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1.
Sheng Wu Gong Cheng Xue Bao ; 37(9): 3101-3107, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34622620

RESUMO

Viral myocarditis (VMC) is a disease characterized by inflammation of myocardial cells caused by viral infection. Since the pathogenesis mechanism of VMC has not been fully elucidated, the diagnosis and treatment of this disease remains extremely challenging. Non-coding RNAs (ncRNAs) are a class of RNAs that do not encode proteins. An increasing number of studies have shown that ncRNAs are involved in regulating the occurrence and development of VMC, thus providing potential new targets for the treatment and diagnosis of VMC. This review summarizes the possible roles of ncRNAs in the pathogenesis and diagnosis of VMC revealed recently.


Assuntos
Infecções por Coxsackievirus , Miocardite , Viroses , Enterovirus Humano B , Humanos , Inflamação , Miocardite/genética , Viroses/diagnóstico , Viroses/genética
2.
Plant Sci ; 312: 111055, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620449

RESUMO

High salt environments can induce stress in different plants. The genes containing the ZAT domain constitute a family that belongs to a branch of the C2H2 family, which plays a vital role in responding to abiotic stresses. In this study, we identified 169 ZAT genes from seven plant species, including 44 ZAT genes from G. hirsutum. Phylogenetic tree analysis divided ZAT genes in six groups with conserved gene structure, protein motifs. Two C2H2 domains and an EAR domain and even chromosomal distribution on At and Dt sub-genome chromosomes of G. hirsutum was observed. GhZAT6 was primarily expressed in the root tissue and responded to NaCl and ABA treatments. Subcellular localization found that GhZAT6 was located in the nucleus and demonstrated transactivation activity during a transactivation activity assay. Arabidopsis transgenic lines overexpressing the GhZAT6 gene showed salt tolerance and grew more vigorously than WT on MS medium supplemented with 100 mmol NaCl. Additionally, the silencing of the GhZAT6 gene in cotton plants showed more obvious leaf wilting than the control plants, which were subjected to 400 mmol NaCl treatment. Next, the expressions of GhAPX1, GhFSD1, GhFSD2, and GhSOS3 were significantly lower in the GhZAT6-silenced plants treated with NaCl than the control. Based on these findings, GhZAT6 may be involved in the ABA pathway and mediate salt stress tolerance by regulating ROS-related gene expression.

3.
Cancer Commun (Lond) ; 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563100

RESUMO

BACKGROUND: Gastrointestinal (GI) cancers were responsible for 26.3% of cancer cases and 35.4% of deaths worldwide in 2018. This study aimed to analyze the global incidence, mortality, prevalence, and contributing risk factors of the 6 major GI cancer entities [esophageal cancer (EC), gastric cancer (GC), liver cancer (LC), pancreatic cancer (PC), colon cancer, and rectal cancer]. METHODS: Using the Global Cancer Observatory and the Global Health Observatory databases, we reviewed the current GI cancer incidence, prevalence, and mortality, analyzed the association of GI cancer prevalence with national human development indices (HDIs), identified the contributing risk factors, and estimated developing age- and sex-specific trends in incidence and mortality. RESULTS: In 2020, the trend in age-standardized rate of incidence of GI cancers closely mirrored that of mortality, with the highest rates of LC, EC, and GC in Asia and of colorectal cancer (CRC) and PC mainly in Europe. Incidence and mortality were positively, but the mortality-to-incidence ratio (MIR) was inversely correlated with the national HDI levels. High MIRs in developing countries likely reflected the lack of preventive strategies and effective treatments. GI cancer prevalence was highest in Europe and was also positively correlated with HDIs and lifestyle-associated risk factors, such as alcohol consumption, smoking, obesity, insufficient physical activity, and high blood cholesterol level, but negatively correlated with hypertension and diabetes. Incidences of EC were consistently and those of GC mostly decreasing, whereas incidences of CRC were increasing in most countries/regions, especially in the younger populations. Incidences of LC and PC were also increasing in all age-gender populations except for younger males. Mortalities were decreasing for EC, GC, and CRC in most countries/regions, and age-specific trends were observed in PC and LC with a decrease in the younger but an increase in the older population. CONCLUSIONS: On the global scale, higher GI cancer burden was accompanied, for the most part, by factors associated with the so-called Western lifestyle reflected by high and very high national HDI levels. In countries/regions with very high HDI levels, patients survived longer, and increasing GI cancer cases were observed with increasing national HDI levels. Optimizing GI cancer prevention and improving therapies, especially for patients with comorbid metabolic diseases, are thus urgently recommended.

4.
Planta ; 254(4): 75, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533620

RESUMO

MAIN CONCLUSION: Brassinosteroid (BR) synthesis genes in different cotton species was comprehensively identified, and the participation of GhCPD-3 in the BR synthesis signaling pathway for regulating plant development was verified. Brassinosteroid is a natural steroidal phytohormone that plays fundamental roles in plant growth and development. In cotton, detailed characterization and functional validation of BR biosynthesis genes remain rare. Here, 16, 8 and 9 BR biosynthesis genes were identified in Gossypium hirsutum, Gossypium raimondii and Gossypium arboreum, respectively, and their phylogenetic relationships, gene structures, conserved motifs of the encoded proteins, chromosomal locations were determined and a synteny analysis was performed. Gossypium hirsutum and Arabidopsis BR biosynthesis genes closely clustered in the phylogenetic tree and fragment duplication was likely the primary cause promoting gene family expansion in G. hirsutum. Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis showed their relevance as BR biosynthesis genes. GhCPD-3 was highly expressed in roots and stems and the loci of single nucleotide polymorphisms (SNPs) were significantly associated with these traits.Ectopic overexpression of GhCPD-3 in the cpd91 Arabidopsis mutant rescued the mutant phenotype by increasing plant height and leaf size in comparison to those of cpd91 and WT plants. Moreover, overexpressed GhCPD-3 in cpd91 mutants showed greater hypocotyl and root lengths than those of cpd91 and WT plants under light and dark conditions, respectively, indicating that BR actively promotes hypocotyl and root growth. Similar to CPD (CONSTITUTIVE PHOTOMORPHOGENIC DWARF), GhCPD-3 restores BR biosynthesis thereby mediating plant growth and development.


Assuntos
Regulação da Expressão Gênica de Plantas , Gossypium , Gossypium/genética , Gossypium/metabolismo , Filogenia , Desenvolvimento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
5.
Anal Chem ; 93(37): 12514-12523, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34490773

RESUMO

Despite that the currently discovered CRISPR-Cas12a system is beneficial for improving the detection accuracy and design flexibility of luminescent biosensors, there are still challenges to extend target species and strengthen adaptability in complicated biological media. To conquer these obstacles, we present here some useful strategies. For the former, the limitation to nucleic acids assay is broken through by introducing a simple functional DNA regulation pathway to activate the unique trans-cleavage effect of this CRISPR system, under which the expected biosensors are capable of effectively transducing a protein (employing dual aptamers) and a metal ion (employing DNAzyme). For the latter, a time-gated luminescence resonance energy transfer imaging manner using a long-persistent nanophosphor as the energy donor is performed to completely eliminate the background interference and a nature-inspired biomimetic periodic chip constructed by photonic crystals is further combined to enhance the persistent luminescence. In line with the above efforts, the improved CRISPR-Cas12a luminescent biosensor not only exhibits a sound analysis performance toward the model targets (carcinoembryonic antigen and Na+) but also owns a strong anti-interference feature to actualize accurate sensing in human plasma samples, offering a new and applicative analytical tool for laboratory medicine.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Biomimética , Sistemas CRISPR-Cas/genética , DNA/genética , Humanos , Luminescência
6.
J Cell Mol Med ; 25(17): 8127-8139, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34350711

RESUMO

Pre-eclampsia (PE) is the leading cause of maternal death; however, the causative molecular basis remains largely unknown. Recent studies have revealed the important role microRNAs (miRNAs) play in PE. We aimed to explore the effects of let-7d on trophoblast proliferation, migration, invasion and apoptosis in PE and its underlying mechanism. Placental tissues were collected from PE patients and healthy pregnant women, and it was found that let-7d expression was increased, while KDM3A and ENO2 expression was decreased in PE tissues and cells. Bioinformatics analysis indicated the interaction among let-7d, KDM3A and ENO2, confirmed by dual luciferase reporter gene assay; ChIP experiment identified methylated modification to ENO2 by KDM3A. With gain- and loss-function method, silencing of let-7d increased KDM3A expression and enhanced the binding between KDM3A and ENO2. Furthermore, overexpression of let-7d suppressed cell proliferation, migration and invasion of trophoblasts, and induced apoptosis of trophoblasts, while these capacities were restored upon additional treatment of overexpressed ENO2. PE rat models were established to explore the effects of let-7d and ENO2 on PE in vivo. The results established that the silencing of let-7d alleviated the tissue injury and PE-related symptoms when reducing urine protein, TUNEL-positive cells and increasing ENO2, and KDM3A expression in rats. Cumulatively, let-7d suppressed cell progression of trophoblasts, and induced apoptosis through the down-regulation of KDM3A to promote ENO2 methylation, thereby promoting progression of PE. Such an epigenetic network of let-7d, KDM3A and ENO2 in the pathogenesis of PE might provide novel insight into targeted therapy against this disorder.

7.
Mol Med Rep ; 24(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34414459

RESUMO

Increasing uric acid (UA) could induce renal tubular epithelial cell (NRK­52E) injury. However, the specific mechanism by which UA induces renal tubular epithelial cell injury remains unknown. It was hypothesized that UA induces renal tubular epithelial cell injury through reactive oxygen species (ROS) and the Never in mitosis gene A (NIMA)­related kinase 7 (NEK7)/NLR family pyrin domain containing 3 (NLRP3) signaling pathway. TUNEL assay and flow cytometry were applied to measure apoptosis, and the results of the present study showed that UA treatment induced apoptosis of NRK­52E cells in a concentration­dependent manner. Western blotting was performed to determine the expression levels of cleaved caspase­3, Bax and Bcl­xl, it was found that levels were significantly increased after UA treatment in NRK­52E cells. ROS and apoptosis were predominantly induced in NRK­52E cells and there was an association between ROS and apoptosis. Enhanced expression of NEK7, NLRP3, apoptosis­associated speck­like and caspase­1 were observed in NRK­52E cells treated with UA. The ROS inhibitor, N­acetyl­l­cysteine, exerted a protective effect on the UA­induced apoptosis of tubular epithelial cells by reducing excess ROS production, which significantly inhibited NEK7 and NLRP3 inflammasome activation. These results indicated that UA activates ROS and induces apoptosis of NRK­52E cells. The mechanism might be related to the regulation of the NEK7/NLRP3 signaling pathway.

8.
Biol Trace Elem Res ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398420

RESUMO

Lead (Pb) is a toxic heavy metal and environmental pollutant that adversely affects the nervous system. However, effective therapeutic drugs for Pb-induced neurotoxicity have yet to be developed. In the present study, we investigated the ameliorative effect of sodium para-aminosalicylic acid (PAS-Na) on Pb-induced neurotoxicity. Male Sprague-Dawley rats were treated with (CH3COO)2 Pb•4H2O (6 mg/kg) for 4 weeks, followed by 3 weeks of PAS-Na (100, 200, and 300 mg/kg). The results showed that subacute Pb exposure significantly decreased rats body-weight gains and increased liver coefficient, and impaired spatial learning and memory. HE staining showed that Pb damaged the structure of the hippocampus. Moreover, Pb activated the ERK1/2-p90RSK/ NF-κB pathway concomitant with increased inflammatory cytokine IL-1ß levels in rat hippocampus. PAS-Na reversed the Pb-induced increase in the liver coefficient as well as the learning and memory deficits. In addition, PAS-Na reduced the phosphorylation of ERK1/2, p90RSK and NF-κB p65, decreasing IL-1ß levels in hippocampus. Our findings indicated that PAS-Na showed efficacy in reversing Pb-induced rats cognitive deficits and triggered an anti-inflammatory response. Thus, PAS-Na may be a promising therapy for treating Pb-induced neurotoxicity.

9.
J Colloid Interface Sci ; 606(Pt 1): 1-9, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34384961

RESUMO

Developing durable and efficient photocatalysts for H2 evolution is highly desirable to expedite current research on solar-chemical energy conversion. In this work, a novel photocatalytic H2 evolution system based on Zn0.3Cd0.7S/NiS1.97 nanocomposite was rationally designed for the first time. In this advanced composite structure, NiS1.97 nanosheets as a co-catalyst were intimately coupled to the inner surface of the hollow spherical Zn0.3Cd0.7S. The construction of the hollow spherical shell shortened the distance of charge migration to the surface site and increased the multiple absorption of incident light. The introduction of NiS1.97 nanosheets increased the light absorption capacity of the composite system and also greatly improved the separation and migration behavior of photo-generated carriers due to its narrower band gap and relatively low conduction band position, which had been confirmed by DRS, EIS and PL. As a result, the hollow Zn0.3Cd0.7S/NiS1.97 composite material exhibited excellent photocatalytic activity. At the loading amount of NiS1.97 up to 15 at.%, the hollow Zn0.3Cd0.7S/NiS1.97 composite exhibited the best photocatalytic activity with a corresponding H2 production rate of 22.637 mmol g-1h-1, which was 1.42 times and 1.85 times that of hollow Zn0.3Cd0.7S and solid Zn0.3Cd0.7S, respectively. Moreover, this novel catalyst also displayed a long-term stability without apparent debasement in H2 evolution activity. It is expected that this work could provide new inspiration to the design and development of other highly active photocatalytic systems for water splitting.

10.
Gene ; 804: 145884, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364913

RESUMO

Skeletal muscle is one of the most important economic traits in the poultry industry whose development goes through several processes influenced by several candidate genes. This study explored the regulatory role of DCN on MSTN and the influence of these genes on the proliferation and differentiation of embryonic myoblasts in Leizhou black ducks. Embryonic myoblasts were transfected with over-expressing DCN, Si-DCN, and empty vector and cultured for 24 h, 48 h, and 72 h of proliferation and the comparative expression of DCN and MSTN were measured. The results showed that cells transfected with the over-expression DCN had a significantly (P < 0.05) higher expression of DCN mRNA than the normal group and the expression of MSTN mRNA showed a downward trend during the proliferation of myoblasts. DCN mRNA expression was lower in cells transfected with Si-DCN than the normal group in all stages of proliferation. While the expression of MSTN in the Si-DCN transfected group was higher than the normal group with a significant (P < 0.05) difference at the 72 h stage. DCN mRNA increased at the early stage of differentiation but decreased (P > 0.05) from the 6th day to the 8th day of differentiation. The level of MSTN increased gradually during the differentiation process of myoblasts until it decreased significantly on the 8th day. These results show that DCN enhances the proliferation and differentiation of Leizhou black duck myoblasts and suppresses MSTN activity.


Assuntos
Decorina/metabolismo , Patos/metabolismo , Miostatina/metabolismo , Animais , Proteínas Aviárias/genética , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Decorina/fisiologia , Patos/embriologia , Patos/genética , Músculo Esquelético/embriologia , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Aves Domésticas/genética , Aves Domésticas/metabolismo , RNA Mensageiro/genética
11.
J Mater Sci Mater Med ; 32(9): 95, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34406479

RESUMO

Zinc (Zn) and its alloys have received increasing attention as new alternative biodegradable metals. However, consensus has not been reached on the corrosion behaviour of Zn. As cardiovascular artery stent material, Zn is supposed to contact with plasma that contains inorganic salts and organic components. Protein is one of the most important constitute in the plasma and could adsorb on the material surface. In this paper, bovine serum albumin (BSA) was used as a typical protein. Influences of BSA on pure Zn corrosion in phosphate buffered saline is investigated as a function of BSA concentrations and immersion durations by electrochemical techniques and surface analysis. Results showed that pure Zn corrosion was progressively accelerated with BSA concentrations (ranging from 0.05 to 5 g L-1) at 0.5 h. With time evolves, formation of phosphates as corrosion product was delayed by BSA adsorption, especially at concentration of 2 g L-1. Within 48 h, the corrosion of pure Zn was alleviated by BSA at concentration of 0.1 g L-1, whereas the corrosion was enhanced after 168 h. Addition of 2 g L-1 BSA has opposite influence on the pure Zn corrosion. Furthermore, schematic corrosion behaviour at protein/Zn interfaces was proposed. This work encourages us to think more about the influence of protein on the material corrosion and helps us to better understand the corrosion behaviour of pure Zn.

12.
Nat Commun ; 12(1): 4230, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244494

RESUMO

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXß2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXß2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXß2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXß2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.


Assuntos
Processamento Alternativo , Carcinoma Epitelial do Ovário/genética , Proteínas da Matriz Extracelular/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas da Matriz Extracelular/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Integrina alfaXbeta2/genética , Integrina alfaXbeta2/metabolismo , Estimativa de Kaplan-Meier , Camundongos , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Ovário/patologia , Ovário/cirurgia , Fosforilação/genética , Prognóstico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA-Seq , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Plant Physiol Biochem ; 166: 328-340, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34147725

RESUMO

Cytokinin (CK) is an important plant hormone that promotes plant cell division and differentiation, and participates in salt response under osmotic stress. LOGs (LONELY GUY) are CK-activating enzymes involved in CK synthesis. The LOG gene family has not been comprehensively characterized in cotton. In this study we identified 151 LOG genes from nine plant species, including 28 LOG genes in Gossypium hirsutum. Phylogenetic analysis divided LOG genes into three groups. Exon/intron structures and protein motifs of GhLOG genes were highly conserved. Synteny analysis revealed that several gene loci were highly conserved between the A and D sub-genomes of G. hirsutum with purifying selection pressure during evolution. Expression profiles showed that most LOG genes were constitutively expressed in eight different tissues. Furthermore, LOG genes can be regulated by abiotic stresses and phytohormone treatments. Moreover, subcellular localization revealed that GhLOG3_At resides inside the cell membrane. Overexpression of GhLOG3 enhanced salt tolerance in Arabidopsis. Virus-induced gene silencing (VIGS) of GhLOG3_At in cotton enhanced sensitivity of plants to salt stress with increased H2O2 contents and decreased chlorophyll and proline (PRO) activity. Our results suggested that GhLOG3_At induces salt stress tolerance in cotton, and provides a basis for the use of CK synthesis genes to regulate cotton growth and stress resistance.


Assuntos
Gossypium , Tolerância ao Sal , Regulação da Expressão Gênica de Plantas , Gossypium/genética , Gossypium/metabolismo , Peróxido de Hidrogênio , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética
14.
J Comp Physiol B ; 191(4): 721-729, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33934186

RESUMO

We examined intraspecific scaling of the resting metabolic rate (RMR) of Nile tilapia (Oreochromis niloticus) under different culture conditions and further explored the allometric relationships between organ mass (heart, liver, brain, gills, viscera, and red muscles) and blood parameters (erythrocyte size and red blood cell counts) and body mass. Oreochromis niloticus were bred in individual and group cultures. The scaling exponent of the RMR in the individual cultures was b = 0.620-0.821 (n = 30) and that in the group culture was b = 0.770 [natural logarithm (ln) RMR = 0.770 ln M - 1.107 (n = 76)]. The results of the two experimental methods were similar and were not significantly different from 0.75 (3/4), as predicted by the metabolic theory of ecology. The active and inactive organs were scaled with body mass by an exponent of 0.940 and 1.012, respectively. There was no significant relationship between the blood parameters and body mass. These results suggest that the differences in the culture methods may not have affected the allometric scaling of O. niloticus metabolism. The proportion of active and inactive organs contributed to allometric changes in the metabolic rate with body mass. Red blood cells in fish are not generally representative, and cell size can only partially explain the allometric scaling of metabolism.

15.
J Nurs Manag ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792990

RESUMO

AIM: To elucidate the effects of workplace violence on turnover intention among Chinese health care workers, and to identify the potential mediators in this relationship. BACKGROUND: Workplace violence has emerged as a crucial determinant of turnover intention for health care workers. METHODS: A cross-sectional survey was conducted among Chinese health care workers (N = 1,063) between 13 and 20 February 2020. Mediation effects were tested using structural equation modelling with weighted least squares mean and variance adjusted (WLSMV) estimator. RESULTS: Workplace violence had both direct and indirect effects on turnover intention among Chinese health care workers. Specifically, perceived social support, mental health and perceived social support together with mental health partially mediated the relationship between workplace violence and turnover intention. CONCLUSIONS: Chinese health care workers experiencing violence during the COVID-19 outbreak were more likely to report turnover intention. Enhancing social support and reducing mental health problems would be beneficial in decreasing the detrimental effects of workplace violence on turnover intention. IMPLICATIONS FOR NURSING MANAGEMENT: Ensuring health care workers' health and safety is vital in reducing turnover intention, which in turn ascertains continuity of health care delivery. Health care managers should develop targeted interventions to improve social support and prevent post-violence mental health problems.

16.
Clin Transl Med ; 11(3): e352, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33783988

RESUMO

BACKGROUND: S-adenosylmethionine decarboxylase proenzyme (AMD1) is a key enzyme involved in the synthesis of spermine (SPM) and spermidine (SPD), which are associated with multifarious cellular processes. It is also found to be an oncogene in multiple cancers and a potential target for tumor therapy. Nevertheless, the role AMD1 plays in hepatocellular carcinoma (HCC) is still unknown. METHODS: HCC samples were applied to detect AMD1 expression and evaluate its associations with clinicopathological features and prognosis. Subcutaneous and orthotopic tumor mouse models were constructed to analyze the proliferation and metastasis of HCC cells after AMD1 knockdown or overexpression. Drug sensitive and tumor sphere assay were performed to investigate the effect of AMD1 on HCC cells stemness. Real-time quantitative PCR (qRT-PCR), western blot, immunohistochemical (IHC) and m6A-RNA immunoprecipitation (Me-RIP) sequencing/qPCR were applied to explore the potential mechanisms of AMD1 in HCC. Furthermore, immunofluorescence, co-IP (Co-IP) assays, and mass spectrometric (MS) analyses were performed to verify the proteins interacting with AMD1. RESULTS: AMD1 was enriched in human HCC tissues and suggested a poor prognosis. High AMD1 level could promote SRY-box transcription factor 2 (SOX2), Kruppel like factor 4 (KLF4), and NANOG expression of HCC cells through obesity-associated protein (FTO)-mediated mRNA demethylation. Mechanistically, high AMD1 expression increased the levels of SPD in HCC cells, which could modify the scaffold protein, Ras GTPase-activating-like protein 1 (IQGAP1) and enhance the interaction between IQGAP1 and FTO. This interaction could enhance the phosphorylation and decrease the ubiquitination of FTO. CONCLUSIONS: AMD1 could stabilize the interaction of IQGAP1 with FTO, which then promotes FTO expression and increases HCC stemness. AMD1 shows prospects as a prognostic predictor and a therapeutic target for HCC.

17.
Molecules ; 26(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669157

RESUMO

α-Galacto-oligosaccharides (α-GOSs) have great functions as prebiotics and therapeutics. This work established the method of batch synthesis of α-GOSs by immobilized α-galactosidase for the first time, laying a foundation for industrial applications in the future. The α-galactosidase from Aspergillus niger L63 was immobilized as cross-linked enzyme aggregates (CLEAs) nano-biocatalyst through enzyme precipitating and cross-linking steps without using carriers. Among the tested agents, the ammonium sulfate showed high precipitation efficacy and induced regular structures of α-galactosidase CLEAs (Aga-CLEAs) that had been analyzed by scanning electron microscopy and Fourier-transform infrared spectroscopy. Through optimization by response surface methodology, the ammonium sulfate-induced Aga-CLEAs achieved a high activity recovery of around 90% at 0.55 U/mL of enzymes and 36.43 mM glutaraldehyde with cross-linking for 1.71 h. Aga-CLEAs showed increased thermal stability and organic solvent tolerance. The storage ability was also improved since it maintained 74.5% activity after storing at 4 °C for three months, significantly higher than that of the free enzyme (21.6%). Moreover, Aga-CLEAs exhibited excellent reusability in the α-GOSs synthesis from galactose, retaining above 66% of enzyme activity after 10 batch reactions, with product yields all above 30%.


Assuntos
Galactose/biossíntese , Oligossacarídeos/biossíntese , Prebióticos/análise , alfa-Galactosidase/metabolismo , Aspergillus niger/enzimologia , Biocatálise , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Galactose/química , Oligossacarídeos/química , alfa-Galactosidase/química
18.
Food Chem Toxicol ; 150: 112063, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33596455

RESUMO

Lead is a heavy metal pollutant that is widely present in the environment. It affects every organ system, yet the nervous system appears to be the most sensitive and primary target. Although many countries have made significant strides in controlling Pb pollution, Pb poisoning continuous to be a major public health concern. Exposure to Pb causes neurotoxicity that ranges from neurodevelopmental disorders to severe neurodegenerative lesions, leading to impairments in learning, memory, and cognitive function. Studies on the mechanisms of Pb-induced nervous system injury have convincingly shown that this metal can affect a plethora of cellular pathways affecting on cell survival, altering calcium dyshomeostasis, and inducing apoptosis, inflammation, energy metabolism disorders, oxidative stress, autophagy and glial stress. This review summarizes recent knowledge on multiple signaling pathways associated with Pb-induced neurological disorders in vivo and in vitro.


Assuntos
Doenças do Sistema Nervoso Central/induzido quimicamente , Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Animais , Cálcio/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos
19.
Br J Cancer ; 124(8): 1411-1420, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33558709

RESUMO

BACKGROUND: Recent evidence proves that intravenous human immunoglobulin G (IgG) can impair cancer cell viability. However, no study evaluated whether IgG application benefits cancer patients receiving chemotherapeutics. METHODS: Influence of pharmaceutical-grade human IgG on the viability of a series of patient-derived colon cancer cell lines with and without chemotherapeutic intervention was determined. Cell death was analysed flow cytometrically. In addition, the influence of oxaliplatin and IgG on the ERK1/2-signalling pathway was evaluated by western blots. RESULTS: We evaluated the effects of pharmaceutical IgG, such as PRIVIGEN® IgG and Tonglu® IgG, in combination with chemotherapeutics. We did not observe any significant effects of IgG on tumour cell viability directly; however, human IgG significantly impaired the anti-tumoral effects of oxaliplatin. Primary cancer cell lines express IgG receptors and accumulate human IgG intracellularly. Moreover, while oxaliplatin induced the activation of ERK1/2, the pharmaceutical IgG inhibited ERK1/2 activity. CONCLUSIONS: The present study demonstrates that pharmaceutical IgG, such as PRIVIGEN® IgG and Tonglu® IgG, can impair the anti-carcinoma activity of oxaliplatin. These data strongly suggest that therapeutic IgG as co-medication might have harmful side effects in cancer patients. The clinical significance of these preclinical observations absolutely advises further preclinical, as well as epidemiological and clinical research.


Assuntos
Neoplasias do Colo/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , Imunoglobulinas Intravenosas/administração & dosagem , Oxaliplatina/farmacologia , Idoso , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Interações Medicamentosas , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imunoglobulinas Intravenosas/farmacologia , Masculino , Pessoa de Meia-Idade , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Colloid Interface Sci ; 591: 307-313, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33618290

RESUMO

The specific roles of Ni and Fe in nickel-iron (oxy)hydroxide catalyst (NiFeOx(OH)y) are extensively discussed during oxygen evolution reaction (OER). However, there still remains controversy about whether Ni or Fe species as the dominate active site. In this work, we reported the NiFeOx(OH)y catalysts with varied atomic ratio of nickel and iron for OER to explore the dominate active site during OER processes. From the electrochemical performances, the similar Tafel slopes of catalysts with Fe species can achieve at a level of 40 mV dec-1, outperforming the Tafel slopes of catalysts without Fe species. Thus, it can be concluded that the present Fe site can serve as the dominant active site in NiFeOx(OH)y for OER. Meanwhile, the Ni species is proved as the OH- adsorption site, which is beneficial to the Fe site to deliver a better OER performance. As a result, the catalyst with an optimal Ni/Fe interface (atomic ratio of 1 : 1.18) displays outstanding OER performances. It only requires a low overpotential of 250 mV to deliver current density of 10 mA cm-2 and exhibits a small Tafel slope of 39 mV dec-1. This catalyst also shows remarkable stability with negligible potential decay after 50 h at a current density of 50 mA cm-2. This work offers a new sight into the specific roles of Ni and Fe in NiFeOx(OH)y for OER.

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