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1.
Placenta ; 86: 4-10, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31491693

RESUMO

OBJECTIVE: In the mouse model, manipulations of assisted reproductive technology (ART) can lead to enlarged placentas and influence the expression of glucose transporters (GLUTs) in placentas during mid-to late-gestation. Expression of imprinted genes which plays a vital role in placental growth and function, is also vulnerable to be affected by ART. However, it is uncertain whether those abnormal changes presented in ART mouse placentas also occur in human ART placentas. METHODS: We compared the expression of GLUT family genes (SLC2A1- SLC2A13), mTOR activity, the expression of four imprinted genes (H19, IGF2, CDKN1C and PHLDA2), and KCNQ1OT1 methylation in human placentas conceived naturally or by ART. RESULTS: Our data showed that the placental weight and birthweight were similar between NC (n = 20) and ART group (n = 20). We found that up-regulated mRNA expression of GLUTs and elevated GLUT1 protein level occurred in human ART placentas with unchanged mTOR activity. And we found that mRNA and protein expression of PHLDA2 were significantly increased in ART placentas compared with placentas from natural pregnancies. Additionally, we revealed that ART placentas had increased expression of KCNQ1OT1 which negatively controls PHLDA2 expression. CONCLUSION: This study reveals that the increased expression of GLUTs occurs in human ART placentas with normal mTOR activity. The down-regulated expression of imprinted gene PHLDA2 may account for the up-regulation of GLUTs. Those adaptive changes in ART placentas may explain why most of ART offspring have normal birth weight at born.

2.
Mar Drugs ; 17(9)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487895

RESUMO

Ultraviolet (UV) irradiation is a potent inducer for skin photoaging. This paper investigated the anti-photoaging effects of the acetylated and amidated hexapeptide (AAH), originally identified from Spirulina platensis, in (Ultraviolet B) UVB-irradiated Human immortalized keratinocytes (Hacats) and mice. The results demonstrated that AAH had much lower toxicity on Hacats than the positive matrixyl (81.52% vs. 5.32%). Moreover, AAH reduced MDA content by 49%; increased SOD, CAT, and GSH-Px activities by 103%, 49%, and 116%, respectively; decreased MMP-1 and MMP-3 expressions by 27% and 29%, respectively, compared to UVB-irradiated mice. Employing isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics, 60 differential proteins were identified, and major metabolic pathways were determined. Network analysis indicated that these differential proteins were mapped into an interaction network composed of two core sub-networks. Collectively, AAH is protective against UVB-induced skin photoaging and has potential application in skin care cosmetics.

3.
Bioorg Med Chem Lett ; : 126661, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31515187

RESUMO

To study the novel functionalized heterocyclic molecules with highly potential biological activity, two series of heterocyclic lactam derivatives containing the piperonyl moiety were designed and synthesized. The newly obtained compounds have been identified on the basis of analytical spectral data, including 1H NMR, 13C NMR, and ESI-MS. The target compounds were evaluated for their potential antifungal activities in vitro against twelve species of the plant pathogen fungi (Sclerotinia sclerotiorum, Rhizoctonia solani, Rap Sclerotinia stemrot, Fusarium graminearum, Phomopsis adianticola, Pestallozzia theae, Pestalotiopsis guepinii, Alternaria tenuis Nees, Monilinia fructicola, Colletotrichum gloeosporioides, Phytophthora capsici, Magnaporthe oryzae). Preliminary bioassays suggested that all prepared compounds I1-14 displayed broad-spectrum and moderate antifungal activities compared with the positive control hymexazol, especially for Sclerotinia sclerotiorum, Rap Sclerotinia stemrot, and Monilinia fructicola. In particular, the inhibition rate of compound I9 exhibited good inhibition activity reached 95.16% against Sclerotinia sclerotiorum, and compounds I5, I12 against Phytophthora capsici were 93.44%, 91.25%. Further studies revealed that compounds I5 (IC50 = 19.13 µM) and I12 (IC50 = 9.12 µM) exhibited obviously antifungal activities against Phytophthora capsici, which were better than that of commercial agricultural fungicide hymexazol (IC50 = 325.45 µM). Therefore, these target compounds could be further studied and explored as a lead skeleton for discovery of novel antifungal agents.

4.
Cereb Cortex ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31504279

RESUMO

Integrated neural inputs from different dendrites converge at the soma for action potential generation. However, it is unclear how the convergent dendritic inputs interact at the soma and whether they can be further modified there. We report here an entirely new plasticity rule in hippocampal neurons in which repetitive pairing of subthreshold excitatory inputs from proximal apical and basal dendrites at a precise interval induces persistent bidirectional modifications of the two dendritic inputs. Strikingly, the modification of the dendritic inputs specially occurs at soma in the absence of somatic action potential and requires activation of somatic N-methyl-D-aspartate receptors (NMDARs). Once induced, the somatic modification can also be observed in other unpaired dendritic inputs upon their arrival at the soma. We further reveal that the soma can employ an active mechanism to potentiate the dendritic inputs by promoting sustained activation of somatic NMDARs and subsequent down-regulating of the fast inactivating A-type potassium current (IA) at the soma. Thus, the input-timing-dependent somatic plasticity we uncovered here is in sharp contrast to conventional forms of synaptic plasticity that occur at the dendrites and is important to somatic action potential generation.

5.
Lett Appl Microbiol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31508833

RESUMO

Fermented chopped pepper is a widely used ingredient in traditional Chinese cuisine. In order to improve the quality and solve safety problems during production, it is essential to fully understand the bacterial diversity present during the fermentation process. In this study, the dynamics and diversity of the bacterial community present during the fermentation of chopped pepper were analyzed by high-throughput sequencing. There was a higher level of bacterial diversity at the beginning of fermentation, and Proteobacteria were found to be the dominant group at this stage. However, after 3 days, Proteobacteria decreased in abundance and Firmicutes became the dominant group present in the samples. Interestingly, the relative abundance of Weissella increased during the first 3 days of fermentation and then gradually decreased over the rest of the fermentation process, suggesting that Weissella may play an important role during the initial stage of fermentation. Lactobacillus was found to constitute the majority of bacteria during the fermentation period. This study demonstrates that high-throughput sequencing is a useful tool to evaluate bacterial diversity and monitor microbial quality in fermented chopped pepper. The results obtained in this study advance the current understanding of the bacterial communities present in chopped pepper and provide a theoretical basis for improving the quality of chopped pepper fermentation.

6.
J Food Biochem ; : e13042, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502281

RESUMO

λ-Carrageenan (λcar) interacted with ß-lactoglobulin (ßlg) immediately to form ßlg-λcar complexes when used as an additive in milk. The formation of complexes is the key process through which to explore the bioapplication of λcar, which is a complicated process and influenced by many factors. In this study, the formation process and effect of pH were ascertained by the binding affinity, hydrodynamic diameter, and secondary structure. Results showed that the interaction was spontaneously exothermic and the complexes were soluble. The binding affinities (Ka) decreased from 9.0 ± 1.3 × 105 to 1.3 ± 0.8 × 105  M-1 , and the stoichiometry also decreased as the pH was increased from 4 to 7. Furthermore, DLS showed a larger hydrodynamic diameter of the complexes at lower pH. Moreover, the complexes induced a change in the secondary structural components of ßlg at lower pH. PRACTICAL APPLICATIONS: The secondary structure of ßlg was changed by the interaction of λcar, which resulted in ßlg-λcar complexes under acidic conditions. The soluble ßlg-λcar complexes showed a good stability against aggregation. Thus, they can enhance the textural properties and stability of acidic dairy drinks, and can be used to accurately formulate ingredients in the food ingredient industry.

7.
Lab Chip ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31501848

RESUMO

Microfluidic devices have been increasingly used for low-volume liquid handling operations. However, laboratory automation of such delicate devices has lagged behind due to the lack of world-to-chip (macro-to-micro) interfaces. In this paper, we have presented the first pipette-free robotic-microfluidic interface using a microfluidic-embedded container cap, referred to as a microfluidic cap-to-dispense (µCD), to achieve a seamless integration of liquid handling and robotic automation without any traditional pipetting steps. The µCD liquid handling platform offers a generic and modular way to connect the robotic device to standard liquid containers. It utilizes the high accuracy and high flexibility of the robotic system to recognize, capture and position; and then using microfluidic adaptive printing it can achieve high-precision on-demand volume distribution. With its modular connectivity, nanoliter processability, high adaptability, and multitask capacity, µCD shows great potential as a generic robotic-microfluidic interface for complete pipette-free liquid handling automation.

8.
J Environ Sci (China) ; 85: 94-106, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471036

RESUMO

Titanium dioxide nanoparticles (TiO2 NPs) are subjected to various transformation processes (chemical, physical and biological processes) in the environment, potentially affecting their bioavailability and toxic properties. However, the size variation of TiO2 NPs during aging process and subsequent effects in mammalian cells are largely unknown. The aim of this study was to illustrate the adverse effects of TiO2 NPs in different sizes (5, 15 and <100 nm) during aging process on human-hamster hybrid (AL) cells. There was an aging-time dependent enhancement of average hydrodynamic size in TiO2 NPs stock suspensions. The cytotoxicity of fresh TiO2 NPs increased in a size-dependent manner; in contrast, their genotoxicity decreased with the increasing sizes of NPs. No significant toxicity difference was observed in cells exposed to either fresh or 60 day-aged TiO2 NPs. Both Fresh and aged TiO2 NPs efficiently induced mitochondrial dysfunction and activated Caspase-3/7 in a size-dependent manner. Using mitochondrial-DNA deficient (ρ0) AL cells, we further discovered that mitochondrial dysfunction made significant contribution to the size-dependent toxicity induced by TiO2 NPs during the aging process. Taken together, our data indicated that TiO2 NPs could significantly induced the cytotoxicity and genotoxicity in an aging time-independent and size-dependent manner, which were triggered by mitochondrial dysfunction. Our study suggested the necessity to include size as an additional parameter for the cautious monitoring of TiO2 NPs disposal before entering the environment.


Assuntos
Nanopartículas/toxicidade , Titânio/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Dano ao DNA , Humanos , Testes de Toxicidade
9.
J Mater Chem B ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475276

RESUMO

Combination therapy with multiple chemotherapeutic agents is the main approach for cancer treatment in the clinic. Polyphenol-based materials are found in our diet, demonstrate good biocompatibility, and prevent numerous diseases. In this study, we encapsulate two drugs in a single polyphenol-based polymer with Fe3+ or Mn2+ ions as the cross-linker for cancer therapy. The combination index of two drugs is an essential parameter to evaluate drug combinations. The amphiphilic polymer poly(ethylene glycol)-block-polydopamine (PEG-PDA) was prepared by RAFT polymerization. The nanoparticles were prepared via self-assembly with Fe3+ or Mn2+ ions. Both doxorubicin (DOX) and simvastatin (SV) were encapsulated in the core of the nanoparticles. The cell viability and combination index were evaluated in vitro. The tumor accumulation of the nanoparticles was investigated by positron-emission tomography (PET) and magnetic resonance (MR) imaging. The as-prepared nanoparticles exhibited high drug loading capacity. The drug loaded nanoparticles could kill cancer cells effectively with a combination index <1. Both PET and MRI revealed that the nanoparticles showed long blood circulation time and high tumor accumulation. The nanoparticles could inhibit tumor inhibition via intravenous injection of nanoparticles. The polyphenol-based nanoplatform may serve as a promising theranostic candidate for clinical application.

10.
Front Med ; 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31495906

RESUMO

Pediatric cough is a heterogeneous condition in terms of symptoms and the underlying disease mechanisms. Symptom phenotypes hold complicated interactions between each other to form an intricate network structure. This study aims to investigate whether the network structure of pediatric cough symptoms is associated with the prognosis and outcome of patients. A total of 384 cases were derived from the electronic medical records of a highly experienced traditional Chinese medicine (TCM) physician. The data were divided into two groups according to the therapeutic effect, namely, an invalid group (group A with 40 cases of poor efficacy) and a valid group (group B with 344 cases of good efficacy). Several well-established analysis methods, namely, statistical test, correlation analysis, and complex network analysis, were used to analyze the data. This study reports that symptom networks of patients with pediatric cough are related to the effectiveness of treatment: a dense network of symptoms is associated with great difficulty in treatment. Interventions with the most different symptoms in the symptom network may have improved therapeutic effects.

12.
Plant Biotechnol J ; 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31446669

RESUMO

Fine mapping QTLs and identifying candidate genes for cotton fibre-quality and yield traits would be beneficial to cotton breeding. Here, we constructed a high-density genetic map by specific-locus amplified fragment sequencing (SLAF-seq) to identify QTLs associated with fibre-quality and yield traits using 239 recombinant inbred lines (RILs), which was developed from LMY22 (a high-yieldGossypiumhirsutumL. cultivar) ×LY343 (a superior fibre-qualitygermplasm with G.barbadenseL. introgressions). The genetic map spanned 3,426.57 cM, including 3,556 SLAF-based SNPs and 199 SSR marker loci. A total of 104 QTLs, including 67 QTLs for fibre quality and 37 QTLs for yield traits, were identified with phenotypic data collected from 7 environments. Among these, 66 QTLs were co-located in 19 QTLclusters on 12 chromosomes, and24 QTLs were detected in three or more environments and determined tobe stable. We also investigatedthe genomiccomponentsofLY343 and their contributions to fibre-related traits by deep-sequencing the whole genome of LY343, and wefound that genomic components from G. hirsutum races (which entered LY343 via itsG. barbadenseparent) contributed more favourable alleles than those from G. barbadense. We furtheridentified six putative candidate genes for stable QTLs, including Gh_A03G1147 (GhPEL6), Gh_D07G1598 (GhCSLC6)and Gh_D13G1921 (GhTBL5) for fibre-length QTLs andGh_D03G0919 (GhCOBL4), Gh_D09G1659 (GhMYB4) and Gh_D09G1690 (GhMYB85) for lint-percentage QTLs. Our results provide comprehensive insight into the genetic basis of the formation of fibre-related traits and would be helpful for cloning fibre-development-related genes as well as for marker-assisted genetic improvement incotton. This article is protected by copyright. All rights reserved.

13.
Fish Shellfish Immunol ; 93: 823-831, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31422181

RESUMO

Calreticulin (CRT) is a highly conserved and multi-functional protein with diverse localizations. CRT has lectin-like properties and possesses important immunological activities in mammalian. In teleost, very limited studies on CRT immunologic function have been documented. In the present study, a CRT homologue (SsCRT) was cloned, identified and characterized from black rockfish, Sebastes schlegeli, an important aquaculture species in East Asia. The full length of SsCRT cDNA is 2180 bp and encoded a polypeptide of 425 amino acids. SsCRT contains a signal peptide, three distinct structural and functional domains (N-, P- and C-domains), and an endoplasmic reticulum (ER) retrieval signal sequence (KDEL). The deduced amino acid sequence of SsCRT shares 89-92% overall sequence identities with the CRT proteins of several fish species. SsCRT was distributed ubiquitously in all the detected tissues and was highly expressed in the spleen, muscle and liver. After the infection of fish extracellular bacterial pathogen Vibrio anguillarum and intracellular bacterial pathogen Edwardsiella tarda, the mRNA transcripts of SsCRT in spleen, liver, and head kidney were significantly up-regulated. The expression patterns were time-dependent and tissue-dependent. Recombinant SsCRT (rSsCRT) exhibited apparent binding activities against different bacteria and PAMPs. In vivo studies showed that the expressions of multiple immune-related genes such as TNF13B, IL-1ß, IL-8, SAA, Hsp70, and ISG15 in head kidney were significantly enhanced when black rockfish were treated with rSsCRT. Furthermore, rSsCRT reduced pathogen dissemination and replication in fish kidney and spleen. These results indicated that SsCRT served as an immune receptor to recognize and eliminate the invading pathogens, which played a vital role in the immune response of Sebastes schlegeli. These findings provide new insights into understanding the roles of CRT proteins in immune response and pathogen infection in teleost.

14.
Virol J ; 16(1): 105, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426820

RESUMO

BACKGROUND: The gut microbiome is closely associated with the health of the host; although the interaction between the bacterial microbiome and the whole virome has rarely been studied, it is likely of medical importance. Examination of the interactions between the gut bacterial microbiome and virome of rhesus monkey would significantly contribute to revealing the gut microbiome composition. METHODS: Here, we conducted a metagenomic analysis of the gut microbiome of rhesus monkeys in a longitudinal cohort treated with an antibiotic cocktail, and we documented the interactions between the bacterial microbiome and virome. The depletion of viral populations was confirmed at the species level by real-time PCR. We also detected changes in the gut metabolome by GC-MS and LC-MS. RESULTS: A majority of bacteria were depleted after treatment with antibiotics, and the Shannon diversity index decreased from 2.95 to 0.22. Furthermore, the abundance-based coverage estimator (ACE) decreased from 104.47 to 33.84, and the abundance of eukaryotic viruses also changed substantially. In the annotation, 6 families of DNA viruses and 1 bacteriophage family were present in the normal monkeys but absent after gut bacterial microbiome depletion. Intriguingly, we discovered that changes in the gut bacterial microbiome composition may promote changes in the gut virome composition, and tryptophan, arginine, and quinone may play roles in the interaction between the bacterial microbiome and virome. CONCLUSION: Our results indicated that the clearly altered composition of the virome was correlated with depletion in the bacterial community and that metabolites produced by bacteria possibly play important roles in the interaction.

15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(7): 837-841, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31441406

RESUMO

OBJECTIVE: To analyze the incidence of acute kidney injury (AKI) in elderly patients with sepsis, compare the clinical characteristics and prognosis between AKI and non-AKI elderly patients with sepsis, and to investigate the impact of classification of AKI and renal replacement therapy (RRT) on the outcome of elderly patients with sepsis. METHODS: The clinical data of 490 septic patients over 65 years old, admitted to intensive care unit (ICU) of Tianjin First Center Hospital from April 1st, 2016 to December 31st, 2018 were retrospectively analyzed. The patients were divided into two groups according to those with or without AKI. The clinical characteristics of patients were compared, and subgroup analysis of elderly septic patients with AKI was performed according to Kidney Disease: Improving Global Outcomes (KDIGO) staging criteria and whether RRT was performed, to observe the effects of AKI staging and RRT on the prognosis of elderly septic patients with AKI. Multivariate Cox regression analysis was used to screen the risk factors of death in elderly patients with sepsis associated AKI. RESULTS: (1) A total of 490 septic elderly patients were enrolled, including 249 patients with AKI and 241 patients without AKI, with the AKI incidence of 50.8%. Compared with non-AKI group, the patients in AKI group were older (years old: 72.0±7.2 vs. 68.8±5.1), acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score were evidently higher (23.1±6.1 vs. 22.0±3.7, 9.4±3.8 vs. 6.1±3.5); the duration of mechanical ventilation [days: 7.0 (5.0, 10.0) vs. 6.0 (3.0, 9.0)], length of ICU stay [days: 12.0 (7.0, 15.0) vs. 7.0 (4.0, 13.0)] and total length of hospital stay [days: 15.0 (10.0, 21.5) vs. 12.0 (7.0, 15.0)] were longer, and ICU mortality and 28-day mortality were evidently higher [22.9% (57/249) vs. 14.1% (34/241), 36.1% (90/249) vs. 24.5% (59/241), all P < 0.05]. (2) According to KDIGO staging, 93 patients were in stage 1, 70 in stage 2 and 86 in stage 3 of AKI. The rate of RRT was increased with increase in KDIGO staging [14.0% (13/93), 30.0% (21/70), 88.4% (76/86)], the duration without mechanical ventilation within 28 days was shortened [days: 20.0 (0, 23.0), 8.0 (0, 20.5), 8.0 (0, 13.0)], the rate of kidney recovery was decreased [71.0% (66/93), 51.4% (36/70), 37.2% (32/86)], meanwhile, the ICU and 28-day mortality was increased [12.9% (12/93), 38.6% (27/70), 20.9% (18/86), and 26.9% (25/93), 35.7% (25/70), 46.5% (40/86), all P < 0.05]. (3) 110 elderly septic patients with AKI were treated with RRT, and 139 without RRT. Compared with non-RRT group, the ratio of mechanical ventilation in RRT group was lowered [46.4% (51/110) vs. 68.3% (95/139)], the duration without mechanical ventilation within 28 days [days: 18.0 (0, 23.0) vs. 10.0 (0, 13.0)], the length of ICU stay [days: 13.0 (12.0, 17.9) vs. 10.0 (6.0, 14.0)] and the total length of hospital stay [days: 22.5 (15.0, 46.0) vs. 16.0 (12.0, 23.0)] were prolonged, and the 28-day mortality was evidently increased [50.0% (55/110) vs. 25.2% (35/139), all P < 0.01], however, no significant difference in ICU mortality was found [27.3% (30/110) vs. 19.4% (27/139), P > 0.05]. (4) Cox regression analysis showed that SOFA score [relative risk (RR) = 1.214, 95% confidence interval (95%CI) = 1.117-1.319], KDIGO stage (RR = 4.077, 95%CI = 1.850-8.982), vasoactive substance usage (RR = 2.896, 95%CI = 1.502-5.584), and mechanical ventilation (RR = 5.787, 95%CI = 1.512-22.156) were the risk factors of 28-day mortality in elderly septic patients with AKI (all P < 0.05). CONCLUSIONS: The incidence of AKI for elderly septic patients with AKI was about 50%, who had a worse prognosis as compared with non-septic AKI patients. The higher the stage of KDIGO, the higher the mortality in elderly septic patients with AKI was. RRT can decrease the rate of mechanical ventilation, whereas, it may not improve the prognosis of elderly septic patients with AKI.

16.
Environ Pollut ; 254(Pt A): 113021, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31415976

RESUMO

Cadmium (Cd) is a ubiquitous toxic heavy metal derived mainly from industrial processes. In industrialized societies, individuals are exposed to a plethora of sources of Cd pollution. Cd can trigger serious diseases such as rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) by the over-activating immune system. As an effector mechanism in innate immunity, neutrophil extracellular traps (NETs) not only play an important role in defending against infection but also lead to tissue damage. However, the role of NETs in Cd-induced lung damage process has not been previously studied. In this study, we aimed to investigate the potential effects of Cd-induced NETs on lung injury in vivo and further to clarify the molecular mechanisms of Cd-induced NETs formation. In vivo, Cd treatment destroyed the structural integrity of lung tissue and significantly increased the levels of NETs in the bronchoalveolar lavage fluid (BALF). The known NETs inhibitor DNase I ameliorated pathologic changes and significantly decreased levels of NETs in BALF, which suggesting the curial role of NETs in Cd-induced lung injury. Further investigation showed that Cd could significantly trigger NETs formation, which is composed of DNA backbone decorated with histones (H3) and neutrophils elastase (NE). The inhibitors of NADPH oxidase, ERK1/2 and p38 MAPK-signaling pathways significantly reduced the formation of NETs, and western blotting analysis also showed that Cd significantly increased the phosphorylation of p38 and ERK1/2 signaling pathways. Above results confirmed that NADPH oxidase, ERK1/2 and p38 MAPK-signaling pathways were related to Cd-induced NETs formation. In conclusion, NETs was involved in Cd-induced lung injury, and the mechanisms of Cd-induced NETs formation was via activating NADPH oxidase, ERK1/2 and p38 MAPK-signaling pathways, which might provide a new perspective in Cd-induced lung injury.

17.
J Neurochem ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31465551

RESUMO

Traumatic brain injury (TBI) is a dominant cause of death and permanent disability worldwide. Although TBI could significantly increase the proliferation of adult neural stem cells in the hippocampus, the survival and maturation of newborn cells is markedly low. Increasing evidence suggests that the secretome derived from mesenchymal stem cells (MSCs) would be an ideal alternative to MSC transplantation. The successive and microenvironmentally responsive secretion in MSCs may be critical for the functional benefits provided by transplanted MSCs after TBI. Therefore, it is reasonable to hypothesize that the signaling molecules secreted in response to local tissue damage can further facilitate the therapeutic effect of the MSC secretome. To simulate the complex microenvironment in the injured brain well, we used traumatically injured brain tissue extracts to pretreat umbilical cord mesenchymal stem cells (UCMSCs) in vitro and stereotaxically injected the secretome from traumatic injury-preconditioned UCMSCs into the dentate gyrus of the hippocampus in a rat severe TBI model. The results revealed that compared with the normal secretome, the traumatic injury-preconditioned secretome could significantly further promote the differentiation, migration and maturation of newborn cells in the dentate gyrus and ultimately improve cognitive function after TBI. Cytokine antibody array suggested that the increased benefits of secretome administration were attributable to the newly produced proteins and upregulated molecules from the MSC secretome preconditioned by a traumatically injured microenvironment. Our study utilized the traumatic injury-preconditioned secretome to amplify neurogenesis and improve cognitive recovery, suggesting this method may be a novel and safer candidate for nerve repair. This article is protected by copyright. All rights reserved.

18.
Prenat Diagn ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31441071

RESUMO

OBJECTIVES: To quantitatively assess prenatal diagnostic performance of three-dimensional ultrasound (3D-US) for posterior fossa anomalies (PFA) and establish a preliminarily 3D-US prediction model. METHODS: Sixty singleton fetuses suspected of PFA by 2D-US presented their detailed 3D-US evaluation. The surface area of vermis (SAV), brainstem-vermis, and brainstem-tentorium angles were measured by 3D-US. The good prognosis was defined as normal neurodevelopmental outcome. MRI and autopsy were the diagnostic reference standard. RESULTS: There was a significant difference between 2D-US (60.0%, 36/60) and 3D-US (94.8%, 55/58) for the diagnostic accuracy (P < .01). Prenatal 3D-US prediction model was established with observed/expected SAV as the main predictor (area under the curve [AUC]: 0.901; 95% CI, 0.810-0.992, P < .001). When it was more than 107.5%, the prognosis seemed to be good (sensitivity: 96.4%, specificity: 26.7%), which led to consideration of mega cisterna magna, Blake pouch cyst, or small arachnoid cyst. The prognosis appeared to be poor when it was less than 73% (sensitivity: 71.4%, specificity: 100%), and the diagnosis tended to be a Dandy-Walker malformation, vermian hypoplasia, and cerebellar hypoplasia. Brainstem-vermis and brainstem-tentorium angles were the secondary indicators (AUC: 0.689 vs 0.761; 95% CI, 0.541-0.836 vs 0.624-0.897, P = .014 vs.001). CONCLUSIONS: It seems that the exact types of PFA can be effectively diagnosed by quantitative indicators of 3D-US.

19.
Oncogene ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417183

RESUMO

Bone morphogenetic protein 10 (BMP10), one member of the BMP family, is involved in various development events. Dysregulation of BMP10 has been observed in several diseases, including hypertensive cardiac hypertrophy, Hirschsprung disease and blood vessel formation. However, its role in liver cancer remains largely unknown. In this study, we reported that BMP10 was significantly downregulated in HCC at both mRNA and protein level. Decreased BMP10 was associated with bigger tumor size, worse TNM stage, earlier recurrence and poorer survival. BMP10 negatively regulated HCC cell proliferation in vitro and in vivo. Mechanism study revealed that BMP10 suppressed tumor cell growth by inhibiting STAT3 signaling. Interestingly, we found that cytoplasmic BMP10 interacted with both receptor protein tyrosine phosphatase sigma (PTPRS) and STAT3, which facilitated dephosphorylation of STAT3 by PTPRS. Altogether, our study has revealed the clinical significance of BMP10 in HCC, and suppression of HCC cell growth by BMP10 via PTPRS-STAT3 axis, providing a potential therapeutic strategy for targeting STAT3 signaling in HCC.

20.
Int J Mol Sci ; 20(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31409031

RESUMO

Little information is available regarding the effect of melatonin on the quality and fertilization capability of sex-sorted bull sperm, and even less about the associated mechanism. Sex-sorted sperm from three individual bulls were washed twice in wash medium and incubated in a fertilization medium for 1.5 h, and each was supplemented with melatonin (0, 10-3 M, 10-5 M, 10-7 M, and 10-9 M). The reactive oxygen species (ROS) and endogenous antioxidant activity (glutathione peroxidase (GPx); superoxide dismutase (SOD); catalase (CAT)), apoptosis (phosphatidylserine [PS] externalization; mitochondrial membrane potential (Δψm)), acrosomal integrity events (malondialdehyde (MDA) level; acrosomal integrity), capacitation (calcium ion [Ca2+]i level; cyclic adenosine monophosphate (cAMP); capacitation level), and fertilization ability of the sperm were assessed. Melatonin receptor 1 (MT1) and 2 (MT2) expression were examined to investigate the involvement of melatonin receptors on sex-sorted bull sperm capacitation. Our results show that treatment with 10-5 M melatonin significantly decreased the ROS level and increased the GPx, SOD, and CAT activities of sex-sorted bull sperm, which inhibited PS externalization and MDA levels, and improved Δψm, acrosomal integrity, and fertilization ability. Further experiments showed that melatonin regulates sperm capacitation via MT1. These findings contribute to improving the fertilization capacity of sex-sorted bull sperm and exploring the associated mechanism.

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