomics analysis revealed a total of 110 flavonoids including flavones, flavanols, flavonols, flavone and flavonol derivatives, flavanones, isoflavonoids, chalcones and dihydrochalcones, and anthocyanins in O. japonicus, among which flavones, flavonols, flavone and flavonol derivatives, and anthocyanins increased under Cd stress. The transcriptomics analysis identified several key flavonoid biosynthesis-associated genes with up-regulated expression under Cd stress, including 14 genes encoding 4-coumarate CoA ligase (4CL), 2 genes encoding chalcone isomerase (CHI), and 14 genes encoding phenylalanine ammonia lyase (PAL). The gene-metabolite regulatory network indicated significant positive correlations of 4CL (Cluster-21637.5012, Cluster-21637.90648, and Cluster-21637.62637) and CHI (Cluster-21637.111909 and Cluster-21637.123300) with flavonoid metabolites, suggesting that these genes promoted the synthesis of specific flavonoid metabolites, which led to the accumulation of total flavonoids under Cd stress. These findings provide theoretical support for the cultivation and utilization of medicinal plants in Cd-contaminated environments and offered new perspectives for studying plant responses to heavy metal stress.
Cadmium/toxicity* ; Flavonoids/biosynthesis* ; Metabolomics ; Ophiopogon/drug effects* ; Stress, Physiological ; Transcriptome ; Gene Expression Profiling ; Gene Expression Regulation, Plant

Soil cadmium pollution can adversely affect the cultivation of the ornamental plant, Coleus scutellarioides. Upon cadmium contamination of the soil, the growth of C. scutellarioides is impeded, and it may even succumb to the toxic accumulation of cadmium. In this study, we investigated the effects of arbuscular mycorrhizal fungi (AMF) on the adaptation of C. scutellarioides to cadmium stress, by measuring the physiological metabolism and the degree of root damage of C. scutellarioides, with Aspergillus oryzae as the test fungi. The results indicated that cadmium stress increased the activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the content of malondialdehyde (MDA) and proline (Pro) within the cells of C. scutellarioides, but inhibited mycorrhizal infestation rate, root vigour and growth rate to a great degree. With the same cadmium concentration, the inoculation of AMF significantly improved the physiological indexes of C. scutellarioides. The maximum decrease of MDA content was 42.16%, and the content of secondary metabolites rosemarinic acid and anthocyanosides could be increased by up to 27.43% and 25.72%, respectively. Meanwhile, the increase of root vigour was as high as 35.35%, and the DNA damage of the root system was obviously repaired. In conclusion, the inoculation of AMF can promote the accumulation of secondary metabolites, alleviate root damage, and enhance the tolerance to cadmium stress in C. scutellarioides.
Cadmium/toxicity* ; Mycorrhizae/physiology* ; Plant Roots/drug effects* ; Soil Pollutants/toxicity* ; Stress, Physiological ; Superoxide Dismutase/metabolism*

Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]₄P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism* ; Adenosine Triphosphatases/metabolism* ; Ophiopogon/drug effects* ; Soil Pollutants/toxicity* ; Plant Proteins/metabolism* ; Stress, Physiological ; Multigene Family ; Gene Expression Regulation, Plant

Cadmium/metabolism* ; Kidney ; Cells, Cultured ; Mitochondria ; Metallothionein/metabolism* ; Liver

It has been confirmed that exposure to various metal pollutants can induce neurotoxicity, which is closely associated with the occurrence and development of neurological disorders. Ferroptosis is a form of cell death in response to metal pollutant exposure and it is closely related to oxidative stress, iron metabolism and lipid peroxidation. Recent studies have revealed that ferroptosis plays a significant role in the neurotoxicity induced by metals such as lead, cadmium, manganese, nickel, and antimony. Lead exposure triggers ferroptosis through oxidative stress, iron metabolism disorder and inflammation. Cadmium can induce ferroptosis through iron metabolism, oxidative stress and ferroptosis related signaling pathways. Manganese can promote ferroptosis through mitochondrial dysfunction, iron metabolism disorder and oxidative stress. Nickel can promote ferroptosis by influencing mitochondrial function, disrupting iron homeostasis and facilitating lipid peroxidation in the central nervous system. Antimony exposure can induce glutathione depletion by activating iron autophagy, resulting in excessive intracellular iron deposition and ultimately causing ferroptosis. This article reviews the effects of metal pollutants on ferroptosis-related indicators and discusses the specific mechanisms by which each metal triggers ferroptosis. It provides a reference for identifying targets for preventing neurotoxicity and for developing treatment strategies for neurological disorders.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Oxidative Stress/drug effects* ; Neurotoxicity Syndromes/metabolism* ; Cadmium/adverse effects* ; Animals ; Lipid Peroxidation/drug effects* ; Metals/metabolism* ; Lead/adverse effects* ; Environmental Pollutants/toxicity* ; Manganese/adverse effects* ; Nickel/adverse effects* ; Mitochondria/drug effects* ; Signal Transduction/drug effects*

Objective: To investigate the spatial distribution characteristics and correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in coal-fired fluorosis areas. Methods: Based on the survey data on the prevalence of dental fluorosis at CDC in Guizhou Province in 2022, 274 original surface drinking water sources were collected in typical coal-fired fluorosis areas, and fluoride (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb) 17 elements; apply Moran's I index, Getis-Ord Gi* hotspot analysis of the global spatial autocorrelation of chemical elements in drinking water and the degree of aggregation of each element on the local area, and correlation analysis with the prevalence of dental fluorosis in the region. Results: Except for Cu, Zn, and Cd, global spatial autocorrelation Moran's I was negative, and all other elements were positive. F, Ca, Al, Ti, As, Mo, Cd, and Cu elements showed high values of aggregation in the southeastern low-altitude area; Mg, Ba, Pb, Cr, Mn, and Fe elements were mainly aggregated in the central altitude terrain transition area, Zn and Se elements in water sources are significantly positively correlated with the prevalence of dental fluorosis (P<0.05). In contrast, F, Mg, Al, Ti, As, Mo, Cd, Ba, and Pb elements negatively correlate (P<0.05). Elements in the central region were high-high aggregation, as a hot spot aggregation area with high disease incidence, while F, Al, Mn, Mo, Cd, and Ba elements in the western region were low-low aggregation, as a cold spot aggregation area with a low incidence of fluorosis. Conclusions: The risk of population fluoride exposure in surface drinking water sources is shallow. However, the chemical element content of drinking water sources in coal-fired polluted endemic fluorosis areas has prominent spatial geographical distribution characteristics. There is a significant spatial aggregation effect with the prevalence of dental fluorosis, which may play a synergistic or antagonistic effect on the occurrence and prevalence of dental fluorosis.
Humans ; Drinking Water ; Prevalence ; Coal ; Fluorides/adverse effects* ; Cadmium ; Fluorosis, Dental/epidemiology* ; Lead ; Selenium ; Arsenic

Objective: To analyze the levels and distribution characteristics of blood cadmium and urinary cadmium in American adults, to analyze the relationship between blood cadmium and urinary cadmium and pulmonary function dose response, and to explore the effect of this index on the risk of chronic obstructive pulmonary disease. Methods: In March 2022, 3785 patients from 2007 to 2012 in NHANES database were selected as the subjects. Collect demography data such as gender and age, and test data such as lung function, blood cadmium concentration and Urine cadimium concentration. The relationship between blood and urine cadmium levels and lung function and pulmonary function and chronic obstructive pulmonary diease (COPD) was analyzed by Mann-Whitney U test or Kruskal-Wallis H test, multivariate linear regression and restricted cubic spline method. Results: The geometric mean of blood cadmium and urine cadmium in American adults was 0.37 g/L and 0.28 g/L, FEV(1) and FEV(1)/FVC among different cadmium exposure groups was statistically significant, and there was a negative linear dose-response relationship between serum Cd and urine Cd concentrations and FEV(1)/FVC levels (P(overall)<0.001, P(non-linear)=0.152; P(overall)<0.001, P(non-linear)=0.926). Compared with the lowest quartile concentration (Q1), the highest quartile blood cadmium concentration (Q4) (OR=1.934, P(trend)=0.000) and urinary cadmium concentration (OR=1.683, P(trend)=0.000) may increased the risk of chronic obstructive pulmonary disease. Conclusion: There is a negative correlation between blood cadmium, urinary cadmium levels and lung function in American adults, and cadmium may increase the risk of chronic obstructive pulmonary disease.
Adult ; Humans ; Cadmium ; Nutrition Surveys ; Lung ; Pulmonary Disease, Chronic Obstructive ; Respiratory Function Tests

Objective: To study the effects of cadmium chloride (CdCl(2)) exposure on testicular autophagy levels and blood-testis barrier integrity in prepubertal male SD rats and testicular sertoli (TM4) cells. Methods: In July 2021, 9 4-week-old male SD rats were randomly divided into 3 groups: control group (normal saline), low dose group (1 mg/kg·bw CdCl(2)) and high dose group (2 mg/kg·bw CdCl(2)), and were exposed with CdCl(2) by intrabitoneal injection. 24 h later, HE staining was used to observe the morphological changes of testis of rats, biological tracer was used to observe the integrity of blood-testis barrier, and the expression levels of microtubule-associated protein light chain 3 (LC3) -Ⅰ and LC3-Ⅱ in testicular tissue were detected. TM4 cells were treated with 0, 2.5, 5.0 and 10.0 μmol/L CdCl(2) for 24 h to detect the toxic effect of cadmium. The cells were divided into blank group (no exposure), exposure group (10.0 μmol/L CdCl(2)), experimental group[10.0 μmol/L CdCl(2)+60.0 μmol/L 3-methyladenine (3-MA) ] and inhibitor group (60.0 μmol/L 3-MA). After 24 h of treatment, Western blot analysis was used to detect the expression levels of LC3-Ⅱ, ubiquitin binding protein p62, tight junction protein ZO-1 and adhesion junction protein N-cadherin. Results: The morphology and structure of testicular tissue in the high dose group were obvious changed, including uneven distribution of seminiferous tubules, irregular shape, thinning of seminiferous epithelium, loose structure, disordered arrangement of cells, abnormal deep staining of nuclei and vacuoles of Sertoli cells. The results of biological tracer method showed that the integrity of blood-testis barrier was damaged in the low and high dose group. Western blot results showed that compared with control group, the expression levels of LC3-Ⅱ in testicular tissue of rats in low and high dose groups were increased, the differences were statistically significant (P<0.05). Compared with the 0 μmol/L, after exposure to 5.0, 10.0 μmol/L CdCl(2), the expression levels of ZO-1 and N-cadherin in TM4 cells were significantly decreased, and the expression level of p62 and LC3-Ⅱ/LC3-Ⅰ were significantly increased, the differences were statistically significant (P<0.05). Compared with the exposure group, the relative expression level of p62 and LC3-Ⅱ/LC3-Ⅰ in TM4 cells of the experimental group were significantly decreased, while the relative expression levels of ZO-1 and N-cadherin were significantly increased, the differences were statistically significant (P<0.05) . Conclusion: The mechanism of the toxic effect of cadmium on the reproductive system of male SD rats may be related to the effect of the autophagy level of testicular tissue and the destruction of the blood-testis barrier integrity.
Rats ; Male ; Animals ; Testis ; Cadmium Chloride/metabolism* ; Cadmium ; Blood-Testis Barrier/metabolism* ; Rats, Sprague-Dawley ; Cadherins/metabolism* ; Autophagy