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1.
Opt Express ; 29(21): 33491-33501, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34809160

RESUMO

We demonstrate an approach to ultra-short pulse train generation with a low time jitter based on pulse compression of a frequency comb generated by a dual-loop optoelectronic oscillator (OEO). The proposed dual-loop OEO consists of two feedback loops, with one having a long loop length and the other a short loop length. In the long loop, a phase modulator (PM) cascaded with a Mach-Zehnder modulator (MZM) are employed, and in the short loop, only the MZM is included. Due to the Vernier effect, the use of the dual-loop structure can facilitate mode selection to generate a single-frequency microwave carrier with multiple optical sidebands corresponding to an optical comb. By adjusting the phase relationship between the optical sidebands using a dispersion compensating fiber (DCF), a stable optical pulse train is generated. Thanks to the low phase noise nature of an OEO, the generated pulse train has a low time jitter. The proposed approach is evaluated experimentally. A pulse train with a repetition frequency of 2.023 GHz and a pulse width of 40 ps is generated. The single-sideband (SSB) phase noise of the carrier frequency generated by the OEO is measured to be -118 dBc/Hz at a 10-kHz offset frequency, corresponding to a time jitter of the pulse train of 391.2 fs. The phase noise can be further reduced if an active cavity stabilization mechanism is adopted, enabling further reduction in the time jitter to the order of tens of femtoseconds.

2.
Front Public Health ; 9: 764069, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820352

RESUMO

In contemporary "high-risk" society, unexpected disasters (epidemics and extreme weather) and chronic pressures (aging problems) put tremendous pressure on healthcare facilities. Enhancing the healthcare facilities' resilience ability to resist, absorb, and respond to disaster disruptions is urgent. This study presents a scientometric review for healthcare facility resilience research. A total of 374 relevant articles published between 2000 and 2020, collected from Web of Science (WoS) core collection database, Scopus database and MEDLINE database were reviewed and analyzed. The results indicated that research on resilience in healthcare facilities went through three development periods, and the research involved countries or institutions that are relatively scattered. The studies have been focused on the subject categories of engineering, public, environmental, and occupational health. The keywords of "resilience," "hospital," "disaster," "healthcare," and "healthcare facility" had the most frequency. Furthermore, based on the literature co-citation networks and content analysis, the detected seven co-citation clusters were grouped into four knowledge domains: climate change impact, strengthening resilience in response to war and epidemic, resilience assessment of healthcare facility, and the applications of information system. Moreover, the timeline view of literature reflected the evolution of each domain. Finally, a knowledge map for resilience of healthcare facilities was put forward, in which critical research contents, current knowledge gaps, and future research work were discussed. This contribution will promote researchers and practitioners to detect the hot topics, fill the knowledge gaps, and extend the body of research on resilience of healthcare facilities.

3.
J Hazard Mater ; 424(Pt C): 127521, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34736187

RESUMO

Ionic liquids (ILs), owing to their low vapor pressure and excellent solvating ability, are being increasingly applied in various industries to replace highly toxic organic solvents. They mainly pollute aquatic environment and soils, directly endangering eco-environment and human health. Therefore, it is critical to understand and optimize structural motifs of ILs with reduced toxicity. Considering human oral exposure is the major route, our investigations employed a human cell panel (modeling oral exposures) including human stomach (GES-1), intestinal (FHC), liver (HepG2) and kidney (HEK293) cells using a series of experimental and computational approaches to explore the cytotoxicity and molecular mechanism of ILs. We discovered that the cytotoxicity of triazolium and imidazolium ILs was human cell line-dependent with cytotoxicity in an order of FHC > GES-1 > HepG2 > HEK293. For this reason, a toxicity assay using a single cell line was highly inappropriate. Compared to anions (Br-, OTs-, OTMBS-) we tested, the cation of ILs played a major role in causing cytotoxicity. Ionic liquids with cations having longer hydrophobic sidechains (IL09 vs. IL01) readily insert into cell membranes with enhanced membrane and lipidomic perturbations, induce cytotoxicity by triggering cell cycle arrest and apoptosis. Reducing sidechain length and incorporating three nitrogen atoms (triazolium) instead of two (imidazolium) in the cation core alleviated cytotoxicity by reducing cell membrane perturbations and cell function interference. These findings provide important guiding principles for the design of the next-generation of "green" and safe ILs.

4.
Mutagenesis ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34791379

RESUMO

Obese subjects have a high baseline of genotoxic stress, but the underlying mechanism is poorly understood. Given that obesity is associated with high bile acids (BA) and low folate, we aimed to determine the interactive effect of folate deficient or supplementation to the genotoxicity and cytotoxicity of BA in human colon and liver cells. NCM460 and L-02 cells were cultured in folate deficient (22.6 nM) and replete (2260 nM) RPMI 1640 medium with or without 50 µM deoxycholic acid (DCA) or lithocholic acid (LCA) for 7 days. Moreover, these cells were cultured in folate supplemented (5.65, 11.3 and 22.6 µM) and standard (2.26 µM) medium with 200 µM DCA or LCA for 7 days. Genotoxicity and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. Our results showed that under folate-replete condition, 50 µM DCA or LCA significantly increased the rate of micronuclei in NCM460 and L-02 cells. Significantly, the micronuclei-inducing effect of 50 µM DCA or LCA was further enhanced by folate deficiency. Interestingly, folate supplementation exerted a dose-dependent manner to significantly decrease the rates of micronuclei, nucleoplasmic bridges, nuclear buds, apoptosis and necrosis induced by 200 µM DCA or LCA in NCM460 and L-02 cells. In conclusion, the genotoxicity of moderate BA (50 µM) was exacerbated by folate deficiency and folate supplementation could efficiently protect cells against the genotoxicity and cytotoxicity of high BA (200 µM).

5.
Am J Infect Control ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34742749

RESUMO

BACKGROUND: Healthcare-associated infections (HAIs) are a persistent clinical challenge caused primarily by bacteria on the skin. Proper utilization of optimized antiseptic skin preparation solutions helps reduce the prevalence and impact of HAIs by decreasing patient skin microorganisms preoperatively. The purpose of this study was to evaluate the efficacy of two antimicrobial solutions containing iodine and isopropyl alcohol (IPA): Povidone iodine (PVP-I) with IPA (i.e., PVP-I+IPA, PurPrep™) and Iodine Povacrylex+IPA (DuraPrep™). METHODS: The antimicrobial activity of the test solutions was evaluated in vitro by determinations of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) against 1105 diverse microbial isolates and a time-kill assay to evaluate efficacy against 120 strains of Gram-positive and Gram-negative bacteria and yeasts. Peel tests were performed between skin samples treated with test solutions and representative drape/dressing materials to determine effects of test solutions on the biomechanical adhesion properties. Finally, an Institutional Review Board (IRB)-approved, randomized, controlled, single-center, partially blinded in vivo study was performed to assess the immediate and persistent antimicrobial activity of the test solutions on the abdomen and groin. RESULTS: Both PVP-I+IPA and Iodine Povacrylex+IPA solutions demonstrated broad-spectrum antimicrobial activity with MIC and MBC at less than 1% of the full-strength concentration of each product against a wide variety of microorganisms. In the time-kill tests, both solutions were able to successfully reduce all microbial populations by 99.99% (i.e., 4log10) at the contact times of 30 seconds, 2 minutes and 10 minutes. The two solutions showed relatively similar adhesion results when tested with three representative operating room materials. Both PVP-I+IPA and Iodine Povacrylex+IPA met the expected Food and Drug Administration (FDA) efficacy requirements at 10 minutes and 6 hours post-treatment for both anatomical sites (i.e., groin and abdomen) in the clinical study, with no safety issues or adverse events. CONCLUSIONS: Analysis of the in vitro antimicrobial activity, biomechanical adhesive strength, and in vivo efficacy of PVP-I+IPA demonstrated similar results compared to Iodine Povacrylex+IPA. Both products were efficacious at reducing or eliminating a wide range of clinically-relevant microorganisms in lab-based and clinical settings, supporting their use as antiseptic skin preparation solutions to reduce bacteria on the skin that can cause infection.

7.
J Nat Prod ; 84(11): 3001-3007, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34677966

RESUMO

The pressing need for SARS-CoV-2 controls has led to a reassessment of strategies to identify and develop natural product inhibitors of zoonotic, highly virulent, and rapidly emerging viruses. This review article addresses how contemporary approaches involving computational chemistry, natural product (NP) and protein databases, and mass spectrometry (MS) derived target-ligand interaction analysis can be utilized to expedite the interrogation of NP structures while minimizing the time and expense of extraction, purification, and screening in BioSafety Laboratories (BSL)3 laboratories. The unparalleled structural diversity and complexity of NPs is an extraordinary resource for the discovery and development of broad-spectrum inhibitors of viral genera, including Betacoronavirus, which contains MERS, SARS, SARS-CoV-2, and the common cold. There are two key technological advances that have created unique opportunities for the identification of NP prototypes with greater efficiency: (1) the application of structural databases for NPs and target proteins and (2) the application of modern MS techniques to assess protein-ligand interactions directly from NP extracts. These approaches, developed over years, now allow for the identification and isolation of unique antiviral ligands without the immediate need for BSL3 facilities. Overall, the goal is to improve the success rate of NP-based screening by focusing resources on source materials with a higher likelihood of success, while simultaneously providing opportunities for the discovery of novel ligands to selectively target proteins involved in viral infection.

8.
Neural Plast ; 2021: 6718184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497641

RESUMO

Several clinical parameters and biomarkers have been proposed as prognostic markers for stroke. However, it has not been clarified whether the risk factors affecting the prognosis of patients with recurrent and first-ever stroke are similar. In this study, we aimed to explore the relationship between soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) levels and the prediction of the functional outcome in patients with recurrent and first-ever stroke. A total of 266 patients with recurrent and first-ever stroke, who underwent follow-up for 3 months, were included in this study. Plasma samples were collected within 24 h after onset. The results showed that biomarkers for the prognosis of patients with recurrent stroke were different from that of those with first-ever stroke. sLOX-1 levels were correlated with modified Rankin Scale scores of patients with recurrent stroke alone (r = 0.3232, p = 0.001). sLOX-1 levels were also associated with an increased risk of unfavorable outcomes in patients with recurrent stroke with an adjusted odds ratio of 1.489 (95% confidence interval, 1.204-1.842, p < 0.0001). Combining the risk factors showed greater accuracy for prognosis, yielding a sensitivity of 93.2% and a specificity of 75%, with an area under the curve of 0.916, evaluated by the receiver operating characteristic curve. These findings suggest that the diagnosis and prognosis are different between patients with recurrent stroke and those with first-ever stroke, and sLOX-1 level is an independent prognostic marker in patients with recurrent stroke.

9.
Comput Math Methods Med ; 2021: 3957738, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527075

RESUMO

Introduction: To investigate the function of miR-190a-3p on the proliferation and migration of glioma. Methods: Twenty glioma samples and 6 normal brain tissue samples were collected. Normal human glial cell line HEB and glioma cell lines were used for the experiments. We then used TargetScan to predict the target genes of miR-190a-3p. Dual-luciferase reporter assay was also used to validate. Results: Combined with dual-luciferase reporter experiment, we finally verified that YOD1 was the aim, and it was low-expressed in glioma. Besides, a series of mechanism experiments then proved that miR-190a-3p negatively regulates YOD1 expression. Conclusions: Our research was the first to demonstrate the promoting function of miR-190a-3p in the proliferation and migration of glioma and provided new views for the treatment of glioma. miR-190a-3p was expected to be a new target for molecular therapy of glioma.

10.
Front Immunol ; 12: 720393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335634

RESUMO

Atopic dermatitis (AD) is a public health concern and is increasing in prevalence in urban areas. Recent advances in sequencing technology have demonstrated that the development of AD not only associate with the skin microbiome but gut microbiota. Gut microbiota plays an important role in allergic diseases including AD. The hypothesis of the "gut-skin" axis has been proposed and the cross-talk mechanism between them has been gradually demonstrated in the research. Probiotics contribute to the improvement of the intestinal environment, the balance of immune responses, regulation of metabolic activity. Most studies suggest that probiotic supplements may be an alternative for the prevention and treatment of AD. This study aimed to discuss the effects of probiotics on the clinical manifestation of AD based on gut microbial alterations. Here we reviewed the gut microbial alteration in patients with AD, the association between gut microbiota, epidermal barrier, and toll-like receptors, and the interaction of probiotics and gut microbiota. The potential mechanisms of probiotics on alleviating AD via upregulation of epidermal barrier and regulation of immune signaling had been discussed, and their possible effective substances on AD had been explored. This provides the supports for targeting gut microbiota to attenuate AD.

11.
Front Neurol ; 12: 691886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421795

RESUMO

Hepatocyte growth factor (HGF) is a potential prognostic factor for acute ischemic stroke (AIS). In this study, we sought to validate its earlier predictive accuracy within 24 h for first-ever AIS. Moreover, as HGF interacts with interleukins, their associations may lead to novel immunomodulatory therapeutic strategies. Patients with first-ever AIS (n = 202) within 24 h were recruited. Plasma HGF and related interleukin concentrations were measured by multiplex immunoassays. The primary and secondary outcomes were major disability (modified Rankin scale score ≥3) at 3 months after AIS and death, respectively. Elastic net regression was applied to screen variables associated with stroke outcome; binary multivariable logistic analysis was then used to explore the relationship between HGF level and stroke outcome. After multivariate adjustment, upregulated HGF levels were associated with an increased risk of the primary outcome (odds ratio, 7.606; 95% confidence interval, 3.090-18.726; p < 0.001). Adding HGF to conventional risk factors significantly improved the predictive power for unfavorable outcomes (continuous net reclassification improvement 37.13%, p < 0.001; integrated discrimination improvement 8.71%, p < 0.001). The area under the receiver operating characteristic curve value of the traditional model was 0.8896 and reached 0.9210 when HGF was introduced into the model. An elevated HGF level may also be a risk factor for mortality within 3 months poststroke. The HGF level was also positively correlated with IL-10 and IL-16 levels, and HGF before interaction with all interleukins was markedly negatively correlated with the lymphocyte/neutrophil ratio. HGF within 24 h may have prognostic potential for AIS. Our findings reinforce the link between HGF and interleukins.

12.
Int J Mol Sci ; 22(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299216

RESUMO

Bifidobacterium bifidum strains, an important component of probiotic foods, can form biofilms on abiotic surfaces, leading to increased self-resistance. However, little is known about the molecular mechanism of B. bifidum biofilm formation. A time series transcriptome sequencing and untargeted metabolomics analysis of both B. bifidum biofilm and planktonic cells was performed to identify key genes and metabolites involved in biofilm formation. Two hundred thirty-five nonredundant differentially expressed genes (DEGs) (including vanY, pstS, degP, groS, infC, groL, yajC, tadB and sigA) and 219 nonredundant differentially expressed metabolites (including L-threonine, L-cystine, L-tyrosine, ascorbic acid, niacinamide, butyric acid and sphinganine) were identified. Thirteen pathways were identified during the integration of both transcriptomics and metabolomics data, including ABC transporters; quorum sensing; two-component system; oxidative phosphorylation; cysteine and methionine metabolism; glutathione metabolism; glycine, serine and threonine metabolism; and valine, leucine and isoleucine biosynthesis. The DEGs that relate to the integration pathways included asd, atpB, degP, folC, ilvE, metC, pheA, pstS, pyrE, serB, ulaE, yajC and zwf. The differentially accumulated metabolites included L-cystine, L-serine, L-threonine, L-tyrosine, methylmalonate, monodehydroascorbate, nicotinamide, orthophosphate, spermine and tocopherol. These results indicate that quorum sensing, two-component system and amino acid metabolism are essential during B. bifidum biofilm formation.


Assuntos
Proteínas de Bactérias/metabolismo , Bifidobacterium bifidum/fisiologia , Biofilmes/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Bifidobacterium bifidum/genética , Bifidobacterium bifidum/metabolismo , Perfilação da Expressão Gênica , Metaboloma , Percepção de Quorum , Transcriptoma , Triticum/microbiologia
13.
Cells ; 10(5)2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062929

RESUMO

Understanding asymptomatic moyamoya disease (aMMD), for which treatment options are currently limited, is key to the development of therapeutic strategies that will slow down the progression of this disease, as well as facilitate the discovery of therapeutic targets for symptomatic MMD. Newly found transfer RNA-derived small RNAs (tsRNAs) perform potential regulatory functions in neovascularization, which is a well-known pathological manifestation of MMD. In this study, the neutrophilic tsRNA transcriptome in aMMD was profiled using next-generation RNA sequencing in five patients and five matched healthy subjects. A negative binominal generalized log-linear regression was used to identify differentially expressed (DE)-tsRNAs in aMMD. Gene Ontology and functional pathway analyses were used to identify biological pathways involved with the targeted genes of the DE-tsRNAs. Four tsRNAs were selected and validated using quantitative reverse transcription polymerase chain reaction. In total, 186 tsRNAs were DE between the two groups. Pathophysiological events, including immune response, angiogenesis, axon guidance, and metabolism adjustment, were enriched for the DE-tsRNAs. The expression levels of the four DE-tsRNAs were consistent with those in the neutrophilic transcriptome. These aberrantly expressed tsRNAs and their targeted pathophysiological processes provide a basis for potential future interventions for aMMD.


Assuntos
Doença de Moyamoya/genética , Doença de Moyamoya/metabolismo , Pequeno RNA não Traduzido/genética , Axônios , Proliferação de Células , Biologia Computacional , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Sistema Imunitário , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , RNA de Transferência/metabolismo , Análise de Regressão , Transdução de Sinais , Transcriptoma
14.
Int Immunopharmacol ; 96: 107760, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33991998

RESUMO

Considerable data have suggested that acute kidney injury (AKI) is often incompletely repaired and could lead to chronic kidney disease (CKD). As we known, toxin-induced nephropathy triggers the rapid production of proinflammatory mediators and the prolonged inflammation allows the injured kidneys to develop interstitial fibrosis. In our previous study, fatty acid-binding protein 4 (Fabp4) has been reported to be involved in the process of AKI. However, whether Fabp4 plays crucial roles in toxin-induced kidney injury remained unclear. To explore the effect and mechanism of Fabp4 on toxin induced kidney injury, folic acid (FA) and aristolochic acid (AA) animal models were used. Both FA and AA injected mice developed severe renal dysfunction and dramatically inflammatory response (IL-6, MCP1 and TNF-a), which further lead to early fibrosis confirmed by the accumulation of extracellular matrix proteins (α-Sma, Fn, Col1 and Col4). Importantly, we found that FA and AA induced-kidney injury triggered the high expression of Fabp4 mRNA/protein in tubular epithelial cells. Furthermore, pharmacological and genetic inhibition of Fabp4 significantly attenuated FA and AA induced renal dysfunction, pathological damage, and early fibrosis via the regulation of inflammation, which is mediated by suppressing p-p65/p-stat3 expression via enhancing Pparγ activity. In summary, Fabp4 in tubular epithelial cells exerted the deleterious effects during the recovery of FA and AA induced kidney injury and the inhibition of Fabp4 might be an effective therapeutic strategy against the progressive AKI.

16.
J Fish Dis ; 44(8): 1155-1168, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33831221

RESUMO

Pathogens adapted to sub-lethal acidic conditions could increase the virulence and survival ability under lethal conditions. In the aquaculture industry, feed acidifiers have been used to increase the growth of aquatic animals. However, there is limited study on the effects of acidic condition on the virulence and survival of pathogens in aquaculture. In this study, we investigated the survival ability of Vibrio parahaemolyticus at lethal acidic pH (4.0) after adapted the bacteria to sub-lethal acidic pH (5.5) for 1 hr. Our results indicated that the adapted strain increased the survival ability at lethal acidic pH invoked by an inorganic (HCl) or organic (citric) acid. RNA-sequencing (RNA-seq) results revealed that 321 genes were differentially expressed at the sub-lethal acidic pH including cadC, cadBA and groES/groEL relating to acid tolerance response (ATR), as well as genes relating to outer membrane, heat-shock proteins, phosphotransferase system and flagella system. Quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that cadC and cadBA were upregulated under sub-lethal acidic conditions. The CadC protein could directly regulate the expression of cadBA to modulate the ATR in V. parahaemolyticus. RNA-seq data also indicated that 113 genes in the CadC-dependent way and 208 genes in the CadC-independent way were differentially expressed, which were related to the regulation of ATR. Finally, the motility and cytotoxicity of the sub-lethal acidic adapted wild type (WT) were significantly increased compared with the unadapted strain. Our results demonstrated that the dietary acidifiers may increase the virulence and survival of V. parahaemolyticus in aquaculture.


Assuntos
Proteínas de Bactérias/metabolismo , Ácido Cítrico/metabolismo , Expressão Gênica , Genes Bacterianos , Ácido Clorídrico/metabolismo , Vibrio parahaemolyticus/fisiologia , Vibrio parahaemolyticus/patogenicidade , Concentração de Íons de Hidrogênio , RNA-Seq
17.
Foods ; 10(4)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33924002

RESUMO

Influenza A virus induces severe respiratory tract infection and results in a serious global health problem. Influenza infection disturbs the cross-talk connection between lung and gut. Probiotic treatment can inhibit influenza virus infection; however, the mechanism remains to be explored. The mice received Lactobacillus mucosae 1025, Bifidobacterium breve CCFM1026, and their mixture MIX for 19 days. Effects of probiotics on clinical symptoms, immune responses, and gut microbial alteration were evaluated. L. mucosae 1025 and MIX significantly reduced the loss of body weight, pathological symptoms, and viral loading. B. breve CCFM1026 significantly reduced the proportion of neutrophils and increased lymphocytes, the expressions of TLR7, MyD88, TRAF6, and TNF-α to restore the immune disorders. MIX increased the antiviral protein MxA expression, the relative abundances of Lactobacillus, Mucispirillum, Adlercreutzia, Bifidobacterium, and further regulated SCFA metabolism resulting in an enhancement of butyrate. The correlation analysis revealed that the butyrate was positively related to MxA expression (p < 0.001) but was negatively related to viral loading (p < 0.05). The results implied the possible antiviral mechanisms that MIX decreased viral loading and increased the antiviral protein MxA expression, which was closely associated with the increased butyrate production resulting from gut microbial alteration.

18.
Cells ; 10(2)2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670114

RESUMO

Accumulating evidence supports the role of PDZ-binding kinase (PBK)/T-lymphokine-activated killer-cell-originated protein kinase (TOPK) in mitosis and cell-cycle progression of mitotically active cells, especially proliferative malignant cells. PBK/TOPK was confirmed to be associated with the development, progression, and metastasis of malignancies. Therefore, it is a potential therapeutic target in cancer therapy. Many studies have been conducted to explore the clinical applicability of potent PBK/TOPK inhibitors. However, PBK/TOPK has also been shown to be overexpressed in normal proliferative cells, including sperm and neural precursor cells in the subventricular zone of the adult brain, as well as under pathological conditions, such as ischemic tissues, including the heart, brain, and kidney, and plays important roles in their physiological functions, including proliferation and self-renewal. Thus, more research is warranted to further our understanding of PBK/TOPK inhibitors before we can consider their applicability in clinical practice. In this study, we first review the findings, general features, and signaling mechanisms involved in the regulation of mitosis and cell cycle. We then review the functions of PBK/TOPK in pathological conditions, including tumors and ischemic conditions in the heart, brain, and kidney. Finally, we summarize the advances in potent and selective inhibitors and describe the potential use of PBK/TOPK inhibitors in clinical settings.


Assuntos
Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia
19.
Cell Transplant ; 30: 9636897211004089, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787356

RESUMO

Massive cerebral infarction (MCI) is a life-threatening disease and may lead to cerebral herniation. Neutrophil degranulation contributes to ischemic injury in the early stage. To investigate whether neutrophil degranulating factors can predict cerebral herniation and the long-term prognosis of patients with MCI and to investigate the relationship between neutrophil degranulation and blood brain barrier (BBB) damage. In this case-control study of 14 MCI patients, we divided the patients into a cerebral hernia group and no cerebral hernia group according to whether they developed cerebral herniation within 5 days. The prognosis of MCI patients was assessed using the Modified Rankin Scale (mRS) score at 6 months, which was the primary end point. The composition of white blood cells (WBC) and degranulating factors for neutrophils in the plasma of MCI patients was determined on days 2 and 4. Baseline characteristics were comparable in both groups. The neurological functional scores and long-term prognosis showed no difference between patients with or without cerebral herniation, while the mortality rate of the cerebral hernia group in the short term was higher (P < 0.05). The WBC count, neutrophil to lymphocyte ratio (NLR) and plasma myeloperoxidase (MPO) levels of patients with cerebral hernia were significantly higher than those of patients without cerebral hernia (all P < 0.05). MPO is a better predictor of cerebral herniation, and the NLR showed superior predictive value in the prognosis of MCI patients. neutrophil degranulation may play an important role in malignant cerebral hernia during MCI. These data suggest that, MPO and the NLR might be predictive factors for cerebral herniation and the prognosis of MCI patients.


Assuntos
Infarto Cerebral/sangue , Neutrófilos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
20.
J Sci Food Agric ; 101(13): 5563-5573, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33709404

RESUMO

BACKGROUND: Asthma is increasingly prevalent worldwide, and novel strategies to prevent or treat this disease are needed. Probiotic intervention has recently been reported to be effective for asthma prevention. Here, we explored the effects of Faecalibacterium prausnitzii on the development of allergic airway inflammation in a murine model of house dust mite (HDM)-induced allergic asthma. RESULTS: Supplementation with living and dead F. prausnitzii blocked eosinophil, neutrophil, lymphocyte and macrophage influx and alleviated the pathological changes. Moreover, both living and dead F. prausnitzii administration decreased the levels of interleukin (IL)-4, IL-5, IL-13 and immunoglobulin G1, elevated regulatory T cell (Tregs) ratio, improved microbial dysbiosis and enhanced short-chain fatty acid (SCFA) production. Network correlation analysis revealed that the immune indicators were strongly associated with SCFA production. Based on the linear discriminant analysis effect size, Turicibacter was found to be the core genus related to HDM-induced asthma. Living F. prausnitzii treatment enriched Faecalibaculum, Dubosiella and Streptococcus, while dead F. prausnitzii treatment increased Muribaculaceae and Parabacteroides. Interestingly, both living and dead F. prausnitzii administration enriched Lachnoclostridium and normalized the pathways involving carbohydrate and lipid metabolism, which might be related to SCFA production. CONCLUSION: Faecalibacterium prausnitzii exerts an anti-asthmatic effect partly by gut microbiota modulation and SCFA production, suggesting its potential as a probiotic agent for allergic asthma prevention. © 2021 Society of Chemical Industry.


Assuntos
Asma/tratamento farmacológico , Asma/microbiologia , Bactérias/metabolismo , Faecalibacterium prausnitzii/fisiologia , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Pyroglyphidae/imunologia , Animais , Asma/genética , Asma/imunologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Eosinófilos/imunologia , Feminino , Humanos , Interleucina-13/genética , Interleucina-13/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Linfócitos T Reguladores/imunologia
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