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1.
Cell ; 187(9): 2305-2323.e33, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38614099

RESUMEN

Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation. Treatment with a neutralizing antibody against ITPRIPL1 restrained tumor growth and promoted T cell infiltration in mouse models across various solid tumor types. The antibody targeting canine ITPRIPL1 exhibited notable therapeutic efficacy against naturally occurring tumors in pet clinics. These findings highlight the role of ITPRIPL1 (or CD3L1, CD3ε ligand 1) in impeding T cell activation during the critical "signal one" phase. This discovery positions ITPRIPL1 as a promising therapeutic target against multiple tumor types.


Asunto(s)
Complejo CD3 , Activación de Linfocitos , Linfocitos T , Escape del Tumor , Microambiente Tumoral , Animales , Complejo CD3/metabolismo , Complejo CD3/inmunología , Humanos , Ratones , Linfocitos T/inmunología , Linfocitos T/metabolismo , Microambiente Tumoral/inmunología , Perros , Neoplasias/inmunología , Línea Celular Tumoral , Femenino , Unión Proteica , Proteína Tirosina Quinasa ZAP-70/metabolismo , Anticuerpos Neutralizantes/inmunología , Ratones Endogámicos C57BL
2.
Cell Mol Life Sci ; 81(1): 249, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38836877

RESUMEN

Protein ubiquitination is one of the most important posttranslational modifications (PTMs) in eukaryotes and is involved in the regulation of almost all cellular signaling pathways. The intracellular bacterial pathogen Legionella pneumophila translocates at least 26 effectors to hijack host ubiquitination signaling via distinct mechanisms. Among these effectors, SidC/SdcA are novel E3 ubiquitin ligases with the adoption of a Cys-His-Asp catalytic triad. SidC/SdcA are critical for the recruitment of endoplasmic reticulum (ER)-derived vesicles to the Legionella-containing vacuole (LCV). However, the ubiquitination targets of SidC/SdcA are largely unknown, which restricts our understanding of the mechanisms used by these effectors to hijack the vesicle trafficking pathway. Here, we demonstrated that multiple Rab small GTPases and target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins are bona fide ubiquitination substrates of SidC/SdcA. SidC/SdcA-mediated ubiquitination of syntaxin 3 and syntaxin 4 promotes their unconventional pairing with the vesicle-SNARE protein Sec22b, thereby contributing to the membrane fusion of ER-derived vesicles with the phagosome. In addition, our data reveal that ubiquitination of Rab7 by SidC/SdcA is critical for its association with the LCV membrane. Rab7 ubiquitination could impair its binding with the downstream effector Rab-interacting lysosomal protein (RILP), which partially explains why LCVs avoid fusion with lysosomes despite the acquisition of Rab7. Taken together, our study reveals the biological mechanisms employed by SidC/SdcA to promote the maturation of the LCVs.


Asunto(s)
Legionella pneumophila , Fagosomas , Proteínas SNARE , Ubiquitinación , Proteínas de Unión al GTP rab , Legionella pneumophila/metabolismo , Humanos , Fagosomas/metabolismo , Fagosomas/microbiología , Proteínas SNARE/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Animales , Proteínas Qa-SNARE/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Vacuolas/metabolismo , Vacuolas/microbiología , Células HEK293 , Ratones , Proteínas de Unión a GTP rab7/metabolismo , Proteínas de Unión al GTP Monoméricas/metabolismo , Retículo Endoplásmico/metabolismo
3.
BMC Musculoskelet Disord ; 25(1): 101, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38287387

RESUMEN

BACKGROUND: The hip joint capsule is an essential component of hip joint function and stability, and its thickness is closely associated with certain medical conditions, surgical outcomes, and rehabilitation treatments. Currently, in clinical practice, hip joint capsule thickness is predominantly measured using magnetic resonance imaging (MRI), with limited utilization of ultrasound examinations for this purpose. METHODS: We retrospectively evaluated patients who visited our Sports Medicine Department between February 2017 and March 2023 and underwent both hip joint MRI and ultrasound imaging on the same side. All patients had undergone preoperative hip joint MRI and ultrasound examinations, with the time gap between the two examinations not exceeding three months. Measurements of hip joint capsule thickness were taken on both MRI and ultrasound images for the same patients to analyze their consistency. Additionally, we measured the alpha angle, lateral center-edge angle, acetabular anteversion angle, and femoral anteversion angle of the patients' hip joints and analyzed their correlation with hip joint capsule thickness measure by ultrasound. RESULTS: A total of 307 patients were included in this study, with hip joint capsule thickness measured by MRI and ultrasound being 5.0 ± 1.2 mm and 5.0 ± 1.5 mm, respectively. The Bland-Altman analysis demonstrates good agreement or consistency. The paired t-test resulted in a p-value of 0.708, indicating no significant statistical difference between the two methods. The correlation analysis between acetabular anteversion angle and ultrasound-measured capsule thickness yielded a p-value of 0.043, indicating acetabular anteversion angle and capsular thickness may have negative correlation. CONCLUSIONS: The measurements of joint capsule thickness obtained through ultrasound and MRI showed good consistency, suggesting that ultrasound can be used in clinical practice as a replacement for MRI in measuring hip joint capsule thickness. There was a significant correlation between acetabular anteversion angle and hip joint capsule thickness, indicating potential for further research in this area.


Asunto(s)
Acetábulo , Articulación de la Cadera , Humanos , Estudios Retrospectivos , Articulación de la Cadera/cirugía , Acetábulo/cirugía , Cápsula Articular/diagnóstico por imagen , Ultrasonografía
4.
J Stroke Cerebrovasc Dis ; 33(7): 107731, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38657831

RESUMEN

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.


Asunto(s)
Hemorragia Cerebral , Progresión de la Enfermedad , Hematoma , Valor Predictivo de las Pruebas , Humanos , Masculino , Hemorragia Cerebral/diagnóstico por imagen , Hematoma/diagnóstico por imagen , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Reproducibilidad de los Resultados , Interpretación de Imagen Radiográfica Asistida por Computador , Máquina de Vectores de Soporte , Tomografía Computarizada por Rayos X , Pronóstico , Factores de Riesgo , Anciano de 80 o más Años
5.
J Sci Food Agric ; 104(4): 2110-2119, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-37919871

RESUMEN

BACKGROUND: This study explores the use of liquid-liquid extraction with thermosensitive polymers for producing laccase (Lac) from Pleurotus sajor-caju. This process leverages liquid waste from the citrus industry, specifically pulp wash. The research delves into extractive fermentation and thermoseparation, both processes being facilitated by a polymer exhibiting a lower critical solution temperature transition. RESULTS: Key factors considered include the choice of polymer, its concentration, pH, separation temperature, and the behavior of the polymer-rich phase post-extractive fermentation concerning the lower critical solution temperature. Notably, under conditions of 45% by weight of Pluronic L-61 and pH 5.0 at 25 °C, the Lac resulted in an enhancement in the purification factor of 28.4-fold, compared with the Lac obtained directly from the fermentation process on the eighth day. There was an 83.6% recovery of the Lac enzyme in the bottom phase of the system. Additionally, the unique properties of Pluronic L-61, which can induce phase separation and also allow for thermoseparation, led to a secondary fraction (aqueous solution) of Lac with purification factor of 2.1 ± 0.1-fold (at 32 ± 0.9 °C and 30 ± 0.3 min without stirring) from the polymeric phase (top phase). Fourier-transform infrared analysis validated the separation data, particularly highlighting the α-helix content in the amide I region (1600-1700 cm-1 ). CONCLUSION: In summary, the insights from this study pave the way for broader industrial applications of these techniques, underscoring benefits like streamlined process integration, heightened selectivity, and superior separation efficacy. © 2023 Society of Chemical Industry.


Asunto(s)
Lacasa , Pleurotus , Lacasa/metabolismo , Polímeros/química , Poloxámero , Temperatura , Fermentación , Pleurotus/metabolismo
6.
J Org Chem ; 88(24): 17381-17388, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38055052

RESUMEN

Sulfolenodipyrrins are employed as building blocks to concisely and efficiently construct aromatic rings (e.g., naphthoquinone, anthraquinone, fullerenes, and phthalimide) from fused dipyrrins by programmed [4 + 2]-cycloaddition reactions. Notably, alkylamino-substitution at the α-position not only enhances the reactivity of sulfolenodipyrrins but also results in the regio-selectivity of the cycloaddition reactions. Theoretical calculations in terms of frontier orbitals of dienes, energy of dienes, steric hindrance, and aromaticity have been conducted to understand the reason in depth. Additionally, the fusion of aromatic groups enables bathochromic absorption with up to ∼130 nm for the monoadducts and to ∼200 nm for the bis-adducts. The phthalimide annulation dipyrrin displays red emission, while the other mono- or bis-adducts do not, owing to the presence of typical acceptors such as quinone analogs or fullerene.

7.
Nano Lett ; 22(14): 5929-5935, 2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-35833705

RESUMEN

The photothermoelectric effect, directly converting light energy into electrical energy, shows promising prospects in self-powered broad-band optical detection, which can extend to various applications, such as sensing, optoelectronic communications, and wide-temperature-range measurements. However, the low photosensitivity, narrow-band response, and rapid performance degeneration under continuous illumination restrict its broad application. Herein, we propose a simple bottom-up strategy to manipulate nanowires (NWs) into a well-defined multilayer Te-Ag2Te-Ag NW film, resulting in a high-performance photothermoelectric photodetector with a broad-band responsivity (4.1 V/W), large detectivity (944 MHz1/2 W-1), and fast response speed (0.4-0.7 s from 365 to 1200 nm). In addition, the ultrathin structure endows this device with slow and weak transverse heat conduction, enabling a stable voltage without an obvious degeneration over 1500 s. The highly anisotropic arrangement of NWs gives this device a prominent polarization sensitivity. Prospectively, this hierarchically designed nanowire film provides a promising pathway toward engineering photodetectors with high performance.

8.
Environ Monit Assess ; 194(9): 607, 2022 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-35867174

RESUMEN

The health risk of antibiotic-resistant genes (ARGs) has been a global concern, while the report on occurrence and prevalence of ARGs in coastal zone is relatively scarce. This study investigated typical ARGs in soil and sediment in coastal line of eastern China and assessed its relationship with antibiotics and heavy metals as well as microbial community. Results showed that eight ARGs were all detected in the samples, and ß-lactam resistance gene blaTEM reached the highest absolute abundance (6.28 × 107 ~ 6.48 × 108 copies/g) and relative abundance (2.3 × 10-2 copies/16S rRNA) among samples. Amoxicillin and tetracycline were most frequently detected with the average concentration of 2.28 µg/kg and 3.48 µg/kg, respectively. Cr and Zn were found to be most abundant heavy metals with average value of 82.1 and 59.1 mg/kg, respectively. Proteobacteria, Campilobacterota, Bacteroidota, and Firmicutes were dominant phyla in most samples, while bacterial community varied significantly among samples. Redundancy analyses (RDA) showed that microbial community and antibiotics (amoxicillin and tetracycline) were driving factors of ARGs distribution, while heavy metals were not significantly correlated with ARGs. This study is helpful to understand the fate of ARGs in coastal zone.


Asunto(s)
Metales Pesados , Microbiota , Amoxicilina/análisis , Antibacterianos/farmacología , China , Farmacorresistencia Microbiana/genética , Monitoreo del Ambiente , Genes Bacterianos , Metales Pesados/análisis , ARN Ribosómico 16S/genética , Suelo , Tetraciclina/análisis
9.
Hepatology ; 71(5): 1643-1659, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31509262

RESUMEN

BACKGROUND AND AIMS: Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. We report that PDZ and LIM domain protein 1 (PDLIM1) is significantly down-regulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis. APPROACH AND RESULTS: Functional studies indicate that PDLIM1 knockdown induces epithelial-to-mesenchymal transition (EMT) of HCC cells, elevates their invasive capacity, and promotes metastasis in vitro and in vivo, whereas overexpression of PDLIM1 exhibits opposite phenotypes. Mechanistically, PDLIM1 competitively binds to the cytoskeleton cross-linking protein alpha-actinin 4 (ACTN4), leading to the disassociation of ACTN4 from F-actin, thus preventing F-actin overgrowth. In contrast, loss of PDLIM1 induces excessive F-actin formation, resulting in dephosphorylation of large tumor suppressor kinase 1 and activation of Yes-associated protein, thereby promoting HCC metastasis. Moreover, Asn145 (N145) of PDLIM1 is critical for its interaction with ACTN4, and N145A mutation abolishes its regulatory function in Hippo signaling and HCC metastasis. CONCLUSIONS: Our findings indicate that PDLIM1 suppresses HCC metastasis by modulating Hippo signaling, suggesting that PDLIM1 may be a potential prognostic marker for metastatic HCC.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundario , Proteínas con Dominio LIM/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Factores de Transcripción/metabolismo , Actinina/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Vía de Señalización Hippo , Humanos , Proteínas con Dominio LIM/genética , Neoplasias Hepáticas/genética , Metástasis de la Neoplasia , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Factores de Transcripción/genética , Proteínas Señalizadoras YAP
10.
Sensors (Basel) ; 20(19)2020 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-32993194

RESUMEN

With the rapid development of the social economy, high-voltage transmission lines as power supply infrastructure are increasing, subsequently presenting a new challenge to the effective monitoring of transmission lines. The dynamic sensor network integrated with robots can effectively solve the elastic monitoring of transmission lines, but the problems of real-time performance, energy consumption and economy of the network need to be solved. To solve this problem, a dynamic network deployment method based on the hybrid hierarchical network (HHN) is proposed to realize a low-cost, energy-saving and real-time dynamic sensing system for overhead high-voltage transmission lines. Through case analysis and simulation, combined with the vague set multi-attribute decision-making method (MADM) with scheme preference, the network deployment and optimization results under multi-parameter constraints are obtained.

11.
J Hepatol ; 70(1): 66-77, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30287340

RESUMEN

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a common cancer worldwide and remains a major clinical challenge. Ketoconazole, a traditional antifungal agent, has attracted considerable attention as a therapeutic option for cancer treatment. However, its mechanism of action is still not clearly defined. We aimed to evaluate the effect of ketoconazole on HCC and investigate the underlying mechanisms. METHODS: We examined the antitumor effect of ketoconazole on HCC cells, cell line-derived xenografts, and a patient-derived xenograft (PDX) model. Ketoconazole-induced mitophagy was quantified by immunofluorescence, immunoblotting and transmission electron microscopy analysis. We used mitophagy inhibitors to study the role of mitophagy on HCC cell death induced by ketoconazole. The role of cyclooxygenase-2 (COX-2 [encoded by PTGS2]) on ketoconazole-induced mitophagy was evaluated using gain- and loss-of-function methods. The synergistic effect of ketoconazole with sorafenib on HCC was measured in vivo and in vitro. RESULTS: Ketoconazole stimulated apoptosis in HCC cells by triggering mitophagy in vitro and in vivo. Mechanistically, ketoconazole downregulated COX-2, which led to PINK1 accumulation and subsequent mitochondrial translocation of Parkin (PRKN), and thereby promoted mitophagy-mediated mitochondrial dysfunction. Inhibiting mitophagy alleviated ketoconazole-induced mitochondrial dysfunction and apoptosis, supporting a causal role for mitophagy in the antitumor effect of ketoconazole. In the HCC PDX model, ketoconazole demonstrated a marked antitumor effect characterized by COX-2 downregulation, mitophagy activation, and apoptosis induction. Moreover, ketoconazole acted synergistically with sorafenib to suppress HCC xenograft growth in vivo. CONCLUSION: Our results demonstrate a novel link between ketoconazole and mitophagy machinery, providing preclinical proof of concept for the use of ketoconazole in HCC treatment. LAY SUMMARY: Hepatocellular carcinoma (HCC) is a common malignancy worldwide and remains a major clinical challenge. Our study reveals that ketoconazole, a broad-spectrum antifungal agent, activates PINK1/Parkin-mediated mitophagy by downregulating COX-2, consequently resulting in the acceleration of apoptosis and thereby inhibiting the growth of HCC. Furthermore, ketoconazole acts synergistically with sorafenib in the suppression of HCC growth in vitro and in vivo.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Ciclooxigenasa 2/biosíntesis , Regulación hacia Abajo/fisiología , Hepatocitos/patología , Cetoconazol/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Mitofagia/efectos de los fármacos , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Inhibidores del Citocromo P-450 CYP3A/farmacología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología
12.
Proc Natl Acad Sci U S A ; 113(6): 1522-7, 2016 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-26811444

RESUMEN

The ability of surface acoustic waves to trap and manipulate micrometer-scale particles and biological cells has led to many applications involving "acoustic tweezers" in biology, chemistry, engineering, and medicine. Here, we present 3D acoustic tweezers, which use surface acoustic waves to create 3D trapping nodes for the capture and manipulation of microparticles and cells along three mutually orthogonal axes. In this method, we use standing-wave phase shifts to move particles or cells in-plane, whereas the amplitude of acoustic vibrations is used to control particle motion along an orthogonal plane. We demonstrate, through controlled experiments guided by simulations, how acoustic vibrations result in micromanipulations in a microfluidic chamber by invoking physical principles that underlie the formation and regulation of complex, volumetric trapping nodes of particles and biological cells. We further show how 3D acoustic tweezers can be used to pick up, translate, and print single cells and cell assemblies to create 2D and 3D structures in a precise, noninvasive, label-free, and contact-free manner.


Asunto(s)
Impresión Tridimensional , Análisis de la Célula Individual/métodos , Sonido , Calibración , Supervivencia Celular , Simulación por Computador , Células HeLa , Humanos , Microfluídica , Análisis Numérico Asistido por Computador , Pinzas Ópticas , Vibración
13.
Molecules ; 23(7)2018 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-30004438

RESUMEN

The present study investigated the adsorptive and enzymatic removal of aniline blue dye (AB) from aqueous solution using waxy riceprocessing waste (RW), peanut shell (PS), microbial waste of Aspergillus niger (MW) as low cost adsorbents, and laccase (Lac) as a biocatalyst. Commercial activated carbon (AC) was also employed to compare the adsorption performance with the three adsorbents. Dye removal was examined under various parameters in batch experiments. It was found that dye removal by RW and Lac was 89⁻94% noticeably better than that by MW and PS (20⁻70%). In any cases, AC produced the highest dye removal among the tested materials. The kinetics, isotherms, and thermodynamics were then analyzed to elucidate the adsorption process by the four adsorbents. The pseudo-second order kinetic was superior to the pseudo first order kinetic model in describing adsorption for all adsorbents. The Langmuir model fitted the adsorption process very well, indicating monolayer coverage of dyes on a solid surface. A thermodynamic analysis of enthalpy (ΔH°), entropy (ΔS°), and Gibbs free energy (ΔG°) classified the adsorption as a nonspontaneous and endothermic process. The results reveal diverse natural materials (e.g., processing waste RW) as novel substitutes for traditional activated carbon, as well as laccase as a green catalyst for the treatment of dye wastewater.


Asunto(s)
Compuestos de Anilina/química , Contaminantes Químicos del Agua/química , Agua/química , Adsorción , Carbón Orgánico/química , Colorantes/química , Entropía , Cinética , Temperatura , Termodinámica
14.
South Med J ; 109(12): 792-797, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27911976

RESUMEN

OBJECTIVES: Information regarding Hispanics with inflammatory bowel disease (IBD) is scarce. In this study we aimed to describe a predominantly Hispanic population with IBD in a city located along the US-Mexico border and to identify clinical or demographic differences between Hispanics and non-Hispanics. METHODS: Retrospective cohort analysis of patients with IBD between 2003 and 2013 at a tertiary care center. Information collected included age, sex, ethnicity, diagnosis, diagnosis status (new vs old), endoscopic extent of disease (EOD), extraintestinal manifestations, medical treatment, and surgeries performed. Continuous and categorical variables were compared using a two-sided unpaired t test/Wilcoxon rank sum test and the Fisher exact test, respectively. Results with P ≤ 5% were considered statistically significant. RESULTS: Hispanics accounted for 71% of the population sample. A total of 141 patients (68%) were diagnosed as having ulcerative colitis (UC) and 67 (32%) as having Crohn disease (CD). The only statistically significant differences between Hispanics and non-Hispanics were older age at diagnosis and a higher proportion of new diagnoses in Hispanics with CD (P = 0.008 and 0.009, respectively) The most common EOD in patients with UC was extensive colitis, whereas isolated colonic disease predominated in CD, regardless of ethnicity. Immunomodulators and biologics were used in 3% and 1% of cases, respectively. Treatment regimens were similar in both ethnic groups. Patients with CD were more likely than those with UC to have undergone surgery (27% vs 11%, P = 0.004). Surgery rates did not differ between Hispanics and non-Hispanics. CONCLUSIONS: In our population, UC was more common than CD, and the EOD of both conditions differed from the one previously described in other Hispanic populations in the United States. The use of immunomodulators and biologics is the lowest reported to date in the country. No clinically relevant differences were seen between Hispanics and non-Hispanics.


Asunto(s)
Colitis Ulcerosa/patología , Enfermedad de Crohn/patología , Hispánicos o Latinos/estadística & datos numéricos , Adulto , Factores de Edad , Productos Biológicos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/etnología , Colonoscopía/estadística & datos numéricos , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/etnología , Demografía , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Masculino , México/etnología , Persona de Mediana Edad , Estudios Retrospectivos , Estadísticas no Paramétricas , Estados Unidos
15.
Int J Mol Sci ; 17(6)2016 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-27240345

RESUMEN

Two CHI genes from Chitinolyticbacter meiyuanensis SYBC-H1 encoding chitinases were identified and their protein 3D structures were predicted. According to the amino acid sequence alignment, CHI1 gene encoding 166 aa had a structural domain similar to the GH18 type II chitinase, and CHI2 gene encoding 383 aa had the same catalytic domain as the glycoside hydrolase family 19 chitinase. In this study, CHI2 chitinase were expressed in Escherichia coli BL21 cells, and this protein was purified by ammonium sulfate precipitation, DEAE-cellulose, and Sephadex G-100 chromatography. Optimal activity of CHI2 chitinase occurred at a temperature of 40 °C and a pH of 6.5. The presence of metal ions Fe(3+), Fe(2+), and Zn(2+) inhibited CHI2 chitinase activity, while Na⁺ and K⁺ promoted its activity. Furthermore, the presence of EGTA, EDTA, and ß-mercaptoethanol significantly increased the stability of CHI2 chitinase. The CHI2 chitinase was active with p-NP-GlcNAc, with the Km and Vm values of 23.0 µmol/L and 9.1 mM/min at a temperature of 37 °C, respectively. Additionally, the CHI2 chitinase was characterized as an N-acetyl glucosaminidase based on the hydrolysate from chitin. Overall, our results demonstrated CHI2 chitinase with remarkable biochemical properties is suitable for bioconversion of chitin waste.


Asunto(s)
Quitinasas/química , Quitinasas/genética , Clonación Molecular/métodos , Neisseriaceae/aislamiento & purificación , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Quitinasas/metabolismo , Escherichia coli/genética , Cinética , Modelos Moleculares , Neisseriaceae/química , Neisseriaceae/enzimología , Neisseriaceae/genética , Filogenia , Estabilidad Proteica , Estructura Secundaria de Proteína , Análisis de Secuencia de Proteína , Microbiología del Suelo , Homología Estructural de Proteína
16.
Subst Abus ; 36(3): 318-24, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25492554

RESUMEN

BACKGROUND: This study examines factors related to general health and health behavior, including smoking, that may be associated with binge drinking, drinking "at risk," and potential for alcohol use disorder among young adults of Mexican ancestry. METHODS: A total of 2191 young adult emergency department (ED) patients (18-30 years) of Mexican ancestry in a public hospital proximate to the US-Mexico border completed health surveys while they were waiting to be treated, including questions on general health, drinking, smoking, and drug use. RESULTS: Thirty-seven percent of the study participants reported binge drinking, 38% were "at-risk" alcohol users (above National Institute on Alcohol Abuse and Alcoholism guidelines), and 22% were Rapid Alcohol Problem Screen (RAPS) positive (indicating potential for alcohol use disorder). Smoking was reported by 31%, marijuana use by 16%, and other drug use by 9%. Multiple variable models revealed that smoking was the strongest factor associated with binge drinking. Those who smoked were 3.1 (P < .0001) times more likely to binge drink. Other factors independently associated with binge drinking were age 22-25 years (odds ratio [OR] = 1.5, P = .003), male gender (OR = 1.5, P = .0001), and ED visit for injury (OR = 1.4, P = .007). CONCLUSIONS: There is a strong association of smoking and binge drinking. Study findings suggest that brief interventions designed to reduce preventable health risks for young Hispanics should include discussion of both binge drinking and smoking behaviors.


Asunto(s)
Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Fumar Marihuana/epidemiología , Americanos Mexicanos/psicología , Fumar/epidemiología , Adolescente , Conducta del Adolescente , Adulto , Factores de Edad , Femenino , Humanos , Masculino , México/etnología , Factores de Riesgo , Factores Sexuales , Texas/epidemiología , Adulto Joven
17.
J Neurovirol ; 20(6): 591-602, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25227932

RESUMEN

Effective combined antiretroviral therapy (cART) in HIV-infected patients has made HIV a treatable infection; however, debilitating HIV-associated neurocognitive disorders (HAND) can still affect approximately 50% of HIV-infected individuals even under cART. While cART has greatly reduced the prevalence of the most severe form of HAND, milder forms have increased in prevalence, leaving the total proportion of HIV-infected individuals suffering from HAND relatively unchanged. In this study, an in vitro drug screen identified fluconazole and paroxetine as protective compounds against HIV gp120 and Tat neurotoxicity. Using an accelerated, consistent SIV/macaque model of HIV-associated CNS disease, we tested the in vivo neuroprotective capabilities of combination fluconazole/paroxetine (FluPar) treatment. FluPar treatment protected macaques from SIV-induced neurodegeneration, as measured by neurofilament light chain in the CSF, APP accumulation in axons, and CaMKIIα in the frontal cortex, but did not significantly reduce markers of neuroinflammation or plasma or CNS viral loads. Since HIV and SIV neurodegeneration is often attributed to accompanying neuroinflammation, this study provides proof of concept that neuroprotection can be achieved even in the face of ongoing neuroinflammation and viral replication.


Asunto(s)
Fluconazol/farmacología , Neuronas/efectos de los fármacos , Nootrópicos/farmacología , Paroxetina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Complejo SIDA Demencia/tratamiento farmacológico , Complejo SIDA Demencia/fisiopatología , Complejo SIDA Demencia/virología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Síndrome de Inmunodeficiencia Adquirida/virología , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Modelos Animales de Enfermedad , Expresión Génica/efectos de los fármacos , Humanos , Macaca nemestrina , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Proteínas de Neurofilamentos/genética , Neuronas/patología , Neuronas/virología , Cultivo Primario de Células , Ratas , Síndrome de Inmunodeficiencia Adquirida del Simio/líquido cefalorraquídeo , Síndrome de Inmunodeficiencia Adquirida del Simio/fisiopatología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Virus de la Inmunodeficiencia de los Simios/fisiología , Carga Viral/efectos de los fármacos , Replicación Viral/efectos de los fármacos
18.
Pol J Microbiol ; 63(3): 323-33, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25546943

RESUMEN

The present study focused on laccase production, characterization, and its involvement in chlorophyll decolorization. Extracellular laccase, with the highest activity of 11 U/ml on day 8, was efficiently produced from Trametes hirsuta in 5 l bioreactor with optimized media comprising dual carbon sources, glucose and water hyacinth. A laccase was then purified from the supernatant to homogeneity with purification fold of 9.51 and recovery of 39.8% and an estimated molecular mass of 62 kDa by SDS-PAGE. The laccase showed activity at pH 2-6 and temperature 30-80°C and was relatively thermally stable at below 70°C and neutral pH. The laccase was applied to decolorize chlorophyll under different factors: temperature, pH, mediator, metal ions, and enzyme dosage. Other fungal laccases were also found to be able to degrade chlorophyll with rating from 52% to 88% following 1 h treatment with two laccase dosages (5 or 10 U/ml) in the absence of any other mediators at room temperature. These findings may be an important step in developing new, important, and commercially viable industrial applications for laccase enzymes.


Asunto(s)
Clorofila/metabolismo , Regulación Enzimológica de la Expresión Génica/fisiología , Regulación Fúngica de la Expresión Génica/fisiología , Lacasa/metabolismo , Trametes/enzimología , Clorofila/química , Electroforesis en Gel de Poliacrilamida , Concentración de Iones de Hidrógeno , Lacasa/genética , Estructura Molecular , Trametes/genética , Trametes/metabolismo
19.
Neural Netw ; 174: 106266, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38552353

RESUMEN

In network systems, control using minimum nodes or pinning control can be effectively used for stabilization problems to cut down the cost of control. In this paper, we investigate the set stabilization problem of logical control networks. In particular, we study the set stabilization problem of probabilistic Boolean networks (PBNs) and probabilistic Boolean control networks (PBCNs) via controlling minimal nodes. Firstly, an algorithm is given to search for the minimum index set of pinning nodes. Then, based on the analysis of its high computational complexity, we present optimized algorithms with lower computational complexity to ascertain the network control using minimum node sets. Moreover, some sufficient and necessary conditions are proposed to ensure the feasibility and effectiveness of the proposed algorithms. Furthermore, a theorem is presented for PBCNs to devise all state-feedback controllers corresponding to the set of pinning nodes. Finally, two models of gene regulatory networks are considered to show the efficacy of obtained results.


Asunto(s)
Algoritmos , Redes Reguladoras de Genes
20.
Chemosphere ; 361: 142464, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38810795

RESUMEN

Hydrogen peroxide (H2O2) synthesis by electrochemical two-electron oxygen reduction has garnered increasing interest as a wide range of potential applications. Gas diffusion electrodes (GDEs) can effectively promote the H2O2 production efficiency by overcoming the oxygen mass transfer limitations but strongly influenced by the electrowetting process along the long-term operation. In this study, the effect of trans-electrode pressure (TEP) of GDE cathode on the electrowetting process was further elucidated. We controlled the TEP values of four types of GDEs: two Ni-based GDEs and two carbon cloth GDEs prepared by hot-pressing or brushing carbon black. SBA-15 was further used to regulate the microstructure of one Ni-based GDE. It was found that an optimal range of TEP occurred for all tested GDEs in terms of the max. concentration, the yield efficiency, the energy consumption, and the stability because TEP may change the triple-phase interface and influence the anti-electrowetting effect. The porosity of hot-pressed Ni GDE can maintain the TEP window and thus enhance the production of H2O2, likely via creating oxygen-containing functional groups and a bimodal pore structure on the electrode, revealed with several characterization techniques including SEM, CA, XPS, Raman spectra, CV and EIS. The porous Ni GDE presented an efficient and stable production of H2O2 for 10 cycles: yielding H2O2 at 4393.2-4602.2 mmol m-2 h-1 with current efficiencies of 94.2-98.7%. The best accumulated H2O2 concentration can reach up to 3.58 ωt% H2O2 at 10 h. The results provide an important reference for the industrial scaleup of electro-production of H2O2 with GDEs.


Asunto(s)
Electrodos , Peróxido de Hidrógeno , Peróxido de Hidrógeno/química , Presión , Oxidación-Reducción , Difusión , Técnicas Electroquímicas/métodos , Oxígeno/química , Gases/química , Porosidad , Níquel/química
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