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2.
Cell Mol Biol (Noisy-le-grand) ; 67(2): 95-100, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817333

RESUMO

To explore the diagnostic value of MRI-DWI signal intensity value combined with serum PGI. PGII and CA199 in early gastric cancer. Sixty cases of gastric cancer patients admitted to our hospital from December 2019 to December 2020 were selected as the gastric cancer group and 80 cases of healthy volunteers who underwent physical examination in our hospital during the same period were selected as the healthy group. All the 60 patients underwent MRI-DWI examination, and the pathological diagnosis results were regarded as the gold standard. MRI-DWI images, MRI-DWI signal intensity values of patients with different degrees of gastric cancer differentiation. Serum PGI, PGII and CA199 levels of subjects in the two groups were compared. AUC was used to evaluate the diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PG II and CA199 for early gastric cancer. In the healthy group, T1W1 showed relatively uniform low signal intensity. While T2WI showed no significant increase in signal intensity. In the gastric cancer group. There was diffuse gastric wall thickening, local thickening or mass formation; T1WI and WATS showed slightly lower signal intensity in the lesion area. T2WI, FLAIR and B-TFE showed slightly uneven or moderately increased signal intensity. DWI showed limited diffusion, and the signal intensity increased uniformly or more uniformly, and the range of increase was clear. The signal intensity of MRI-DWI was 89.12 ± 8.14 in patients with low differentiation, 82.17 ± 6.35 in patients with moderate differentiation, and 74.52 ± 4.53 in patients with high differentiation. There were significant differences in the signal intensity of MRI-DWI among the three groups, and the difference was statistically significant (F=12.214, P <0.05). Serum PGI levels of subjects in the gastric cancer group were significantly lower than those in the healthy group, and the levels of PGII and CA199 were significantly higher than that in the healthy group, with statistical significance (P <0.05). The AUC, sensitivity and specificity of MRI-DWI signal intensity value and serum PGI, PGII and CA199 combined indexes in the diagnosis of gastric cancer were significantly higher than those of the independent indexes, with statistical significance (P <0.05). Conclusion: MRI-DWI signal strength value, serum PGI, PGII and CA199 levels are closely related to the occurrence and development of early gastric cancer. The combined detection and diagnosis efficiency is higher, which is helpful to improve the detection rate of early gastric cancer and is worthy of extensive clinical application.

3.
J Hazard Mater ; : 127826, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34823951

RESUMO

With increasing plastic consumption, the large amount of polystyrene nanoplastics (PS-NPs) in agricultural soil may not only directly affect the plant growth, but also indirectly affect the abiotic stress tolerance in crops. In this study, the barley (Hordeum vulgare L.) was irrigated with 2 g L-1 PS-NPs (65.776 ± 0.528 nm) solution for 7 days, then subjected to low temperature (2 â„ƒ) for 24 h. The imaging of protoplasts indicated that polymethylmethacrylate nanoplastics could across the cell wall and accumulate in plant cells. The PS-NPs significantly decreased Rubisco activities and ATP production, hence limiting the photosynthetic carbon assimilation in barley under low temperature. The PS-NPs accumulated in cells also caused the significantly decreased activities of key enzymes involved in sucrolytic, glycolysis and starch metabolism pathways, including UDP-glucose pyrophorylase, ADP-Glucose pyrophosphorylase, phosphoglucomutase, glucose-6-phosphate dehydrogenase, phosphoglucoisomerase, fructokinase and phosphofructokinase. In addition, under low temperature, the PS-NPs presence significantly reduced the activities of superoxide dismutase, ascorbate peroxidase and catalase in chloroplasts, and significantly reduced the activities of ascorbate peroxidase and catalase in mitochondria. Thus, it is suggested that the PS-NPs accumulated in plant cells impaired the low temperature tolerance in barley mainly by the negative effects on photosynthetic carbon assimilation, carbohydrate metabolism and ROS homeostasis in sub-cellular level.

4.
Avian Res ; 12(1): 59, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745642

RESUMO

Plastic waste and debris have caused substantial environmental pollution globally in the past decades, and they have been accumulated in hundreds of terrestrial and aquatic avian species. Birds are susceptible and vulnerable to external environments; therefore, they could be used to estimate the negative effects of environmental pollution. In this review, we summarize the effects of macroplastics, microplastics, and plastic-derived additives and plastic-absorbed chemicals on birds. First, macroplastics and microplastics accumulate in different tissues of various aquatic and terrestrial birds, suggesting that birds could suffer from the macroplastics and microplastics-associated contaminants in the aquatic and terrestrial environments. Second, the detrimental effects of macroplastics and microplastics, and their derived additives and absorbed chemicals on the individual survival, growth and development, reproductive output, and physiology, are summarized in different birds, as well as the known toxicological mechanisms of plastics in laboratory model mammals. Finally, we identify that human commensal birds, long-life-span birds, and model bird species could be utilized to different research objectives to evaluate plastic pollution burden and toxicological effects of chronic plastic exposure.

5.
Eur J Pharmacol ; 912: 174613, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740581

RESUMO

Pulmonary fibrosis (PF) is a chronic, progressive heterogeneous disease of lung tissues with poor lung function caused by scar tissue. Due to our limited understanding of its mechanism, there is currently no treatment strategy that can prevent the development of PF. In recent years, iron accumulation and mitochondrial damage have been reported to participate in PF, and drugs that reduce iron content and improve mitochondrial function have shown significant efficacy in animal experimental models. Excessive iron leads to mitochondrial impairment, which may be the key cause that results in the dysfunction of various kinds of pulmonary cells and further promotes PF. As an emerging research hotspot, there are few targeted effective therapeutic strategies at present due to limited mechanistic understanding. In this review, the roles of iron homeostasis imbalance and mitochondrial damage in PF are summarized and discussed, highlighting a promising direction for finding truly effective therapeutics for PF.

6.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2658-2667, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472286

RESUMO

Lipids are important components of living organisms that participate in and regulate a variety of life activities. Lipids in plants also play important physiological functions in response to a variety of abiotic stresses (e.g. salt stress, drought stress, temperature stress). However, most research on lipids focused on animal cells and medical fields, while the functions of lipids in plants were overlooked. With the rapid development of "omics" technologies and biotechnology, the lipidomics has received much attention in recent years because it can reveal the composition and function of lipids in a deep and comprehensive way. This review summarizes the recent advances in the functions and classification of lipids, the development of lipidomics technology, and the responses of plant lipids against drought stress, salt stress and temperature stress. In addition, challenges and prospects were proposed for future lipidomics research and further exploration of the physiological functions of lipids in plant stress resistance.


Assuntos
Secas , Regulação da Expressão Gênica de Plantas , Lipídeos , Plantas , Estresse Fisiológico
7.
J Chromatogr A ; 1654: 462462, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34411835

RESUMO

The identification of ILRs in fire investigations has attracted great attention for decades, and background at fire scenes caused complex interference on ILR identification by contributing characteristic compounds. Aiming at exploring the correlation between the interference extent to gasoline identification and chemical composition/structure, two polystyrene-butadiene rubbers (SBr) with typical styrene contents involving alkylbenzene in molecules were selected particularly. The free burning residues in the presence and absence of gasoline were collected and analyzed via gas chromatography-mass spectrometry. It is striking that SBr with typical styrene content caused the most remarkable interference to gasoline identification as far as reported since it is even impossible to be distinguished from gasoline through chromatography profiles. Additionally, the molecular structure together with the chemical composition influences the interference extent as well. To trace the source of the remarkable interference from SBr, polystyrene, polybutadiene, as well as one polystyrene-butadiene-styrene block copolymer, were picked particularly due to their specific chemical relations. The results of target compounds analysis on the corresponding combustion residues revealed that the remarkable interference of SBrs originated from the combination of 'styrene' and 'butadiene' by contributing different target compounds. The results provide further support for the proposal of the correlation of the interferents chemical compositions with the interference extent. Furthermore, this study provides important references for fire debris analysis by predicting the interference of different substrates on the basis of their chemical composition.


Assuntos
Butadienos , Incêndios , Ciências Forenses , Gasolina , Butadienos/química , Ciências Forenses/métodos , Cromatografia Gasosa-Espectrometria de Massas , Gasolina/análise , Poliestirenos/química
8.
J Pineal Res ; 71(3): e12761, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34392562

RESUMO

With increasing plastic production and consumption, large amounts of polystyrene nanoplastics are accumulated in soil due to improper disposal causing pollution and deleterious effects to environment. However, little information is available about how to alleviate the adverse impacts of nanoplastics on crops. In this study, the involvement of melatonin in modulating nanoplastic uptake, translocation, and toxicity in wheat plant was investigated. The results demonstrated that exogenous melatonin application reduced the nanoplastic uptake by roots and their translocation to shoots via regulating the expression of genes associated with aquaporin, including the upregulation of the TIP2-9, PIP2, PIP3, and PIP1.2 in leaves and TIP2-9, PIP1-5, PIP2, and PIP1.2 in roots. Melatonin activated the ROS scavenging system to maintain a better redox homeostasis and ameliorated the negative effects of nanoplastics on carbohydrate metabolism, hence ameliorated the plant growth and enhanced the tolerance to nanoplastics toxicity. This process was closely related to the exogenous melatonin application induced melatonin accumulation in leave. These results suggest that melatonin could alleviate the adverse effects of nanoplastics on wheat, and exogenous melatonin application might be used as a promising management strategy to sustain crop production in the nanoplastic-polluted soils.

9.
Chemosphere ; 284: 131329, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34198061

RESUMO

Cu(II) is generally considered to be a poor activator for PMS decomposition, thus the potential impact of trace Cu(II) on PMS induced oxidation of typical pollutants is always overlooked. In this study, we reported that trace Cu(II) could significantly promote PMS induced degradation of four selected sulfonamide antibiotics (SAs), namely, sulfamehoxazole (SMX), sulfathiazole (STZ), sulfamerazine (SMZ), and sulfamonomethoxine (SMM). Different from conventional PMS-induced oxidation process, high-valent Cu(III) was ascertained as the primary reactive intermediate for SAs degradation, which was confirmed by raman tests and electron paramagnetic resonance (EPR). High concentrations of Cu(II) or PMS were beneficial to degradation of the selected contaminants. In PMS/Cu(II) oxidation system, all the selected SAs could undergo several different degradation pathways including continuous oxidation of aniline group, hydroxylation and S-N bond cleavage. In particular, for six-membered SAs, such as SMZ and SMM, a SO2 extrusion pathway was also detected. The potential mechanism for Cu(III) formation was also proposed, which was believed to be highly related to the nature of the SAs. Hydroxylamine-SAs (N4-OH-SAs), generated from direct PMS oxidation of SAs, was deduced as the "promoter" for the whole oxidation process. And the generation of Cu(III) was likely to proceed through the interaction between PMS and Cu(I), which possibly derived from the reduction of Cu(II) by N4-OH-SAs. The results obtained in this study validated the contribution of Cu(III) to the elimination of pollutants and expanded our understanding of the oxidation process of PMS in the presence of trace amounts of Cu(II).


Assuntos
Antibacterianos , Poluentes Químicos da Água , Oxirredução , Peróxidos , Sulfonamidas , Poluentes Químicos da Água/análise
10.
J Fish Dis ; 44(10): 1609-1617, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34192354

RESUMO

The expression of herpesvirus genes during infection of tissue culture cells can be classified into three main classes: immediate-early (IE), early and late. The transcriptional regulation of herpesvirus IE genes is a critical regulatory step in the initiation of viral infection, with their regulation differing from that of early and late genes. Herein, we report that an IE gene (ORF3) promoter in channel catfish virus (CCV, Ictalurid herpesvirus 1) can be activated regardless of the presence or absence of CCV infection, indicating that the ORF3 promoter is efficiently driven by host-cell transcription factors in a viral infection-independent manner. The analysis of truncated promoter activity suggested that several transcription elements play a role in activating the ORF3 promoter, with the key cis-elements seemingly located in the flanking sequence of the start codon ATG. We further found that this flanking sequence contained multiple AT-rich sequences, and systematic mutational analyses showed that these AT-rich sequences affected normal transcription levels of the ORF3 promoter. To summarize, multiple AT-rich domains, representing the novel architecture of IE gene promoters in Ictalurid herpesvirus 1, serve as a cis-element for ORF3 transcription.


Assuntos
Doenças dos Peixes/virologia , Infecções por Herpesviridae/veterinária , Ictaluridae , Ictalurivirus/genética , Regiões Promotoras Genéticas , Proteínas Virais/genética , Animais , Linhagem Celular , Infecções por Herpesviridae/virologia
11.
Exp Dermatol ; 30(9): 1332-1339, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34089547

RESUMO

Screening for wound infection relies on the expertise of the provider. Clinical diagnosis of infections based on wound swab/biopsy results often takes a few days and may not assess the full wound. There is a need for a non-invasive tool that can quickly and accurately diagnose wound infection. Leukocyte esterase strips are used to identify various infectious diseases. However, it is not clear whether infected wounds also have elevated leukocyte esterase activities as compared with non-infected wounds. To achieve the objective, a device was developed to detect elevated leukocyte esterase activities in wounds by measuring wound exudates adsorbed onto wound dressings in 3 minutes. The efficacy of the device in assessing leukocyte esterase activities across various chronic wounds was tested. Such measurements were unaffected by the type of underlying wound dressing. By correlating the device outputs with clinical adjudication of infection, we found that this device had high positive predictive values for diagnosing wound infection in a wide variety of chronic wounds. In addition, a positive device output increases the probability of detecting infected wounds, while the negative device output reduces the probability of detecting infected wounds. This rapid non-contact and disposable diagnostic tool may serve as a rapid and accurate indication of infection in the chronic wound.

12.
Nat Commun ; 12(1): 3845, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158506

RESUMO

Atr is a serine/threonine kinase, known to sense single-stranded DNA breaks and activate the DNA damage checkpoint by phosphorylating Chek1, which inhibits Cdc25, causing cell cycle arrest. This pathway has not been implicated in neuroregeneration. We show that in Drosophila sensory neurons removing Atr or Chek1, or overexpressing Cdc25 promotes regeneration, whereas Atr or Chek1 overexpression, or Cdc25 knockdown impedes regeneration. Inhibiting the Atr-associated checkpoint complex in neurons promotes regeneration and improves synapse/behavioral recovery after CNS injury. Independent of DNA damage, Atr responds to the mechanical stimulus elicited during regeneration, via the mechanosensitive ion channel Piezo and its downstream NO signaling. Sensory neuron-specific knockout of Atr in adult mice, or pharmacological inhibition of Atr-Chek1 in mammalian neurons in vitro and in flies in vivo enhances regeneration. Our findings reveal the Piezo-Atr-Chek1-Cdc25 axis as an evolutionarily conserved inhibitory mechanism for regeneration, and identify potential therapeutic targets for treating nervous system trauma.


Assuntos
Axônios/metabolismo , Quinase 1 do Ponto de Checagem/genética , Canais Iônicos/genética , Regeneração Nervosa/genética , Animais , Animais Geneticamente Modificados , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Quinase 1 do Ponto de Checagem/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Células HEK293 , Humanos , Canais Iônicos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/genética
13.
Neurobiol Dis ; 155: 105389, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33975016

RESUMO

Promoting the combination of robust regeneration of damaged axons and synaptic reconnection of these growing axon populations with appropriate neuronal targets represents a major therapeutic goal following spinal cord injury (SCI). A key impediment to achieving this important aim includes an intrinsic inability of neurons to extend axons in adult CNS, particularly in the context of the chronically-injured spinal cord. We tested whether an inhibitory peptide directed against phosphatase and tensin homolog (PTEN: a central inhibitor of neuron-intrinsic axon growth potential) could restore inspiratory diaphragm function by reconnecting critical respiratory neural circuitry in a rat model of chronic cervical level 2 (C2) hemisection SCI. We found that systemic delivery of PTEN antagonist peptide 4 (PAP4) starting at 8 weeks after C2 hemisection promoted substantial, long-distance regeneration of injured bulbospinal rostral Ventral Respiratory Group (rVRG) axons into and through the lesion and back toward phrenic motor neurons (PhMNs) located in intact caudal C3-C5 spinal cord. Despite this robust rVRG axon regeneration, PAP4 stimulated only minimal recovery of diaphragm function. Furthermore, re-lesion through the hemisection site completely removed PAP4-induced functional improvement, demonstrating that axon regeneration through the lesion was responsible for this partial functional recovery. Interestingly, there was minimal formation of putative excitatory monosynaptic connections between regrowing rVRG axons and PhMN targets, suggesting that (1) limited rVRG-PhMN synaptic reconnectivity was responsible at least in part for the lack of a significant functional effect, (2) chronically-injured spinal cord presents an obstacle to achieving synaptogenesis between regenerating axons and post-synaptic targets, and (3) addressing this challenge is a potentially-powerful strategy to enhance therapeutic efficacy in the chronic SCI setting. In conclusion, our study demonstrates a non-invasive and transient pharmacological approach in chronic SCI to repair the critically-important neural circuitry controlling diaphragmatic respiratory function, but also sheds light on obstacles to circuit plasticity presented by the chronically-injured spinal cord.

14.
Environ Sci Pollut Res Int ; 28(40): 56418-56431, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34053046

RESUMO

The microbial community and functional flora in rare earth mining areas are correlated, but the characteristics and metabolic pathways of pollutant in such mining areas are still poorly known. The heavy metals, rare earth elements, and microorganisms present after mining of rare earth mine sites were analyzed. After mining, all sampling sites exhibited low pH and low total organic carbon levels, accompanied by high iron and aluminum concentrations. The development of vegetation is closely related to the development of microorganisms. In the complex environment of rare earth mining areas, Proteobacteria exhibit an absolute competitive advantage. During mine environmental recovery, the relative abundances of Acidobacteria and Chloroflexi will increase markedly, and with further restoration the relative abundance of Firmicutes will gradually decrease. Many genera of bacteria related to the N cycle and heavy metal metabolism were detected in the study area, indicating the important metabolic pathways for ammonia nitrogen and heavy metals in rare earth mining areas. Bacterial genera that promote plant nitrogen fixation also occur in the area, further revealing the nitrogen cycle. This research is important for health assessment and recovery of rare earth mines.


Assuntos
Metais Terras Raras , Microbiota , Poluentes do Solo , China , Metais Terras Raras/análise , Mineração , Solo , Microbiologia do Solo , Poluentes do Solo/análise
15.
Dev Comp Immunol ; 121: 104078, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33794278

RESUMO

Host protective inflammatory caspase activity must be tightly regulated to prevent pathogens infection, however, the inflammatory caspase-engaged inflammasome activation in teleost fish remains largely unknown. In this study, we reveal a bifurcated evolutionary role of the inflammatory caspase in mediating both non-canonical and canonical inflammasome pathways in teleost fish. Through characterization of a unique inflammatory SmCaspase from the teleost Scophthalmus maximus (turbot), we found it can directly recognize cytosolic lipopolysaccharide (LPS) via its N-terminal CARD domain, resulting in caspase-5-like proteolytic enzyme activity-mediated pyroptosis in Turbot Muscle Fibroblasts. Interestingly, we also found that this inflammatory caspase can be recruited to SmNLRP3-SmASC to form the NLRP3 inflammasome complex, engaging the SmIL-1ß release in Head Kidney-derived Macrophages. Consequently, the SmCaspase activation can recognize and cleave the SmGSDMEb to release its N-terminal domain, mediating both pyroptosis and bactericidal activities. Furthermore, the SmCaspase-SmGSDMEb axis-gated pyroptosis governs the bacterial clearance and epithelial desquamation in fish gill filaments in vivo. To our knowledge, this study is the first to identify an inflammatory caspase acting as a central coordinator in NLRP3 inflammasome, as well as a cytosolic LPS receptor; thus uncovering a previously unrecognized function of inflammatory caspase in turbot innate immunity.

16.
Front Cell Dev Biol ; 9: 653638, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842481

RESUMO

Paralysis following spinal cord injury (SCI) is due to failure of axonal regeneration. It is believed that axon growth is inhibited by the presence of several types of inhibitory molecules in central nervous system (CNS), including the chondroitin sulfate proteoglycans (CSPGs). Many studies have shown that digestion of CSPGs with chondroitinase ABC (ChABC) can enhance axon growth and functional recovery after SCI. However, due to the complexity of the mammalian CNS, it is still unclear whether this involves true regeneration or only collateral sprouting by uninjured axons, whether it affects the expression of CSPG receptors such as protein tyrosine phosphatase sigma (PTPσ), and whether it influences retrograde neuronal apoptosis after SCI. In the present study, we assessed the roles of CSPGs in the regeneration of spinal-projecting axons from brainstem neurons, and in the process of retrograde neuronal apoptosis. Using the fluorochrome-labeled inhibitor of caspase activity (FLICA) method, apoptotic signaling was seen primarily in those large, individually identified reticulospinal (RS) neurons that are known to be "bad-regenerators." Compared to uninjured controls, the number of all RS neurons showing polycaspase activity increased significantly at 2, 4, 8, and 11 weeks post-transection (post-TX). ChABC application to a fresh TX site reduced the number of polycaspase-positive RS neurons at 2 and 11 weeks post-TX, and also reduced the number of active caspase 3-positive RS neurons at 4 weeks post-TX, which confirmed the beneficial role of ChABC treatment in retrograde apoptotic signaling. ChABC treatment also greatly promoted axonal regeneration at 10 weeks post-TX. Correspondingly, PTPσ mRNA expression was reduced in the perikaryon. Previously, PTPσ mRNA expression was shown to correlate with neuronal apoptotic signaling at 2 and 10 weeks post-TX. In the present study, this correlation persisted after ChABC treatment, which suggests that PTPσ may be involved more generally in signaling axotomy-induced retrograde neuronal apoptosis. Moreover, ChABC treatment caused Akt activation (pAkt-308) to be greatly enhanced in brain post-TX, which was further confirmed in individually identified RS neurons. Thus, CSPG digestion not only enhances axon regeneration after SCI, but also inhibits retrograde RS neuronal apoptosis signaling, possibly by reducing PTPσ expression and enhancing Akt activation.

18.
J Biol Chem ; 296: 100666, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33862082

RESUMO

Heme oxygenases (HOs) play a critical role in recouping iron from the labile heme pool. The acquisition and liberation of heme iron are especially important for the survival of pathogenic bacteria. All characterized HOs, including those belonging to the HugZ superfamily, preferentially cleave free b-type heme. Another common form of heme found in nature is c-type heme, which is covalently linked to proteinaceous cysteine residues. However, mechanisms for direct iron acquisition from the c-type heme pool are unknown. Here we identify a HugZ homolog from the oligopeptide permease (opp) gene cluster of Paracoccus denitrificans that lacks any observable reactivity with heme b and show that it instead rapidly degrades c-type hemopeptides. This c-type heme oxygenase catalyzes the oxidative cleavage of the model substrate microperoxidase-11 at the ß- and/or δ-meso position(s), yielding the corresponding peptide-linked biliverdin, CO, and free iron. X-ray crystallographic analysis suggests that the switch in substrate specificity from b-to c-type heme involves loss of the N-terminal α/ß domain and C-terminal loop containing the coordinating histidine residue characteristic of HugZ homologs, thereby accommodating a larger substrate that provides its own iron ligand. These structural features are also absent in certain heme utilization/storage proteins from human pathogens that exhibit low or no HO activity with free heme. This study thus expands the scope of known iron acquisition strategies to include direct oxidative cleavage of heme-containing proteolytic fragments of c-type cytochromes and helps to explain why certain oligopeptide permeases show specificity for the import of heme in addition to peptides.


Assuntos
Proteínas de Bactérias/metabolismo , Biliverdina/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Heme/análogos & derivados , Heme/metabolismo , Ferro/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Paracoccus denitrificans/enzimologia , Catálise , Cristalografia por Raios X , Heme Oxigenase (Desciclizante)/química , Especificidade por Substrato
19.
Am J Respir Cell Mol Biol ; 65(2): 189-200, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33861690

RESUMO

Strict control of iron homeostasis is critical for the maintenance of normal lung function. Iron accumulates in the lungs of patients with idiopathic pulmonary fibrosis (PF), but the characteristics of iron metabolism in the pathogenesis of PF and related targeting therapeutics are not well studied. In this study, we investigated the cellular and molecular characteristics of iron metabolism in fibrotic lungs and further explored the efficacy of clioquinol (CQ) for the treatment of PF as well as its functional mechanism. Iron aggregates accumulated in the lungs of patients with idiopathic PF, and FTL (ferritin light chain) transcripts were increased in their pulmonary fibroblasts. In the bleomycin (BLM)-induced PF (BLM-PF) mouse model, pulmonary iron accumulation is a very early and concomitant event of PF. Labile iron pool levels in both fibroblasts and macrophages from the BLM-PF model were elevated, and iron metabolism was dysregulated. CQ attenuated PF induced by BLM and FITC, and iron-saturated CQ did not alleviate BLM-PF. Furthermore, CQ inhibited the activation of fibroblasts, including proliferation, fibrotic differentiation, proinflammatory cytokine secretion, and migration. In conclusion, our study demonstrated that CQ, acting as an iron chelator, attenuates experimental PF through inactivation of fibroblasts, providing support for targeting iron metabolism as a basis for PF treatment.


Assuntos
Quelantes/farmacologia , Clioquinol/farmacologia , Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Ferro/metabolismo , Animais , Bleomicina/efeitos adversos , Bleomicina/farmacologia , Modelos Animais de Doenças , Feminino , Fibroblastos/patologia , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia , Masculino , Camundongos
20.
Materials (Basel) ; 14(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33671935

RESUMO

Compared with standard-ply composites, thin-ply composites exhibit a superior mechanical performance under various operating conditions due to their positive size effects. Thin-ply laminate failure modes, including matrix initial damage (MID), matrix failure (MF), and fiber failure (FF), have been distinguished through a systematic acoustic emission (AE) signals analysis combined with scanning electron microscopy (SEM). First, the characteristic frequencies of various failure modes are identified based on unidirectional laminates ([90] 68 and [0] 68). Then, according to the identified frequencies corresponding to distinctive damage modes, four lay-up sequences (02[[90m/0m]ns]02, m = 1, 2, 4, 8, n × m = 16) with a constant total thickness are designed, and the effects of the number of identical plies in the laminate thickness on the damage evolution characteristics and the damage process under uniaxial tension loads are dynamically monitored. The obtained results indicate that the characteristic frequency ranges for MID, MF, and FF are identified as 0-85 kHz, 165-260 kHz, and 261-304 kHz, respectively. The thickness of identical plies has a significant effect on onset damage. With the decrease of the number of identical plies (i.e., m in the stacking sequences), the thin-ply laminates exhibit the initiation of damage suppression effects and crack propagation resistance.

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