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1.
Appl Environ Microbiol ; 90(2): e0157423, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38236018

RESUMO

ATP-dependent energy-consuming enzymatic reactions are widely used in cell-free biocatalysis. However, the direct addition of large amounts of expensive ATP can greatly increase cost, and enzymatic production is often difficult to achieve as a result. Although a polyphosphate kinase (PPK)-polyphosphate-based ATP regeneration system has the potential to solve this challenge, the generally poor thermal stability of PPKs limits the widespread use of this method. In this paper, we evaluated the thermal stability of a PPK from Sulfurovum lithotrophicum (SlPPK2). After directed evolution and computation-supported design, we found that SlPPK2 is very recalcitrant and cannot acquire beneficial mutations. Inspired by the usually outstanding stability of ancestral enzymes, we reconstructed the ancestral sequence of the PPK family and used it as a guide to construct three heat-stable variants of SlPPK2, of which the L35F/T144S variant has a half-life of more than 14 h at 60°C. Molecular dynamics simulations were performed on all enzymes to analyze the reasons for the increased thermal stability. The results showed that mutations at these two positions act synergistically from the interior and surface of the protein, leading to a more compact structure. Finally, the robustness of the L35F/T144S variant was verified in the synthesis of nucleotides at high temperature. In practice, the use of this high-temperature ATP regeneration system can effectively avoid byproduct accumulation. Our work extends the temperature boundary of ATP regeneration and has great potential for industrial applications.IMPORTANCEATP regeneration is an important basic applied study in the field of cell-free biocatalysis. Polyphosphate kinase (PPK) is an enzyme tool widely used for energy regeneration during enzymatic reactions. However, the thermal stability of the PPKs reported to date that can efficiently regenerate ATP is usually poor, which greatly limits their application. In this study, the thermal stability of a difficult-to-engineer PPK from Sulfurovum lithotrophicum was improved, guided by an ancestral sequence reconstruction strategy. The optimal variant has a 4.5-fold longer half-life at 60°C than the wild-type enzyme, thus enabling the extension of the temperature boundary for ATP regeneration. The ability of this variant to regenerate ATP was well demonstrated during high-temperature enzymatic production of nucleotides.


Assuntos
Trifosfato de Adenosina , Epsilonproteobacteria , Fosfotransferases (Aceptor do Grupo Fosfato) , Trifosfato de Adenosina/metabolismo , Temperatura , Fosfotransferases (Aceptor do Grupo Fosfato)/genética , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Nucleotídeos
2.
Helicobacter ; 29(1): e13054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38900537

RESUMO

BACKGROUND: The amoxicillin dose used in dual therapy to eradicate Helicobacter pylori varies across studies and the optimal amoxicillin dose for vonoprazan-based dual therapies remains unclear. We aimed to investigate the efficacy and safety of low- and high-dose amoxicillin in vonoprazan-amoxicillin dual therapy. MATERIALS AND METHODS: A comprehensive systematic review was conducted by searching databases from inception to October 2023. All trials that evaluated the effectiveness and safety of vonoprazan-amoxicillin dual therapy for eradicating H. pylori were included. Pooled eradication rate, incidence of adverse events, relative risks, and 95% confidence intervals are presented. RESULTS: Eighteen studies with 12 low-dose amoxicillin (VLA) and 13 high-dose amoxicillin (VHA) arms were included. The pooled eradication rates were 82.4% and 86.8% for VLA therapy, and 86.0% and 90.9% for VHA therapy by the intention-to-treat and per-protocol analyses, respectively. In the subgroup analysis stratified by duration, the eradication rates achieved in 7 days, 10 days, and 14 days treatments with VLA and VHA dual therapies were 80.8%, 84.2%, 83.1%, and 67.3%, 88.8%, 87.5%, respectively. In the four randomized controlled trials that directly compared VLA and VHA dual therapies, the efficacy was not statistically different in the intention-to-treat (76.9% vs 81.4%, p = 0.337) and per-protocol (81.6% vs 84.0%, p = 0.166) analyses. Additionally, the incidence of adverse events (p = 0.965) and compliance (p = 0.994) were similar in both groups. CONCLUSION: VLA therapy demonstrated comparable efficacy and safety to VHA therapy, along with regional differences. An appropriately extended treatment duration may be critical for therapeutic optimization of vonoprazan-amoxicillin treatment.


Assuntos
Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Pirróis , Sulfonamidas , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Humanos , Infecções por Helicobacter/tratamento farmacológico , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Pirróis/administração & dosagem , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Resultado do Tratamento , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos
3.
Digestion ; 105(3): 157-165, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38198754

RESUMO

INTRODUCTION: The safety and efficacy of cold snare polypectomy (CSP) compared to those of cold endoscopic mucosal resection (CEMR) have been reported. This meta-analysis compared the efficacy and safety of CEMR and CSP. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials comparing the efficacy and safety of CEMR and CSP in removing 3-10 mm polyps. The outcomes assessed included complete resection rate, intraoperative bleeding rate, delayed bleeding rate, perforation, and polyp removal time. The results are reported as risk ratios (RR) and 95% confidence intervals (CIs) derived from a Mantel-Haenszel random-effects model. RESULTS: Seven studies comprising 1,911 polyps were included in the analysis. The complete resection rate of CEMR was comparable to that of CSP (RR: 1.01, 95% CI: 0.99-1.04, p = 0.32). Comparable results were also demonstrated for intraoperative bleeding rate (polyp-based analysis: RR: 1.22, 95% CI: 0.33-4.43, p = 0.77), delayed bleeding rate (polyp-based analysis: RR: 1.34, 95% CI: 0.44-4.15, p = 0.61), and polyp removal time (mean difference: 28.31 s, 95% CI: -21.40-78.02, p = 0.26). No studies reported cases of perforation. CONCLUSION: CEMR has comparable efficacy and safety to CSP in removing 3-10 mm polyps. Further randomized controlled trials with long-term follow-up are warranted to compare and validate efficacy.


Assuntos
Pólipos do Colo , Ressecção Endoscópica de Mucosa , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Perda Sanguínea Cirúrgica/prevenção & controle , Pólipos do Colo/cirurgia , Pólipos do Colo/patologia , Colonoscopia/métodos , Colonoscopia/efeitos adversos , Colonoscopia/instrumentação , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Ressecção Endoscópica de Mucosa/instrumentação , Duração da Cirurgia , Resultado do Tratamento
4.
Dig Dis Sci ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700630

RESUMO

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

5.
J Asian Nat Prod Res ; 26(6): 681-689, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38329449

RESUMO

Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds (1-11), including two γ-aromatic butenolides (γ-AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ-butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish.


Assuntos
4-Butirolactona , 4-Butirolactona/análogos & derivados , Aspergillus , Família Multigênica , Peptídeo Sintases , Peptídeo Sintases/genética , Estrutura Molecular , 4-Butirolactona/farmacologia , 4-Butirolactona/química , Aspergillus/enzimologia , Aspergillus/química , Aspergillus/genética , Animais , Peixe-Zebra
6.
J Gastroenterol Hepatol ; 38(12): 2097-2103, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37702104

RESUMO

BACKGROUND AND AIM: After three treatment failures, Helicobacter pylori infection is deemed refractory as antibiotic treatment options become significantly limited. This study evaluated the efficacy and safety of a 14-day modified concomitant therapy for managing refractory H. pylori infection. METHODS: Patients who had failed to respond to three or more rounds of H. pylori therapies were recruited for this study. They received a 14-day modified concomitant therapy, including esomeprazole 40 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily and tetracycline 500 mg four times daily. Demographic data, adverse events, and patient compliance were recorded. The presence of H. pylori was reevaluated 6 weeks following treatment. Eradication rate was assessed as the primary outcome. RESULTS: Overall, 59 participants received the 14-day modified concomitant therapy. In the intention-to-treat and per-protocol analyses, the eradication rate was 84.7% (50/59) and 89.3% (50/56), respectively. H. pylori was successfully isolated from 75.0% (12/16) of patients. The resistance rate of H. pylori to metronidazole, levofloxacin, and clarithromycin was 91.7% (11/12), 58.3% (7/12), and 50.0% (6/12), respectively. Resistance to amoxicillin, furazolidone, or tetracycline was not observed. The frequency of adverse events was 35.6% (21/59), with no serious adverse events reported. CONCLUSION: The 14-day modified concomitant therapy appears to be appropriate for refractory H. pylori infection and is particularly promising for the Chinese population. A randomized controlled trial is warranted to verify its efficacy, especially in the current environment of increasing antibiotic resistance.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/etiologia , Projetos Piloto , Furazolidona/efeitos adversos , Quimioterapia Combinada , Antibacterianos , Amoxicilina , Metronidazol , Claritromicina/efeitos adversos , Resultado do Tratamento
7.
Surg Today ; 53(4): 451-458, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36098805

RESUMO

PURPOSE: The present study discussed the effects of accidental parathyroid resection on hypoparathyroidism and investigated the risk factors associated with accidental parathyroid resection. METHODS: Clinical data from patients who have undergone thyroidectomy at a university hospital in the period from November 2018 and October 2020 were entered into the database and analyzed. Risk factors for accidental parathyroid resection were recorded. RESULTS: A total of 1775 cases were included in this study. The analysis showed that lymph-node dissection (p < 0.001), T staging (p = 0.037), and treatment group (p < 0.001) were independent risk factors for accidental parathyroid resection. Different treatment groups were important risk factors for accidental parathyroid resection. There were significant differences between the professional and non-professional groups in the following aspects: accidental parathyroid resection (p < 0.001), Scope (p < 0.001), T stage (p = 0.009), N stage (p < 0.001), range of lymph-node dissection (p < 0.001), number of lymph nodes dissected in central area (p < 0.001), and number of lymph-node metastases in the central region (p < 0.001). CONCLUSIONS: The causes of accidental parathyroid resection are multifactorial. The predictors for accidental parathyroid resection include lymph-node dissection in the central region, T staging, as well as the operating surgeons' experience.


Assuntos
Esvaziamento Cervical , Neoplasias da Glândula Tireoide , Humanos , Estudos Retrospectivos , Esvaziamento Cervical/efeitos adversos , Neoplasias da Glândula Tireoide/etiologia , Glândulas Paratireoides/cirurgia , Glândulas Paratireoides/patologia , Excisão de Linfonodo/efeitos adversos , Linfonodos/patologia , Tireoidectomia/efeitos adversos , Fatores de Risco
8.
Chem Biodivers ; 20(6): e202201095, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37026436

RESUMO

The pollution of heavy metals in soil to the environment is becoming more and more serious, resulting in the reduction of crop production and the occurrence of medical accidents. In order to remove heavy metal ions from soil and reduce the harm of heavy metals to the environment, modified peanut shell was used to adsorb Cr3+ in this article. The effects of different adsorption conditions on the adsorption rate and adsorption capacity of Cr3+ on ZnCl2 modified peanut shell were studied, the best adsorption conditions were explored, and the relationship of kinetics, thermodynamics and adsorption isotherm properties of adsorption process were explored. The results showed that the optimum adsorption pH value, dosage, initial concentration, adsorption temperature and contact time of ZnCl2 modified peanut shell were 2.5, 2.5 g/L, 75 µg/mL, 25 °C and 40 min, respectively. The prepared materials were characterized and analyzed by scanning electron microscope (SEM) and X-ray diffraction (XRD) analyzer. It was concluded that the modified peanut shell had a good adsorption capacity to Cr3+ . The kinetic study showed that the adsorption process of Cr3+ on peanut shell modified by zinc chloride was in accordance with the quasi-second-order kinetic model. The adsorption process belonged to exothermic reaction and belonged to spontaneous reaction process. In summary, it is proved that zinc chloride modified peanut shell can efficiently adsorb Cr3+ , which can be used for the treatment of heavy metal wastes in industry, which is beneficial to environmental protection and avoid heavy metal pollution.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Cromo/análise , Cromo/química , Arachis , Adsorção , Cinética , Termodinâmica , Solo , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Bioorg Chem ; 124: 105810, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35447407

RESUMO

Three previously undescribed polyketides [proliferatin A-C (1-3)] with anti-inflammatory activity were isolated from Fusarium proliferatum. 1-3 attenuated the production of inflammatory signal messengers including nitric oxide (NO), reactive oxygen species, proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), as well as the related proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the potential anti-inflammatory mechanism of 1-3 involved in the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinases (MAPKs) signaling pathways. Experimental evaluation of the protein levels revealed that 1-3 can inhibit the phosphorylation of IκB kinase (IKK), the degradation of NF-κB Inhibitor-α (IκBα), the phosphorylation of nuclear factor-κB (NF-κB) and can reduce NF-κB transportation to the nucleus. Interestingly, 1-3 decreased the phosphorylation of MAPKs including p-p38, p-ERK, and p-JNK. Molecular docking models suggest that binding of 1-3 to TLR4-MD-2 complex may lead to inhibition of NF-κB and MAPK signaling pathways, which was confirmed in vitro by surface plasmon resonance (SPR) assays. 1-3 can thus constitute potential therapeutic candidates for the treatment of inflammation-associated diseases.


Assuntos
Lipopolissacarídeos , NF-kappa B , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
J Chem Phys ; 157(18): 184504, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36379802

RESUMO

Establishing the structure-property relationship is an important goal of glassy materials, but it is usually impeded by their disordered structure and non-equilibrium nature. Recent studies have illustrated that secondary (ß) relaxation is closely correlated with several properties in a range of glassy materials. However, it has been challenging to identify the pertinent structural features that govern it. In this work, we show that the so-called polyamorphous transition in metallic glasses offers an opportunity to distinguish the structural length scale of ß relaxation. We find that, while the glass transition temperature and medium-range orders (MROs) change rapidly across the polyamorphous transition, the intensity of ß relaxation and the short-range orders (SROs) evolve in a way similar to those in an ordinary reference glass without polyamorphous transition. Our findings suggest that the MRO accounts mainly for the global stiffening of the materials and the glass transition, while the SRO contributes more to ß relaxation per se.

11.
Am J Emerg Med ; 52: 1-7, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34856439

RESUMO

BACKGROUND: Limited data are available on the discriminatory capacity of quick sequential [sepsis-related] organ failure assessment (qSOFA) versus IDSA/ATS minor criteria for predicting mortality in patients with community-acquired pneumonia (CAP). METHODS: An observational prospective cohort study of 2116 patients with CAP was performed. Construct validity was determined using Cronbach α. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI). RESULTS: Overall in-hospital mortality was 6.43%. Mortality was 25.96% for patients with a qSOFA score of 2 or higher versus 3.05% for those with a qSOFA score less than 2 (odds ratio for mortality 6.57, P < 0.0001), and 13.85% for patients with at least 3 minor criteria versus 2.03% for those with 2 or fewer minor criteria (odds ratio for mortality 2.27, P < 0.0001). qSOFA had a higher correlation with mortality than minor criteria, as well as higher internal consistency (Cronbach alpha 0.43 versus 0.14) and diagnostic values of individual elements (larger AUROCs and higher Youden's indices). qSOFA ≥2 was less sensitive but more specific for predicting mortality than ≥3 minor criteria (qSOFA sensitivity 59.6%, specificity 88.3% and positive likelihood ratio 5.11 versus ≥3 minor criteria sensitivity 80.1%, specificity 65.8% and positive likelihood ratio 2.34). The predictive validity of qSOFA was good for mortality (AUROC = 0.868), was statistically greater than minor criteria, was equal to pneumonia severity index, and was inferior compared with CURB-65 (AUROC, 0.824, 0.902, 0.919; NRI, 0.088, -0.068, -0.103; respectively). CONCLUSIONS: The qSOFA predicted mortality in CAP better than IDSA/ATS minor criteria and worse than CURB-65 with robust elements and higher convergence. qSOFA as a bedside prompt might be positioned as a proxy for minor criteria and increase the recognition and thus merit more appropriate management of CAP patients likely to fare poorly, which might have implications for more accurate clinical triage decisions.


Assuntos
Escores de Disfunção Orgânica , Pneumonia/mortalidade , Sepse/mortalidade , Adulto , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/diagnóstico , Valor Preditivo dos Testes , Estudos Prospectivos , Sepse/diagnóstico , Sepse/etiologia
12.
BMC Cancer ; 21(1): 127, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549042

RESUMO

BACKGROUND: Sodium butyrate (NaB) is produced through the fermentation of dietary fiber that is not absorbed and digested by the small intestine. PURPOSE: Here, we aimed to investigate the effects of NaB on the proliferation, invasion, and metastasis of CRC cells and their potential underlying molecular mechanism(s). METHODS: The cell counting kit-8 (CCK-8) assay and EdU assay were used to detect cell proliferation ability, flow cytometry was used to investigate the induction of apoptosis and cell cycle progression, and the scratch-wound healing and transwell assays were used to evaluate cell migration and invasion, respectively. The human CRC genome information for tissues and CRC cells treated with NaB obtained from the NCBI GEO database was reannotated and used for differential RNA analysis. Functional and pathway enrichment analyses were performed for differentially expressed lncRNAs and mRNAs. A protein-protein interaction (PPI) network for the hub genes was constructed using the Cytoscape software. Targeted miRNAs were predicted based on the lnCeDB database, and a ceRNA network was constructed using the Cytoscape software. The Kaplan-Meier method was used to analyze patient prognosis using the clinical information and exon-seq data for CRC obtained from the Broad Institute's GDAC Firehose platform. RESULTS: NaB decreased the proliferation ability of CRC cells in a dose- and time-dependent manner. The number of apoptotic CRC cells increased with the increase in NaB concentrations, and NaB induced a G1 phase block in CRC cells. Moreover, NaB suppressed the migratory and invasive capabilities of CRC cells. There were 666 differentially expressed mRNAs and 30 differentially expressed lncRNAs involved in the CRC inhibition by NaB. The PPI network and ceRNA network were constructed based on the differentially expressed mRNAs and lncRNAs. Three differentially expressed mRNAs, including HMGA2, LOXL2, and ST7, were significantly correlated with the prognosis of CRC. CONCLUSION: NaB induces the apoptosis and inhibition of CRC cell proliferation, invasion, and metastasis by modulating complex molecular networks. RNA prediction and molecular network construction need to be the focus of further research in this direction.


Assuntos
Ácido Butírico/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Mapas de Interação de Proteínas , Apoptose , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Bases de Dados Genéticas , Relação Dose-Resposta a Droga , Fase G1/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/metabolismo , Invasividade Neoplásica , Prognóstico , RNA Longo não Codificante/metabolismo
13.
FASEB J ; 34(10): 13809-13825, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32808389

RESUMO

Human infection of orthohantavirus can cause potentially fatal diseases, such as hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) in Eurasia. Exosomes are new carriers for information exchange between cells. Cumulative findings suggest that exosomes released from parental infected cells can block or promote viral infection in recipient cells, but the role of exosomes in hantavirus infection is poorly understood. In our study, we identified the exosomes derived from HTNV-infected human vascular endothelial cells (HUVECs) (Exo-HV) and found the antiviral properties of Exo-HV in the uninfected recipient cells. High-throughput sequencing revealed the distinctly expressed miRNAs transcriptomes in Exo-HV. MiR-145-5p, one of the abundant miRNAs packaged into Exo-HV, was found to be able to transferred to recipient cells and functioned by directly targeting M RNA of HTNV 76-118 and inducing type I interferon (IFN-I) response, thus, blocking the viral replication. Concluding, this study indicated that exosomes released by HTNV-infected HUVECs were able to transfer active molecules, miR-145-5p as a proving sample, to mediate novel anti-HTNV activity in the neighboring uninfected cells, which will help us to explore new strategies for the treatment of infectious disease utilizing exosomes with miRNA.


Assuntos
Exossomos/genética , Vírus Hantaan/fisiologia , Células Endoteliais da Veia Umbilical Humana/virologia , MicroRNAs/metabolismo , Orthohepadnavirus/patogenicidade , Replicação Viral , Exossomos/metabolismo , Vírus Hantaan/patogenicidade , Interações Hospedeiro-Patógeno , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interferons/genética , Interferons/metabolismo , MicroRNAs/genética , Transcriptoma
14.
J Nat Prod ; 84(12): 3044-3054, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34846889

RESUMO

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1ß, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.


Assuntos
Anti-Inflamatórios/farmacologia , Chaetomium/química , Furanos/farmacologia , Microglia/efeitos dos fármacos , Resorcinóis/farmacologia , Animais , Ésteres/química , Furanos/química , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/antagonistas & inibidores , Resorcinóis/química , Análise Espectral/métodos
15.
Respir Res ; 21(1): 192, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689999

RESUMO

BACKGROUND: Severity of community-acquired pneumonia (CAP) depends on microbial pathogenicity, load and virulence, and immune responses. The Infectious Disease Society of America and the American Thoracic Society (IDSA/ATS) minor criteria responsible for clinical triage of patients with CAP are of unequal weight in predicting mortality. It is unclear whether the IDSA/ATS major/minor criteria might be strongly and positively associated with the immune responses. It is warranted to explore this intriguing hypothesis. METHODS: A prospective cohort study of 404 CAP patients was performed. Cold-inducible RNA-binding protein (CIRP) levels were measured using a sandwich-based enzyme-linked immunosorbent assay. The receiver operating characteristic curves were created and the areas under the curves were calculated to illustrate and compare the accuracy of the indices. RESULTS: Severe CAP patients meeting the major criteria had the highest plasma concentrations of CIRP. The more the number of most predictive minor criteria strongly associated to mortality, i.e. arterial oxygen pressure/fraction inspired oxygen ≤ 250 mmHg, confusion, and uremia, present, the higher the CIRP level. Interestingly, the patients with non-severe CAP meeting the most predictive minor criteria demonstrated unexpectedly higher CIRP level compared with the patients with severe CAP not fulfilling the criteria. Procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores, and mortality confirmed similar intriguing patterns. CIRP was strongly linked to PCT, IL-6, CRP, minor criteria, SOFA and PSI scores, and mortality (increased odds ratio 3.433). The pattern of sensitivity, specificity, positive predictive value, and Youden's index of CIRP ≥ 3.50 ng/mL for predicting mortality was the optimal. The area under the receiver operating characteristic curve of CIRP was the highest among the indices. CONCLUSIONS: CIRP levels were strongly correlated with the IDSA/ATS major/minor criteria. CIRP might determine the severity and the presences of major/minor criteria and best predicted mortality, and a CIRP of ≥ 3.50 ng/mL might be more valuable cut-off value for severe CAP, suggesting that CIRP might be a novel and intriguing biomarker for pneumonia to monitor host response and predict mortality, which might have implications for more accurate clinical triage decisions.


Assuntos
Pneumonia/sangue , Pneumonia/mortalidade , Proteínas de Ligação a RNA/sangue , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Pneumonia/diagnóstico , Prognóstico , Estudos Prospectivos
16.
Neuroradiology ; 62(5): 601-607, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31996968

RESUMO

PURPOSE: Microcystic meningioma (MCM) appears similar to atypical meningioma(AM) as per conventional diagnostic imaging. However, considering their different recurrence rate and prognosis, accurate differential diagnosis is essential for determine the appropriate treatment strategy. The aim of the study was to differentiate MCM from AM by diffusion-weighted imaging (DWI), in order to provide the basis for accurate preoperative diagnosis. METHODS: The preoperative clinical data, conventional MRI and DWI data of 15 MCM and 30 AM cases were retrospectively analyzed. The average apparent diffusion coefficient (ADCmean), minimum ADC (ADCmin) and normalized ADC (nADC) between MCM and AM were compared using two sample t-tests. The value of ADCmean, ADCmin and nADC in the differential diagnosis of MCM and AM were calculated by the receiver operating curve (ROC) analysis. RESULTS: The ADCmean (1.06 ± 0.10 vs 0.80 ± 0.11 × 10-3 mm2/s; P < 0.001), ADCmin (0.99 ± 0.10 vs 0.74 ± 0.12 × 10-3 mm2/s; P < 0.001) and nADC (1.45 ± 0.17 vs 1.07 ± 0.17; P < .0001) were significantly higher in MCM compared to AM. ADCmean of 0.91 × 10-3 mm2/s showed an optimum area under the ROC curve of 0.967 ± 0.022, and distinguished between MCM and AM with 86.67% sensitivity, 100% specificity and 88.89% accuracy. In addition, its positive and negative predictive values were 96.29% and 77.78% respectively. CONCLUSIONS: DWI can differentially diagnose MCM and AM, and ADCmean is a potential quantitative tool that can improve preoperative diagnosis of both tumors.


Assuntos
Cistos/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Adulto , Idoso , Cistos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Water Sci Technol ; 81(10): 2092-2108, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32701489

RESUMO

Mesocellular foam (MCF) silica molecular sieve material was successfully synthesized using a hydrothermal method. X-ray diffraction, infrared spectroscopy, low nitrogen adsorption-desorption, scanning electron microscopy, and transmission electron microscopy (TEM) characterization techniques were used to characterize the material. Low temperature nitrogen adsorption-desorption method showed that pore size of the synthesized MCF was 12 nm. TEM study showed that the synthesized MCFs had honeycomb structure pores, which can be good for the absorbance of dye organic macromolecule substances. This work studied the adsorption of crystal violet by MCF and the results showed that when the adsorptive conditions were pH = 9.0, MCF:crystal violet = 150:1, and when the contact time was 10 min at room temperature of 25 ± 1 °C, the adsorption rate reached 99.71% and adsorption capacity was 6.646 mg/g. This study found that the adsorption is a Freundlich type, it is a multimolecular layer adsorption, and it belongs to the pseudo-second-order kinetic model. According to the ΔG0 obtained from adsorption thermodynamics, when the temperature is 25-40 °C, the adsorption enthalpy change ΔH0 = -25.65 kJ/mol, ΔG0 < 0, the adsorption is an exothermic reaction and can spontaneously occur. The adsorption entropy change ΔS0 = 5.54 J/(mol·K) and the entropy of system increased.


Assuntos
Violeta Genciana , Dióxido de Silício , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Temperatura , Termodinâmica
19.
Respir Res ; 20(1): 22, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704469

RESUMO

BACKGROUND: Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality, but the major problem associated with IDSA/ATS minor criteria might be a lack of consideration of weight in prediction in clinical practice. Would awarding different points to the presences of the minor criteria improve the accuracy of the scoring system? It is warranted to explore this intriguing hypothesis. METHODS: A total of 1230 CAP patients were recruited to a retrospective cohort study. This was tested against a prospective two-center cohort of 1749 adults with CAP. 2 points were assigned for the presence of PaO2/FiO2 ≤ 250 mmHg, confusion, or uremia on admission and 1 point for each of the others. RESULTS: The mortality rates, and sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores increased significantly with the numbers of IDSA/ATS minor criteria present and minor criteria scores. The correlations of the minor criteria scores with the mortality rates were higher than those of the numbers of IDSA/ATS minor criteria present. As were the correlations of the minor criteria scores with SOFA and PSI scores, compared with the numbers of IDSA/ATS minor criteria present. The pattern of sensitivity, specificity, positive predictive value, and Youden's index of scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria for prediction of mortality was the best in the retrospective cohort, and the former was better than the latter. The validation cohort confirmed a similar pattern. The area under the receiver operating characteristic curve of scored minor criteria was higher than that of IDSA/ATS minor criteria in the retrospective cohort, implying higher accuracy of scored version for predicting mortality. The validation cohort confirmed a similar paradigm. CONCLUSIONS: Scored minor criteria orchestrated improvements in predicting mortality and severity in patients with CAP, and scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria might be more valuable cut-off value for severe CAP, which might have implications for more accurate clinical triage decisions.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Pneumonia/diagnóstico , Pneumonia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Coortes , Confusão/etiologia , Confusão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Oxigênio/sangue , Valor Preditivo dos Testes , Padrões de Referência , Estudos Retrospectivos , Uremia/etiologia , Adulto Jovem
20.
Future Oncol ; 15(14): 1655-1666, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31044617

RESUMO

Colorectal cancer (CRC) is a common type of malignant cancer worldwide. Recent studies have identified the gut microbiota as the origin of CRC, and T lymphocyte-mediated immune functions have been shown to play an important role in this disease. By summarizing previous literature, we found that Fusobacterium nucleatum may protect CRC from immune cell attack by inhibiting T cells and influencing the production of many chemokines and cytokines. Some bacterial metabolites and probiotics have been shown to participate in the regulation of CRC through T cell-mediated molecular pathways. To visualize the relevant data, an association network of intestinal microorganisms and T lymphocytes associated with CRC was constructed. This work may provide direction for - and insight into - further research on the relationship between intestinal microorganisms and T lymphocytes in CRC.


Assuntos
Neoplasias Colorretais/etiologia , Microbioma Gastrointestinal , Linfócitos T/imunologia , Animais , Biomarcadores , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Suscetibilidade a Doenças , Humanos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/metabolismo
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