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1.
ACS Synth Biol ; 2022 Apr 28.
Article in English | MEDLINE | ID: mdl-35481381

ABSTRACT

Objectives: Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants pose a great threat and burden to global public health. Here, we evaluated a clustered regularly interspaced short palindromic repeat-associated enzyme 12a (CRISPR-Cas12a)-based method for detecting major SARS-CoV-2 variants of concern (VOCs) in SARS-CoV-2 positive clinical samples. Methods: Allele-specific CRISPR RNAs (crRNAs) targeting the signature mutations in the spike protein of SARS-CoV-2 are designed. A total of 59 SARS-CoV-2 positive oropharyngeal swab specimens were used to evaluate the performance of the CRISPR-Cas12a-mediated assay to identify major SARS-CoV-2 VOCs. Results: Compared with Sanger sequencing, the eight allele-specific crRNAs analyzed can specifically identify the corresponding mutations with a positive predictive value of 83.3-100% and a negative predictive value of 85.7-100%. Our CRISPR-Cas12a-mediated assay distinguished wild-type and four major VOCs (Alpha, Beta, Delta, and Omicron) of SARS-CoV-2 with a sensitivity of 93.8-100.0% and a specificity of 100.0%. The two methods showed a concordance of 98.3% (58/59) with a κ value of 0.956-1.000, while seven (11.9%) samples were found to be positive for extra mutations by the CRISPR-based assay. Furthermore, neither virus titers nor the sequences adjacent to the signature mutations were associated with the variation of fluorescence intensity detected or the false-positive reaction observed when testing clinical samples. In addition, there was no cross-reaction observed when detecting 33 SARS-CoV-2 negative clinical samples infected with common respiratory pathogens. Conclusions: The CRISPR-Cas12a-based genotyping assay is highly sensitive and specific when detecting both the SARS-CoV-2 wild-type strain and major VOCs. It is a simple and rapid assay that can monitor and track the circulating SARS-CoV-2 variants and the dynamics of the coronavirus disease 2019 (COVID-19) pandemic and can be easily implemented in resource-limited settings.

2.
Ecotoxicol Environ Saf ; 236: 113494, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35413622

ABSTRACT

Cadmium could induce cell apoptosis, probably related to the dysfunction of the mitochondrial respiratory chain. The human renal proximal tubule (HK-2) was used to explore the mechanism of mitochondrial respiratory chain dysfunction during apoptosis induced by cadmium chloride (CdCl2). Cell viability was evaluated by cell proliferation assay and different concentrations of 60, 80 and 100 µM were selected to evaluate the mitochondrial toxicity of CdCl2 respectively. Under the CdCl2 treatment for 24 h, the mitochondrial reactive oxygen species (ROS) of HK-2 cells increased and the superoxide dismutase (SOD) activity was inhibited at the above three concentrations separately. Both ATP content and mitochondrial membrane potential decreased significantly at 100 µM concentration. The levels of procaspase-3 and Bcl-2 had fallen in a concentration-dependent manner and Bax was significantly increased at 60, 80 and 100 µM concentration compared with no CdCl2 treatment respectively, which activated the mitochondrial apoptosis pathway. N-acetyl-cysteine (NAC) could partially resist CdCl2-induced cell apoptosis, while myxothiazol (Myx) promoted the process. Mitochondria relative alterations manifested as inhibition of complex III and V. In addition, both the quantity of mitochondrial coenzyme Q-binding protein CoQ10 homolog B (CoQ10B) and cytochrome c (Cyt c) had decreased significantly. Taken together, CdCl2 induced HK-2 apoptosis due to the mitochondrial respiratory chain dysfunction by reducing the CoQ10B level, offering a novel evaluating indicator for the environmental toxicity of CdCl2.


Subject(s)
Apoptosis , Cadmium Chloride , Cadmium/toxicity , Cadmium Chloride/toxicity , Electron Transport , Humans , Membrane Potential, Mitochondrial , Oxidative Stress , Reactive Oxygen Species/metabolism
3.
Front Med (Lausanne) ; 9: 761060, 2022.
Article in English | MEDLINE | ID: mdl-35308488

ABSTRACT

Background: The Spring Festival is one of the most important traditional festivals in China. This study aimed to estimate the mortality risk attributable to the Spring Festival. Methods: Between 2013 and 2017, daily meteorological, air pollution, and mortality data were collected from 285 locations in China. The Spring Festival was divided into three periods: pre-Spring Festival (16 days before Lunar New Year's Eve), mid-Spring Festival (16 days from Lunar New Year's Eve to Lantern Festival), and post-Spring Festival (16 days after Lantern Festival). The mortality risk attributed to the Spring Festival in each location was first evaluated using a distributed lag nonlinear model (DLNM), and then it was pooled using a meta-analysis model. Results: We observed a dip/rise mortality pattern during the Spring Festival. Pre-Spring Festival was significantly associated with decreased mortality risk (ER: -1.58%, 95%CI: -3.09% to -0.05%), and mid-Spring Festival was unrelated to mortality risks, while post-Spring Festival was significantly associated with increased mortality risk (ER: 3.63%, 95%CI: 2.15-5.12%). Overall, a 48-day Spring Festival period was associated with a 2.11% (95%CI: 0.91-3.33%) increased mortality. We also found that the elderly aged over 64 years old, women, people with cardiovascular disease (CVD), and people living in urban areas were more vulnerable to the Spring Festival. Conclusion: Our study found that the Spring Festival significantly increased the mortality risk in China. These findings suggest that it is necessary to develop clinical and public health policies to alleviate the mortality burden associated with the Spring Festival.

4.
Front Public Health ; 10: 773271, 2022.
Article in English | MEDLINE | ID: mdl-35252083

ABSTRACT

BACKGROUND: Non-pharmaceutical interventions were implemented in most countries to reduce the transmission of COVID-19. We aimed to describe the incidence of influenza in four countries in the 2019-2020 season and examined the effect of these non-pharmaceutical interventions on the incidence of influenza. METHODS: We used the network surveillance data from 2015 to 2020 to estimate the percentage increase in influenza cases to explore the effect of non-pharmaceutical interventions implemented to control the COVID-19 on the incidence of influenza in China, the United States, Japan, and Singapore. RESULTS: We found that the incidence of influenza has been almost zero and reached a persistent near-zero level for a continuous period of six months since epidemiologic week 14 of 2020 in the four countries. Influenza incidence decreased by 77.71% and 60.50% in the early days of COVID-19 in the 2019-2020 season compared to the same period in preceding years in Japan and Singapore, respectively. Furthermore, influenza incidence decreased by 60.50-99.48% during the period of compulsory interventions in the 2019-2020 season compared to the same period in preceding years in the four countries. CONCLUSION: These findings suggest that the application of non-pharmaceutical interventions, even everyday preventive action, was associated with a reduction of influenza incidence, which highlights that more traditional public health interventions need to be reasserted and universalized to reduce influenza incidence.


Subject(s)
COVID-19 , Influenza, Human , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Humans , Incidence , Influenza, Human/epidemiology , Influenza, Human/prevention & control , SARS-CoV-2
5.
Ecotoxicol Environ Saf ; 231: 113180, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35026584

ABSTRACT

1,2-Dichloroethane (1,2-DCE) is a pervasive environmental pollutant, and overexposure to this hazardous material causes brain edema and demyelination in humans. We found that 1,2-DCE inhibits aquaporin 4 (AQP4) and is a primary pathogenic effector of 1,2-DCE-induced brain edema in animals. However, AQP4 down-regulation's link with cortex demyelination after 1,2-DCE exposure remains unclear. Thus, we exposed wild-type (WT) CD-1 mice and AQP4 knockout (AQP4-KO) mice to 0, 100, 350 and 700 mg/m3 1,2-DCE by inhalation for 28 days. We applied label-free proteomics and a cell co-culture system to elucidate the role of AQP4 inhibition in 1,2-DCE-induced demyelination. The results showed that 1,2-DCE down-regulated AQP4 in the WT mouse cortexes. Both 1,2-DCE exposure and AQP4 deletion induced neurotoxicity in mice, including increased brain water content, abnormal pathological vacuolations, and neurobehavioral damage. Tests for interaction of multiple regression analysis highlighted different effects of 1,2-DCE exposure level depending on the genotype, indicating the core role of AQP4 in regulation on 1,2-DCE-caused neurotoxicity. We used label-free quantitative proteomics to detect differentially expressed proteins associated with 1,2-DCE exposure and AQP4 inhibition, and identified down-regulation in myelin basic protein (MBP) and tyrosine-protein kinase Fyn (FYN) in a dose-dependent manner in WT mice but not in AQP4-KO mice. 1,2-DCE and AQP4 deletion separately resulted in demyelination, as detected by Luxol fast blue staining, and manifested as disordered nerve fibers and cavitation in the cortexes. Western blot and immunofluorescence confirmed the decreased AQP4 in the astrocytes and the down-regulated MBP in the oligodendrocytes by 1,2-DCE exposure and AQP4 inhibition, respectively. Finally, the co-culture results of SVG p12 and MO3.13 cells showed that 1,2-DCE-induced AQP4 down-regulation in the astrocytes was responsible for demyelination, by decreasing MBP in the oligodendrocytes. In conclusion, 1,2-DCE induced cortex demyelination by depressing MBP via AQP4 inhibition in the mice.


Subject(s)
Aquaporin 4 , Demyelinating Diseases , Animals , Aquaporin 4/genetics , Demyelinating Diseases/chemically induced , Ethylene Dichlorides/toxicity , Mice , Myelin Basic Protein/genetics
6.
Microbiol Spectr ; 9(3): e0101721, 2021 12 22.
Article in English | MEDLINE | ID: mdl-34787487

ABSTRACT

A big challenge for the control of COVID-19 pandemic is the emergence of variants of concern (VOCs) or variants of interest (VOIs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may be more transmissible and/or more virulent and could escape immunity obtained through infection or vaccination. A simple and rapid test for SARS-CoV-2 variants is an unmet need and is of great public health importance. In this study, we designed and analytically validated a CRISPR-Cas12a system for direct detection of SARS-CoV-2 VOCs. We further evaluated the combination of ordinary reverse transcription-PCR (RT-PCR) and CRISPR-Cas12a to improve the detection sensitivity and developed a universal system by introducing a protospacer adjacent motif (PAM) near the target mutation sites through PCR primer design to detect mutations without PAM. Our results indicated that the CRISPR-Cas12a assay could readily detect the signature spike protein mutations (K417N/T, L452R/Q, T478K, E484K/Q, N501Y, and D614G) to distinguish alpha, beta, gamma, delta, kappa, lambda, and epsilon variants of SARS-CoV-2. In addition, the open reading frame 8 (ORF8) mutations (T/C substitution at nt28144 and the corresponding change of amino acid L/S) could differentiate L and S lineages of SARS-CoV-2. The low limit of detection could reach 10 copies/reaction. Our assay successfully distinguished 4 SARS-CoV-2 strains of wild type and alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2) variants. By testing 32 SARS-CoV-2-positive clinical samples infected with the wild type (n = 5) and alpha (n = 11), beta (n = 8), and delta variants (n = 8), the concordance between our assay and sequencing was 100%. The CRISPR-based approach is rapid and robust and can be adapted for screening the emerging mutations and immediately implemented in laboratories already performing nucleic acid amplification tests or in resource-limited settings. IMPORTANCE We described CRISPR-Cas12-based multiplex allele-specific assay for rapid SARS-CoV-2 variant genotyping. The new system has the potential to be quickly developed, continuously updated, and easily implemented for screening of SARS-CoV-2 variants in resource-limited settings. This approach can be adapted for emerging mutations and implemented in laboratories already conducting SARS-CoV-2 nucleic acid amplification tests using existing resources and extracted nucleic acid.


Subject(s)
COVID-19 Testing/methods , COVID-19/virology , CRISPR-Cas Systems , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Alleles , COVID-19/diagnosis , Databases, Nucleic Acid , Humans , Mass Screening , Mutation , Polymerase Chain Reaction , Public Health , Spike Glycoprotein, Coronavirus/genetics
7.
Toxicol Lett ; 354: 1-13, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34718095

ABSTRACT

Aurantio-obtusin (AO) is a major anthraquinone (AQ) compound derived from Cassiae semen (CS). Although pharmacological studies have shown that the CS extracts can serve as effective agents in preclinical and clinical practice, AQ-induced hepatotoxicity in humans has attracted widespread attention. To explore whether AO induces hepatotoxicity and its underlying mechanisms, we exposed larval zebrafish and mice to AO. We found that AO delayed yolk sac absorption, and increased liver area and inflammation in the larval zebrafish. This inflammation was manifested as an increase in liver neutrophils and the up-regulated mRNA expression of interleukin-6 (Il-6) and tumor necrosis factor-α (Tnf-α) in the larval zebrafish. Furthermore, a pharmacokinetics study showed that AO was quickly absorbed into the blood and rapidly metabolized in the mice. Of note, AO induced hepatotoxicity in a gender-dependent manner, characterized by liver dysfunction, increased hepatocyte necrosis with inflammatory infiltration, and up-regulated mRNAs of Il-6, Tnf-α and monocyte chemotactic protein 1(Mcp1) in the female mice after 28-day oral administration. It also highlighted that AO triggered NOD-like receptor protein (NLRP) signaling in the female mice, as evidenced by the increased NLRP3, Caspase-1, pro-IL-1ß, IL-1ß and IL-18. Finally, we found that AO led to a significant increase in potassium calcium-activated channel, subfamily N, member 4 (KCNN4) and reactive oxygen species (ROS) levels, along with decreased nuclear factor kappa B p65 (NF-κB p65), in the female mouse livers. In conclusion, AO induced hepatotoxicity by activating NLRP3 inflammasome signaling, at least in part, through increased KCNN4 and ROS production, and NF-κB inhibition.


Subject(s)
Anthraquinones/toxicity , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/physiopathology , Inflammasomes/metabolism , Inflammation/chemically induced , Inflammation/physiopathology , Zebrafish/metabolism , Animals , Cassia/chemistry , Disease Models, Animal , Drugs, Chinese Herbal/toxicity , Female , Humans , Larva/drug effects , Mice , Signal Transduction/drug effects
8.
Front Cell Infect Microbiol ; 11: 729756, 2021.
Article in English | MEDLINE | ID: mdl-34660342

ABSTRACT

Background: Hand, foot and mouth disease (HFMD) is an acute enterovirus-induced disease. Gut microbiota dysbiosis has been identified as a factor that plays an important role in enteral virus infection, but the gut microbiota profile in hand, foot and mouth disease has rarely been studied in a large population. Methods: A total of 749 children (HFMD: n = 262, healthy control: n = 487) aged 2 to 7 years were recruited from hospitals and communities in the period from May to July, 2017. Clinical and demographical information was collected by trained personnel, and fecal samples were collected and processed for 16S ribosomal RNA(rRNA) gene sequencing. Results: We observed a significant alteration in the microbiota profile of children with HFMD compared with that of control children. Patients with enteroviruses A71(EV71) positive had more dysbiotic gut microbiota than those with coxsackievirus A16 (CAV16) positive. We found that Prevotella and Streptococcus were enriched in children with HFMD, whereas beneficial bacteria, including Bifidobacterium and Faecalibacterium, were depleted. Children with synbiotics supplements had lower risk of HFMD and we observed that the gut microbiota of HFMD patients who were administered synbiotics exhibited potential resistance to the dysbiosis detected in HFMD. Conclusions: This study suggested that the gut microbiota of patients with hand, foot and mouth disease exhibits dysbiosis and that synbiotics supplements potentially helps maintain the homeostasis of the gut flora.


Subject(s)
Enterovirus A, Human , Enterovirus , Gastrointestinal Microbiome , Hand, Foot and Mouth Disease , Synbiotics , Child , China , Dysbiosis , Hand, Foot and Mouth Disease/prevention & control , Humans , Infant
9.
Toxicol Appl Pharmacol ; 430: 115728, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34560092

ABSTRACT

1,2-Dichloroethane (1,2-DCE) is a pervasive environmental pollutant found in ambient and residential air, as well as ground and drinking water. Overexposure to it results in cortex edema, in both animals and humans. 1,2-DCE induces apoptosis in the cerebellum, liver and testes. This promotes the hypothesis that 1,2-DCE may induce apoptosis in the cortex as brain edema progresses. To validate our hypothesis, 40 NIH male mice were exposed to 0, 100, 350, 700 mg/m3 1,2-DCE by whole-body dynamic inhalation for 28 consecutive days. MicroRNA (miRNA) and mRNA microarray combined with TdT-mediated dUTP nick-end labeling, flow cytometry, and mitochondrial membrane potential (mtΔΨ) measurement were applied to identify the cortex apoptosis pathways' specific responses to 1,2-DCE, in vitro and in vivo. The results showed that 1,2-DCE caused brain edema and increased apoptosis in the mouse cortexes. We confirmed that 1,2-DCE induced increased apoptosis via mitochondrial pathway, both in vitro and in vivo, as evidenced by increased Caspase-3, cleaved Caspase-3, Cytochrome c and Bax expression, and decreased Bcl-2 expression. Additionally, mtΔΨ decreased after 1,2-DCE treatment in vitro. 1,2-DCE exposure increased miR-182-5p and decreased phospholipase D1 (PLD1) in the cerebral cortex of mice. MiR-182-5p overexpression and PLD1 inhibition reduced mtΔΨ and increased astrocyte apoptosis, yet miR-182-5p inhibition alleviated the 1,2-DCE-induced PLD1 down-regulation and the increased apoptosis. Finally, PLD1 was confirmed to be a target of miR-182-5p by luciferase assay. Taken together, our findings indicate that 1,2-DCE exposure induces apoptosis in the cortex via a mitochondria-dependent pathway. This pathway is regulated by a miR-182-5p⊣PLD1 axie.


Subject(s)
Apoptosis/drug effects , Brain Edema/chemically induced , Cerebral Cortex/drug effects , Environmental Pollutants/toxicity , Ethylene Dichlorides/toxicity , MicroRNAs/metabolism , Mitochondria/drug effects , Phospholipase D/metabolism , Animals , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Brain Edema/enzymology , Brain Edema/genetics , Brain Edema/pathology , Cell Line , Cerebral Cortex/enzymology , Cerebral Cortex/pathology , Disease Progression , Male , Membrane Potential, Mitochondrial/drug effects , Mice , MicroRNAs/genetics , Mitochondria/enzymology , Mitochondria/genetics , Mitochondria/pathology , Phospholipase D/genetics , Signal Transduction
10.
Arch Toxicol ; 95(11): 3497-3513, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34510229

ABSTRACT

Cadmium (Cd) has been reported to induce kidney damage by triggering oxidative stress and inflammation. The NLR family Pyrin Domain Containing 3 (NLRP3) inflammasome has been implicated a role in the pathogenesis of inflammation. However, the connection between Cd and NLRP3 inflammasome in the development of renal inflammation remains unknown. In this study, in vitro experiments based on the telomerase-immortalized human renal proximal-tubule epithelial cell line (RPTEC/TERT1) were carried out. Results revealed that CdCl2 (2-8 µM) increased ROS production and activated NLRP3, thereby enhancing secretion of IL-1ß and IL-18 (P < 0.05). Knock-down of NLRP3 rescued the RPTEC/TERT1 cells from Cd-induced inflammatory damage. Cd activated the MAPK/NF-κB signaling pathway in RPTEC/TERT1 cells (P < 0.05). In addition, treatment with N-acetylcysteine (NAC) improved inflammation and blocked the upregulation of the MAPK/NF-κB signaling pathway. Pre-treatment with MAPK and NF-κB inhibitors also suppressed NLRP3 inflammasome activation (P < 0.05). Moreover, CdCl2 (25-00 mg/L) stimulated the MAPK/NF-κB signaling pathway, activated the NLRP3 inflammasome, and increased inflammatory response (P < 0.05) leading to renal injury in rats. Exposure to cadmium elevated serum levels of NLRP3 and IL-1ß in populations (P < 0.05). Further analysis found that serum NLRP3 and IL-1ß levels were positively correlated with urine cadmium (UCd) and urine N-acetyl-ß-D-glucosaminidase (UNAG). Overall, Cd induced renal inflammation through the ROS/MAPK/NF-κB signaling pathway by activating the NLRP3 inflammasome. Our research thus provides new insights into the molecular mechanism that NLRP3 contributes to Cd-induced kidney damage.


Subject(s)
Acute Kidney Injury/chemically induced , Cadmium/toxicity , Inflammation/etiology , Kidney/drug effects , Animals , Cadmium/urine , Cell Line, Transformed , Female , Humans , Inflammasomes , Kidney/pathology , Kidney Tubules, Proximal , Mitogen-Activated Protein Kinase Kinases/metabolism , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Signal Transduction
11.
J Hazard Mater ; 420: 126550, 2021 10 15.
Article in English | MEDLINE | ID: mdl-34252664

ABSTRACT

The critical health risks caused by cadmium (Cd) via dietary exposure are commonly assessed by detecting Cd concentrations in foods. Differently, in this study, the bioaccessibility and bioavailability of Cd in major local harvests were introduced to assess the dietary exposure of local residents from a high-level environmental Cd region. The results indicated that certain Cd was released into the digestive juice after in vitro digestion with a bioaccessibility of 20-63% for rice and 3-32% for leafy vegetables, and the released portion was partially absorbed by Caco-2 cells with a bioavailability of 2-21% for rice and 0.2-13% for leafy vegetables. The results obtained from the toxicokinetic model revealed that the predicted urinary Cd values from the estimated daily intake (EDI) of Cd, which accounted for bioaccessibility and bioavailability, were consistent with the actual measured values, and the EDIs were considerably lower than the acceptable daily intake. This suggests that the bioaccessibility and bioavailability adjusted dietary Cd exposure should be more precise. The key issues addressed in our study implores that a potential health risk cannot be neglected in people with high consumption of rice from high-level zone.


Subject(s)
Cadmium , Soil Pollutants , Biological Availability , Caco-2 Cells , Cadmium/analysis , Cadmium/toxicity , Dietary Exposure , Food Contamination/analysis , Humans , Soil Pollutants/analysis , Soil Pollutants/toxicity
12.
Aging (Albany NY) ; 13(13): 17211-17226, 2021 07 01.
Article in English | MEDLINE | ID: mdl-34197336

ABSTRACT

Saxitoxin (STX), as a type of paralytic shellfish poisoning (PSP), is gaining widespread attention due to its long existence in edible shellfish. However, the mechanism underlying STX chronic exposure-induced effect is not well understood. Here, we evaluated the neurotoxicity effects of long-term low-dose STX exposure on C57/BL mice by behavioral tests, pathology analysis, and hippocampal proteomics analysis. Several behavioral tests showed that mice were in a cognitive deficiency after treated with 0, 0.5, 1.5, or 4.5 µg STX equivalents/kg body weight in the drinking water for 3 months. Compared with control mice, STX-exposed mice exhibited brain neuronal damage characterized by decreasing neuronal cells and thinner pyramidal cell layers in the hippocampal CA1 region. A total of 29 proteins were significantly altered in different STX dose groups. Bioinformatics analysis showed that protein phosphatase 1 (Ppp1c) and arylsulfatase A (Arsa) were involved in the hippo signaling pathway and sphingolipid metabolism pathway. The decreased expression of Arsa indicates that long-term low doses of STX exposure can cause neuronal inhibition, which is a process related to spatial memory impairment. Taken together, our study provides a new understanding of the molecular mechanisms of STX neurotoxicity.


Subject(s)
Neurotoxicity Syndromes/pathology , Saxitoxin/toxicity , Animals , Behavior, Animal/drug effects , CA1 Region, Hippocampal/pathology , Cognition Disorders/chemically induced , Cognition Disorders/psychology , Dose-Response Relationship, Drug , Hippocampus/drug effects , Hippocampus/metabolism , Memory Disorders/chemically induced , Memory Disorders/psychology , Mice , Mice, Inbred C57BL , Neurons/pathology , Neurotoxicity Syndromes/psychology , Proteomics , Pyramidal Cells/pathology
13.
Part Fibre Toxicol ; 18(1): 20, 2021 06 07.
Article in English | MEDLINE | ID: mdl-34098985

ABSTRACT

BACKGROUND: Micro- and nanoplastic pollution has become a global environmental problem. Nanoplastics in the environment are still hard to detect because of analysis technology limitations. It is believed that when microplastics are found in the environment, more undetected nanoplastics are around. The current "microplastic exposure" is in fact the mixture of micro- and nanoplastic exposures. Therefore, the biological interaction between organisms among different sizes of micro- and nanoplastics should not be neglected. RESULTS: We measured the biodistribution of three polystyrene (PS) particles (50 nm PS, PS50; 500 nm PS, PS500; 5000 nm PS, PS5000) under single and co-exposure conditions in mice. We explored the underlying mechanisms by investigating the effects on three major components of the intestinal barrier (the mucus layer, tight junctions and the epithelial cells) in four intestine segments (duodenum, jejunum, ileum and colon) of mice. We found that the amounts of both PS500 and PS5000 increased when they were co-exposed with PS50 for 24 h in the mice. These increased amounts were due primarily to the increased permeability in the mouse intestines. We also confirmed there was a combined toxicity of PS50 and PS500 in the mouse intestines. This manifested as the mixture of PS50 and PS500 causing more severe dysfunction of the intestinal barrier than that caused by PS50 or PS500 alone. We found that the combined toxicity of PS micro- and nanoplastics on intestinal barrier dysfunction was caused primarily by reactive oxygen species (ROS)-mediated epithelial cell apoptosis in the mice. These findings were further confirmed by an oxidants or antioxidants pretreatment study. In addition, the combined toxicity of PS micro- and nanoplastics was also found in the mice after a 28-day repeated dose exposure. CONCLUSIONS: There is a combined toxicity of PS50 and PS500 in the mouse intestines, which was caused primarily by ROS-mediated epithelial cell apoptosis in the mice. Considering that most recent studies on PS micro- and nanoplastics have been conducted using a single particle size, the health risks of exposure to PS micro- and nanoplastics on organisms may be underestimated.


Subject(s)
Microplastics , Polystyrenes , Animals , Apoptosis , Epithelial Cells , Mice , Microplastics/toxicity , Plastics , Polystyrenes/toxicity , Reactive Oxygen Species , Tissue Distribution
14.
BMC Public Health ; 21(1): 796, 2021 04 26.
Article in English | MEDLINE | ID: mdl-33902517

ABSTRACT

BACKGROUND: We investigated college students' attitude and compliance towards a prevention strategy involving use of non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19). METHODS: We conducted a cross-sectional online survey in four universities in Guangdong Province (China) based on purposive sampling. A self-administered questionnaire was given to College students (CSs) to measure the supportive attitude towards an outbreak control strategy and adoption of NPIs in respondents. RESULTS: A total of 44,446 CSs participated between 31 January and 10 February 2020; 92.7% of respondents supported the outbreak control strategy. The proportion of respondents who avoided public places, wore a facemask, avoid gatherings, and washed hands more frequently than usual was 94.8, 92.8, 91.2 and 86.9%. respectively. A total of 76.5% respondents adopted all four measures. A supportive attitude was associated with NPI adoption. Students who were female, postgraduate, anxious, and not depressed tended to have a higher supportive attitude and higher chance of NPI adoption. CONCLUSIONS: Higher supportiveness towards the disease control strategy for the Chinese public may lead to higher adoption rate of NPIs. Psychosocial factors were related to a supportive attitude and adoption of the NPI. We believe that our findings could aid policymakers to create NPIs to prevent and control emerging infectious diseases such as COVID-19.


Subject(s)
COVID-19 , China , Cross-Sectional Studies , Female , Humans , Male , SARS-CoV-2 , Students , Surveys and Questionnaires
15.
Ecotoxicol Environ Saf ; 216: 112204, 2021 Apr 09.
Article in English | MEDLINE | ID: mdl-33845364

ABSTRACT

The mitoepigenetic modifications may be closely related to cellular fate. Both the replicative and hydrogen peroxide (H2O2)-induced premature senescence models were used to detect the mitochondrial biological characteristics and the epigenetic factors during senescence of human embryonic lung fibroblasts. The mitochondrial quantity was decreased in two senescence stages, while the mitochondrial DNA (mtDNA) copy number was increased significantly and the methyltransferases activity likewise. And the acute mtROS accumulation could launch premature senescence. Later, the persistent premature senescence owned the higher level of adenosine triphosphate (ATP) and mitochondrial 5-methylcytosine (mt-5-mC), and the less level of 8-hydroxydeoxyguanosine (8-OHdG) than those of replicative senescence. The mtDNA methylation-related enzymes, binding protein and the mitochondrial transcription regulators presented the differentially expressed profiles in both senescent states. Interestingly, the hypermethylation in the CpG region of mitochondrial transcription factor B2 (TFB2M) contributed to its downregulation of mRNA level in replicative senescence. The alterations of the mitochondrial biological functions and mtDNA features would be novel candidate biomarkers involved in cellular senescence. The specific methylation status of mtDNA may also have a crosstalk with oxidative stress to the mitochondrial function, contributing to cellular senescence.

16.
J Food Sci ; 86(3): 1132-1143, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33598948

ABSTRACT

As a persistent organic pollutant, pentachlorophenol (PCP) has serious impacts on human health. However, its presence in animal source food products sold in the Guangdong Province (GD) of China, and the resultant dietary exposure have not been elucidated. To address this gap, 3,100 samples from seven food categories, including beef, pork, mutton, offals, broilers, hen eggs, and farmed freshwater fish, marketed throughout four geographical regions of GD, were collected from 2015 to 2018. Gas chromatography coupled with mass spectrometry was employed to detect PCP levels in these food matrices. PCP was found in all food categories, but the average contamination levels were low, ranging from 0.40 µg/kg wet weight (ww) (hen eggs) to 5.85 µg/kg ww (offals). However, higher concentrations of PCP were detected (P < 0.05) in animal source food from the North region. Additionally, a temporal declining trend was observed in this four-year consecutive survey. The estimated human dietary exposure of PCP to population groups, including the general population and subgroups (male and female, children, and adults), was found to be far below the permissible daily intake (3 µg/kg body weight). Therefore, the health impacts of PCP should be correspondingly low for local residents, based on current toxicological knowledge. Regional exposure patterns varied due to different extents of contamination in the four areas, and pork, broilers, and freshwater fish were the major sources of dietary PCP exposure. PRACTICAL APPLICATION: As a persistent organic pollutant, pentachlorophenol (PCP) has serious impacts on human health. However, its presence in animal source food products sold in Guangdong Province of China, and the resultant dietary exposure have not been elucidated. In this study, we conducted an in-depth investigation on the occurrence of PCP in major foodstuff categories, including beef, pork, mutton, broilers, offals, hen eggs, and farmed freshwater fish, marketed in all 21 prefecture-level divisions of Guangdong Province, in order to provide integral insights for regulatory authorities.


Subject(s)
Dietary Exposure/analysis , Food Contamination/analysis , Meat/analysis , Pentachlorophenol/analysis , Risk Assessment/methods , Adult , Animals , Child , China , Dietary Exposure/adverse effects , Female , Fishes/metabolism , Food Analysis , Humans , Livestock/metabolism , Male , Pentachlorophenol/adverse effects , Poultry/metabolism
17.
Lancet Reg Health West Pac ; 8: 100094, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33585828

ABSTRACT

BACKGROUND: China implemented containment measures to stop SARS-CoV-2 transmission in response to the COVID-19 epidemic. After the first epidemic wave, we conducted population-based serological surveys to determine extent of infection, risk factors for infection, and neutralization antibody levels to assess the real infections in the random sampled population. METHODS: We used a multistage, stratified cluster random sampling strategy to conduct serological surveys in three areas - Wuhan, Hubei Province outside Wuhan, and six provinces selected on COVID-19 incidence and containment strategy. Participants were consenting individuals >1 year old who resided in the survey area >14 days during the epidemic. Provinces screened sera for SARS-CoV-2-specific IgM, IgG, and total antibody by two lateral flow immunoassays and one magnetic chemiluminescence enzyme immunoassay; positive samples were verified by micro-neutralization assay. FINDINGS: We enrolled 34,857 participants (overall response rate, 92%); 427 were positive by micro-neutralization assay. Wuhan had the highest weighted seroprevalence (4•43%, 95% confidence interval [95%CI]=3•48%-5•62%), followed by Hubei-ex-Wuhan (0•44%, 95%CI=0•26%-0•76%), and the other provinces (<0•1%). Living in Wuhan (adjusted odds ratio aOR=13•70, 95%CI= 7•91-23•75), contact with COVID-19 patients (aOR=7•35, 95%CI=5•05-10•69), and age over 40 (aOR=1•36, 95%CI=1•07-1•72) were significantly associated with SARS-CoV-2 infection. Among seropositives, 101 (24%) reported symptoms and had higher geometric mean neutralizing antibody titers than among the 326 (76%) without symptoms (30±2•4 vs 15±2•1, p<0•001). INTERPRETATION: The low overall extent of infection and steep gradient of seropositivity from Wuhan to the outer provinces provide evidence supporting the success of containment of the first wave of COVID-19 in China. SARS-CoV-2 infection was largely asymptomatic, emphasizing the importance of active case finding and physical distancing. Virtually the entire population of China remains susceptible to SARS-CoV-2; vaccination will be needed for long-term protection. FUNDING: This study was supported by the Ministry of Science and Technology (2020YFC0846900) and the National Natural Science Foundation of China (82041026, 82041027, 82041028, 82041029, 82041030, 82041032, 82041033).

18.
Ecotoxicol Environ Saf ; 211: 111897, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33493719

ABSTRACT

Chronic cadmium (Cd) toxicity is a significant health concern, and the mechanism of long-term low-dose Cd exposure on bone has not been fully elucidated yet. This study aimed to assess the association between long-term environmental Cd exposure and bone remodeling in women who aged over 50. A total of 278 non-smoking subjects from Cd-polluted group (n = 191) and non-Cd polluted group (n = 87) were investigated. Bone mineral density (BMD), the levels of three bone turnover markers (BTMs), including total procollagen type 1 amino-terminal propeptide (P1NP), collagen type 1 cross-linked C-telopeptide (ß-CTX), bone-specific alkaline phosphatase (BALP), together with serum soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin (OPG) were determined. Early markers of renal dysfunction were measured as well. Urinary Cd concentrations ranged from 0.41 to 87.31 µg/g creatinine, with a median of 4.91 µg/g creatinine. Age, BMD, T-score, and prevalence of osteoporosis showed no statistical differences among the quartiles of urinary Cd concentrations, while serum levels of P1NP, ß-CTX, and OPG were higher in the upper quartiles. Multivariate linear regression models indicated significantly positive associations of urinary Cd concentration with serum levels of P1NP, ß-CTX, BALP, sRANKL, and OPG. A ridge regression analysis with T-score and the three BTMs, sRANKL, and OPG, adjusted for age and body mass index (BMI), indicated that except for age and Cd exposure, ß-CTX was a predictor of T-score. These findings demonstrated that Cd may directly accelerate bone remodeling. Serum ß-CTX might be an appropriate biochemical marker for evaluating and monitoring Cd-related bone loss. Capsule: Cadmium (Cd) may directly accelerate bone remodeling and serum ß-CTX is a valuable biochemical marker for evaluating Cd-related bone loss.


Subject(s)
Bone Remodeling , Cadmium/blood , Environmental Exposure/statistics & numerical data , Environmental Pollutants/blood , Adult , Aged , Alkaline Phosphatase , Biomarkers/blood , Body Mass Index , Bone Density , Bone and Bones , Collagen Type I , Female , Humans , Middle Aged , Osteoporosis/blood , Osteoprotegerin , Peptides , RANK Ligand/blood
19.
Sci Total Environ ; 769: 144649, 2021 May 15.
Article in English | MEDLINE | ID: mdl-33493913

ABSTRACT

The blood lead levels (BLLs) of children in China remain notably high in many areas. We aimed to summarise the relevant regional characteristics, identifying problematic areas and the causes of lead pollution. We searched the databases of PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Data, systematically reviewing 219 articles published from January 2010 to September 2020. In doing so, we assessed the BLLs noted in 220 prefectures across China. Data were organised using Geographic Information Systems (GIS) mapping. Out of a total of 629,627 children sampled, we found that the average blood lead level (BLL) of children included in our study is 50.61 ± 13.63 µg/L, which slightly exceeds the 50.00 µg/L US standard. Within the sample, 8.75% had BLLs higher than 100.00 µg/L. Children living in Liaoning, Hebei, Shanxi, Jiangxi, Anhui, Fujian, Guizhou, Yunnan, and Guangxi had notably high BLLs, at more than 60.00 µg/L. A total of 112 municipalities had an average children's BLL above 50.00 µg/L. Furthermore, Chenzhou, Linfen, Yuncheng, and Hechi had the highest children's BLLs, with average values above 100.00 µg/L. The leading contributors to lead pollution are lead mining, lead recovery and the smelting industry. Nonetheless, the lead-acid battery industry needs more attention. Although data suggest that BLLs are decreasing in China, many areas still have high BLLs that need to be monitored. Moreover, national standards must improve to decrease acceptable BLL thresholds for children.


Subject(s)
Lead Poisoning , Lead , Child , China , Cities , Environmental Exposure , Humans , Lead Poisoning/epidemiology
20.
Phytother Res ; 2021 Jan 13.
Article in English | MEDLINE | ID: mdl-33440461

ABSTRACT

The continued global rise in papillary thyroid carcinoma (PTC) combined with potential adverse effects of regular treatments calls for an alternative therapy. Prunella vulgaris L. (PV) is commonly used as a herbal remedy for thyroid diseases in China, but its influence on PTC is unclear. This study investigated the effect of PV aqueous extract on PTC and its underlying mechanism using a mouse xenograft model and the human PTC cell line K1. PV suppressed tumor growth in PTC-bearing mice at 0.05 and 0.1 g/kg bw, accompanied by improvements in autophagy-related protein expressions in xenografts. In K1 cells, PV inhibited cell growth and induced autophagic flux, manifesting as changes in autophagy-related proteins, the presence of autophagosomes, and a further increase in LC3-II by co-incubation with bafilomycin A1. Autophagy inhibitor 3-methyladenine ameliorated the autophagic cell death caused by PV. The mammalian target of rapamycin (mTOR) activator MHY1485 blocked the antiproliferative activity of PV by regulating mTOR, unc-51-like autophagy activating kinase 1 (ULK1), autophagosomes formation, and autophagy-related proteins. The adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C attenuated PV-induced inhibition of mTOR. Our results suggest that PV inhibits the growth of PTC in vivo and in vitro via autophagy, which is associated with the AMPK/mTOR/ULK1 pathway. Thus, PV has the potential to function as a therapeutic agent against PTC.

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