Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
1.
Front Endocrinol (Lausanne) ; 15: 1327903, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846495

RESUMEN

Objectives: To research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke. Methods: Data of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyG-WC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome. Results: The study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of moderate-severe stroke [Q3: OR: 0.355, 95%CI (0.173-0.728), P = 0.005; Q4: OR: 0.140, 95%CI (0.056-0.351), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of short-term adverse outcomes [Q3: OR: 0.350, 95%CI (0.175-0.700), P = 0.003; Q4: OR: 0.178, 95%CI (0.071-0.451), P <0.001]. Conclusions: TyG-WC and TyG-BMI were correlated with the severity and short-term outcome of new-onset acute ischemic stroke. As TyG-WC and TyG-BMI increased, stroke severity decreased and short-term outcome was better.


Asunto(s)
Glucemia , Índice de Masa Corporal , Accidente Cerebrovascular Isquémico , Índice de Severidad de la Enfermedad , Triglicéridos , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/sangre , Persona de Mediana Edad , Anciano , Triglicéridos/sangre , Pronóstico , Glucemia/análisis , Glucemia/metabolismo , Circunferencia de la Cintura , Obesidad/sangre , Obesidad/complicaciones
2.
Cyborg Bionic Syst ; 5: 0125, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841725

RESUMEN

Depression is a common and severely debilitating neuropsychiatric disorder. Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression. The basolateral amygdala (BLA) is crucial in the cognitive and physiological processing and control of emotion. However, due to the lack of detection tools, the neural activity of the BLA during depression is not well understood. In this study, a microelectrode array (MEA) based on the shape and anatomical location of the BLA in the brain was designed and manufactured. Rats were injected with lipopolysaccharide (LPS) for 7 consecutive days to induce depressive behavior. We used the MEA to detect neural activity in the BLA before modeling, during modeling, and after LPS administration on 7 consecutive days. The results showed that after LPS treatment, the spike firing of neurons in the BLA region of rats gradually became more intense, and the local field potential power also increased progressively. Further analysis revealed that after LPS administration, the spike firing of BLA neurons was predominantly in the theta rhythm, with obvious periodic firing characteristics appearing after the 7 d of LPS administration, and the relative power of the local field potential in the theta band also significantly increased. In summary, our results suggest that the enhanced activity of BLA neurons in the theta band is related to the depressive state of rats, providing valuable guidance for research into the neural mechanisms of depression.

3.
Adv Sci (Weinh) ; 11(24): e2305706, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38582509

RESUMEN

Haplotype-resolved 3D chromatin architecture related to allelic differences in avian skeletal muscle development has not been addressed so far, although chicken husbandry for meat consumption has been prevalent feature of cultures on every continent for more than thousands of years. Here, high-resolution Hi-C diploid maps (1.2-kb maximum resolution) are generated for skeletal muscle tissues in chicken across three developmental stages (embryonic day 15 to day 30 post-hatching). The sequence features governing spatial arrangement of chromosomes and characterize homolog pairing in the nucleus, are identified. Multi-scale characterization of chromatin reorganization between stages from myogenesis in the fetus to myofiber hypertrophy after hatching show concordant changes in transcriptional regulation by relevant signaling pathways. Further interrogation of parent-of-origin-specific chromatin conformation supported that genomic imprinting is absent in birds. This study also reveals promoter-enhancer interaction (PEI) differences between broiler and layer haplotypes in skeletal muscle development-related genes are related to genetic variation between breeds, however, only a minority of breed-specific variations likely contribute to phenotypic divergence in skeletal muscle potentially via allelic PEI rewiring. Beyond defining the haplotype-specific 3D chromatin architecture in chicken, this study provides a rich resource for investigating allelic regulatory divergence among chicken breeds.


Asunto(s)
Pollos , Haplotipos , Músculo Esquelético , Animales , Pollos/genética , Haplotipos/genética , Músculo Esquelético/metabolismo , Mapeo Cromosómico/métodos , Genoma/genética
4.
Cell Div ; 19(1): 15, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38679705

RESUMEN

E3 ubiquitin ligase synoviolin (SYVN1) has been reported to participate in many human cancers. This study aimed to investigate SYVN1's roles and molecular pathways in papillary thyroid cancer (PTC). The functions of SYVN1 in PTC were further analyzed using gain- and loss-of-function methods and numerous investigations in cellular function and molecular biology. The findings demonstrated that the overexpression of SYVN1 markedly suppressed the proliferation, migration, and invasion of PTC cell lines (NPA87 and TPC-1). We found that SYVN1 interacted with HMGB1 and promoted its ubiquitination and degradation. In addition, SYVN1 effectively impairs cell proliferation, migration, invasion, and the formation of tumor xenografts in mice models. However, this effect may be partly reversed by overexpressing HMGB1. Thus, SYVN1 may inhibit the proliferation, migration, and invasion of PTC cells by disrupting HMGB1. Consequently, SYVN1 might be considered a promising therapeutic target for PTC.

5.
Genome Res ; 34(2): 310-325, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38479837

RESUMEN

In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data revealed the tissue dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic differences of long-range promoter-enhancer contacts, which likely contribute to the phenotypic differences between the parental pig breeds. We also observe the fine structure of somatically paired homologous chromosomes in the pig genome, which has a functional implication genome-wide. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, as well as the possible consequential phenotypic changes in mammals.


Asunto(s)
Cromatina , Cromosomas , Animales , Porcinos/genética , Cromatina/genética , Haplotipos , Cromosomas/genética , Genoma , Mamíferos/genética
6.
Wei Sheng Yan Jiu ; 53(1): 60-65, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38443173

RESUMEN

OBJECTIVE: To investigate the inhibitory mechanisms of ginsenoside F1 on hydrogen peroxide induced cholesterol metabolism disorder and oxidative stress in HepG2 cells. METHODS: 1, 1-diphenyl-2-picrylhydrazyl(DPPH) and oxygen radical absorbance capacity(ORAC) tests were used to detect the scavenging effect of ginsenoside F1 on nitrogen and oxygen free radicals. HepG2 cells were treated with 400 µmol/L hydrogen peroxide and pretreated with 10, 20 and 40 µmol/L ginsenoside F1. Mitochondrial membrane potential(MMP) and total cholesterol levels were detected by JC-1 method and cholesterol kit, respectively. The protein expression levels of sterol-regulatory element binding proteins(SREBP2)and 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR) in cholesterol synthesis pathway were detected by Western blot. RESULTS: The DPPH clearance rate of ginsenoside F1 was much lower than that of 6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid(Trolox), but the ORAC capability of ginsenoside F1 was stronger, which was comparable to Trolox. The MMP and protein expression of SREBP2 were significantly decreased in injured group(P<0.05). The cholesterol and protein expression of HMGCR were significantly increased(P<0.05). Whereas, compared with the injured group, the MMP and protein expression of SREBP2 were significantly increased after 10, 20 and 40 µmol/L ginsenoside F1 pretreatment of injured cells(P<0.05). The cholesterol level and protein expression of HMGCR were significantly lower than injured group with concentration-dependent decreases(P<0.05). CONCLUSION: Ginsenoside F1 can protect against hydrogen peroxide induced oxidative stress in HepG2 cells by inhibiting oxygen free radicals and protecting mitochondria. And its mechanism may be related to the intervention of SREBP2/HMGCR pathway in regulating cellular cholesterol anabolism.


Asunto(s)
Ginsenósidos , Peróxido de Hidrógeno , Estrés Oxidativo , Colesterol , Oxígeno
7.
J Alzheimers Dis Rep ; 8(1): 461-477, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38549642

RESUMEN

Background: Neuronal loss occurs early and is recognized as a hallmark of Alzheimer's disease (AD). Promoting neurogenesis is an effective treatment strategy for neurodegenerative diseases. Traditional Chinese herbal medicines serve as a rich pharmaceutical source for modulating hippocampal neurogenesis. Objective: Gallic acid (GA), a phenolic acid extracted from herbs, possesses anti-inflammatory and antioxidant properties. Therefore, we aimed to explore whether GA can promote neurogenesis and alleviate AD symptoms. Methods: Memory in mice was assessed using the Morris water maze, and protein levels were examined via western blotting and immunohistochemistry. GA's binding site in the promoter region of transcription regulator nuclear factor erythroid 2-related factor 2 (Nrf2) was calculated using AutoDock Vina and confirmed by a dual luciferase reporter assay. Results: We found that GA improved spatial memory by promoting neurogenesis in the hippocampal dentate gyrus zone. It also improved synaptic plasticity, reduced tau phosphorylation and amyloid-ß concentration, and increased levels of synaptic proteins in APP/PS1 mice. Furthermore, GA inhibited the activity of glycogen synthase kinase-3ß (GSK-3ß). Bioinformatics tools revealed that GA interacts with several amino acid sites on GSK-3ß. Overexpression of GSK-3ß was observed to block the protective effects of GA against AD-like symptoms, while GA promoted neurogenesis via the GSK-3ß-Nrf2 signaling pathway in APP/PS1 mice. Conclusions: Based on our collective findings, we hypothesize that GA is a potential pharmaceutical agent for alleviating the pathological symptoms of AD.

8.
Front Bioeng Biotechnol ; 12: 1347625, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38357703

RESUMEN

17ß-Estradiol (E2) is a critical sex steroid hormone, which has significant effects on the endocrine systems of both humans and animals. E2 is also believed to play neurotrophic and neuroprotective roles in the brain. Biosensors present a powerful tool to detect E2 because of their small, efficient, and flexible design. Furthermore, Biosensors can quickly and accurately obtain detection results with only a small sampling amount, which greatly meets the detection of the environment, food safety, medicine safety, and human body. This review focuses on previous studies of biosensors for detecting E2 and divides them into non-biometric sensors, enzyme biosensors, antibody biosensors, and aptamer biosensors according to different bioreceptors. The advantages, disadvantages, and design points of various bioreceptors for E2 detection are analyzed and summarized. Additionally, applications of different bioreceptors of E2 detection are presented and highlight the field of environmental monitoring, food and medicine safety, and disease detection in recent years. Finally, the development of E2 detection by biosensor is prospected.

9.
Molecules ; 29(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38276613

RESUMEN

The specific and sensitive detection of 17ß-estradiol (E2) is critical for diagnosing and treating numerous diseases, and aptamers have emerged as promising recognition probes for developing detection platforms. However, traditional long-sequence E2 aptamers have demonstrated limited clinical performance due to redundant structures that can affect their stability and recognition ability. There is thus an urgent need to further optimize the structure of the aptamer to build an effective detection platform for E2. In this work, we have designed a novel short aptamer that retains the key binding structure of traditional aptamers to E2 while eliminating the redundant structures. The proposed aptamer was evaluated for its binding properties using microscale thermophoresis, a gold nanoparticle-based colorimetric method, and electrochemical assays. Our results demonstrate that the proposed aptamer has excellent specific recognition ability for E2 and a high affinity with a dissociation constant of 92 nM. Moreover, the aptamer shows great potential as a recognition probe for constructing a highly specific and sensitive clinical estradiol detection platform. The aptamer-based electrochemical sensor enabled the detection of E2 with a linear range between 5 pg mL-1 and 10 ng mL-1 (R2 = 0.973), and the detection capability of a definite low concentration level was 5 pg mL-1 (S/N = 3). Overall, this novel aptamer holds great promise as a valuable tool for future studies on the role of E2 in various physiological and pathological processes and for developing sensitive and specific diagnostic assays for E2 detection in clinical applications.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas del Metal , Aptámeros de Nucleótidos/química , Nanopartículas del Metal/química , Estradiol/metabolismo , Oro/química , Colorimetría , Técnicas Biosensibles/métodos , Límite de Detección
10.
Theriogenology ; 215: 302-311, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38128223

RESUMEN

Neurokinin B (NKB), a peptide encoded by the tachykinin 3 (TAC3), is critical for reproduction in all studied species. However, its potential roles in birds are less clear. Using the female chicken (c-) as a model, we showed that cTAC3 is composed of five exons with a full-length cDNA of 787 bp, which was predicted to generate the mature NKB peptide containing 10 amino acids. Using cell-based luciferase reporter assays, we demonstrated that cNKB could effectively and specifically activate tachykinin receptor 3 (TACR3) in HEK293 cells, suggesting its physiological function is likely achieved via activating cTACR3 signaling. Notably, cTAC3 and cTACR3 were predominantly and abundantly expressed in the hypothalamus of hens and meanwhile the mRNA expression of cTAC3 was continuously increased during development, suggesting that NKB-TACR3 may emerge as important components of the neuroendocrine reproductive axis. In support, intraperitoneal injection of cNKB could significantly promote hypothalamic cGnRH-Ι, and pituitary cFSHß and cLHß expression in female chickens. Surprisingly, cTAC3 and cTACR3 were also expressed in the pituitary gland, and cNKB treatment significantly increased cLHß and cFSHß expression in cultured primary pituitary cells, suggesting cNKB can also act directly at the pituitary level to stimulate gonadotropin synthesis. Collectively, our results reveal that cNKB functionally regulate GnRH/gonadotropin synthesis in female chickens.


Asunto(s)
Pollos , Gonadotropinas , Humanos , Femenino , Animales , Pollos/genética , Pollos/metabolismo , Células HEK293 , Neuroquinina B/genética , Neuroquinina B/metabolismo , Hormona Liberadora de Gonadotropina/genética , Hormona Liberadora de Gonadotropina/farmacología , Hormona Liberadora de Gonadotropina/metabolismo
11.
ACS Sens ; 8(12): 4765-4773, 2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-38015643

RESUMEN

The functioning of place cells requires the involvement of multiple neurotransmitters, with dopamine playing a critical role in hippocampal place cell activity. However, the exact mechanisms through which dopamine influences place cell activity remain largely unknown. Herein, we present the development of the integrated three-electrode dual-mode detection chip (ITDDC), which enables simultaneous recording of the place cell activity and dopamine concentration fluctuation. The working electrode, reference electrode, and counter electrode are all integrated within the ITDDC in electrochemical detection, enabling the real-time in situ monitoring of dopamine concentrations in animals in motion. The reference, working, and counter electrodes are surface-modified using PtNPs and polypyrrole, PtNPs and PEDOT:PSS, and PtNPs, respectively. This modification allows for the detection of dopamine concentrations as low as 20 nM. We conducted dual-mode testing on mice in a novel environment and an environment with food rewards. We found distinct dopamine concentration variations along different paths within a novel environment, implying that different dopamine levels may contribute to spatial memory. Moreover, environmental food rewards elevate dopamine significantly, followed by the intense firing of reward place cells, suggesting a crucial role of dopamine in facilitating the encoding of reward-associated locations in animals. The real-time and in situ recording capabilities of ITDDC offer new opportunities to investigate the interplay between electrophysiology and dopamine during animal exploration and reward-based memory and provide a novel glimpse into the correlation between dopamine levels and place cell activity.


Asunto(s)
Dopamina , Células de Lugar , Ratones , Animales , Polímeros , Pirroles , Electrodos , Recompensa
12.
Front Microbiol ; 14: 1239847, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37928663

RESUMEN

Introduction: Obesity is closely related to gut microbiota, however, the dynamic change of microbial diversity and composition during the occurrence and development process of obesity is not clear. Methods: A weight-change model of adult Bama pig (2 years, 58 individuals) was established, and weight gain (27 weeks) and weight loss (9 weeks) treatments were implemented. The diversity and community structures of fecal microbiota (418 samples) was investigated by using 16S rRNA (V3-V4) high-throughput sequencing. Results: During the weight gain period (1~27 week), the alpha diversity of fecal microbiota exhibited a "down-up-down" fluctuations, initially decreasing, recovering in the mid-term, and decreasing again in the later stage. Beta diversity also significantly changed over time, indicating a gradual deviation of the microbiota composition from the initial time point. Bacteroides, Clostridium sensu stricto 1, and Escherichia-Shigella showed positive correlations with weight gain, while Streptococcus, Oscillospira, and Prevotellaceae UCG-001 exhibited negative correlations. In the weight loss period (30~38 week), the alpha diversity further decreased, and the composition structure underwent significant changes compared to the weight gain period. Christensenellaceae R-7 group demonstrated a significant increase during weight loss and showed a negative correlation with body weight. Porphyromonas and Campylobacter were positively correlated with weight loss. Discussion: Both long-term fattening and weight loss induced by starvation led to substantial alterations in porcine gut microbiota, and the microbiota changes observed during weight gain could not be recovered during weight loss. This work provides valuable resources for both obesity-related research of human and microbiota of pigs.

13.
Research (Wash D C) ; 6: 0229, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37719050

RESUMEN

Epilepsy severely impairs the cognitive behavior of patients. It remains unclear whether epilepsy-induced cognitive impairment is associated with neuronal activities in the medial entorhinal cortex (MEC), a region known for its involvement in spatial cognition. To explore this neural mechanism, we recorded the spikes and local field potentials from MEC neurons in lithium-pilocarpine-induced epileptic rats using self-designed microelectrode arrays. Through the open field test, we identified spatial cells exhibiting spatially selective firing properties and assessed their spatial representations in relation to the progression of epilepsy. Meanwhile, we analyzed theta oscillations and theta modulation in both excitatory and inhibitory neurons. Furthermore, we used a novel object recognition test to evaluate changes in spatial cognitive ability of epileptic rats. After the epilepsy modeling, the spatial tuning of various types of spatial cells had suffered a rapid and pronounced damage during the latent period (1 to 5 d). Subsequently, the firing characteristics and theta oscillations were impaired. In the chronic period (>10 d), the performance in the novel object experiment deteriorated. In conclusion, our study demonstrates the detrimental effect on spatial representations and electrophysiological properties of MEC neurons in the epileptic latency, suggesting the potential use of these changes as a "functional biomarker" for predicting cognitive impairment caused by epilepsy.

14.
J Reprod Immunol ; 159: 104132, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37591181

RESUMEN

Active immunization against gonadotropin-releasing hormone (GnRH) inhibits animal reproduction and has become a friendly alternative to surgical castration, which has been reported to affect the proportion of thymic T cell subpopulations. The effects of active immunization against GnRH on T cell migration from the thymus to the periphery and T cell distribution in lymphoid tissues remain unclear. Here, we showed that active immunization against GnRH increased thymic size and weight, enlarged the number of thymocytes, and enhanced CD4+ recent thymic emigrants (RTEs) and CD8+ RTEs migration to the blood and spleen. Active immunization against GnRH had no significant effect on naïve CD4+, naïve CD8+, CD4+ memory/activated, or CD8+ memory/activated T cells. In addition, active immunization against GnRH increased the proportion of CD3+ T cells in the spleen and lymph nodes. The percentages of CD3+CD4+ and CD3+CD8+ T cells in the blood, spleen, and lymph nodes were not significantly affected by GnRH immunization. Overall, these results enhance our understanding of thymic T cell production, migration, and colonization in rat lymphoid tissues affected by GnRH immunization.


Asunto(s)
Linfocitos T CD8-positivos , Timo , Masculino , Animales , Ratas , Tejido Linfoide , Vacunación , Hormona Liberadora de Gonadotropina
15.
Clin Med Res ; 21(2): 79-86, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37407213

RESUMEN

Objective: We aimed to investigate preoperative esketamine alleviating postoperative pain in children after endoscopic plasma total adenotonsillectomy.Methods: We recruited 200 children with adenotonsillar hypertrophy at Wuhan Children's Hospital between September 2021 and April 2022. The children were randomly assigned to receive preoperative esketamine (ESK group) or fentanyl (FEN group). The primary endpoint was serum c-fos and c-jun levels. The secondary endpoints were face, legs, activity, cry, and consolability (FLACC) score and adverse events.Results: After surgery, c-fos and c-jun mRNA levels were increased significantly in both groups. Postoperatively, c-fos and c-jun mRNA levels were higher in FEN group compared with the ESK group (P<0.05). The FLACC scores were higher in the FEN group compared with the ESK group at 1 and 24 hours after surgery (P<0.05). Prediction probability (Pk) values indicated that c-fos and c-jun mRNA levels were quantitative predictors for early postoperative pain and stress reaction after surgery.Conclusions: Esketamine-based anesthesia (1mg/kg) can alleviate postoperative pain and regulate the inflammatory reaction in children undergoing endoscopic plasma adenotonsillectomy.


Asunto(s)
Ketamina , Tonsilectomía , Niño , Humanos , Tonsilectomía/efectos adversos , Adenoidectomía/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Ketamina/uso terapéutico
16.
Nat Commun ; 14(1): 3457, 2023 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-37308492

RESUMEN

Using an adult female miniature pig model with diet-induced weight gain/weight loss, we investigated the regulatory mechanisms of three-dimensional (3D) genome architecture in adipose tissues (ATs) associated with obesity. We generated 249 high-resolution in situ Hi-C chromatin contact maps of subcutaneous AT and three visceral ATs, analyzing transcriptomic and chromatin architectural changes under different nutritional treatments. We find that chromatin architecture remodeling underpins transcriptomic divergence in ATs, potentially linked to metabolic risks in obesity development. Analysis of chromatin architecture among subcutaneous ATs of different mammals suggests the presence of transcriptional regulatory divergence that could explain phenotypic, physiological, and functional differences in ATs. Regulatory element conservation analysis in pigs and humans reveals similarities in the regulatory circuitry of genes responsible for the obesity phenotype and identified non-conserved elements in species-specific gene sets that underpin AT specialization. This work provides a data-rich tool for discovering obesity-related regulatory elements in humans and pigs.


Asunto(s)
Cromatina , Aumento de Peso , Adulto , Humanos , Femenino , Porcinos , Animales , Obesidad , Tejido Adiposo , Ensamble y Desensamble de Cromatina , Pérdida de Peso , Mamíferos
17.
J Biol Chem ; 299(6): 104757, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37116707

RESUMEN

Elucidating the regulatory mechanisms of human adipose tissues (ATs) evolution is essential for understanding human-specific metabolic regulation, but the functional importance and evolutionary dynamics of three-dimensional (3D) genome organizations of ATs are not well defined. Here, we compared the 3D genome architectures of anatomically distinct ATs from humans and six representative mammalian models. We recognized evolutionarily conserved and human-specific chromatin conformation in ATs at multiple scales, including compartmentalization, topologically associating domain (TAD), and promoter-enhancer interactions (PEI), which have not been described previously. We found PEI are much more evolutionarily dynamic with respect to compartmentalization and topologically associating domain. Compared to conserved PEIs, human-specific PEIs are enriched for human-specific sequence, and the binding motifs of their potential mediators (transcription factors) are less conserved. Our data also demonstrated that genes involved in the evolutionary dynamics of chromatin organization have weaker transcriptional conservation than those associated with conserved chromatin organization. Furthermore, the genes involved in energy metabolism and the maintenance of metabolic homeostasis are enriched in human-specific chromatin organization, while housekeeping genes, health-related genes, and genetic variations are enriched in evolutionarily conserved compared to human-specific chromatin organization. Finally, we showed extensively divergent human-specific 3D genome organizations among one subcutaneous and three visceral ATs. Together, these findings provide a global overview of 3D genome architecture dynamics between ATs from human and mammalian models and new insights into understanding the regulatory evolution of human ATs.


Asunto(s)
Tejido Adiposo , Cromatina , Genoma , Animales , Humanos , Cromatina/genética , Ensamble y Desensamble de Cromatina , Genómica , Homeostasis , Mamíferos , Tejido Adiposo/metabolismo
18.
Nanomaterials (Basel) ; 13(7)2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-37049316

RESUMEN

Doxorubicin (DOX) is the most clinically important antibiotic in cancer treatment, but its severe cardiotoxicity and other side effects limit its clinical use. Therefore, monitoring DOX concentrations during therapy is essential to improve efficacy and reduce adverse effects. Here, we fabricated a sensitive electrochemical aptasensor for DOX detection. The sensor used gold wire as the working electrode and was modified with reduced graphene oxide (rGO)/gold nanoparticles (AuNPs) to improve the sensitivity. An aptamer was used as the recognition element for the DOX. The 5' end of the aptamer was modified with a thiol group, and thus immobilized to the AuNPs, and the 3' end was modified with methylene blue, which acts as the electron mediator. The combination between the aptamer and DOX would produce a binding-induced conformation, which changes the electron transfer rate, yielding a current change that correlates with the concentration of DOX. The aptasensor exhibited good linearity in the DOX concentration range of 0.3 µM to 6 µM, with a detection limit of 0.1 µM. In addition, the aptasensor was used for DOX detection in real samples and results, and showed good recovery. The proposed electrochemical aptasensor will provide a sensitive, fast, simple, and reliable new platform for detecting DOX.

19.
Int J Med Mushrooms ; 25(4): 43-53, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37075083

RESUMEN

We investigated the chemical constituents and anti-tumor activity of cultivated Pholiota adiposa in vitro using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. HepG-2, A549, HeLa, and MCF-7 cells, which are 4 kinds of human cancer cell lines, were cultured in vitro, treated with different concentrations of the ethanol extract of Ph. adiposa (EPA), and cytotoxicity was determined using the cell counting kit-8 assay. Flow cytometry was used to analyze the apoptosis of HepG-2 cells via annexin V-fluorescein isothiocyanate/propidium iodide double staining. Expression levels of apoptosis-associated proteins were determined via Western blotting analysis. Thirty-five components were consistent with those recorded in the chemical composition database, with sterols, fatty acids, and polysaccharide compounds accounting for a relatively high proportion. EPA showed the strongest cytotoxicity against HepG-2 cells, increasing the apoptosis rate up to 23.71 ± 1.59% at a concentration of 50 µg/mL. Ph. adiposa has various functional chemical constituents and potential anti-tumor applications. We found that the functional constituents exerted anti-tumor activity by inducing apoptosis. Furthermore, the expression levels of BCL-2-associated X were increased, whereas those of BCL-2 were decreased in cells after treatment with EPA. These results suggest that EPA induces HepG-2 cell apoptosis via a caspase-mediated pathway.


Asunto(s)
Agaricales , Basidiomycota , Pholiota , Humanos , Agaricales/metabolismo , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2 , Pholiota/metabolismo , Basidiomycota/metabolismo
20.
Int J Mol Sci ; 24(5)2023 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-36902252

RESUMEN

Spexin2 (SPX2), a paralog of SPX1, is a newly identified gene in non-mammalian vertebrates. Limited studies in fish have evidenced its important role in food intake and energy balance modulation. However, little is known about its biological functions in birds. Using the chicken (c-) as a model, we cloned the full-length cDNA of SPX2 by using RACE-PCR. It is 1189 base pair (bp) in length and predicted to generate a protein of 75 amino acids that contains a 14 amino acids mature peptide. Tissue distribution analysis showed that cSPX2 transcripts were detected in a wide array of tissues, with abundant expression in the pituitary, testis, and adrenal gland. cSPX2 was also observed to be ubiquitously expressed in chicken brain regions, with the highest expression in the hypothalamus. Its expression was significantly upregulated in the hypothalamus after 24 or 36 h of food deprivation, and the feeding behavior of chicks was obviously suppressed after peripheral injection with cSPX2. Mechanistically, further studies evidenced that cSPX2 acts as a satiety factor via upregulating cocaine and amphetamine regulated transcript (CART) and downregulating agouti-related neuropeptide (AGRP) in hypothalamus. Using a pGL4-SRE-luciferase reporter system, cSPX2 was demonstrated to effectively activate a chicken galanin II type receptor (cGALR2), a cGALR2-like receptor (cGALR2L), and a galanin III type receptor (cGALR3), with the highest binding affinity for cGALR2L. Collectively, we firstly identified that cSPX2 serves as a novel appetite monitor in chicken. Our findings will help clarify the physiological functions of SPX2 in birds as well as its functional evolution in vertebrates.


Asunto(s)
Pollos , Hipotálamo , Neuropéptidos , Hormonas Peptídicas , Animales , Masculino , Pollos/genética , Pollos/metabolismo , Galanina/metabolismo , Hipotálamo/metabolismo , Neuropéptidos/metabolismo , Receptores de Galanina/metabolismo , Proteína Relacionada con Agouti/genética , Proteína Relacionada con Agouti/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...