BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

OBJECTIVE: To investigate the effect of Arsenic trioxide (ATO) combined with Norcantharidin (NCTD) on the proliferation and apoptosis of Jurkat cells, and to evaluate its effect on the proliferation and apoptosis of acute T-lymphoblastic leukemia (T-ALL) based on the Wnt/β-catenin signaling pathway. METHODS: Jurkat cell lines were used as the study subjects and treated with different concentrations of ATO (0, 2, 4, 8, 16 μmol/L) and NCTD (0, 10, 25, 50, 100 μmol/L) for 72 hours, and the cell proliferation was detected by CCK-8. Meanwhile, flow cytometry was used to detect the apoptosis rate, EdU staining to detect cell proliferation viability, cell clone formation assay to assess cell cloning ability, Transwell assay to assess cell invasion ability, and Western blot to detect apoptosis and the expression of Wnt/β-catenin signaling pathway-related proteins. RESULTS: Compared with the control group, both ATO and NCTD effectively inhibited Jurkat cell proliferation when used alone, and the inhibition effect was more significant when used in combination ( P < 0.05). The combination significantly increased the apoptosis rate of Jurkat cells ( P < 0.05). Meanwhile, the combination significantly decreased the proliferation vitality and clone formation ability of the cells ( P < 0.05), and inhibited the invasion ability of Jurkat cells ( P < 0.05). Western blot analysis showed that the combination of ATO and NCTD significantly up-regulated the expression of pro-apoptotic proteins Bax and E-cadherin, and down-regulated the expression of anti-apoptotic proteins Bcl-2, c-myc and Cyclin D1 ( P < 0.05). CONCLUSION The combination of ATO and NCTD had a synergistic effect in inhibiting proliferation and promoting apoptosis in Jurkat cells, which may be related to the inhibition of Wnt/β-catenin signaling pathway.
Humans ; Apoptosis/drug effects* ; Jurkat Cells ; Cell Proliferation/drug effects* ; Arsenic Trioxide ; Wnt Signaling Pathway/drug effects* ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; beta Catenin/metabolism* ; Arsenicals/pharmacology* ; Oxides/pharmacology*

OBJECTIVE: To investigate the effect of non-chemotherapy strategy of retinoic acid (ATRA) combined with arsenic trioxide (ATO) on the survival of patients with acute promyelocytic leukemia (APL). METHODS: The data of APL patients with complete information diagnosed in the hematology department of our hospital from June 2009 to November 2024 were retrospective analyzed. All patients in the non-CHT group received ATRA-ATO induction, consolidation and maintenance therapy. Patients in the CHT group received ATRA-ATO+chemotherapy induction therapy, followed by 3 cycles of ATRA-ATO+CHT consolidation therapy and 6-10 cycles of ATRA-ATO maintenance therapy. The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS), remission rate, differentiation syndrome (DS) and safety. RESULTS: There were 182 patients with APL and 15 patients with early death (ED), accounting for 8.24%, which was related to age and risk stratification. There was no significant difference in remission rate between the non-CHT group and the CHT group (P =0.486). As of February 2025, the median follow-up time of patients was 39.5 months. The EFS of the non-CHT group was significantly better than that of the CHT group (P =0.038). There was no significant difference in OS between the two groups (P =0.442). Subgroup analysis showed that EFS in the non-CHT was longer in standard-risk patients (P =0.012). There was no significant difference in EFS (P =0.585) and OS (P =0.473) between the CHT and non-CHT groups in high-risk patients. The incidence of mild DS was 23.6% in the non-CHT group and 23.1% in the CHT group, respectively, with no statistically significant difference(P =0.937). Compared with CHT group, the incidence of serious adverse events was lower in the non-CHT group. CONCLUSION The non-chemotherapy regimen of ATRA combined with ATO is a feasible method to cure APL patients.
Humans ; Leukemia, Promyelocytic, Acute/drug therapy* ; Arsenic Trioxide/therapeutic use* ; Tretinoin/administration & dosage* ; Retrospective Studies ; Female ; Treatment Outcome ; Male ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Middle Aged ; Remission Induction

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

Objective To investigate the protective effect of curcumin (Cur) against arsenic-induced neuroimmune toxicity and the underlying molecular mechanisms in vivo. Methods Eighty SPF female C57BL/6 mice were randomly assigned to four groups: a control group, an arsenic-treated group, a Cur-treated group and an arsenic+Cur group, with 20 mice in each group. The control group received distilled water; the arsenic-treated group was given 50 mg/L NaAsO₂ in the drinking water; the Cur-treated group was gavaged with 200 mg/kg of curcumin for 45 days; and the arsenic+Cur group received distilled water and was gavaged with 200 mg/kg of curcumin. Y-maze and Morris water maze experiments were conducted to assess the learning and memory ability of the mice. Western blot analysis was used to detect protein levels of blood-brain barrier tight junction proteins zonula occludens protein 1(ZO-1) and claudin 5, T lymphocyte subpopulation CD4 and CD8, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules JAK2 and STAT3. Real-time PCR was used to assess the mRNA levels of CD4⁺ T lymphocyte subsets type 1 T helper (Th1), Th2, Th17 and regulatory T cells (Treg) transcription factors and cytokines in hippocampus. Results Compared with the control group, the arsenic-treated group showed a significantly decreased correct rate, increased latency to reach the platform on the third and fifth days, and reduced times of crossing the platform. The expression of ZO-1 and claudin 5 protein decreased significantly, and the protein levels of CD4 and CD8 were up-regulated. The mRNA levels of Th1, Th17, and Treg transcription factor T-box expressed in T cell(T-bet), retinoid-related orphan receptor gamma t(RORγt), and forkhead box protein 3(FOXP3) in the arsenic-treated group were decreased. Th1 and Th17 cytokines interferon γ(IFN-γ) and interleukin 17(IL-17) were markedly decreased. In contrast, the mRNA levels of the Th2 transcription factor GATA binding protein 3(GATA3) and cytokine IL-4 in arsenic-treated group were higher than those in the control group. Furthermore, the protein levels of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) increased. Compared with the arsenic-treated group, the arsenic+Cur group demonstrated a significantly increased correct rate, decreased latency to reach the platform on the third and fifth days, and increased times of crossing the platform. The protein expression levels of ZO-1 and claudin 5 increased significantly, and the protein levels of CD4 and CD8 were down-regulated. The mRNA levels of Th2 transcription factor GATA3 and cytokine IL-4 were decreased. The mRNA levels of Th17 transcription factor RORγt and cytokine IL-17 were markedly increased. Furthermore, the protein levels of p-JAK2 and p-STAT3 decreased. Conclusion Through inhibiting the JAK2/STAT3 signaling pathway, curcumin could improve arsenic-induced decline in learning and memory abilities in mice, reverse the destruction of blood-brain barrier permeability of innate immune system components in arsenic-exposed mice, and antagonize arsenic-induced increase in the number of renal CD4 and CD8 molecule as well as the imbalance of CD4⁺ T lymphocyte subsets (Th1, Th2, Th17 and Treg), ultimately counteracting arsenic-induced neurotoxicity.
Animals ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Female ; Curcumin/pharmacology* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Mice ; Arsenic/toxicity*

Arsenic (As) is a common toxic pollution element. The microorganism-mediated transformation of arsenic forms is an important part in the biogeochemical cycle of As. In the various microbial metabolic processes involving As, the coupling reduction of As has a great impact on the environment and is a process that is easily overlooked. From the biogeochemical cycle of As, this review introduces the microorganism-mediated methane oxidation, anaerobic ammonium oxidation, and iron (Fe)-sulfur (S) oxidation coupled with As reduction. Organic matter, pH, and redox potential are the main factors affecting the coupling reduction. After the coupling reduction, the toxicity and migration of As are greatly enhanced, which may increase the risk of As pollution. Therefore, it is of great significance to clarify the influences of carbon, nitrogen, Fe, S and other elements on the coupling process and explore more microbial processes coupled with As reduction for the prevention and control of As pollution.
Arsenic/metabolism* ; Oxidation-Reduction ; Bacteria/metabolism* ; Environmental Pollutants/metabolism* ; Biodegradation, Environmental ; Methane/metabolism* ; Iron/metabolism* ; Ammonium Compounds/metabolism*

Objective To reveal the spatial distribution patterns of key pollutants in the Huaihe River Basin and quantify the risks and burdens of non-gastrointestinal cancers by the grade of pollution,providing targets and data support for enhanced management of water pollution in the Huaihe River Basin. Methods Surface water quality data of the Huaihe River Basin were obtained from the National Surface Water Environmental Quality Monitoring Network(2021).Incidence data of seven cancers were extracted from the 2019 Annual Report of the China Cancer Registry.Random forest and SHapley Additive exPlanations were employed to select key pollutants,and pollution was graded based on the spatial analysis of the Huaihe River Basin.The cancer risks and population attributable fractions were calculated under pollution grades. Results Five key pollutants linked to cancers were identified,including total nitrogen,total phosphorus,chemical oxygen demand,biochemical oxygen demand after 5 days,and arsenic.Pollution was graded into three levels regarding the combined effects of pollutants.Compared with the low pollution areas,high pollution areas showed increased risks of lung cancer(RR=1.26,95%CI:1.06-1.50),breast cancer(female)(RR=1.46,95%CI:1.21-1.77),pancreatic cancer(RR=1.46,95%CI:1.06-2.01),brain cancer(RR=1.44,95%CI:1.05-1.98),and gallbladder cancer(RR=1.60,95%CI:1.03-2.50).The grade of pollution contributed to more than 5% of cases for most cancers above. Conclusions The potential cancer risks and burdens attributed to surface water pollution cannot be overlooked.Addressing this challenge necessitates close collaboration of various stakeholders to strengthen policy development,enhance environmental governance,and implement public health interventions.
Humans ; China/epidemiology* ; Rivers/chemistry* ; Neoplasms/etiology* ; Water Quality ; Environmental Monitoring ; Water Pollutants, Chemical/analysis* ; Phosphorus/analysis* ; Spatial Analysis ; Nitrogen/analysis* ; Arsenic/analysis* ; Water Pollution/adverse effects* ; Female

OBJECTIVE: To explore the treatment of children with high-risk acute promyelocytic leukemia (APL), aiming to improve the prognosis. METHODS: The clinical datas of 24 children with high-risk APL in our hospital from January 2015 to June 2021 were retrospectively analyzed. RESULTS: The main manifestations of 24 children (including 15 males and 9 females) were purpura, gingiva bleeding and nasal hemorrhage, with a median age of 7 years old and a median leukocyte count of 28.98 (10-232)×10⁹/L, including 15 cases with leukocyte count between 10×10⁹/L and 50×10⁹/L, 2 cases between 50×10⁹/L and 100×10⁹/L, and 7 cases >100×10⁹/L. The leukocyte count of 2 cases in 3 children admitted from 2015 to November 2016 was >100×10⁹/L, in which 1 case was first treated with homoharringtonine for cytoreduction, 7 days later treated with all-trans retinoic acid (ATRA) after genetic diagnosis, then died of differentiation syndrome and pulmonary hemorrhage after 3 days. The other one was treated with reduced ATRA+daunorubicin+arsenic trioxide (ATO) for induction, then achieved complete remission. The third one with leukocyte count 12×10⁹/L had cerebral hemorrhage before admission and died on the 7th day of treatment. The remaining 21 children were treated with chemotherapy according to the APL regimen for children in South China, including 14 cases with leukocyte count between 10×10⁹/L and 50×10⁹/L, 2 cases between 50×10⁹/L and 100×10⁹/L, and 5 cases >100×10⁹/L. In the 5 children with leukocyte count >100×10⁹/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines, 3 cases died of cerebral hemorrhage after the addition of anthracyclines to chemotherapy on the second day of oral ATRA, and another one developed differentiation syndrome after the addition of mitoxantrone on the second day of oral ATRA, then achieved complete remission after ATRA reduction chemotherapy and survived without disease till now. In the 2 children with leukocyte count between 50×10⁹/L and 100×10⁹/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines. All the children were followed up until 1st August, 2021, with a median follow-up time of 40 months, including 7 deaths and 1 recurrence in maintenance therapy who achieved second remission after chemotherapy, 14 cases survived in 3 years and 13 cases survived without event. The 7 dead children had a median time from treatment to death of 5 days, including 1 case with leukocyte count between 10×10⁹/L and 50×10⁹/L, 1 case between 50×10⁹/L and 100×10⁹/L, and 5 cases >100×10⁹/L. CONCLUSION High-risk APL children with leukocyte count >100×10⁹/L have a high mortality rate. Gradual addition of chemotherapy starting at small doses and early addition of ATO may help to improve the prognosis.
Male ; Female ; Humans ; Child ; Leukemia, Promyelocytic, Acute/drug therapy* ; Retrospective Studies ; Arsenic Trioxide/therapeutic use* ; Tretinoin/therapeutic use* ; Remission Induction ; Anthracyclines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

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: Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome). METHODS: We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period. RESULTS: Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated. CONCLUSION Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
Rats ; Animals ; Arsenic/toxicity* ; Fluorides ; RNA, Ribosomal, 16S/genetics* ; Rats, Sprague-Dawley ; Metabolome ; Microbiota