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1.
Clin Sci (Lond) ; 137(2): 195-217, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36597894

RESUMO

BACKGROUND: Autoimmune disorder is the emerging mechanism of atrial fibrillation (AF). The ß1-adrenergic receptor antibody (ß1-AAb) is associated with AF progress. Our study aims to investigate whether ß1-AAbs involves in atrial vulnerable substrate by mediating Ca2+ mishandling and atrial fibrosis in autoimmune associated AF. METHODS: Active immunization models were established via subcutaneous injection of the second extracellular loop (ECL2) peptide for ß1 adrenergic receptor (ß1AR). Invasive electrophysiologic study and ex vivo optical mapping were used to evaluate the changed electrophysiology parameters and calcium handling properties. Phospho-proteomics combined with molecular biology assay were performed to identify the potential mechanisms of remodeled atrial substrate elicited by ß1-AAbs. Exogenous ß1-AAbs were used to induce the cellular phenotypes of HL-1 cells and atrial fibroblasts to AF propensity. RESULTS: ß1-AAbs aggravated the atrial electrical instability and atrial fibrosis. Bisoprolol alleviated the alterations of action potential duration (APD), Ca2+ transient duration (CaD), and conduction heterogeneity challenged by ß1-AAbs. ß1-AAbs prolonged calcium transient refractoriness and promoted arrhythmogenic atrial alternans and spatially discordant alternans, which were partly counteracted through blocking ß1AR. Its underlying mechanisms are related to ß1AR-drived CaMKII/RyR2 activation of atrial cardiomyocytes and the myofibroblasts phenotype formation of fibroblasts. CONCLUSION: Suppressing ß1-AAbs effectively protects the atrial vulnerable substrate by ameliorating intracellular Ca2+ mishandling and atrial fibrosis, preventing the process of the autoimmune associated AF.

2.
J Magn Reson Imaging ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36625533

RESUMO

BACKGROUND: Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. PURPOSE: To assess the temporal dynamics of N-acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6-24 hours) hyperacute stroke groups. STUDY TYPE: Cross-sectional cohort. POPULATION: A total of 73 ischemic stroke patients scanned at 1.8-302.5 hours after symptom onset, including 25 patients with follow-up scans. FIELD STRENGTH/SEQUENCE: A 3 T/magnetization-prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion-weighted imaging and fluid-attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. ASSESSMENT: Patients were divided into hyperacute (0-24 hours), acute (24 hours to 1 week), and subacute (1-2 weeks) groups, and into early (<6 hours) and late (6-24 hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. STATISTICAL TESTS: Linear mixed effects modeling was applied for group-wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. RESULTS: Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F = 14.321) and creatine (F = 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r = -0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r = -0.472; lactate: r = 0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC] = 0.90). DATA CONCLUSION: High-resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

3.
Technol Cancer Res Treat ; 22: 15330338221148802, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36628459

RESUMO

In the era of precision medicine, with the deepening of the research on malignant tumor driving genes, clinical oncology has fully entered the era of targeted therapy. For non-small-cell lung cancer (NSCLC), the development of targeted drugs targeting driver genes, such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has successfully opened up a new model of targeted therapy. At present, proto-oncogene rearranged during transfection (RET) fusion gene is an important novel oncogenic driving target, and specific receptor tyrosine kinase inhibitors (TKIs) targeting RET fusion have been approved. This article will review the latest research about the molecular characteristics, pathogenesis, detection, and clinical treatment strategies of RET rearrangements especially in China.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Rearranjo Gênico , Oncogenes , Proto-Oncogenes , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/uso terapêutico
4.
Phytochemistry ; : 113585, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36693580

RESUMO

Nine undescribed phloroglucinol derivatives (dryatraols A-I) with five different backbones and three known dimeric acylphloroglucinols were isolated from the rhizome of Dryopteris atrata (Wall. Ex Kunze) Ching (Dryopteridaceae). Dryatraol A contains an unprecedented carbon skeleton-a butyrylphloroglucinol and a rulepidanol-type sesquiterpene are linked via a furan ring to form a 6/5/6/6 ring system. Dryatraols B and C are the first examples of monomeric phloroglucinols coupled with the aristolane-type sesquiterpene through the C-C bond. Dryatraol D features a rare spiro [benzofuran-2',5″-furan] backbone. Dryatraols E-I are five undescribed adducts with a butyrylphloroglucinol or filicinic acid incorporated into the germacrene-type sesquiterpene via a pyran ring. These undescribed structures were determined by comprehensively analysing the spectroscopic data, X-ray diffraction results, and electronic circular dichroism calculations. The result of in vitro antiviral activity evaluation indicated that dryatraol C displayed the strongest antiviral effect against both respiratory syncytial virus and influenza A virus (H1N1), with IC50 values of 11.9 µM and 5.5 µM, respectively. Dryatraols F-H exhibited considerable inhibitory activity against herpes simplex virus type 1 (HSV-1), with IC50 values ranging from 2.6 to 6.3 µM. Analysis of the inhibitory mechanism using a time-of-addition assay revealed that dryatraol G may inhibit the replication of HSV-1 by interfering with the late stage of the viral life cycle.

5.
Int J Biol Macromol ; : 123383, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36693601

RESUMO

Octenyl succinic anhydride modified starch is a common green and safe emulsifier. Although the conventional pretreatment method of free enzyme hydrolysis increases the hydroxyl content on the starch surface, thus improving the grafting degree of octenyl succinic anhydride and the amphiphilicity of the modified starch, the amylose and amylopectin structures are indiscriminately hydrolyzed, reducing the emulsion stability of modified starch. In this work, α-amylase organic-inorganic hybrid nanoflower biocatalyst is designed and synthesized for pretreatment of synthetic octenyl succinic anhydride modified starch. The α-amylase organic-inorganic hybrid nanoflower biocatalyst with a unique micro-nano spatial structure can selectively hydrolyze the amylopectin and protect the amylose of starch. The amylose ratio of starch pretreated by nanoflower biocatalyst is about twice that of starch pretreated by free enzyme, reaching 22.62 %. Meanwhile, the granular structure of starch is not damaged. The obtained octenyl succinic anhydride modified starch exhibits a high degree of substitution, up to 0.0213. The emulsion prepared with this modified starch maintains excellent emulsifying properties and stability. This study provides a novel strategy for the preparation of octenyl succinic anhydride modified starch with excellent emulsifying properties, which promote the application of octenyl succinic anhydride modified starch in food, pharmaceutical and cosmetic industries.

6.
J Neurol ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631678

RESUMO

BACKGROUND: Charcot-Marie-Tooth disease and related inherited peripheral neuropathies (CMT&RIPNs) brings great suffering and heavy burden to patients, but its global prevalence rates have not been well described. METHODS: We searched major English and Chinese databases for studies reporting the prevalence of CMT&RIPNs from the establishment of the databases to September 26, 2022. Based on the age, gender, study design, study region, and disease subtype, the included studies were correspondingly synthesized for meta-analyses on the overall prevalence and/or the subgroup analyses by using pool arcsine transformed proportions in the random-effects model. RESULTS: Of the finally included 31 studies, 21 studied the whole age population and various types of CMT&RIPNs, and the others reported specific disease subtype(s) or adult or non-adult populations. The pooled prevalence was 17.69/100,000 (95% CI 12.32-24.33) for the whole age population and significantly higher for CMT1 [10.61/100,000 (95% CI 7.06-14.64)] than for other subtypes (P' < 0.001). Without statistical significance, the prevalence seemed higher in those aged ≥ 16 or 18 years (21.02/100,000) than in those aged < 16 years (16.13/100,000), in males (22.50/100,000) than in females (17.95/100,000), and in Northern Europe (30.97/100,000) than in other regions. CONCLUSION: CMT&RIPNs are relatively more prevalent as CMT1 in the disease subtypes, and probably prevalent in older ages, males, and Northern Europe. More studies on the epidemiological characteristics of CMT&RIPNs with well-defined diagnosis criteria are needed to improve the prevalence evaluation and to arouse more attention to health care support.

7.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36674614

RESUMO

In this study, an efficient phosphorus-containing flame retardant, PAPBTCA, was synthesized from phytic acid, pentaerythritol, and 1,2,3,4-butane tetracarboxylic acid, and its structure was characterized. PAPBTCA was finished on cotton fabrics by the pad-dry-curing process, and the flame retardancy, flame-retardant durability, and wrinkle resistance of the obtained flame-retardant fabrics were investigated. It should be noted that the heat release rate value of the flame-retardant cotton fabrics treated with 200 g/L PAPBTCA decreased by 90% and its excellent flame retardancy was maintained after 5 washing cycles. Meanwhile, the wrinkle resistance of flame-retardant cotton fabrics has been significantly improved. In addition, compared with the control, the breaking force loss of PAPBTCA-200 in the warp and weft directions was 24% and 21%, respectively. This study provides a new way to utilize natural phosphorus-based flame retardants to establish multifunctional finishing for cotton fabrics.


Assuntos
Fibra de Algodão , Retardadores de Chama , Ácido Fítico , Têxteis , Fósforo
8.
Opt Express ; 31(1): 56-64, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36606949

RESUMO

We introduce a calcium carbonate birefringent crystal into an Er-fiber laser mode-locked by a saturable absorber, where dual-comb ultrashort pulses with orthogonal polarization have been obtained. The two ultrashort pulse trains from the laser exhibit polarization contrast ratios of 30 dB and 20 dB, indicating that the dual-comb mode-locking is due to the polarization-multiplexing mechanism. The dual-comb ultrashort pulses have central wavelengths of 1564.41 nm and 1564.51 nm, and pulse durations of 825 fs and 805 fs respectively. The optical spectra and pulse durations of the asynchronous ultrashort pulses are nearly identical, so that the output of the laser could be directly used for dual-comb applications. Besides, the repetition-rate difference of the two mode-locked pulses is 673 Hz, while its drift is only 0.093 Hz within 2 hours' time. The low drift of the repetition-rate difference manifests the single-cavity dual-comb Er-fiber laser has a high stability and high common-mode noise suppression. At last, we have tested the dual-comb fiber laser in a ranging experiment, where clear interferogram signal can be observed. The experimental results prove that this single-cavity dual-comb Er-fiber laser based on the birefringent crystal and saturable absorber can be a potential source for spectroscopy, optical imaging, absolute distance measurement and other dual-comb applications.

9.
Food Funct ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36648420

RESUMO

Turtle shell as a food residue of Pelodiscus sinensis (a type of edible aquatic animal) is widely used in Traditional Chinese Medicine for hepatic fibrosis therapy. Previous studies have demonstrated that the peptides (<6 kDa) derived from turtle shells are considered effective components. The protein of turtle shells has important potential as a source of bioactive peptides which may play a role as ingredients in functional foods. In the present study, the protein of turtle shell was hydrolyzed using a two-enzyme combination. It was found that the hydrolysates obtained by a combination of pepsin and trypsin showed the highest anti-liver fibrosis activity relative to other combinations in a cell viability assay. The hydrolysates were separated and purified by ultra-filtration (<6 kDa), gel filtration chromatography (GFC) and high-performance liquid chromatography (HPLC). Subsequently, the sequences of purified peptides were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). Molecular docking was used to analyze the interaction of these peptides with the transforming growth factor-ß1 (TGF-ß1) receptor. Two (GPPGVPGPGPL, TSLPVPAPV) of these novel peptides displayed lower binding energies to the TGF-ß1 receptor (-8.18 kcal mol-1, -8 kcal mol-1). Finally, the above two peptides were synthesized chemically and their in vitro anti-liver fibrosis activity was verified by MTT assay. Among them, GPPGVPGPGPL showed a better in vitro anti-liver fibrosis activity (IC50: 80.13 µM). We established a method to obtain anti-liver fibrosis peptides from turtle shells by using bioactivity-guided isolation with molecular docking. Turtle shell protein is an excellent source of anti-liver fibrosis peptides which can offer therapeutic and commercial benefits as an ingredient in functional foods.

10.
Bioresour Technol ; 370: 128573, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36603754

RESUMO

Oleaginous yeasts-derived microbial lipids provide a promising alternative feedstock for the biodiesel industry. However, hyperosmotic stress caused by high sugar concentration during fermentation significantly prevents high cell density and productivity. Isolation of new robust osmophilic oleaginous species from specific environment possibly resolves this issue to some extent. In this study, the cultivable yeast composition of honeycombs was investigated. Totally, 11 species of honeycomb-associated cultivable yeast were identified and characterized. Among them, an osmophilic yeast strain, designated as Rhodotorula toruloides C23 was featured with excellent lipogenic and carotenogenic capacity and remarkable cell growth using glucose, xylose or glycerol as feedstock, with simultaneous production of 24.41 g/L of lipids and 15.50 mg/L of carotenoids from 120 g/L glucose in 6.7-L fermentation. Comparative transcriptomic analysis showed that C23 had evolved a dedicated molecular regulation mechanism to maintain their high simultaneous accumulation of intracellular lipids and carotenoids and cell growth under high sugar concentration.


Assuntos
Lipídeos , Rhodotorula , Leveduras , Rhodotorula/genética , Carotenoides , Glucose
11.
EMBO Mol Med ; : e16525, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36645044

RESUMO

Iron accumulation causes cell death and disrupts tissue functions, which necessitates chelation therapy to reduce iron overload. However, clinical utilization of deferoxamine (DFO), an iron chelator, has been documented to give rise to systemic adverse effects, including ocular toxicity. This study provided the pathogenic and molecular basis for DFO-related retinopathy and identified retinal pigment epithelium (RPE) as the target tissue in DFO-related retinopathy. Our modeling demonstrated the susceptibility of RPE to DFO compared with the neuroretina. Intriguingly, we established upregulation of hypoxia inducible factor (HIF) 2α and mitochondrial deficit as the most prominent pathogenesis underlying the RPE atrophy. Moreover, suppressing hyperactivity of HIF2α and preserving mitochondrial dysfunction by α-ketoglutarate (AKG) protects the RPE against lesions both in vitro and in vivo. This supported our observation that AKG supplementation alleviates visual impairment in a patient undergoing DFO-chelation therapy. Overall, our study established a significant role of iron deficiency in initiating DFO-related RPE atrophy. Inhibiting HIF2α and rescuing mitochondrial function by AKG protect RPE cells and can potentially ameliorate patients' visual function.

12.
Theranostics ; 13(2): 849-866, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632224

RESUMO

Background: Increasing evidence suggests that acute traumatic spinal cord injury (SCI)-induced defects in autophagy and autophagy-lysosomal pathway (ALP) may contribute to endothelial barrier disruption following injury. Recently, Kruppel-like factor 2 (KLF2) was reported as a key molecular switch on regulating autophagy. Whether KLF2 coordinates endothelial endothelial ALP in SCI is not known. Methods: Genetic manipulations of KLF2 were performed in bEnd.3 cells and SCI model. Western blot, qRT-PCR, immunofluorescence staining and Lyso-Tracker Red staining, Evans blue dye extravasation, behavioral assessment via Basso mouse scale (BMS), electrophysiology and footprint analysis were performed. Results: In SCI, autophagy flux disruption in endothelial cells contributes to TJ proteins degradation, leading to blood-spinal cord barrier (BSCB) impairment. Furthermore, the KLF2 level was decreased in SCI, overexpression of which alleviated TJ proteins loss and BSCB damage, which improve motor function recovery in SCI mice, while knockdown of KLF2 displayed the opposite effects. At the molecular level, KLF2 overexpression alleviated the TJ proteins degradation and the endothelial permeability by tuning the ALP dysfunction caused by SCI and oxygen glucose deprivation (OGD). Conclusions: Endothelial KLF2 as one of the key contributors to SCI-mediated ALP dysfunction and BSCB disruption. KLF2 could be a promising pharmacological target for the management and treatment of SCI.


Assuntos
Células Endoteliais , Traumatismos da Medula Espinal , Ratos , Camundongos , Animais , Células Endoteliais/metabolismo , Recuperação de Função Fisiológica , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Barreira Hematoencefálica/metabolismo , Fatores de Transcrição/metabolismo , Autofagia , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo
13.
BMC Neurol ; 23(1): 17, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639743

RESUMO

BACKGROUND: Tropomyosin 4 (TPM4), a member of the tropomyosin family, is aberrantly expressed and plays an important role in a variety of cancers. However, studies on TPM4 in glioma patients are currently lacking. OBJECTIVE: Our study aimed to evaluate the diagnostic and prognostic characteristics of TPM4 in glioma and its correlation with immune infiltration. METHODS: Bioinformatic analysis was performed to determine whether TPM4 has diagnostic and prognostic value for glioma. The following databases and analytical tools were used to explore the clinical significance of TPM4 in glioma: TCGA, GTEx, GEO, STRING, and TISIDB. RESULTS: Our study showed that the mRNA and protein expression levels of TPM4 were significantly higher in glioma than in healthy brain tissue. Kaplan-Meier analysis indicated that high expression of TPM4 in glioma correlated with poor prognosis. Univariate Cox analysis indicated that the high expression level of TPM4 in glioma was an independent prognostic characteristic for low overall survival (OS). The areas under the 1-year survival ROC, 2-year survival ROC, and 3-year survival ROC were all greater than 0.8. GO and KEGG enrichment analysis and GSEA showed that humoral immune response and cytokine receptor interaction were significantly enriched in the TPM4 high expression group, where M phase of the cell cycle, neutrophil degranulation, signaling by interleukins, and signaling by rho GTPases were significantly enriched. Furthermore, according to the analysis of immune cell infiltration, TPM4 was associated with tumor infiltration of a variety of immune cells. CONCLUSIONS: In conclusion, our study suggests that TPM4 may be an effective prognostic biomarker for glioma patients, providing new ideas and research directions for glioma research.


Assuntos
Glioma , Tropomiosina , Humanos , Tropomiosina/genética , Glioma/genética , Prognóstico , Encéfalo
14.
Nat Cell Biol ; 25(1): 159-169, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36635501

RESUMO

Oncogenic KRAS mutations occur in approximately 30% of lung adenocarcinoma. Despite several decades of effort, oncogenic KRAS-driven lung cancer remains difficult to treat, and our understanding of the regulators of RAS signalling is incomplete. Here to uncover the impact of diverse KRAS-interacting proteins on lung cancer growth, we combined multiplexed somatic CRISPR/Cas9-based genome editing in genetically engineered mouse models with tumour barcoding and high-throughput barcode sequencing. Through a series of CRISPR/Cas9 screens in autochthonous lung cancer models, we show that HRAS and NRAS are suppressors of KRASG12D-driven tumour growth in vivo and confirm these effects in oncogenic KRAS-driven human lung cancer cell lines. Mechanistically, RAS paralogues interact with oncogenic KRAS, suppress KRAS-KRAS interactions, and reduce downstream ERK signalling. Furthermore, HRAS and NRAS mutations identified in oncogenic KRAS-driven human tumours partially abolished this effect. By comparing the tumour-suppressive effects of HRAS and NRAS in oncogenic KRAS- and oncogenic BRAF-driven lung cancer models, we confirm that RAS paralogues are specific suppressors of KRAS-driven lung cancer in vivo. Our study outlines a technological avenue to uncover positive and negative regulators of oncogenic KRAS-driven cancer in a multiplexed manner in vivo and highlights the role RAS paralogue imbalance in oncogenic KRAS-driven lung cancer.


Assuntos
Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Camundongos , Animais , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transformação Celular Neoplásica/metabolismo , Transdução de Sinais/genética , Neoplasias Pulmonares/genética , Genes ras , Mutação , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-36689163

RESUMO

In this work, Monascus fermentation and cellulase hydrolysis (MCF) of oats (Avena sativa L.) to release and convert phenolic fraction was investigated. Results showed the fungus Monascus grew well with a biomass of 27.03 mg/g glucosamine equivalent in MCF, following the destruction of oat cellular structures. SDS-PAGE revealed lots of enzymes were regulated with the α-amylase and FPase activity achieved 139.25 U/g and 1.84 U/g in MCF, respectively. Compared with unfermented oats, content of the total phenolic fractions was increased by 19.2 times in MCF, suggesting a phenolic release process occurred during fermentation. Moreover, the soluble-free chlorogenic acid upregulated to 510.00 mg/kg whereas the insoluble-bound ferulic acid downregulated to 193.36 mg/kg in MCF, indicating a transformation process of chlorogenic acid from ferulic acid in oats was enhanced. Based on this, a possible pathway of phenolic release and conversion in oats during fermentation with Monascus spp. was revealed. This study was helpful to enrich the theory of microbial metabolism and transformation in grain materials.

16.
ACS Omega ; 8(1): 1191-1205, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36643522

RESUMO

The paper elaborates the effects of ionic liquids (ILs) on the phase equilibrium temperature, induction time, gas consumption, gas consumption rate, and water to hydrate conversion in the presence of 0.25, 0.63, 0.95, 1.25, 3.75, 6.25, and 10.00 wt % ethyltributylphosphonium hexafluorophosphate ([P2 4 4 4][PF6]), tributylhexylphosphonium hexafluorophosphate ([P6 4 4 4][PF6]), tetraethylammonium bromide ([N2 2 2 2]Br), tetraethylammonium bistrifluoromethanesulfonimide ([N2 2 2 2][NTf2]), and tetraethylammonium hexafluorophosphate ([N2 2 2 2][PF6]) under a pressure of 2 MPa. The results indicate that all five ILs could increase CO2 consumption and enhance the water to hydrate conversion. Compared with the pure water system, [P2 4 4 4][PF6] and [P6 4 4 4][PF6] shifted the phase equilibrium temperature of CO2 hydrates to a slightly higher temperature with reduced induction times by boosting CO2 hydrate nucleation, showing the dual function promotion effects. In contrast, [N2 2 2 2]Br, [N2 2 2 2][NTf2], and [N2 2 2 2][PF6] shifted the phase equilibrium temperature of CO2 hydrates to a lower temperature and prolonged the induction time by slowing down CO2 hydrate nucleation. The inhibition effects of anions on CO2 hydrates follow an order of Br- > [NTf2]- > [PF6]-. Besides, the density functional theory and molecular dynamic calculations were conducted to explain the inconsistent influences of [N2 2 2 2]Br and [N4 4 4 4]Br on CO2 hydrate formation. It was found that the anion-cation interaction of [N2 2 2 2]Br was stronger than that of [N4 4 4 4]Br, and Br- in [N2 2 2 2]Br is less likely to participate in the formation of hydrate cages in the [N2 2 2 2]Br + H2O + CO2 system according to the intermolecular anion-water, anion-CO2, and water-water radial distribution function in [N2 2 2 2]Br + H2O + CO2 and [N4 4 4 4]Br + H2O + CO2 systems.

17.
Therap Adv Gastroenterol ; 16: 17562848221147756, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36644129

RESUMO

Background and objective: Recently, a large number of trials on proton pump inhibitor-amoxicillin-containing high-dose dual therapy (HDDT) versus bismuth-containing quadruple therapy (BQT) for Helicobacter pylori (H. pylori) eradication have been published with controversial and inconsistent conclusions. The aim of this meta-analysis was to determine the effects of HDDT for H. pylori eradication compared to BQT. Design: A systematic review and meta-analysis was conducted. Methods: PubMed, Embase, and the Cochrane library database were searched to collect all randomized controlled trials (RCTs) assessing the effects of HDDT versus BQT to H. pylori eradication from inception to September 2022. Meta-analysis was conducted to estimate the pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effects model. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis (TSA) was performed to determine the reliability and conclusiveness. Results: A total of 14 RCTs with 5121 patients were included. The results of meta-analysis showed that there was no statistical significance in the eradication rate between HDDT and BQT (intention-to-treat analysis: 86.7% versus 85.1%, RR = 1.01, 95% CI: 0.98-1.04; per-protocol analysis: 89.9% versus 89.4%, RR = 1.01, 95% CI: 0.98-1.03; moderate-quality evidence). The incidence of total adverse effects in HDDT group was significantly lower than in BQT group (5.9% versus 34.1%, RR = 0.42, 95% CI: 0.34-0.50; low-quality evidence). No statistical significance was observed in compliance between HDDT and BQT (RR = 1.01, 95% CI, 1.00-1.03, p = 0.07; low-quality evidence). The TSA result for H. pylori eradication rate indicated that the effect was conclusive. Conclusions: Evidence from our updated meta-analysis suggests that HDDT is as effective as BQT in eradicating H. pylori, with fewer adverse effects and similar compliance. Registration: Open Science Framework registries (No: osf.io/th4vd).

18.
J Clin Neurosci ; 108: 13-18, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36565522

RESUMO

BACKGROUND: The neutrophil/lymphocyte ratio (NLR) has been considered a prognostic indicator for determining the systemic inflammatory response and atherosclerosis. We aimed to determine the relationship between NLR and the development of cerebral collateral circulation in patients with symptomatic severe stenosis or occlusion of intracranial arteries. METHODS: All patients underwent digital subtraction angiography (DSA) within 14 days of admission and were divided into a group with good collateral circulation (77 patients) and a group with poor collateral circulation (86 patients) according to the DSA collateral compensation grading method. Apo B, total cholesterol, LDL, and Neutrophil count in the poor side branch group were significantly higher than in the good side branch group. Multifactorial analysis showed that high NLR levels were a valid predictor of poor collateral circulation in patients with symptomatic severe intracranial artery stenosis or occlusion. Spearman correlation analysis showed that the size of the collateral branch score was negatively correlated with NLR (r = -0.509, P < 0.001) and cholesterol content (r = -0.249, P = 0.002). NLR predicted poor collateral circulation with an AUC of 0.620 (sensitivity 66.7 %, specificity 61.3 %, 95 % CI = 0.517-0.723,P < 0.05). CONCLUSION: We demonstrate a correlation between NLR levels and the development of collateral circulation in the brain in patients with symptomatic severe stenosis or occlusion of the intracranial arteries.


Assuntos
Estenose das Carótidas , Neutrófilos , Humanos , Constrição Patológica/diagnóstico por imagem , Circulação Colateral/fisiologia , Linfócitos , Artérias , Circulação Cerebrovascular/fisiologia
19.
ACS Nano ; 17(1): 437-452, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36534945

RESUMO

In tumor nanovaccines, nanocarriers enhance the delivery of tumor antigens to antigen-presenting cells (APCs), thereby ensuring the robust activation of tumor antigen-specific effector T-cells to kill tumor cells. Through employment of their high immunogenicity and nanosize, we have developed a "Plug-and-Display" delivery platform on the basis of bacterial outer membrane vesicles (OMVs) for tumor nanovaccines (NanoVac), which can rapidly display different tumor antigens and efficiently eliminate lung metastases of melanoma. In this study, we first upgraded the NanoVac to increase their antigen display efficiency. However, we found that the presence of a subcutaneous xenograft seriously hampered the efficiency of NanoVac to eliminate lung metastases, with the subcutaneous xenograft mimicking the primary tumor burden in clinical practice. The primary tumor secreted significant amounts of granulocyte colony-stimulating factor (G-CSF) and altered the epigenetic features of granulocyte monocyte precursor cells (GMPs) in the bone marrow, thus disrupting systemic immunity, particularly the function of APCs, and ultimately resulting in NanoVac failure to affect metastases. These changes in the systemic immune macroenvironment were plastic, and debulking surgery of primary tumor resection reversed the dysfunction of APCs and failure of NanoVac. These results demonstrate that, in addition to the formulation design of the tumor nanovaccines themselves, the systemic immune macroenvironment incapacitated by tumor development is another key factor that cannot be ignored to affect the efficiency of tumor nanovaccines, and the combination of primary tumor resection with NanoVac is a promising radical treatment for widely metastatic tumors.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Pulmonares , Humanos , Células Apresentadoras de Antígenos , Linfócitos T , Antígenos de Neoplasias
20.
Bioorg Chem ; 131: 106305, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36495679

RESUMO

Phytochemical investigation on the rhizomes of Paris fargesii var. petiolata (Baker ex C. H. Wright) Wang et Tang led to the isolation of five previously undescribed steroidal saponins, parpetiosides A-E (1-5), and six known analogs (6-11). Their structures were established by extensive spectroscopic data analysis and chemical methods. Compound 5 was a rare steroidal saponin with disaccharide moiety linked at C-26 of dehydrokryptogenin that was hardly seen in the genus Paris. The cytotoxicities of the isolated compounds against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated, and compound 1 displayed certain inhibitory effect with IC50 values of 8.02 ± 0.45, 8.24 ± 0.57 and 6.20 ± 0.79 µM, respectively. Moreover, the preliminary mechanism of 1 inhibiting the proliferation of the three cancer cell lines might be related to cell cycle distribution and the induction of S phase arrest.


Assuntos
Antineoplásicos , Liliaceae , Neoplasias , Saponinas , Humanos , Rizoma/química , Antineoplásicos/farmacologia , Antineoplásicos/análise , Liliaceae/química , Esteroides/farmacologia , Esteroides/química , Saponinas/farmacologia , Saponinas/química
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