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1.
Virol Sin ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411169

RESUMO

African swine fever (ASF) is an infectious disease caused by African swine fever virus (ASFV) with clinical symptoms of high fever, hemorrhages and high mortality rate, posing a threat to the global swine industry and food security. Quarantine and control of ASFV is crucial for preventing swine industry from ASFV infection. In this study, a recombinase polymerase amplification (RPA)-CRISPR-based nucleic acid detection method was developed for diagnosing ASF. As a highly sensitive method, RPA-CRISPR can detect even a single copy of ASFV plasmid and genomic DNA by determining fluorescence signal induced by collateral cleavage of CRISPR-lwCas13a (previously known as C2c2) through quantitative real-time PCR (qPCR) and has the same or even higher sensitivity than the traditional qPCR method. A lateral flow strip was developed and used in combination with RPA-CRISPR for ASFV detection with the same level of sensitivity of TaqMan qPCR. Likewise, RPA-CRISPR is capable of distinguishing ASFV genomic DNA from viral DNA/RNA of other porcine viruses without any cross-reactivity. This diagnostic method is also available for diagnosing ASFV clinical DNA samples with coincidence rate of 100% for both ASFV positive and negative samples. RPA-CRISPR has great potential for clinical quarantine of ASFV in swine industry and food security.

2.
Int Immunopharmacol ; 92: 107346, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412390

RESUMO

AIM: Due to the significant increase in the antimicrobial resistance of Acinetobacter baumannii (A. baumannii), new drugs to block the progression of infection are strongly needed. Epigallocatechin-3-gallate (EGCG), a major component of green tea, has exhibited potential activity against A. baumannii in vitro. The aim of this study was to determine if EGCG could be used for pretreating stress-related effects, liver damage, and immune dysfunction caused by A. baumannii infection in vivo. METHODS: Levels of stress hormones, oxidative stress, liver damage, and immune components were analyzed in a murine infection model in which the mice were pretreated with EGCG for one week then intranasally inoculated with A. baumannii. The mice were restrained for 12 h to promote infection because A. baumannii is an opportunistic pathogen. The pretreatment efficacy of EGCG against A. baumannii in mice was assessed for 24 h after the bacterial infection. RESULTS: Restraint stress strengthened the damage from the A. baumannii infection. Pretreatment with EGCG in the murine pneumonia model markedly reduced stress hormones, oxidative metabolites, and proinflammatory cytokine production. EGCG also increased the immune function by increasing the levels of sIgA, T cells and neutrophils after infection. Moreover, pretreatment with EGCG significantly decreased the liver damage by inhibiting the levels of transaminases, oxidative stress metabolites, and cytokines, while maintaining the normal activity of CYP450 enzymes in the liver. CONCLUSION: EGCG was efficacious as a preventative treatment for the damage seen in an experimental model of A. baumannii infection.

3.
Ecotoxicol Environ Saf ; 208: 111656, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396170

RESUMO

Although copper is among the indispensable trace elements in animal physiological processes, it exerts toxicity upon over-exposure. The present study aimed to investigate hepatocyte autophagy induced by CuSO4 and its potential mechanism. A total of 240 ICR mice (four-week-old, 120 males and 120 females) were randomly divided into four groups, in which mice separately received 0, 4, 8, and 16 mg/kg of Cu (Cu2+-CuSO4) for 42 d. The results of increased autophagosomes and autophagy marker LC3B brown cell staining showed that excessive intake of Cu enhanced hepatocyte autophagy. Simultaneously, Cu inhibited the activity of mTOR through suppressing mRNA and protein expressions in mTOR, which in turn up-regulated expression levels of ULK1 and initiated autophagy. Also, over-exposure to Cu increased mRNA and protein expressions of Beclin1, Atg12, Atg5, Atg16L1, Atg7, Atg3, and LC3 and decreased mRNA and protein expressions of p62. These results indicate that excess Cu can enhance hepatocyte autophagy via inhibiting the mTOR signaling pathway and regulating mRNA and protein expressions of factors implicated to autophagy in mice.

4.
Food Microbiol ; 93: 103605, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32912580

RESUMO

This work aimed to determine the effects of partial substitution of NaCl with 0% (control), 30%, 50%, and 70% of KCl on the bacterial communities, proteolysis and lipid oxidation of Chinese bacon during processing. The proportion of genus Lactobacillus increased from 22.45% (fresh meat) to 72.78%, 81.64%, 76.53% and 85.63% at the end of processing for 0%, 30%, 50% and 70% KCl replacement samples, respectively. During the processing, Lactobacillus gradually became the dominant one, and higher the KCl ratio, more rapid was the process. After salting, the TBARS of control was markedly higher (P < 0.05) than that of the others, while a similar lipid oxidation level (P > 0.05) was observed at the end of processing for different groups. After salting, there was no difference in total free amino acids (TFAA) content among four treatments (P > 0.05), whereas KCl replacement samples shared significantly higher (P < 0.05) values than control at the end of processing. Redundancy analysis and Pearson correlation showed positive correlation between Lactobacillus versus TBARS and TFAA. Partial replacement of NaCl with KCl could, directly or subsequently by promoting the growth of Lactobacillus, influence proteolysis and lipid oxidation over the manufacturing process.

5.
J Hazard Mater ; 402: 123462, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32683155

RESUMO

Mobile metal Cu colloids can be formed in periodically flooded paddy soils, potentially aggravating the risks to rice cultivated in these soils. Here, we investigated the formation and fate of Cu colloids in flooded soil as influenced by soil reducible sulfate and temperature. In microcosms with different initial sulfate availability (1.30, 5.34, or 7.38 mmol/kg), we found the treatments with higher sulfate concentrations showed the greater and faster release of metal colloids. Sulfate reduction resulted in the transformation of copper in the colloids from Cu(0) to CuxS, and the percentage of CuxS in the colloid phase increased with increasing sulfate content according to the Cu K-edge EXAFS spectra. The batch experiments incubated at 5, 25 or 35 °C proved that high temperature enhanced the microbial activity and released more Cu colloids during flooding. The colloid formation was delayed at low temperature but persisted longer in the soil, which led to greater particle average size because of slow growth and uniform agglomeration. Low temperature appeared to only influence the formation and growth but not the speciation of Cu colloids. Our results highlight the importance of soil reducible sulfate and temperature in mediating the dynamics of colloidal metals in flooded soil.

6.
J Agric Food Chem ; 69(1): 146-158, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33356234

RESUMO

The aim of this study was to isolate the angiotensin I-converting enzyme (ACE) inhibitory peptides from the skirt of Chlamys farreri fermented with Bacillus natto and to explore the antihypertension effect through in vivo studies. ACE inhibitory peptides were purified from the fermentation mixture by ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography sequentially. The amino acids' sequence of the five novel ACE inhibitory peptides were identified by liquid chromatography-tandem mass spectrometry. Animal experiments demonstrated that the novel ACE inhibitory peptides significantly reduced the blood pressure in spontaneously hypertensive rats after a single or long-time treatment. Potential mechanisms were explored, and the results indicated that the novel peptides could regulate the renal renin-angiotensin system, improve vascular remodeling, inhibit myocardial fibrosis, and rebalance the gut microbial dysbiosis. Our results suggest that the fermentation products of the Chlamys farreri skirt by B. natto are potential sources of active peptides processing antihypertension activities.

7.
J Hazard Mater ; 401: 123438, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32763717

RESUMO

Cadmium (Cd), a well-known environmental pollutant, can lead to placental insufficiency and fetal growth restriction. However, the underlying mechanism is unknown. The purpose of our study is to explore the effect of Cd on placental angiogenesis and its mechanism using in vitro and in vivo models. Results found that gestational Cd exposure obviously decreased placental weight and impaired placental vascular development in mice. Correspondingly, Cd exposure evidently downregulated the expression of VEGF-A protein (a key indicator of angiogenesis) and progesterone receptor (PR) in placental trophoblasts. Further experiment showed that lentivirus PR overexpression reversed Cd-caused the reduction of VEGF-A level in human placental trophoblasts. In addition, Cd significantly reduced progesterone level, down-regulated the expression of key progesterone synthase (StAR, CYP11A1), and activated mitochondrial stress response and GCN-2/p-eIF2α signaling in placental trophoblasts. Additional experiment showed that GCN-2 siRNA pretreatment markedly alleviated Cd-activated mitochondrial stress response, restored Cd-downregulated the expression of CYP11A1, reversed Cd-reduced the level of progesterone and VEGF-A in human placental trophoblasts. Finally, our case-control study confirmed that impaired placental angiogenesis and reduced progesterone level occurred in all-cause small for gestational age placenta. Taken together, environmental exposure to Cd impairs fetal growth and placental angiogenesis via GCN-2-mediated mitochondrial stress.

8.
Ecotoxicol Environ Saf ; 208: 111423, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33075586

RESUMO

The toxic alga Heterosigma akashiwo (Raphidophyceae) is known to form harmful algal blooms (HABs), which can have serious negative effects on the aquatic ecosystem and human life. Previous study has shown that Nω-acetylhistamine (N-AcH), an algicidal compound secreted by algicidal bacteria Bacillus sp. Strain B1, can inhibit the growth of H. akashiwo. In this study, the algicidal mechanism of N-AcH against H. akashiwo was explored, and the changes of toxicity of H. akashiwo treated with N-AcH were investigated. The algal inhibition rate was calculated by the optical density method, and the results showed that the growth inhibition rate of H. akashiwo was about 90% when treated in the medium with 40 µg/mL N-AcH at 96 h. After 72 h treatment, transmission electron microscopy (TEM) showed that the microstructure of H. akashiwo cell was seriously damaged at this concentration. The content of Chlorophyll a and Chlorophyll b decreased while malonaldehyde levels increased, and superoxide dismutase activity first increased and then decreased as well as soluble protein content. GC-MS revealed that the type and content of fatty acids cut down after 48 h and 96 h treatment. Hemolytic test, MTT assay, and micronucleus test all demonstrated the decrease in the toxicity of H. akashiwo treated with 40 µg/mL N-AcH. In brief, N-AcH mainly kills H. akashiwo cell through oxidative stress and can also reduce its toxicity, so it is a promising algicide with the dual functions of killing algae and inhibiting algal toxic effects.


Assuntos
Desinfetantes/toxicidade , Proliferação Nociva de Algas , Toxinas Marinhas/análise , Estramenópilas/efeitos dos fármacos , Bacillus , Bactérias , Clorofila A , Dinoflagelados , Ecossistema , Humanos , Malondialdeído
9.
Chemosphere ; 266: 128991, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33250221

RESUMO

Phosphorus (P) is a valuable resource, while it is vastly lost with wastewater causing eutrophication. In this study, to recover P, composite biochars were prepared by pyrolyzing biowaste impregnated with FeCl3 or MgCl2. It was found that inherent mineral profiles in the biowastes played important roles in interacting with metal chlorides and determined P sorption and precipitation. Specifically, two biowastes containing distinct mineral contents, sawdust and sediment, were selected as model components, being alone or mixed at 1:1 (w/w) to prepare biochars with low, moderate and high mineral contents. Results showed that biochar itself could not absorb P, while loading FeCl3 or MgCl2 achieved P recovery rates of approximate 60-100% and 50-100%, respectively, via electrostatic attraction or ligand exchange of PO43- with -OH/-COOH, which was attributed to the enhanced positive charges and -OH/-COOH on the materials by these metal chlorides. Inherent minerals inhibited FeCl3 transforming into Fe3O4 in pyrolysis and promoted generation of Fe4(PO4)3(OH)3 in P sorption, thus high-mineral content was more appropriate for FeCl3 loading; however, precursors with low-mineral content was suitable for MgCl2 loading, since the bulk-C in biochar acted as porous structure to support MgO crystals with high superficial area (∼255.85 m2 g-1). Besides, FeCl3 and MgCl2 both drove dissolution of inherent minerals significantly, while inherent minerals inhibited release of soluble Fe and Mg2+ into solution, which minimized secondary pollution. This study implied that in constructing composite biochar for catching P, the type of metal chloride should match the inherent minerals in biowastes to maximize P recovery and minimize secondary pollution.


Assuntos
Cloretos , Fósforo , Adsorção , Carvão Vegetal , Minerais
10.
Huan Jing Ke Xue ; 42(1): 386-393, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372491

RESUMO

A pot experiment and field experiment were designed to study the changes in the grain methyl mercury content in paddy soil and rice yield by sowing soil amendments that contained weathered coal, CaCO3, and Na2SeO3 as the main raw materials, combined with water management in a paddy field (80% field capacity after the heading and flowering periods). The results showed that:① In pot experiment, the content of methylmercury in rice rhizosphere soil decreased by 86.6% and the content of methylmercury in the rice grains decreased by 65.2% compared with that of the control. In field experiment, the content of methylmercury in rice rhizosphere soil decreased by 77.4% and the content of methylmercury in rice grains decreased by 60.6% upon adding the amendment+water management compared with that of CK. ② The soil pH increased by more than 0.3 in the pot experiment and 0.2 in the field experiment compared with that of the control. Furthermore, rice yield and plant biomass did not decrease in the two parts of the experiment. It can be inferred that the soil amendment and agronomic regulation measures (water management) used in this study have the advantages of quick effects, convenient use, and remarkable control effects and without secondary pollution. More, they can effectively reduce the risk of rice methylmercury exposure.

11.
Nanoscale ; 13(1): 300-310, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33336675

RESUMO

A dielectric film with a trilayer structure is fabricated to obtain both a high dielectric constant and superior electrical breakdown strength simultaneously. The outer layers of the trilayered composite film are composed of barium titanate (BTO) particles dispersed in poly(vinylidene fluoride) (PVDF) to ensure a relatively high dielectric constant, while the central layer of the composite film consists of exfoliated hexagonal boron nitride nanosheets (BNNS) dispersed in PVDF to provide high electrical breakdown strength. Compared with pristine PVDF, the dielectric constant and breakdown strength are simultaneously enhanced due to the sandwich structure, and the dielectric loss is maintained at a low level. Most important of all, positron annihilation lifetime spectroscopy (PALS) is applied to study the atomic-scale free volume holes of PVDF composite films and the effect of free volume holes on the dielectric constant and breakdown strength. Results show that the size of free volume holes of PVDF increased with the addition of BTO, but it decreased firstly and then increased with the BNNS loading. The correlation between dielectric properties and the size of free volume holes of the PVDF matrix was discussed in each layer. It is illustrated that the experimental dielectric constant of the PVDF/BTO single-layered film is consistent with the theoretical value at a lower BTO loading but smaller than the theoretical value at a higher BTO loading, which is probably ascribed to the increased size of free volume holes. The breakdown strength of the PVDF/BNNS film increased with the introduction of BNNS and the reduced size of free volume holes, which is ascribed to the reduced partial discharge phenomenon. The atomic-scale microstructure analysis based on free volume holes provides valuable ideas and new understanding for the study of the mechanism of the dielectric behaviour of polymer composites.

12.
Food Chem Toxicol ; 149: 111938, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33348051

RESUMO

The objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ) proteomic technology to systematically analyze the hepatotoxic mechanism of aflatoxin B1 (AFB1) and its prevention by Se in broilers. Four groups of day-old broilers were allocated into a 2 × 2 factorial design trial that fed a Se-deficient based diet (BD) or the BD + 1.0 mg AFB1/kg, 0.3 mg Se/kg, or 1.0 mg AFB1/kg plus 0.3 mg Se/kg for 3 wk. Dietary AFB1 increased serum ALT and decreased total protein and albumin concentrations, and induced hepatic histopathological lesions in Se adequate groups. Notably, Se deficiency exacerbated these AFB1-induced changes. Furthermore, Se deficiency reduced hepatic glutathione peroxidase but increased thioredoxin reductase and glutathione S-transferase activities and 8-hydroxydeoxyguanosine concentration in AFB1 administrated groups. Moreover, AFB1 dysregulated 261 co-differentially expressed proteins (DEPs) in both Se adequate and deficiency diets, and Se deficiency dysregulated 64 DEPs in AFB1 administrated diets. These DEPs are mainly related to phase I and II metabolizing enzymes, heat shock proteins, DNA repair, fatty acid metabolism and apoptosis. The in vitro study has verified that aldo-keto reductase family1, member10 plays an important role in AFB1-induced hepatotoxicity and Se-mediated detoxification of AFB1 in a chicken leghorn male hepatoma cells. Conclusively, this study has analyzed the hepatic proteome response to dietary AFB1 and Se, and thus shed new light on the mechanisms of hepatotoxicity of AFB1 and its detoxification by Se in broilers.

13.
J Gen Virol ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284098

RESUMO

Rabies is a lethal disease caused by Rabies lyssavirus, commonly known as rabies virus (RABV), and results in nearly 100 % death once clinical symptoms occur in human and animals. Long non-coding RNAs (lncRNAs) have been reported to be associated with viral infection. But the role of lncRNAs involved in RABV infection is still elusive. In this study, we performed global transcriptome analysis of both of lncRNA and mRNA expression profiles in wild-type (WT) and lab-attenuated RABV-infected mouse brains by using next-generation sequencing. The differentially expressed lncRNAs and mRNAs were analysed by using the edgeR package. We identified 1422 differentially expressed lncRNAs and 4475 differentially expressed mRNAs by comparing WT and lab-attenuated RABV-infected brains. Then we predicted the enriched biological pathways by the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) database based on the differentially expressed lncRNAs and mRNAs. Our analysis revealed the relationships between lncRNAs and RABV-infection-associated immune response and ion transport-related pathways, which provide a fresh insight into the potential role of lncRNA in immune evasion and neuron injury induced by WT RABV.

14.
Leukemia ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33299144

RESUMO

Most AML patients exhibit mutational activation of the PI3K/AKT signaling pathway, which promotes downstream effects including growth, survival, DNA repair, and resistance to chemotherapy. Herein we demonstrate that the inv(16)/KITD816Y AML mouse model exhibits constitutive activation of PI3K/AKT signaling, which was enhanced by chemotherapy-induced DNA damage through DNA-PK-dependent AKT phosphorylation. Strikingly, inhibitors of either PI3K or DNA-PK markedly reduced chemotherapy-induced AKT phosphorylation and signaling leading to increased DNA damage and apoptosis of inv(16)/KITD816Y AML cells in response to chemotherapy. Consistently, combinations of chemotherapy and PI3K or DNA-PK inhibitors synergistically inhibited growth and survival of clonogenic AML cells without substantially inhibiting normal clonogenic bone marrow cells. Moreover, treatment of inv(16)/KITD816Y AML mice with combinations of chemotherapy and PI3K or DNA-PK inhibitors significantly prolonged survival compared to untreated/single-treated mice. Mechanistically, our findings implicate that constitutive activation of PI3K/AKT signaling driven by mutant KIT, and potentially other mutational activators such as FLT3 and RAS, cooperates with chemotherapy-induced DNA-PK-dependent activation of AKT to promote survival, DNA repair, and chemotherapy resistance in AML. Hence, our study provides a rationale to select AML patients exhibiting constitutive PI3K/AKT activation for simultaneous treatment with chemotherapy and inhibitors of DNA-PK and PI3K to improve chemotherapy response and clinical outcome.

15.
Int J Nanomedicine ; 15: 9799-9821, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324053

RESUMO

Curcumin (CUR), as a traditional Chinese medicine monomer extracted from the rhizomes of some plants in Ginkgo and Araceae, has shown a wide range of therapeutic and pharmacological activities such as anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, anti-liver fibrosis, anti-atherosclerosis, and anti-Alzheimer's disease. However, some issues significantly affect its biological activity, such as low aqueous solubility, physico-chemical instability, poor bioavailability, and low targeting efficacy. In order to further improve its curative effect, numerous efficient drug delivery systems have been carried out. Among them, physicochemical targeting preparations could improve the properties, targeting ability, and biological activity of CUR. Therefore, in this review, CUR carrier systems are discussed that are driven by physicochemical characteristics of the microenvironment (eg, pH variation of tumorous tissues), affected by external influences like magnetic fields and vehicles formulated with thermo-sensitive materials.


Assuntos
Fenômenos Químicos , Curcumina/química , Portadores de Fármacos/química , Curcumina/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Campos Magnéticos
16.
Integr Cancer Ther ; 19: 1534735420980825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33307864

RESUMO

BACKGROUND: Radiation-induced xerostomia is one of the most common symptoms experienced by cancer patients. The aim of our study is to evaluate the preventive and therapeutic effect of acupuncture for radiation-induced xerostomia in cancer patients. METHODS: Eight databases were searched for all published randomized clinical trials (RCTs) on acupuncture for radiation-induced xerostomia in cancer patients up to December 31, 2019. Manual searching included other conference abstracts and reference lists. Meta-analysis was conducted using Revman V.5.3, and risks of bias for included studies was assessed following the Cochrane Handbook. RESULTS: Eight clinical trials (725 participants) were analyzed, and 3 were included in a meta-analysis. All included trials had a high risk of bias, such as selection, performance, and detection bias. Analysis indicated favorable effects of acupuncture regarding the improvement of xerostomia symptoms (MD -3.05, P = 0.02, 95% CI -5.58 to -0.52), compared with sham acupuncture. There were no significant differences between real acupuncture and sham acupuncture regarding the stimulated salivary flow rate (MD 0.37, P = 0.08, 95% CI -0.05 to 0.79) and unstimulated salivary flow rate (MD 0.09, P = 0.12, 95% CI -0.02 to 0.21), which were whole salivary flow rate. Compared with no acupuncture (standard oral care, usual care, or no treatment), acupuncture produced a significant improvement in patient-reported xerostomia, without causing serious adverse effects. However, a Grading of Recommended Assessments analysis revealed that the quality of all acupuncture outcome measures was low. CONCLUSION: The present meta-analysis and systematic review suggests that acupuncture is effective at improving xerostomia symptoms in cancer patients but not at objective salivary flow measurements. The evidence is still limited due to the low quality of the published studies.

17.
Spectrochim Acta A Mol Biomol Spectrosc ; 248: 119267, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310271

RESUMO

Flexible organic light emitting diodes (OLEDs) have attracted considerable attention for the reason of light weight, high mechanical flexibility in display and lighting. The most widely used transparent anode indium tin oxide (ITO) is unsuitable for flexible OLEDs because of its easy cracking upon bending. In this paper, we proposed a simple two steps solution processing method to fabricate flexible PEDOT:PSS:GO/Ag NWs composite electrodes. The optimized PEDOT:PSS:GO/Ag NWs composite electrode exhibits an optical transmittance of 88.7% at a wavelength of 550 nm and a low sheet resistance of 17 Ω/sq, which arecomparable to that of ITO. With PEDOT:PSS:GO/Ag NWs composite electrodes, the turn on voltage, current density and maximum brightness of OLEDs based on composite electrode were 2.1 V, 6.2 cd/A and 22894 cd/m2, respectively, which were superior to that OLED based on ITO anode. The enhanced performance of OLEDs based on composite anode mainly attributed to the lower sheet resistance, smoother surface of the composite anode and the far surface plasma resonance (Far SPR) effect, a lower waveguide optical loss because of the introduction of Ag NWs in the electrode.

18.
Environ Int ; 147: 106319, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33348103

RESUMO

Cadmium (Cd), an environmental toxicant, is positively associated with fetal growth restriction (FGR). However, the mechanism by which gestational exposure to Cd induces FGR remains unclear. This study designed in vitro and in vivo experiments to explore the role of placental mitophagy in Cd-impaired fetal growth. Based on our case-control study, we also investigated the association of placental mitophagy with reduced progesterone (P4) level and all-cause FGR. We firstly found environmental Cd exposure lowered the P4 content in maternal sera, placentae and amnioticfluids of mice. The level of three mitochondrial P4 synthases, including StAR, CYP11A1 and 3ß-HSD, was also reduced in Cd-treated placentae. Furthermore, Cd triggered mitophagy, as determined by the degradation of two mitochondrial proteins HSP60 and COX IV, and the accumulation of co-localizations of TOM20 with LC3B or Parkin in placental trophoblasts. Correspondingly, Cd elevated mitochondrial Parkin level in placental trophoblasts. Mdivi-1, a mitophagy inhibitor, obviously attenuated Cd-induced reduction of placental P4 and FGR in mice. Moreover, mdivi-1 and Parkin siRNA (siR) markedly reversed Cd-caused P4 synthesis inhibition in human placental trophoblasts. Interestedly, the PERK/ATF4 signaling was activated in Cd-stimulated placental trophoblasts. PERK siR inhibited mitochondrial proteins degradation in Cd-stimulated placental trophoblasts. In particularly, mitophagy activation and P4 synthesis suppression occurred in small-for-gestational-age placentae based on our case-control study. Environmental Cd exposure induced FGR via activating PERK-regulated mitophagy and inhibiting P4 synthesis in placentaltrophoblasts. Furthermore, placental mitophagy was related to the reduced progesterone level and all-cause fetal growth restriction based on our case-control study. As above, placental mitophagy maybe the common mechanism of environmental toxicants-impaired fetal growth.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33230792

RESUMO

Nickel (Ni) is a widely distributed metal in the environment and an important pollutant due to its widespread industrial applications. Ni has various toxicity in humans and experimental animals, including carcinogenicity. However, the carcinogenic effects of Ni remain troublesome. Cell cycle dysregulation may be an important carcinogenic mechanism and is also a potential molecular mechanism for Ni complexes anti-cancerous effects. Therefore, we conducted a literature review to summarize the effects of Ni on cell cycle. Up to now, there were three different reports on Ni-induced cell cycle arrest: (i) Ni can induce cell cycle arrest in G0/G1 phase, phosphorylation and degradation of IkappaB kinase-alpha (IKKα)-dependent cyclin D1 and phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway-mediated down-regulation of expressions of cyclin-dependent kinases 4 (CDK4) play important role in it; (ii) Ni can induce cell cycle arrest in S phase, but the molecular mechanism is not known; (iii) G2/M phase is the target of Ni toxicity, and Ni compounds cause G2/M cell cycle phase arrest by reducing cyclinB1/Cdc2 interaction through the activation of the ataxia telangiectasia mutated (ATM)-p53-p21 and ATM-checkpoint kinase inhibitor 1 (Chk1)/Chk2-cell division cycle 25 (Cdc25) pathways. Revealing the mechanisms of cell cycle dysregulation associated with Ni exposure may help in the prevention and treatment of Ni-related carcinogenicity and toxicology.

20.
Asian J Psychiatr ; : 102468, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33183989

RESUMO

BACKGROUND: Schizophrenia (SZ) and bipolar disorder with psychosis (BDP) can be clinically confusing. The specific connectomic changes in SZ compared with BDP may lead to a deeper comprehension of the pathophysiological core of SZ. Therefore, this study explored the common and distinct white matter (WM) structural connectomic alterations between these two diseases. METHOD: Diffusion tensor imaging data were collected from 19 drug-naïve patients with first episode SZ, 19 drug-naïve patients with BDP, and 19 healthy controls (HC). A graph theoretical approach was used to assess the brain WM network properties. RESULTS: Except for the clustering coefficients, no significant differences in the global parameters was found between SZ and BDP. Five brain regions, the right precentral, right post-cingulum, right insula, left superior occipital, and left inferior temporal gyri, showed specific differences in the nodal parameters in SZ compared with BDP and HC. Nine brain regions, the left rectus, left lingual, right inferior parietal, left superior temporal, right precentral, right postcentral, bilateral middle frontal, and right post-cingulum gyri, showed specific differences in the nodal parameters in BDP. Significant correlations between clinical symptoms and connectomic changes were detected in the right insula and left superior occipital gyrus in patients with SZ but in the left lingual gyrus in patients with BDP. CONCLUSIONS: Identifying shared and distinct WM structural networks between SZ and BDP may improve the understanding of the neuroanatomy of mental diseases. Specifically, the insula, the inferior temporal, superior temporal, and the lingual gyri may help to distinguish between SZ and BDP.

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