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1.
Proc Natl Acad Sci U S A ; 121(5): e2318718121, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38252820

RESUMEN

Several compounds have been used for atherosclerosis treatment, including clinical trials; however, no anti-atherosclerotic drugs based on hemodynamic force-mediated atherogenesis have been discovered. Our previous studies demonstrated that "small mothers against decapentaplegic homolog 1/5" (Smad1/5) is a convergent signaling molecule for chemical [e.g., bone morphogenetic proteins (BMPs)] and mechanical (e.g., disturbed flow) stimulations and hence may serve as a promising hemodynamic-based target for anti-atherosclerosis drug development. The goal of this study was to develop a high-throughput screening (HTS) platform to identify potential compounds that can inhibit disturbed flow- and BMP-induced Smad1/5 activation and atherosclerosis. Through HTS using a Smad1/5 downstream target inhibitor of DNA binding 1 (Id-1) as a luciferase reporter, we demonstrated that KU-55933 and Apicidin suppressed Id-1 expression in AD-293 cells. KU-55933 (10 µM), Apicidin (10 µM), and the combination of half doses of each [1/2(K + A)] inhibited disturbed flow- and BMP4-induced Smad1/5 activation in human vascular endothelial cells (ECs). KU-55933, Apicidin, and 1/2(K + A) treatments caused 50.6%, 47.4%, and 73.3% inhibitions of EC proliferation induced by disturbed flow, respectively, whereas EC inflammation was only suppressed by KU-55933 and 1/2(K + A), but not Apicidin alone. Administrations of KU-55933 and 1/2(K + A) to apolipoprotein E-deficient mice inhibited Smad1/5 activation in ECs in athero-susceptible regions, thereby suppressing endothelial proliferation and inflammation, with the attenuation of atherosclerotic lesions in these mice. A unique drug screening platform has been developed to demonstrate that KU-55933 and its combination with Apicidin are promising therapeutic compounds for atherosclerosis based on hemodynamic considerations.


Asunto(s)
Aterosclerosis , Células Endoteliales , Morfolinas , Pironas , Humanos , Animales , Ratones , Evaluación Preclínica de Medicamentos , Ensayos Analíticos de Alto Rendimiento , Aterosclerosis/tratamiento farmacológico , Hemodinámica , Inflamación
2.
Oncologist ; 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39245044

RESUMEN

BACKGROUND: The impact of sidedness on survival of later-line treatment in patients with metastatic colorectal cancer (mCRC) is undetermined. This study aimed to investigate the association between sidedness and survival among chemotherapy refractory patients with mCRC treated with trifluridine/tipiracil (TAS-102) or regorafenib or both. PATIENTS AND METHODS: Patients with mCRC treated with TAS-102 or regorafenib between 2015 and 2020 was retrospectively collected. Patients were stratified into TAS-102 first and regorafenib first, then subdivided into TAS-102 followed by regorafenib (T-R) and regorafenib followed by TAS-102 (R-T) groups. The oncologic outcomes were presented with time-to-treatment failure (TTF) and overall survival (OS). RESULTS: After matching, 376 TAS-102 patients and 376 regorafenib patients were included for outcomes comparison. TTF had insignificant differences while OS was significantly different between TAS-102 and regorafenib groups. Median TTF and OS were 1.9 months versus 2.0 months (P = .701) and 9.1 months versus 7.0 months (P = .008) in TAS-102 and regorafenib, respectively. The OS benefits were consistent regardless primary tumor location. Subgroup analysis with 174 T-R patients and 174 R-T patients was investigated for treatment sequences. TTF and OS had significant differences in both groups. Median TTF and OS were 8.5 months versus 6.3 months (P = .001) and 14.4 months versus 12.6 months (P = .035) in T-R and R-T groups, respectively. The TTF and OS benefits were persisted regardless primary tumor location. CONCLUSION: TAS-102 first provided a better survival benefit in chemotherapy refractory patients with mCRC across all sidedness. Further prospective studies are warranted to validate our conclusions.

3.
FASEB J ; 37(4): e22849, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36884358

RESUMEN

DCAF13 is a substrate recognition protein in the ubiquitin-proteasome system with oncogenic effects in several malignant tumors. However, it is unclear that the relationship between DCAF13 expression pattern and prognosis across different cancer types. Also unknown is the biological function or effects on the immune microenvironment of DCAF13. In this study, we parsed multiple public databases to explore the potential tumorigenic actions of DCAF13, including correlations with prognosis, microsatellite instability (MSI), tumor mutational burden (TMB), immune checkpoint genes, immune cell infiltration, and immunotherapy response in pan-cancer. Moreover, we validated DCAF13 expression in a tissue microarray by immunohistochemistry and investigate its effects in vitro and in vivo. The results showed that DCAF13 was upregulated in 17 cancer types and correlated with poor prognosis in many cancers. Also, the correlation between DCAF13 and TMB was found in 14 cancers as well as MSI in nine. The expression level of DCAF13 was found to be notably correlated with immune cell infiltration, showing a negative correlation with CD4 T cell infiltration and a positive correlation with neutrophil infiltration. The oncogene DCAF13 expression was shown to have a positive correlation with CD274 or ADORA2A and negative correlation with VSIR, TNFRSF4, or TNFRSF14 across large subsets of human cancers. Finally, we observed that DCAF13 was highly expressed in a tissue microarray of lung cancer. In immunocompromised mouse models, xenograft growth of human lung cancer cells was significantly inhibited by DCAF13 knockdown. Our results highlighted the value of DCAF13 as a promising independent predictor of poor prognosis through numerous biological processes. High DCAF13 expression often predicts suppressive immune microenvironment and immunotherapy resistance in a pan-cancer context.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Animales , Ratones , Humanos , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Oncogenes , Carcinogénesis , Linfocitos T CD4-Positivos , Microambiente Tumoral , Proteínas de Unión al ARN
4.
Nutr Neurosci ; 27(4): 342-352, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36976719

RESUMEN

INTRODUCTION: Insulin resistance (IR) is a feature of metabolic syndrome and plays an important role in cognitive impairment (CI). The triglyceride-glucose (TyG) index is a convenient and cost-effective surrogate for assessing IR. This study aimed to assess the association between the TyG index and CI. METHODS: This community population-based cross-sectional study used a cluster-sampling methodology. All participants underwent the education-based Mini-Mental State Examination (MMSE), and those with CI were identified using standard thresholds. The fasting blood triglyceride and glucose levels were measured in the morning, and the TyG index was calculated as ln (½ fasting triglyceride level [mg/dL] × fasting blood glucose level [mg/dL]). Multivariable logistic regression and subgroup analysis were used to assess the relationship between the TyG index and CI. RESULTS: This study included 1484 subjects, of which 93 (6.27%) met the CI criteria. Multivariable logistic regression showed that CI incidence increased by 64% per unit increase in the TyG index (odds ratio [OR] = 1.64, 95% confidence interval [CI]: 1.02-2.63, p = 0.042). CI risk was 2.64-fold higher in the highest TyG index quartile compared to the lowest TyG index quartile (OR = 2.64, 95% CI: 1.19-5.85, p = 0.016). Finally, interaction analysis showed that sex, age, hypertension, and diabetes did not significantly affect the association between the TyG index and CI. CONCLUSION: The present study suggested that an elevated TyG index was associated with a higher CI risk. Subjects with a higher TyG index should manage and treat at an early stage to alleviate the cognitive decline.


Asunto(s)
Glucosa , Resistencia a la Insulina , Humanos , Glucemia/metabolismo , Estudios Transversales , Factores de Riesgo , Triglicéridos , Biomarcadores , China/epidemiología
5.
Appl Microbiol Biotechnol ; 108(1): 134, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38229304

RESUMEN

Old yellow enzymes (OYEs) have been proven as powerful biocatalysts for the asymmetric reduction of activated alkenes. Fungi appear to be valuable sources of OYEs, but most of the fungal OYEs are unexplored. To expand the OYEs toolbox, a new thermophilic-like OYE (AfOYE1) was identified from Aspergillus flavus strain NRRL3357. The thermal stability analysis showed that the T1/2 of AfOYE1 was 60 °C, and it had the optimal temperature at 45 °C. Moreover, AfOYE1 exhibited high reduction activity in a wide pH range (pH 5.5-8.0). AfOYE1 could accept cyclic enones, acrylamide, nitroalkenes, and α, ß-unsaturated aldehydes as substrates and had excellent enantioselectivity toward prochiral alkenes (> 99% ee). Interestingly, an unexpected (S)-stereoselectivity bioreduction toward 2-methylcyclohexenone was observed. The further crystal structure of AfOYE1 revealed that the "cap" region from Ala132 to Thr182, the loop of Ser316 to Gly325, α short helix of Arg371 to Gln375, and the C-terminal "finger" structure endow the catalytic cavity of AfOYE1 quite deep and narrow, and flavin mononucleotide (FMN) heavily buried at the bottom of the active site tunnel. Furthermore, the catalytic mechanism of AfOYE1 was also investigated, and the results confirmed that the residues His211, His214, and Tyr216 compose its catalytic triad. This newly identified thermophilic-like OYE would thus be valuable for asymmetric alkene hydrogenation in industrial processes. KEY POINTS: A new thermophilic-like OYE AfOYE1 was identified from Aspergillus flavus, and the T1/2 of AfOYE1 was 60 °C AfOYE1 catalyzed the reduction of 2-methylcyclohexenone with (S)-stereoselectivity The crystal structure of AfOYE1 was revealedv.


Asunto(s)
Aspergillus flavus , NADPH Deshidrogenasa , Aspergillus flavus/metabolismo , NADPH Deshidrogenasa/metabolismo , Dominio Catalítico , Catálisis , Alquenos
6.
Food Microbiol ; 121: 104524, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38637086

RESUMEN

Aspergillus flavus colonization on agricultural products during preharvest and postharvest results in tremendous economic losses. Inspired by the synergistic antifungal effects of essential oils, the aims of this study were to explore the mechanism of combined cinnamaldehyde and nonanal (SCAN) against A. flavus and to evaluate the antifungal activity of SCAN loading into diatomite (DM). Shriveled mycelia were observed by scanning electron microscopy, especially in the SCAN treatment group. Calcofluor white staining, transmission electron microscopy, dichloro-dihydro-fluorescein diacetate staining and the inhibition of key enzymes in tricarboxylic acid cycle indicated that the antifungal mechanism of SCAN against A. flavus was related to the cell wall damage, reactive oxygen species accumulation and energy metabolism interruption. RNA sequencing revealed that some genes involved in antioxidation were upregulated, whereas genes responsible for cell wall biosynthesis, oxidative stress, cell cycle and spore development were significantly downregulated, supporting the occurrence of cellular apoptosis. In addition, compared with the control group, conidia production in 1.5 mg/mL DM/cinnamaldehyde, DM/nonanal and DM/SCAN groups were decreased by 27.16%, 48.22% and 76.66%, respectively, and the aflatoxin B1 (AFB1) contents decreased by 2.00%, 73.02% and 84.15%, respectively. These finding suggest that DM/SCAN complex has potential uses in food preservation.


Asunto(s)
Acroleína/análogos & derivados , Aldehídos , Antifúngicos , Aspergillus flavus , Antifúngicos/farmacología , Antifúngicos/metabolismo , Aflatoxina B1/metabolismo , Conservación de Alimentos
7.
Food Microbiol ; 123: 104588, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39038893

RESUMEN

Aspergillus flavus infects important crops and produces carcinogenic aflatoxins, posing a serious threat to food safety and human health. Biochemical analysis and RNA-seq were performed to investigate the effects and mechanisms of piperitone on A. flavus growth and aflatoxin B1 biosynthesis. Piperitone significantly inhibited the growth of A. flavus, AFB1 production, and its pathogenicity on peanuts and corn flour. Differentially expressed genes (DEGs) associated with the synthesis of chitin, glucan, and ergosterol were markedly down-regulated, and the ergosterol content was reduced, resulting in a disruption in the integrity of the cell wall and cell membrane. Moreover, antioxidant genes were down-regulated, the correspondingly activities of antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase were reduced, and levels of superoxide anion and hydrogen peroxide were increased, leading to a burst of reactive oxygen species (ROS). Accompanied by ROS accumulation, DNA fragmentation and cell autophagy were observed, and 16 aflatoxin cluster genes were down-regulated. Overall, piperitone disrupts the integrity of the cell wall and cell membrane, triggers the accumulation of ROS, causes DNA fragmentation and cell autophagy, ultimately leading to defective growth and impaired AFB1 biosynthesis.


Asunto(s)
Aflatoxina B1 , Antifúngicos , Aspergillus flavus , Especies Reactivas de Oxígeno , Zea mays , Aspergillus flavus/efectos de los fármacos , Aspergillus flavus/genética , Aspergillus flavus/crecimiento & desarrollo , Aspergillus flavus/metabolismo , Zea mays/microbiología , Antifúngicos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Arachis/microbiología , Pared Celular/efectos de los fármacos , Pared Celular/metabolismo
8.
Ecotoxicol Environ Saf ; 284: 116940, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39232296

RESUMEN

BACKGROUND: Individuals diagnosed with type 2 diabetes (T2D) frequently exhibit chronic kidney disease (CKD) which may be caused by environmental hazards such as exposure to air pollutants. However, limited research has explored the effects of prolonged exposure to air pollutants on CKD development in this population. This study examines the relationship between long-term exposure to air pollutants and CKD incidence in a longitudinal cohort of individuals with type 2 diabetes in Taiwan METHODS: Between 2003 and 2005, we recruited 1316 T2D patients (693 females [52.66 %]; mean age 56.16 ± 8.97 years). Patients were followed until December 31, 2012, with at least two clinical visits. Baseline demographics, medical history, and biomarker levels were collected. The development of CKD was determined by eGFR level < 60 mL/min/1.73 m2. Monthly averages of nitrogen dioxide (NO2) and fine particulate matter [PM ≤ 2.5 µm in aerodynamic diameter (PM2.5)] were acquired from 72 ambient air monitoring stations. The kriging method was employed to estimate the exposure levels to PM2.5, NO2, temperature, and relative humidity in the participants' residential areas. Cox regression with time-dependent covariates regression was applied to assess the impact of long-term exposure to air pollutants and CKD risk. RESULTS: Of 992 patients with normal renal function at baseline, 411 (41.43 %) experienced CKD occurrence over a median follow-up period of 5.45 years. The incidence of CKD was 93.96 cases per 1000 person-years. In multivariable adjusted models, patients exposed to PM2.5 levels above the third quartile of (>33.44 µg/m3) and NO2 levels above the fourth quartile (>22.55 ppb) were found to have an increased risk of CKD occurrence compared to lower exposure levels. CONCLUSIONS: This longitudinal study highlights the increased risk of CKD in individuals with type 2 diabetes due to prolonged exposure to NO2 and PM2.5, emphasizing the need for tailored air quality management strategies for this high-risk population.

9.
J Environ Manage ; 359: 120989, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38678906

RESUMEN

The efficient utilization of food waste (FW) resources through Food Waste Valorization (FWV) has received increasing attention in recent years. Various decision-making studies have been undertaken to facilitate FWV implementation, such as the studies on decision-making framework and FWV technology assessment. Food waste hierarchy is a widely discussed framework in FW management, but it was found too simplified and does not always contribute positively to environmental sustainability. Moreover, decision-making studies in FWV often focus on specific aspects of the food system and employ distinctive decision-making approaches, making it difficult to compare the results from different studies. Therefore, our literature review is conducted to provide a comprehensive understanding of FWV decision-making. This study identifies what decisions are needed, and three levels of decisions are revealed: system-level, FW stream-level, and FWV option-level. The assessment approaches and criteria used to support decision-making in FWV are also collected and analyzed. Building upon these findings, an hourglass model is synthesized to provide a holistic illustration of decision-making in FWV. This study untangles the complexities of FWV decision-making and sheds light on the limitations of current studies. We anticipate this study will make more people realize that FWV is a multidisciplinary issue and requires the collective participation of researchers, practitioners, policymakers, and consumers. Such collective engagement is essential to effectively address practical challenges and propel the transition of the current food system toward a more resource-efficient paradigm.


Asunto(s)
Toma de Decisiones , Alimentos , Administración de Residuos/métodos , Alimento Perdido y Desperdiciado
10.
BMC Genomics ; 24(1): 624, 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37858069

RESUMEN

Anaerobic parasitic ciliates are a specialized group of ciliates that are adapted to anoxic and oxygen-depleted habitats. Among them, Balantidium polyvacuolum, which inhabits the hindgut of Xenocyprinae fishes, has received very limited scientific attention, so the molecular mechanism of its adaptation to the digestive tract microenvironment is still unclear. In this study, transmission electron microscopy (TEM) and single-cell transcriptome analysis were used to uncover the metabolism of B. polyvacuolum. Starch granules, endosymbiotic bacteria, and multiple specialized mitochondrion-related organelles (MROs) of various shapes were observed. The MROs may have completely lost the electron transport chain (ETC) complexes I, III, IV, and V and only retained succinate dehydrogenase subunit A (SDHA) of complex II. The tricarboxylic acid (TCA) cycle was also incomplete. It can be inferred that the hypoxic intestinal environment has led to the specialization of the mitochondria in B. polyvacuolum. Moreover, carbohydrate-active enzymes (CAZymes), including carbohydrate esterases, enzymes with a carbohydrate-binding module, glycoside hydrolases, and glycosyltransferases, were identified, which may constitute evidence that B. polyvacuolum is able to digest carbohydrates and starch. These findings can improve our knowledge of the energy metabolism and adaptive mechanisms of B. polyvacuolum.


Asunto(s)
Balantidium , Cipriniformes , Animales , Carbohidratos , Metabolismo Energético , Almidón
11.
Mol Ecol ; 32(17): 4709-4712, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37455332

RESUMEN

Rodent virus communities (viromes) are overrepresented with zoonotic viruses, and as such are a key host system for the study of zoonotic viruses. However, the extent of viral diversity beyond characterized zoonotic viruses, and the factors that modulate the viromes of rodents remain opaque. In this issue of Molecular Ecology, Raghwani et al. (2023) use rodents as a model to understand the role of seasonality in dictating virome abundance and composition-a factor known to play an important role in most animal one-host, one-pathogen systems. These data are not only highly relevant to rodents, but have broad applications across understanding and disentangling animal virome ecology.


Asunto(s)
Viroma , Virus , Animales , Roedores , Virus/genética , Estaciones del Año , Filogenia , Metagenómica
12.
Opt Express ; 31(25): 41026-41033, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38087511

RESUMEN

We present a size-based sorting method for nanoparticles in microfluidics with the aid of light-patterned dielectrophoresis (DEP) force. In a microfluidic channel, we have succeeded in manipulating a random distribution of particles into a single stream with the DEP force as well as the hydrodynamic force, and more strikingly, the trajectory of particles is found to be size-dependent, implicating that we can precisely separate nanoparticles based on their sizes even if they are identical in mass. We have numerically predicted the behavior of sorting nanoparticles, emphasizing on the size, velocity and electrical permittivity, so as to know their influences on the effective sorting, particularly in terms of high throughput. Our work confirms that what we believe to be the novel manipulation of nanoparticles features its flexibility as well as high throughput.

13.
Neuroepidemiology ; 57(2): 100-111, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36228596

RESUMEN

INTRODUCTION: The relationship between obesity and cognitive impairment (CI) is highly heterogeneous in previous studies, which may be due to insufficient consideration of anthropometric indicators and sex. This study compared the cross-sectional relationships among body mass index (BMI), waist-to-hip ratio (WHR), and CI among people aged ≥40 years, and sex-specific relationships were also considered. METHODS: This was a population-based cross-sectional study with a cluster sampling design. CI was defined as a Mini-Mental State Examination score lower than the cutoff value. Multivariate logistic regression was used. BMI and WHR were fitted as both restricted cubic splines and categorical data. Stratified analysis and interaction analysis were performed to explore the sex-specific relationship. RESULTS: A total of 1,792 subjects (40.5% male) were analyzed, and 230 were confirmed to have CI. The relationships among BMI, WHR, and CI were significant (poverall = 0.023, pnonlinear = 0.097; poverall = 0.017, pnonlinear = 0.078, respectively) but exhibited an opposite trend in the total population in the analyses with BMI and WHR as restricted cubic splines. Further categorical analyses showed that subjects with a BMI <23 kg/m2 tended to have a higher risk of CI than those with BMI ≥23 kg/m2 (16.2% vs. 11.8%, p = 0.017; OR = 1.366 [0.969-1.926], p = 0.075), and subjects with a WHR >0.92 had a significantly higher risk of CI than those with a WHR ≤0.92 (11.7% vs. 16.2%, p = 0.011; OR = 1.619 [1.161-2.258], p = 0.005). In addition, the relationship between a low BMI and CI was more significant in males (p = 0.034), while the relationship between a high WHR and CI was more significant in females (p = 0.002). Further studies are needed to confirm the sex differences because of the marginal significance result in the interaction analysis (p = 0.051 for interaction term BMI × sex; p = 0.056 for interaction term WHR × sex). CONCLUSION: The relationships among BMI, WHR, and CI exhibit an opposite trend. A low BMI or high WHR was positively associated with CI, which was more prominent in males for a low BMI and females for a high WHR.


Asunto(s)
Disfunción Cognitiva , Humanos , Masculino , Femenino , Relación Cintura-Cadera , Índice de Masa Corporal , Estudios Transversales , Factores de Riesgo , Disfunción Cognitiva/epidemiología , China/epidemiología
14.
Environ Res ; 217: 114968, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36455628

RESUMEN

Evaluation joint cadmium (Cd) and copper (Cu) phytotoxicity in wide range of subtropical agricultural soils is highly vital for phytoremediation of soils contaminated with Cd and Cu. In this study, barley root elongation assays were performed in 30 representative soils in response to single and combined Cd and Cu inhibition. The single Cd caused nearly 50% inhibition of barley root elongation, and Cu induced more than 50% inhibition in most soils. Mixed Cd + Cu caused significant inhibition on barley growth with average relative root elongation values of 20.0% and 30.4% in soil with a pH < 7 and pH > 7, respectively. An antagonistic interaction was evaluated in combined Cd + Cu toxicity, which was strong in soils containing low soluble Cu and Cd contents. Soil pH was the controlling factor in predicting single and mixed Cd and Cu phytotoxicity, which could explain 44% and 46% variation of single Cd and Cu toxicity, respectively. Soil organic carbon and effective cation exchange capacity were another important factor positively influencing metal toxicity, which further improved empirical prediction models accuracy, with determined coefficient (r2) values of 0.44-0.84. These results provide a theoretical basis for soils Cd and Cu pollution control.


Asunto(s)
Intoxicación por Cadmio , Hordeum , Contaminantes del Suelo , Cobre/toxicidad , Cobre/análisis , Suelo/química , Cadmio/toxicidad , Carbono , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis
15.
World J Surg ; 47(5): 1144-1150, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36401089

RESUMEN

INTRODUCTION: Non-technical skills complement technical skills in surgeons to provide best possible care for patients. The former is essential to promote patient engagement. Coaching has been introduced to surgeons as a method to improve non-technical skills. We aimed to investigate the impact of coaching for surgeons on patient engagement in the outpatient consultation setting. METHODS: This was a single-centre cohort study conducted in South Australia. Consultant surgeons, suitable coaches, and patients were recruited. Coaches underwent further training by a human factors psychologist on being an effective coach. Outpatient consultations were recorded in an audio-visual format and analysed by investigators. Patient talking time, mutual eye gaze between surgeon and patient, and number of questions asked by the patient were measured as outcomes for patient engagement. RESULTS: 182 patients, 12 surgeons, and 4 coaches participated in the study. Each surgeon underwent 3 coaching sessions, 5 to 6 weeks apart. There were 62 pre-coaching patient consultations, 63 patient consultations after one coaching session, and 57 patient consultations after two coaching sessions. The mean talking time of the patient increased significantly after a single coaching session (P < 0.05) without making significant difference to the total consultation time (p = 0.76). Coaching sessions did not have a significant effect on mutual eye gaze or mean number of questions asked by the patient. CONCLUSION: Coaching of non-technical skills for surgeons appears to objectively improve patient engagement during the outpatient consultation. This would suggest that tailored coaching programs should be developed and delivered to surgeons to improve care delivery.


Asunto(s)
Tutoría , Cirujanos , Humanos , Tutoría/métodos , Participación del Paciente , Estudios de Cohortes , Cirujanos/educación
16.
Appl Microbiol Biotechnol ; 107(7-8): 2501-2514, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36809388

RESUMEN

Aspergillus niger produces genotoxic and carcinogenic ochratoxin A (OTA) that severely threatens human and animal health. Transcription factor Azf1 is essential in regulating fungal cell development and primary metabolism. However, its effect and mechanism on secondary metabolism are unclear. Here, we characterized and deleted a Azf1 homolog gene, An15g00120 (AnAzf1), in A. niger, which completely blocked OTA production, and repressed the OTA cluster genes, p450, nrps, hal, and bzip at the transcriptional level. The results indicated that AnAzf1 was a positive regulator of OTA biosynthesis. Transcriptome sequencing results showed that the AnAzf1 deletion significantly upregulated antioxidant genes and downregulated oxidative phosphorylation genes. Enzymes involved in reactive oxygen species (ROS) scavenging, including catalase (CAT) and peroxidase (POD) were increased, and the corresponding ROS levels were decreased. Upregulation of genes (cat, catA, hog1, and gfd) in the MAPK pathway and downregulation of genes in iron homeostasis were associated with decreased ROS levels, linking the altered MAPK pathway and iron homeostasis to lower ROS levels caused by AnAzf1 deletion. Additionally, enzymes including complex I (NADH-ubiquinone oxidoreductase), and complex V (ATP synthase), as well as ATP levels, were significantly decreased, indicating impaired oxidative phosphorylation caused by the AnAzf1-deletion. During lower ROS levels and impaired oxidative phosphorylation, OTA was not produced in ∆AnAzf1. Together, these results strongly suggested that AnAzf1 deletion blocked OTA production in A. niger by a synergistic interference of ROS accumulation and oxidative phosphorylation. KEY POINTS: • AnAzf1 positively regulated OTA biosynthesis in A. niger. • Deletion of AnAzf1 decreased ROS levels and impaired oxidative phosphorylation. • An altered MAPK pathway and iron homeostasis were associated with lower ROS levels.


Asunto(s)
Aspergillus niger , Ocratoxinas , Humanos , Aspergillus niger/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Metabolismo Secundario , Ocratoxinas/metabolismo , Hierro/metabolismo , Adenosina Trifosfato/metabolismo
17.
Appl Microbiol Biotechnol ; 107(23): 7213-7230, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37733053

RESUMEN

Plant volatile compounds have great potential for preventing and controlling fungal spoilage in post-harvest grains. Recently, we have reported the antifungal effects of trans-anethole, the main volatile constituent of the Illicium verum fruit, on Aspergillus flavus. In this study, the inhibitory mechanisms of trans-anethole against the growth of A. flavus mycelia were investigated using transcriptomic and biochemical analyses. Biochemical and transcriptomic changes in A. flavus mycelia were evaluated after exposure to 0.2 µL/mL trans-anethole. Scanning electron microscopy showed that trans-anethole treatment resulted in the surface wrinkling of A. flavus mycelia, and calcofluor white staining confirmed that trans-anethole treatment disrupted the mycelial cell wall structure. Annexin V-fluorescein isothiocyanate/propidium iodide double staining suggested that trans-anethole induced apoptosis in A. flavus mycelia. Reduced mitochondrial membrane potential and DNA damage were observed in trans-anethole-treated A. flavus mycelia using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine and 4',6-diamidino-2-phenylindole staining, respectively. 2',7'- Dichloro-dihydro-fluorescein diacetate staining and biochemical assays demonstrated that trans-anethole treatment cause the accumulation of reactive oxygen species in the A. flavus mycelia. Transcriptome results showed that 1673 genes were differentially expressed in A. flavus mycelia exposed to trans-anethole, which were mainly associated with multidrug transport, oxidative phosphorylation, citric acid cycle, ribosomes, and cyclic adenosine monophosphate signaling. We propose that trans-anethole can inhibit the growth of A. flavus mycelia by disrupting the cell wall structure, blocking the multidrug transport process, disturbing the citric acid cycle, and inducing apoptosis. This study provides new insights into the inhibitory mechanism of trans-anethole on A. flavus mycelia and will be helpful for the development of natural fungicides. KEY POINTS: • Biochemical analyses of A. flavus mycelia exposed to trans-anethole were performed • Transcriptomic changes in trans-anethole-treated A. flavus mycelia were analyzed • An inhibitory mechanism of trans-anethole on the growth of A. flavus mycelia was proposed.


Asunto(s)
Derivados de Alilbenceno , Antifúngicos , Antifúngicos/química , Aspergillus flavus , Transcriptoma , Derivados de Alilbenceno/metabolismo , Derivados de Alilbenceno/farmacología
18.
Appl Microbiol Biotechnol ; 107(1): 341-354, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36477927

RESUMEN

The prevention of fungal proliferation in postharvest grains is critical for maintaining grain quality and reducing mycotoxin contamination. Fumigation with natural gaseous fungicides is a promising and sustainable approach to protect grains from fungal spoilage. In this study, the antifungal activities of (E)-2-alkenals (C5-C10) on Aspergillus flavus were tested in the vapor phase, and (E)-2-heptenal showed the highest antifungal activity against A. flavus. (E)-2-Heptenal completely inhibited A. flavus growth at 0.0125 µL/mL and 0.2 µL/mL in the vapor phase and liquid contact, respectively. (E)-2-Heptenal can disrupt the plasma membrane integrity of A. flavus via leakage of intracellular electrolytes. Scanning electron microscopy indicated that the mycelial morphology of A. flavus was remarkably affected by (E)-2-heptenal. Metabolomic analyses indicated that 49 metabolites were significantly differentially expressed in A. flavus mycelia exposed to 0.2 µL/mL (E)-2-heptenal; these metabolites were mainly involved in galactose metabolism, starch and sucrose metabolism, the phosphotransferase system, and ATP-binding cassette transporters. ATP production was reduced in (E)-2-heptenal-treated A. flavus, and Janus Green B staining showed reduced cytochrome c oxidase activity. (E)-2-Heptenal treatment induced oxidative stress in A. flavus mycelia with an accumulation of superoxide anions and hydrogen peroxide and increased activities of superoxide dismutase and catalase. Simulated storage experiments showed that fumigation with 400 µL/L of (E)-2-heptenal vapor could completely inhibit A. flavus growth in wheat grains with 20% moisture; this demonstrates its potential use in preventing grain spoilage. This study provides valuable insights into understanding the antifungal effects of (E)-2-heptenal on A. flavus. KEY POINTS : • (E)-2-Heptenal vapor showed the highest antifungal activity against A. flavus among (C5-C10) (E)-2-alkenals. • The antifungal effects of (E)-2-heptenal against A. flavus were determined. • The antifungal actions of (E)-2-heptenal on A. flavus were revealed by metabolomics and biochemical analyses.


Asunto(s)
Antifúngicos , Aspergillus flavus , Antifúngicos/farmacología , Antifúngicos/metabolismo , Aldehídos/metabolismo , Metabolómica
19.
Biol Pharm Bull ; 46(6): 764-772, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37258141

RESUMEN

Diabetic peripheral neuropathy (DPN) is an early developing complication of diabetes mellitus associated with nerve dysfunction. Artesunate (ART), a natural compound extracted from the herb Artemisia annua L., was reported to benefit neural injury. However, whether ART has a role in preventing DPN is still unknown. In this study, a rat model of DPN with a high fat diet feeding and streptozotocin (STZ) injection was established. The findings indicated that ART treatment significantly ameliorated hyperglycemia-induced hot plate reaction latency (HPRL) decline, cold sensitivity and mechanical allodynia, and nerve injury by inhibiting sciatic nerve apoptosis. Further, ART restored high glucose (HG)-induced elevated apoptosis and deficient survival in rat neuronal Schwann cells, RSC96 cells. We demonstrated that ART promoted protein kinase B (AKT) phosphorylation as well as its downstream factor mammalian target of rapamycin (mTOR) in vivo and in vitro. Of note, the protective effects of ART in RSC96 cells under HG condition could be counteracted by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Taken together, ART mitigated hyperglycemia-induced nerve injury by suppressing apoptosis and promoting the viability of Schwann cells via the PI3K/AKT/mTOR signaling pathway.


Asunto(s)
Diabetes Mellitus , Neuropatías Diabéticas , Hiperglucemia , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Artesunato/farmacología , Artesunato/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/metabolismo , Células de Schwann/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Hiperglucemia/metabolismo , Apoptosis , Mamíferos/metabolismo , Diabetes Mellitus/metabolismo
20.
BMC Pregnancy Childbirth ; 23(1): 174, 2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36918869

RESUMEN

BACKGROUND: GnRH agonist (GnRHa) has been reported to have direct effects and functional roles in the endometrium and embryos. Several meta-analyses have shown that GnRHa administration in the luteal phase improved the live birth rate or pregnancy rate in both fresh and frozen embryo transfer (FET) cycles. The aim of this study was to investigate whether luteal GnRHa administration could also improve in vitro fertilization (IVF) outcomes in patients undergoing hormone replacement therapy (HRT) cycles with GnRHa suppression. METHODS: The retrospective cohort study included a total of 350 patients undergoing GnRHa-HRT FET cycles. The study group included 179 patients receiving an additional single dose of GnRHa in the luteal phase following embryo transfer. A total of 171 patients in the control group did not receive luteal GnRHa. The baseline and cycle characteristics and reproductive outcomes were compared between the two groups. RESULTS: Baseline and cycle characteristics were similar between the two groups, except lower AMH levels were found in the luteal GnRHa group than in the control group. The luteal GnRHa group had a significantly higher ongoing pregnancy rate and live birth rate than the control group. The multivariate analysis revealed that luteal GnRHa administration was positively associated with ongoing pregnancy (OR 2.04, 95% CI 1.20-3.47, P = 0.008) and live birth (OR 2.03, 95% CI 1.20-3.45, P = 0.009). When the subgroup of patients with recurrent implantation failure was analyzed, the multivariate analysis also showed that luteal GnRHa administration had beneficial effects on ongoing pregnancy (OR 4.55, 95% CI 1.69-12.30, P = 0.003) and live birth (OR 4.30, 95% CI 1.59-11.65, P = 0.004). CONCLUSIONS: Our data suggest that the addition of one luteal dose of GnRHa may improve the live birth rate in patients undergoing the GnRHa-HRT protocol.


Asunto(s)
Tasa de Natalidad , Fase Luteínica , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Hormona Liberadora de Gonadotropina , Transferencia de Embrión/métodos , Índice de Embarazo , Fertilización In Vitro , Nacimiento Vivo
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