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1.
Toxicol Appl Pharmacol ; 434: 115799, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34798142

RESUMO

Arsenic is a naturally occurring element present in food, soil and water and human exposure is associated with increased cancer risk. Arsenic inhibits DNA repair at low, non-cytotoxic concentrations and amplifies the mutagenic and carcinogenic impact of other DNA-damaging agents, such as ultraviolet radiation (UVR). Arsenic exposure leads to oxidation of zinc coordinating cysteine residues, zinc loss and decreased activity of the DNA repair protein poly(ADP)ribose polymerase (PARP)-1. Because arsenic stimulates NADPH oxidase (NOX) activity leading to generation of reactive oxygen species (ROS), the goal of this study was to investigate the role of NOX in arsenic-induced inhibition of PARP activity and retention of DNA damage. NOX involvement in the arsenic response was assessed in vitro and in vivo. Keratinocytes were treated with or without arsenite, solar-simulated UVR, NOX inhibitors and/or isoform specific NOX siRNA. Knockdown or inhibition of NOX decreased arsenite-induced ROS, PARP-1 oxidation and DNA damage retention, while restoring arsenite inhibition of PARP-1 activity. The NOX2 isoform was determined to be the major contributor to arsenite-induced ROS generation and DNA damage retention. In vivo DNA damage was measured by immunohistochemical staining and analysis of dorsal epidermis sections from C57BI/6 and p91phox knockout (NOX2-/-) mice. There was no significant difference in solar-simulated UVR DNA damage as detected by percent PH2AX positive cells within NOX2-/- mice versus control. In contrast, arsenite-dependent retention of UVR-induced DNA damage was markedly reduced. Altogether, the in vitro and in vivo findings indicate that NOX is involved in arsenic enhancement of UVR-induced DNA damage.

2.
Sci Rep ; 11(1): 22121, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764389

RESUMO

Arsenic exposure poses numerous threats to human health. Our previous work in mice has shown that arsenic causes anemia by inhibiting erythropoiesis. However, the impacts of arsenic exposure on human erythropoiesis remain largely unclear. We report here that low-dose arsenic exposure inhibits the erythroid differentiation of human hematopoietic progenitor cells (HPCs). The impacts of arsenic (in the form of arsenite; As3+) on red blood cell (RBC) development was evaluated using a long-term culture of normal human bone marrow CD34+-HPCs stimulated in vitro to undergo erythropoiesis. Over the time course studied, we analyzed the expression of the cell surface antigens CD34, CD71 and CD235a, which are markers commonly used to monitor the progression of HPCs through the stages of erythropoiesis. Simultaneously, we measured hemoglobin content, which is an important criterion used clinically for diagnosing anemia. As compared to control, low-dose As3+ exposure (100 nM and 500 nM) inhibited the expansion of CD34+-HPCs over the time course investigated; decreased the number of committed erythroid progenitors (BFU-E and CFU-E) and erythroblast differentiation in the subsequent stages; and caused a reduction of hemoglobin content. These findings demonstrate that low-dose arsenic exposure impairs human erythropoiesis, likely by combined effects on various stages of RBC formation.

3.
Front Microbiol ; 12: 746006, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690992

RESUMO

Due to the increasing prevalence of drug-resistant fungi and the limitations of current treatment strategies to fungal infections, exploration and development of new antifungal drugs or substituents are necessary. In the study, a novel antimicrobial peptide, named Sparamosin, was identified in the mud crab Scylla paramamosain, which contains a signal peptide of 22 amino acids and a mature peptide of 54 amino acids. The antimicrobial activity of its synthetic mature peptide and two truncated peptides (Sparamosin1-25 and Sparamosin26-54) were determined. The results showed that Sparamosin26-54 had the strongest activity against a variety of Gram-negative bacteria, Gram-positive bacteria and fungi, in particular had rapid fungicidal kinetics (killed 99% Cryptococcus neoformans within 10 min) and had potent anti-biofilm activity against C. neoformans, but had no cytotoxic effect on mammalian cells. The RNA-seq results showed that after Sparamosin26-54 treatment, the expression of genes involved in cell wall component biosynthesis, cell wall integrity signaling pathway, anti-oxidative stress, apoptosis and DNA repair were significantly up-regulated, indicating that Sparamosin26-54 might disrupt the cell wall of C. neoformans, causing oxidative stress, DNA damage and cell apoptosis. The underlying mechanism was further confirmed. Sparamosin26-54 could bind to several phospholipids in the cell membrane and effectively killed C. neoformans through disrupting the integrity of the cell wall and cell membrane observed by electron microscope and staining assay. In addition, it was found that the accumulation of reactive oxygen species (ROS) increased, the mitochondrial membrane potential (MMP) was disrupted, and DNA fragmentation was induced after Sparamosin26-54 treatment, which are all hallmarks of apoptosis. Taken together, Sparamosin26-54 has a good application prospect as an effective antimicrobial agent, especially for C. neoformans infections.

4.
Metabolites ; 11(10)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34677366

RESUMO

Pubertal molt is a vital stage in the cultivation of mature female crabs in the aquacultural industry of Scylla paramamosain. Since fasting occurs during molting, which requires a large supply of energy, internal energy reserves are critical. However, the dynamics of energy supply during pubertal molt is not clear. This study focuses on the variations of carbohydrates and lipids in serum during the pubertal molt of S. paramamosain via a metabolomics approach. Eleven lipid or carbohydrate metabolic pathways were significantly influenced postmolt. A remarkable decrease in carbohydrates in serum suggested that free sugars were consumed for energy. A significant decrease in glucose and alpha-d-glucosamine 1-phosphate showed that chitin synthesis exhausted glycogen, resulting in insufficient glucose supply. An increase in l-carnitine and acetylcarnitine, and a significant decrease in 15 fatty acyls and 8 glycerophosphocholines in serum indicated that carnitine shuttle was stimulated, and ß-oxidation was upregulated postmolt. In addition, astaxanthin, ponasterone A, and riboflavin in serum were significantly decreased postmolt. Eleven potential metabolite biomarkers were identified for pubertal molt. Taken together, carbohydrates and lipids were possibly major energy reserves in pubertal molt. This study suggests that an increase in carbohydrate and lipid levels in crab feed may alleviate the effects of fasting during molt and improve farm productivity in mature female crabs.

5.
Front Cell Infect Microbiol ; 11: 752637, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676176

RESUMO

The emergence of multidrug-resistant (MDR) pathogens has become a global public health crisis. Among them, MDR Pseudomonas aeruginosa is the main cause of nosocomial infections and deaths. Antimicrobial peptides (AMPs) are considered as competitive drug candidates to address this threat. In the study, we characterized two AMPs (AS-hepc3(41-71) and AS-hepc3(48-56)) that had potent activity against 5 new clinical isolates of MDR P. aeruginosa. Both AMPs destroyed the integrity of the cell membrane, induced leakage of intracellular components, and ultimately led to cell death. A long-term comparative study on the bacterial resistance treated with AS-hepc3(41-71), AS-hepc3(48-56) and 12 commonly used antibiotics showed that P. aeruginosa quickly developed resistance to the nine antibiotics tested (including aztreonam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, gentamicin, and piperacillin) as early as 12 days after 150 days of successive culture generations. The initial effective concentration of 9 antibiotics against P. aeruginosa was greatly increased to a different high level at 150 days, however, both AS-hepc3(41-71) and AS-hepc3(48-56) maintained their initial MIC unchangeable through 150 days, indicating that P. aeruginosa did not produce any significant resistance to both AMPs. Furthermore, AS-hepc3(48-56) did not show any toxic effect on mammalian cells in vitro and mice in vivo. AS-hepc3(48-56) had a therapeutic effect on MDR P. aeruginosa infection using a mouse lung infection model and could effectively increase the survival rate of mice by inhibiting bacterial proliferation and attenuating lung inflammation. Taken together, the short peptide AS-hepc3(48-56) would be a promising agent for clinical treatment of MDR P. aeruginosa infections.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Aminoácidos , Animais , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Proteínas Citotóxicas Formadoras de Poros , Infecções por Pseudomonas/tratamento farmacológico
6.
Bioengineered ; 12(1): 7376-7416, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34612807

RESUMO

Antibiotics, as antimicrobial drugs, have been widely applied as human and veterinary medicines. Recently, many antibiotics have been detected in the environments due to their mass production, widespread use, but a lack of adequate treatment processes. The environmental occurrence of antibiotics has received worldwide attention due to their potential harm to the ecosystem and human health. Research status of antibiotics in the environment field is presented by bibliometrics. Herein, we provided a comprehensive overview on the following important issues: (1) occurrence of antibiotics in different environmental compartments, such as wastewater, surface water, and soil; (2) toxicity of antibiotics toward non-target organisms, including aquatic and terrestrial organisms; (3) current treatment technologies for the degradation and removal of antibiotics, including adsorption, hydrolysis, photodegradation and oxidation, and biodegradation. It was found that macrolides, fluoroquinolones, tetracyclines, and sulfonamides were most frequently detected in the environment. Compared to surface and groundwaters, wastewater contained a high concentration of antibiotic residues. Both antibiotics and their metabolites exhibited toxicity to non-target organisms, especially aquatic organisms (e.g., algae and fish). Fluoroquinolones, tetracyclines, and sulfonamides can be removed through abiotic process, such as adsorption, photodegradation, and oxidation. Fluoroquinolones and sulfonamides can directly undergo biodegradation. Further studies on the chronic effects of antibiotics at environmentally relevant concentrations on the ecosystem were urgently needed to fully understand the hazards of antibiotics and help the government to establish the permissible limits. Biodegradation is a promising technology; it has numerous advantages such as cost-effectiveness and environmental friendliness.

7.
Front Cell Neurosci ; 15: 714171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475814

RESUMO

Hemorrhagic transformation (HT) is a severe complication following acute ischemic stroke, particularly with reperfusion interventions, leading to poor prognosis. Serum occludin level is related with blood brain barrier disruption, and the National Institute of Health stroke scale (NIHSS) score reflects stroke severity. We investigated whether the two covariates are independently associated with HT and their combination can improve the accuracy of HT prediction in ischemic stroke patients with reperfusion therapy. Seventy-six patients were screened from the established database of acute ischemic stroke in our previous study, which contains all clinical information, including serum occludin levels, baseline NIHSS score, and hemorrhagic events. Multivariate logistic regression analysis showed that serum occludin level (OR = 4.969, 95% CI: 2.069-11.935, p < 0.001) and baseline NIHSS score (OR = 1.293, 95% CI 1.079-1.550, p = 0.005) were independent risk factors of HT after adjusting for potential confounders. Compared with non-HT patients, HT patients had higher baseline NIHSS score [12 (10.5-18.0) versus 6 (4-12), p = 0.003] and serum occludin level (5.47 ± 1.25 versus 3.81 ± 1.19, p < 0.001). Moreover, receiver operating characteristic curve based on leave-one-out cross-validation showed that the combination of serum occludin level and NIHSS score significantly improved the accuracy of predicting HT (0.919, 95% CI 0.857-0.982, p < 0.001). These findings suggest that the combination of two methods may provide a better tool for HT prediction in acute ischemic stroke patients with reperfusion therapy.

8.
Front Cell Neurosci ; 15: 710129, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512266

RESUMO

Hemorrhagic transformation (HT), which occurs with or without reperfusion treatments (thrombolysis and/or thrombectomy), deteriorates the outcomes of ischemic stroke patients. It is essential to find clinically reliable biomarkers that can predict HT. In this study, we screened for potential serum biomarkers from an existing blood bank and database with 243 suspected acute ischemic stroke (AIS) patients. A total of 37 patients were enrolled, who were diagnosed as AIS without receiving reperfusion treatment. They were divided into two groups based on whether they were accompanied with HT or not (five HT and 32 non-HT). Serum samples were labeled by isobaric tags for relative and absolute quantitation (iTRAQ) and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and compared under NCBInr database. A total of 647 proteins in sera samples were captured, and the levels of 17 proteins (12 upregulated and five downregulated) were significantly different. These differentially expressed proteins were further categorized with Gene Ontology functional classification annotation and Kyoto Encyclopedia of Genes and Genomes metabolic pathway analysis into biological processes. Further protein-protein interaction analysis using String database discovered that, among the differentially expressed proteins, 10 pairs of proteins were found to have crosstalk connections, which may have direct (physical) and indirect (functional) interactions for the development of HT. Our findings suggest that these differentially expressed proteins could serve as potential biomarkers for predicting HT after ischemic stroke.

9.
Rev Cardiovasc Med ; 22(3): 613-624, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565064

RESUMO

Our objective was to provide evidence for exercise-based cardiac rehabilitation (ECR) for patients with aortic dissection (AD), so as to better improve the prognosis of patients and improve the quality of life (QoL) after discharge. The database PubMed, Embase, MEDLINE, Web of Science, Cochrane Library, WanFang Chinese database, ZhiWang Chinese database, Chinese Clinical Trials Registry from establishment of each database until February 2021 were included. A total of 1684 records were found by searching the database and clinical trial registry, 178 duplicate records were deleted, and 11 records met the inclusion criteria according to the screening process. We can conclude that ECR for patients with AD can effectively reduce complications and shorten the course of the disease. In addition, it is very safe because there are no serious adverse events occurring. Further research should be developed from three aspects, including the development of systematic evaluation indicators and standardized clinical exercise rehabilitation pathway, more randomized controlled trials, and the development of individualized exercise program so as to help patients with AD better improve the prognosis and QoL.


Assuntos
Aneurisma Dissecante , Reabilitação Cardíaca , Aneurisma Dissecante/diagnóstico , Exercício Físico , Terapia por Exercício , Humanos , Qualidade de Vida
10.
Physiol Plant ; 173(4): 2191-2206, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34549440

RESUMO

Water-saving and drought-resistant rice (WDR) is widely grown in central China in recent years. However, studies have not explored the interaction effect of WDR and irrigation regimes on drought-resistance capacities under severe drought at sensitive growth periods. A pot experiment was conducted using a WDR cultivar Hanyou73 (HY73) and traditional high-yielding and drought-sensitive cultivar Huiliangyou 898 (HLY898). Three irrigation regimes, including flooding irrigation (W1), mild wetting-drying alternation irrigation (W2), and severe wetting-drying alternation irrigation (W3), were applied before heading. At heading, severe drought with -50 KPa soil water potential was established for all treatments and cultivars. The findings showed that cultivar HY73 under W2 treatment had the highest yield, 1000-grain yield, filled grain, relative water content, and photosynthesis potential compared with the other combinations. The higher net photosynthetic rate (Pn ) was attributed to larger mesophyll conductance (gm ) in drought for cultivar HY73 under W2 treatment compared with that for cultivar HLY898 and the other water treatments. Enhanced photo-respiration rate may be an important photoprotection mechanism for achieving high Pn for cultivar HY73 coupled with W2 treatment than for other combinations in drought. The relative expression level of OsPIP1;1 gene was significantly down-regulated during drought in all cultivars and water regimes. But OsPIP1;2, OsPIP2;3, OsTIP2;2, and OsTIP3;1 genes were upregulated to alleviate the significant decrease in gs and gm under drought. These results suggest that WDR and mild wetting-drying alternation irrigation (W2) have significant interaction effects in improving photosynthetic production potential by maintaining higher gm under severe drought.


Assuntos
Oryza , Irrigação Agrícola , Biomassa , Secas , Oryza/genética , Fotossíntese , Triticum
11.
Chem Commun (Camb) ; 57(74): 9390-9393, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528958

RESUMO

Herein, a highly regioselective alkylation of propargylic carbonates for trisubstituted allenes with alkyl 1,4-dihydropyridine derivatives (1,4-DHPs) is developed via a photoredox/nickel dual-catalyzed process, which represents the first direct approach to access alkylated allene products without alkyl organometallic reagents. This method features a broad substrate scope and mild conditions. A hypothetical mechanism with an alkyl radical and an allenyl Ni(III) species is proposed. Benzylation products were also obtained to be the complement building blocks for the potential synthesis of pharmaceuticals.


Assuntos
Alcadienos/síntese química , Carbonatos/química , Níquel/química , Alcadienos/química , Alquilação , Catálise , Estrutura Molecular , Oxirredução , Processos Fotoquímicos , Estereoisomerismo
12.
Nanomaterials (Basel) ; 11(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34361140

RESUMO

In this work, FeCr-based films with different Y2O3 contents were fabricated using radio frequency (RF) magnetron sputtering. The effects of Y2O3 content on their microstructure and mechanical properties were investigated through scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), inductive coupled plasma emission spectrometer (ICP) and a nanoindenter. It was found that the Y2O3-doped FeCr films exhibited a nanocomposite structure with nanosized Y2O3 particles uniformly distributed into a FeCr matrix. With the increase of Y2O3 content from 0 to 1.97 wt.%, the average grain size of the FeCr films decreased from 12.65 nm to 7.34 nm, demonstrating a grain refining effect of Y2O3. Furthermore, the hardness of the Y2O3-doped FeCr films showed an increasing trend with Y2O3 concentration, owing to the synergetic effect of dispersion strengthening and grain refinement strengthening. This work provides a beneficial guidance on the development and research of composite materials of nanocrystalline metal with a rare earth oxide dispersion phase.

13.
World J Clin Cases ; 9(21): 5889-5899, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34368307

RESUMO

BACKGROUND: There is no research on quantitative pleural line movement. In this study, we assume that tissue Doppler and its quantitative technology can quantify the pleural line movement and can be used to diagnose pneumothorax. AIM: To evaluate the quantitative assessment of pleural line movement measured by tissue Doppler imaging (TDI) for pneumothorax diagnosis. METHODS: Adult patients (n = 45) diagnosed with unilateral pneumothorax were included in this study. Each patient underwent TDI of both lungs. The pneumothorax side and contralateral normal lung side were compared using several indices obtained from TDI: peak pleural line velocity (PVmax), peak chest wall tissue velocity (CVmax), peak pleural line strain value (PSmax), peak chest wall tissue strain value (CSmax), PVmax/CVmax and PSmax/CSmax. The receiver operating characteristic analysis was used to evaluate the performance of these quantitative assessments for pneumothorax diagnosis. RESULTS: Various quantitative variables of the pneumothorax side were all lower than that of the non-pneumothorax side and included the PVmax (0.36 cm/s vs 0.59 cm/s, P < 0.001), PSmax (1.14% vs 1.90%, P = 0.001), PVmax/CVmax (1.06 vs 4.93, P < 0.001), and PSmax/CSmax (0.76 vs 1.74, P < 0.001). For the discrimination of pneumothorax, the cut-off values of the PVmax, PSmax, PVmax/CVmax, and PSmax/CSmax were calculated as 0.50 cm/s, 0.94%, 1.96, and 1.12, respectively. Similarly, the sensitivities and specificities of PVmax, PSmax, PVmax/CVmax, and PSmax/CSmax were 96% and 62%, 47% and 91%, 93% and 96%, and 82% and 93%, respectively. The area under the receiver operating characteristic curve were 0.84, 0.72, 0.99, and 0.91, respectively, for PVmax, PSmax, PVmax/CVmax, and PSmax/CSmax. CONCLUSION: Quantification analysis of pleural line movement using TDI is a useful tool for the diagnosis of pneumothorax.

14.
Radiat Res ; 196(4): 429-435, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34399423

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) is the key rate-limiting enzyme in the regulation of nicotinamide adenine dinucleotide (NAD) biosynthesis, and its activity is critical for the replenishment of NAD level as well as cell survival or death. As one of the most important components in the electron transport chain of complex I in mitochondrion, sustained supply of NAD is essential to the maintenance of energy metabolism both in normal and cancer cells. Recent research showed that X-ray radiation sharply downregulated the expression of NAMPT, which may be the main cause of radiation damage in salivary gland. Consistently, upregulation of NAMPT by phenylephrine restored the function and tissue structure of salivary gland, indicating the cytoprotective role of NAMPT in preventing radiation damage in normal tissues of patients with head and neck cancer during radiotherapy. On the other hand, NAMPT downregulation and NAD depletion could induce cell death in oral squamous cell cancer, suggesting that a combination of NAMPT inhibitor and radiotherapy presents a promising therapeutic strategy for cancer treatment. Based on our and other's studies, NAMPT may have dual roles in cancer radiotherapy: the upregulation of NAMPT could serve to suppress radiotherapy complications such as radiation sialadenitis, and combination regimens that involve NAMPT inhibitors may enhance efficacy of radiotherapy for cancer treatment.

15.
Chemosphere ; 281: 130977, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34289625

RESUMO

Per-, Poly-fluoroalkyl substances (PFASs) accumulation in benthic environments is mainly determined by material mixing and represents a significant challenge to river remediation. However, less attention has been paid to the effects of sediment distribution on PFASs accumulation, and how PFASs influence microbial community coalescence and biogeochemical processes. In order to identify correlations between PFASs distribution and benthic microbial community functions, we conducted a field study and quantified the ecological constrains of material transportation on benthic microorganisms. Perfluorohexanoic acid (PFHxA) contributed most to the taxonomic heterogeneity of both archaeal (12.199%) and bacterial (13.675%) communities. Genera Methanoregula (R2 = 0.292) and Bacillus (R2 = 0.791) were identified as indicators that respond to PFASs. Phylogenetic null modeling indicated that deterministic processes (50.0-82.2%) dominated in spatial assembly of archaea, while stochasticity (94.4-97.8%) dominated in bacteria. Furthermore, spatial mixing of PFASs influenced broadly in nitrogen cycling of archaeal genomes, and phosphorus mineralization of bacterial genomes (p < 0.05). Overall, we quantified the effect of PFASs on community assembly and highlighted the constrains of PFASs influence on benthic geochemical potentials, which may provide new insights into riverine remediation.


Assuntos
Fluorcarbonetos , Microbiota , Archaea/genética , Ecossistema , Fluorcarbonetos/análise , Sedimentos Geológicos , Filogenia , Rios
16.
Chemosphere ; 281: 131001, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34289638

RESUMO

Studies on the symbiosis of microalgae-bacteria have been accelerating as a mean for wastewater remediation. However, there were few reports about the microalgae-bacteria consortia for chemical wastewater treatment. The aim of the present study is to develop an autotrophic and heterotrophic consortium for chemical wastewater treatment and probe whether and how bacteria could benefit from the microalgae during the treatment process, using PTA wastewater as an approach. A process-dependent strategy was applied. First of all, the results showed that the sludge beads with the sludge concentration of 30 g/L were the optimal one with the COD removal rate at 84.8% but the ceiling effect occurred (COD removal rate < 90%) even several common reinforcement methods were applied. Additionally, by adding the microalgae Chlorella vulgaris, a microalgae-activated sludge consortium was formed inside the immobilized beads, which provided better performance to shatter the ceiling effect. The COD remove rate was higher than 90%, regardless of the activated sludge was pre-culture or not. COD removal capacity could also be improved (COD removal rate > 92%) when LEDs light belt was offered as an advanced light condition. Biochemical assay and DNA analysis indicated that the microalgae could form an internal circulation of substances within the activated sludge and drove the microbial community to success and the corresponding gene functions, like metabolism and.


Assuntos
Chlorella vulgaris , Microalgas , Purificação da Água , Biomassa , Nitrogênio , Águas Residuárias
17.
Toxicol Lett ; 350: 111-120, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34274428

RESUMO

Strong epidemiological evidence demonstrates an association between chronic arsenic exposure and anemia. We recently found that As+3 impairs erythropoiesis by disrupting the function of GATA-1; however the downstream pathways impacted by the loss of GATA-1 function have not been evaluated. Additionally, our previous findings indicate that the predominant arsenical in the bone marrow of mice exposed to As+3 in their drinking water for 30 days was MMA+3, but the impacts of this arsenical on erythorpoisis also remain largely unknown. The goal of this study was to address these critical knowledge gaps by evaluating the comparative effects of arsenite (As+3) and the As+3 metabolite, monomethyarsonous acid (MMA+3) on two critical regulatory pathways that control the differentiation and survival of early erythroid progenitor cells. We found that 500 nM As+3 and 100 and 500 nM MMA+3 suppress erythropoiesis by impairing the differentiation of early stage erythroid progenitors. The suppression of early erythroid progenitor cell development was attributed to combined effects on differentiation and survival pathways mediated by disruption of GATA-1 and STAT5. Our results show that As+3 primarily disrupted GATA-1 function; whereas, MMA+3 suppressed both GATA-1 and STAT5 activity. Collectively, these findings provide novel mechanistic insights into arsenic-induced dyserythropoiesis and suggest that MMA+3 may be more toxic than As+3 to early developing erythroid cells.


Assuntos
Anemia/induzido quimicamente , Arsênio/toxicidade , Arsenitos/toxicidade , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Precursoras Eritroides/efeitos dos fármacos , Eritropoese/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Animais , Humanos , Camundongos , Modelos Animais
18.
J Cereb Blood Flow Metab ; : 271678X211028475, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187233

RESUMO

Hemorrhagic stroke is a leading cause of death. The causes of intracerebral hemorrhage (ICH)-induced brain damage are thought to include lysis of red blood cells, hemin release and iron overload. These mechanisms, however, have not proven very amenable to therapeutic intervention, and so other mechanistic targets are being sought. Here we report that accumulation of endogenously formed zinc protoporphyrin (ZnPP) also critically contributes to ICH-induced brain damage. ICH caused a significant accumulation of ZnPP in brain tissue surrounding hematoma, as evidenced by fluorescence microscopy of ZnPP, and further confirmed by fluorescence spectroscopy and supercritical fluid chromatography-mass spectrometry. ZnPP formation was dependent upon both ICH-induced hypoxia and an increase in free zinc accumulation. Notably, inhibiting ferrochelatase, which catalyzes insertion of zinc into protoporphyrin, greatly decreased ICH-induced endogenous ZnPP generation. Moreover, a significant decrease in brain damage was observed upon ferrochelatase inhibition, suggesting that endogenous ZnPP contributes to the damage in ICH. Our findings reveal a novel mechanism of ICH-induced brain damage through ferrochelatase-mediated formation of ZnPP in ICH tissue. Since ferrochelatase can be readily inhibited by small molecules, such as protein kinase inhibitors, this may provide a promising new and druggable target for ICH therapy.

19.
Zhen Ci Yan Jiu ; 46(6): 464-8, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34190448

RESUMO

Although the basic mechanism of acupuncture-moxibustion has been revealed from many aspects, there are still many shackles in the transformation of the related research achievements. The transformation of academic achievements of experimental acupunctology is an urgent issue to be solved at present. Network regulation is the basic action mode of acupuncture therapy. In the present paper, we proposed that the "acupuncture network drug" could carry a variety of effective active ingredients which may be the core component of network regulation of acupuncture therapy. The "exosomes", polyvesicle derived from the intracellular lysosomal microparticles invagination, contain complex RNAs and proteins and exist in the body fluids and function in secreting abundant activate substances to participate in intercellular communication, which is the research hotspot in the field of frontier life science in the world. They play an important role in the diagnosis and treatment of diseases, and drug development, etc.. Our studies using rats with adjuvant arthritis and mice with sepsis displayed that after intraperitoneal administration of serum exosomes derived from normal animals receiving acupuncture intervention, an acupuncture-like analgesic effect and an anti-inflammatory effect were achieved, respectively. It is thus possible that acupuncture network drugs could be developed from serum exosomes secreted by exosome autogenous living cells after acupuncture intervention by virtue of the characteristics of low immunogenicity and may have great advantages in drug development and modification. It is also expected to provide new ideas for the transformation of experimental research results and to in depth give explanations about the underlying mechanisms of acupuncture therapy.


Assuntos
Terapia por Acupuntura , Acupuntura , Exossomos , Moxibustão , Preparações Farmacêuticas , Animais , Exossomos/genética , Camundongos , Ratos
20.
Chemosphere ; 282: 130966, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34082314

RESUMO

Biological methods are promising treatment methods to remove pollutants from wastewater. Recently, microalgae have been proved to be of strong application potential in wastewater treatment. In this study, a microalga - antibiotic treatment system was built to evaluate the treatment capacity of microalgae in antibiotic wastewater. In the group with Chlorella pyrenoidosa, the removal rate of cefradine was 41.47 ± 0.62% after 24 h of treatment, which was 3.4 times higher than that without microalgae (12.37 ± 2.30%). Algal decomposition was the main removal mechanism. Meanwhile, the effect of multiple microalgae species on antibiotic treatment was studied. The removal rates of cefradine by C. pyrenoidosa cultivated in the filtered fluid of Microcystis aeruginosa were 75.48 ± 0.29%, which was significantly higher than those by C. pyrenoidosa only. Those indicated that multiple microalgae species strategy was a potential enhancement strategy for algae-based antibiotic treatment. Finally, amoxicillin and norfloxacin were used to study the treatment potential of this technology for more different kinds antibiotics and the integration of microalgae with activated sludge was also investigated. Amoxicillin can be quickly removed by microalgae, but the removal effect of norfloxacin by microalgae is poor. The refractory antibiotic norfloxacin can be treated by co-culturing microalgae and activated sludge. Those showed the good expansibility of microalgae-based technology. The findings indicated that with microalgae-based antibiotic removal method has good application potential, and combined with other technologies, it can effectively remove the refractory antibiotics.


Assuntos
Chlorella , Microalgas , Antibacterianos , Biomassa , Esgotos , Águas Residuárias
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