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1.
Chem Commun (Camb) ; 60(20): 2764-2767, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38353608

RESUMO

In this article, we report a general protocol for the direct decarboxylative chlorination, iodination, and bromination of aliphatic carboxylic acids catalyzed by iron salts under visible light. This method enjoys a broad substrate scope with good functional group compatibility, including complex natural products. Benzylic and allylic C(sp3)-H bonds can be retained under the oxidative halogenation conditions. This method also shows application potential for late-stage functionalization.

2.
Front Cell Infect Microbiol ; 13: 1225285, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37886665

RESUMO

Bacterial brown stripe disease caused by Acidovorax oryzae is a major threat to crop yields, and the current reliance on pesticides for control is unsustainable due to environmental pollution and resistance. To address this, bacterial-based ligands have been explored as a potential treatment solution. In this study, we developed a protein-protein interaction (PPI) network for A. oryzae by utilizing shared differentially expressed genes (DEGs) and the STRING database. Using a maximal clique centrality (MCC) approach through CytoHubba and Network Analyzer, we identified hub genes within the PPI network. We then analyzed the genomic data of the top 10 proteins, and further narrowed them down to 2 proteins by utilizing betweenness, closeness, degree, and eigenvector studies. Finally, we used molecular docking to screen 100 compounds against the final two proteins (guaA and metG), and Enfumafungin was selected as a potential treatment for bacterial resistance caused by A. oryzae based on their binding affinity and interaction energy. Our approach demonstrates the potential of utilizing bioinformatics and molecular docking to identify novel drug candidates for precision treatment of bacterial brown stripe disease caused by A. oryzae, paving the way for more targeted and sustainable control strategies. The efficacy of Enfumafungin in inhibiting the growth of A. oryzae strain RS-1 was investigated through both computational and wet lab methods. The models of the protein were built using the Swiss model, and their accuracy was confirmed via a Ramachandran plot. Additionally, Enfumafungin demonstrated potent inhibitory action against the bacterial strain, with an MIC of 100 µg/mL, reducing OD600 values by up to 91%. The effectiveness of Enfumafungin was further evidenced through agar well diffusion assays, which exhibited the highest zone of inhibition at 1.42 cm when the concentration of Enfumafungin was at 100 µg/mL. Moreover, Enfumafungin was also able to effectively reduce the biofilm of A. oryzae RS-1 in a concentration-dependent manner. The swarming motility of A. oryzae RS-1 was also found to be significantly inhibited by Enfumafungin. Further validation through TEM observation revealed that bacterial cells exposed to Enfumafungin displayed mostly red fluorescence, indicating destruction of the bacterial cell membrane.


Assuntos
Oryza , Oryza/microbiologia , Simulação de Acoplamento Molecular , Biologia Computacional
3.
PLoS One ; 18(8): e0289877, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37561714

RESUMO

There is some evidence that self-harm presentations in children and young people have increased over the past decade, yet there are few up-to-date studies examining these trends. This study aims to describe trends in the rates and severity of emergency department self-harm presentations for youth aged 5-24 years in New South Wales, Australia between 1 January 2012 and 31 December 2020. We analysed self-harm hospital presentations using join point analysis to compare quarterly growth in rates and urgency of presentation since 2012 by age group and sex. Binomial logistic modelling was used to identify risks for re-presentation for self-harm, including age group, sex, country of birth, mode of arrival, inpatient status, triage category, rurality, and socio-economic disadvantage. In total, 83,111 self-harm presentations for 51,181 persons were analysed. Overall rates of self-harm among those aged 5-24 years increased by 2.4% (p < .001) per quarter in females and 1.6% (p < .001) per quarter in males, with statistically significant average quarterly increases observed across all age groups. Overall and age-specific self-harm triage urgency rates increased statistically significantly for potentially serious, and potentially- and immediately life-threatening categories. A higher likelihood of re-presentation to any emergency department for self-harm was associated with younger age, female, residing in a regional area, arriving by ambulance, admitted as an in-patient, and a more severe index self-harm presentation. Hospital self-harm presentations have been growing steadily over the past decade, with the greatest growth in the youngest people. Understanding the reasons for these sustained upward trends is a priority for suicide prevention.


Assuntos
Comportamento Autodestrutivo , Masculino , Criança , Adolescente , Humanos , Feminino , New South Wales/epidemiologia , Estudos Retrospectivos , Comportamento Autodestrutivo/epidemiologia , Austrália , Serviço Hospitalar de Emergência , Hospitais
4.
JBI Evid Synth ; 21(11): 2239-2246, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37555780

RESUMO

OBJECTIVE: The objective of this review is to examine the association between proton pump inhibitors (PPIs) and neurological and/or psychiatric disorders in adults. INTRODUCTION: The association between PPIs and neurological and/or psychiatric disorders remains unclear, despite the widespread use of the medications. A systematic review is required to investigate the risk of developing neurological and/or psychiatric disorders following the use of PPIs. INCLUSION CRITERIA: Studies including participants aged ≥18 years and using any PPIs, including participants with comorbid conditions or using other medications, will be considered for inclusion. Randomized controlled trials, quasi-experimental studies, and observational studies examining the association of neurological and/or psychiatric disorders with the use of PPIs among adults will be included. METHODS: MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases will be searched from inception until the present. Two authors will independently screen and review the titles, abstracts, and full texts. The methodological quality of included studies will be assessed using the JBI critical appraisal checklists. Study characteristics, populations, type and duration of PPI usage, status of existing neurological and/or psychiatric disorders, comorbidity conditions, use of other medications, identification of neurological and/or psychiatric disorders (International Classification of Diseases codes vs others), and estimation of the associated neurological and/or psychiatric disorders will be extracted. Studies will be pooled using statistical meta-analysis where available; otherwise, the findings will be presented in narrative format. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading the certainty of evidence will be followed. REVIEW REGISTRATION: PROSPERO CRD42022355543.


Assuntos
Transtornos Mentais , Inibidores da Bomba de Prótons , Adulto , Humanos , Adolescente , Inibidores da Bomba de Prótons/efeitos adversos , Revisões Sistemáticas como Assunto , Lista de Checagem , Transtornos Mentais/epidemiologia , Metanálise como Assunto , Literatura de Revisão como Assunto
5.
Vaccine ; 41(38): 5587-5591, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37524631

RESUMO

BACKGROUND: There is limited data directly comparing the effectiveness of different COVID-19 vaccines. METHODS: We compared rates of SARS-CoV-2 Omicron BA.1/2 infection during March to May 2022 in Australian adults who had received one of four COVID-19 vaccines in the last 14-63 days as either a primary course or a booster dose using Cox proportional hazards models adjusting for age and other characteristics. RESULTS: As a primary course, over 2318 person-years and 1033 infections, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82-1.30), 1.19 (0.95-1.49), 1.70 (1.46-1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For the booster dose, over 154,984 person-years and 93,580 infections the respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00-1.04), 1.20 (1.10-1.32), 1.39 (1.20-1.60). CONCLUSIONS: Our findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines and provide clinical confirmation of immunological data on differences in COVID-19 vaccine performance.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , ChAdOx1 nCoV-19 , Vacina de mRNA-1273 contra 2019-nCoV , Vacina BNT162 , SARS-CoV-2 , COVID-19/prevenção & controle , Austrália/epidemiologia , RNA Mensageiro/genética
6.
Microbiol Spectr ; 11(3): e0004023, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37154708

RESUMO

Metabolism associated with energy production is highly compartmentalized in eukaryotic cells. During this process, transporters that move metabolites across organelle membranes play pivotal roles. The highly conserved ADP/ATP carrier (AAC) involved in ATP and ADP exchange between the mitochondria and cytoplasm is key to linking the metabolic activities in these 2 compartments. The ATP produced in mitochondria can be exchanged with cytoplasmic ADP by AAC, thus satisfying the energy needs in the cytoplasm. Toxoplasma gondii is an obligate intracellular parasite with a wide range of hosts. Previous studies have shown that mitochondrial metabolism helps Toxoplasma to parasitize diverse host cells. Here, we identified 2 putative mitochondria ADP/ATP carriers in Toxoplasma with significant sequence similarity to known AACs from other eukaryotes. We examined the ATP transport function of TgAACs by expressing them in Escherichia coli cells and found that only TgAAC1 had ATP transport activity. Moreover, knockdown of TgAAC1 caused severe growth defects of parasites and heterologous expression of mouse ANT2 in the TgAAC1 depletion mutant restored its growth, revealing its importance for parasite growth. These results verified that TgAAC1 functions as the mitochondrial ADP/ATP carrier in T. gondii and the functional studies demonstrated the importance of TgAAC1 for tachyzoites growth. IMPORTANCE T. gondii has an efficient and flexible energy metabolism system to meet different growth needs. ATP is an energy-carrying molecule and needs to be exchanged between organelles with the assistance of transporters. However, the function of TgAACs has yet to be characterized. Here, we identified 2 putative AACs of T. gondii and verified that only TgAAC1 had ATP transport activity with expression in the intact E. coli cells. Detailed analyses found that TgAAC1 is critical for the growth of tachyzoites and TgAAC2 is dispensable. Moreover, complementation with mouse ANT2 restored the growth speed of iTgAAC1, further suggesting TgAAC1 functions as a mitochondrial ADP/ATP carrier. Our research demonstrated the importance of TgAAC1 for tachyzoites growth.


Assuntos
Parasitos , Toxoplasma , Animais , Camundongos , Parasitos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Mitocôndrias/metabolismo , Trifosfato de Adenosina/metabolismo
7.
Plants (Basel) ; 12(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37176969

RESUMO

Targeted genome editing technologies are becoming the most important and widely used genetic tools in studies of phytopathology. The "clustered regularly interspaced short palindromic repeats (CRISPR)" and its accompanying proteins (Cas) have been first identified as a natural system associated with the adaptive immunity of prokaryotes that have been successfully used in various genome-editing techniques because of its flexibility, simplicity, and high efficiency in recent years. In this review, we have provided a general idea about different CRISPR/Cas systems and their uses in phytopathology. This review focuses on the benefits of knock-down technologies for targeting important genes involved in the susceptibility and gaining resistance against viral, bacterial, and fungal pathogens by targeting the negative regulators of defense pathways of hosts in crop plants via different CRISPR/Cas systems. Moreover, the possible strategies to employ CRISPR/Cas system for improving pathogen resistance in plants and studying plant-pathogen interactions have been discussed.

8.
Emerg Infect Dis ; 29(5): 1070-1073, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37015284

RESUMO

Using linked public health data from Australia to measure uptake of COVID-19 vaccination by infection status, we found coverage considerably lower among infected than uninfected persons for all ages. Increasing uptake of scheduled doses, including among previously infected persons after the recommended postinfection delay, is needed to reduce COVID-19 illness rates.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , New South Wales/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Austrália/epidemiologia , Saúde Pública , Vacinação
9.
JMIR Ment Health ; 10: e44862, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36995752

RESUMO

BACKGROUND: Loneliness is commonly reported by young people and has been shown to contribute to the rapid onset and escalation of depression and suicidal ideation during adolescence. Lonely people may also be particularly susceptible to disengaging from treatment early given the likelihood of their more complex clinical profiles leading to cognitive fatigue. While a smartphone intervention (LifeBuoy) has been shown to effectively reduce suicidal ideation in young adults, poor engagement is a well-documented issue for this therapeutic modality and has been shown to result in poorer treatment outcomes. OBJECTIVE: This study aims to determine whether loneliness affects how young people experiencing suicidal ideation engage with and benefit from a therapeutic smartphone intervention (LifeBuoy). METHODS: A total of 455 community-based Australian young adults (aged 18-25 years) experiencing recent suicidal ideation were randomized to use a dialectical behavioral therapy-based smartphone intervention (LifeBuoy) or an attention-matched control app (LifeBuoy-C) for 6 weeks. Participants completed measures of suicidal ideation, depression, anxiety, and loneliness at baseline (T0), post intervention (T1), and 3 months post intervention (T2). Piecewise linear mixed models were used to examine whether loneliness levels moderated the effect of LifeBuoy and LifeBuoy-C on suicidal ideation and depression across time (T0 to T1; T1 to T2). This statistical method was then used to examine whether app engagement (number of modules completed) influenced the relationship between baseline loneliness and suicidal ideation and depression across time. RESULTS: Loneliness was positively associated with higher levels of overall suicidal ideation (B=0.75, 95% CI 0.08-1.42; P=.03) and depression (B=0.88, 95% CI 0.45-1.32; P<.001), regardless of time point or allocated condition. However, loneliness did not affect suicidal ideation scores across time (time 1: B=1.10, 95% CI -0.25 to 2.46; P=.11; time 2: B=0.43, 95% CI -1.25 to 2.12; P=.61) and depression scores across time (time 1: B=0.00, 95% CI -0.67 to 0.66; P=.99; time 2: B=0.41, 95% CI -0.37 to 1.18; P=.30) in either condition. Similarly, engagement with the LifeBuoy app was not found to moderate the impact of loneliness on suicidal ideation (B=0.00, 95% CI -0.17 to 0.18; P=.98) or depression (B=-0.08, 95% CI -0.19 to 0.03; P=.14). CONCLUSIONS: Loneliness was not found to affect young adults' engagement with a smartphone intervention (LifeBuoy) nor any clinical benefits derived from the intervention. LifeBuoy, in its current form, can effectively engage and treat individuals regardless of how lonely they may be. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619001671156; https://tinyurl.com/yvpvn5n8. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/23655.

10.
Prev Sci ; 24(7): 1292-1301, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36800134

RESUMO

Means restriction interventions are recognised as highly effective for the deterrence of suicide attempts by jumping. While such interventions can lead to significant reductions in suicide, it is unclear whether these reductions represent a displacement effect, whereby individuals are instead choosing to attempt suicide at other nearby locations which offer the same means. The potential displacement of suicides as an unintended consequence of means restriction has been relatively unexplored to date. The only studies exploring displacement effects have focused on bridges, which are relatively easily contained sites; no studies have yet explored displacement effects at cliff-based high risk suicide locations (hotspots). Using Australian coronial data for the period of 2006-2019, we undertook joinpoint and kernel density analysis of suicides by jumping at a well-known cliff-based hotspot in Sydney, Australia, to determine whether there was evidence of displacement to local and broader surrounding cliffs following the installation of a multi-component harm minimization intervention (the Gap Park Masterplan). While slight decreases were noted in the immediate area subject to the structural intervention in the post-implementation period, alongside slight increases in the surrounding cliffs, there was no evidence for statistically significant changes. While kernel density analyses did not identify the emergence of any new hotspot locations in the post-implementation period, three existing hotspot sites of concern were found in our total area of interest, with greater than expected growth in the density of one of the hotspots. While we found no persuasive evidence of displacement, ongoing monitoring of the cliff-based location where the structural interventions were implemented is needed to ensure the ongoing safety of the area.


Assuntos
Prevenção ao Suicídio , Humanos , Austrália , Análise Espacial
11.
Soc Psychiatry Psychiatr Epidemiol ; 58(6): 843-859, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36805762

RESUMO

BACKGROUND: Little is known about what impact the use of different spatial methodological approaches may have on understanding the relationship between area-level socio-economic factors and suicide. METHODS: In this systematic review, we searched PubMed, Embase, CINAHL and PsycInfo for original empirical studies examining the relationship between socio-economic factors and suicide with a spatial lens, published up to January 22, 2022. Data on applied spatial methods, indicators of socio-economic factors, and risk of suicide related to socio-economic factors were extracted. The protocol for this systematic review was registered with PROSPERO (CRD42021251387). RESULTS: A systematic search yielded 6290 potentially relevant results; 58 studies met the inclusion criteria for review. Of the 58 included studies, more than half of the studies (n = 34; 58.6%) used methods that accounted for spatial effects in analyses of the association between socio-economic factors and suicide or examined spatial autocorrelation, while 24 (41.4%) studies applied univariate and multivariate models without considering spatial effects. Bayesian hierarchical models and spatial regression models were commonly used approaches to correct for spatial effects. The risk of suicide relating to socio-economic factors varied greatly by local areas and between studies using various socio-economic indicators. Areas with higher deprivation, higher unemployment, lower income, and lower education level were more likely to have higher suicide risk. There was no significant difference in results between studies using conventional versus spatial statistic methods. CONCLUSION: An increasing number of studies have applied spatial methods, including Bayesian spatial models and spatial regression models, to explore the relationship between area-level socio-economic factors and suicide. This review of spatial studies provided further evidence that area-level socio-economic factors are generally inversely associated with suicide risk, with or without accounting for spatial autocorrelation.


Assuntos
Suicídio , Humanos , Teorema de Bayes , Renda , Fatores Econômicos , Análise Espacial , Fatores Socioeconômicos
12.
J Affect Disord ; 321: 191-200, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36280199

RESUMO

BACKGROUND: Self-harm is a critical issue affecting young people which could result in adverse outcomes including repeat episodes and suicide. In this study, we aimed to estimate the short-term and long-term risk of repeat self-harm and subsequent suicide death following self-harm presentations among adolescents and young adults. METHODS: Using linked data from the New South Wales (NSW) Emergency Department Data Collection (EDDC), the NSW Admitted Patient Data Collection (APDC), and cause of death unit record file (COD-URF), we collected all self-harm presentations to emergency departments and/or hospitals and suicide deaths between 2012 and 2019 in NSW, Australia. We used survival analysis models to estimate the incidence of repeat self-harm and suicide by time since the index self-harm and relative risks by sex, type of hospital presentation and count of self-harm records. RESULTS: In total, we identified 81,133 self-harm episodes among 48,547 individuals aged 10-29 years. Of 48,547 individuals who engaged in an index self-harm during the study period, 39.5 % (19,180) were aged between 15 and 19 years. The incidence of both repeat self-harm and suicide were highest in the year following the index self-harm presentation (repeat self-harm: 188.84 per 1000 person-years; suicide: 3.30 per 1000 person-years) and declined to 14.51 and 0.28 per 1000 person-years after five years. Among individuals indexed for self-harm at 15-29 years, males and those who were admitted to hospital for the index self-harm had the highest risk of both subsequent repeat self-harm and suicide death and those with 2 or more self-harm presentation records had the higher risk for subsequent suicide death. CONCLUSION: Adolescents and young adults with self-harm presentations were at a high risk of subsequent repeat self-harm and suicide death, especially the first year after presentations. Youth-specific early intervention and long-term management should be delivered accordingly, especially for those at early adolescence .


Assuntos
Comportamento Autodestrutivo , Suicídio , Humanos , Adolescente , Adulto Jovem , Masculino , Adulto , Comportamento Autodestrutivo/epidemiologia , Incidência , Serviço Hospitalar de Emergência , Hospitais , Fatores de Risco
13.
PLoS Pathog ; 18(11): e1010998, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36445866

RESUMO

[This corrects the article DOI: 10.1371/journal.ppat.1010665.].

14.
J Psychiatr Res ; 155: 579-588, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36206602

RESUMO

Research has posited that machine learning could improve suicide risk prediction models, which have traditionally performed poorly. This systematic review and meta-analysis evaluated the performance of machine learning models in predicting longitudinal outcomes of suicide-related outcomes of ideation, attempt, and death and examines outcome, data, and model types as potential covariates of model performance. Studies were extracted from PubMed, Web of Science, Embase, and PsycINFO. A bivariate mixed effects meta-analysis and meta-regression analyses were performed for studies using machine learning to predict future events of suicidal ideation, attempts, and/or deaths. Risk of bias was assessed for each study using an adaptation of the Prediction model Risk Of Bias Assessment Tool. Narrative review included 56 studies, and analyses examined 54 models from 35 studies. The models achieved a very good pooled AUC of 0.86, sensitivity of 0.66 (95% CI [0.60, 0.72)], and specificity of 0.87 (95% CI [0.84, 0.90]). Pooled AUCs for ideation, attempt, and death were similar at 0.88, 0.87, and 0.84 respectively. Model performance was highly varied; however, meta-regressions did not provide evidence that performance varied by outcome, data, or model types. Findings suggest that machine learning has the potential to improve suicide risk detection, with pooled estimates of machine learning performance comparing favourably to performance of traditional suicide prediction models. However, more studies with lower risk of bias are necessary to improve the application of machine learning in suicidology.


Assuntos
Ideação Suicida , Suicídio , Área Sob a Curva , Humanos , Aprendizado de Máquina , Tentativa de Suicídio
15.
Org Lett ; 24(32): 5972-5976, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35950813

RESUMO

An efficient and inexpensive protocol for the direct decarboxylative fluorination of aliphatic carboxylic acids catalyzed with iron salts under visible light is presented. This new method allows the facile fluorination of a diverse array of carboxylic acids even on gram scale using a Schlenk flask without loss of efficiency. Mechanistic studies suggest that the photoinduced ligand-to-metal charge transfer process enables the generation of the key step to generate the carboxyl radical intermediates.

16.
ChemSusChem ; 15(20): e202201241, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-35916215

RESUMO

An iron-catalyzed remote C(sp3 )-H amination of alcohols through 1,5-hydrogen atom transfer is developed. This protocol provides a method to generate δ-C(sp3 )-N bonds from primary, secondary, and tertiary alcohols under mild conditions. A wide substrate scope and a good functional group tolerance are presented. Mechanistic studies show that a LMCT course of an Fe-OR species and a chlorine radical-induced hydrogen abstraction of an alcohol are possible to generate the alkoxy radical intermediate.


Assuntos
Álcoois , Ferro , Aminação , Álcoois/química , Ferro/química , Cloro , Estrutura Molecular , Hidrogênio/química , Luz , Catálise
17.
PLoS Pathog ; 18(7): e1010665, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35788770

RESUMO

The lumen of the endoplasmic reticulum (ER) is the subcellular site where secretory protein folding, glycosylation and sulfation of membrane-bound proteins, proteoglycans, and lipids occur. The protein folding and degradation in the lumen of the ER require high levels of energy in the form of ATP. Biochemical and genetic approaches show that ATP must first be translocated across ER membrane by particular transporters before serving as substrates and energy sources in the lumenal reactions. Here we describe an ATP/ADP transporter residing in the ER membranes of T.gondii. Immunofluorescence (IFA) assay in transgenic TgANT1-HA tag revealed that TgANT1 is a protein specifically expressed in the ER. In vitro assays, functional integration of TgANT in the cytoplasmic membrane of intact E. coli cells reveals high specificity for an ATP/ADP antiport. The depletion of TgANT leads to fatal growth defects in T.gondii, including a significant slowdown in replication, no visible plaque formation, and reduced ability to invade. We also found that the amino acid mutations in two domains of TgANT lead to the complete loss of its function. Since these two domains are conserved in multiple species, they may share the same transport mechanism. Our results indicate that TgANT is the only ATP/ADP transporter in the ER of T. gondii, and the lack of ATP in the ER is the cause of the death of T. gondii.


Assuntos
Toxoplasma , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Retículo Endoplasmático/metabolismo , Escherichia coli/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Toxoplasma/genética , Toxoplasma/metabolismo
18.
Biomed Chromatogr ; 36(11): e5469, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35904380

RESUMO

Silybin, an active component in the plant Silybum marianum (L.) Gaertn., is commonly used to protect against liver disease. We investigated silybin's protective potential in rat liver against emodin-induced liver injury 4 weeks. It was found that aspartate aminotransferase and direct bilirubin serum biomarkers for liver toxicity significantly increased, and liver histopathology revealed cholestasis and necrosis in rats administered emodin alone, whereas aspartate aminotransferase and total bile acid levels in rats administered emodin and silybin simultaneously were changed compared to rats administered emodin alone. Liver mRNA and protein levels of Cyp7a1-which plays roles in cholesterol metabolism and bile acid synthesis-and Abcb11 (Bsep)-which facilitates bile salt secretion in hepatocyte canaliculi-were significantly altered with emodin, whereas cotreatment with silybin attenuated emodin's adverse effect. Metabolomic analysis using ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry determined eight potential metabolite biomarkers in serum, urine, and liver tissue. Network analysis was conducted to conceptualize the interplay of genes, metabolites, and metabolic pathways for cholesterol metabolism and bile acid synthesis for liver injury. Overall, rats administered only emodin were shown to be a sound model to investigate fat-associated drug-induced hepatoxicity or liver injury and cotreatment of emodin with silybin prevents fatty liver injury. This metabolomic study revealed that emodin-induced fatty liver injury disrupted bile acid synthesis, vitamin B6 , and glycerophospholipid metabolism pathways and that silybin ameliorates liver injury on these compromised pathways.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Emodina , Fígado Gorduroso , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Animais , Aspartato Aminotransferases , Ácidos e Sais Biliares/metabolismo , Bilirrubina/metabolismo , Bilirrubina/farmacologia , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Colesterol , Cromatografia Líquida , Emodina/metabolismo , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Glicerofosfolipídeos/metabolismo , Fígado/metabolismo , Espectrometria de Massas , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , Ratos , Silibina/metabolismo , Silibina/farmacologia , Vitaminas/metabolismo , Vitaminas/farmacologia
19.
Viruses ; 14(5)2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35632829

RESUMO

Phage therapy is a promising biocontrol management on plant diseases caused by bacterial pathogens due to its specificity, efficiency and environmental friendliness. The emergence of natural phage-resistant bacteria hinders the application of phage therapy. Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of the devastating bacterial leaf blight disease of rice. Here, we obtained a spontaneous mutant C2R of an Xoo strain C2 showing strong resistance to the lytic phage X2. Analysis of the C2R genome found that the CDS2289 gene encoding glycosyltransferase acquired a frameshift mutation at the 180th nucleotide site, which also leads to a premature stop mutation at the 142nd amino acid. This mutation confers the inhibition of phage adsorption through the changes in lipopolysaccharide production and structure and bacterial surface morphology. Interestingly, glycosyltransferase-deficient C2R and an insertional mutant k2289 also showed reduced virulence, suggesting the trade-off costs of phage resistance. In summary, this study highlights the role of glycosyltransferase in interactions among pathogenic bacteria, phages and plant hosts, which provide insights into balanced coevolution from environmental perspectives.


Assuntos
Bacteriófagos , Siphoviridae , Bacteriófagos/genética , Glicosiltransferases/genética , Lipopolissacarídeos , Mutação , Xanthomonas
20.
Support Care Cancer ; 30(6): 5221-5229, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35260921

RESUMO

BACKGROUND: The study aimed to compare the predictive values of three widely used nutritional assessment methods, body mass index (BMI), Nutritional Risk Screening 2002 (NRS 2002), and the prognostic nutritional index (PNI), for different clinical prognostic indicators of ovarian cancer patients. METHODS: Patients diagnosed with ovarian cancer treated in our hospital between January 2017 and March 2019 were retrospectively included. The three nutritional assessment methods were assessed, and multivariable analysis was conducted to explore predictive factors for clinical prognoses. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUROC) were generated to evaluate the discriminative abilities of the three nutritional assessment tools. RESULTS: A total of 442 patients were recruited. Multivariable analysis revealed that the PNI value predicted 1-year death and 1-year recurrence and that both the NRS 2002 score and the PNI value predicted 30-day readmission (P < 0.05). For PNI, AUROCs were 0.834 for predicting 1-year death and 0.719 for 1-year recurrence prediction; for NRS, the AUROC was 0.820 2002 for predicting 30-day readmission. The optimal cutoff values that maximized the prognostic prediction ability were PNI values of 47.75 g/L and 50.40 g/L for 1-year death and 1-year recurrence, respectively, and an NRS 2002 score of 3 points for 30-day readmission following discharge. CONCLUSION: For ovarian cancer patients, the PNI is better at predicting 1-year death and 30-day readmission after discharge, and the NRS 2002 is superior for predicting 1-year recurrence.


Assuntos
Avaliação Nutricional , Neoplasias Ovarianas , Feminino , Humanos , Estado Nutricional , Neoplasias Ovarianas/diagnóstico , Prognóstico , Estudos Retrospectivos
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