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1.
Front Immunol ; 15: 1354593, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500874

RESUMO

Background: There is no consensus on the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitors on lipid profiles in patients with psoriasis. This study aimed to investigate the effects of TNF-alpha inhibitors on lipid profiles (triglycerides, total cholesterol, low-density lipoprotein, or high-density lipoprotein) in patients with psoriasis. Methods: We searched PubMed, Embase, and Cochrane Library databases for articles published before October 17, 2023. Four TNF-alpha inhibitors (infliximab, etanercept, adalimumab, and certolizumab) were included in our study. (PROSPERO ID: CRD42023469703). Results: A total of twenty trials were included. Overall results revealed that TNF-alpha inhibitors elevated high-density lipoprotein levels in patients with psoriasis (WMD = 2.31; 95% CI: 0.96, 3.67; P = 0.001), which was supported by the results of sensitivity analyses excluding the effect of lipid-lowering drugs. Subgroup analyses indicated that high-density lipoprotein levels were significantly increased in the less than or equal to 3 months group (WMD = 2.88; 95% CI: 1.37, 4.4; P < 0.001), the etanercept group (WMD = 3.4; 95% CI = 1.71, 5.09, P < 0.001), and the psoriasis group (WMD = 2.52; 95% CI = 0.57, 4.48, P = 0.011). Triglyceride levels were significantly increased in the 3 to 6-month group (WMD = 4.98; 95% CI = 1.97, 7.99, P = 0.001) and significantly decreased in the 6-month and older group (WMD = -19.84; 95% CI = -23.97, -15.7, P < 0.001). Additionally, Triglyceride levels were significantly increased in the psoriasis group (WMD = 5.22; 95% CI = 2.23, 8.21, P = 0.001). Conclusion: Our results revealed that TNF-alpha inhibitors might temporarily increase high-density lipoprotein levels in patients with psoriasis. However, changes in triglycerides were not consistent among the different durations of treatment, with significant increases after 3 to 6 months of treatment. Future prospective trials with long-term follow-up contribute to confirming and extending our findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023469703.


Assuntos
Psoríase , Fator de Necrose Tumoral alfa , Humanos , Etanercepte/farmacologia , Etanercepte/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Psoríase/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Triglicerídeos , Lipoproteínas HDL
2.
Mar Drugs ; 21(12)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38132942

RESUMO

Epigenetic modifications, mainly aberrant DNA methylation, have been shown to silence the expression of genes involved in epigenetic diseases, including cancer suppression genes. Almost all conventional cancer therapeutic agents, such as the DNA hypomethylation drug 5-aza-2-deoxycytidine, have insurmountable side effects. To investigate the role of the well-known DNA protectant (ectoine) in skin cell DNA methylation and cancer cell proliferation, comprehensive methylome sequence analysis, 5-methyl cytosine (5mC) analysis, proliferation and tumorigenicity assays, and DNA epigenetic modifications-related gene analysis were performed. The results showed that extended ectoine treatment globally hypomethylated DNA in skin cells, especially in the CpG island (CGIs) element, and 5mC percentage was significantly reduced. Moreover, ectoine mildly inhibited skin cell proliferation and did not induce tumorigenicity in HaCaT cells injected into athymic nude mice. HaCaT cells treated with ectoine for 24 weeks modulated the mRNA expression levels of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3l, Hdac1, Hdac2, Kdm3a, Mettl3, Mettl14, Snrpn, and Mest. Overall, ectoine mildly demethylates DNA in skin cells, modulates the expression of epigenetic modification-related genes, and reduces cell proliferation. This evidence suggests that ectoine is a potential anti-aging agent that prevents DNA hypermethylation and subsequently activates cancer-suppressing genes.


Assuntos
Metilação de DNA , Neoplasias , Animais , Camundongos , Camundongos Nus , DNA/metabolismo , Proliferação de Células , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética
3.
Environ Sci Pollut Res Int ; 30(51): 110590-110599, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37792198

RESUMO

Engine oil spills have been associated with a wide range of human health problems. However, little is known about the effects of petroleum hydrocarbon pollution on soil microbial communities. In this study, three samples were collected from oil-polluted soils (OPS), and one control soil (CS) from Taolin town, China, near the old engine's scrapes was used. The aims of this study were to conduct metagenomic sequencing and subsequently perform resistome and virulome analysis. We also aimed to validate anti-microbial resistance and virulence genes and anti-bacterial sensitivity profiles among the isolates from oil-polluted soils. The OPS microbial community was dominated by bacterial species compared to the control samples which were dominated by metazoans and other organisms. Secondly, the resistosome and virulome analysis showed that ARGs and virulence factors were higher among OPS microbial communities. Antibiotic susceptibility assay and qPCR analysis for ARGs and virulence factors showed that the oil-polluted soil samples had remarkably enhanced expression of these ARGs and some virulence genes. Our study suggests that oil pollution contributes to shifting microbial communities to more resilient types that could survive the toxicity of oil pollution and subsequently become more resilient in terms of higher resistance and virulence potential.


Assuntos
Bactérias , Genes Bacterianos , Humanos , Virulência , Bactérias/genética , Solo , Resistência Microbiana a Medicamentos/genética , China , Fatores de Virulência , Microbiologia do Solo , Antibacterianos/farmacologia
4.
Int J Anal Chem ; 2023: 6350669, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37877028

RESUMO

Antibiotics and pesticides are widespread in most rivers and lakes due to the overuse of antibiotics and pesticides, but there are few methods for simultaneous analysis of antibiotics and pesticides in aquatic environments. To address this knowledge gap, a concise and sensitive analytical method is proposed in which three classes of human and veterinary drugs (sulfonamides, macrolides, and hormones) and two classes of pesticides (organophosphorus and neonicotinoids) are simultaneously extracted and determined in surface water. The solid-phase extraction column with Cleanert PEP-2 was preconditioned sequentially with 6 mL of methanol, ultrapure water, and citric acid buffer (pH 3.0) each for simultaneous extraction and further purification. The forty-seven target analytes were analysed by LC-MS/MS in positive and negative ion modes. The LC separation was performed using a Sigma-Aldrich C18 column with 0.1% formic acid in water and acetonitrile as a gradient eluting mobile phase in positive ion mode. The internal standard method was used to overcome the inevitable matrix effects in LC-MS/MS analysis. The matrix effects of most target analytes were in the range of 27-151%. The recoveries of forty analytes in the three concentrations (10, 50, and 100 ng L-1) of surface water spiked samples ranged from 41 to 127%. The method quantitative limits of the analytes were in the range of 0.40-5.49 ng L-1. Application of the method to analyze samples in the eight runoff outlets of the Pearl River Delta showed that some antibiotics and pesticides were detected, and the concentration of parathion was as high as 154 ng L-1. A powerful tool for quickly and efficiently screening for contaminants in surface water has been presented.

5.
Chemosphere ; 340: 139815, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37586489

RESUMO

In this study, a novel oil-degrading strain Enterobacter kobei DH7 was isolated from petroleum-contaminated soil samples from the industrial park in Taolin Town, Lianyungang, China. The whole genome of the strain was sequenced and analyzed to reveal its genomic potential. The oil degradation and growth conditions including nitrogen, and phosphorus sources, degradation cycle, biological dosing, pH, and oil concentration were optimized to exploit its commercial application. The genome of the DH7 strain contains 4,705,032 bp with GC content of 54.95% and 4653 genes. The genome analysis revealed that there are several metabolic pathways and enzyme-encoding genes related to oil degradation in the DH7 genome, such as the paa gene cluster which is involved in the phenylacetic acid degradation pathway, and complete degradation pathways for fatty acid and benzoate, genes related to chlorinated alkanes and olefins degradation pathway including adhP, frmA, and adhE, etc. The strain DH7 under the optimized conditions has demonstrated a maximum degradation efficiency of 84.6% after 14 days of treatment using synthetic oil, which comparatively displays a higher oil degradation efficiency than any Enterobacter species known to date. To the best of our knowledge, this study presents the first-ever genomic studies related to the oil degradation potential of any Enterobacter species. As Enterobacter kobei DH7 has demonstrated significant oil degradation potential, it is one of the good candidates for application in the bioremediation of oil-contaminated environments.


Assuntos
Petróleo , Poluentes do Solo , Petróleo/análise , Enterobacter/genética , Enterobacter/metabolismo , Genômica , Solo/química , Biodegradação Ambiental , Microbiologia do Solo , Poluentes do Solo/análise , Hidrocarbonetos/metabolismo
6.
BMC Gastroenterol ; 23(1): 232, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37430251

RESUMO

OBJECTIVE: To investigate the correlation between the grade and type of color Doppler flow imaging (CDFI) and tumor-related cytokines in elderly patients with colon cancer. METHODS: Seventy-six elderly patients with colorectal cancer admitted to Zhejiang Provincial People's Hospital from July 2020 to June 2022 were selected. CDFI was used to analyze the blood flow grade and distribution type of tumor tissues, and ELISA was used to detect the levels of tumor-related cytokines in serum. Preoperative clinical data were collected and analyzed, and the correlation between measured cytokine levels and CDFI analysis results was further explored. RESULTS: CDFI blood flow grade showed significant difference in the different lengths, invasion depths and lymph node metastasis of tumors (all P < 0.001). In addition, serum levels of TNF-α, IL-6 and VEGF also showed statistical difference in all above different tumor-related factors (all P < 0.001). Further Pearson correlation analysis showed that CDFI blood flow grade and distribution types were both significantly positively correlated with above serum cytokine levels (r > 0, all P < 0.001). Kaplan-Meier survival analysis showed that both CDFI blood flow grade and distribution types were poor prognostic factors in elderly patients with colon cancer. Regression analysis showed that serum levels of TNF-α, IL-6 and VEGF were independent risk factors for poor prognosis of colon cancer in elderly patients. CONCLUSION: CDFI blood flow grade and tumor tissue distribution have potential significant correlations with tumor-associated cytokines in the serum of colon cancer patients. CDFI blood flow grading technique provides an important imaging method for dynamic observation of angiogenesis and blood flow changes in elderly patients with colon cancer. Abnormal changes in serum levels of tumor-related factors can be used as sensitive indicators to evaluate the therapeutic effect and prognosis of colon cancer.


Assuntos
Neoplasias do Colo , Fator de Necrose Tumoral alfa , Idoso , Humanos , Interleucina-6 , Fator A de Crescimento do Endotélio Vascular , Neoplasias do Colo/diagnóstico por imagem , Biologia Molecular , Citocinas
7.
Aging (Albany NY) ; 15(9): 3410-3426, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37179119

RESUMO

Anoikis plays a critical role in variable cancer types. However, studies that focus on the prognostic values of anoikis-related genes (ANRGs) in OV are scarce. Cohorts with transcriptome data and corresponding clinicopathologic data of OV patients were collected and consolidated from public databases. Multiple bioinformatics approaches were used to screen key genes from 446 anoikis-related genes, including Cox regression analysis, random survival forest analysis, and Kaplan-Meier analysis of best combinations. A five-gene signature was constructed in the discovery cohort (TCGA) and validated in four validation cohorts (GEO). Risk score of the signature stratified patients into high-risk (HRisk) and low-risk (LRisk) subgroups. Patients in the HRisk group were associated with worse OS than those in the LRisk group in both the TCGA cohort (p<0.0001, HR=2.718, 95%CI:1.872-3.947) and the four GEO cohorts (p<0.05). Multivariate Cox regression analyses confirmed that the risk score served as an independent prognostic factor in both cohorts. The signature's predictive capacity was further demonstrated by the nomogram analysis. Pathway enrichment analysis revealed that immunosuppressive and malignant progression-related pathways were enriched in the HRisk group, including TGF-ß, WNT and ECM pathways. The LRisk group was characterized by immune-active signaling pathways (interferon-gamma, T cell activation, etc.) and higher proportions of anti-tumor immune cells (NK, M1, etc.) while HRisk patients were associated with higher stromal scores and less TCR richness. In conclusion, the signature reveals a close relationship between the anoikis and prognosis and may provide a potential therapeutic target for OV patients.


Assuntos
Anoikis , Neoplasias Ovarianas , Humanos , Feminino , Anoikis/genética , Neoplasias Ovarianas/genética , Prognóstico , Nomogramas , Fatores de Risco
8.
PLoS One ; 18(4): e0284871, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37083591

RESUMO

Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase, which is overexpressed in colorectal cancer cells. FAK could be activated by phosphorylation to participate in the transduction of multiple signaling pathways and self-renewal of cancer stem cells. Whether the downregulation of FAK inhibits the metastasis in colorectal cancer through the weakening of stem cell-like properties and its mechanisms has yet to be established. CD44, CD133, c-Myc, Nanog, and OCT4 were known to mark colorectal cancer stem cell properties. In this study, AKT inhibitor (MK-2206 2HCl) or FAK inhibitor (PF-562271) decreased the expression of stem cell markers (Nanog, OCT4, CD133, CD44, c-Myc) and spheroid formation in colorectal cancer. Moreover, FAK and AKT protein was shown to interact verified by co-immunoprecipitation. Furthermore, downregulation of FAK, transfected Lenti-FAK-EGFP-miR to colorectal cancer cells, reduced p-AKT but not AKT and decreased the expression of stem cell markers and spheroid formation in colorectal cancer. In conclusion, we demonstrated that downregulation of FAK inhibited stem cell-like properties and migration of colorectal cancer cells partly due to altered modulation of AKT phosphorylation by FAK.


Assuntos
Neoplasias Colorretais , Transdução de Sinais , Humanos , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/patologia , Regulação para Baixo , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Fosforilação , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo
9.
Environ Toxicol ; 38(6): 1226-1238, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36891622

RESUMO

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer and an endocrine disruptor. Microplastics (MPs) are pathogenic small plastic particles and abundant in the aqueous environment. The problem of residual hazards of plastic products is worthy of study, especially the joint exposure of a variety of plastic-related products to the toxic effect. We used 200 mg/kg DEHP and 10 mg/L MPs to establish exposure model in vivo and 2 mM DEHP and 200 µg/L MPs to establish AML12 cell exposure model in vitro. In vivo study results showed that compared with the control group (NC) group, DEHP and MPs significantly increased the contents of malondialdehyde and hydrogen peroxide, and significantly decreased the contents of glutathione and the activity of superoxide dismutase, total antioxidant capacity, catalase and glutathione peroxidase. The level of oxidative stress was further aggravated after combined exposure. The reactive oxygen species level of AML12 exposed to DEHP and MPs in vitro was significantly higher than NC group, and the combined exposure was significantly higher than the single exposure. The in vivo and in vitro also confirmed that DEHP and MPs could significantly increase the mRNA and protein levels of apoptosis markers and necroptosis markers and there was an additive effect. After N-acetylcysteine treatment in vitro, the above-mentioned oxidative stress level and cell damage decreased significantly. This study provided a reference for advocating the reduction of the mixed use of plastic products, and provided a basis for preventing the harm of plastic products residues.


Assuntos
Dietilexilftalato , Camundongos , Animais , Dietilexilftalato/toxicidade , Plásticos/toxicidade , Microplásticos , Necroptose , Estresse Oxidativo , Hepatócitos , Apoptose
10.
Microbiol Spectr ; 11(1): e0199222, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36475724

RESUMO

Infections caused by colistin-resistant P. aeruginosa strains pose a serious threat to public health. It is therefore urgent to find new strategies to deal with these bacterial infections. We aimed to investigate the efficacy and mechanisms of the colistin/resveratrol combination in eradicating colistin-resistant P. aeruginosa isolates and their biofilms both in vitro and in vivo. The results revealed that six clinically isolated colistin-resistant P. aeruginosa strains were multidrug resistant (MDR) strains, and resveratrol showed no antimicrobial activity against eight P. aeruginosa strains. Checkerboard assay and time-kill assays indicated that the combination therapy of resveratrol and colistin indicated a remarkable synergistic effect in vitro, and biofilm assays and SEM indicated synergistic antibiofilm activity. Furthermore, this combination could efficiently eliminate MDR bacteria in a murine infection model and improve the survival rate of Galleria mellonella. Fluorescence analysis, ALP, and ß-galactosidase activity test results indicated that the colistin/resveratrol combination increased the membrane permeability of bacteria. In conclusion, our results may provide an efficient alternative pathway against colistin-resistant P. aeruginosa infections. IMPORTANCE P. aeruginosa is a ubiquitous Gram-negative opportunistic pathogen associated with a wide array of life-threatening acute and chronic infections. However, the improper and excessive use of antibiotics has contributed to the increasing emergence of multidrug-resistant (MDR) P. aeruginosa, even colistin-resistant strains, which presents a major challenge to clinical anti-infection treatment. Resveratrol, a naturally occurring polyphenolic antioxidant, can effectively slow down or avoid the occurrence and development of bacterial resistance and is expected to offer a promising strategy to overcome bacterial infections. In this study, colistin/resveratrol combination could synergistically damage the bacterial cell membrane, thereby inducing cell lysis while addressing the emergence of drug resistance. Moreover, this combination therapy may provide an efficient alternative pathway to combat the colistin-resistant P. aeruginosa in clinical practice.


Assuntos
Colistina , Infecções por Pseudomonas , Animais , Camundongos , Colistina/farmacologia , Pseudomonas aeruginosa , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia
11.
Biochem Pharmacol ; 202: 115120, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35760111

RESUMO

Acute lung injury (ALI) is a severe clinical disease marked by uncontrolled inflammation response which lacks effective medicines. Accumulative evidence has indicated that macrophages are therapeutic targets for treating ALI because of its critical role in the inflammatory response.Palmatine (PAL), an isoquinoline alkaloid extracted from natural plants, exhibits effective anti-inflammatory, anti-tumor, and anti-oxidation activities. Here we reported that PAL alleviated LPS-induced acute lung injury and attenuated inflammatory cell infiltration especially neutrophils. Moreover, PAL also attenuated the production of TNF-α, CXCL-1, CXCL-2 and nitric oxide in bronchoalveolar lavage fluid. In addition, PAL remarkably reduced LPS-induced expression of TNF-α, CXCL-1 and CXCL-2 in bone marrow derived macrophages (BMDMs) and alveolar macrophages (AMs). Treatment with PAL inhibited the phosphorylation and interaction of TAK1/TAB1, which in turn attenuated the p38 MAPK and NF-κB signal pathways in BMDMs. Our results indicated that PAL ameliorated LPS-induced ALI by inhibiting macrophage activation through inhibiting NF-κB and p38 MAPK pathways, suggesting that PAL has anti-inflammation effect on ALI.


Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Alcaloides de Berberina , Citocinas/metabolismo , Humanos , Pulmão , MAP Quinase Quinase Quinases/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
BMC Plant Biol ; 22(1): 12, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979929

RESUMO

BACKGROUND: Taxol from Taxus species is a precious drug used for the treatment of cancer and can effectively inhibit the proliferation of cancer cells. However, the growth of Taxus plants is very slow and the content of taxol is quite low. Therefore, it is of great significance to improve the yield of taxol by modern biotechnology without destroying the wild forest resources. Endophytic fungus which symbiosis with their host plants can promote the growth and secondary metabolism of medicinal plants. RESULTS: Here, an endophytic fungus KL27 was isolated from T. chinensis, and identified as Pseudodidymocyrtis lobariellae. The fermentation broth of KL27 (KL27-FB) could significantly promote the accumulation of taxol in needles of T. chinensis, reaching 0.361 ± 0.082 mg/g·DW (dry weight) at 7 days after KL27-FB treatment, which is 3.26-fold increase as compared to the control. The RNA-seq and qRT-PCR showed that KL27-FB could significantly increase the expression of key genes involved in the upstream pathway of terpene synthesis (such as DXS and DXR) and those in the taxol biosynthesis pathway (such as GGPPS, TS, T5OH, TAT, T10OH, T14OH, T2OH, TBT, DBAT and PAM), especially at the early stage of the stimulation. Moreover, the activation of jasmonic acid (JA) biosynthesis and JA signal transduction, and its crosstalk with other hormones, such as gibberellin acid (GA), ethylene (ET) and salicylic acid (SA), explained the elevation of most of the differential expressed genes related to taxol biosynthesis pathway. Moreover, TF (transcriptional factor)-encoding genes, including MYBs, ethylene-responsive transcription factors (ERFs) and basic/helix-loop-helix (bHLH), were detected as differential expressed genes after KL27-FB treatment, further suggested that the regulation of hormone signaling on genes of taxol biosynthesis was mediated by TFs. CONCLUSIONS: Our results indicated that fermentation broth of endophytic fungus KL27-FB could effectively enhance the accumulation of taxol in T. chinensis needles by regulating the phytohormone metabolism and signal transduction and further up-regulating the expression of multiple key genes involved in taxol biosynthesis. This study provides new insight into the regulatory mechanism of how endophytic fungus promotes the production and accumulation of taxol in Taxus sp.


Assuntos
Ascomicetos/fisiologia , Endófitos/fisiologia , Regulação da Expressão Gênica de Plantas , Paclitaxel/biossíntese , Reguladores de Crescimento de Plantas/metabolismo , Transdução de Sinais , Taxus/metabolismo , Genes de Plantas , Paclitaxel/metabolismo , Taxus/microbiologia , Regulação para Cima
13.
Exp Lung Res ; 48(2): 53-60, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35075953

RESUMO

BACKGROUND: Excessive macrophage-mediated inflammation participates in the development of Staphylococcus aureus (S. aureus)-induced pneumonia. Checkpoint kinase 2 (Chek2) was screened out as macrophage-related infantile pneumonia gene after the differentially expressed analysis of RNAseq data derived from pam3CSK4 stimulated bone marrow-derived macrophages (BMDMs). METHODS: RAW264.7 macrophage cells were transfected with Chek2-specific gRNA, which were further overexpressed with wide-type Chek2 or Chek2 kinase activity mutant (Chek2 KD, D368N). At the same time, the relative protein and mRNA expression of inflammatory cytokines were determined. C57BL/6J WT mice were intranasally infected with S. aureus to induce S. aureus-induced pneumonia, which was treated with BML-277, an inhibitor of Chek2. The symptoms of pneumonia mice and inflammatory cytokines associated with the nuclear factor kappa B (NF-κB) signaling pathways were further examined. RESULTS: In vivo, BML-277 significantly promoted pneumonia symptoms, including mortality, lung infiltration of immune cells, and the abundance of lung pro-inflammatory cytokines. Mechanically, BML-277 did not affect BMDMs survival but up-regulated the mRNA expression of tumor necrosis factor (Tnf), nitric oxide synthase 2 (Nos2), interleukin (Il)23a, and the secretion of Tnf-α and Il-23a. At the same time, genetic complementation experiment testified that Chek2 KD did not inhibit NF-κB and relevant inflammatory cytokines expression. CONCLUSION: Chek2 functions through the kinase mechanism to down-regulate the NF-κB pathway in macrophages to alleviate S. aureus-induced pneumonia in mice.


Assuntos
NF-kappa B , Pneumonia , Animais , Camundongos , NF-kappa B/metabolismo , Staphylococcus aureus , Quinase do Ponto de Checagem 2/metabolismo , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Citocinas/metabolismo , Pneumonia/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ciclo Celular , RNA Mensageiro/metabolismo , Lipopolissacarídeos/farmacologia
14.
Braz. J. Pharm. Sci. (Online) ; 58: e201026, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1420474

RESUMO

Abstract Serum uric acid (UA) is a traditional biomarker in the clinical diagnosis of gout and hyperuricemia. However, serum treatment and storage are cumbersome, and wounds are susceptible to infection. Therefore, in this study, a simple and noninvasive method was developed to detect the UA in human saliva to monitor the gout. An Inertsil ODS-3 column was used for the analysis under the condition of isocratic elution with the mixed solution phosphate buffer (74 mM, pH=2.2): Methanol=98:2 (v:v) and the UV detection at 284 nm. Using salivary UA data from healthy volunteers (HVs) (n=68) and gout patients (GPs) (n=14), we examined the salivary UA difference in their content. The intra-and inter-day accuracy and precision (RSD %) were less than 2.56%, the limit of detection (LOD) of UA was 5.0 ng/mL, the mean recoveries of the corresponding compounds were 102.48%. Saliva levels of UA in HVs and GPs were 35.26±14.06 µg/mL and 91.96±23.90 µg/mL, respectively. The concentrations of salivary UA in GPs were significantly higher than those in HVs ( p < 0.001). This method was also expected to monitor the hyperuricemia and other metabolic disorders in the future


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Saliva , Ácido Úrico/análise , Estudo de Validação , Voluntários Saudáveis/classificação , Gota/patologia , Pacientes/classificação , Cromatografia Líquida de Alta Pressão/métodos
16.
Am J Transl Res ; 13(8): 9679-9686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540095

RESUMO

OBJECTIVE: To explore the effects of bundle nursing on PICC-related upper extremity deep venous thrombosis (PICC-UEDVT) in patients with non-Hodgkin's lymphoma (NHL) who are undergoing chemotherapy, and contributing factors toward PICC-UEDVT. METHODS: 370 NHL patients undergoing chemotherapy in the Department of Hematology were selected prospectively and randomized into a control group (receiving routine nursing) and an observation group (receiving bundle nursing) using random number method. There were 185 patients in each group. The incidence of PICC-UEDVT and satisfaction rate towards nursing were calculated and risk factors for PICC-UEDVT were explored in the two groups. RESULTS: The incidence of PICC-UEDVT was lower in the observation group (18 patients, 9.73%) than that of the control group (35 patients, 18.92%; P<0.05); the satisfaction rate towards nursing was higher in the observation group than the control group (P<0.05). Tumor stage, ECOG score >2, hemoglobin <100 g/L, and D-dimer >0.5 mg/L were factors that contributed to the occurrence of PICC-UEDVT in NHL patients (P<0.05). CONCLUSION: Tumor stage, ECOG score >2, reduced hemoglobin, and increased D-dimer levels are predisposing factors for PICC-UEDVT in NHL patients. However, bundle nursing can reduce the incidence of PICC-UEDVT and increase the satisfaction rate towards nursing.

17.
Echocardiography ; 38(8): 1474-1477, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34286882

RESUMO

A primary cardiac angiosarcoma (PCA) is very rare, highly aggressive, and metastatic in nature. The manifestations are often nonspecific, and the overall prognosis is extremely poor. The diagnosis of PCA can be complex and remains challenging. The key for diagnosis is echocardiography, and multimodality imaging is a more advantageous modality. Here, we present a rare case of a 41-year-old man who was diagnosed with PCA with multiple lung and bone metastases using multimodal imaging technology. Our case emphasizes the value of multimodality imaging in diagnosing PCA and suggests that patients showing intra-cardiac thrombus and hemorrhagic effusion on echocardiography without a clear explanation should be further investigated or closely followed.


Assuntos
Neoplasias Cardíacas , Hemangiossarcoma , Adulto , Ecocardiografia , Neoplasias Cardíacas/diagnóstico por imagem , Hemangiossarcoma/diagnóstico por imagem , Humanos , Masculino , Imagem Multimodal , Prognóstico
19.
BMC Infect Dis ; 21(1): 597, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34157983

RESUMO

BACKGROUND: Klebsiella pneumoniae is a primary pathogen of pyogenic liver abscess (PLA). However, little data are available on combination with sepsis. In this study, we aimed to evaluate the clinical characteristics and prognostic differences of PLA patients with sepsis. METHODS: This retrospective cohort study was conducted to investigate 135 patients with confirmed Klebsiella pneumoniae-caused liver abscesses (KPLA) from a tertiary teaching hospital, from 2013 to 2019. The patients were divided into two groups, KPLA with sepsis and KPLA without sepsis. The demographic characteristics, clinical features as well as laboratory and microbiologic findings were analyzed. RESULTS: A total of 135 patients with KPLA were analyzed. The mean age of patients was 60.9 ± 12.7 years, and the percentage of men was 59.3%. Among them, 37/135 (27.4%) of patients had sepsis and the mortality rate was 1.5%. The most common symptom was fever (91.1%). KPLA patients with sepsis had a significantly higher proportion of frailty, diarrhea, fatty liver, chronic renal insufficiency, and hepatic dysfunction compared to KPLA patients without sepsis (p < 0.05). Antibiotic therapy and percutaneous drainage were most frequently therapeutic strategy. Furthermore, the incidences of sepsis shock and acute respiratory distress syndrome were higher in the sepsis group compared to the non-sepsis group. As for metastatic infections, the lung was the most common site. In addition, KPLA patients with sepsis showed respiratory symptoms in 11 patients, endophthalmitis in 4 patients, and meningitis in 1 patient. CONCLUSION: Our findings emphasize that KPLA patients combined with or without sepsis have different clinical features, but KPLA patients with sepsis have higher rates of complications and metastatic infections. Taken together, further surveillance and control of septic spread is essential for KPLA patients.


Assuntos
Infecções por Klebsiella/complicações , Klebsiella pneumoniae , Abscesso Hepático Piogênico/complicações , Sepse/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
J Air Waste Manag Assoc ; 71(11): 1361-1374, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34096835

RESUMO

Along with the increasingly stringent dust emission concentration standards for the thermal power plants and the challenge of market competition, wet electrostatic precipitators (ESPs) have been widely used as terminal equipment for the flue gas treatment. The wet ESPs pilot test platform using the modified carbon steel collectors with hydrophilic properties was established in this paper and the experimental research on PM2.5 removal characteristics were carried out. The mechanism of the particles removal efficiency enhancement by water film on the surface of modified collectors was studied. The effect of gas temperature, residence time, working voltage, inlet concentration, and flushing water flowrate on the particles removal efficiency was investigated. The results indicated that the fibrous layer over the surface of the modified collectors could reduce the effect of the airflow recoil and the electromigration resistance of particles. The surface of the modified collectors could also maintain a uniform and stable water film with a lower amount of water consumption. The water film could restrain the back corona and the re-entrainment of dust. And the evaporation of water film increased the humidity of the flue gas, meanwhile, the particles charge capacity and electromigration velocity increased. Those all could improve the particles removal efficiency. The particles removal efficiency increased with the increase of the flue gas residence time and the applied voltage, but the particles removal efficiency improved less with the increase of the particles inlet concentration and flushing water flow rate after maintaining uniform and stable water film. The modified rigid collector provided high removal efficiency for particles with diameters of 0.04~0.48 µm under lower energy and water consumption.Implications: The wet electrostatic precipitators (ESPs) have been widely used as terminal equipment of the flue gas treatment to purify the flue gas deeply. The surface of the modified carbon steel collectors with hydrophilic properties could maintain a uniform and stable water film with a lower amount of water consumption. The evaporation of water film improved the particle charge capacity and electromigration velocity. The wet ESPs using the modified rigid collector exhibited significantly higher removal efficiency of particles than using the conventional rigid collector especially to the particles with diameter of 0.04~0.48 µm.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Carbono , Poeira , Tamanho da Partícula , Eletricidade Estática , Aço
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