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1.
Int J Mol Med ; 47(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33448325

RESUMO

Metabolism reprogramming influences the severity of organ dysfunction, progression to fibrosis, and development of disease in acute kidney injury (AKI). Previously we showed that inhibition of aerobic glycolysis improved survival rates and protected septic mice from kidney injury. However, the underlying mechanisms remain unclear. In the present study, it was revealed that sepsis or lipopolysaccharide (LPS) enhanced aerobic glycolysis as evidenced by increased lactate production and upregulated mRNA expression of glycolysis­related genes in kidney tissues and human renal tubular epithelial (HK­2) cells. The aerobic glycolysis inhibitor 2­deoxy­D­glucose (2­DG) downregulated glycolysis, and improved kidney injury induced by sepsis. 2­DG treatments increased the expression of sirtuin 3 (SIRT3) and phosphorylation­AMP­activated protein kinase (p­AMPK), following promoted autophagy and attenuated apoptosis of tubular epithelial cells in septic mice and in LPS­treated HK­2 cells. However, the glycolysis metabolite lactate downregulated SIRT3 and p­AMPK expression, inhibited autophagy and enhanced apoptosis in LPS­treated HK­2 cells. Furthermore, pharmacological blockade of autophagy with 3­methyladenine (3­MA) partially abolished the protective effect of 2­DG in sepsis­induced AKI. These findings indicated that inhibition of aerobic glycolysis protected against sepsis­induced AKI by promoting autophagy via the lactate/SIRT3/AMPK pathway.

2.
Sci Rep ; 11(1): 1205, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441740

RESUMO

The ovules and egg cells are well developed to be fertilized at anthesis in many flowering plants. However, ovule development is triggered by pollination in most orchids. In this study, we characterized the function of a Bsister gene, named PeMADS28, isolated from Phalaenopsis equestris, the genome-sequenced orchid. Spatial and temporal expression analysis showed PeMADS28 predominantly expressed in ovules between 32 and 48 days after pollination, which synchronizes with integument development. Subcellular localization and protein-protein interaction analyses revealed that PeMADS28 could form a homodimer as well as heterodimers with D-class and E-class MADS-box proteins. In addition, ectopic expression of PeMADS28 in Arabidopsis thaliana induced small curled rosette leaves, short silique length and few seeds, similar to that with overexpression of other species' Bsister genes in Arabidopsis. Furthermore, complementation test revealed that PeMADS28 could rescue the phenotype of the ABS/TT16 mutant. Together, these results indicate the conserved function of Bsister PeMADS28 associated with ovule integument development in orchid.

3.
Sci Rep ; 11(1): 1184, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441928

RESUMO

An important mechanism involved in dry eye (DE) is the association between tear hyperosmolarity and inflammation severity. Inflammation in DE might be mediated by the NLRP3 inflammasome, which activated by exposure to reactive oxygen species (ROS). A combination of carboxymethylcellulose (CMC) and α-melanocyte stimulating hormone (α-MSH) may influence DE through this mechanism, thus avoiding defects of signal drug. In this study, we assessed whether treatment comprising CMC combined with α-MSH could ameliorate ocular surface function; we found that it promoted tear secretion, reduced the density of fluorescein sodium staining, enhanced the number of conjunctival goblet cells, and reduced the number of corneal apoptotic cells. Investigation of the underlying mechanism suggested that the synergistic effect of combined treatment alleviated DE inflammation through reduction of ROS level and inhibition of the NLRP3 inflammasome in human corneal epithelial cells. These findings indicate that combined CMC + α-MSH treatment could ameliorate lesions and restore ocular surface function in patients with DE through reduction of ROS level and inhibition of NLRP3 signalling.

4.
J Med Chem ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417771

RESUMO

Coibamide A (1) is a highly N-methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (1a), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of 1a, two novel peptide-drug conjugates RGD-SS-CA (2) and RGD-VC-CA (3) were designed, synthesized, and evaluated. Composed of cyclodepsipeptide 1a, a tumor-homing RGD motif, and a conditionally labile linker, the conjugates are expected to release 1a tracelessly in specific tumor microenvironments. Compared with RGD-VC-CA (3), RGD-SS-CA (2) proved to be superior in in vitro drug release and cytotoxicity tests. Notably, intravenous injection of RGD-SS-CA (2) into mice-bearing human tumor xenografts induced significant tumor growth suppression with negligible toxicity. Therefore, as a novel prodrug of the coibamide A analogue, conjugate 2 has great potential for further exploration in cancer drug discovery.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33404680

RESUMO

OBJECTIVE: To investigate the microvasculature and structural characteristics of the eyes of myopic patients and their association with posterior staphyloma (PS). METHODS: This was a retrospective, case-control study comprising of 106 eyes from 72 individuals. Using 1:1 matching of axial length (AL) of their eyes, patients were allocated into a PS group or no posterior staphyloma (NPS) group. All patients were examined using ultra-widefield fundus imaging, optical coherence tomography angiography, and ocular biometry to acquire microvasculature and microstructure parameters. RESULTS: The anterior chamber depth (ACD) of the PS group was significantly different from that of the NPS group (3.56 mm vs 3.76 mm, P < 0.001), as was 1ens thickness (3.72 mm vs 3.57 mm, P = 0.005) and spherical equivalent (SE)(-10.11D vs -8.80D, P = 0.014). The PS group had reduced choriocapillaris flow, subfoveal choroidal thickness (SFCT), and a thinner retinal layer compared with the NPS group. No difference in retinal blood flow between the two groups was observed. The PS group exhibited a smaller disc area (15082.89 vs 17,043.32, P = 0.003) and angle α between temporal retinal arterial vascular arcades (113.29°vs 128.39°, P = 0.003), a larger disc tilt ratio (1.41 vs 1.24, P < 0.001) and parapapillary atrophy (PPA) area (13840.98 vs 8753.86, P = 0.020), compared with the NPS group. Multivariate regression analysis indicated that disc tilt ratio (P = 0.031) and SFCT (P = 0.015) were significant predictors of PS. In addition, PS (P = 0.049), AL (P = 0.003), corneal refractive power (P < 0.001), ACD (P = 0.022), relative lens position (P = 0.045), and disc area (P = 0.011) were significant predictors of SE. CONCLUSIONS: PS was found to be closely linked to a reduction in choriocapillaris perfusion and anatomical abnormalities including posterior and anterior segments. Furthermore, PS exacerbated the progression of myopia.

6.
Carbohydr Polym ; 255: 117328, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33436171

RESUMO

In crystalline cellulose I, all glucan chains are ordered from reducing ends to non-reducing ends. Thus, the polarity of individual chains is added forming a large dipole within the crystal. If one can engineer unidirectional alignment (parallel packing) of cellulose crystals, then it might be possible to utilize the material properties originating from polar crystalline structures. However, most post-synthesis manipulation methods reported so far can only achieve the uniaxial alignment with bi-directionality (antiparallel packing). Here, we report a method to induce the parallel packing of bacterial cellulose microfibrils by applying unidirectional shear stress during the synthesis and deposition through the rising bubble stream in a culture medium. Driving force for the alignment is explained with mathematical estimation of the shear stress. Evidences of the parallel alignment of crystalline cellulose Iα domains were obtained using nonlinear optical spectroscopy techniques.

7.
FEBS J ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400393

RESUMO

Coronaviruses (CoVs) are positive single-stranded RNA viruses that cause severe respiratory syndromes in humans, including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Coronavirus Disease 2019 (COVID-19) caused by a novel Severe Acute Respiratory Syndrome CoV (SARS-CoV-2) at the end of 2019 became a global pandemic. The 3C-like cysteine protease (3CLpro) process viral polyproteins to yield mature non-structural proteins, thus playing an important role in the CoV life cycle and therefore is considered a prominent target for anti-viral drugs. To date, many 3CLpro inhibitors have been reported, and their molecular mechanisms have been illustrated. Here, we briefly introduce the structural features of 3CLpro of the human-related SARS-CoV, MERS-CoV and SARS-CoV-2, and explore the potency and mechanism of their cognate inhibitors. This information will shed light on the development and optimization of CoV 3CLpro inhibitors, which may benefit further designation of therapeutic strategies to treat CoV diseases.

8.
Mol Cell Biochem ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33389496

RESUMO

Melanoma ranks second in aggressive tumors, and the occurrence of metastasis in melanoma results in a persistent drop in the survival rate of patients. Therefore, it is very necessary to find a novel therapeutic method for treating melanoma. It has been reported that lncRNA XIST could promote the tumorigenesis of melanoma. However, the mechanism by which lncRNA XIST regulates the progression of melanoma remains unclear. The proliferation of A375 cells was measured by clonal formation. Cell viability was detected by MTT assay. Flow cytometry was performed to detect cell apoptosis and cycle. The level of GINS2, miR-23a-3p, and lncRNA XIST was investigated by qRT-PCR. Protein level was detected by Western blot, and the correctness of prediction results was confirmed by Dual luciferase. In present study, GINS2 and lncRNA XIST were overexpressed in melanoma, while miR-23a-3p was downregulated. Silencing of GINS2 or overexpression of miR-23a-3p reversed cell growth and promoted apoptosis in A375 cells. Mechanically, miR-23a-3p directly targeted GINS2, and XIST regulated GINS2 level though mediated miR-23a-3p. Moreover, XIST exerted its function on cell proliferation, cell viability, and promoted the cell apoptosis of A375 cells though miR-23a-3p/GINS2 axis. LncRNA XIST significantly promoted the tumorigenesis of melanoma via sponging miR-23a-3p and indirectly targeting GINS2, which can be a potential new target for treating melanoma.

9.
Arch Virol ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33394172

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV, species Betaarterivirus suid 1 or 2) is a major pathogen affecting pigs on farms throughout the world. miR-296-3p is a multifunctional microRNA involved in the regulation of the inflammatory response in mice and humans. However, little is known about the biological functions of miR-296-3p in pigs. In this study, we used a highly pathogenic PRRSV-2 (species Betaarterivirus suid 2) strain to show that PRRSV infection robustly downregulates the expression of miR-296-3p in porcine alveolar macrophages (PAMs). Furthermore, we demonstrated that overexpression of miR-296-3p increases the replication of highly pathogenic (HP)-PRRSV in PAMs. Notably, the overexpression of miR-296-3p inhibited the induction of TNF-α, even with increased viral replication, compared with that in the HP-PRRSV-infected control group. We also demonstrated that miR-296-3p targets IRF1-facilitated viral infection and modulates the expression of TNF-α in PAMs during HP-PRRSV infection and that IRF1 regulates the expression of TNF-α by activating the TNF promoter via IRF1 response elements. In summary, these findings show that HP-PRRSV infection activates the IRF1/TNF-α signaling axis in PAMs by downregulating host miR-296-3p. This extends our understanding of the inflammatory response induced by HP-PRRSV infection.

10.
Toxicol Appl Pharmacol ; 411: 115362, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33279514

RESUMO

Arsenic exposure is well established to impair the function of zinc finger proteins, including PARP-1. Previous studies from our lab show that early developing T cells in the thymus are very sensitive to arsenite (As+3)-induced genotoxicity mediated through PARP-1 inhibition. Additionally, it has been shown that uranium (in the form of uranyl acetate, UA) also suppresses PARP-1 activity in HEK cells. However, very little is known about whether the As+3 metabolite, monomethylarsonous acid (MMA+3), also inhibits PARP-1 activity and if this is modified by combined exposures with other metals, such as uranium. In the present study, we found that MMA+3 significantly suppressed PARP-1 function, whereas UA at high concentrations significantly increased PARP-1 activity. To evaluate whether the effects on PARP-1 activity were mediated through oxidative stress, we measured the induction of hemoxygenase-1 (Hmox-1) expression by qPCR. MMA+3, but not UA, significantly induced oxidative stress; however, the inhibition of PARP-1 produced by MMA+3 was not reversed by the addition of the antioxidant, Tempol. Further evaluation revealed minimal interactive effects of MMA+3 and UA on PARP-1 function. Collectively, our results show that contrary to As+3, the suppressive effects of MMA+3 on PARP-1 were not substantially driven by oxidative stress. in mouse thymus cells. Results for this study provide important insights into the effects of MMA+3 and uranium exposures on PARP-1 function, which is essential for future studies focused on understanding the effects of complex environmentally relevant metal mixtures.

11.
Toxicol Appl Pharmacol ; 410: 115360, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33279515

RESUMO

People living in southwest part of United States are exposed to uranium (U) through drinking water, air, and soil. U is radioactive, but independent of this radioactivity also has important toxicological considerations as an environmental metal. At environmentally relevant concentrations, U is both mutagenic and carcinogenic. Emerging evidence shows that U inhibits DNA repair activity, but how U interacts with DNA repair proteins is still largely unknown. Herein, we report that U directly interacts with the DNA repair protein, Protein Poly (ADP-ribose) Polymerase 1 (PARP-1) through direct binding with the zinc finger motif, resulting in zinc release from zinc finger and DNA binding activity loss of the protein. At the peptide level, instead of direct competition with zinc ion in the zinc finger motif, U does not show thermodynamic advantages over zinc. Furthermore, zinc pre-occupied PARP-1 zinc finger is insensitive to U treatment, but U bound to PARP-1 zinc finger can be partially replaced by zinc. These results provide mechanistic basis on molecular level to U inhibition of DNA repair.


Assuntos
Reparo do DNA/fisiologia , Reparo do DNA/efeitos da radiação , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/efeitos da radiação , Urânio/metabolismo , Urânio/toxicidade , Sequência de Aminoácidos , Células Cultivadas , Exposição Ambiental/efeitos adversos , Humanos , Recém-Nascido , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Poli(ADP-Ribose) Polimerase-1/genética , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia
12.
Toxicol Appl Pharmacol ; 410: 115363, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33290780

RESUMO

Tongue cancer is one of the most common oral malignancies. Quisinostat is a histone deacetylase inhibitor with antitumor activity. The aim of this study was to evaluate the effects of quisinostat on the viability of tongue squamous cell carcinoma (TSCC) cells (CAL-27, TCA-8113) in vitro and in vivo. Cell viability, cell morphological observation, scratch wound-healing assay, transwell migration assay, transmission electron microscope, flow cytometry and cellular reactive oxygen species were assessed in vitro. The results showed that quisinostat can significantly inhibit the viability, growth and migration of TSCC cells. And quisinostat could significantly induce TSCC cells apoptosis, pyroptosis, and ferroptosis. Quisinostat significantly inhibited tumor tissue growth in animal experiments. Up-regulation of the expression of Bax, cleaved-caspase3, caspase-1, p53, phospho-p53 and down-regulated of the expression of caspase-3, Bcl-2, GPX4 in cell lines and tumor tissues of nude mice were observed by Western blotting analysis. Up-regulation of the expression of caspase-1, Bax, cleaved-caspase3, p53 and down-regulated of the expression of ki67, caspase-3, Bcl-2, GPX4 in tumor tissues of nude mice were observed by immunohistochemistry. TUNEL analysis showed that quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Based on these findings, quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.


Assuntos
Apoptose/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Piroptose/efeitos dos fármacos , Neoplasias da Língua/tratamento farmacológico , Animais , Apoptose/fisiologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ferroptose/fisiologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Piroptose/fisiologia , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
13.
J Proteome Res ; 20(1): 576-590, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33200940

RESUMO

Rapid early triage and dose estimation is vital for limited medical resource allocation and treatment of a large number of the wounded after radiological accidents. Lipidomics has been utilized to delineate biofluid lipid signatures after irradiation. Here, high-coverage targeted lipidomics was employed to screen radiosensitive lipids after 0, 1, 2, 3, 5, and 8 Gy total body irradiation at 4, 24, and 72 h postirradiation in rat plasma. Ultra-performance liquid chromatography-tandem mass spectrometry with a multiple reaction monitoring method was utilized. In total, 416 individual lipids from 18 major classes were quantified and those biomarkers altered in a dose-dependent manner constituted panel A-panel D. Receiver operator characteristic curve analysis using combined lipids showed good to excellent sensitivity and specificity in triaging different radiation exposure levels (area under curve = 0.814-1.000). The equations for dose estimation were established by stepwise regression analysis for three time points. A novel strategy for radiation early triage and dose estimation was first established and validated using panels of lipids. Our study suggests that it is feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage, which can provide further insights in developing lipidomics strategies for radiation biodosimetry in humans.

14.
IEEE Trans Nanobioscience ; 20(1): 2-8, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33079655

RESUMO

Recently, drug abuse has become a worldwide concern. Among varieties of drugs, KET is found to be favorite in drug addicts, especially teenagers, for recreational purposes. KET is a kind of analgesic and anesthetic drug which can induce hallucinogenic and dissociative effects after high-dose abuse. Hence, it is critical to develop a rapid and sensitive detection method for strict drug control. In this study, we proposed a cloud-enabled smartphone based fluorescence sensor for quantitative detection of KET from human hair sample. The lateral flow immunoassay (LFIA) was used as the detecting strategy where UCNPs were introduced as fluorescent labels. The sensor was capable of identifying the up-converted fluorescence and calculating the signal intensities on TL and CL to obtain a T/C value, which was corresponding to the KET concentration. The sensor transmitted the test data to the cloud-enabled smartphone through Type-C interface, and the data were further uploaded to the edge of the network for cloud-edge computing and storage. The entire detection took only 5 minutes with high stability and reliability. The detection limit of KET was 1 ng/mL and a quantitative detection range from 1 to 150 ng/mL. Furthermore, based on the huge development of Internet of Things (IoT), an App was developed on the smartphone for anti-drug situational awareness. Based on this system, it was convenient for Police Department to perform on-site KET detection. Moreover, it was critical for prediction of the development trend of future events, benefiting much to constructing a harmonious society.

15.
J Surg Res ; 258: 389-404, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33109405

RESUMO

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a common clinical event with high mortality, but its mechanism is elusive. Although long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in I/R damage in other organs, the changes in their expression and potential roles in intestinal I/R remain unclear. METHODS: The expression profiles of both lncRNAs and mRNAs in mouse intestinal mucosa after intestinal I/R were explored by a microarray approach, and their biological functions were elucidated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Then, some lncRNAs were further verified by qRT-PCR. Based on the coding-noncoding gene coexpression (CNC) network analyses, the role of lncRNA AK089510 in intestinal I/R-induced intestinal mucosa apoptosis was investigated by knockdown assay in vitro. RESULTS: A total of 3602 aberrantly expressed lncRNAs (1503 upregulated and 2099 downregulated) and 3158 mRNAs (1528 upregulated and 1630 downregulated) were identified. The dysregulated transcripts were enriched in the lipid metabolic process, apoptotic process, reactive oxygen species metabolic process, MAPK, TNF, ErbB, mTOR, and FoxO signaling pathways, and so on. The overexpression of lncRNA AK089510 was validated by qRT-PCR, and the CNC analysis revealed its target mRNAs. AK089510-siRNA reduced Casp6 and Casp7 expression and suppressed intestinal epithelial cell apoptosis after oxygen-glucose deprivation treatment. CONCLUSIONS: Our study revealed the lncRNA and mRNA expression patterns in mouse intestinal mucosa after intestinal I/R and predicted their potential functions and pathways. We identified AK089510 as a novel lncRNA involved in the apoptosis of intestinal mucosa, advancing our understanding of the molecular mechanisms of intestinal I/R injury.

16.
J Chin Med Assoc ; 84(1): 38-45, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32898087

RESUMO

BACKGROUND: A number of anesthetics have protective effect against ischemia-reperfusion (I/R) injury, including desflurane. But the function and molecular mechanism of desflurane in liver I/R injury have not been fully understood. The aim of this study was to investigate the effect of desflurane on liver I/R injury and further investigated the molecular mechanisms involving in miR-135b-5p. METHODS: The models of liver I/R injury in rats were established, and received desflurane treatment throughout the injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) were measured and compared between groups. H/R-induced cell model in L02 was established, and were treated with desflurane before hypoxia. Quantitative real-time polymerase chain reaction was performed to determine the expression of miR-135b-5p in different groups. The cell apoptosis was detected using flow cytometry assay. Western blot was used for the measurement of protein levels. RESULTS: I/R significantly increased serum levels of ALT and AST in rats, which were reversed by desflurane treatment. Desflurane also significantly attenuated the increase of cell apoptosis induced by I/R in both vivo and vitro. MiR-135b-5p significantly reversed the protective effect of desflurane against liver I/R injury. Additionally, Janus protein tyrosine kinase (JAK)2 was shown to be a target gene of miR-135b-5p, and miR-135b-5p overexpression significantly decreased the protein levels of p-JAK2, JAK2, p-STAT3. CONCLUSION: Desflurane attenuated liver I/R injury through regulating miR-135b-5p, and JAK2 was the target gene of mIR-135b-5p. These findings provide references for further development of therapeutic strategies in liver injury.

17.
Aerosp Med Hum Perform ; 92(1): 25-31, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33357269

RESUMO

INTRODUCTION: Allergic rhinitis (AR) is a global health problem with gradually increasing prevalence. No large-scale, systematic, and comprehensive study on AR among civil aviation aircrew of China has been reported. We aimed to demonstrate the prevalence of and risk factors for self-reported AR among Chinese civil aviation aircrew.METHODS: This study randomly surveyed 4059 civil aviation aircrew members from 12 cities in mainland China. A structured questionnaire was tailored, designed, and electronically delivered to all participants. Based on self-reported results, prevalence of and risk factors for AR were calculated/analyzed.RESULTS: The prevalence of self-reported AR was 23.38%. Among aircrew members, 10.37% presented with ear barotraumas, whereas 9.95% reported symptom aggravation during flight. Of aircrew members, 10.32% had symptoms related to flight duration, whereas 4.43% of symptoms related to flight altitude. Significant differences between rhinorrhea and sneezing, as well as between nasal itching and sneezing, were observed in the Total Nasal Symptoms Scores (TNSS). The Rhino-conjunctivitis Quality of Life Questionnaire (RQLQ) showed significant correlation between each section. TNSS was significantly related to RQLQ. Both TNSS and RQLQ significantly correlated with flight time.CONCLUSIONS: The prevalence of self-reported AR among civil aviation aircrew is higher than the general population in China. The severity of nasal symptoms and complications are significantly associated with quality of life and flying duties.Bai Y, Hu M, Ma F, Liu K, Xu H, Wu X, Wang H. Self-reported allergic rhinitis prevalence and related factors in civil aviation aircrew of China. Aerosp Med Hum Perform. 2021; 92(1):2531.

18.
Chemosphere ; 265: 129109, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33280847

RESUMO

AIMS: This study evaluated the neurodevelopmental toxicity of isoniazid (INH) in zebrafish embryos and the underlying mechanism. METHODS: Zebrafish embryos were exposed to different concentrations (2 mM, 4 mM, 8 mM, 16 mM, 32 mM) INH for 120 hpf. During the exposure period, the percentage of embryo/larva mortality, hatching, and morphological malformation were checked every 24 h until 120 hpf. The development of blood vessels in the brain was observed at 72 hpf and 120 hpf, and behavioral capacity and acridine orange (AO) staining were measured at 120 hpf. Alterations in the mRNA expression of apoptosis and dopamine signaling pathway related genes were assessed by real-time quantitative PCR (qPCR). RESULTS: INH considerably inhibited zebrafish embryo hatching and caused zebrafish larval malformation (such as brain malformation, delayed yolk sac absorption, spinal curvature, pericardial edema, and swim bladder defects). High concentration of INH (16 mM, 32 mM) even induced death of zebrafish. In addition, INH exposure markedly restrained the ability of the zebrafish autonomous movement, shortened the length of dopamine neurons and inhibited vascular development in the brain. No obvious apoptotic cells were observed in the control group, whereas considerable numbers of apoptotic cells appeared in the head of INH-treated larvae at 120 hpf. PCR results indicated that INH significantly raised the transcription levels of caspase-3, -8, -9, and bax and significantly decreased bcl-2 and bcl-2/bax in the zebrafish apoptotic signaling pathway. INH also markedly decreased the genes related to dopamine signaling pathway (th1, dat, drd1, drd2a, drd3, and drd4b). CONCLUSIONS: Experimental results indicated that INH had obvious neurodevelopmental toxicity in zebrafish. Persistent exposure to INH for 120 h caused apoptosis, decreased dopaminergic gene expression, altered vasculature, and reduced behaviors.


Assuntos
Embrião não Mamífero , Peixe-Zebra , Animais , Dopamina , Isoniazida/toxicidade , Larva , Transdução de Sinais , Peixe-Zebra/genética
19.
Talanta ; 222: 121645, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33167274

RESUMO

This paper reviews the recent development of electrochemical sensors for the detection of vitamins over the past three years. Vitamins present in natural foodstuffs are a group of organic compounds that are indispensable to maintain human health. While they are only present in minute amounts, they still play a significant role in healthy metabolism. The deficiency of vitamins in the human body often leads to numerous diseases. Because the human body cannot synthesize most vitamins, it is necessary to obtain them from dietary sources. For these reasons, the detection of vitamins has gained widespread attention in recent years. As it is well known, almost all vitamins are electrochemically active. Based on the electrochemical oxidation or reduction reaction of the vitamins in an electrolyte, electrochemical sensors can obtain the concentration of the vitamins by measurement of the current at the working electrode. Electrochemical sensors for detecting water-soluble vitamins, such as vitamin B1, vitamin B2, vitamin B6, vitamin B9, vitamin B12, and vitamin C are discussed in detail. A comprehensive overview of electrochemical sensors for detecting fat-soluble vitamins, such as vitamin A, vitamin D, vitamin E, and vitamin K, is also provided. Furthermore, the strategies employed and the performance of the electrochemical sensors for detecting vitamins are described. Finally, current challenges and future prospects of electrochemical sensors for the detection of vitamins are discussed.

20.
Virus Res ; 292: 198256, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33285172

RESUMO

The SD12-F120 is a live-attenuated genotype I strain of Japanese encephalitis virus (JEV) and was obtained by serial passage of wild-type strain SD12 on BHK-21 cells combined with multiple plaque purification and virulence selection in mice. The large scale production and vast clinical trials always demand ideal safety and efficacy profile of live-attenuated vaccines. In the present study, SD12-F120VC has undergone serial passaging of P1-P30 in WHO qualified Vero cells to assess the potential effect of adaptation to growth on Vero cells. The series of experiments showed that vaccine SD12-F120VC (Vero cell adapted) variants have consistently increased in peak virus titer compared to early passages and have good adaptation to growth in Vero cells. The animal experiments showed that Vero cell adapted SD12-F120VC variants have attenuation phenotype in suckling mice and the plaque morphology for all SD12-F120VC variants was small. Vaccination of mice with SD12-F120VC vaccine produced complete protection for homologous SD12 genotype I strain, but failed to give the complete protection of vaccinated mice against the challenge of heterologous N28 genotype III strain. In response to immunization of SD12-F120VC in mice, the neutralizing antibodies titer against homologous SD12-F120VC and SD12 (GI) was higher than heterologous N28 (GIII) strain. The prM protein has 6 amino acid substitutions, of which 5 amino acid changes were confined at the start of the pr domain in the ∼40 amino acids, and some mutations in the pr domain of prM might contribute to Vero cell adaptation. Our findings in this study are important for validation, evaluation and quality control study of live attenuated flaviviruses vaccines and show that Vero cells are a suitable substrate for the production of a safe and stable live-attenuated JEV vaccine.

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