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1.
Molecules ; 29(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38792114

RESUMO

Flavonoids and stilbenoids, crucial secondary metabolites abundant in plants and fungi, display diverse biological and pharmaceutical activities, including potent antioxidant, anti-inflammatory, and antimicrobial effects. However, conventional production methods, such as chemical synthesis and plant extraction, face challenges in sustainability and yield. Hence, there is a notable shift towards biological production using microorganisms like Escherichia coli and yeast. Yet, the drawbacks of using E. coli and yeast as hosts for these compounds persist. For instance, yeast's complex glycosylation profile can lead to intricate protein production scenarios, including hyperglycosylation issues. Consequently, Corynebacterium glutamicum emerges as a promising alternative, given its adaptability and recent advances in metabolic engineering. Although extensively used in biotechnological applications, the potential production of flavonoid and stilbenoid in engineered C. glutamicum remains largely untapped compared to E. coli. This review explores the potential of metabolic engineering in C. glutamicum for biosynthesis, highlighting its versatility as a cell factory and assessing optimization strategies for these pathways. Additionally, various metabolic engineering methods, including genomic editing and biosensors, and cofactor regeneration are evaluated, with a focus on C. glutamicum. Through comprehensive discussion, the review offers insights into future perspectives in production, aiding researchers and industry professionals in the field.


Assuntos
Corynebacterium glutamicum , Flavonoides , Engenharia Metabólica , Estilbenos , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/genética , Engenharia Metabólica/métodos , Flavonoides/biossíntese , Flavonoides/metabolismo , Estilbenos/metabolismo
2.
J Extracell Vesicles ; 13(5): e12454, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38760878

RESUMO

Extracellular vesicles (EVs) are emerging as a promising drug delivery vehicle as they are biocompatible and capable of targeted delivery. However, clinical translation of EVs remains challenging due to the lack of standardized and scalable manufacturing protocols to consistently isolate small EVs (sEVs) with both high yield and high purity. The heterogenous nature of sEVs leading to unknown composition of biocargos causes further pushback due to safety concerns. In order to address these issues, we developed a robust quality-controlled multi-stage process to produce and isolate sEVs from human embryonic kidney HEK293F cells. We then compared different 2-step and 3-step workflows for eliminating protein impurities and cell-free nucleic acids to meet acceptable limits of regulatory authorities. Our results showed that sEV production was maximized when HEK293F cells were grown at high-density stationary phase in semi-continuous culture. The novel 3-step workflow combining tangential flow filtration, sucrose-cushion ultracentrifugation and bind-elute size-exclusion chromatography outperformed other methods in sEV purity while still preserved high yield and particle integrity. The purified HEK293F-derived sEVs were thoroughly characterized for identity including sub-population analysis, content profiling including proteomics and miRNA sequencing, and demonstrated excellent preclinical safety profile in both in-vitro and in-vivo testing. Our rigorous enrichment workflow and comprehensive characterization will help advance the development of EVs, particularly HEK293F-derived sEVs, to be safe and reliable drug carriers for therapeutic applications.


Assuntos
Vesículas Extracelulares , Humanos , Vesículas Extracelulares/metabolismo , Células HEK293 , Proteômica/métodos , Fluxo de Trabalho , Ultracentrifugação/métodos , MicroRNAs/metabolismo
3.
Cogn Emot ; : 1-11, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532640

RESUMO

Pride expressions draw attention to one's achievement, and therefore can enhance one's status. However, such attention has been linked to negative interpersonal consequences (i.e. envy). Fortunately, people have been found to regulate their pride expressions accordingly. Specifically, pride expressions are lower when the domain of the achievement is of high relevance to observers. We set out to replicate this effect in a non-Western sample. Additionally, we extended the current finding by investigating the moderating role of self-monitoring, an individual's ability and willingness to adjust their behaviours under different social contexts to cultivate status. This allows us to explore the previously assumed underlying status motive in regulating pride expressions. Data from two preregistered studies (N1 = 913; N2 = 1081) replicated the effect that pride expressions are inhibited when the achievement domain is relevant. A significant main effect of self-monitoring was found, such that high self-monitors express more pride than low self-monitors, consistent with the conceptualisation of self-monitoring as rooted within a status-enhancement motive. The assumed interaction effect between domain relevance and self-monitoring was not significant. Our findings suggest that the effect of domain relevance on pride expression is robust and status driven.

4.
BMC Health Serv Res ; 23(1): 1126, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37858102

RESUMO

BACKGROUND: Diabetic foot infection (DFI), including diabetic foot ulcer, is a serious complication of diabetes, particularly in the South Western Sydney (SWS) region where it is a leading cause of diabetes-related hospitalisations. Multidisciplinary team (MDT) involvement is effective at improving the health outcomes of DFI patients. This study investigated the impact of MDT (High Risk Foot Service, HRFS) on the length of stay and surgical outcomes of inpatients with DFI in a Sydney tertiary hospital. METHOD: A retrospective audit of electronic medical records of inpatient admissions for DFI at Campbelltown Hospital between January 2019 - December 2021, was performed. The main outcome of the study was MDT involvement, defined as having two or more specialities involved in the patient's treatment. The other measured variables included length of stay (defined as the total duration from admission to discharge), and surgical outcomes including debridement, minor amputation, and major amputation. RESULTS: Over the three years, 78 participants presented to the hospital for 89 unique DFI admissions. There were 24 admissions in 2019, 28 admissions in 2020, and 37 admissions in 2021, with MDT attendance showing a steady increase at 62.5%, 75.0% and 83.8% respectively. Patients with serious comorbidities such as chronic kidney disease were more likely to have MDT involvement (84.8% vs. 15.2%, P = 0.048). Imaging was more likely to be performed with MDT involvement (78.8% vs. 21.3%, p < 0.05). Comparing patients who received and did not receive MDT care, the mean HbA1c (%) (8.4 ± 2.0 vs. 8.2 ± 2.7, P = 0.701), median length of stay (LOS: 7.8, IQR 15.0 days vs. 4.8 IQR 7.9 days, P = 0.243) and rate of surgical outcomes (74.6% vs. 72.7%, P = 0.262) were similar. Patients who required major amputation had significantly longer LOS (24 days, IQR 21.5 vs. 5.2 days, IQR 13.0, P = 0.004) but similar HbA1c (P = 0.552) compared to those who had conservative intervention. CONCLUSION: Adopting an MDT approach was associated with more thorough investigation of DFI, with similar rates of surgical outcomes. Further research on the impacts of MDT on length of stay and surgical outcomes of DFI patients in other SWS hospitals is needed.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/epidemiologia , Pé Diabético/cirurgia , Pacientes Internados , Estudos Retrospectivos , Hemoglobinas Glicadas , Centros de Atenção Terciária
5.
Nat Commun ; 14(1): 5832, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730693

RESUMO

Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1ß secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1ß secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1ß secretion. While IL-1ß release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity of ExoS. Genetic and pharmacologic approaches using MCC950 reveal that NLRP3 is also essential for bacterial killing and disease severity in a murine model of P. aeruginosa corneal infection (keratitis). Overall, these findings reveal a function for ExoS ADPRT in regulating inflammasome subtype usage in neutrophils versus macrophages and an unexpected role for NLRP3 in P. aeruginosa keratitis.


Assuntos
Doenças da Córnea , Pseudomonas aeruginosa , Animais , Camundongos , Inflamassomos , Neutrófilos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Gravidade do Paciente
6.
Chempluschem ; 88(8): e202300264, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37540494

RESUMO

A novel cyanine compound based on the conjugated perylene-benzothiazole system (PBI) as a colorimetric and fluorometric dual-channel sensor for cyanide (CN- ) detection was synthesized and characterized via UV-vis and fluorescence spectroscopy. PBI exhibited a high sensitivity and rapid optical response for CN- due to the intramolecular charge transfer (ICT) mechanism. The detection limit of PBI for CN- was 1.15×10-7  M in the mixture of DMSO/H2 O (1 : 1, v/v). Moreover, probe PBI demonstrated high selectivity and sensitivity for CN- over other common anions, including Cl- , Br- , F- , I- , AcO- , ClO4 - , HSO4 - , SO4 2- , NO2 - , NO3 - and SCN- . This work provided a simple and effective approach to trace the toxic CN- ion with rapid response, high selectivity, and sensitivity that is possibly applied in environmental control and agricultural management.

7.
J Bacteriol ; 205(6): e0011823, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37289078

RESUMO

The control of virulence two-component gene regulatory system (CovRS) is critical to the pathogenesis of many medically important streptococci. In emm1 group A streptococci (GAS), CovR directly binds the promoters of numerous GAS virulence factor-encoding genes. Elimination of CovS phosphatase activity increases CovR phosphorylation (CovR~P) levels and abrogates GAS virulence. Given the emm type-specific diversity of CovRS function, in this study we used chromatin immunoprecipitation sequencing (ChIP-seq) to define global CovR DNA occupancy in the wild-type emm3 strain MGAS10870 (medium CovR~P) and its CovS phosphatase-negative derivative 10870-CovS-T284A (high CovR~P). In the wild-type emm3 strain, 89% of the previously identified emm1 CovR binding sites present in the emm3 genome were also enriched; additionally, we ascertained unique CovR binding, primarily to genes in mobile genetic elements and other sites of interstrain chromosomal differences. Elimination of CovS phosphatase activity specifically increased CovR occupancy at the promoters of a broad array of CovR repressed virulence factor-encoding genes, including those encoding the key GAS regulator Mga and M protein. However, a limited number of promoters had augmented enrichment at low CovR~P levels. Differential motif searches using sequences enriched at high versus low CovR~P levels revealed two distinct binding patterns. At high CovR~P, a pseudopalindromic AT-rich consensus sequence (WTWTTATAAWAAAAWNATDA) consistent with CovR binding as a dimer was determined. Conversely, sequences specifically enriched at low CovR~P contained isolated ATTARA motifs suggesting an interaction with a monomer. These data extend understanding of global CovR DNA occupancy beyond emm1 GAS and provide a mechanism for previous observations regarding hypovirulence induced by CovS phosphatase abrogation. IMPORTANCE Given its key role in pathogenesis of Gram-positive bacteria, CovR is one of the most important members of the OmpR/PhoB family of transcriptional regulators. Herein we extend recent GAS CovR global binding analyses done in emm1 to a non-emm1 strain, which is important considering the known inter-emm-type heterogeneity in GAS CovRS function. Our data provide mechanistic understanding for variation in CovRS function between emm types and the profound hypovirulence of CovS phosphatase-negative strains in addition to indicating differential targeting by phosphorylated and nonphosphorylated CovR isoforms at specific CovR binding sites. These findings advance knowledge regarding how a key bacterial virulence regulator impacts pathogenesis and add to the growing appreciation of the function of nonphosphorylated OmpR/PhoB family members.


Assuntos
Infecções Estreptocócicas , Fatores de Virulência , Humanos , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Histidina Quinase/metabolismo , Streptococcus pyogenes/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Infecções Estreptocócicas/microbiologia , Regulação Bacteriana da Expressão Gênica
8.
mSystems ; 8(4): e0022723, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37358280

RESUMO

Group A streptococcal (GAS) strains causing severe, invasive infections often have mutations in the control of virulence two-component regulatory system (CovRS) which represses capsule production, and high-level capsule production is considered critical to the GAS hypervirulent phenotype. Additionally, based on studies in emm1 GAS, hyperencapsulation is thought to limit transmission of CovRS-mutated strains by reducing GAS adherence to mucosal surfaces. It has recently been identified that about 30% of invasive GAS strains lacks capsule, but there are limited data regarding the impact of CovS inactivation in such acapsular strains. Using publicly available complete genomes (n = 2,455) of invasive GAS strains, we identified similar rates of CovRS inactivation and limited evidence for transmission of CovRS-mutated isolates for both encapsulated and acapsular emm types. Relative to encapsulated GAS, CovS transcriptomes of the prevalent acapsular emm types emm28, emm87, and emm89 revealed unique impacts such as increased transcript levels of genes in the emm/mga region along with decreased transcript levels of pilus operon-encoding genes and the streptokinase-encoding gene ska. CovS inactivation in emm87 and emm89 strains, but not emm28, increased GAS survival in human blood. Moreover, CovS inactivation in acapsular GAS reduced adherence to host epithelial cells. These data suggest that the hypervirulence induced by CovS inactivation in acapsular GAS follows distinct pathways from the better studied encapsulated strains and that factors other than hyperencapsulation may account for the lack of transmission of CovRS-mutated strains. IMPORTANCE Devastating infections due to group A streptococci (GAS) tend to occur sporadically and are often caused by strains that contain mutations in the control of virulence regulatory system (CovRS). In well-studied emm1 GAS, the increased production of capsule induced by CovRS mutation is considered key to both hypervirulence and limited transmissibility by interfering with proteins that mediate attachment to eukaryotic cells. Herein, we show that the rates of covRS mutations and genetic clustering of CovRS-mutated isolates are independent of capsule status. Moreover, we found that CovS inactivation in multiple acapsular GAS emm types results in dramatically altered transcript levels of a diverse array of cell-surface protein-encoding genes and a unique transcriptome relative to encapsulated GAS. These data provide new insights into how a major human pathogen achieves hypervirulence and indicate that factors other than hyperencapsulation likely account for the sporadic nature of the severe GAS disease.


Assuntos
Proteínas de Bactérias , Transcriptoma , Humanos , Transcriptoma/genética , Proteínas de Bactérias/genética , Virulência/genética , Mutação/genética , Fenótipo , Streptococcus pyogenes/genética
9.
Opt Lett ; 48(9): 2397-2400, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37126282

RESUMO

Few-cycle, long-wavelength sources for generating isolated attosecond soft x ray pulses typically rely upon complex laser architectures. Here, we demonstrate a comparatively simple setup for generating sub-two-cycle pulses in the short-wave infrared based on multidimensional solitary states in an N2O-filled hollow-core fiber and a two-channel light-field synthesizer. Due to the temporal phase imprinted by the rotational nonlinearity of the molecular gas, the redshifted (from 1.03 to 1.36 µm central wavelength) supercontinuum pulses generated from a Yb-doped laser amplifier are compressed from 280 to 7 fs using only bulk materials for dispersion compensation.

10.
Nanomedicine (Lond) ; 18(7): 599-611, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37194929

RESUMO

Aims: The authors investigated whether displaying more than one homing peptide enhanced the tumor-targeting efficiency of exosomes. Materials & methods: Exosomes from human embryonic kidney cells (HEK293F) were engineered to display either mono- or dual-tumor-penetrating peptides, iRGD and tLyp1. Exosomes were purified via tangential flow filtration followed by ultracentrifugation. Results: When loaded with doxorubicin (Dox), the dual iRGD-tLyp1 exosomes strongly enhanced Dox uptake in both MCF-7 and MDA-MB-231 breast cancer cell lines, superior to single iRGD or tLyp1 exosomes. The dual iRGD-tLyp1 exosomal Dox was also the most potent, with IC50/GI50 values being 3.7-17.0-times lower than those of free Dox and other exosomal Dox. Conclusion: Selecting appropriate combinatorial homing peptides could be an approach for future precision nanomedicine.


Assuntos
Neoplasias da Mama , Exossomos , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Doxorrubicina/farmacologia , Peptídeos , Linhagem Celular Tumoral
11.
Biochem Biophys Res Commun ; 653: 47-52, 2023 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-36857899

RESUMO

Redox regulation is a posttranslational modification based on the redox reaction of protein thiols. A small ubiquitous protein thioredoxin (Trx) plays a central role in redox regulation, but a unique redox-regulatory factor called NADPH-Trx reductase C (NTRC) is also found in plant chloroplasts and some cyanobacteria. Several important functions of NTRC have been suggested, but the mechanism for controlling NTRC activity remains undetermined. Cystathionine-ß-synthase X (CBSX) proteins have been previously shown to interact with NTRC physically. Based on these observations, this study biochemically investigated the functional interaction between CBSX proteins and NTRC from Arabidopsis thaliana in vitro. Consequently, we concluded that CBSX proteins act as negative regulators of NTRC in the presence of AMP.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Antioxidantes/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Cloroplastos/metabolismo , Cistationina/metabolismo , Cistationina beta-Sintase/metabolismo , Oxirredução , Tiorredoxina Dissulfeto Redutase/metabolismo , Tiorredoxinas/metabolismo
12.
Int J Mol Sci ; 24(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36835188

RESUMO

Derived from the natural language processing (NLP) algorithms, protein language models enable the encoding of protein sequences, which are widely diverse in length and amino acid composition, in fixed-size numerical vectors (embeddings). We surveyed representative embedding models such as Esm, Esm1b, ProtT5, and SeqVec, along with their derivatives (GoPredSim and PLAST), to conduct the following tasks in computational biology: embedding the Saccharomyces cerevisiae proteome, gene ontology (GO) annotation of the uncharacterized proteins of this organism, relating variants of human proteins to disease status, correlating mutants of beta-lactamase TEM-1 from Escherichia coli with experimentally measured antimicrobial resistance, and analyzing diverse fungal mating factors. We discuss the advances and shortcomings, differences, and concordance of the models. Of note, all of the models revealed that the uncharacterized proteins in yeast tend to be less than 200 amino acids long, contain fewer aspartates and glutamates, and are enriched for cysteine. Less than half of these proteins can be annotated with GO terms with high confidence. The distribution of the cosine similarity scores of benign and pathogenic mutations to the reference human proteins shows a statistically significant difference. The differences in embeddings of the reference TEM-1 and mutants have low to no correlation with minimal inhibitory concentrations (MIC).


Assuntos
Algoritmos , Proteínas , Humanos , Sequência de Aminoácidos , Aminoácidos , Biologia Computacional , Proteínas/química , Saccharomyces cerevisiae/genética , Proteômica
13.
Sci Rep ; 13(1): 3143, 2023 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823360

RESUMO

People with ULV (visual acuity ≤ 20/1600 or 1.9 logMAR) lack form vision but have rudimentary levels of vision that can be used for a range of activities in daily life. However, current clinical tests are designed to assess form vision and do not provide information about the range of visually guided activities that can be performed in daily life using ULV. This is important to know given the growing number of clinical trials that recruit individuals with ULV (e.g., gene therapy, stem cell therapy) or restore vision to the ULV range in the blind (visual prosthesis). In this study, we develop a set of 19 activities (items) in virtual reality involving spatial localization/detection, motion detection, and direction of motion that can be used to assess visual performance in people with ULV. We estimated measures of item difficulty and person ability on a relative d prime (d') axis using a signal detection theory based analysis for latent variables. The items represented a range of difficulty levels (- 1.09 to 0.39 in relative d') in a heterogeneous group of individuals with ULV (- 0.74 to 2.2 in relative d') showing the instrument's utility as an outcome measure in clinical trials.


Assuntos
Realidade Virtual , Baixa Visão , Humanos , Baixa Visão/diagnóstico , Inquéritos e Questionários , Transtornos da Visão , Cegueira
14.
Glob Cardiol Sci Pract ; 2023(4): e202326, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38623555

RESUMO

Background: Mitral regurgitation (MR) is a common heart valve disease, causing many serious complications in several organ systems, especially the cardiovascular system. The 2D speckle tracking echocardiography (STE) is a new technique for detecting potential cardiac dysfunction when only tissue function abnormalities are present. The study aimed to assess left ventricular (LV) systolic function early by STE in patients with primary MR through global LV deformity along the global longitudinal strain (GLS). Methods: An analytical cross-sectional study was performed on 46 patients with moderate to severe primary MR as recommended by the American Society of Echocardiography (ASE) 2017. Results: The prevalence of patients with GLS reduction with ejection fraction (EF) >60%, New York Heart Association (NYHA) I, and left ventricular internal diameter systolic (LVIDs) <40 mm was 38.1%, 35.7%, and 39.5%, respectively. 100% of patients with EF<60% and LVIDs ≥40 mm had reduced GLS (<16%). The GLS index strongly correlates with the NYHA classification, degree of MR, EF, and echocardiographic parameters. Conclusion: GLS index gives a significant sign in the early detection of cardiac function abnormalities before symptoms or other echocardiographic parameters in patients with MR.

15.
Front Neurosci ; 17: 1251935, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38178831

RESUMO

Introduction: Ultra low vision (ULV) refers to profound visual impairment where an individual cannot read even the top line of letters on an ETDRS chart from a distance of 0.5 m. There are limited tools available to assess visual ability in ULV. The aim of this study was to develop and calibrate a new performance test, Wilmer VRH, to assess hand-eye coordination in individuals with ULV. Methods: A set of 55 activities was developed for presentation in a virtual reality (VR) headset. Activities were grouped into 2-step and 5-step items. Participants performed a range of tasks involving reaching and grasping, stacking, sorting, pointing, throwing, and cutting. Data were collected from 20 healthy volunteers under normal vision (NV) and simulated ULV (sULV) conditions, and from 33 participants with ULV. Data were analyzed using the method of successive dichotomizations (MSD), a polytomous Rasch model, to estimate item (difficulty) and person (ability) measures. MSD was applied separately to 2-step and 5-step performance data, then merged to a single equal interval scale. Results: The mean ±SD of completion rates were 98.6 ± 1.8%, 78.2 ± 12.5% and 61.1 ±34.2% for NV, sULV and ULV, respectively. Item measures ranged from -1.09 to 5.7 logits and - 4.3 to 4.08 logits and person measures ranged from -0.03 to 4.2 logits and -3.5 to 5.2 logits in sULV and ULV groups, respectively. Ninety percent of item infits were within the desired range of [0.5,1.5], and 97% of person infits were within that range. Together with item and person reliabilities of 0.94 and 0.91 respectively, this demonstrates unidimensionality of Wilmer VRH. A Person Item map showed that the items were well-targeted to the sample of individuals with ULV in the study. Discussion: We present the development of a calibrated set of activities in VR that can be used to assess hand-eye coordination in individuals with ULV. This helps bridge a gap in the field by providing a validated outcome measure that can be used in vision restoration trials that recruit people with ULV, and to assess rehabilitation outcomes in people with ULV.

17.
Sci Rep ; 12(1): 13574, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945451

RESUMO

The propolis industry is well established in European, South American and East Asian countries. Within Australia, this industry is beginning to emerge with a few small-scale producers. To contribute to the development of the Australian propolis industry, the present study aimed to examine the quality and chemical diversity of propolis collected from various regions across Australia. The results of testing 158 samples indicated that Australian propolis had pure resin yielding from 2 to 81% by weight, total phenolic content and total flavonoid content in one gram of dry extract ranging from a few up to 181 mg of gallic acid equivalent and 145 mg of quercetin equivalent, respectively. Some Australian propolis showed more potent antioxidant activity than the well-known Brazilian green, Brazilian red, and Uruguayan and New Zealand poplar-type propolis in an in vitro DPPH assay. In addition, an HPLC-UV analysis resulted in the identification of 16 Australian propolis types which can be considered as high-grade propolis owing to their high total phenolic content. Chemometric analysis of their 1H NMR spectra revealed that propolis originating from the eastern and western coasts of Australia could be significantly discriminated based on their chemical composition.


Assuntos
Própole , Animais , Antioxidantes/análise , Austrália , Abelhas , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Fenóis/análise , Própole/química
18.
Oncotarget ; 13: 785-799, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677533

RESUMO

Interleukin-33 (IL-33) is an IL-1 family cytokine known to promote T-helper (Th) type 2 immune responses that are often deregulated in gastric cancer (GC). IL-33 is overexpressed in human gastric tumours suggesting a role in driving GC progression although a causal link has not been proven. Here, we investigated the impact of IL-33 genetic deficiency in the well-characterized gp130 F/F mouse model of GC. Expression of IL-33 (and it's cognate receptor, ST2) was increased in human and mouse GC progression. IL-33 deficient gp130 F/F /Il33 -/- mice had reduced gastric tumour growth and reduced recruitment of pro-tumorigenic myeloid cells including key mast cell subsets and type-2 (M2) macrophages. Cell sorting of gastric tumours revealed that IL-33 chiefly localized to gastric (tumour) epithelial cells and was absent from tumour-infiltrating immune cells (except modest IL-33 enrichment within CD11b+ CX3CR1+CD64+MHCII+ macrophages). By contrast, ST2 was absent from gastric epithelial cells and localized exclusively within the (non-macrophage) immune cell fraction together with mast cell markers, Mcpt1 and Mcpt2. Collectively, we show that IL-33 is required for gastric tumour growth and provide evidence of a likely mechanism by which gastric epithelial-derived IL-33 drives mobilization of tumour-promoting inflammatory myeloid cells.


Assuntos
Interleucina-33 , Neoplasias Gástricas , Animais , Receptor gp130 de Citocina , Citocinas , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Interleucina-33/metabolismo , Camundongos , Camundongos Knockout , Células Mieloides/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia
19.
Aging Male ; 25(1): 125-133, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35416126

RESUMO

OBJECTIVE: To explore the microbial etiology of urethritis in Vietnamese men and the association with patients' characteristics, especially their sexual behaviors. METHODS: This study was conducted on 349 men who presented with symptomatic urethritis and evidence of STIs (determined by multiplex PCR tests) at the Department of Andrology and Sexual Medicine-Hanoi Medical University Hospital. All information regarding medical history, sexual activities, and symptoms of urethritis was documented. RESULTS: C. trachomatis and N. gonorrhoea remained the two most common causative pathogens, followed by an unexpectedly high prevalence of Mycoplasma and Ureaplasma species. Coinfection was significant with a rate of 40.7%. Men who had sex with female sex workers (FSWs) were more likely to be positive with N. gonorrhoea but less likely to be positive with C. trachomatis and M. genitalium than those having sex with only one romantic partner. CONCLUSIONS: Our findings suggested the important role of other microorganisms, especially M. genitalium, in the etiology of urethritis in men besides the previously well-known causes of STIs. Since the coinfection rate is quite high, targeted treatment with clear microbial evidence should be considered rather than empiric antimicrobial therapy.


Assuntos
Coinfecção , Gonorreia , Infecções por Mycoplasma , Mycoplasma genitalium , Profissionais do Sexo , Infecções Sexualmente Transmissíveis , Uretrite , Chlamydia trachomatis , Coinfecção/complicações , Coinfecção/epidemiologia , Feminino , Gonorreia/complicações , Heterossexualidade , Humanos , Masculino , Infecções por Mycoplasma/complicações , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/epidemiologia , Prevalência , Infecções Sexualmente Transmissíveis/complicações , Infecções Sexualmente Transmissíveis/epidemiologia , Uretrite/diagnóstico , Uretrite/epidemiologia , Uretrite/etiologia , Vietnã/epidemiologia
20.
Nutrients ; 14(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35276914

RESUMO

Lactococcus lactis strain Plasma (LC-Plasma) is reported to have anti-viral effects via direct activation of plasmacytoid dendritic cells, which upregulate the production of type I and III interferons. A randomized, placebo-controlled, double-blind, parallel group study was designed for elementary schoolchildren, grades 1 to 3, in Vietnam. LC-Plasma or a control were administered to schoolchildren as a beverage (1.0 × 1011 count LC-Plasma/day/person). The primary endpoint was to determine the efficacy of LC-Plasma in reducing the cumulative days absent from school due to upper respiratory disease (URID) and gastrointestinal disease (GID), and the secondary endpoint was to evaluate the potency of LC-Plasma on URID/GID symptoms and general well-being scores. LC-Plasma intake significantly reduced the cumulative days absent from school due to URID/GID (Odds ratio (OR) = 0.57, p = 0.004) and URID alone (OR = 0.56, p = 0.005); LC-Plasma also significantly reduced the number of cumulative fever positive days during the first 4 weeks of intervention (OR = 0.58, p = 0.001) and cumulative days with diarrhea during the last 4 weeks of the intervention period (OR = 0.78, p = 0.01). The number of positive general wellbeing days was significantly improved in the LC-Plasma group compared with the control throughout the intervention period (OR = 0.93, 0.93, p = 0.03, 0.04 in the first and last 4 weeks of the intervention, respectively). These data suggest that LC-Plasma seems to improve the health condition of elementary schoolchildren and reduces school absenteeism due to infectious disease, especially URID.


Assuntos
Doenças Transmissíveis , Lactococcus lactis , Povo Asiático , Criança , Método Duplo-Cego , Humanos , Lactococcus lactis/fisiologia , Vietnã/epidemiologia
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