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1.
Sci Total Environ ; : 155570, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35504371

RESUMO

Developing chrome-free and sustainable tanning agents is extremely important to the sustainability of the leather industry. Herein, we have synthesized an Al-Zr-oligosaccharides tanning agent via a simultaneous degradation and oxidation of cellulose in waste paper. The influence of the temperature and the concentrations of AlCl3 and H2O2 during the synthesis were thoroughly investigated on the properties of the tanning agent and the leather produced. The synthesis temperature and the concentration of AlCl3 were the factors primarily affecting the effective depolymerization of cellulose. They controlled the conversion of waste paper into oligosaccharides with an appropriate molecular weight to efficiently penetrate the leather matrix. In parallel, the H2O2 concentration substantially influenced the tanning performance of the Al-Zr-oligosaccharides, diminishing the chromaticity of the tanning liquid via oxidation and promoting the conversion of C2/C3/C6-OH moieties into -CHO/-COOH. These functional groups increased the surface charge of the oligosaccharides allowing more effective coordination with Al/Zr, which facilitated the penetration of Al/Zr species into the leather matrix. Once inside the leather matrix, Al and Zr were released and reacted with the collagen fibers in leather, which resulted in effective leather tanning. The process optimization revealed that up to 57% of waste paper could be converted into a low-chromaticity (4350 AU) liquid hydrolysate with the synthesis conducted at 177 °C in a system comprising 47 mM AlCl3 and 5 vol% H2O2. The application of this liquid for tanning provided leather with a shrinkage temperature (86.5 °C) sufficiently high for commercial applications. These excellent results, combined with the intrinsic green nature of our approach, exemplify a step forward to simultaneously reduce pollution and hazards in leather industries giving a second life to waste paper.

2.
Sci Adv ; 8(15): eabk2376, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35417232

RESUMO

Mitochondrial quality control plays an important role in maintaining mitochondrial homeostasis and function. Disruption of mitochondrial quality control degrades brain function. We found that flunarizine (FNZ), a drug whose chronic use causes parkinsonism, led to a parkinsonism-like motor dysfunction in mice. FNZ induced mitochondrial dysfunction and decreased mitochondrial mass specifically in the brain. FNZ decreased mitochondrial content in both neurons and astrocytes, without affecting the number of nigral dopaminergic neurons. In human neural progenitor cells, FNZ also induced mitochondrial depletion. Mechanistically, independent of ATG5- or RAB9-mediated mitophagy, mitochondria were engulfed by lysosomes, followed by a vesicle-associated membrane protein 2- and syntaxin-4-dependent extracellular secretion. A genome-wide CRISPR knockout screen identified genes required for FNZ-induced mitochondrial elimination. These results reveal not only a previously unidentified lysosome-associated exocytosis process of mitochondrial quality control that may participate in the FNZ-induced parkinsonism but also a drug-based method for generating mitochondria-depleted mammal cells.

3.
Front Med (Lausanne) ; 9: 811975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360751

RESUMO

Background and Objectives: Accumulating evidence suggests that oxidative stress is involved in the development of chronic obstructive pulmonary disease (COPD) and its progression. Activity of extracellular superoxide dismutase (ecSOD), the only extracellular enzyme eliminating superoxide radicals, has been reported to decline in acute exacerbations of COPD (AECOPD). However, the association between serum ecSOD activity and 1-year all-cause mortality in AECOPD patients remains unclear. The objective of our study was to explore the usefulness of ecSOD activity on admission in AECOPD as an objective predictor for 1-year all-cause mortality. Methods: We measured serum ecSOD activity in AECOPD patients on admission in a prospective cohort study. We also recorded their laboratory and clinical data. Multivariate Cox regression was used to analyze the association between ecSOD activity and the risk of 1-year all-cause mortality. Restricted cubic spline curves were used to visualize the relationship between ecSOD activity and the hazard ratio of 1-year all-cause mortality. Results: A total of 367 patients were followed up for 1 year, and 29 patients died during a 1-year follow-up period. Compared with survivors, the non-survivors were older (79.52 ± 8.39 vs. 74.38 ± 9.34 years old, p = 0.004) and had increased levels of tobacco consumption (47.07 ± 41.67 vs. 33.83 ± 31.79 pack-years, p = 0.037). Having an ecSOD activity ≤ 98.8 U/ml was an independent risk factor of 1-year all-cause mortality after adjustment for baseline differences, clinical variables and comorbidities [hazard ratio = 5.51, 95% confidence interval (CI): 2.35-12.95, p < 0.001]. Conclusion: Lower serum ecSOD activity was a strong and independent predictor of 1-year all-cause mortality in AECOPD patients.

4.
Environ Pollut ; 292(Pt B): 118464, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34763019

RESUMO

The use of biomass for cooking and heating is considered an important factor associated with chronic obstructive pulmonary disease (COPD), but few studies have previously addressed its underlying mechanisms. Therefore, this research aimed to evaluate the effects of biomass-related PM2.5 (BRPM2.5) exposure on 16HBE human airway epithelial cells and in mice with regard to mitochondrial dysfunction. Our study indicated that BRPM2.5 exposure of 16HBE cells resulted in mitochondrial dysfunction, including decreased mitochondrial membrane potential, increased expression of fission proteins-phospho-DRP1, increased mitochondrial ROS (mtROS), and decreased levels of ATP. BRPM2.5 altered the mitochondrial metabolism of 16HBE cells by decreasing mitochondrial oxygen consumption and glycolysis. However, Mitochondria targeted peptide SS-31 eliminated mitochondrial ROS and alleviated the ATP deficiency and proinflammatory cytokines release. BRPM2.5 exposure resulted in abnormal mitochondrial morphological alterations both in 16HBE and in lung tissue. Taken together, these results suggest that BRPM2.5 has detrimental effects on human airway epithelial cells, leading to mitochondrial dysfunction, abnormal mitochondrial metabolism and altered mitochondrial dynamics. The present study provides the first evidence that disruption of mitochondrial structure and mitochondrial metabolism may be one of the mechanisms of BRPM2.5-induced respiratory dysfunction.


Assuntos
Células Epiteliais , Pulmão , Animais , Biomassa , Humanos , Pulmão/química , Camundongos , Material Particulado/análise , Material Particulado/toxicidade , Espécies Reativas de Oxigênio
5.
Biomed Res Int ; 2021: 5521058, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337018

RESUMO

BACKGROUND: Gastric cancer (GC) is the most common type of cancer. It is highly malignant and is characterized by rapid and uncontrolled growth. The antitumour activity of Baicalin was studied in multiple cancers. However, its mechanism of action has not been fully elucidated. We provided a systematic understanding of the mechanism of action of baicalin against GC using a transcriptome analysis of RNA-seq. METHODS: Human GC cells (SGC-7901) were exposed to 200 µg/ml baicalin for 24 h. RNA-seq with a transcriptome, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the antitumour effects of baicalin on SGC-7901 cells in vitro. A protein-protein interaction (PPI) network of differentially expressed genes (DEGs) was constructed. A competitive endogenous RNA (ceRNA) network was constructed and further analysed after validation using qRT-PCR. RESULTS: A total of 68 lncRNAs, 20 miRNAs, and 1648 mRNAs were differentially expressed in baicalin-treated SGC-7901 GC cells. Three lncRNAs, 6 miRNAs, and 7 mRNAs were included in the ceRNA regulatory network. GO analysis revealed that the main DEGs were involved in the biological processes of the cell cycle and cell death. KEGG pathway analysis further suggested that the p53 signalling pathway was involved in the baicalin-induced antitumour effect on SGC-7901 cells. Further confirmation using qPCR indicated that baicalin induced an antitumour effect on SGC-7901 cells, which is consistent with the results of the sequencing data. CONCLUSIONS: In summary, the mechanism of baicalin against GC involves multiple targets and signalling pathways. These results provide new insight into the antitumour mechanism of baicalin and help the development of new strategies to cure GC.


Assuntos
Flavonoides/uso terapêutico , Perfilação da Expressão Gênica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Mapas de Interação de Proteínas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes
6.
Bioengineered ; 12(1): 5173-5183, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34405758

RESUMO

The gut microbiota is widely considered to be involved in several diseases, including atherosclerosis, obesity, chronic obstructive pulmonary disease (COPD) and pulmonary arterial hypertension (PAH). This study aimed to determine if changes in the gut microbiome and metabolome play a major role in the early pathogenesis of PAH. Male Wistar rats were injected with monocrotaline (MCT) (55 mg/kg) at day 1 and injected with calcium-sensing receptor (CaSR) antagonist NPS2143 (4.5 mg/kg/d) from days 1 to 21. Fecal samples were obtained. The gut microbiota and metabolome were analyzed by 16S rRNA gene sequencing and mass spectrometry-based analysis to investigate the effect of PAH in this rat model. MCT injection had a marked effect on the composition of the gut microbiota. This finding was further confirmed by metabolomic analysis with identification of several metabolites relevant to the gut microflora. However, NPS2143 partially abrogated this intestinal flora disorder and reversed fecal metabolite abnormalities. In conclusion, our study shows correlations between changes in the gut microbiome and the metabolome in PAH, which are affected by NPS2143.


Assuntos
Microbioma Gastrointestinal , Metaboloma , Hipertensão Arterial Pulmonar , Animais , Cálcio/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Masculino , Metaboloma/efeitos dos fármacos , Metaboloma/genética , Metaboloma/fisiologia , Monocrotalina/efeitos adversos , Naftalenos/metabolismo , Naftalenos/farmacologia , Hipertensão Arterial Pulmonar/induzido quimicamente , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/fisiopatologia , Ratos , Ratos Wistar , Receptores de Detecção de Cálcio/metabolismo
7.
Biomed Res Int ; 2021: 9984112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337069

RESUMO

BACKGROUND: Baicalin is an extract from the traditional Chinese herb Scutellaria baicalensis and has the potential to treat osteosarcoma (OS). However, the transcriptome-level mechanism of baicalin-mediated antitumor effects in OS has not yet been investigated. The aim of this study was to analyze the competitive endogenous RNA (ceRNA) regulatory network involved in baicalin-induced apoptosis of OS cells. METHODS: In this study, CCK-8 and flow cytometry assays were used to detect the antitumor effects of baicalin on human OS MG63 cells. Furthermore, transcriptome sequencing was employed to establish the long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA profiles. RESULTS: Baicalin inhibited MG63 cell proliferation and induced apoptosis. Totals of 58 lncRNAs, 31 miRNAs, and 2136 mRNAs in the baicalin-treated MG63 cells were identified as differentially expressed RNAs compared to those in control cells. Of these, 2 lncRNAs, 3 miRNAs, and 18 mRNAs were included in the ceRNA regulatory network. The differentially expressed RNAs were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSIONS: By identifying the ceRNA network, our results provide new information about the possible molecular basis of baicalin, which has potential applications in OS treatment.


Assuntos
Apoptose/genética , Flavonoides/farmacologia , Redes Reguladoras de Genes , Osteossarcoma/genética , Osteossarcoma/patologia , RNA Neoplásico/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Mapas de Interação de Proteínas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Reprodutibilidade dos Testes
8.
Cells Tissues Organs ; 210(2): 118-134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182545

RESUMO

Based on the characteristics of modern weapon injury, a repetitive model of traumatic systemic inflammatory response syndrome (SIRS) and an evaluation system were established. The models were treated with GFP-labeled tree shrew umbilical cord mesenchymal stem cells (UCMSCs). Forty out of 50 tree shrews were used to make a unilateral femoral comminuted fracture. Lipopolysaccharide was injected intravenously to create a traumatic SIRS model. The other 10 shrews were used as normal controls. After the model was established for 10 days, 20 tree shrews were injected intravenously with GFP-labeled UCMSCs, and 18 tree shrews were not injected as the model control group. The distribution of GFP-labeled cells in vivo was measured at 2 and 10 days after injection. Twenty days after treatment, the model group, the normal control group, and the treatment group were taken to observe the pathological changes in each tissue, and blood samples were taken for the changes in liver, renal, and heart function. Distribution of GFP-positive cells was observed in all tissues at 2 and 10 days after injection. After treatment, the HE staining results of the treatment group were close to those of the normal group, and the model group had a certain degree of lesions. The results of liver, renal, and heart function tests in the treatment group were returned to normal, and the results in the model group were abnormally increased. UCMSCs have a certain effect on the treatment of traumatic SIRS and provide a new technical solution for modern weapon trauma treatment.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Rim , Síndrome de Resposta Inflamatória Sistêmica/terapia , Cordão Umbilical
9.
Adv Sci (Weinh) ; 8(10): 2004680, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34026460

RESUMO

Mitochondrial DNA depletion syndrome (MDS) is a group of severe inherited disorders caused by mutations in genes, such as deoxyribonucleoside kinase (DGUOK). A great majority of DGUOK mutant MDS patients develop iron overload progressing to severe liver failure. However, the pathological mechanisms connecting iron overload and hepatic damage remains uncovered. Here, two patients' skin fibroblasts are reprogrammed to induced pluripotent stem cells (iPSCs) and then corrected by CRISPR/Cas9. Patient-specific iPSCs and corrected iPSCs-derived high purity hepatocyte organoids (iHep-Orgs) and hepatocyte-like cells (iHep) are generated as cellular models for studying hepatic pathology. DGUOK mutant iHep and iHep-Orgs, but not control and corrected one, are more sensitive to iron overload-induced ferroptosis, which can be rescued by N-Acetylcysteine (NAC). Mechanically, this ferroptosis is a process mediated by nuclear receptor co-activator 4 (NCOA4)-dependent degradation of ferritin in lysosome and cellular labile iron release. This study reveals the underlying pathological mechanisms and the viable therapeutic strategies of this syndrome, and is the first pure iHep-Orgs model in hereditary liver diseases.


Assuntos
Células-Tronco Pluripotentes Induzidas/patologia , Falência Hepática/patologia , Doenças Mitocondriais/patologia , Mutação , Organoides/patologia , Transtornos Respiratórios/patologia , DNA Mitocondrial/genética , Ferritinas/metabolismo , Ferroptose , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Sobrecarga de Ferro/fisiopatologia , Fígado/metabolismo , Fígado/patologia , Falência Hepática/genética , Falência Hepática/metabolismo , Lisossomos/metabolismo , Doenças Mitocondriais/genética , Doenças Mitocondriais/metabolismo , Coativadores de Receptor Nuclear/genética , Coativadores de Receptor Nuclear/metabolismo , Organoides/metabolismo , Transtornos Respiratórios/etiologia , Transtornos Respiratórios/metabolismo
10.
J Hazard Mater ; 413: 125425, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33626472

RESUMO

Chrome-free metal tanning agent has been considered as eco-friendly in the leather industry. However, extensive crosslinking reactions of metal species on the leather surface restrain their uniform penetration into the hierarchical nanoscale leather matrix. Thus, masking agents with appropriate coordination ability are needed. Herein, the selective degradation of hemicellulose in corncob was achieved with 92.5% of conversion in an AlCl3-H2O system, obtaining oligosaccharides masking agent with high purity and leaving cellulose and lignin in the solid residue for other valuable use. Subsequently, H2O2 oxidation was performed to introduce -CHO/-COOH into oligosaccharides and reduce their molecular weights, thereby enhancing coordination ability and reducing ligand dimension. The post-oxidized reaction fluids together with additional Zr species were subjected to leather tanning, in which the oligosaccharides could coordinate with Al/Zr species and promote the penetration of metal species into the leather matrix. By controlling the hemicellulose degradation and oligosaccharide oxidation, an appropriate concentration of oligosaccharides with proper -CHO/-COOH contents allowed the efficient masking effect of the oligosaccharides. As a result, a uniform distribution of Al/Zr species was observed on the cross section, and 83.5 °C of shrinkage temperature was obtained for the chrome-free tanned leather.


Assuntos
Curtume , Zea mays , Biomassa , Peróxido de Hidrogênio , Oligossacarídeos , Polissacarídeos
12.
Nat Metab ; 2(9): 882-892, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32839595

RESUMO

Somatic cell reprogramming provides insight into basic principles of cell fate determination, which remain poorly understood. Here we show that the transcription factor Glis1 induces multi-level epigenetic and metabolic remodelling in stem cells that facilitates the induction of pluripotency. We find that Glis1 enables reprogramming of senescent cells into pluripotent cells and improves genome stability. During early phases of reprogramming, Glis1 directly binds to and opens chromatin at glycolytic genes, whereas it closes chromatin at somatic genes to upregulate glycolysis. Subsequently, higher glycolytic flux enhances cellular acetyl-CoA and lactate levels, thereby enhancing acetylation (H3K27Ac) and lactylation (H3K18la) at so-called 'second-wave' and pluripotency gene loci, opening them up to facilitate cellular reprogramming. Our work highlights Glis1 as a powerful reprogramming factor, and reveals an epigenome-metabolome-epigenome signalling cascade that involves the glycolysis-driven coordination of histone acetylation and lactylation in the context of cell fate determination.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Epigenoma , Células-Tronco Pluripotentes Induzidas , Metaboloma , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Acetilcoenzima A/metabolismo , Animais , Reprogramação Celular , Senescência Celular , Imunoprecipitação da Cromatina , Glucose/metabolismo , Ácido Láctico/metabolismo , Masculino , Camundongos , Plasmídeos/genética
13.
Am J Respir Cell Mol Biol ; 61(5): 584-596, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31050548

RESUMO

Abnormal expression of long noncoding RNAs (lncRNAs) has been confirmed to be associated with many diseases, including chronic obstructive pulmonary disease (COPD). To gain better understanding of the mechanism of COPD, we investigated the lncRNA and mRNA profiles in the lung tissue of patients with COPD. According to the analysis, one of the significantly different lncRNAs, COPDA1, might participate in the occurrence and development of COPD. Lung tissues were collected from nonsmokers, smokers, or smokers with COPD for RNA sequencing. Bioinformatic analysis and cell experiments were used to define the function of COPDA1, and the effects of COPDA1 on intracellular Ca2+ concentration and cell proliferation were examined after knockdown or overexpression of COPDA1. A number of variations of lncRNAs were found in the comparison of nonsmokers, smokers, and smokers with COPD. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses indicated that smoking was involved in the activation of cytokines and the cell cycle, which is associated with COPD. According to the lncRNA-mRNA-coexpressing network and enrichment analysis, COPDAz1 and one of its target genes, MS4A1 (membrane-spanning 4-domains family, subfamily A) were investigated, and we discovered that the expression of MS4A1 was closely associated with lncRNA COPDA1 expression in human bronchial smooth muscle cells (HBSMCs). Further study showed that lncRNA COPDA1 upregulated the expression of MS4A1 to increase store-operated calcium entry in the HBSMCs, resulting in the promotion of the proliferation of smooth muscle cells as well as of airway remodeling. COPDA1 might be involved in the regulation of certain signaling pathways in COPD, might promote the proliferation of HBSMCs, and might also be involved in facilitating airway remodeling.


Assuntos
Remodelação das Vias Aéreas/genética , Proliferação de Células/genética , Doença Pulmonar Obstrutiva Crônica/genética , RNA Longo não Codificante/genética , Proliferação de Células/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Pulmão/metabolismo , Masculino , Miócitos de Músculo Liso/metabolismo , Fumar/metabolismo
14.
Oncol Lett ; 17(2): 2237-2243, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30675289

RESUMO

MicroRNA-155 (miRNA-155) is a typical multifunctional miRNA, which serves a crucial role in the regulation of numerous vessel cells. However, its effects on dysfunctional endothelial cells have not been completely elucidated. In order to investigate the signaling pathway of miRNA-155-induced cell injury, H2O2 was used to establish an oxidative stress cell model, and miR-155 was transfected into H2O2-treated cells. The CCK8 assay was then employed to examine the effect of miR-155 on the cell proliferations of H2O2-treated cells, and the expressions of Microtubule Associated Protein 1 Light Chain 3 (LC3) and Sequestosome 1 (P62) were detected to examine the effect of miR-155 on the autophagy of Human umbilical vein endothelial cells, and then the formation of intracellular autophagosomes was observed. The results indicated that endothelial cell proliferation was promoted, and oxidant-induced injury was decreased when the expression of miR-155 was inhibited. In addition, the results also demonstrated that when the miR-155 inhibitor was used, the expression of LC3 was increased and the expression of P62 was decreased. This suggests that modulated miR-155 can prevent oxidative damage in endothelial cells, by regulating the level of autophagy. Furthermore, the present study also demonstrated that miR-155 regulated autophagy via promotion of the expression of the autophagy-related gene, Autophagy Related 5 (ATG5). In conclusion, the attenuated expression of miR-155 can decrease oxidant-induced injury and promote cell proliferation via upregulating autophagy, which subsequently affects the expression of ATG5. The present study provides a novel insight into microRNAs as potential therapeutics for the treatment of heart disease.

15.
Cell Death Dis ; 9(10): 966, 2018 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-30237514

RESUMO

Hexadimethrine bromide (Polybrene) was once used clinically as a heparin neutralizer and has recently found use as a promoter in virus-mediated gene therapy trials and gene transfer in research. However, the potential for tissue-specific toxicity of polybrene at low doses has been ignored so far. Here, we found that after intracerebroventricular (ICV) polybrene injection, mice showed disability of movement accompanied neural death and gliosis in brain, and in human neurons, polybrene induces concentration-dependent neuritic beading and fragmentation. Mechanistically, polybrene induces a rapid voltage-dependent calcium channel (VDCC)-mediated influx of extracellular Ca2+. The elevated cytoplasmic Ca2+ activates DRP1, which leads to mitochondrial fragmentation and metabolic dysfunction. At the same time, Ca2+ influx induces endoplasmic reticulum (ER) fragmentation and tightened associations between ER and mitochondria, which makes mitochondria prone to Ca2+ overloading and ensuing permeability transition. These results reveal an unexpected neuronal toxicity of polybrene, wherein Ca2+ influx serves as a regulator for both mitochondrial dynamics and ER-mitochondrial remodeling.


Assuntos
Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Brometo de Hexadimetrina/toxicidade , Mitocôndrias/metabolismo , Degeneração Neural/induzido quimicamente , Neurônios/citologia , Neurônios/efeitos dos fármacos , Animais , Células Cultivadas , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Dinâmica Mitocondrial , Espécies Reativas de Oxigênio/metabolismo
16.
Cytotechnology ; 70(5): 1447-1468, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30066056

RESUMO

Umbilical cord mesenchymal stem cells (UC-MSCs) exert strong immunomodulatory effects and can repair organs. However, their roles in radiation injury remain unclear. We show that in tree shrews with acute radiation injury, injected UC-MSCs significantly improved survival rates, reduced lung inflammation and apoptosis, prevented pulmonary fibrotic processes, recovered hematopoiesis, and increased blood counts. A protein microarray analysis showed that serum levels of the anti-inflammatory cytokines IL-10 and IL-13 and the growth factors BMP-5, BMP-7, HGF, insulin, NT-4, VEGFR3, and SCF were significantly higher, while those of the inflammatory cytokines IL-2, TIMP-2, TNF-α, IFN-γ, IL-1ra, and IL-8 and the fibrosis-related factors PDGF-BB, PDGF-AA, TGF-ß1, IGFBP-2, and IGFBP-4 were significantly lower in UC-MSC-injected animals. A transcriptome analysis of PBMCs showed that the mRNA expression of C1q was upregulated, while that of HLA-DP was downregulated after UC-MSC injection. These results confirm the immunohistochemistry results. eGFP-labeled UC-MSCs were traced in vivo and found in the heart, liver, spleen, lungs, kidneys, thymus, small intestine and bone marrow. Our findings suggest that UC-MSC transplantation may be a novel therapeutic approach for treating acute radiation injury.

17.
Autophagy ; 13(9): 1543-1555, 2017 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-28722510

RESUMO

Induced pluripotent stem cells (iPSCs) have fewer and immature mitochondria than somatic cells and mainly rely on glycolysis for energy source. During somatic cell reprogramming, somatic mitochondria and other organelles get remodeled. However, events of organelle remodeling and interaction during somatic cell reprogramming have not been extensively explored. We show that both SKP/SKO (Sox2, Klf4, Pou5f1/Oct4) and SKPM/SKOM (SKP/SKO plus Myc/c-Myc) reprogramming lead to decreased mitochondrial mass but with different kinetics and by divergent pathways. Rapid, MYC/c-MYC-induced cell proliferation may function as the main driver of mitochondrial decrease in SKPM/SKOM reprogramming. In SKP/SKO reprogramming, however, mitochondrial mass initially increases and subsequently decreases via mitophagy. This mitophagy is dependent on the mitochondrial outer membrane receptor BNIP3L/NIX but not on mitochondrial membrane potential (ΔΨm) dissipation, and this SKP/SKO-induced mitophagy functions in an important role during the reprogramming process. Furthermore, endosome-related RAB5 is involved in mitophagosome formation in SKP/SKO reprogramming. These results reveal a novel role of mitophagy in reprogramming that entails the interaction between mitochondria, macroautophagy/autophagy and endosomes.


Assuntos
Reprogramação Celular , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Mitofagia , Animais , Embrião de Mamíferos/citologia , Endossomos/metabolismo , Endossomos/ultraestrutura , Fibroblastos/metabolismo , Potencial da Membrana Mitocondrial , Camundongos , Mitocôndrias/ultraestrutura , Modelos Biológicos , Fatores de Transcrição/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo
18.
Environ Sci Pollut Res Int ; 24(7): 6512-6522, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28074367

RESUMO

The Hun River is a major tributary of the Liao River in the northeast area of China and provides drinking water for 23 million local residents. This study was designed to assess the severity of metal contamination in the Hun River and the potential use of indigenous organisms (the fish Zacco platypus and the snail Radix swinhoei) as biomonitors of metal contamination. Water, sediment, and the native fish and snails were collected at four sampling sites that differed in their physicochemical characteristics and their contamination levels. The samples were analyzed for Cd, Cr, Cu, Ni, Pb, and Zn by ICP-MS. The results showed that although the overall potential ecological risks of the metals were low at our sampling sites, Cd posed a noteworthy ecological risk. Strong correlations were obtained between Cd concentrations in the organisms and in the environment. The results indicated that Z. platypus and R. swinhoei can be useful biomonitoring species for assessing Cd contamination. Biomonitoring with the snail may be most effective when focused on the gonad/digestive tissue (because of the high metal accumulation there), but further work is needed to confirm this.


Assuntos
Cyprinidae/crescimento & desenvolvimento , Monitoramento Ambiental/métodos , Metais Pesados/análise , Rios/química , Caramujos/crescimento & desenvolvimento , Poluentes Químicos da Água/análise , Animais , China , Ecologia , Sedimentos Geológicos/química , Medição de Risco
19.
Arch Environ Contam Toxicol ; 71(1): 87-96, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26979742

RESUMO

This study assessed the contamination extent and potential ecological and human health impacts for chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) in sediments and indigenous benthic organisms along the coastal area of Huludao, China. We analyzed a total of eight species: two benthic fish species, two bivalves, two snails, and two decapod crustaceans. Cu, Zn, and Cd levels in sediment exceeded the Chinese marine sediment quality criteria. The geoaccumulation index was highest for Cd followed in a decreasing order by Zn, Pb, Cu, Ni, and Cr. Metal levels were highest in the four mollusk species. The oyster and veined rapa whelk had the highest bioaccumulation factors, indicating that these two species would be well suited for monitoring the metal pollution in this area. Our comparison of estimated daily intake values for human consumption of the seafood species to the Food and Agricultural Organization-recommended daily dietary allowances indicate potential health risks from the intake of Cd from all shellfish other than our crab species and Zn intake from oyster consumption. An analysis of target hazard quotients identified noncarcinogenic health risks from Cd (in all shellfish analyzed except for our crab species), Cu, and Zn (in oysters and veined rapa whelks). Moreover, an analysis of cancer risk from Pb ingestion detected an increased risk for consumption of all shellfish except for the crab species. Health risks seem especially pronounced for the consumption of oysters and the veined rapa whelks; a seafood advisory may be warranted for these mollusks.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Sedimentos Geológicos/química , Metais/análise , Poluentes Químicos da Água/análise , Animais , Biota , Dieta/estatística & dados numéricos , Humanos , Metais/metabolismo , Medição de Risco , Alimentos Marinhos/estatística & dados numéricos , Poluentes Químicos da Água/metabolismo , Poluição Química da Água/estatística & dados numéricos
20.
Stem Cells ; 34(1): 83-92, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26388522

RESUMO

Somatic cell reprogramming is accompanied by changes in lipid metabolism. While attempting to dissect the molecular mechanisms of the lipid metabolic switch during reprogramming, we found that overexpression of sterol regulatory element binding protein-1 (Srebp-1), a transcriptional factor required for lipid homeostasis, enhances reprogramming efficiency, while knockdown or pharmaceutical inhibition of Srebp-1 is inhibitory. Srebp-1 overexpression blocks the formation of partially reprogrammed cells, and functions in the early phase of reprogramming. Furthermore, Srebp-1 functions in nucleus and depends on its transcriptional activity but not its ability to bind the E-box motif and regulation of canonical targets. Mechanistically, Srebp-1 interacts with c-Myc, facilitates its binding to downstream pluripotent targets, strengthens the function of c-Myc in enhancing other Yamanaka factors' binding, and thereby promotes the expression of pluripotent genes. These results elucidate a novel role for Srebp-1 in somatic cell reprogramming and provide insights into understanding the metabolic switch during reprogramming.


Assuntos
Reprogramação Celular , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Reprogramação Celular/genética , Regulação da Expressão Gênica , Camundongos , Células-Tronco Pluripotentes/metabolismo , Ligação Proteica
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