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1.
Glia ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724258

RESUMO

Myelin sheath is an important structure to maintain functions of the nerves in central nervous system. Protein palmitoylation has been established as a sorting determinant for the transport of myelin-forming proteins to the myelin membrane, however, its function in the regulation of oligodendrocyte development remains unknown. Here, we show that an Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC5, is involved in the control of oligodendrocyte development. Loss of Zdhhc5 in oligodendrocytes inhibits myelination and remyelination by reducing total myelinating oligodendrocyte population. STAT3 is the primary substrate for DHHC5 palmitoylation in oligodendrocytes. Zdhhc5 ablation reduces STAT3 palmitoylation and suppresses STAT3 phosphorylation and activation. As a result, the transcription of the myelin-related and anti-apoptosis genes is inhibited, leading to suppressed oligodendrocyte development and myelination. Our findings demonstrate a key role DHHC5 in controlling myelinogenesis.

2.
Chem Biodivers ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786852

RESUMO

A new globoscinic acid derivative, aspertubin A (1) along with four known compounds, were obtained from the co-culture of Aspergillus tubingensis S1120 with red ginseng. The chemical structures of compounds were characterized by using spectroscopic methods, the calculated and experimental electronic circular dichroism. Panaxytriol (2) from red ginseng, and asperic acid (4) showed significant antifeedant effect with the antifeedant rates of 75 % and 80 % at the concentrations of 50 µg/cm2. Monomeric carviolin (3) and asperazine (5) displayed weak attractant activity on silkworm. All compounds were assayed for antifungal activities against phytopathogens A. tubingensis, Nigrospora oryzae and Phoma herbarum and the results indicated that autotoxic aspertubin A (1) and panaxytriol (2) possessed selective inhibition against A. tubingensis with MIC values at 8 µg/mL. The co-culture extract showed higher antifeedant and antifungal activities against P. herbarum than those of monoculture of A. tubingensis in ordinary medium. So the medicinal plant and endophyte showed synergistic effect on the plant disease resistance by active compounds from the coculture of A. tubingensis S1120 and red ginseng.

3.
Opt Lett ; 46(19): 4888-4891, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598226

RESUMO

The time-delay signature (TDS) suppression of semiconductor lasers with external optical feedback is necessary to ensure the security of chaos-based secure communications. Here we numerically and experimentally demonstrate a technique to effectively suppress the TDS of chaotic lasers using quantum noise. The TDS and dynamical complexity are quantified using the autocorrelation function and normalized permutation entropy at the feedback delay time, respectively. Quantum noise from quadrature fluctuations of the vacuum state is prepared through balanced homodyne measurement. The effects of strength and bandwidth of quantum noise on chaotic TDS suppression and complexity enhancement are investigated numerically and experimentally. Compared to the original dynamics, the TDS of this quantum noise improved chaos is suppressed up to 94%, and the bandwidth suppression ratio of quantum noise to chaotic laser is 1:25. The experiment agrees well with the theory. The improved chaotic laser is potentially beneficial to chaos-based random number generation and secure communication.

4.
Food Funct ; 12(19): 9261-9272, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606526

RESUMO

Isorhamnetin (ISO), a flavonoid compound isolated from sea-buckthorn (Hippophae rhamnoides L.) fruit, has anti-inflammatory effects. However, the effects of ISO on neuroinflammation and cognitive function are still unclear. The purpose of this study was to evaluate the protective effect of ISO on cognitive impairment in obese mice induced by a high-fat and high fructose diet (HFFD). It has been found that oral administration of ISO (0.03% w/w and 0.06% w/w) for 14 weeks significantly reduced the body weight, food intake, liver weight, liver lipid level, and serum lipid level of HFFD-fed mice. ISO can also significantly prevent HFFD-induced neuronal working, spatial, and long-term memory impairment. Notably, the ISO treatment activated the CREB/BDNF pathway and increased neurotrophic factors in the brains of mice. Furthermore, ISO inhibited HFFD-induced microglial overactivation and down-regulated inflammatory cytokines in both serum and the brain. It can also inhibit the expression of p-JNK, p-p38, and p-NFκB protein in the mouse brain. In conclusion, these results indicated that ISO mitigated HFFD-induced cognitive impairments by inhibiting the MAPK and NFκB signaling pathways, suggesting that ISO might be a plausible nutritional intervention for metabolic syndrome-related cognitive complications.

5.
Bioorg Med Chem Lett ; 53: 128409, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34628036

RESUMO

Tropomyosin receptor kinases (TRKA, TRKB, TRKC) are transmembrane receptor tyrosine kinases, which are respectively encoded by NTRK1, NTRK2, and NTRK3 genes. Herein, we reported the design, synthesis and Structure-Activity Relationship (SAR) investigation of a series of macrocyclic derivatives as new TRK inhibitors. Among these compounds, compound 9e exhibited strong kinase inhibitory activity (TRKG595R IC50 = 13.1 nM) and significant antiproliferative activity in the Ba/F3-LMNA-NTRK1 cell line (IC50 = 0.080 µM) and compound 9e has shown a better inhibitory effect (IC50 = 0.646 µM) than control drug LOXO-101 in Ba/F3-LMNA-NTRK1-G595R cell line. These results indicate that compound 9e is a potential TRK inhibitor for further investigation.

6.
Ecotoxicol Environ Saf ; 227: 112912, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34673409

RESUMO

Urban fine particulate matter (PM2.5) is a deleterious risk factor in the ambient air and is recognized to exacerbate atherosclerosis. Perivascular adipose tissue (PVAT) secretes a large number of inflammatory cytokines and plays a crucial role in the pathogenic microenvironment of atherogenesis. However, there is a lack of knowledge about the role of PVAT inflammation in the genesis of PM2.5-related atherosclerosis. The aim of this research was to probe the latent links between PM2.5 exposure and PVAT inflammation and further discovered the underlying mechanisms of PM2.5-triggered atherosclerosis pathogenesis. Apolipoprotein E-deficient (ApoE-/-) mice were exposed to real-world atmospheric PM2.5 or filtered clean air for three months, the Wnt5a inhibitor Box5 and the Ror2 inhibitor ß-Arrestin2 were applied to verify the possible mechanisms. We noticed that the average daily PM2.5 mass concentration was 84.27 ± 28.84 µg/m3. PM2.5 inhalation might significantly expedite the deterioration of atherosclerosis, increase the protein and mRNA expressions of MCP-1, IL-6, TNF-α, Wnt5a, and Ror2 in PVAT tissues, upregulate the distributions of IL-6, TNF-α, MCP-1, and leptin in the histological sections of PVAT, promote lipid deposition in the aorta, elevate the plasma levels of leptin, MCP-1, IL-6, TNF-α, LDL-C, TC, and TG, however, decrease the plasma levels of adiponectin and HDL-C, downregulate the distribution of adiponectin. Nevertheless, these effects caused by PM2.5 exposure were dramatically diminished after the administration of Box5 or ß-Arrestin2. This research illuminated that PVAT inflammation was involved in the PM2.5-induced atherosclerosis process, as well as lipid deposition, which was closely associated with the activation of the Wnt5a/Ror2 signaling pathway.


Assuntos
Poluição do Ar , Aterosclerose , Tecido Adiposo , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Animais , Apolipoproteínas E/genética , Aterosclerose/induzido quimicamente , Inflamação/induzido quimicamente , Camundongos , Material Particulado/toxicidade , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase , Transdução de Sinais
7.
Perfusion ; : 2676591211051860, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34689640

RESUMO

OBJECTIVE: Levosimendan has been demonstrated to reduce the incidence of cardiogenic shock and facilitate weaning from cardiopulmonary bypass. However, the beneficial effects of levosimendan treatment on hospital outcomes in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) are uncertain. We performed a systematic review and meta-analysis to evaluate the short-term effects of levosimendan use for patients undergoing VA-ECMO. METHODS: We searched PubMed, Embase, and the Cochrane Library for English articles published from inception to July 15, 2021. Observational studies comparing levosimendan versus non- levosimendan for VA-ECMO were considered eligible for the current study. RESULTS: Nine observational studies with 1058 patients were included. In-hospital mortality was 46.3% in the levosimendan group as compared with 50.7% in the control group. Levosimendan significantly reduced in-hospital mortality in patients undergoing VA-ECMO compared with the control group (RR, 0.80; 95% CI, 0.67-0.95; p = 0.013). The incidence of weaning from VA-ECMO was 79.3% in the levosimendan group as compared with 63.4% in the control group. Levosimendan significantly increase the incidence of weaning from VA-ECMO in patients as compared with the control group (RR, 1.20; 95% CI, 1.07-1.34; p = 0.002). In the one-way sensitivity analysis for estimating the effect of each study on mortality or weaning from VA-ECMO, omission of each study did not make a significant difference. CONCLUSIONS: Our study indicates that levosimendan use significantly reduced in-hospital mortality and increase the incidence of weaning in patients undergoing VA-ECMO.

8.
Front Genet ; 12: 747270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567094

RESUMO

Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies and mortality for PAAD have remained increasing under the conditions of substantial improvements in mortality for other major cancers. Although multiple of studies exists on PAAD, few studies have dissected the oncogenic mechanisms of PAAD based on genomic variation. In this study, we integrated somatic mutation data and gene expression profiles obtained by high-throughput sequencing to characterize the pathogenesis of PAAD. The mutation profile containing 182 samples with 25,470 somatic mutations was obtained from The Cancer Genome Atlas (TCGA). The mutation landscape was generated and somatic mutations in PAAD were found to have preference for mutation location. The combination of mutation matrix and gene expression profiles identified 31 driver genes that were closely associated with tumor cell invasion and apoptosis. Co-expression networks were constructed based on 461 genes significantly associated with driver genes and the hub gene FAM133A in the network was identified to be associated with tumor metastasis. Further, the cascade relationship of somatic mutation-Long non-coding RNA (lncRNA)-microRNA (miRNA) was constructed to reveal a new mechanism for the involvement of mutations in post-transcriptional regulation. We have also identified prognostic markers that are significantly associated with overall survival (OS) of PAAD patients and constructed a risk score model to identify patients' survival risk. In summary, our study revealed the pathogenic mechanisms and prognostic markers of PAAD providing theoretical support for the development of precision medicine.

9.
Acta Pharm Sin B ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34485029

RESUMO

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

10.
Biochem Biophys Res Commun ; 576: 53-58, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34481235

RESUMO

Cold atmospheric plasma (CAP) has attracted significant attention and has been widely used to inactivate pathogens based on its excellent effect; however, the mechanisms underlying the interactions between plasma-generated species and organisms have not yet been fully elucidated. In this paper, the interactions of reactive oxygen plasma species (O, OH and H2O2) with chitin polymer (the skeletal component of the Candida albicans cell wall) were investigated by means of reactive molecular dynamics simulations from a microscopic point of view. Our simulations show that O and OH species can break important structural bonds (e.g., N-H bonds, O-H bonds and C-H bonds) of chitin. This is followed by a cascade of bond cleavage and double bond formation events. This simulation study aimed to improve the understanding of the micromechanism of plasma-inactivated Candida albicans at the atomic level.

11.
J Integr Med ; 19(5): 418-427, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34454893

RESUMO

OBJECTIVE: Exercise, as a common non-drug intervention, is one of several lifestyle choices known to reduce the risk of cancer. Mitochondrial division has been reported to play a key role in the occurrence and transformation of hepatocellular carcinoma (HCC). This study investigated whether exercise could regulate the occurrence and development of HCC through mitosis. METHODS: Bioinformatics technology was used to analyze the expression level of dynamin-related protein 1 (DRP1), a key protein of mitochondrial division. The effects of DRP1 and DRP1 inhibitor (mdivi-1) on the proliferation and migration of liver cancer cells BEL-7402 were observed using cell counting kit-8, plate colony formation, transwell cell migration, and scratch experiments. Enzyme-linked immunosorbent assay, Western blot and real-time polymerase chain reaction were used to detect the expression of DRP1 and its downstream phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. A treadmill exercise intervention was tested in a nude mouse human liver cancer subcutaneous tumor model expressing different levels of DRP1. The size and weight of subcutaneous tumors in mice were detected before and after exercise. RESULTS: The expression of DRP1 in liver cancer tissues was significantly upregulated compared with normal liver tissues (P < 0.001). The proliferation rate and the migration of BEL-7402 cells in the DRP1 over-expression group were higher than that in the control group. The mdivi-1 group showed an inhibitory effect on the proliferation and migration of BEL-7402 cells at 50 µmol/L. Aerobic exercise was able to inhibit the expression of DRP1 and decrease the size and weight of subcutaneous tumors. Moreover, the expression of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) decreased in the exercise group. However, exercise could not change p-PI3K and p-AKT levels after knocking down DRP1 or using mdivi-1 on subcutaneous tumor. CONCLUSION: Aerobic exercise can suppress the development of tumors partially by regulating DRP1 through PI3K/AKT pathway.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Dinaminas , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Camundongos , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
12.
Cell Prolif ; 54(9): e13100, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34347352

RESUMO

OBJECTIVES: To evaluate the long-term biosafety and efficacy of transplantation of human embryonic stem cells-derived retinal pigment epithelial (hESC-RPE) cells in early-stage of Stargardt macular degeneration (STGD1). MATERIALS AND METHODS: Seven patients participated in this prospective clinical study, where they underwent a single subretinal transplantation of 1 × 105 hESC-RPE cells in one eye, whereas the fellow eye served as control. These patients were reassessed for a 60-month follow-up through systemic and ophthalmic examinations. RESULTS: None of the patients experienced adverse reactions systemically or locally, except for two who had transiently high intraocular pressure post-operation. Functional assessments demonstrated that all of the seven operated eyes had transiently increased or stable visual function 1-4 months after transplantation. At the last follow-up visit, two of the seven eyes showed visual function loss than the baseline; however, one of them showed a stable visual acuity when compared with the change of fellow eye. Obvious small high reflective foci in the RPE layer were displayed after the transplantation, and maintained until the last visit. Interestingly, three categories of patients who were classified based on autofluorescence, exhibited distinctive patterns of morphological and functional change. CONCLUSIONS: Subretinal transplantation of hESC-RPE in early-stage STGD1 is safe and tolerated in the long term. Further investigation is needed for choosing proper subjects according to the multi-model image and function assessments.


Assuntos
Células Epiteliais/citologia , Células-Tronco Embrionárias Humanas/citologia , Degeneração Macular/patologia , Epitélio Pigmentado da Retina/citologia , Pigmentos da Retina/fisiologia , Doença de Stargardt/patologia , Adulto , Diferenciação Celular/fisiologia , Linhagem Celular , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Transplante de Células-Tronco/métodos , Acuidade Visual/fisiologia , Adulto Jovem
13.
Microb Pathog ; 159: 105134, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34400283

RESUMO

Aeromonas veronii (A. veronii, AV) strains are emerging zoonotic and aquatic pathogens, yet we know very little about their genomics. This study aims to utilize comparative genomics to investigate the intraspecific genetic diversity, differences in virulence factors and evolutionary mechanisms of A. veronii strains from diverse sources and to fundamentally demonstrate their pathogenic mechanisms. We conducted comparative genomics analysis of 39 A. veronii strains from different sources and found that 1993 core genes are shared by these strains and that these shared core genes may be necessary to maintain the basic characteristics of A. veronii. Additionally, phylogenetic relationship analysis based on these shared genes revealed that a distant relationship between the AMC34 strain and the other 38 strains but that, the genetic relationship among the 38 strains is relatively close, indicating that AMC34 may not belong to A. veronii. Furthermore, analysis of shared core genes and average nucleotide identity (ANI) values showed no obvious correlation with the location of A. veronii isolation and genetic relationship. Our research indicates the evolutionary mechanism of A. veronii from different sources and provides new insights for a deeper understanding of its pathogenic mechanism.


Assuntos
Aeromonas , Infecções por Bactérias Gram-Negativas , Aeromonas/genética , Aeromonas veronii/genética , Genômica , Humanos , Filogenia , Fatores de Virulência/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-34460385

RESUMO

Detecting anomalies on graph data has two types of methods. One is pattern mining that discovers strange structures globally such as quasi-cliques, bipartite cores, or dense blocks in the graph's adjacency matrix. The other is feature learning that mainly uses graph neural networks (GNNs) to aggregate information from local neighborhood into node representations. However, there is a lack of study that utilizes both the global and local information for graph anomaly detection. In this article, we propose a synergistic approach that leverages pattern mining to inform the GNN algorithms on how to aggregate local information through connections to capture the global patterns. Specifically, it uses a GNN encoder to perform feature aggregation, and the pattern mining algorithms supervise the GNN training process through a novel loss function. We provide theoretical analysis on the effectiveness of the loss function, as well as empirical analysis on the proposed approach across a variety of GNN algorithms and pattern mining methods. Experiments on real-world data show that the synergistic approach performs significantly better than existing graph anomaly detection methods.

15.
Pak J Pharm Sci ; 34(2): 513-519, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34275824

RESUMO

Severe oxidative stress triggered by acute hypobaric hypoxia (AHH) is harmful for lots of organs in body, especial brain and heart. Flavonoids with antioxidant properties can protect organs from oxidative stress. Our previous study found that 5,6,7,8-trtrahydroxyflavone (5,6,7,8-THF), a flavones with four consecutive hydrogen group on ring A, showed excellent antioxidant properties in vitro. In the present study, the protective of 5,6,7,8-THF against oxidative stress caused by AHH was investigated. Mice were administered with 5,6,7,8-THF(500mg/kg) for 5 consecutive days before HH exposure. The heart rate (HR) and blood pressure (BP) was measured. The activity of SOD, CAT, GSH-Px, LDH, Na+-K+-ATPase and Ca2+-Mg2+-ATPase and the content of H2O2, MDA, LD and ATP in brain and heart tissue was evaluated using commercial kit. AHH led to a significant increase in HR and decrease in BP. Pretreatment of 5,6,7,8-THF could reversed these changes. In addition, administration of 5,6,7,8-THF could significantly increase the activity of SOD, CAT and GSH-Px and decrease the content of H2O2 and MDA in the brain and heart of mice under AHH. Furthermore, 5,6,7,8-THF inhibited the activity of LDH, decreased the level of LD and improved ATPase activity. These results indicate that 5,6,7,8-THF may protect the mice against AHH injury via scavenging free radical, inhibiting lipid peroxidation, enhancing antioxidant enzyme activity, preserving energy metabolism and can be further explored as an excellent anti-hypoxia agent for preventing acute mountain sickness.

16.
Am J Cancer Res ; 11(6): 2960-2974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249438

RESUMO

Apatinib is an oral tyrosine kinase inhibitor that targets VEGFR2 signaling and shows potent antitumor effects in various cancers. In this study, we explored the efficacy of apatinib against oral squamous cell carcinoma (OSCC). The relationships between VEGFR2 protein expression and clinical variables were investigated in OSCC patients. OSCC tissues had higher VEGFR2 levels than paracancerous tissues. Compared to patients with low VEGFR2 expression, patients with high VEGFR2 expression had poorer overall survival (OS) and disease-free survival (DFS). Apatinib significantly induced G0/G1 phase arrest and apoptosis, inhibited cell growth and colony formation ability, and blocked autophagic flux by downregulating p-AKT and p-mTOR signaling via the VEGFR2/AKT/mTOR pathway in vitro. Moreover, the inhibition of ERK phosphorylation increased apatinib-induced apoptosis in vitro and in vivo. Apatinib synergized with SCH772984 to achieve a more significant suppression of tumor growth than individual treatment, suggesting the combination of apatinib and SCH772984 as a potent OSCC therapy.

17.
Cell Rep ; 36(1): 109314, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34233190

RESUMO

MED20 is a non-essential subunit of the transcriptional coactivator Mediator complex, but its physiological function remains largely unknown. Here, we identify MED20 as a substrate of the anti-obesity CRL4-WDTC1 E3 ubiquitin ligase complex through affinity purification and candidate screening. Overexpression of WDTC1 leads to degradation of MED20, whereas depletion of WDTC1 or CUL4A/B causes accumulation of MED20. Depleting MED20 inhibits adipogenesis, and a non-degradable MED20 mutant restores adipogenesis in WDTC1-overexpressing cells. Furthermore, knockout of Med20 in preadipocytes abolishes development of brown adipose tissues. Removing one allele of Med20 in preadipocytes protects mice from diet-induced obesity and reverses weight gain in Cul4a- or Cul4b-depleted mice. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis reveals that MED20 organizes the early adipogenic complex by bridging C/EBPß and RNA polymerase II to promote transcription of the central adipogenic factor, PPARγ. Our findings have thus uncovered a critical role of MED20 in promoting adipogenesis, development of adipose tissue and diet-induced obesity.

18.
Ir J Med Sci ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264426

RESUMO

BACKGROUND: Callispheres® microspheres (CSM) are the first drug-eluting bead (DEB) product developed in China; meanwhile, DEB-transarterial chemoembolization (TACE) with CSM is effective and safe in the treatment of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, the data regarding the role of irinotecan-eluting beads-TACE (DEBIRI-TACE) using CSM for colorectal cancer liver metastases (CRLM) treatment is limited. Therefore, the present study aimed to investigate the efficacy and safety of DEBIRI-TACE using CSM in the patients with unresectable CRLM. METHODS: Totally, 42 unresectable CRLM patients treated with DEBIRI-TACE using CSM were continuously enrolled in this study. Postoperative treatment response (including complete response rate (CR), objective response rate (ORR), and disease control rate (DCR)), survival data (overall survival (OS)), liver function, and adverse events were documented during the follow-up. RESULTS: CR, ORR, and DCR were 19.0%, 92.9%, and 100.0%, respectively, at month (M) 1; were 23.8%, 92.9%, and 97.6%, respectively, at M3; then were 14.3%, 78.6%, and 90.5%, respectively at M6. Regarding survival profiles, 1-year OS was 81.0%; 2-year OS was 58.5%; median OS was 25.0 months (95%CI: 19.3-30.7 months). Additionally, ALT and AST experienced an obviously increased trend at 4 days, but a declined trend at 7 days, while ALB and TBIL had no obvious change. No grade 3 or grade 4 adverse event was observed, and main adverse events included fever (95.3%), pain (57.1%), fatigue (50.0%), and nausea/vomiting (42.8%). CONCLUSION: DEBIRI-TACE with CSM achieves high treatment response, acceptable survival benefits, and good toleration in unresectable CRLM treatment.

19.
Ecotoxicol Environ Saf ; 222: 112485, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34246944

RESUMO

Ambient fine particulate matter (PM2.5) and high-fat diet (HFD) are linked to the development of atherosclerosis. However, there is still unknown about the PM2.5-induced atherosclerosis formation on vascular endothelial injury after co-exposed to PM2.5 and HFD. Thus, the aim of this study was to evaluate the effects of PM2.5 on atherogenesis in C57BL/6 mice and endothelial cells, as well as the co-exposure effect of PM2.5 and HFD. In vivo study, C57BL/6 mice exposed to PM2.5 and fed with standard chow diet (STD) or HFD for 1 month. PM2.5 could increase vascular stiffness accessed by Doppler ultrasound, and more serious in co-exposure group. PM2.5 impaired vascular endothelial layer integrity, exfoliated endothelial cells, and inflammatory cells infiltration through H&E staining. PM2.5 reduced the expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1) in vessel. Moreover, PM2.5 could induce systemic inflammation detected by Mouse Inflammation Array. In vitro study, PM2.5 triggered markedly mitochondrial damage by transmission electron microscope (TEM) and flow cytometer. Inflammatory cytokines were significantly increased in PM2.5-exposed group. The cell viability and migration of endothelial cells were significantly suppressed. In addition, PM2.5 remarkably declined the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and increased the expression of somatostatin (SST) and its receptor. In conclusion, co-exposure of PM2.5 and HFD might induce systemic inflammation and endothelial dysfunction in normal mice. Moreover, PM2.5 could reduce vascular endothelial repair capacity through inhibiting the proliferation and migration of endothelial cells.


Assuntos
Células Endoteliais , Material Particulado , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Material Particulado/toxicidade , Fator A de Crescimento do Endotélio Vascular
20.
Front Cell Infect Microbiol ; 11: 676638, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295834

RESUMO

Introduction: Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA), are a main cause of nosocomial infection in the world. The majority of nosocomial S. aureus-infection are traced back to a source of contaminated surfaces including surgery tables. We assessed the efficacy of a mixture of levulinic acid (LA) and sodium dodecyl sulfate (SDS), hereafter called MoWa, to eradicate nosocomial pathogens from contaminated surfaces. Methods and Results: A dose response study demonstrated that MoWa killed 24 h planktonic cultures of S. aureus strains starting at a concentration of (LA) 8.2/(SDS) 0.3 mM while 24 h preformed biofilms were eradicated with 32/1.3 mM. A time course study further showed that attached MRSA bacteria were eradicated within 4 h of incubation with 65/2 mM MoWa. Staphylococci were killed as confirmed by bacterial counts, and fluorescence micrographs that were stained with the live/dead bacterial assay. We then simulated contamination of hospital surfaces by inoculating bacteria on a surface prone to contamination. Once dried, contaminated surfaces were sprayed with MoWa or mock-treated, and treated contaminated surfaces were swabbed and bacteria counted. While bacteria in the mock-treated samples grew at a density of ~104 cfu/cm2, those treated for ~1 min with MoWa (1.0/0.04 M) had been eradicated below limit of detection. A similar eradication efficacy was obtained when surfaces were contaminated with other nosocomial pathogens, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, or Staphylococcus epidermidis. Conclusions: MoWa kills planktonic and biofilms made by MRSA and MSSA strains and showed great efficacy to disinfect MRSA-, and MSSA-contaminated, surfaces and surfaces contaminated with other important nosocomial pathogens.


Assuntos
Infecção Hospitalar , Desinfetantes , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Desinfetantes/farmacologia , Hospitais , Humanos , Staphylococcus aureus
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