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1.
Sci Total Environ ; 786: 147515, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33975103

RESUMO

Freshwater reservoirs are an important source of the greenhouse gas methane (CH4). However, little is known about the activity and structure of microbial communities involved in methanogenic decomposition of sediment organic matter (SOM) in cascade hydropower reservoirs. In this study, we targeted on sediments of three cascade reservoirs in Wujiang River, Southwest China. Our results showed that the content of sediment organic carbon (SOC) was between 3% and 11%, and it's positively correlated with both C/N ratio and recalcitrant organic carbon content of SOM. Meanwhile, SOC content was positively correlated with CH4 production rates but had no significant correlation with total CO2 production rates of the sediments, when rates were normalized to sediment volume. Resultantly, the sediment anaerobic decomposition rates hardly significantly increase along with the SOC content. These results suggested that the terrestrial organic matter accumulated after damming stimulated CH4 production from the reservoir sediments even though its decomposition rate was limited. Meantime, high throughput sequencing of 16S rRNA genes indicated that not only the hydrogenotrophic and acetoclastic, but also the methylotrophic methanogens (Methanomassiliicoccus) are abundant in the reservoir sediments. Moreover, metagenomic sequencing also suggested that methylotrophic methanogenesis are potentially important in the sediment of cascade reservoirs. Finally, the hydraulic residence time of the reservoir could be the key controlling factor of the structures of bacterial and archaeal communities as well as the CH4 production rates of the reservoir sediments.

2.
ISME J ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953361

RESUMO

Carbon fixation by chemoautotrophic microbes such as homoacetogens had a major impact on the transition from the inorganic to the organic world. Recent reports have shown the presence of genes for key enzymes associated with the Wood-Ljungdahl pathway (WLP) in the phylum Actinobacteria, which adds to the diversity of potential autotrophs. Here, we compiled 42 actinobacterial metagenome-assembled genomes (MAGs) from new and existing metagenomic datasets and propose three novel classes, Ca. Aquicultoria, Ca. Geothermincolia and Ca. Humimicrobiia. Most members of these classes contain genes coding for acetogenesis through the WLP, as well as a variety of hydrogenases (NiFe groups 1a and 3b-3d; FeFe group C; NiFe group 4-related hydrogenases). We show that the three classes acquired the hydrogenases independently, yet the carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS) was apparently present in their last common ancestor and was inherited vertically. Furthermore, the Actinobacteria likely donated genes for CODH/ACS to multiple lineages within Nitrospirae, Deltaproteobacteria (Desulfobacterota), and Thermodesulfobacteria through multiple horizontal gene transfer events. Finally, we show the apparent growth of Ca. Geothermincolia and H2-dependent acetate production in hot spring enrichment cultures with or without the methanogenesis inhibitor 2-bromoethanesulfonate, which is consistent with the proposed homoacetogenic metabolism.

4.
Oxid Med Cell Longev ; 2021: 6640751, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936382

RESUMO

Background: Inflammation plays an important role in intervertebral disc degeneration (IDD). The protein follistatin-like 1 (FSTL1) plays a proinflammatory role in a variety of inflammatory diseases. Objectives: The purpose of this study was to investigate whether IDD could be delayed by inhibiting FSTL-1 expression. Methods: We established a puncture-induced IDD model in wild-type and FSTL-1+/- mice and collected intervertebral discs (IVDs) from the mice. Safranin O staining was used to detect cartilage loss of IVD tissue, and HE staining was used to detect morphological changes of IVD tissue. We measured the expression of FSTL-1 and related inflammatory indicators in IVD tissues by immunohistochemical staining, real-time PCR, and Western blotting. Results: In the age-induced model of IDD, the level of FSTL-1 increased with the exacerbation of degeneration. In the puncture-induced IDD model, FSTL-1-knockdown mice showed a reduced degree of degeneration compared with that of wild-type mice. Further experiments showed that FSTL-1 knockdown also significantly reduced the level of related inflammatory factors in IVD. In vitro experiments showed that FSTL-1 knockdown significantly reduced TNF-α-induced inflammation. Specifically, the expression levels of the inflammatory factors COX-2, iNOS, MMP-13, and ADAMTS-5 were reduced. Knockdown of FSTL-1 attenuated inflammation by inhibiting the expression of P-Smad1/5/8, P-Erk1/2, and P-P65. Conclusion: Knockdown of FSTL-1 attenuated inflammation by inhibiting the TNF-α response and Smad pathway activity and ultimately delayed IDD.

5.
Kidney Int ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33940111

RESUMO

The thiazide-sensitive sodium-chloride-cotransporter (NCC) in the kidney distal convoluted tubule (DCT) plays an essential role in sodium and potassium homeostasis. Here, we demonstrate that NCC activity is increased by the ß2-adrenoceptor agonist salbutamol, a drug prevalently used to treat asthma. Relative to ß1-adrenergic receptors, the ß2-adrenergic receptors were greatly enriched in mouse DCT cells. In mice, administration of salbutamol increased NCC phosphorylation (indicating increased activity) within 30 minutes but also caused hypokalemia, which also increases NCC phosphorylation. In ex vivo kidney slices and isolated tubules, salbutamol increased NCC phosphorylation in the pharmacologically relevant range of 0.01-10 µM, an effect observed after 15 minutes and maintained at 60 minutes. Inhibition of the inwardly-rectifying potassium channel (Kir)4.1 or the downstream with-no-lysine kinases (WNKs) and STE20/SPS1-related proline alanine-rich kinase (SPAK) pathway, greatly attenuated, but did not prevent, salbutamol-induced NCC phosphorylation. Salbutamol increased cAMP in tubules, kidney slices and mpkDCT cells (model of DCT). Phosphoproteomics indicated that protein phosphatase 1 (PP1) was a key upstream regulator of salbutamol effects. A role for PP1 and the PP1 inhibitor 1 (I1) was confirmed in tubules using inhibitors of PP1 or kidney slices from I1 knockout mice. On normal and high salt diets, salbutamol infusion increased systolic blood pressure, but this increase was normalized by thiazide suggesting a role for NCC. Thus, ß2-adrenergic receptor signaling modulates NCC activity via I1/PP1 and WNK-dependent pathways and chronic salbutamol administration may be a risk factor for hypertension.

6.
J Environ Manage ; 289: 112513, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33823416

RESUMO

Effects of external disturbances such as the population change on dynamics of water supply, power generation and environmental (WPE) systems have seldom been investigated. Following the WPE nexus profiled in the study of Feng et al. (2016), this study incorporated stochasticity of population, water supply and power generation into the modeling of the dynamical system in the Hehuang region of China, and further quantified resilience measures to understand the system's ability to withstand stochastic disturbances. First, the stochastic differential equations were used to improve the simulation of stochasticity in the WPE nexus. Next, the transient probability distribution functions (pdfs) of system variables, obtained by Monte Carlo simulation, were used to describe the evolutionary process of the system. Finally, the stationary pdfs of variables which reflect stable states of the system were derived to calculate four resilience measures. It is shown that: (1) The system approached a stable state after Year 2400 by calculating the L2 norm of the difference between transient and stationary pdfs. (2) The environmental system was identified as the most vulnerable subsystem because of its long convergence time. (3) The water supply system did not change greatly and it would remain stable at its current low level, i.e., water consumption per capita would be less than 80m3. The method adopted in this study is conducive to avoiding risk and the results provide valuable insights for regional management of a WPE nexus.


Assuntos
Abastecimento de Água , Água , China , Simulação por Computador , Método de Monte Carlo
7.
Food Funct ; 12(8): 3692-3704, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33900309

RESUMO

Monascin (MS) and ankaflavin (AK), as typical yellow lipid-soluble pigments identified from Monascus-fermented products, have been confirmed to possess diverse biological activities such as anti-oxidation, reversing diabetes, and anti-atherosclerosis, and have received increasing attention in recent years. Certainly Monascus-fermented product with a high content of MS/AK is also a concern. The current work explored interactions between MS/AK and human serum albumin (HSA) as well as their influence on the anti-oxidant properties of MS/AK. Moreover, the anti-glycation potential of Monascus-fermented products rich in MS and AK (denoted as Mps) was assessed. The results showed that the fluorescence emission of HSA was quenched by MS/AK through a static quenching mechanism, and MS-HSA and AK-HSA complexes were mainly formed by van der Waals forces and hydrophobic interactions, but AK showed a higher binding affinity than MS. Although the DPPH radical-scavenging abilities of MS-HSA and AK-HSA complexes declined, Mps significantly reduced the formation of fructosamine, α-dicarbonyl compounds and advanced glycation end products (AGEs) in the in vitro glycation model (HSA-glucose). Notably, approximately 80% of fluorescent-AGEs were suppressed by Mps at a concentration of 0.95 mg mL-1, while aminoguanidine (AG, a reference standard) caused only 65% decrease at the same concentration. Although radical scavenging and metal chelating activities could justify the observed anti-glycation activity of Mps, in-depth research on the structures of other functional compounds present in Mps except MS/AK and reaction mechanisms should be performed. Overall, the present study proved that Mps would be promising sources of food-based anti-glycation agents because of their superior inhibitory effect on AGEs.

8.
Neuroreport ; 32(7): 555-561, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33850083

RESUMO

l-dopa and dopamine D2 receptor (D2R) agonists are commonly used to relieve the motor deficits of Parkinson's disease. However, long-term treatment with l-dopa or D2R agonists can induce adverse effects such as abnormal involuntary movements (AIMs), which are major limiting factors in achieving long-term control of parkinsonian syndromes. The pathophysiological mechanisms involved in the development of dopaminergic agonist-induced adverse effects are not well understood. Here, we examined the role of two D2R isoforms, D2S and D2L, in l-dopa-induced AIMs using dopamine D2L knockout (D2L KO) mice (expressing purely D2S) and wild-type mice (expressing predominantly D2L). We found that D2L KO mice displayed markedly enhanced AIMs in response to chronic treatment of l-dopa compared to wild-type mice. The l-dopa-induced enhancement of AIMs in D2L KO mice was significantly reduced by the D2R antagonist eticlopride. D2L KO mice also displayed markedly enhanced AIMs in response to chronic treatment with quinpirole, a preferential D2R agonist. These results suggest that D2S contributes more than D2L to dopaminergic agonist-induced AIMs. Our findings may uncover a new factor that contributes to the pathophysiology of dopaminergic drug-induced AIMs, a characteristic manifestation of dyskinesia and also present in psychosis. There is a possibility that the increased ratio of D2S to D2L in the brain plays a significant role in the development of AIM side effects induced by l-dopa or D2R agonists. See Video Abstract, http://links.lww.com/WNR/A622.

9.
Polymers (Basel) ; 13(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800358

RESUMO

The incidence of dental caries, especially root caries, has risen in elderly populations in recent years. Specialized restorative materials are needed due to the specific site of root caries and the age-related changes in general and oral health in the elderly. Unfortunately, the restorative materials commonly used clinically cannot fully meet the requirements in this population. Specifically, the antibacterial, adhesive, remineralization, mechanical, and anti-aging properties of the materials need to be significantly improved for dental caries in the elderly. This review mainly discusses the strengths and weaknesses of currently available materials, including amalgam, glass ionomer cement, and light-cured composite resin, for root caries. It also reviews the studies on novel anti-caries materials divided into three groups, antimicrobial, remineralization, and self-healing materials, and explores their potential in the clinical use for caries in the elderly. Therefore, specific restorative materials for caries in the elderly, especially for root caries, need to be further developed and applied in clinical practice.

11.
Nature ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33911286

RESUMO

Asgard is a recently discovered superphylum of archaea that appears to include the closest archaeal relatives of eukaryotes1-5. Debate continues as to whether the archaeal ancestor of eukaryotes belongs within the Asgard superphylum or whether this ancestor is a sister group to all other archaea (that is, a two-domain versus a three-domain tree of life)6-8. Here we present a comparative analysis of 162 complete or nearly complete genomes of Asgard archaea, including 75 metagenome-assembled genomes that-to our knowledge-have not previously been reported. Our results substantially expand the phylogenetic diversity of Asgard and lead us to propose six additional phyla that include a deep branch that we have provisionally named Wukongarchaeota. Our phylogenomic analysis does not resolve unequivocally the evolutionary relationship between eukaryotes and Asgard archaea, but instead-depending on the choice of species and conserved genes used to build the phylogeny-supports either the origin of eukaryotes from within Asgard (as a sister group to the expanded Heimdallarchaeota-Wukongarchaeota branch) or a deeper branch for the eukaryote ancestor within archaea. Our comprehensive protein domain analysis using the 162 Asgard genomes results in a major expansion of the set of eukaryotic signature proteins. The Asgard eukaryotic signature proteins show variable phyletic distributions and domain architectures, which is suggestive of dynamic evolution through horizontal gene transfer, gene loss, gene duplication and domain shuffling. The phylogenomics of the Asgard archaea points to the accumulation of the components of the mobile archaeal 'eukaryome' in the archaeal ancestor of eukaryotes (within or outside Asgard) through extensive horizontal gene transfer.

12.
J Periodontol ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33913537

RESUMO

OBJECTIVE: GroEL, a bacterial metabolite, is an important stimulator of inflammation. The aim of this study is to confirm the effect of the virulence factor GroEL on differentiation potential of periodontal ligament stem cells (PDLSCs) and the potential mechanisms. METHODS: PDLSCs were obtained from extracted human premolars. GroEL was administered to osteogenic- and adipogenic-induced hPDLSCs. Alkaline phosphatase staining, Alizarin Red staining and Oil Red staining were performed. Gene and protein expression were separately measured by qPCR and western blotting. The expression and localization of activated signaling factors were confirmed by immunofluorescence staining. The inhibitors of myeloid differentiation factor 88 (MyD88, an adaptor protein of TLRs), JNK/MAPK and NF-κB signaling were used to verify their specific effects. RESULTS: First, we found that GroEL inhibited the osteogenic differentiation and enhanced the adipogenic differentiation of hPDLSCs. Next, we found that GroEL increased the expression of TLR2 and TLR4 and GroEL activated JNK/MAPK and NF-κB signaling, which can be blocked by inhibition of MyD88. Finally, we found that inhibition of MyD88 restored GroEL-induced osteogenic and adipogenic differentiation and blocking JNK/MAPK or NF-κB signaling partly restored GroEL effects. CONCLUSION: In the current study, we revealed a potential interaction between bacteria and host cells by showing that GroEL directs the osteogenic and adipogenic differentiation of hPDLSCs by the involvement of JNK/MAPK and NF-κB signaling. This study provides evidence that bacterial products can influence the differentiation of stem cells and reveals potential effect of GroEL on the context of tissue regeneration. This article is protected by copyright. All rights reserved.

13.
J Am Soc Nephrol ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727367

RESUMO

BACKGROUND: MicroRNAs (miRNAs), formed by cleavage of pre-microRNA by the endoribonuclease Dicer, are critical modulators of cell function by post-transcriptionally regulating gene expression. METHODS: Selective ablation of Dicer in AQP2-expressing cells (DicerAQP2Cre+ mice) was used to investigate the role of miRNAs in the kidney collecting duct of mice. RESULTS: The mice had severe polyuria and nephrogenic diabetes insipidus, potentially due to greatly reduced AQP2 and AQP4 levels. Although epithelial sodium channel levels were decreased in cortex and increased in inner medulla, amiloride-sensitive sodium reabsorption was equivalent in DicerAQP2Cre+ mice and controls. Small-RNA sequencing and proteomic analysis revealed 31 and 178 significantly regulated miRNAs and proteins, respectively. Integrated bioinformatic analysis of the miRNAome and proteome suggested alterations in the epigenetic machinery and various transcription factors regulating AQP2 expression in DicerAQP2Cre+ mice. The expression profile and function of three miRNAs (miR-7688-5p, miR-8114, and miR-409-3p) whose predicted targets were involved in epigenetic control (Phf2, Kdm5c, and Kdm4a) or transcriptional regulation (GATA3, GATA2, and ELF3) of AQP2 were validated. Luciferase assays could not demonstrate direct interaction of AQP2 or the three potential transcription factors with miR-7688-5p, miR-8114, and miR-409-3p. However, transfection of respective miRNA mimics reduced AQP2 expression. Chromatin immunoprecipitation assays demonstrated decreased Phf2 and significantly increased Kdm5c interactions at the Aqp2 gene promoter in DicerAQP2Cre+ mice, resulting in decreased RNA Pol II association. CONCLUSIONS: Novel evidence indicates miRNA-mediated epigenetic regulation of AQP2 expression.

14.
BMC Cancer ; 21(1): 238, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676449

RESUMO

BACKGROUND: Liver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM). METHODS: Data on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients. RESULTS: Young age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88-3.66; P < 0.001) and HR-/HER2+ (HR = 3.43; 95% CI = 2.28-5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001). CONCLUSIONS: Breast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/terapia , Quimiorradioterapia Adjuvante/métodos , Conjuntos de Dados como Assunto , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Prognóstico , Receptor ErbB-2/análise , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/análise , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/terapia , Adulto Jovem
15.
J Nanosci Nanotechnol ; 21(9): 4565-4572, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33691834

RESUMO

The objective of this study was to prepare doxorubicin-loaded EGF modified PEG-nanoparticles and evaluate its targeting capability and therapeutic effects with EGFR-expressing hepatocellular carcinoma cells. The morphology, particle size distribution, and doxorubicin content of the nanoparticles were measured, and the drug loading and encapsulation efficiency were calculated. The doxorubicin nanoparticles prepared were regular circular, with good dispersibility, no adhesion, and the average particle size was (136.7±9.3) nm. The average encapsulation efficiency was (76.67±8.63)%, the average drug loading was (3.86±0.55)%; the drug release rate of doxorubicin was 100% for 12 h, and the doxorubicin nanometer was loaded. The drug release rate of the granules was 52.9% at 24 h and 81.2% at 144 h. The inhibition rate of the proliferation of hepatocarcinoma cells by the doxorubicin-containing nanoparticles was slower than that of doxorubicin, and the IC50 of the two cells was 1.844 and 0.345 µg/mL, respectively. At the same time, apoptosis and cycle analysis showed that the doxorubicin nanoparticles could significantly inhibit the cell cycle of hepatoma cells and promote the apoptosis of hepatoma cells. This study successfully produced nanoparticles loaded with doxorubicin targeting EGFR, which has a good sustained release effect, and its antitumor effect is stronger than free doxorubicin.

16.
Int J Cancer ; 149(1): 84-96, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33728681

RESUMO

Notch signaling pathway plays crucial roles in progression of colorectal cancer (CRC), likely affecting overall survival (OS). In a two-stage survival analysis of 1116 CRC patients in East China, we found that one locus at MINAR1 out of 133 genes in the Notch signaling pathway was significantly associated with OS (P < 1 × 10-6 , false discovery rate < 0.01). This locus containing seven single-nucleotide polymorphisms (SNPs) in high linkage disequilibrium (R2 = 1) is located on chromosome 15, of which the MINAR1 rs72430409 G allele was associated with a greater death risk (HR = 1.98, 95% CI = 1.55-2.54, P = 6.8 × 10-8 ). Further analysis of ChIP-sequencing data from the encyclopedia of DNA Elements showed that rs72430409 and rs72630408 were potential cis-regulatory elements for the MINAR1 promoter. Additional expression quantitative trait loci analysis revealed that rs72430409 G>A and rs72630408 A>G were correlated with increased MINAR1 expression levels in both blood cells and colon tissues. Dual luciferase assays revealed that the rs72430409 A allele increased MINAR1 promoter activity. The Cancer Genome Atlas data showed that expression levels of MINAR1 in CRC samples were significantly higher than that in normal colorectal tissue and that high expression of MINAR1 was associated with a shortened OS, likely via activating the epithelial mesenchymal transition (EMT) pathway as shown in the gene-set enrichment analysis. In vitro, RNAi-mediated silencing of MINAR1 led to decreased migration and proliferation in CRC cancer cells, and MINAR1 silencing could downregulate the expression of key effector genes in EMT and glycolysis. Larger cohort studies and further experiments are needed to validate our findings.

17.
Chem Res Toxicol ; 34(4): 1114-1123, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739826

RESUMO

Methylmercury (MeHg) is a common organic form of mercury in water, which has been linked to several forms of biological toxicity. However, studies on the ecotoxicity risk of long-term exposure to low-dose MeHg are insufficient for the assessment of environmental safety. In the present study, the effects of MeHg on multiple generations (P0-F3) and population of Caenorhabditis elegans were investigated under long-term, low-dose exposure. We investigated the multigenerational toxicity of MeHg by analyzing reproductive and developmental indicators. According to our results, exposure to 100 nM MeHg had little effect on the parental generation (P0) but caused serious reproductive toxicity in the offspring (F1-F3), and the effect of MeHg was aggravated with each passing generation. The genes related to apoptosis and DNA damage were upregulated in the F3 generation. Pearson correlation analysis showed that the changes in these genes were closely related to the apoptosis of gonadal cells. Furthermore, chronic exposure to MeHg (from 100 to 1000 nM group) caused a sharp decline in population size and triggered the "bag of worms" phenotype. Genes related to vulvar development were downregulated in the F3 generation after treatment with 100 nM MeHg. These data suggest that long-term low-dose MeHg exposure adversely affected C. elegans and its offspring and triggered multigenerational toxicity and population discrepancy.

18.
Exp Cell Res ; 402(1): 112547, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33722639

RESUMO

The high aggressiveness of gliomas remains a huge challenge to clinical therapies, and the hypoxic microenvironment in the core region is a critical contributor to glioma aggressiveness. In this study, it was found that miR-485-5p was low expressed within glioma tissue samples and cells. GO enrichment annotation indicated that the predicted downstream targets miR-485-5p were enriched in hypoxia response and decreased oxygen level. In glioma cells, miR-485-5p overexpression suppressed cell viability, migratory ability, and invasive ability under both normoxic and hypoxic conditions. Through direct binding, miR-485-5p suppressed SRPK1 expression. Under hypoxia, SRPK1 overexpression enhanced hypoxia-induced glioma cell aggressiveness and significantly reversed the effects of miR-485-5p overexpression. Moreover, HIF1A could target the miR-485-5p promoter region to inhibit the transcription. HIF1A, miR-485-5p, and SRPK1 form a regulatory axis, which modulates glioma cell aggressiveness under hypoxia. In conclusion, we identify a HIF1A/miR-485-5p/SRPK1 axis that modulates the aggressiveness of glioma cells under hypoxia. The axis could potentially provide new research avenues in the treatment of gliomas considering the hypoxic environment in its core.

19.
Am J Physiol Renal Physiol ; 320(5): F908-F921, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33779313

RESUMO

The hormone aldosterone is essential for maintaining K+ and Na+ balance and controlling blood pressure. Aldosterone has different effects if it is secreted due to hypovolemia or hyperkalemia. The kidney distal convoluted tubule (DCT) is believed to play a central role in mediating the differential responses to aldosterone. To determine the alterations in the DCT that may be responsible for these effects, male mice with green fluorescent protein expression specifically in the DCT were maintained on diets containing low NaCl (hypovolemic state) or high potassium citrate (hyperkalemic state) for 4 days, and DCT cells were isolated using fluorescence-activated cell sorting. This pure population of DCT cells was subjected to analysis by liquid chromatography-coupled tandem mass spectrometry. Over 3,000 proteins were identified in the DCT, creating the first proteome of the mouse DCT. Of the identified proteins, 210 proteins were altered in abundance following a low-NaCl diet and 625 proteins following the high-K+ diet. Many of these changes were not detectable by analyzing whole kidney samples from the same animals. When comparing responses to high-K+ versus low-Na+ diets, protein translation, chaperone-mediated protein folding, and protein ubiquitylation were likely to be significantly altered in the DCT subsequent to a high-K+ diet. In conclusion, this study defines an in vivo protein landscape of the DCT in male mice following either a low-NaCl or a high-K+ diet and acts as an essential resource for the kidney research community.NEW & NOTEWORTHY The mineralocorticoid aldosterone, essential for maintaining body K+ and Na+ balance, has different effects if secreted due to hypovolemia or hyperkalemia. Here, we used proteomics to profile kidney distal convoluted tubule (DCT) cells isolated by a novel FACS approach from mice fed a low-Na+ diet (mimicking hypovolemia) or a high-K+ diet (mimicking hyperkalemia). The study provides the first in-depth proteome of the mouse DCT and insights into how it is physiologically regulated.

20.
J Pediatr Oncol Nurs ; : 1043454221992304, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33686896

RESUMO

Background: Fatigue is a prevalent and distressing symptom in children and adolescents with cancer. Objectives: This study aimed to (1) investigate the current fatigue status reported by Chinese children and adolescents with cancer during active cancer treatment and (2) examine whether sociodemographic information, disease and treatment information, co-occurring symptoms, function and related clinical data are significantly associated with fatigue according to the biopsychosocial model. Methods: Participants were children aged 8-17 years, who had undergone treatment for cancer at four hospitals in China. Children completed the Chinese version of the Pediatric Patient-Reported Outcomes Measurement Information System short forms. Results: In total, 187 children (33.16% female, mean age 10.28 years) participated. The mean T-score for child-reported fatigue was 48.52 (34-72). Multiple linear regression analysis showed that fatigue in pediatric active cancer treatment could be significantly predicted by greater child-reported pain interference (ß = 0.391, p < .001), greater depressive symptoms (ß = 0.443, p < .001), and reduced mobility (ß = -0.226, p = .004) (adjusted R2 = 0.613, F = 16.476, p < .001). Conclusions: Children and adolescents with cancer experience multiple, intersecting troubling symptoms during their treatment. There is a need to attend to the biopsychosocial aspects of care for children and adolescents during active cancer treatment. To reduce pediatric oncology patients' fatigue level, clinicians could develop culturally sensitive interventions to alleviate children's pain interference, treat depressive symptoms, and maximize their physical mobility.

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