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2.
Artículo en Inglés | MEDLINE | ID: mdl-39317941

RESUMEN

INTRODUCTION: A comprehensive and global knowledge of protein target engagement is of vital importance for mechanistic studies and in drug development. Since its initial introduction, the cellular thermal shift assay (CETSA) has proven to be a reliable and flexible technique that can be widely applied to multiple contexts and has profound applications in facilitating the identification and assessment of protein target engagement. AREAS COVERED: This review introduces the principle of CETSA, elaborates on western blot-based CETSA and MS-based thermal proteome profiling (TPP) as well as the major applications and prospects of these approaches. EXPERT OPINION: CETSA primarily evaluates a given ligand binding to a particular target protein in cells and tissues with the protein thermal stabilities analyzed by western blot. When coupling mass spectrometry with CETSA, thermal proteome profiling allows simultaneous proteome-wide experiment that greatly increased the efficiency of target engagement evaluation, and serves as a promising strategy to identify protein targets and off-targets as well as protein-protein interactions to uncover the biological effects. The CETSA approaches have broad applications and potentials in drug development and clinical research.

3.
J Acoust Soc Am ; 156(2): 912-921, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39120870

RESUMEN

The study of acoustic radiation from spherical sound sources plays a crucial role in understanding the thermoviscous effects in practical acoustic problems. However, finding a general solution of acoustic radiation from spherical sound sources in thermoviscous fluids remains a formidable challenge. To advance this issue, an analytical method is developed in this paper to calculate the acoustic field radiated by spherical sound sources with the isothermal boundary condition and arbitrary velocity boundary condition. The developed method is utilized to present the solutions of the acoustic field generated by an oscillating sphere and a general spherical sound source, and the accuracy and validity of these solutions are verified through analytical and numerical methods.

4.
Neuroscience ; 554: 96-106, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38964451

RESUMEN

Cerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18ß-GA) in ameliorates CIRI. Our results showed that 18ß-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18ß-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18ß-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18ß-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18ß-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18ß-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18ß-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.


Asunto(s)
Autofagia , Infarto de la Arteria Cerebral Media , Janus Quinasa 2 , Fármacos Neuroprotectores , Ratas Sprague-Dawley , Daño por Reperfusión , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Janus Quinasa 2/metabolismo , Janus Quinasa 2/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Autofagia/efectos de los fármacos , Autofagia/fisiología , Masculino , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Fármacos Neuroprotectores/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/patología , Ácido Glicirrínico/farmacología , Ratas , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología
5.
Int J Biol Macromol ; 275(Pt 1): 133594, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38960258

RESUMEN

Exosomal miRNAs have vital functions in mediating intercellular communication as well as tumor occurrence and development. Thus, our research was aimed at exploring the regulatory mechanisms of exosomal miR-130b-3p/DEP domain containing 1 (DEPDC1)/transforming growth factor-ß (TGF-ß) signaling pathway in non-small cell lung cancer (NSCLC). Here we indicated that exosomal miR-130b-3p expression decreased in the serum of NSCLC patients, and it was of significant diagnostic value. Moreover, elevated miR-130b-3p levels suppressed the proliferation and migration of NSCLC cells, and enhanced their apoptosis. Conversely, miR-130b-3p down-regulation led to an opposite effect. As the upstream of DEPDC1, miR-130b-3p directly bound to 3'UTR in DEPDC1 to regulate its expression. DEPDC1 levels affected the proliferation, migration, and apoptosis of NSCLC cells via TGF-ß signaling pathway. Exosomal miR-130b-3p was highly expressed in BEAS-2B cells, besides, BEAS-2B cells transferred exosomal miR-130b-3p to NSCLC cells. Finally, exosomal miR-130b-3p suppressed NSCLC cell growth and migration, promoted their apoptosis via TGF-ß signaling pathway by decreasing DEPDC1 expression, and suppressed epithelial-mesenchymal transition (EMT) in NSCLC cells. In conclusion, exosomal miR-130b-3p has the potential to be a predictive biomarker for NSCLC, thereby stimulating the exploration of diagnostic and therapeutic approaches targeting NSCLC.


Asunto(s)
Apoptosis , Carcinoma de Pulmón de Células no Pequeñas , Movimiento Celular , Proliferación Celular , Exosomas , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , MicroARNs , Transducción de Señal , Factor de Crecimiento Transformador beta , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Proliferación Celular/genética , Movimiento Celular/genética , Línea Celular Tumoral , Apoptosis/genética , Exosomas/metabolismo , Exosomas/genética , Proteínas Activadoras de GTPasa/genética , Proteínas Activadoras de GTPasa/metabolismo , Masculino , Femenino , Metástasis de la Neoplasia , Persona de Mediana Edad
6.
Eur Spine J ; 33(8): 3191-3212, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38965088

RESUMEN

OBJECTIVE: To compare the efficacy and safety of vertebroplasty through different pedicle approaches in the treatment of osteoporotic vertebral compression fracture osteoporotic vertebral compression fractures (OVCF) by network meta-analysis. METHODS: Pubmed, Embase, Cochrane Library, Web of Science. Database for literature retrieval, retrieval time from the establishment of the database to April 2023, the randomized controlled trials of unilateral vertebroplasty (UVP), bilateral vertebroplasty (BVP), unilateral kyphoplasty (UKP), bilateral kyphoplasty (BKP), curved vertebroplasty (CVP) and curved kyphoplasty (CKP) were screened, evaluated and the data were extracted and included in the analysis. STATA 15.0 and ReMan 5.3 were used for data analysis. This study was registered in the National Institute for Health Research (NIHR) with the registration number CRD42023405181. RESULTS: This study included 16 articles with a total of 1712 patients. The order of visual analogue scale (VAS) improvement from good to bad is CVP > BVP > UVP > CKP > BKP > UKP. The order of kyphotic angles improvement from good to bad is CKP > UKP > UKP > UVP > BVP > CVP. The order of bone cement injection from less to more is UVP > CVP > UKP > CKP > BVP > BKP. The order of bone cement leakage rate from less to more is CKP > CVP > UKP > BKP > UVP > BVP. The order of X-ray exposure time from less to more is CKP > CVP > UVP > BVP > UKP > BKP. The order of operation time from less to more is CVP > UVP > UKP > CKP > BVP > BKP. CONCLUSION: For patients with kyphotic angles, kyphoplasty has unique advantages in improving kyphotic angles. But generally speaking, curved approach can optimize the distribution of bone cement through unilateral approach to achieve the orthopedic effect of bilateral approach, which is a minimally invasive technique with better curative effect and higher safety in the treatment of OVCF.


Asunto(s)
Fracturas por Compresión , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Humanos , Vertebroplastia/métodos , Fracturas Osteoporóticas/cirugía , Fracturas de la Columna Vertebral/cirugía , Fracturas por Compresión/cirugía , Resultado del Tratamiento , Cifoplastia/métodos , Metaanálisis en Red
7.
Front Plant Sci ; 15: 1368885, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006957

RESUMEN

Introduction: Global illegal trade in timbers is a major cause of the loss of tree species diversity. The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) has been developed to combat the illegal international timber trade. Its implementation relies on accurate wood identification techniques for field screening. However, meeting the demand for timber field screening at the species level using the traditional wood identification method depending on wood anatomy is complicated, time-consuming, and challenging for enforcement officials who did not major in wood science. Methods: This study constructed a CITES-28 macroscopic image dataset, including 9,437 original images of 279 xylarium wood specimens from 14 CITES-listed commonly traded tree species and 14 look-alike species. We evaluated a suitable wood image preprocessing method and developed a highly effective computer vision classification model, SE-ResNet, on the enhanced image dataset. The model incorporated attention mechanism modules [squeeze-and-excitation networks (SENet)] into a convolutional neural network (ResNet) to identify 28 wood species. Results: The results showed that the SE-ResNet model achieved a remarkable 99.65% accuracy. Additionally, image cropping and rotation were proven effective image preprocessing methods for data enhancement. This study also conducted real-world identification using images of new specimens from the timber market to test the model and achieved 82.3% accuracy. Conclusion: This study presents a convolutional neural network model coupled with the SENet module to discriminate CITES-listed species with their look-alikes and investigates a standard guideline for enhancing wood transverse image data, providing a practical computer vision method tool to protect endangered tree species and highlighting its substantial potential for CITES implementation.

8.
ACS Nano ; 18(26): 16658-16673, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38907726

RESUMEN

Current therapies primarily targeting inflammation often fail to address the root relationship between intestinal mucosal integrity and the resulting dysregulated cell death and ensuing inflammation in ulcerative colitis (UC). First, UC tissues from human and mice models in this article both emphasize the crucial role of Gasdermin E (GSDME)-mediated pyroptosis in intestinal epithelial cells (IECs) as it contributes to colitis by releasing proinflammatory cytokines, thereby compromising the intestinal barrier. Then, 4-octyl-itaconate (4-OI), exhibiting potential for anti-inflammatory activity in inhibiting pyroptosis, was encapsulated by butyrate-modified liposome (4-OI/BLipo) to target delivery for IECs. In brief, 4-OI/BLipo exhibited preferential accumulation in inflamed colonic epithelium, attributed to over 95% of butyrate being produced and absorbed in the colon. As expected, epithelium barriers were restored significantly by alleviating GSDME-mediated pyroptosis in colitis. Accordingly, the permeability of IECs was restored, and the resulting inflammation, mucosal epithelium, and balance of gut flora were reprogrammed, which offers a hopeful approach to the effective management of UC.


Asunto(s)
Colitis Ulcerosa , Células Epiteliales , Mucosa Intestinal , Piroptosis , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Piroptosis/efectos de los fármacos , Animales , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Ratones , Humanos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Células Epiteliales/metabolismo , Liposomas/química , Ratones Endogámicos C57BL , Sistemas de Liberación de Medicamentos
9.
Food Res Int ; 190: 114553, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38945595

RESUMEN

Consumer preferences for walnut products are largely determined by the flavors released during mastication. In this study, a peeled walnut kernel (PWK) model was established with oral parameters decoupled using a Hutchings 3D model. The model explored in vitro variations using head-space solid-phase microextraction-gas chromatography-mass spectrometry and intelligent sensory techniques. The fracture strength, hardness, particle size, adhesiveness, springiness, gumminess, and chewiness were significantly reduced during mastication. We identified 61 volatile compounds and found that 2,5-dimethyl-3-ethylpyrazine is a key component, releasing predominantly baking and milky notes. Glutamic acid, alanine, arginine, and sucrose were identified as the key compounds in taste perception. The method can help establish a mastication model for nuts and facilitate breakthroughs in the development of walnut products and processing methods.


Asunto(s)
Cromatografía de Gases y Espectrometría de Masas , Juglans , Masticación , Nueces , Gusto , Compuestos Orgánicos Volátiles , Juglans/química , Nueces/química , Compuestos Orgánicos Volátiles/análisis , Humanos , Microextracción en Fase Sólida , Dureza , Tamaño de la Partícula , Aromatizantes/análisis
10.
Front Immunol ; 15: 1371365, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887298

RESUMEN

Hypoxia exerts a profound influence on the tumor microenvironment and immune response, shaping treatment outcomes and prognosis. Utilizing consistency clustering, we discerned two hypoxia subtypes in OPSCC bulk sequencing data from GEO. Key modules within OPSCC were identified through weighted gene correlation network analysis (WGCNA). Core modules underwent CIBERSORT immune infiltration analysis and GSEA functional enrichment. Univariate Cox and LASSO analyses were employed to construct prognostic models for seven hypoxia-related genes. Further investigation into clinical characteristics, the immune microenvironment, and TIDE algorithm prediction for immunotherapy response was conducted in high- and low-risk groups. scRNA-seq data were visually represented through TSNE clustering, employing the scissors algorithm to map hypoxia phenotypes. Interactions among cellular subpopulations were explored using the Cellchat package, with additional assessments of metabolic and transcriptional activities. Integration with clinical data unveiled a prevalence of HPV-positive patients in the low hypoxia and low-risk groups. Immunohistochemical validation demonstrated low TDO2 expression in HPV-positive (P16-positive) patients. Our prediction suggested that HPV16 E7 promotes HIF-1α inhibition, leading to reduced glycolytic activity, ultimately contributing to better prognosis and treatment sensitivity. The scissors algorithm effectively segregated epithelial cells and fibroblasts into distinct clusters based on hypoxia characteristics. Cellular communication analysis illuminated significant crosstalk among hypoxia-associated epithelial, fibroblast, and endothelial cells, potentially fostering tumor proliferation and metastasis.


Asunto(s)
Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Pronóstico , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Comunicación Celular , Hipoxia/genética , Hipoxia/metabolismo , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Masculino
11.
Proc Natl Acad Sci U S A ; 121(24): e2321619121, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38833475

RESUMEN

Angiotensin-convertingenzyme 2 (ACE2) has dual functions, regulating cardiovascular physiology and serving as the receptor for coronaviruses. Bats, the only true flying mammals and natural viral reservoirs, have evolved positive alterations in traits related to both functions of ACE2. This suggests significant evolutionary changes in ACE2 during bat evolution. To test this hypothesis, we examine the selection pressure in ACE2 along the ancestral branch of all bats (AncBat-ACE2), where powered flight and bat-coronavirus coevolution occurred, and detect a positive selection signature. To assess the functional effects of positive selection, we resurrect AncBat-ACE2 and its mutant (AncBat-ACE2-mut) created by replacing the positively selected sites. Compared to AncBat-ACE2-mut, AncBat-ACE2 exhibits stronger enzymatic activity, enhances mice's performance in exercise fatigue, and shows lower affinity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings indicate the functional pleiotropy of positive selection in the ancient ACE2 of bats, providing an alternative hypothesis for the evolutionary origin of bats' defense against coronaviruses.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Quirópteros , Selección Genética , Quirópteros/virología , Quirópteros/genética , Animales , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Ratones , Pleiotropía Genética , Evolución Molecular , SARS-CoV-2/genética , COVID-19/virología , COVID-19/genética , Coronavirus/genética , Humanos , Filogenia
12.
Int Immunopharmacol ; 135: 112298, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38776854

RESUMEN

BACKGROUND: Excessive activation of colonic fibroblasts and differentiation of T helper 17 (Th17) cells are the key steps for intestinal fibrogenesis in the process of inflammatory bowel disease (IBD). Although both transforming growth factor-beta (TGF-ß)/Mothers Against Decapentaplegic Homolog (SMAD) 3-induced fibroblasts activation and interleukin (IL)-6/signal transducer and activator of transcription (STAT) 3-induced Th17 differentiation have been well studied, the crosstalk between fibroblasts and Th17 cells in the process of intestinal fibrogenesis needs to be unveiled. METHODS: In this study, the activation of colonic fibroblasts was induced with dextran sulfate sodium salt (DSS) and TGF-ß in vivo and in vitro respectively. P-SMAD3 and its downstream targets were quantified using RT-PCR, western blot and immunofluorescence. The differentiation of programmed death 1 (PD-1) + Th17 and activation of fibroblasts were quantified by FACS. PD-1+ Th17 cells and fibroblasts were co-cultured and cytokines in the supernatant were tested by ELISA. The anti-fibrosis effects of different chemical compounds were validated in vitro and further confirmed in vivo. RESULTS: The colonic fibroblasts were successfully activated by DSS and TGF-ß in vivo and in vitro respectively, as activation markers of fibroblasts (p-SMAD3 and its downstream targets such as Acta2, Col1a1 and Ctgf) were significantly increased. The activated fibroblasts produced more IL-6 compared with their inactivated counterparts in vivo and in vitro. The proinflammatory cytokine IL-6 induced PD-1+ Th17 differentiation and TGF-ß that in return promoted the activation of colonic fibroblasts. Fraxinellone inhibited TGF-ß+ PD-1+ Th17 cells via deactivating STAT3. CONCLUSIONS: The reciprocal stimulation constructed a circuit of PD-1+ Th17 cells and fibroblasts that accelerated the fibrosis process. Fraxinellone was selected as the potential inhibitor of the circuit of PD-1+ Th17 cells and fibroblasts in vivo and in vitro. Inhibiting the circuit of PD-1+ Th17 cells and fibroblasts could be a promising strategy to alleviate intestinal fibrosis.


Asunto(s)
Colitis , Sulfato de Dextran , Fibroblastos , Fibrosis , Ratones Endogámicos C57BL , Células Th17 , Animales , Fibroblastos/efectos de los fármacos , Células Th17/inmunología , Células Th17/efectos de los fármacos , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/inmunología , Ratones , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Colon/patología , Colon/efectos de los fármacos , Colon/inmunología , Células Cultivadas , Proteína smad3/metabolismo , Masculino , Factor de Crecimiento Transformador beta/metabolismo , Humanos , Transducción de Señal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos
13.
Immunol Invest ; 53(5): 766-787, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38622991

RESUMEN

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.


Asunto(s)
Condrocitos , Células Asesinas Naturales , Osteoartritis , Humanos , Osteoartritis/inmunología , Células Asesinas Naturales/inmunología , Animales , Condrocitos/inmunología , Osteoclastos/inmunología , Sinoviocitos/inmunología , Sinoviocitos/metabolismo , Comunicación Celular/inmunología , Macrófagos/inmunología
14.
Plant Methods ; 20(1): 56, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38659006

RESUMEN

BACKGROUND: Traditional method of wood species identification involves the use of hand lens by wood anatomists, which is a time-consuming method that usually identifies only at the genetic level. Computer vision method can achieve "species" level identification but cannot provide an explanation on what features are used for the identification. Thus, in this study, we used computer vision methods coupled with deep learning to reveal interspecific differences between closely related tree species. RESULT: A total of 850 images were collected from the cross and tangential sections of 15 wood species. These images were used to construct a deep-learning model to discriminate wood species, and a classification accuracy of 99.3% was obtained. The key features between species in machine identification were targeted by feature visualization methods, mainly the axial parenchyma arrangements and vessel in cross section and the wood ray in tangential section. Moreover, the degree of importance of the vessels of different tree species in the cross-section images was determined by the manual feature labeling method. The results showed that vessels play an important role in the identification of Dalbergia, Pterocarpus, Swartzia, Carapa, and Cedrela, but exhibited limited resolutions on discriminating Swietenia species. CONCLUSION: The research results provide a computer-assisted tool for identifying endangered tree species in laboratory scenarios, which can be used to combat illegal logging and related trade and contribute to the implementation of CITES convention and the conservation of global biodiversity.

15.
J Med Chem ; 67(9): 7635-7646, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38661304

RESUMEN

The T-cell receptor (TCR) is a crucial molecule in cellular immunity. The single-chain T-cell receptor (scTCR) is a potential format in TCR therapeutics because it eliminates the possibility of αß-TCR mispairing. However, its poor stability and solubility impede the in vitro study and manufacturing of therapeutic applications. In this study, some conserved structural motifs are identified in variable domains regardless of germlines and species. Theoretical analysis helps to identify those unfavored factors and leads to a general strategy for stabilizing scTCRs by substituting residues at exact IMGT positions with beneficial propensities on the consensus sequence of germlines. Several representative scTCRs are displayed to achieve stability optimization and retain comparable binding affinities with the corresponding αß-TCRs in the range of µM to pM. These results demonstrate that our strategies for scTCR engineering are capable of providing the affinity-enhanced and specificity-retained format, which are of great value in facilitating the development of TCR-related therapeutics.


Asunto(s)
Receptores de Antígenos de Linfocitos T , Humanos , Receptores de Antígenos de Linfocitos T/química , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Estabilidad Proteica , Receptores de Antígenos de Linfocitos T alfa-beta/química , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Secuencia de Aminoácidos , Modelos Moleculares , Ingeniería de Proteínas , Unión Proteica
16.
Crit Rev Food Sci Nutr ; : 1-29, 2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38644658

RESUMEN

As one of the most important vegetables and oils consumed globally, cruciferous foods are appreciated for their high nutritional value. However, there is no comprehensive knowledge to sufficiently unravel the "flavor mystery" of cruciferous foods. The present review provides a comprehensive literature on the recent advances regarding the contribution of glucosinolates (GSL) degradation products to cruciferous foods odor, which focuses on key GSL degradation products contributing to distinct odor of cruciferous foods (Brassica oleracea, Brassica rapa, Brassica napus, Brassica juncea, Raphanus sativus), and key factors affecting GSL degradation pathways (i.e., enzyme-induced degradation, thermal-induced degradation, chemical-induced degradation, microwave-induced degradation) during different processing and cooking. A total of 93 volatile GSL degradation products (i.e., 36 nitriles, 33 isothiocyanates, 3 thiocyanates, 5 epithionitriles, and 16 sulfides) and 29 GSL (i.e., 20 aliphatic, 5 aromatic, and 4 indolic) were found in generalized cruciferous foods. Remarkably, cruciferous foods have a distinctive pungent, spicy, pickled, sulfur, and vegetable odor. In general, isothiocyanates are mostly present in enzyme-induced degradation of GSL and are therefore often enriched in fresh-cut or low-temperature, short-time cooked cruciferous foods. In contrast, nitriles are mainly derived from thermal-induced degradation of GSL, and are thus often enriched in high-temperature, long-time cooked cruciferous foods.


Processing and cooking can cause degradation of glucosinolates and formation of volatiles.Structure­odor relationship of glucosinolates degradation products is discussed.Nitriles, isothiocyanates, and sulfides play an important role in cruciferous foods odor.Both enzyme- and thermal-induced degradation of glucosinolates is strongly pH-dependent.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38591204

RESUMEN

BACKGROUND: Inguinal hernia in adults is a common and frequent disease in surgery, prone to occur in the elderly or in those with a weak abdominal wall. Despite its prevalence, Molecular mechanisms underlying inguinal hernia formation are unclear. OBJECTIVE: This study aims to identify potential gene markers for inguinal hernia and available drugs. METHODS: Pubmed2Ensembl text mining was used to identify genes related to "inguinal hernia" keywords. The GeneCodis system was used to specify GO biological process terms and KEGG pathways defined in the Kyoto Encyclopedia of Genes and Genomes (KEGG). The STRING tool was used to construct protein-protein interaction networks, which were then visualized using Cytoscape.CytoHubba and Molecular Complex Detection were utilized to analyze the module (MCODE). A GO and KEGG analysis of gene modules was conducted using the DAVID platform database. Hub genes are those that are concentrated in prominent modules. The druggene interaction database was also used to identify potential drugs for inguinal hernia patients based on their interactions between the hub genes. Finally, a Mendelian randomization study was conducted based on genome-wide association studies to determine whether hub genes cause inguinal hernias. RESULTS: The identification of 96 genes associated with inguinal hernia was carried out using text mining techniques. It was constructed using PPI networks with 80 nodes and 476 edges, and the sequence of the genes was performed using CytoHubba. MCODE analysis identified three gene modules. Three modules contain 37 genes clustered as hub candidate genes associated with inguinal hernia patients. The PI3K-Akt, MAPK, AGE-RAGE, and HIF-1 pathways were found to be enriched in signaling pathways. Sixteen of the 37 genes were found to be targetable by 30 existing drugs. The relationship between hub genes and inguinal hernia was examined using Mendelian randomization. The research revealed nine genes that may be connected with inguinal hernia, such as POMC, CD40LG, TFRC, VWF, LOX, IGF2, BRCA1, TNF, and HGF in the plasma. By inverse variance weighting, ALB was associated with an increased risk of inguinal hernia with an OR of 1.203 (OR [95%] = 1,04 [1.012 to 1.089], p = 0.008). CONCLUSION: We identified potential hub genes for inguinal hernia, predicted potential drugs for inguinal hernia, and reverse-validated potential genes by Mendelian randomization. This may provide further insights into asymptomatic pre-diagnostic methods and contribute to studies to understand the molecular mechanisms of risk genes associated with inguinal hernia.

18.
Eur J Surg Oncol ; 50(6): 108280, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38537365

RESUMEN

BACKGROUND: The impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed. METHODS: Patients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors. RESULTS: Among 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61-0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66-0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33-39% and 28-37%, respectively. CONCLUSIONS: TOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement.


Asunto(s)
Gastrectomía , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Quimioterapia Adyuvante , Tasa de Supervivencia , Terapia Neoadyuvante , Estudios Retrospectivos , Supervivencia sin Enfermedad , Estadificación de Neoplasias , Factores de Riesgo , Adulto , Resultado del Tratamiento
19.
Viruses ; 16(3)2024 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-38543730

RESUMEN

Members of the Flaviviridae family, encompassing the Flavivirus and Hepacivirus genera, are implicated in a spectrum of severe human pathologies. These diseases span a diverse spectrum, including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, and adverse fetal outcomes, such as congenital heart defects and increased mortality rates. Notably, infections by Flaviviridae viruses have been associated with substantial cardiovascular compromise, yet the exploration into the attendant cardiovascular sequelae and underlying mechanisms remains relatively underexplored. This review aims to explore the epidemiology of Flaviviridae virus infections and synthesize their cardiovascular morbidities. Leveraging current research trajectories and our investigative contributions, we aspire to construct a cogent theoretical framework elucidating the pathogenesis of Flaviviridae-induced cardiovascular injury and illuminate prospective therapeutic avenues.


Asunto(s)
Enfermedades Cardiovasculares , Infecciones por Flaviviridae , Flaviviridae , Flavivirus , Humanos , Enfermedades Cardiovasculares/epidemiología , Flaviviridae/genética , Hepacivirus
20.
Food Chem ; 448: 139124, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38554586

RESUMEN

In this study, we applied various thermal pretreatment methods (e.g., hot-air, microwave, and stir-frying) to process walnut kernels, and conducted comparative analysis of the physicochemical properties, nutritional components, in vitro antioxidant activity, and flavor substances of the extracted walnut oil (WO). The results indicated that, thermal pretreatment significantly increased the extraction of total trace nutrients (e.g., total phenols, tocopherols, and phytosterols) in WO. The WO produced using microwave had 2316.71 mg/kg of total trace nutrients, closely followed by the stir-frying method, which yielded an 11.22% increase compared to the untreated method. The WO obtained by the microwave method had a higher Oxidative inductance period (4.05 h) and oil yield (2.48%). After analyzing the flavor in WO, we found that aldehydes accounted for 28.77% of the 73 of volatile compounds and 58.12% of the total flavor compound content in microwave-pretreated WO, these percentages were higher than those recorded by using other methods. Based on the comprehensive score obtained by the PCA, microwave-pretreatment might be a promising strategy to improve the quality of WO based on aromatic characteristics.


Asunto(s)
Aromatizantes , Juglans , Oxidación-Reducción , Aceites de Plantas , Gusto , Compuestos Orgánicos Volátiles , Juglans/química , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/análisis , Aromatizantes/química , Aromatizantes/análisis , Aceites de Plantas/química , Antioxidantes/análisis , Antioxidantes/química , Calor , Microondas
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