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1.
PLoS Biol ; 22(5): e3002628, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38814940

RESUMO

The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria.


Assuntos
Trifosfato de Adenosina , Divisão Celular , Proteínas de Escherichia coli , Escherichia coli , Peptidoglicano , Peptidoglicano/metabolismo , Hidrólise , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Escherichia coli/genética , Trifosfato de Adenosina/metabolismo , Microscopia Crioeletrônica , Parede Celular/metabolismo , Conformação Proteica , Modelos Moleculares , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , N-Acetil-Muramil-L-Alanina Amidase/genética , Proteínas da Membrana Bacteriana Externa , Transportadores de Cassetes de Ligação de ATP , Regulador de Condutância Transmembrana em Fibrose Cística , Lipoproteínas , Proteínas de Ciclo Celular
2.
Immunol Invest ; 53(4): 559-573, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38329469

RESUMO

OBJECTIVE: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a form of SLE associated with severe NP syndromes causing mortality and morbidity. Respecting the fundamental of BAFF in NPSLE pathophysiology, we investigated its clinical value. METHODS: Totally 105 NPSLE and 101 SLE cases without NPSLE (non-NPSLE, control) were included. Serum BAFF/TNF-α/IL-6/IL-10 levels were measured using ELISA kits. T lymphocytes were detected by flow cytometry. The independent influencing factors for NPSLE, and the auxiliary diagnostic efficacy and the ability of BAFF levels to predict adverse prognosis of NPSLE patients were analyzed by multiple factor logistic regression, and ROC curve and survival curve. RESULTS: In NPSLE patients, serum BAFF level was increased and positively correlated with SLEDAI-2k, serum proinflammatory cytokines, while negatively correlated with CD4+T/CD8+T cells, and anti-inflammatory cytokine. High serum BAFF protein level was associated with a higher risk of developing NPSLE. The AUC of serum BAFF > 301.7 assisting in NPSLE diagnosis was 0.8196. Furthermore, high levels of serum BAFF were associated with a higher risk of adverse outcomes in NPSLE patients. . CONCLUSION: Serum BAFF level in NPSLE patients was correlated with lymphocytes and high serum BAFF protein level could assist in diagnosis and to predict adverse outcomes in NPSLE patients.


Assuntos
Fator Ativador de Células B , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Humanos , Fator Ativador de Células B/sangue , Feminino , Masculino , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Adulto , Pessoa de Meia-Idade , Biomarcadores/sangue , Prognóstico , Citocinas/sangue , Inflamação/sangue , Inflamação/imunologia , Inflamação/diagnóstico , Adulto Jovem
3.
J Asthma ; 61(9): 1089-1102, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38478043

RESUMO

Objective: In a previous study we have shown that, in the presence of interleukin (IL)-33, repeated, per-nasal challenge of murine airways with Streptococcus pneumoniae (S. pneumoniae) organisms induces human asthma-like airways inflammation. It is not clear, however, whether this effect is unique or manifest in response to other common respiratory pathogens.Methods: To explore this, airways of BALB/c mice were repeatedly challenged per-nasally with formaldehyde-inactivated bacterial bodies in the presence or absence of murine recombinant IL-33. Serum concentrations of S.pneumoniae, Moraxella catarrhalis (M.catarrhalis) and Haemophilus influenzae (H.influenzae) lysates-specific IgE were measured in patients with asthma and control subjects.Results: We showed that in the presence of IL-33, repeated, per-nasal airways exposure to the bodies of these bacteria induced airways hyperresponsiveness (AHR) in the experimental mice. This was accompanied by cellular infiltration into bronchoalveolar lavage fluid (BALF), eosinophilic infiltration and mucous hypertrophy of the lung tissue, with elevated local expression of some type 2 cytokines and elevated, specific IgG and IgE in the serum. The precise characteristics of the inflammation evoked by exposure to each bacterial species were distinguishable.Conclusions: These results suggest that in the certain circumstances, inhaled or commensal bacterial body antigens of both Gram-positive (S. pneumoniae) and Gram-negative (M. catarrhalis and H. influenzae) respiratory tract bacteria may initiate type 2 inflammation typical of asthma in the airways. In addition, we demonstrated that human asthmatic patients manifest elevated serum concentrations of M.catarrhalis- and H.influenzae-specific IgE.


Assuntos
Antígenos de Bactérias , Asma , Haemophilus influenzae , Imunoglobulina E , Camundongos Endogâmicos BALB C , Streptococcus pneumoniae , Asma/imunologia , Asma/microbiologia , Animais , Camundongos , Streptococcus pneumoniae/imunologia , Haemophilus influenzae/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Humanos , Antígenos de Bactérias/imunologia , Feminino , Moraxella catarrhalis/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Masculino , Interleucina-33/imunologia , Interleucinas/imunologia , Interleucinas/sangue , Adulto , Pessoa de Meia-Idade
4.
Pacing Clin Electrophysiol ; 47(4): 564-567, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37428888

RESUMO

An 83-year-old Chinese man presented with a huge left chest wall hematoma and hemorrhagic shock 4 months after permanent pacemaker implantation. Computed Tomography of Angiogram of the left subclavian artery revealed a pseudoaneurysm. He underwent radiologically guided stenting followed by hematoma clearance. It is rare to have delayed formation of pseudoaneurysm at 4 months post pacemaker implantation. Radiologically guided stenting is the preferred treatment, followed by hematoma clearance. It is strongly advised against blind surgery for wound debridement or bleeding detection. Familiarizing with axillary vein anatomy, improving axillary vein cannulation skills, and detecting early complications of artery injury are key strategies in preventing pseudoaneurysm formation post pacemaker implantation.


Assuntos
Falso Aneurisma , Marca-Passo Artificial , Parede Torácica , Masculino , Humanos , Idoso de 80 Anos ou mais , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/terapia , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Artéria Subclávia , Marca-Passo Artificial/efeitos adversos
5.
Nutr Metab Cardiovasc Dis ; 34(2): 515-520, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38161112

RESUMO

BACKGROUND AND AIMS: Increasing numbers of studies have sought to uncover the relationship between serum uric acid (UA) levels and the risk of aortic aneurysm (AA) or aortic dissection (AD), but the causality of the associations has not been established yet. To assess this potential relationship, we conducted a two-sample Mendelian randomization (MR) analysis. METHODS AND RESULTS: We performed two-sample Mendelian randomization (MR) analysis using independent genetic variants for UA levels from a published genome-wide association study (GWAS). Summary statistics for instrument-outcome associations from FinnGen database for AA and AD. Various sensitivity analyses were performed using different MR methods including random effects inverse variance weighting, fix effects inverse variance weighting, MR-Egger, weighted median/mode, and the contamination mixture method. Genetically predicted UA levels was associated with a higher AA risk (odds ratio (OR), 1.223; 95 % confidence interval (CI), 1.058-1.388; p = 0.017) in a simple size of 209,366 individuals. No association was found between uric acid levels and the risk of AD (OR,0.812; 95 % CI, 0.423-1.200; p = 0.293). CONCLUSION: Our study suggests a significant and robust causal association between UA levels and risk of AA but did not support such a relationship between UA levels and AD risk, which might be interpreted with caution and further confirmed. These findings support a clinically relevant causal effect of serum urate levels on the risk of AA.


Assuntos
Aneurisma Aórtico , Dissecção Aórtica , Humanos , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/epidemiologia , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Ácido Úrico
6.
Cell Mol Biol Lett ; 29(1): 47, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589823

RESUMO

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in vascular smooth muscle cell (VSMC) phenotypic switching, which is an early pathogenic event in various vascular remodeling diseases (VRDs). However, the underlying mechanism is not fully understood. METHODS: An IP‒LC‒MS/MS assay was conducted to identify new binding partners of G6PD involved in the regulation of VSMC phenotypic switching under platelet-derived growth factor-BB (PDGF-BB) stimulation. Co-IP, GST pull-down, and immunofluorescence colocalization were employed to clarify the interaction between G6PD and voltage-dependent anion-selective channel protein 1 (VDAC1). The molecular mechanisms involved were elucidated by examining the interaction between VDAC1 and apoptosis-related biomarkers, as well as the oligomerization state of VDAC1. RESULTS: The G6PD level was significantly elevated and positively correlated with the synthetic characteristics of VSMCs induced by PDGF-BB. We identified VDAC1 as a novel G6PD-interacting molecule essential for apoptosis. Specifically, the G6PD-NTD region was found to predominantly contribute to this interaction. G6PD promotes VSMC survival and accelerates vascular neointimal hyperplasia by inhibiting VSMC apoptosis. Mechanistically, G6PD interacts with VDAC1 upon stimulation with PDGF-BB. By competing with Bax for VDAC1 binding, G6PD reduces VDAC1 oligomerization and counteracts VDAC1-Bax-mediated apoptosis, thereby accelerating neointimal hyperplasia. CONCLUSION: Our study showed that the G6PD-VDAC1-Bax axis is a vital switch in VSMC apoptosis and is essential for VSMC phenotypic switching and neointimal hyperplasia, providing mechanistic insight into early VRDs.


Assuntos
Glucosefosfato Desidrogenase , Músculo Liso Vascular , Canal de Ânion 1 Dependente de Voltagem , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Becaplermina/genética , Becaplermina/metabolismo , Proliferação de Células , Proteína X Associada a bcl-2/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Músculo Liso Vascular/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Neointima/genética , Neointima/metabolismo , Neointima/patologia , Apoptose , Miócitos de Músculo Liso/metabolismo , Movimento Celular/genética , Células Cultivadas , Fenótipo
7.
Ren Fail ; 46(2): 2387205, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39120130

RESUMO

BACKGROUND: To compare the impact of tunneled cuffed catheters (TCCs) and arteriovenous fistulas (AVFs) on outcomes in elderly hemodialysis (HD) patients. METHODS: A retrospective matched cohort study was performed. Propensity score matching (PSM) was applied to balance the baseline conditions, and we compared all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCEs), hospitalization, and infection rates between AVF and TCC patients ≥70 years old. Cox survival analysis was used to analyze the risk factors for death. RESULTS: There were 2119 patients from our center in the Chinese National Renal Data System (CNRDS) between 1 January 2010 and 10 October 2023. Among these patients, 77 TCC patients were matched with 77 AVF patients. There was no significant difference in all-cause mortality between the TCC and AVF groups (30.1/100 vs. 33.3/100 patient-years, p = 0.124). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank p = 0.242). The TCC group had higher rates of MACCEs, hospitalization, and infection than the AVF group (33.7/100 vs. 29.5/100 patient-years, 101.2/100 vs. 79.5/100 patient-years, and 30.1/100 vs. 14.1/100 patient-years, respectively). Multivariate analysis showed that high Charlson comorbidity index (CCI) score was a risk factor for death. CONCLUSIONS: There was no significant difference in all-cause mortality between elderly HD patients receiving TCCs and AVFs. Compared with those with a TCC, elderly HD patients with an AVF have a lower risk of MACCEs, hospitalization, and infection.


Assuntos
Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica , Pontuação de Propensão , Diálise Renal , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Fatores de Risco , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Idoso de 80 Anos ou mais , Hospitalização/estatística & dados numéricos , China/epidemiologia , Prognóstico , Estimativa de Kaplan-Meier
8.
J Sci Food Agric ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38877788

RESUMO

This overview summarizes the latest research progress on the aroma absorption mechanism and aroma fixation pathway of jasmine green tea, and discusses in depth the aroma absorption mechanism of green tea, the aroma release mechanism of jasmine flowers, as well as the absorption and fixation mechanism of the aroma components of jasmine green tea in the process of scenting, to provide a theoretical basis for the improvement of the quality of jasmine green tea and the innovation of processing technology. It was found that the aroma absorption mechanism of jasmine green tea is mainly associated with both physical and chemical adsorption, aroma release in jasmine involves the phenylpropanoid/benzoin biosynthetic pathway, ß-glycosidase enzymes interpreting putative glycosidic groups, and heat shock proteins (HSPs) as molecular chaperones to prevent stress damage in postharvest flowers due to high temperatures and to promote the release of aroma components, and so forth. The preparation of aroma-protein nano-complexes, heat stress microcapsules, and the spraying of polymeric substances - ß-cyclodextrin are three examples of aroma-fixing pathways. This overview also summarizes the problems and future development trends of the current research and proposes the method of loading benzyl acetate, the main aroma component of jasmine, through konjac glucomannan (KGM)-based gel to solve the problem of volatile aroma and difficult-to-fix aroma, which provides a reference for the sustainable development of the jasmine green tea industry. © 2024 Society of Chemical Industry.

9.
J Sci Food Agric ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39032018

RESUMO

BACKGROUND: To produce jasmine tea of excellent quality, it is crucial to select jasmine flowers at their optimal growth stage during harvesting. However, achieving this goal remains a challenge due to environmental and manual factors. This study addresses this issue by classifying different jasmine flowers based on visual attributes using the YOLOv7 algorithm, one of the most advanced algorithms in convolutional neural networks. RESULTS: The mean average precision (mAP value) for detecting jasmine flowers using this model is 0.948, and the accuracy for five different degrees of openness of jasmine flowers, namely small buds, buds, half-open, full-open and wiltered, is 87.7%, 90.3%, 89%, 93.9% and 86.4%, respectively. Meanwhile, other ways of processing the images in the dataset, such as blurring and changing the brightness, also increased the credibility of the algorithm. CONCLUSION: This study shows that it is feasible to use deep learning algorithms for distinguishing jasmine flowers at different growth stages. This study can provide a reference for jasmine production estimation and for the development of intelligent and precise flower-picking applications to reduce flower waste and production costs. © 2024 Society of Chemical Industry.

10.
Angew Chem Int Ed Engl ; : e202410557, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38932706

RESUMO

The performance and stability of organic metal halide perovskite (OMHP) optoelectronic devices have been associated with ion migration. Understanding of nanoscale resolved organic cation migration mechanism would facilitate structure engineering and commercialization of OMHP. Here, we report a three-dimensional approach for in situ nanoscale infrared imaging of organic ion migration behavior in OMHPs, enabling to distinguish migrations along grain boundary and in crystal lattice. Our results reveal that organic cation migration along OMHP film surface and grain boundaries (GBs) occurs at lower biases than in crystal lattice. We visualize the transition of organic cation migration channels from GBs to volume upon increasing electric field. The temporal resolved results demonstrate the fast MA+ migration kinetics at GBs, which is comparable to diffusivity of halide ions. Our findings help understand the role of organic cations in the performance of OMHP devices, and the proposed approach holds broad applicability for revealing migration mechanisms of organic ions in OMHPs based optoelectronic devices.

11.
BMC Nephrol ; 24(1): 313, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884871

RESUMO

BACKGROUND: Studies comparing the survival of hemodialysis (HD) and peritoneal dialysis (PD) patients are controversial. This study evaluated the impact of initial dialysis modality on the survival of patients with end-stage renal disease (ESRD) in a matched-pair cohort. METHODS: A retrospective cohort study was performed on ESRD patients who initiated renal replacement treatment between January 1, 2010, and December 31, 2018. Propensity score matching was applied to balance the baseline conditions, and multivariate Cox regression analysis was applied to compare mortality between HD and PD patients and evaluate correlations between mortality and various baseline characteristics. Subgroup analysis was performed with respect to diabetes status. RESULTS: There were 739 patients in our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2018. Of these, 125 PD patients were matched with 125 HD patients. The 1-, 2-, and 3-year survival rates were 96.5%, 90.7%, and 82.5%, respectively, in the HD group and 99.5%, 97.8%, and 92.5%, respectively, in the PD group (log-rank P < 0.001). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank P = 0.514). Age at dialysis initiation, CCI, congestive heart failure and cerebrovascular disease were risk factors in the multivariable-adjusted model. In subgroups defined by diabetes status, the Kaplan‒Meier survival curve showed that PD survival was significantly higher than that of HD (log-rank P = 0.022). CONCLUSIONS: HD and PD were not significantly different regarding the survival of patients with ESRD. PD was associated with better survival in diabetic ESRD patients.


Assuntos
Diabetes Mellitus , Falência Renal Crônica , Humanos , Diálise Renal , Estudos Retrospectivos , Pontuação de Propensão , Falência Renal Crônica/complicações , Fatores de Risco , Modelos de Riscos Proporcionais
12.
Clin Exp Hypertens ; 45(1): 2272581, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37902269

RESUMO

BACKGROUND: The triglyceride and glucose (TyG) index has been found to be significantly associated with a higher risk of mortality. However, there has been a lack of studies exploring the specific relationship between the TyG index and all-cause and cardiovascular mortality among middle-aged and elderly with hypertension. METHODS: A total of 3,614 participants with hypertension were enrolled from the National Health and Nutrition Examination Survey. The TyG index was calculated using the formula log [fasting triglycerides (mg/dL) x fasting glucose (mg/dL)/2]. The Cox proportional hazard ratios were used to evaluate the association between the TyG index and the risk of mortality. RESULTS: Over a follow-up period of 7.87 years, 991 all-cause death and 189 cardiovascular deaths occurred. Compared with the reference quartile, the multivariate-adjusted hazard ratios and 95% confidence intervals were 1.28 (1.07-1.53; p = .006) in the fourth quartile for all-cause mortality and 0.63 (0.42-0.96; p = .031) in the second quartile for cardiovascular mortality. Dose-response analysis indicated an L-shaped relationship. CONCLUSIONS: The TyG index exhibited an L-shaped association with the risk of all-cause mortality among middle-aged and elderly with hypertension.


Assuntos
Glucose , Hipertensão , Idoso , Pessoa de Meia-Idade , Humanos , Seguimentos , Fatores de Risco , Glicemia , Triglicerídeos , Inquéritos Nutricionais , Biomarcadores , Medição de Risco
13.
J Sci Food Agric ; 103(11): 5261-5269, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37005375

RESUMO

BACKGROUND: The high viscosity of konjac glumannan (KGM) limits its application in meat processing. In this work, the effects of konjac oligo-glucomannan (KOG), as a derivative of KGM, on the emulsifying properties of myofibrillar protein (MP) and the related mechanism were investigated. RESULTS: It was found that the addition of KOG had no significant effect on the secondary structure of MP, but altered the tertiary conformation of MP, resulting in exposure of tyrosine residues to polar microenvironments and decreased intrinsic fluorescence intensity. In addition, the addition of KOG increased the emulsifying activity of MP, resulting in decreased particle size and improved physical stability of the emulsion. The emulsifying activity of MP reached the maximum value when 1.0 wt% KOG was added. Moreover, the interfacial tension and interfacially adsorbed protein content of MP/KOG emulsions decreased with the increase in KOG concentration. CONCLUSION: These findings demonstrated that KOG mainly interacted with MP and changed the amphipathy of the KOG-MP at the oil-water interface, forming a stable interface film to improve the emulsifying properties of MP. © 2023 Society of Chemical Industry.


Assuntos
Amorphophallus , Amorphophallus/química , Proteínas/química , Reologia/métodos , Emulsões/química , Viscosidade
14.
Cell Immunol ; 376: 104536, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35594699

RESUMO

Respiratory tract infection early in life plays a significant role in the pathogenesis of asthma. In the present study we examine, using a murine surrogate, the effects of early life respiratory infection with Streptococcus pneumoniae (SP) on adult asthma induced by sensitisation and exposure to house dust mite (HDM) allergen. Mice (one week old) were infected with SP, then 3 weeks later sensitised to HDM emulsified with Al (OH)3 intraperitoneally and challenged intranasally with same allergen for up to a further 5 weeks to establish the asthma surrogate. Outcome measures were quantified using the FlexiVent apparatus, histology and immunohistology, ELISA and flow cytometry. The murine surrogates of asthma infected with SP early in life exhibited significantly more severe disease compared with the controls of mice without SP infection, as shown by airways responsiveness, inflammatory cellular infiltration of the airways, expression of markers of airways remodelling, serum concentrations of HDM-specific IgE and the concentrations of Th2-type cytokines and the numbers of activated Th2 and ILC2 cells in the lung tissues. These data are compatible with the hypothesis that early-life infection of the airways with SP exacerbates, at least in some individuals, subsequent HDM-induced allergic airways inflammation and associated asthma in adulthood in this murine surrogate.


Assuntos
Asma , Pyroglyphidae , Alérgenos , Animais , Antígenos de Dermatophagoides , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Imunidade Inata , Pulmão , Linfócitos/metabolismo , Camundongos , Streptococcus pneumoniae/metabolismo , Células Th2
15.
J Sep Sci ; 45(15): 2914-2923, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35689602

RESUMO

Dihydromethysticin, a natural component from Piper methysticum Forst, has been reported to display pharmacological effects in mental disorders and some malignant tumors. However, the metabolism of this component remained unknown. The goal of this work was conducted to discover the metabolic profiles of dihydromethysticin. The in vitro incubation was performed by incubating dihydromethysticin with rat, monkey, and human liver microsomes and hepatocytes. An analytical assay of ultra-high performance liquid chromatography combined with Orbitrap high-resolution mass spectrometry was utilized to detect and identify the metabolites. With high resolution mass spectrometric determination, the accurate mass, elemental composition, and product ions of the metabolites were determined, which enabled structural characterization to become easy. Under the present conditions, four phase-I metabolites, as well as six phase-II metabolites, were detected and their tentative structures were characterized by mass spectra. M4 was found as the most abundant metabolite both in liver microsomes and hepatocytes. Cytochrome P450 1A2, 2C9, and 3A4 contributed to the formation of this metabolite by using human recombinant P450 enzymes. M4 can be oxidized into reactive ortho-quinone intermediate followed by conjugating with glutathione. M4 was also subject to glucuronidation (M1 and M2) and methylation (M5). Demethylenation, oxidation, hydroxylation, glucuronidation, glutathionylation, and methylation were the primary metabolic pathways of dihydromethysticin. This study provides in vitro metabolism data of dihydromethysticin, which is indispensable for understanding the disposition of this compound.


Assuntos
Pironas , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Microssomos Hepáticos/metabolismo , Ratos , Espectrometria de Massas em Tandem/métodos
16.
Proc Natl Acad Sci U S A ; 116(26): 12678-12683, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31189597

RESUMO

Heterogeneous bubble nucleation is one of the most fundamental interfacial processes that has received broad interest from diverse fields of physics and chemistry. While most studies focused on large microbubbles, here we employed a surface plasmon resonance microscopy to measure the nucleation rate constant and activation energy barrier of single nanosized embryo vapor bubbles upon heating a flat gold film with a focused laser beam. Image analysis allowed for simultaneously determining the local temperature and local nucleation rate constant from the same batch of optical images. By analyzing the dependence of nucleation rate constant on temperature, we were able to calculate the local activation energy barrier within a submicrometer spot. Scanning the substrate further led to a nucleation rate map with a spatial resolution of 100 nm, which revealed no correlation with the local roughness. These results indicate that facet structure and surface chemistry, rather than geometrical roughness, regulated the activation energy barrier for heterogeneous nucleation of embryo nanobubbles.

17.
Ren Fail ; 44(1): 1160-1168, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35880645

RESUMO

BACKGROUND: Parathyroidectomy (PTX) is a treatment for hyperparathyroidism (HPT) and has uncertain risks and benefits. The aim of this study was to evaluate the effect of PTX versus nonoperative treatment among nondiabetic hemodialysis patients. METHODS: A retrospective matched cohort study was performed. Each PTX patient was matched with one patient who had severe HPT but rejected PTX. The patients were matched by sex, birth date, date of first dialysis, nondiabetic status, and left ventricular ejection fraction. The serum markers, survival, main adverse cardiovascular and cerebrovascular event (MACCE) rates, and hospitalization were compared between the PTX patients and matched non-PTX patients. RESULTS: There were 1143 patients at our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2020. Of these, 75 PTX patients were matched with 75 non-PTX patients. Rapid decreases in the mean intact parathyroid hormone, calcium and phosphorus concentrations, and a gradual increase in hemoglobin concentration were observed in the PTX group. The mortality was 2.9 per 100 patient-years in the PTX group and 10.9 per 100 patient-years in the non-PTX group (p < 0.001). Compared with non-PTX patients, PTX patients had an adjusted HR for death of 0.236 (95% CI 0.108-0.518). The cumulative MACCE rates were 6.7 per 100 patient-years in the PTX group and 15.2 per 100 patient-years in the non-PTX group (p < 0.001). The adjusted HR of the occurrence of first MACCE for PTX patients compared with non-PTX patients was 0.524 (95% CI 0.279-0.982). The cumulative hospitalization rates were 50.3 per 100 patient-years in the PTX group and 66.5 per 100 patient-years in the matched non-PTX group (p < 0.001). CONCLUSIONS: Compared with non-PTX patients, PTX was associated with an improvement in the biochemical measures and patient-level outcomes in nondiabetic hemodialysis patients with severe HPT.


Assuntos
Hiperparatireoidismo Secundário , Hiperparatireoidismo , Falência Renal Crônica , Estudos de Coortes , Humanos , Hiperparatireoidismo Secundário/complicações , Hiperparatireoidismo Secundário/cirurgia , Falência Renal Crônica/cirurgia , Falência Renal Crônica/terapia , Hormônio Paratireóideo , Paratireoidectomia , Diálise Renal , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
18.
J Sci Food Agric ; 102(14): 6555-6565, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35587687

RESUMO

BACKGROUND: The stabilization of oil-in-water (O/W) emulsions has long been explored. Assembly of polymer networks is an effective method for stabilizing O/W emulsions. Konjac glucomannan (KGM) is a plant polysaccharide and the network of KGM gel is a good candidate for stabilizing O/W emulsions based on its high viscosity and thickening properties. However, natural KGM has strong hydrophilicity and is not able to offer interfacial activity. Octenyl succinic anhydride (OSA) is a hydrophobic molecule, which is widely used as thickener and stabilizer in food emulsions. In this work, the amphiphilic biopolymer (OSA-KGM) was fabricated by modifying the KGM with OSA. Furthermore, OSA-KGM biopolymer was used to prepare O/W emulsions, which were then freeze-dried and used to prepare oleogels as fat substitute for bakery products. RESULTS: OSA-KGM had advanced hydrophobicity with water contact angle 81.13° and adsorption behavior at the oil-water interface, with interfacial tension decreasing from 18.52 to 13.57 mN m-1 within 1 h. The emulsification of OSA-KGM remarkably improved the stability of emulsions without phase separation during storage for 31 days. Oleogels with OSA-KGM showed good thixotropic and structure recovery properties (approximately 100%) and low oil loss (from 69.5% to 50.4%). Cakes made from oleogels had a softer texture than cakes made from peanut oil and margarine. CONCLUSION: Amphiphilic biopolymer OSA-KGM shows advanced interfacial activity and hydrophobicity. This paper provides an insight into preparing stable O/W emulsions with a new biopolymer and oleogels potentially applied as fat substitute in bakery products. © 2022 Society of Chemical Industry.


Assuntos
Substitutos da Gordura , Anidridos Succínicos , Emulsões/química , Mananas , Margarina , Compostos Orgânicos , Óleo de Amendoim , Polímeros , Água/química
19.
Anal Chem ; 93(24): 8544-8552, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34097376

RESUMO

Bacterial infection is one of the major causes of human death worldwide. To prevent bacterial infectious diseases from spreading, it is of critical importance to develop convenient, ultrasensitive, and cost-efficient methods for bacteria detection. Here, an electrochemical detector of a functional two-dimensional (2D) metal-organic framework (MOF) nanozyme was developed for the sensitive detection of pathogenic Staphylococcus aureus. A dual recognition strategy consisting of vancomycin and anti-S. aureus antibody was proposed to specifically anchor S. aureus. The 2D MOFs with excellent peroxidase-like activity can efficiently catalyze o-phenylenediamine to 2,2-diaminoazobenzene, which is an ideal electrochemical signal readout for monitoring the bacteria concentration. Under optimal conditions, the present bioassay provides a wide detection range of 10-7.5 × 107 colony-forming units CFU/mL with a detection limit of 6 CFU/mL, which is better than most of the previous reports. In addition, the established electrochemical sensor can selectively and accurately identify S. aureus in the presence of other bacteria. The present work provides a new pathway for sensitive and selective detection of S. aureus and presents a promising potential in the realm of clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Infecções Estafilocócicas , Catálise , Técnicas Eletroquímicas , Humanos , Limite de Detecção , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus , Vancomicina
20.
Protein Expr Purif ; 178: 105783, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33122138

RESUMO

Natural killer (NK) cells are potent cytotoxic effector cells of the innate immune system and play an important role in tumor immunosurveillance and control. NKG2D is an activating receptor of NK cells. The NKG2D receptor-ligand system has contributed to immune cells recognizing tumor cells and the tumor microenvironment. In order to stretch the application of NK cells on adoptive immunotherapy for B-cell malignancies, we designed and produced a novel bispecific ULBP1×CD19-scFv fusion protein, in which the extracellular domain of NKG2D ligand ULBP1 was fused to a single chain variable fragment (scFv) of anti-CD19. The vector expressing ULBP1×CD19-scFv protein was constructed and expressed in Pichia pastoris. Effects of medium composition, concentration of methanol as the inducer, induction time and broth content in shake flask on the expression of the recombinant protein were investigated. The results showed that the optimized conditions for ULBP1×CD19-scFv expression were 1% methanol induction for 96 h with 15% broth content. The secreted recombinant protein was purified using ammonium sulfate fractionation and Ni-NTA affinity chromatography and the purity is about 93%. The cytotoxicity of NK92-MI cells against CD19+ Raji cells was enhanced in the presence of purified ULBP1×CD19-scFv protein. These results indicated that ULBP1 could be used as an activating element of bispecific killer engagers (BiKEs) and Pichia pastoris yeast might be an alternative expression host for BiKEs production.


Assuntos
Anticorpos Biespecíficos , Antígenos CD19/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Subfamília K de Receptores Semelhantes a Lectina de Células NK , Anticorpos de Cadeia Única , Anticorpos Biespecíficos/química , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/isolamento & purificação , Células Hep G2 , Humanos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/antagonistas & inibidores , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Proteínas Recombinantes de Fusão , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/isolamento & purificação
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