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1.
Eur J Clin Microbiol Infect Dis ; 43(5): 905-914, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38472518

RESUMEN

BACKGROUND: The existing literature lacks studies examining the epidemiological link between scrub typhus and deep vein thrombosis (DVT) or pulmonary embolism (PE), and the long-term outcomes. The objective of this study is to explore the potential association between scrub typhus and the subsequent risk of venous thromboembolism, and long-term mortality. METHOD: This nationwide cohort study identified 10,121 patients who were newly diagnosed with scrub typhus. Patients with a prior DVT or PE diagnosis before the scrub typhus infection were excluded. A comparison cohort of 101,210 patients was established from the general population using a propensity score matching technique. The cumulative survival HRs for the two cohorts were calculated by the Cox proportional hazards model. RESULT: After adjusting for sex, age, and comorbidities, the scrub typhus group had an adjusted HR (95% CI) of 1.02 (0.80-1.30) for DVT, 1.11 (0.63-1.93) for PE, and 1.16 (1.08-1.25) for mortality compared to the control group. The post hoc subgroup analysis revealed that individuals younger than 55 years with a prior scrub typhus infection had a significantly higher risk of DVT (HR: 1.59; 95% CI: 1.12-2.25) and long-term mortality (HR: 1.75; 95% CI, 1.54-1.99). CONCLUSION: The scrub typhus patients showed a 16% higher risk of long-term mortality. For those in scrub typhus cohort below 55 years of age, the risk of developing DVT was 1.59 times higher, and the risk of mortality was 1.75 times higher. Age acted as an effect modifier influencing the relationship between scrub typhus and risk of new-onset DVT and death.


Asunto(s)
Tifus por Ácaros , Tromboembolia Venosa , Humanos , Tifus por Ácaros/complicaciones , Tifus por Ácaros/epidemiología , Tifus por Ácaros/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/mortalidad , Tromboembolia Venosa/etiología , Factores de Riesgo , Estudios de Cohortes , Modelos de Riesgos Proporcionales , Anciano de 80 o más Años , Embolia Pulmonar/mortalidad , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiología , Adulto Joven
2.
Ann Hematol ; 102(12): 3357-3367, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37726492

RESUMEN

Arsenic trioxide (ATO) treatment effectively prolongs the overall survival of patients with acute promyelocytic leukemia (APL). Mutations in the oncogene PML::RARA were found in patients with ATO-resistant and relapsed APL. However, some relapsed patients do not have such mutations. Here, we performed microarray analysis of samples from newly diagnosed and relapsed APL, and found different microRNA (miRNA) expression patterns between these two groups. Among the differentially expressed miRNAs, miR-603 was expressed at the lowest level in relapsed patients. The expression of miR-603 and its predicted target tropomyosin-related kinase B (TrkB) were determined by PCR and Western blot. Proliferation was measured using an MTT assay, while apoptosis, cell cycle and CD11b expression were analyzed using flow cytometry. In APL patients, the expression of miR-603 was negatively correlated with that of TrkB. miR-603 directly targeted TrkB and downregulated TrkB expression in the APL cell line NB4. miR-603 increased cell proliferation by promoting the differentiation and inhibiting the apoptosis of NB4 cells. This study shows that the miR-603/ TrkB axis may be a potent therapeutic target for relapsed APL.


Asunto(s)
Antineoplásicos , Arsenicales , Leucemia Promielocítica Aguda , MicroARNs , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Arsenicales/farmacología , Óxidos/farmacología , Trióxido de Arsénico/farmacología , Trióxido de Arsénico/uso terapéutico , Apoptosis/genética , MicroARNs/genética , Proliferación Celular , Diferenciación Celular/genética , Antineoplásicos/uso terapéutico
3.
Cell Mol Biol (Noisy-le-grand) ; 69(13): 270-278, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38158666

RESUMEN

Long non-coding RNAs (lncRNAs) have a vital potential in premature delivery. This research was intended to explore PSMA3-AS1's role in premature delivery as well as its possible molecular mechanism. We enrolled 100 premature delivery patients and 100 term patients. Fetal membranes were collected. RT-qPCR was adopted for evaluating PSMA3-AS1, miRNA-224-3p, along with Nrf2 expression. Cell function experiments were implemented to clarify PSMA3-AS1 functions in human trophoblast HTR-8/SVneo cells. Rescue together with mechanistic experiments were implemented for assessing the regulatory function and interaction between miR-224-3p and PSMA3-AS1 or Nrf2 axis in human trophoblast cells. The results uncovered that PSMA3-AS1 level presented downregulation in the fetal membrane tissues and human trophoblast cells. Overexpressed PSMA3-AS1 enhanced cell proliferation but suppressed ferroptosis in human trophoblast cells. Besides, PSMA3-AS1 elevation also attenuated the LPS-induced inflammatory response and restored the LPS-induced upregulation of 20α-HSD and downregulation of progesterone (P4). Mechanistically, miR-224-3p could bind to PSMA3-AS1 and present upregulation in fetal membranes and human trophoblast cells. Notably, overexpressed miR-224-3p offset the influences of PSMA3-AS1 on human trophoblast cell proliferation and ferroptosis. Furthermore, Nrf2 was targeted by miR-224-3p. Downregulated Nrf2 offset the influences of the miR-224-3p inhibitor and induced HTR-8/SVneo dysfunction. Additionally, Nrf2 transcriptionally activated PSMA3-AS1 and GPX4. In conclusion, PSMA3-AS1 expression is low during premature delivery and overexpressing PSMA3-AS1 promotes proliferation and suppresses ferroptosis of human trophoblast cells by interacting with miR-224-3p to downregulate Nrf2. Therefore, enhancing PSMA3-AS1 expression may be a promising therapeutic strategy to prevent premature delivery.


Asunto(s)
Ferroptosis , MicroARNs , Nacimiento Prematuro , ARN Largo no Codificante , Femenino , Humanos , Recién Nacido , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Lipopolisacáridos , MicroARNs/genética , MicroARNs/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Nacimiento Prematuro/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Embarazo
4.
Fam Pract ; 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37756627

RESUMEN

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists change the gastric pH and reduce the intestinal absorption of nonheme iron. Case reports and case-control studies have demonstrated that absorption of iron is affected by gastric acidity, but the clinical importance of these drug-drug interactions has remained uncertain. OBJECTIVES: The present case-control study employed 2 million longitudinal claims in 2011-2018 in the Taiwan National Health Insurance Research Database to investigate the impact of PPIs/H2 antagonists on the occurrence of iron-deficiency anaemia (IDA). METHODS: The present study retrospectively compared exposure to PPIs/H2 antagonists for 1 year among 5,326 cases with IDA and 21,304 matched controls. The postdiagnosis prescribing pattern was also calculated to understand current practice. RESULTS: Long-term (≥2 month) use of PPIs/H2 antagonists resulted in a higher risk of developing IDA than noncontinuous use/nonuse of those drugs (adjusted odds ratio [aOR] = 2.36, 95% confidence interval [CI] = 1.94-2.86, P < 0.001). There were significant changes in the postdiagnosis prescribing patterns of PPIs/H2 antagonists. The risk of developing IDA remained significant in the female subgroup (aOR = 2.16, 95% CI = 1.73-2.70, P < 0.001) and was even more prominent in those aged ≥ 50 years (aOR = 2.68, 95% CI = 1.94-3.70, P < 0.05). CONCLUSIONS: This study found that long-term use of PPIs/H2 antagonists increased the risk of developing IDA, and there was strong evidence of prescription pattern adjustments postdiagnosis. Physicians and pharmacists should be aware of this risk when patients are expected to take or have been taking PPIs/H2 antagonists for the long term.


Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists, 2 kinds of gastric suppressants commonly used for gastroesophageal reflux disease, decrease iron absorption in the gut and thus increase the risk of developing iron-deficiency anaemia (IDA). We constructed a retrospective matched case-control study within the Taiwan National Health Insurance Research Database. The longer period of PPIs/H2 antagonists used, the higher risk of IDA was, with the highest risk in female elderly groups (adjusted odds ratio = 2.68 in females aged ≥ 50). PPI users had a higher risk than H2 antagonist users during the 1-year follow-up. The prescription patterns postdiagnosis of IDA witnessed considerable drops for both groups, with less than a 10th of original users remaining the usages (1.72% and 9.85% taking PPIs and H2 antagonists within 90 days after receiving a diagnosis, respectively). Physicians and pharmacists should be aware of the risk of developing IDA in patients currently undergoing or expected to take long-term gastric acid suppressants.

5.
Int J Biometeorol ; 67(7): 1251-1261, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37256387

RESUMEN

This study investigated the applicability of expanded metal meshes (EMMs) in horizontal shading devices. We performed simulations and experiments with EMMs with different opening ratios and directions. We established various experimental and control groups to measure air temperature, surface temperature, and black globe temperature. After the comparison of simulation and experimental data, we used Grasshopper to simulate long-term climate situations. The research results can serve as reference for users in Tainan and provide customized suggestions. The findings can serve as a paradigm for parametric design to analyze EMMs. In design projects involving outdoor horizontal shading devices, these results can be used in the design phase for evaluation. Full-day measurements revealed that EMMs with small openings exhibited favorable shading effects. In the Tainan area, we suggest using north-facing EMMs; in our simulations result, 70% of sunshine did not pass through the mesh in a day. For shading equipment in the morning, west-facing EMMs should be used because they blocked 50-90% of sunshine. For recreational areas in the afternoon and evening, east-facing EMMs can block 50-90% of sunshine after noon. In Taiwan, south-facing EMMs are not advised because their shading performance is suboptimal in the morning and afternoon.


Asunto(s)
Clima , Temperatura , Taiwán
6.
Int J Mol Sci ; 24(8)2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37108681

RESUMEN

Methylotrophic bacteria are widely distributed in nature and can be applied in bioconversion because of their ability to use one-carbon source. The aim of this study was to investigate the mechanism underlying utilization of high methanol content and other carbon sources by Methylorubrum rhodesianum strain MB200 via comparative genomics and analysis of carbon metabolism pathway. The genomic analysis revealed that the strain MB200 had a genome size of 5.7 Mb and two plasmids. Its genome was presented and compared with that of the 25 fully sequenced strains of Methylobacterium genus. Comparative genomics revealed that the Methylorubrum strains had closer collinearity, more shared orthogroups, and more conservative MDH cluster. The transcriptome analysis of the strain MB200 in the presence of various carbon sources revealed that a battery of genes was involved in the methanol metabolism. These genes are involved in the following functions: carbon fixation, electron transfer chain, ATP energy release, and resistance to oxidation. Particularly, the central carbon metabolism pathway of the strain MB200 was reconstructed to reflect the possible reality of the carbon metabolism, including ethanol metabolism. Partial propionate metabolism involved in ethyl malonyl-CoA (EMC) pathway might help to relieve the restriction of the serine cycle. In addition, the glycine cleavage system (GCS) was observed to participate in the central carbon metabolism pathway. The study revealed the coordination of several metabolic pathways, where various carbon sources could induce associated metabolic pathways. To the best of our knowledge, this is the first study providing a more comprehensive understanding of the central carbon metabolism in Methylorubrum. This study provided a reference for potential synthetic and industrial applications of this genus and its use as chassis cells.


Asunto(s)
Metanol , Methylobacterium , Metanol/metabolismo , Biocombustibles , Carbono/metabolismo , Methylobacterium/metabolismo , Genómica
7.
J Environ Manage ; 329: 117037, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36535141

RESUMEN

The decomposition of aquatic plant residues changes by the invasive algal organic matter in eutrophic lakes, however, the driving mechanisms of these biogeochemistry processes are still far from clear. In this study, a series of microcosms was constructed to simulate the mixed decomposition processes of aquatic plant residues with invasive algae as long as 205 days. Three aquatic plants (Potamogeton malaianus, Nymphoides peltatum, and Phragmites australis) and algae were collected from a typical eutrophic lake. The addition of algae promoted the decomposition of three plant residues based on the mass loss, and the positive co-metabolism effect was produced. The co-metabolism intensity was 8%-25% on the water surface and 19%-45% on the water-sediment interface, respectively. In addition, the response of three aquatic plant residues to the algal organic matter was different with their co-metabolism intensities in the order of P. australis > P. malaianus > N. peltatum on both the water surface and water-sediment interface. The phylum number of bacteria attached to the surface of plant residues increased from 27 to 52. The abundance of Bacteroidetes, which had the function of decomposing refractory organic matter, increased most significantly at the final incubation. At present, shallow lakes are under the double pressure of eutrophication and global warming, and the intensity and duration of algal blooms are increasing. Therefore, the co-metabolism effect of the residue decomposition process described here may change the carbon cycle strength and increase the greenhouse gas emissions of lakes and need to be taken into account in future lake management.


Asunto(s)
Eutrofización , Lagos , Lagos/química , Bacterias , Agua
8.
Biochem Biophys Res Commun ; 636(Pt 1): 84-88, 2022 12 25.
Artículo en Inglés | MEDLINE | ID: mdl-36332486

RESUMEN

Pregnenolone (P5) is a steroid that functions in the brain and in zebrafish embryogenesis. It is synthesized from cholesterol via the enzymatic activity of P450scc, encoded by CYP11A1. P5 exerts its function by activating CLIP1, which in turn promotes microtubule assembly necessary for many biological processes including embryogenesis. To examine the functional relatedness of CYP11A1 and CLIP1, we ablated the embryonic expression of both genes in zebrafish, i.e. cyp11a1 and clip1a. Two cyp11a1 knockout fish lines were generated. Both homozygous cyp11a1 knockout lines appeared normal. But the development of fish embryos was delayed and embryonic cell migration was reduced when cyp11a1 function was depleted of by morpholinos. This discrepancy in phenotypes by two different gene depletion methods was also observed for clip1a. While clip1a morphants are defective in embryogenesis, clip1a knockout fish appeared normal. The phenotypes depend on the methods that create gene depletion. While knockout fish lines do not have expected phenotypic defects, clip1a and cyp11a1 morpholinos both reduce embryonic cell migration. We have evaluated the usefulness of both methods of gene ablation, and conclude that CYP11A1 and CLIP1 function in the same pathway to promote embryogenesis.


Asunto(s)
Enzima de Desdoblamiento de la Cadena Lateral del Colesterol , Pez Cebra , Animales , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/genética , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Pregnenolona/metabolismo , Morfolinos/metabolismo , Desarrollo Embrionario/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
9.
Int J Neuropsychopharmacol ; 25(4): 319-327, 2022 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-34958668

RESUMEN

BACKGROUND: The reuniens (Re) and rhomboid (Rh) nuclei (ReRh) of the midline thalamus interconnect the hippocampus and the medial prefrontal cortex. The hippocampus and medial prefrontal cortex are both involved in the acquisition of trace fear conditioning, in which a conditioned stimulus (tone) and an aversive unconditioned stimulus (footshock) are paired but separated in time with a trace interval. Earlier, we demonstrated that ReRh inactivation during trace conditioning impaired the acquisition of cued fear. In contrast, ReRh inactivation during both conditioning and test resulted in heightened fear to tones during retrieval. Because there was a generalized contextual fear on top of heightened fear to tones in the latter experiment, here we aimed to examine the specific importance of the functional ReRh in cued fear and contextual fear through introducing prolonged contextual exposure. METHODS: The ReRh were pharmacologically inactivated with muscimol (or saline as controls) before each experimental session. RESULTS: We showed that although ReRh inactivation before trace fear conditioning impaired the acquisition of cued fear, the animals still acquired a certain level of fear to the tones. However, without the functional ReRh throughout the entire behavioral sessions, these animals showed heightened contextual fear that did not decline much with the passage of time, which generalized to the other context, and fear to tones reoccurred when the tones were presented. CONCLUSIONS: Our results suggested that functional ReRh are important for proper acquisition and expression of fear to context and tones acquired under trace procedure.


Asunto(s)
Miedo , Núcleos Talámicos de la Línea Media , Animales , Condicionamiento Clásico , Señales (Psicología) , Miedo/fisiología , Hipocampo/metabolismo , Núcleos Talámicos de la Línea Media/fisiología , Ratas , Ratas Long-Evans
10.
Sensors (Basel) ; 22(5)2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35271038

RESUMEN

Almond is an extendible open-source virtual assistant designed to help people access Internet services and IoT (Internet of Things) devices. Both are referred to as skills here. Service providers can easily enable their devices for Almond by defining proper APIs (Application Programming Interfaces) for ThingTalk in Thingpedia. ThingTalk is a virtual assistant programming language, and Thingpedia is an application encyclopedia. Almond uses a large neural network to translate user commands in natural language into ThingTalk programs. To obtain enough data for the training of the neural network, Genie was developed to synthesize pairs of user commands and corresponding ThingTalk programs based on a natural language template approach. In this work, we extended Genie to support Chinese. For 107 devices and 261 functions registered in Thingpedia, 649 Chinese primitive templates and 292 Chinese construct templates were analyzed and developed. Two models, seq2seq (sequence-to-sequence) and MQAN (multiple question answer network), were trained to translate user commands in Chinese into ThingTalk programs. Both models were evaluated, and the experiment results showed that MQAN outperformed seq2seq. The exact match, BLEU, and F1 token accuracy of MQAN were 0.7, 0.82, and 0.88, respectively. As a result, users could use Chinese in Almond to access Internet services and IoT devices registered in Thingpedia.


Asunto(s)
Aprendizaje Profundo , Prunus dulcis , China , Humanos , Semántica , Programas Informáticos
11.
Sensors (Basel) ; 22(10)2022 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-35632335

RESUMEN

Automated inspection has proven to be the most effective approach to maintaining quality in industrial-scale manufacturing. This study employed the eye-in-hand architecture in conjunction with deep learning and convolutional neural networks to automate the detection of defects in forged aluminum rims for electric vehicles. RobotStudio software was used to simulate the environment and path trajectory for a camera installed on an ABB robot arm to capture 3D images of the rims. Four types of surface defects were examined: (1) dirt spots, (2) paint stains, (3) scratches, and (4) dents. Generative adversarial network (GAN) and deep convolutional generative adversarial networks (DCGAN) were used to generate additional images to expand the depth of the training dataset. We also developed a graphical user interface and software system to mark patterns associated with defects in the images. The defect detection algorithm based on YOLO algorithms made it possible to obtain results more quickly and with higher mean average precision (mAP) than that of existing methods. Experiment results demonstrated the accuracy and efficiency of the proposed system. Our developed system has been shown to be a helpful rim defective detection system for industrial applications.


Asunto(s)
Aprendizaje Profundo , Robótica , Algoritmos , Redes Neurales de la Computación
12.
Int J Mol Sci ; 23(10)2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35628344

RESUMEN

Hypertension is associated with blood-brain barrier alteration and brain function decline. Previously, we established the 2-kidney,1-clip (2K1C) hypertensive mice model by renin-angiotensin system (RAS) stimulating. We found that 2K1C-induced hypertension would impair hippocampus-related memory function and decrease adult hippocampal neurogenesis. Even though large studies have investigated the mechanism of hypertension affecting brain function, there remains a lack of efficient ways to halt this vicious effect. The previous study indicated that running exercise ameliorates neurogenesis and spatial memory function in aging mice. Moreover, studies showed that exercise could normalize RAS activity, which might be associated with neurogenesis impairment. Thus, we hypothesize that running exercise could ameliorate neurogenesis and spatial memory function impairment in the 2K1C-hypertension mice. In this study, we performed 2K1C surgery on eight-weeks-old C57BL/6 mice and put them on treadmill exercise one month after the surgery. The results indicate that running exercise improves the spatial memory and neurogenesis impairment of the 2K1C-mice. Moreover, running exercise normalized the activated RAS and blood-brain barrier leakage of the hippocampus, although the blood pressure was not decreased. In conclusion, running exercise could halt hypertension-induced brain impairment through RAS normalization.


Asunto(s)
Hipertensión , Condicionamiento Físico Animal , Animales , Barrera Hematoencefálica , Hipocampo , Ratones , Ratones Endogámicos C57BL , Neurogénesis , Permeabilidad , Condicionamiento Físico Animal/métodos , Sistema Renina-Angiotensina , Memoria Espacial
13.
Water Sci Technol ; 84(9): 2601-2614, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34810334

RESUMEN

A cost-effective approach was applied to prepare porous carbon samples by the simple carbonization of wormwood rod followed by salt activator (NaCl) activation. The effect of preparation parameters on the characteristics of the wormwood rod-based porous carbons (WWRs) were studied. The properties of these samples were investigated by SEM, BET surface area, X-ray diffraction, FT-IR spectra and X-ray photoelectron spectrometer. The prepared WWRs were applied as new adsorbent materials to remove methyl orange (MO). The experimental results indicated that WWR-800 activated at 800 °C possesses the best adsorption performance. Several factors that affected the adsorption property of the system such as the solution pH, dosing of adsorbent, initial dye concentration and ionic strength were examined. In addition, the thermodynamic parameters and kinetic parameters of MO with WWR-800 were studied. The results indicated that the adsorption of MO on WWR-800 was an endothermic process and non-spontaneous under standard conditions. The maximum equilibrium adsorption capacity of MO on WWR-800 was 454.55 mg/g. After five adsorption/desorption cycles, the adsorption capacity of MO on WWR-800 remained at 94%, which indicated that wormwood rod-based porous carbon possessed good reusability.


Asunto(s)
Artemisia , Contaminantes Químicos del Agua , Adsorción , Compuestos Azo , Carbono , China , Concentración de Iones de Hidrógeno , Cinética , Porosidad , Espectroscopía Infrarroja por Transformada de Fourier , Contaminantes Químicos del Agua/análisis
14.
BMC Endocr Disord ; 20(1): 106, 2020 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-32680496

RESUMEN

BACKGROUND: Some previous studies have reported inconsistent results on the association between alcohol intake and diabetic retinopathy (DR) risk. This study aimed to evaluate the potential effects of alcohol intake on subsequent DR risk using a meta-analytic approach. METHODS: Three electronic databases (PubMed, EmBase, and the Cochrane library) were systematically searched for observational studies from their inception till November 2019. The pooled odds ratio (OR) with 95% confidence interval (CI) were applied for the summary effect estimate using a random-effects model. RESULTS: A total of 15 studies (5 cohort studies, 4 case-control studies, and 6 cross-sectional studies) with 37,290 participants and 12,711 DR cases were selected for the final meta-analysis. The pooled OR indicated no significant association between alcohol intake and DR risk (OR: 0.91; 95%CI: 0.78-1.06; P = 0.225), irrespective of the studies being pooled cohort (OR: 0.95; 95%CI: 0.66-1.36; P = 0.761), case-control (OR: 0.97; 95%CI: 0.77-1.23; P = 0.818), or cross-sectional (OR: 0.86; 95%CI: 0.69-1.08; P = 0.190) ones. However, this association might have been affected by the type of diabetes mellitus and the adjusted status. CONCLUSION: The results of this study showed that the potential impact of alcohol intake on DR risk may differ according to the type of diabetes mellitus and adjusted status. Further large-scale, prospective cohort studies should be conducted to verify the findings of this study and to evaluate DR risk in relation to the dose and type of alcohol intake.


Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/etiología , Estudios de Cohortes , Retinopatía Diabética/patología , Humanos , Pronóstico , Factores de Riesgo
15.
Bioorg Med Chem Lett ; 28(14): 2493-2497, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29871848

RESUMEN

Histone deacetylases (HDACs) decrease the acetylation level of histones and other non-histone proteins. Over expression of HDACs have been observed in cancers and other diseases. Targeted protein degradation by "hijacking" the natural ubiquitin-proteasome-system (UPS) recently emerged as a novel technology to "knock-out" endogenous disease-causing proteins. We applied this strategy to the development of the first small molecule degraders for zinc-dependent HDACs by conjugating non-selective HDAC inhibitors with E3 ubiquitin ligase ligands. Through cell-based assays, we discovered novel bifunctional molecules (dHDAC6) that could selectively degrade HDAC6. Further mechanistic studies indicated that HDAC6 was selectively removed by the UPS.


Asunto(s)
Histona Desacetilasa 6/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Talidomida/análogos & derivados , Relación Dosis-Respuesta a Droga , Histona Desacetilasa 6/metabolismo , Humanos , Estructura Molecular , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad , Talidomida/síntesis química , Talidomida/química , Talidomida/farmacología
16.
Am J Reprod Immunol ; 91(3): e13826, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38531818

RESUMEN

BACKGROUND: Premature birth (PTB) remains a major global health concern due to its association with neonatal morbidity and mortality. The unfolded protein response (UPR) within the endoplasmic reticulum (ER) is tightly regulated by Inositol-requiring enzyme type 1 (IRE-1), a pivotal cellular modulator. This study seeks to elucidate the role of the ER stress (ERS)-related IRE-1 pathway in PTB. METHODS: Human placental trophoblast cells HTR8/Svneo were exposed to the ER-stress inducer tunicamycin (TM). The expression of IRE-1 and ERS-associated proteins ATF6, GRP78, and XBP-1 was assessed in placental tissues and TM-treated cells. Cellular viability, migration, invasion, and apoptosis were evaluated through a series of experimental assays. Additionally, various methods were employed to assess and verify the activation of autophagy, using the autophagy marker, microtubule-associated protein 1A/1B-light chain 3 (LC3). Additionally, TUDCA (an ERS inhibitor) was used to assess its potential to counteract the TM-induced cell effects. RESULTS: Elevated levels of ATF6, GRP78, and XBP-1 were observed in PTB tissues and cells. TM treatment substantially reduced cell viability, migration, and invasion while promoting apoptosis. Treatment with TUDCA (an ERS inhibitor) counteracted the effects of TM on the cells. Furthermore, we identified an overexpression of IRE-1 in PTB tissues and cells and its knockdown enhanced cell viability, migration, and invasion while suppressed apoptosis and autophagy under TM stimulation. Notably, IRE-1 was found to modulate the activity of the IRE-1/XBP1/CHOP signaling pathway in TM-treated cells. CONCLUSION: The upregulation of IRE-1 in PTB placental tissues is implicated in the pathogenesis of PTB. Importantly, inhibiting the ERS-associated IRE-1/XBP1/CHOP pathway may be a good strategy in mitigating PTB.


Asunto(s)
Chaperón BiP del Retículo Endoplásmico , Nacimiento Prematuro , Ácido Tauroquenodesoxicólico , Recién Nacido , Femenino , Humanos , Embarazo , Placenta , Estrés del Retículo Endoplásmico , Apoptosis
17.
Psychon Bull Rev ; 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38337141

RESUMEN

Crowding, a fundamental limit in object recognition, is believed to result from excessive integration of nearby items in peripheral vision. To understand its pooling mechanisms, we measured subjects' internal response distributions in an orientation crowding task. Contrary to the prediction of an averaging model, we observed a pattern suggesting that the perceptual judgement is made based on choosing the largest response across the noise-perturbed items. A model featuring first-stage averaging and second-stage signed-max operation predicts the diverse errors made by human observers under various signal strength levels. These findings suggest that different rules operate to resolve the bottleneck at early and high-level stages of visual processing, implementing a combination of linear and nonlinear pooling strategies.

18.
Heliyon ; 10(13): e32457, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39027525

RESUMEN

Background: Premature birth (PTB) is a major cause of neonatal mortality and has enduring consequences. LIM Homeobox 1 (LHX1) is vital in embryonic organogenesis, while Inositol-Requiring Enzyme 1 (IRE-1) regulates endoplasmic reticulum stress (ERS). This study explores whether IRE-1 impacts PTB via LHX1 modulation. Methods: We analyzed LHX1 expression in placental samples from PTB patients and examined its impact on the viability, migration, invasion, and apoptosis of the human placental trophoblast cell line HTR8/Svneo, particularly when treated with the ERS inducer tunicamycin (TM). We also assessed the levels of ERS-related genes and autophagy activation in response to LHX1 deficiency. To gain mechanistic insights, we evaluated the ERS-mediated activation of the IRE-1/XBP1/CHOP signaling pathway in LHX1-silenced HTR8/Svneo cells. Additionally, we examined the transcriptional activation of IRE-1 and the binding of LHX1 to the IRE-1 promoter in HTR8/Svneo cells. We overexpressed IRE-1 in LHX1-silenced HTR8/Svneo cells to assess its effects on cell viability, migration, invasion, apoptosis, and autophagy. Finally, we induced LHX1 knockdown in mice through intraperitoneal injections of tunicamycin (TM) and Sh-LHX1 over a 24-h period to evaluate PTB symptoms. Results: We observed LHX1 overexpression in placental tissue from PTB cases and TM-induced HTR8/Svneo cells. LHX1 depletion enhanced cell viability, migration, and invasion while reducing autophagy and apoptosis. This reduction in LHX1 led to decreased levels of IRE-1, XBP1, CHOP, and other ERS-related genes, indicating LHX1's role in ERS induction and the activation of the IRE-1/XBP1/CHOP pathway. Mechanistically, LHX1 was found to bind to the IRE-1 promoter, inducing its transcriptional activation. Notably, overexpressing IRE-1 counteracted the impact of LHX1 depletion on trophoblast cell behavior, suggesting that LHX1 modulates IRE-1. In line with our in vitro studies, LHX1 knockdown ameliorated PTB symptoms in TM-treated mice. Conclusion: LHX1 contributes to the progression of PTB by regulating the IRE-1-XBP1-CHOP pathway.

19.
Nanomaterials (Basel) ; 14(10)2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38786846

RESUMEN

A narrow energy distribution is a prominent characteristic of field-emission cold cathodes. When applied in a vacuum electronic device, the cold cathode is fabricated over a large area and works under a high current and current density. It is interesting to see the energy distribution of the field emitter under such a working situation. In this work, the energy distribution spectra of a single carbon nanotube (CNT) and a CNT film were investigated across a range of currents, spanning from low to high. A consistent result indicated that, at low current emission, the CNT film (area: 0.585 mm2) exhibited a narrow electron energy distribution as small as 0.5 eV, similar to that of a single CNT, while the energy distribution broadened with increased current and voltage, accompanied by a peak position shift. The influencing factors related to the electric field, Joule heating, Coulomb interaction, and emission site over a large area were discussed to elucidate the underlying mechanism. The results provide guidance for the electron source application of nano-materials in cold cathode devices.

20.
Nat Prod Res ; : 1-7, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38534130

RESUMEN

Five trichothecenes including a new one, together with two previously undescribed benzene derivatives were isolated from the solid culture of Trichothecium sp. Their structures were established by 1D and 2D NMR data in conjunction with HR-ESI-MS analysis. Compounds 1-5 exhibited cytotoxicity against MCF-7 cell lines at various levels ranging from IC50 of 7.23 to 16.95 µM. Compound 6 decreased the concentration of blood lipids in zebra fish at the concentration of 20 µM.

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