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1.
Cells ; 13(13)2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38995001

RESUMEN

BACKGROUND: Extravillous trophoblasts (EVTs) form stratified columns at the placenta-uterus interface. In the closest part to fetal structures, EVTs have a proliferative phenotype, whereas in the closest part to maternal structures, they present a migratory phenotype. During the placentation process, Connexin 40 (Cx40) participates in both the proliferation and migration of EVTs, which occurs under hypoxia. However, a possible interaction between hypoxia and Cx40 has not yet been established. METHODS: We developed two cellular models, one with "low Cx40" (Jeg-3), which reflected the expression of this protein found in migratory EVTs, and one with "high Cx40" (Jeg-3/hCx40), which reflected the expression of this protein in proliferative cells. We analyzed the migration and proliferation of these cells under normoxic and hypoxic conditions for 24 h. Jeg-3 cells under hypoxia increased their migratory capacity over their proliferative capacity. However, in Jeg-3/hCx40, the opposite effect was induced. On the other hand, hypoxia promoted gap junction (GJ) plaque formation between neighboring Jeg-3 cells. Similarly, the activation of a nitro oxide (NO)/cGMP/PKG-dependent pathway induced an increase in GJ-plaque formation in Jeg-3 cells. CONCLUSIONS: The expression patterns of Cx40 play a crucial role in shaping the responses of EVTs to hypoxia, thereby influencing their migratory or proliferative phenotype. Simultaneously, hypoxia triggers an increase in Cx40 gap junction (GJ) plaque formation through a pathway dependent on NO.


Asunto(s)
Hipoxia de la Célula , Movimiento Celular , Proliferación Celular , Conexinas , Proteína alfa-5 de Unión Comunicante , Uniones Comunicantes , Trofoblastos , Trofoblastos/metabolismo , Humanos , Uniones Comunicantes/metabolismo , Conexinas/metabolismo , Femenino , Embarazo , Línea Celular , Modelos Biológicos , Trofoblastos Extravellosos
2.
Org Biomol Chem ; 22(19): 3910-3925, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38656328

RESUMEN

Herein, we have showed the photophysical properties of favipiravir and its 6-substituted analogues. Also, we interpreted the origin of fluorescence of favipiravir and its 6-substituted analogues as a function of tautomerism modulation in ground and excited states. Favipiravir, the 6-fluorine derivative, showed the best photophysical profile, exhibiting a dominant emission wavelength of 430 nm, a high quantum yield (Q.Y.) of 1.0 and a long-lived state (10 ns). Its analogues also showed a maximum emission at 430 nm, but their Q.Y. values were 5-fold lower than that found for favipiravir, decreasing as a function of 6-substitution as follows: F > Cl > Br > I > H. Pyrazines bearing the least electronegative 6-substituent (X = Br, I, H) showed an extra lifetime, which was shorter (0.2-0.3 ns) and less abundant (>15%) than the main lifetime (10 ns, 85%). Further 2D excitation-emission matrix and solvent studies supported that these 3-hydroxy-2-pyrazinecarboxamides present two emissive states. The first of them (λem = 430 nm), which was the most abundant, most fluorescent and long-lived state, was characterized as "locally excited" (LE). Its fluorescence was favored with an increase of the hydrogen-donor nature of the solvent and for pyrazines having a high enolic characteristic. Thus, the high LE-fluorescence of these types of pyrazines depends on the keto-tautomerization of the ground state using a protic solvent and its feasible enol-tautomerization upon excitation. Finally, the second excited state (λem = 536 nm) was suggested as an excited-state intramolecular proton-transfer (ESIPT), and it was observed only, although discretely, for pyrazines bearing the least electronegative 6-substituent.

3.
Chemistry ; 30(30): e202400905, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38536766

RESUMEN

Blue LEDs-irradiation of a mixture of N,N,N',N'-tetramethylethylenediamine (TMEDA) and perfluoroalkyl iodides (RF-I) - Electron Donor Acceptor (EDA)-complex - in the presence of triphenylamines (TPAs) in an aqueous solvent mixture afforded mono-perfluoroalkylated triphenylamines (RF-TPA) in good yields. These RF-TPA were further subjected to acetone-sensitized [6π]-electrocyclization at 315 nm-irradiation affording exclusively perfluoroalkylated endo-carbazole derivatives (RF-CBz) in quantitative yields. Mechanistic studies and photophysical properties of products are studied.

4.
Chemistry ; 30(8): e202303229, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38032158

RESUMEN

Carbazole is a heterocyclic motif that can be found in a diverse array of natural and unnatural products displaying a wide range of biological and physiological properties. Furthermore, this heterocycle is part of electronic materials like photoconducting polymers and organic optoelectronic materials owing to its excellent photophysical characteristics. Consequently, the development of synthetic strategies for carbazole scaffolds holds potential significance in biological and material fields. In this regard, a variety of preparation methods has been developed to exploit their efficient and distinct formation of new C-C and C-heteroatom bonds under mild conditions and enabling broad substrate diversity and functional group tolerance. Therefore, this review focuses on the synthesis of a set of carbazole derivatives describing a variety of methodologies that involve direct irradiation, photosensitization, photoredox, electrochemical and thermal cyclization reactions.

5.
Salud Publica Mex ; 65(2 mar-abr): 175-180, 2023 Mar 10.
Artículo en Español | MEDLINE | ID: mdl-38060863

RESUMEN

OBJETIVO: Sistematizar, evaluar y sintetizar la investigación original específica en México sobre la zoonosis por Trypano-soma cruzi, los vectores (Triatominae: Hemiptera: Reduviidae) y la enfermedad de Chagas (EC). Material y métodos. La investigación original fue identificada con PRISMA mediante cuatro sistemas de búsqueda, usando criterios de inclusión, se realizó la asignación a 14 áreas temáticas y fue evaluada mediante criterios técnicos. RESULTADOS: De un total de 1 410 registros, fueron elegidos 659 (46.7%) para la valoración técnica, de los cuales, 221 (15.7%) fueron incluidos como las evidencias de mayor calidad. El buscador PubMed contribuyó con 95% de los registros, mientras que los buscadores BibTri, Lilacs y Scielo aportaron 5%. La tasa de publicación fue constante de 1950 a 1990, con un incremento exponencial de 1995 a 2020. La alta calidad de publicaciones incrementó de 5.3% en 1990 hasta 49.8% en 2020. Los temas de aspectos sistémicos, económicos, antropológicos y sociales de la EC en México fueron los menos representados (8%). CONCLUSIONES: En las dos últimas décadas en México ha incrementado la investigación científica. Sin embargo, son notables las caren- cias en las áreas para poder fundamentar la política pública sanitaria en cuanto a la atención, la prevención y el control de la EC en el país.

6.
Cir Cir ; 91(6): 730-735, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38096870

RESUMEN

OBJECTIVE: The objective of the study is to evaluate the characteristics and outcomes of patients with abdominal aortic aneurysm (AAA) and its correlation with mortality in the first 30 days after the procedure was performed. METHODS: Demographic information, clinical and radiological characteristics, as well as outcomes 30 days after the procedure was performed were assessed and compared. Continuous variables were analyzed with Student's t-test and categorical with Chi-square and Fisher's exact test. RESULTS: Duration of the procedure (p = 0.001), blood loss (p < 0.001), age > 75 years (p = 0.027), aneurysm size > 65 mm (p = 0.01), open surgery (p = 0.001), presence of pain (p = 0.005), chronic kidney disease (p = 0.03), and rupture of the aneurysm (p < 0.001) were the factors significantly associated with mortality. CONCLUSION: It is essential that patient characteristics and comorbidities are assessed, as well as factors that may affect the outcomes to predict the prognosis in patients with AAA. At present, no mortality predictive model is universally applicable and highly variable performance across different populations might need a model that adapts to the population of interest.


OBJETIVO: Evaluar las características y resultados de los pacientes con aneurisma de aorta abdominal y su correlación con la mortalidad en los primeros 30 días después de realizado el procedimiento. MÉTODOS: Se evaluó y comparó la información demográfica, las características clínicas y radiológicas, así como los resultados a los 30 días de realizado el procedimiento. Las variables continuas se analizan con la prueba de t de Student y las categóricas con Chi-cuadrado y la prueba exacta de Fisher. RESULTADOS: La duración del procedimiento (p = 0.001), pérdida de sangre (p < 0.001), edad > 75 años (p = 0.027), tamaño del aneurisma > 65 mm (p = 0.01), cirugía abierta (p = 0.001), presencia de dolor (p = 0.005), enfermedad renal crónica (p = 0.03) y rotura del aneurisma (p < 0.001) fueron los factores asociados significativamente a la mortalidad. CONCLUSIÓN: Es fundamental evaluar las características de los pacientes y las comorbilidades, así como los factores que pueden afectar los resultados para predecir el pronóstico en pacientes con aneurisma de aorta abdominal. En la actualidad, ningún modelo predictivo de mortalidad es universalmente aplicable y la alta variabilidad de resultados entre diferentes poblaciones podría necesitar un modelo que se adapte a la población de interés.


Asunto(s)
Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Anciano , Factores de Riesgo , Estudios Transversales , Procedimientos Endovasculares/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/epidemiología , Implantación de Prótesis Vascular/efectos adversos
7.
Trop Med Infect Dis ; 8(7)2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37505666

RESUMEN

Hepatitis C (HCV) continues to present a global public health challenge, with no vaccine available for prevention. Despite the availability of direct-acting antivirals (DAAs) to cure HCV, it remains prevalent in many regions including the Caribbean. As efforts are made to eliminate HCV from the region, existing barriers, such as the high cost of DAAs and lack of an established database of HCV cases within the Caribbean, must be addressed. This review seeks to assess epidemiologic trends (seroprevalence and genotypic diversity) of HCV in the Caribbean and identify gaps in surveillance of the disease. The literature for the period 1 January 2005 to October 2022 was reviewed to gather country-specific data on HCV across the Caribbean. References were identified through indexed journals accessed through established databases using the following keywords: Caribbean, genotype distribution, and general epidemiologic characteristics. The usage pattern of HCV drugs was determined from information obtained from pharmacists across the Caribbean including Jamaica. The prevalence of HCV in the Caribbean was 1.5%; the region should therefore be considered an area of moderate HCV prevalence. The prevalence of HCV among intravenous drug users (21.9-58.8%), persons living with HIV/AIDS (0.8 to 58.5%), prisoners (32.8-64%), and men who have sex with men (MSM) (0.8-6.9%) was generally higher than in the general population (0.8-2.3%). Genotype 1 (83%) was most prevalent followed by genotypes 2 (7.2%) and 3 (2.1%), respectively. Less than 50% of countries in the Caribbean have reliable or well-curated surveillance data on HCV. Drugs currently being used for treatment of HCV infections across the Caribbean include Epclusa (sofosbuvir/velpatasvir) and Harvoni (ledipasvir/sofosbuvir). Some of these drugs are only available in the private sector and are sourced externally whenever needed. While trends point to a potentially higher prevalence of HCV, it will require well-designed random surveys to obtain better estimates of the infection seroprevalence, supported by strong public health laboratory systems. DAAs that are pan-genotypic should translate into treatments that are affordable, accessible, and available to improve cure rates and reduce the HCV burden in the population.

8.
Int. j. morphol ; 41(3): 881-888, jun. 2023. ilus, tab
Artículo en Español | LILACS | ID: biblio-1514314

RESUMEN

El conocimiento anatómico del canal nasopalatino (CNP) es fundamental para la realización de cirugías en el sector anterior del maxilar y así prever posibles complicaciones. El objetivo de este trabajo es evaluar y determinar las variaciones anatómicas y dimensionales del CNP según sexo, edad y estado dental. Este estudio transversal analizó un total de 251 imágenes de TCHC obtenidas de la base de datos del Servicio de Imagenología Oral y Maxilofacial de la Facultad de Odontología de la Universidad Andrés Bello, Viña del Mar, Chile. Para evaluar la asociación estadística entre variaciones del CNP con sexo, edad y estado dentario se realizó la prueba T de Student, chi-cuadrado y ANOVA (p0,05). Además, se detectó diferencia significativa entre el estado dentario y la dimensión de la tabla vestibular en relación con el CNP (p<0,01). Se deben considerar las variaciones de CNP para evitar posibles complicaciones durante los procedimientos quirúrgicos.


SUMMARY: Anatomical knowledge of the nasopalatine canal (PNC) is essential for performing surgeries in the anterior sector of the maxilla and thus anticipating possible complications. The objective of this work is to evaluate and determine the anatomical and dimensional variations of the CNP according to sex, age and dental status. This cross-sectional study analyzed a total of 251 CBCT images obtained from the database of the Oral and Maxillofacial Imaging Service of the Faculty of Dentistry of the Andrés Bello University, Viña del Mar, Chile. To evaluate the statistical association between CNP variations with sex, age and dental status, the Student's T test, chi-square and ANOVA (p0.05). In addition, a significant difference was detected between the dental state and the dimension of the vestibular table in relation to the CNP (p<0.01). CNP variations should be considered to avoid potential complications during surgical procedures.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Hueso Paladar/diagnóstico por imagen , Nariz/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico , Variación Anatómica , Hueso Paladar/anatomía & histología , Nariz/anatomía & histología , Estudios Transversales , Estudios Retrospectivos , Distribución por Edad y Sexo , Maxilar
9.
Cell Rep ; 42(3): 112190, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36857179

RESUMEN

Although the consumption of carbohydrates is needed for survival, their potent reinforcing properties drive obesity worldwide. In turn, sugar overconsumption reveals a major role for brain reward systems in regulating sugar intake. However, it remains elusive how different cell types within the reward circuitries control the initiation and termination of sugary meals. Here, we identified the distinct nucleus accumbens cell types that mediate the chemosensory versus postprandial properties of sweet sugars. Specifically, D1 neurons enhance sugar intake via specialized connections to taste ganglia, whereas D2 neurons mediate the termination of sugary meals via anatomical connections to circuits involved in appetite suppression. Consistently, D2, but not D1, neurons partially mediate the satiating effects of glucagon-like peptide 1 (GLP-1) agonists. Thus, these nucleus accumbens cell types function as a behavioral switch, enabling positive versus negative control over sugar intake. Our study contributes to unveiling the cellular and circuit substrates of sugar overconsumption.


Asunto(s)
Neuronas , Núcleo Accumbens , Ratones , Animales , Núcleo Accumbens/metabolismo , Neuronas/metabolismo , Encéfalo/metabolismo , Azúcares/metabolismo , Receptores de Dopamina D1/metabolismo
10.
J Org Chem ; 88(7): 4405-4421, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-36976299

RESUMEN

The substituent and solvent effects on the spectroscopic behavior and on the photoinduced [6π]-electrocyclization reaction of substituted triphenylamine derivatives have been investigated. Direct irradiation of triphenylamines bearing electron-donor substituents in different solvents has provided for the first time the substituted exo/endo carbazole derivatives from modest to good yields, whereas triphenylamines bearing electron-withdrawing substituents did not provide the carbazoles due to the formation of charge transfer complexes (CTCs). A corollary of the experiments purports that the photoreaction is favored with weak electron-acceptor groups in polar solvents. The lowest-frequency absorption bands of the triarylamines (π,π* electronic transitions) displayed bathochromic shifts as the solvent polarity is increased. The fluorescence emission spectra of triarylamines bearing electron-donor substituents behave as mirror images of the lowest absorption bands, showing dependence on the solvent polarity. Conversely, triarylamines bearing formyl, acetyl, and nitro groups formed CTCs behaving as good fluorescence chromophores in polar solvents. Hammett correlations on the ΔE(0,0) energies of monosubstituted amines showed a bell-shape behavior where the ρ values depended on the solvent polarity. The physical quenching of the photoreaction of triarylamines has demonstrated for the first time that the triplet excited state is univocally the photoreactive state leading to exo/endo carbazole derivatives.

11.
Gac. méd. Méx ; Gac. méd. Méx;158(6): 410-418, nov.-dic. 2022. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1430371

RESUMEN

Resumen Introducción: La enfermedad de Creutzfeldt-Jakob (ECJ) es una enfermedad del sistema nervioso central rápidamente progresiva y mortal causada por priones. Objetivo: Presentar las principales características clínicas y paraclínicas de pacientes con probable ECJ en un centro de referencia de América Latina. Métodos: Estudio retrospectivo de pacientes diagnosticados con demencia rápidamente progresiva entre 2014 y 2019. Se incluyeron características clínicas, demográficas, del electroencefalograma, imágenes por resonancia magnética, proteína 14-3-3 y tomografía por emisión de positrones (PET), cuando estaba disponible. Resultados: Veinticuatro pacientes cumplieron con los criterios de ECJ esporádica (75 % mujeres), la edad media fue de 59.29 ± 11.67 años, la duración de la enfermedad desde el inicio de los síntomas hasta el ingreso hospitalario fue de 7.41 ± 6.54 meses y las primeras manifestaciones más comunes fueron las alteraciones del comportamiento (41.7 %). Los complejos de ondas delta prevalecieron en el electroencefalograma (54.2 %), la hiperintensidad cortical en la resonancia magnética (83.3 %) y el hipometabolismo frontal en la PET (37.5 %). En el análisis del líquido cefalorraquídeo, siete casos mostraron proteína tau total positiva; cinco, proteína 14-3-3 positiva; y tres, proteína tau hiperfosforilada positiva. Conclusiones: Existe importante heterogeneidad clínica en cuanto a los síntomas iniciales. Los hallazgos de las pruebas auxiliares coincidieron con los de otras series.


Abstract Introduction: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal central nervous system disease caused by prions. Objective: To present the main clinical and paraclinical characteristics of patients with probable CJD in a referral center of Latin America. Methods: Retrospective study of patients diagnosed with rapidly progressive dementia between 2014 and 2019. Clinical, demographic, electroencephalogram, magnetic resonance imaging, and 14-3-3 protein characteristics were included, as well as positron-emission tomography (PET) data when available. Results: Twenty-four patients met the criteria for sporadic CJD (75% were women). Mean age was 59.29 ± 11.67 years, while mean disease duration from symptom onset to hospital admission was 7.41 ± 6.54 months. The most common first symptom was behavioral changes (41.7%). Delta wave complexes prevailed (54.2%) on electroencephalogram, cortical hyperintensity (83.3%) on magnetic resonance and frontal hypometabolism (37.5%) on PET. Seven cases showed positive total Tau; five, positive 14-3-3 protein; and three, positive phosphorylated tau on cerebrospinal fluid analysis. Conclusions: There is significant clinical heterogeneity regarding initial symptoms. Auxiliary test findings were consistent with those of other series.

12.
Front Microbiol ; 13: 951173, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36051765

RESUMEN

Pasteurellaceae family members obtain iron directly from host proteins or through siderophore-dependent mechanisms. Although Gallibacterum anatis expresses different virulence factors, its response to growth under iron restriction is unknown. G. anatis cultured in the presence of 2,2'-dipyridyl, up-expressed an approximately 65 kDa protein and repressed the expression of a 70 kDa protein. MALDI-TOF analysis of those proteins indicated homology with CirA (65 kDa), a protein involved in iron-siderophore acquisition in Mannheimia succinoproducens and a TonB-dependent receptor (70 kDa protein), a protein that binds chicken hemoglobin; however, G. anatis siderophore production was not detected by chromo azurol S (CAS)-BHI agar determination. This putative G. anatis siderophore receptor is under Fur control, but not the hemoglobin binding protein, as observed in G. anatis 12656-12 fur mutant (Ω fur 126.13) grown in the presence or not of 2,2'-dipyridyl. The addition of FeCl3 to the culture medium diminished the growth and biofilm production in approximately 30% and 35%, respectively, in the wild-type strain, but the growth of Ω fur 126.13 strain was not affected and biofilm production increased in 35%. G. anatis Ω fur 126.13 presented lower virulence when it was inoculated to 35-day-old chickens in comparison to the wild-type strain. The induction of more than one iron uptake mechanism could benefit pathogenic microorganisms such as Gallibacterium.

13.
J Otol ; 17(2): 101-106, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35949549

RESUMEN

Background: Vestibular symptoms on sitting-up are frequent on patients seen by vestibular specialists. Recently, a benign paroxysmal positional vertigo (BPPV) variant which elicits vestibular symptoms with oculomotor evidence of posterior semicircular canal (P-SCC) cupula stimulation on sitting-up was described and named sitting-up vertigo BPPV. A periampullar restricted P-SCC canalolithiasis was proposed as a causal mechanism. Objective: To describe new mechanisms of action for the sitting-up vertigo BPPV variant. Methods: Eighteen patients with sitting-up vertigo BPPV were examined with a pre-established set of positional maneuvers and follow-up until they resolved their symptoms and clinical findings. Results: All patients showed up-beating torsional nystagmus (UBTN) and vestibular symptoms on coming up from either Dix-Hallpike (DHM) or straight head-hanging maneuver. Sixteen out of 18 patients presented a sustained UBTN with an ipsitorsional component to the tested side on half-Hallpike maneuver (HH). A slower persistent contratorsional down-beating nystagmus was found in eleven out 18 patients tested on nose down position (ND). Conclusions: Persistent direction changing positional nystagmus on HH and ND positions indicative of P-SCC heavy cupula was found in 11 patients. A sustained UBTN on HH with the absence of findings on ND, which is suggestive of the presence of P-SCC short arm canalolithiasis, was found on 5 patients. All patients were treated with canalith repositioning maneuvers without success, but they resolved their findings by means of Brandt-Daroff exercises. We propose P-SCC heavy cupula and P-SCC short arm canalolithiasis as two new putative mechanisms for the sitting-up vertigo BPPV variant.

14.
J Org Chem ; 87(20): 13439-13454, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-35675160

RESUMEN

Direct irradiation of mono-, di-, and trisubstituted triphenylamine derivatives in acetonitrile as solvent with light of 254 nm has been systematically investigated, revealing that the exo/endo carbazole derivatives were formed as the main photoproducts from modest to good yields for triphenylamines substituted with electron-donor and neutral substituents. The kinetic profiles of the photoreaction were also recorded, and the consumption rate constants (k) were measured. These kinetic parameters show dependence on the nature of the substituents, and linear Hammett correlations were carried out to showcase the substituent effect. On the other hand, the spectroscopic behavior of the electron-rich substituted triphenylamines has been analyzed, suggesting that the fluorescence emission spectra display a mirror image of the lower energy absorption bands, while for those amines bearing electron-acceptor groups the formation of charge-transfer complexes and their fluorescence emissions constitute the main deactivation pathway of the photoreaction.

15.
Cells ; 11(6)2022 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-35326371

RESUMEN

The intake of food with high levels of saturated fatty acids (SatFAs) is associated with the development of obesity and insulin resistance. SatFAs, such as palmitic (PA) and stearic (SA) acids, have been shown to accumulate in the hypothalamus, causing several pathological consequences. Autophagy is a lysosomal-degrading pathway that can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Previous studies showed that PA impairs macroautophagy function and insulin response in hypothalamic proopiomelanocortin (POMC) neurons. Here, we show in vitro that the exposure of POMC neurons to PA or SA also inhibits CMA, possibly by decreasing the total and lysosomal LAMP2A protein levels. Proteomics of lysosomes from PA- and SA-treated cells showed that the inhibition of CMA could impact vesicle formation and trafficking, mitochondrial components, and insulin response, among others. Finally, we show that CMA activity is important for regulating the insulin response in POMC hypothalamic neurons. These in vitro results demonstrate that CMA is inhibited by PA and SA in POMC-like neurons, giving an overview of the CMA-dependent cellular pathways that could be affected by such inhibition and opening a door for in vivo studies of CMA in the context of the hypothalamus and obesity.


Asunto(s)
Autofagia Mediada por Chaperones , Humanos , Insulina/metabolismo , Neuronas/metabolismo , Obesidad/metabolismo , Proopiomelanocortina/metabolismo , Ácidos Esteáricos/metabolismo , Ácidos Esteáricos/farmacología
16.
Nucleic Acids Res ; 50(4): 1875-1887, 2022 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-35037039

RESUMEN

Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.


Asunto(s)
Autofagia Mediada por Chaperones , Histonas , Autofagia , Histonas/metabolismo , Lisosomas/metabolismo , Biosíntesis de Proteínas
17.
Gac Med Mex ; 158(6): 401-409, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36657127

RESUMEN

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal central nervous system disease caused by prions. OBJECTIVE: To present the main clinical and paraclinical characteristics of patients with probable CJD in a referral center of Latin America. METHODS: Retrospective study of patients diagnosed with rapidly progressive dementia between 2014 and 2019. Clinical, demographic, electroencephalogram, magnetic resonance imaging, and 14-3-3 protein characteristics were included, as well as positron-emission tomography (PET) data when available. RESULTS: Twenty-four patients met the criteria for sporadic CJD (75% were women). Mean age was 59.29 ± 11.67 years, while mean disease duration from symptom onset to hospital admission was 7.41 ± 6.54 months. The most common first symptom was behavioral changes (41.7%). Delta wave complexes prevailed (54.2%) on electroencephalogram, cortical hyperintensity (83.3%) on magnetic resonance and frontal hypometabolism (37.5%) on PET. Seven cases showed positive total Tau; five, positive 14-3-3 protein; and three, positive phosphorylated tau on cerebrospinal fluid analysis. CONCLUSIONS: There is significant clinical heterogeneity regarding initial symptoms. Auxiliary test findings were consistent with those of other series.


INTRODUCCIÓN: La enfermedad de Creutzfeldt-Jakob (ECJ) es una enfermedad del sistema nervioso central rápidamente progresiva y mortal causada por priones. OBJETIVO: Presentar las principales características clínicas y paraclínicas de pacientes con probable ECJ en un centro de referencia de América Latina. MÉTODOS: Estudio retrospectivo de pacientes diagnosticados con demencia rápidamente progresiva entre 2014 y 2019. Se incluyeron características clínicas, demográficas, del electroencefalograma, imágenes por resonancia magnética, proteína 14-3-3 y tomografía por emisión de positrones (PET), cuando estaba disponible. RESULTADOS: Veinticuatro pacientes cumplieron con los criterios de ECJ esporádica (75 % mujeres), la edad media fue de 59.29 ± 11.67 años, la duración de la enfermedad desde el inicio de los síntomas hasta el ingreso hospitalario fue de 7.41 ± 6.54 meses y las primeras manifestaciones más comunes fueron las alteraciones del comportamiento (41.7 %). Los complejos de ondas delta prevalecieron en el electroencefalograma (54.2 %), la hiperintensidad cortical en la resonancia magnética (83.3 %) y el hipometabolismo frontal en la PET (37.5 %). En el análisis del líquido cefalorraquídeo, siete casos mostraron proteína tau total positiva; cinco, proteína 14-3-3 positiva; y tres, proteína tau hiperfosforilada positiva. CONCLUSIONES: Existe importante heterogeneidad clínica en cuanto a los síntomas iniciales. Los hallazgos de las pruebas auxiliares coincidieron con los de otras series.


Asunto(s)
Síndrome de Creutzfeldt-Jakob , Priones , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagen , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquídeo , México/epidemiología , Estudios Retrospectivos , Proteínas 14-3-3/líquido cefalorraquídeo , Priones/líquido cefalorraquídeo , Imagen por Resonancia Magnética , Electroencefalografía , Encéfalo
18.
Rev. Cuerpo Méd. Hosp. Nac. Almanzor Aguinaga Asenjo ; 14(Supl. 1): 33-40, oct. 21, 2021.
Artículo en Español, Inglés | LILACS-Express | LILACS | ID: biblio-1354861

RESUMEN

Introducción: La pandemia de la COVID-19 ha generado un incremento de la información sobre esta enfermedad, por lo que es fundamental garantizar la credibilidad y confiabilidad de las páginas web que brindan esta información. Objetivo: Evaluar la confiabilidad de la información sanitaria en español sobre la COVID-19 en el motor de búsqueda Google considerando los criterios de la herramienta HONcode. Material y métodos: Estudio observacional de corte transversal. Las páginas web de Google se analizaron en diciembre del 2020 desde Lima-Perú, utilizando 4 términos de búsqueda. Se evaluó la confiabilidad de la información sanitaria de las páginas web mediante la herramienta HONcode (versión 3.1.3). Se clasificaron según la fuente de información y su procedencia. El análisis estadístico se realizó para un nivel de significancia de p<0,05. Resultados: Se evaluaron 200 páginas web en español, el 16,5% poseían certificado HONcode, la mayoría fue de la OMS (33,3%), la principal fuente de información fue "académica-profesional" (30,0%). Además, el 33,0% de las páginas web eran peruanas, siendo mayormente de tipo gubernamental (42,4%), pero ninguna tenía certificado HONcode. Conclusiones: Solo una de cada seis páginas web proporcionaba información sanitaria confiable sobre la COVID-19. Además, se distingue la presencia de las páginas web de la OMS en proveer información sanitaria sobre la COVID-19 en Google. Si bien este estudio destaca las páginas web de organismos internacionales, se requiere fortalecer la comunicación desde las páginas web gubernamentales peruanas.


Introduction: The COVID-19 pandemic has generated an increase in information about this disease, so it is essential to ensure the credibility and reliability of the web pages that provide this information. Objective: To evaluate the reliability of health information in Spanish on COVID-19 in the Google search engine considering the criteria of the HONcode tool. Material and methods: Observational cross-sectional study. Google web pages were analyzed in December 2020 from Lima-Peru, using 4 search terms. The reliability of the health information on the web pages was assessed using the HONcode tool (version 3.1.3). They were classified according to the source of information and its provenance. Statistical analysis was performed for a significance level of p<0.05. Results: 200 web pages in Spanish were evaluated, 16.5% were HONcode certified, most of them were from the WHO (33.3%), the main source of information was "academic-professional" (30.0%). In addition, 33.0% of the web pages were Peruvian, being mostly governmental (42.4%), but none had HONcode certificate. Conclusions: Only one out of six web pages provided reliable health information on COVID-19. In addition, the presence of WHO web pages in providing health information about COVID-19 on Google stands out. Although this study highlights the web pages of international organizations, there is a need to strengthen communication from Peruvian governmental web pages.

19.
J Phys Chem B ; 125(32): 9268-9285, 2021 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-34357778

RESUMEN

Diverse models of intramolecular charge transfer (ICT) have been proposed for interpreting the origin of the charge-transfer (CT) state in donor-acceptor (D-A) dyes. However, a large variety of fused-heterocyclic dyes containing a pseudo-aromatic ring in the rigid structure have shown to be incompatible with them. To approximate a solution within the ICT concept, we reported a novel ICT model called partially aromatized intramolecular charge transfer (PAICT). PAICT involves the generation of a CT state from an ICT that occurred within a pre-excited D-A fused-heterocyclic structure possessing a pseudo-aromatic or unstable aromatic ring as the acceptor moiety. The model was proposed from the multiple-emissive mesomeric D-A N1-aryl-2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-one, whose excited mesomeric states, which are defined by the aromatic and pseudo-aromatic forms of the pyrindin-4(1H)-one ring, led to a common partial aromatized CT state upon excitation via PAICT. The latter was supported through theoretical calculations on the excited mesomeric states, one-dimensional (1D) and two-dimensional (2D) excitation-emission measurements in different solvents, and the detection of three excited states by lifetime measurements upon 370 nm excitation. The existence of mesomerism was supposed from: (i) two overlapping bands at 370-390 (or 400-420 nm) in UV-vis spectra, (ii) the direct interaction between the pyridinic nitrogen of one molecule and the carbonylic oxygen of the other found in the solid state and, (iii) the detection of three excited states by lifetime measurements. The PAICT opens new perspectives for interpreting the charge-transfer phenomenon in fused-heterocyclic dyes, in particular, those containing a pseudo-aromatic or unstable aromatic ring as an acceptor moiety.


Asunto(s)
Colorantes/química , Solventes
20.
Orinoquia ; 25(1): 35-46, Jan.-June 2021. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1351170

RESUMEN

resumen está disponible en el texto completo


Abstract The growth in broiler chicken production has been a determining factor regarding Colombia's economy and a determining factor in promoting the countryside's economic development. Using probiotics containing lactic acid-producing bacteria in broiler chickens' diet contributes to intestinal flora integrity and stability, thereby hampering pathogen proliferation which helps prevent diseases and improve productivity. This research was aimed at evaluating broiler chicken nutrient digestibility and production parameters by including cayenne pepper flour (Hibiscus rosa-sinensis, L.) with and without a probiotic (Lactobacillus acidophilus) plus pectin in chicken feed to replace concentrated food. This project was carried out in Villavicencio in Colombia's Meta department; 90 broilers were fed on broiler starter concentrate for 15 days. T1 treatment consisted of concentrate commercial (CC) milled crumble, T2 CC plus 6% cayenne flour (CF) and T3 CC plus 12% CF; these treatments were compared with a probiotic (WP) and without it (WoP) plus pectin (PP). Cayenne pepper green stems and leaves were harvested 60 days after the last pruning for making CF; they were dehydrated for 72 hours at 60oC and then ground. The chickens' average weight was 675.1±50g; a randomised complete block design (RCBD) was used, along with Tukey's multiple comparison test for statistical analysis of the resulting data. Excreta were collected over a five-day period for estimating digestibility coefficients (DC). Broiler diets and excreta were analysed regarding dry matter (DM), protein, fibre, fat, non-nitrogenous extract (NNE) and neutral detergent fibre (NDF); % total digestible nutrients (TDN) and protein biological value (BV) were estimated. Production variables such as food consumption rate, weight gain, feed conversion and carcass yield were evaluated. T2 had the highest DM WoP DC (0.91) and DM WP DC (0.93) compared to those for T1 (0.71 DM WoP DC and DM WP DC 0.72) (p<0.05); the same happened for T2 protein (0.88 DM WoP DC and 0.92 DM WP DC) and fibre (0.82 DM WoP DC and 0.84 DM WP DC), such DC being greater (p<0.05) than those for T3 (protein 0.72 DM WoP DC and 0.81 DM WP DC and fibre 0.56 DM WoP DC and 0.57 DM WP DC). T2 had the highest TDN value: 92 (83%) compared to T3: 77 (56%). All treatments had DM similar consumption rates. Daily weight gain was higher (p<0.05) for T1 WoP (93.74g) and WP (89.78g) compared to T3 (84.08g T1 WoP and 81.95g WP); no differences were observed regarding T2. T2 WoP (2.0) and T3 WP (1.95) had the lowest food to weight conversion rates; the probiotic had an effect on this because T2 WP (1.74) was similar to T1 WoP (1.81) and WP (1.86). T1 WP (66.12%) and WoP (65.49%) and T2 WP (64.92%) had promising carcass yields compared to that for the other treatments. There were no differences between T2 and T1 regarding most variables evaluated here, meaning that commercial concentrate can be confidently replaced by 6% cayenne flour in broiler diets during their fattening phase.


Resumo O crescimento da produção avícola tem sido um fator determinante na economia, sendo um dos motores para promover o desenvolvimento econômico do campo colombiano. O uso de probióticos que contêm bactérias produtoras de ácido lático na ração de aves contribui para a integridade e estabilidade da flora intestinal, dificultando a proliferação de patógenos, o que ajuda a prevenir doenças e melhorar o desempenho produtivo. O objetivo desta pesquisa foi avaliar a digestibilidade dos nutrientes e parâmetros produtivos em frangos de corte incluindo a farinha de pimenta de Caiena (Hibiscus rosa sinensis) sem e com probiótico (Lactobacilius acidophilus) mais pectina em substituição ao concentrado. Este projeto foi realizado em Villavicencio, Meta, foram utilizados 90 frangos, durante 15 dias, eles foram alimentados com concentrado inicial. Os tratamentos foram: T1 concentrado comercial moído (CC), T2 CC e farinha de pimenta-caiena 6% (HC) e T3 CC e 12% HC, comparando-se esses tratamentos sem (SP) e com probiótico mais pectina (CP). Para a produção do HC, os caules verdes e as folhas de caiena foram colhidos 60 dias após o último corte, foram desidratados por 72 horas a 60 graus centígrados e moídos. O peso médio dos frangos foi de 675,1 ± 50g, sendo distribuídos em delineamento inteiramente casualizado e aplicado o teste de comparações múltiplas de Tukey. Para estimar os coeficientes de digestibilidade (COD), as excretas foram coletadas por cinco dias. As dietas e excretas foram analisadas: matéria seca (MS), proteína, fibra, gordura, extrato não nitrogenado (ENN) e fibra em detergente neutro (FDN). Foram estimados: nutrientes digestíveis totais (NDT), valor biológico (VB) da proteína. Variáveis ​​produtivas como: consumo de ração, ganho de peso, conversão alimentar e rendimento de carcaça também foram avaliadas. O maior DM COD (P <0,05) foi para T2 SP e CP: 0,91 e 0,93 VS T1 0,71 e 0,72, o mesmo aconteceu com o COD de proteína e fibra de T2 sendo maior (P <0,05) em relação ao T3: 0,88 e 0,92 VS 0,72 e 0,81; 0,82 e 084 VS 0,56 e 0,57, respectivamente. O maior valor de NDT foi para T2: 92,83% VS T3: 77,56%. O consumo de matéria seca foi semelhante para todos os tratamentos. O ganho de peso diário foi maior (P <0,05) em T1 CP e SP 93,74 e 89,78 g em comparação com T3 84,08 e 81,95 g, não foram observadas diferenças com T2. As conversões de alimentação para peso mais baixas foram para T2 SP (2,0) e T3 CP (1,95). Observando o efeito do probiótico em T2 CP (1,74). O desempenho de carcaça foi semelhante para todos os tratamentos, embora valores numericamente superiores tenham sido observados em T1 CP e SP; T2 CP: 66,12, 65,49 e 64,92%), em relação aos demais tratamentos. Na maioria das variáveis ​​avaliadas, T2 não apresentou diferença com T1, o que significa que nas dietas para aves em fase de engorda, o concentrado comercial pode ser substituído por 6% de farinha de pimenta de caiena.

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