Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 442
Filtrar
1.
Chem Commun (Camb) ; 60(59): 7578-7581, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38953148

RESUMO

An assembly between 1,4-dicarboxylbenzene-2,3-dithiol (H2dcbdt) and different transition metal ions successfully produced 2D metal-organic frameworks (M-dcbdt, M = Ni, Co or Fe) composed of unprecedented butterfly-shaped metal-bis(dithiolene) (MS4) linkers in one-pot fashion. Such strategy provides easier access to the [MS4]-rich network and lowers the prerequisite to explore their applications.

2.
iScience ; 27(7): 110024, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38979010

RESUMO

Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10-6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

3.
Liver Int ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037193

RESUMO

BACKGROUND AND AIMS: Distinctive gut microbial profiles have been observed between patients with Wilson disease (WD) and healthy individuals. Despite this, the exact relationship and influence of gut microbiota on the advancement of WD-related liver damage remain ambiguous. This research seeks to clarify the gut microbiota characteristics in both human patients and mouse models of WD, as well as their impact on liver injury. METHODS: Gut microbial features in healthy individuals, patients with WD, healthy mice and mice with early- and late-stage WD were analysed using 16S rRNA gene sequencing. Additionally, WD-afflicted mice underwent treatment with either an antibiotic cocktail (with normal saline as a control) or healthy microbiota (using disease microbiota as a control). The study assessed gut microbiota composition, hepatic transcriptome profiles, liver copper concentrations and hepatic pathological injuries. RESULTS: Patients with hepatic WD and mice with WD-related liver injury displayed altered gut microbiota composition, notably with a significant reduction in Lactobacillus abundance. Additionally, the abundances of several gut genera, including Lactobacillus, Veillonella and Eubacterium coprostanoligenes, showed significant correlations with the severity of liver injury in patients with WD. In WD mice, antibiotic treatment or transplantation of healthy microbiota altered the gut microbial structure, increased Lactobacillus abundance and modified the hepatic transcriptional profile. These interventions resulted in reduced hepatic copper concentration and alleviation of WD-related liver injury. CONCLUSIONS: Individuals and mice with pronounced WD-related liver injury exhibited shifts in gut microbial composition. Regulating gut microbiota through healthy microbiota transplantation emerges as a promising therapeutic approach for treating WD-related liver injury.

4.
Plants (Basel) ; 13(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38999601

RESUMO

The ramet system is a typical structural type in the life history of clonal plants. This massive structure is formed by many similar ramets connected by underground rhizomes, which are independent and mutually influential. Therefore, the ramet system is unique to bamboo forests, and its role in the construction, maintenance, and productivity of bamboo populations is irreplaceable. Mulch management is a high-level cultivation model for bamboo forests that is used to cultivate bamboo shoots. However, the basic conditions of bamboo ramet systems in this managed model are poorly understood. This study analyzed the underground rhizome morphology, bud bank, and branching of bamboo ramets in a Phyllostachys praecox C.D. Chu et C.S. Chao 'Prevernalis' forest to explore the growth patterns of bamboo ramets in high-level management fields. In mulched bamboo forests, the bamboo rhizomes, distributed in intermediate positions of the bamboo ramet system, were long with many lateral buds and branches, and those at the initial and distal ends were short with few lateral buds and branches. The initial end of the ramet system reduced the ramet system, the intermediate part expanded the ramet system, and the distal end promoted ramet system regeneration. Owing to the continuous reduction, expansion, and renewal of ramet systems, the bamboo rhizome system demonstrates mobility and adaptability. This study found that a higher level of bamboo forest management increased the possibility of artificial fragmentation of the ramet system and that improving the efficiency of the ramet system was beneficial for maintaining its high vitality. Thus, this study provides a crucial reference for guiding the precise regulation of bamboo ramet systems in artificial bamboo forests.

5.
Sheng Li Xue Bao ; 76(3): 376-384, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38939932

RESUMO

The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging rats. Ten from 38 male Sprague-Dawley (SD) rats (3-month-old) were randomly selected into young (Y) group, while the rest were raised to 21 months old and randomly divided into elderly control (O), endurance exercise (EN) and resistance exercise (R) groups. After 8 weeks of corresponding exercises training, the gastrocnemius muscles of rats were collected, and the expression of S100B in Schwann cells was detected by immunofluorescence staining. Western blot was used to detect the protein expression levels of agglutinate protein (Agrin), low-density lipoprotein receptor-related protein 4 (Lrp4), muscle- specific kinase protein (MuSK), downstream tyrosine kinase 7 (Dok7), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target rapamycin (p-mTOR), and phosphorylated forkhead box O1 (p-FoxO1) in rat gastrocnemius muscles. The results showed that, endurance and resistance exercises increased the wet weight ratio of gastrocnemius muscle in the aging rats. The protein expression of S100B in the R group was significantly higher than those in the O and EN groups. Proteins related to NMJ function, including Agrin, Lrp4, MuSK, and Dok7 were significantly decreased in the O group compared with those in the Y group. Resistance exercise up-regulated these four proteins in the aging rats, whereas endurance exercise could not reverse the protein expression levels of Lrp4, MuSK and Dok7. Regarding skeletal muscle-related proteins, the O group showed down-regulated p-Akt, and p-mTOR protein expression levels and up-regulated p-FoxO1 protein expression level, compared to the Y group. Resistance and endurance exercises reversed the changes in p-mTOR and p-FoxO1 protein expression in the aging rats. These findings demonstrate that both exercise modes can enhance NMJ function, increase protein synthesis and reduce the catabolism of skeletal muscle-related proteins in aging rats, with resistance exercise showing a more pronounced effect.


Assuntos
Envelhecimento , Músculo Esquelético , Junção Neuromuscular , Condicionamento Físico Animal , Ratos Sprague-Dawley , Animais , Masculino , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Ratos , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Junção Neuromuscular/metabolismo , Junção Neuromuscular/fisiologia , Proteínas Musculares/metabolismo , Treinamento Resistido/métodos , Proteína Forkhead Box O1
6.
Gut Microbes ; 16(1): 2372881, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38940400

RESUMO

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.


Assuntos
Quimiocina CXCL16 , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Fígado , Receptores CXCR6 , Animais , Receptores CXCR6/metabolismo , Quimiocina CXCL16/metabolismo , Camundongos , Humanos , Fígado/metabolismo , Fígado/microbiologia , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Imunidade Inata , Fígado Gorduroso/terapia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/microbiologia , Interleucina 22 , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/imunologia , Interleucinas/metabolismo , Feminino
7.
J Colloid Interface Sci ; 672: 753-764, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38870766

RESUMO

Cobalt phosphide (CoP) with high theoretical capacity as well as ceramic-like and metal-like properties is considered as a promising anode for lithium-ion batteries (LIBs). However, the large volume change and sluggish kinetic response limit its practical application. The optimization of composition, structural control and performance regulation of CoP electrodes can be achieved by the bottom-up assembly technique of metal-organic frameworks (MOFs). Due to the effective electronic regulation and lithiophilicity brought by the multiple heteroatoms doping and the synergistic effect of the unique structure derived from MOFs, the N, O, P triple-doped carbon and CoP composites (ZCP@NOP) exhibited excellent rate capability (554.61 mAh g-1 at 2 A g-1) and cycling stability (806.7 mAh g-1 after 500 cycles at 0.5 A g-1). The essence and evolution of lithium storage mechanism in CoP electrodes are also confirmed by the ex-situ techniques. The synergistic benefits of heteroatom co-doping carbon and cobalt phosphide, such as the decrease of the diffusion energy barrier of Li-ions and the optimization of electronic structures, are highlighted in theoretical calculations. In conclusion, new thoughts and ideas for the creation of future battery anode are provided by the combination of the N, O, P co-doping and the adaptable structural adjustment technique.

8.
J Adv Res ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866179

RESUMO

BACKGROUND: Cancer stem cells (CSCs) are a distinct subpopulation of cancer cells with the capacity to constantly self-renew and differentiate, and they are the main driver in the progression of cancer resistance and relapse. The tumor microenvironment (TME) constructed by CSCs is the "soil" adapted to tumor growth, helping CSCs evade immune killing, enhance their chemical resistance, and promote cancer progression. AIM OF REVIEW: We aim to elaborate the tight connection between CSCs and immunosuppressive components of the TME. We attempt to summarize and provide a therapeutic strategy to eradicate CSCs based on the destruction of the tumor ecological niche. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review is focused on three main key concepts. First, we highlight that CSCs recruit and transform normal cells to construct the TME, which further provides ecological niche support for CSCs. Second, we describe the main characteristics of the immunosuppressive components of the TME, targeting strategies and summarize the progress of corresponding drugs in clinical trials. Third, we explore the multilevel insights of the TME to serve as an ecological niche for CSCs.

9.
Chin J Integr Med ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910191

RESUMO

OBJECTIVE: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. METHODS: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. RESULTS: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. CONCLUSIONS: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

10.
Accid Anal Prev ; 205: 107689, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38945046

RESUMO

Secondary conflicts occur frequently and would cause multi-vehicle collisions. In order to prevent multi-vehicle collisions, a better understanding of the factors that affect secondary conflict propagation is crucial. Previous studies have identified the influencing factors of primary conflicts' occurrence, but have not explored the time-varying factors that affect secondary conflicts' propagation. In addressing this gap, about 20,000 secondary conflicts are extracted from real trajectory dataset, and a multi-level variable system is established, including segment types, traffic status, front chain conflict status, and direct interaction behaviors. Further, a Kaplan-Meyer model and a random parameters hazard-based duration model are constructed to explore the single-factor and multiple-factor influence on the propagation of secondary conflicts, respectively. The results suggest that the first 2.6 s after a conflict is a critical post-monitoring period to prevent the secondary conflicts propagation. In addition, diverging and merging segments shorten the survival time of secondary conflicts by about 12%, indicating a higher occurrence probability of secondary conflicts near the ramps of expressways. More importantly, the front chain conflict status and the front direct conflict status reveal a different effect on the secondary conflicts. The high risk of chain conflict ahead would increase the occurrence probability of secondary conflicts, while the high risk of front conflict would decrease the probability. Overall, this research is of great significance to understand the influencing factors of secondary conflict and avoid secondary crashes.


Assuntos
Acidentes de Trânsito , Causalidade , Humanos , Acidentes de Trânsito/prevenção & controle , Acidentes de Trânsito/estatística & dados numéricos , Fatores de Tempo , Modelos Estatísticos , Estimativa de Kaplan-Meier , Condução de Veículo/estatística & dados numéricos , Modelos Teóricos
11.
Artigo em Inglês | MEDLINE | ID: mdl-38914874

RESUMO

(20 S)-Ginsenoside Rh2 is a natural saponin derived from Panax ginseng Meyer (P. ginseng), which showed significantly potent anticancer properties. However, its low water solubility and bioavailability strongly restrict its pharmaceutical applications. The aim of current research is to develop a modified (20 S)-Ginsenoside Rh2 formulation with high solubility, dissolution rate and bioavailability by combined computational and experimental methodology. The "PharmSD" model was employed to predict the optimal polymer for (20 S)-Ginsenoside Rh2 solid dispersion formulations. The solubility of (20 S)-Ginsenoside Rh2 in various polymers was assessed, and the optimal ternary solid dispersion was evaluated across different dissolution mediums. Characterization techniques included the Powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). Molecular dynamics simulations were employed to elucidate the formation mechanism of the solid dispersion and the interactions among active pharmaceutical ingredient (API) and excipient molecules. Cell and animal experiments were conducted to evaluate the in vivo performance of the modified formulation. The "PharmSD" solid dispersion model identified Gelucire 44/14 as the most effective polymer for enhancing the dissolution rate of Rh2. Subsequent experiment also confirmed that Gelucire 44/14 outperformed the other selected polymers. Moreover, the addition of the third component, sodium dodecyl sulfate (SDS), in the ternary solid dispersion formulation significantly amplified dissolution rates than the binary systems. Characterization experiments revealed that the API existed in an amorphous state and interacted via hydrogen bonding with SDS and Gelucire. Moreover, molecular modeling results provided additional evidence of hydrogen bonding interactions between the API and excipient molecules within the optimal ternary solid dispersion. Cell experiments demonstrated efflux ratio (EfR) of Rh2 ternary solid dispersion was lower than that of pure Rh2. In vivo experiments revealed that the modified formulation substantially improved the absorption of Rh2 in rats. Our research successfully developed an optimal ternary solid dispersion for Rh2 with high solubility, dissolution rate and bioavailability by integrated computational and experimental tools. The combination of Artificial Intelligence (AI) technology and molecular dynamics simulation is a wise way to support the future formulation development.

12.
Crit Rev Food Sci Nutr ; : 1-22, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38779723

RESUMO

A large and growing body of literature has investigated the broad antibacterial spectrum and strong synergistic antimicrobial activity of medium chain monoglycerides (MCMs) have been widely investigated. Recently, more and more researches have focused on the regulation of MCMs on metabolic health and gut microbiota both in vivo and in vitro. The current review summarizes the digestion, absorption and metabolism of MCMs. Subsequently, it focuses on the functional and nutritional properties of MCMs, including the antibacterial and antiviral characteristics, the modulation of metabolic balance, the regulation of gut microbiota, and the improvement in intestinal health. Additionally, we discuss the most recent developments and application of MCMs using nanotechnologies in food industry, poultry and pharmaceutical industry. Additionally, we analyze recent application examples of MCMs and their nanotechnology formation used in food. The development of nanotechnology platforms facilitating molecular encapsulation and functional presentation contribute to the application of hydrophobic fatty acids and monoglycerides in food preservation and their antibacterial effectiveness. This study emphasizes the metabolic mechanisms and biological activity of MCMs by summarizing the prevailing state of knowledge on this topic, as well as providing insights into prospective techniques for developing the beneficial applications of MCMs to realize the industrialized production.

13.
Clin Nutr ESPEN ; 61: 377-384, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38777458

RESUMO

Lactobacillus plantarum has been shown to improve glucose and lipid metabolism in mouse models of type 2 diabetes mellitus (T2DM). However, it remains unclear whether such benefits extend to humans. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to clarify the effect of L. plantarum supplementation on glucose and lipid metabolism in T2DM and prediabetes. The PubMed, Cochrane, and Web of Science databases were searched. A random-effects model was used to estimate the pooled mean difference with 95% CI (confidence interval). L. plantarum supplementation reduced the levels of fasting plasma glucose (-0.41, 95%CI -0.63, -0.19 mg/dL; n = 5) and hemoglobin A1c (-0.2, 95%CI: -0.3, 0%; n = 4). A non-statistically significant tendency towards improvements in the Homeostatic Model Assessment for Insulin Resistance (MD: -0.74, 95%CI: -1.72, 0.25; n = 3), low-density lipoprotein cholesterol (-6.87; 95%CI: -15.03, 1.29 mg/dL; n = 3), high-density lipoprotein cholesterol (MD: 1.34; 95%CI: -0.78, 3.46 mg/dL; n = 3), triglyceride (MD: -3.90; 95%CI: -11.05, 3.24 mg/dL; n = 3), and total cholesterol (MD: -4.88; 95%CI: -11.84, 2.07 mg/dL; n = 3) was observed with the supplementation. In summary, while the evidence from the currently available RCTs provides a crude indication that L. plantarum supplementation might improve glucose and lipid metabolism in patients with T2DM and prediabetes, the benefits of the supplementation are likely subtle, and its clinical significance requires further investigation.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Suplementos Nutricionais , Lactobacillus plantarum , Metabolismo dos Lipídeos , Estado Pré-Diabético , Probióticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Diabetes Mellitus Tipo 2/terapia , Humanos , Estado Pré-Diabético/terapia , Estado Pré-Diabético/dietoterapia , Glicemia/metabolismo , Probióticos/uso terapêutico , Resistência à Insulina , Hemoglobinas Glicadas/metabolismo , Triglicerídeos/sangue
14.
J Nanobiotechnology ; 22(1): 277, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783332

RESUMO

Spinal Cord Injury (SCI) is a condition characterized by complete or incomplete motor and sensory impairment, as well as dysfunction of the autonomic nervous system, caused by factors such as trauma, tumors, or inflammation. Current treatment methods primarily include traditional approaches like spinal canal decompression and internal fixation surgery, steroid pulse therapy, as well as newer techniques such as stem cell transplantation and brain-spinal cord interfaces. However, the above methods have limited efficacy in promoting axonal and neuronal regeneration. The challenge in medical research today lies in promoting spinal cord neuron regeneration and regulating the disrupted microenvironment of the spinal cord. Studies have shown that gas molecular therapy is increasingly used in medical research, with gasotransmitters such as hydrogen sulfide, nitric oxide, carbon monoxide, oxygen, and hydrogen exhibiting neuroprotective effects in central nervous system diseases. The gas molecular protect against neuronal death and reshape the microenvironment of spinal cord injuries by regulating oxidative, inflammatory and apoptotic processes. At present, gas therapy mainly relies on inhalation for systemic administration, which cannot effectively enrich and release gas in the spinal cord injury area, making it difficult to achieve the expected effects. With the rapid development of nanotechnology, the use of nanocarriers to achieve targeted enrichment and precise control release of gas at Sites of injury has become one of the emerging research directions in SCI. It has shown promising therapeutic effects in preclinical studies and is expected to bring new hope and opportunities for the treatment of SCI. In this review, we will briefly outline the therapeutic effects and research progress of gasotransmitters and nanogas in the treatment of SCI.


Assuntos
Gasotransmissores , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/terapia , Humanos , Animais , Gasotransmissores/uso terapêutico , Gasotransmissores/metabolismo , Óxido Nítrico/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Monóxido de Carbono/metabolismo , Monóxido de Carbono/uso terapêutico , Oxigênio/metabolismo , Medula Espinal , Hidrogênio/uso terapêutico , Hidrogênio/farmacologia
15.
BMC Biol ; 22(1): 104, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702712

RESUMO

BACKGROUND: Gonadotropin precisely controls mammalian reproductive activities. Systematic analysis of the mechanisms by which epigenetic modifications regulate the synthesis and secretion of gonadotropin can be useful for more precise regulation of the animal reproductive process. Previous studies have identified many differential m6A modifications in the GnRH-treated adenohypophysis. However, the molecular mechanism by which m6A modification regulates gonadotropin synthesis and secretion remains unclear. RESULTS: Herein, it was found that GnRH can promote gonadotropin synthesis and secretion by promoting the expression of FTO. Highly expressed FTO binds to Foxp2 mRNA in the nucleus, exerting a demethylation function and reducing m6A modification. After Foxp2 mRNA exits the nucleus, the lack of m6A modification prevents YTHDF3 from binding to it, resulting in increased stability and upregulation of Foxp2 mRNA expression, which activates the cAMP/PKA signaling pathway to promote gonadotropin synthesis and secretion. CONCLUSIONS: Overall, the study reveals the molecular mechanism of GnRH regulating the gonadotropin synthesis and secretion through FTO-mediated m6A modification. The results of this study allow systematic interpretation of the regulatory mechanism of gonadotropin synthesis and secretion in the pituitary at the epigenetic level and provide a theoretical basis for the application of reproductive hormones in the regulation of animal artificial reproduction.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Hormônio Liberador de Gonadotropina , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/genética , Animais , Gonadotropinas/metabolismo , Camundongos , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Metilação de RNA
16.
Lipids Health Dis ; 23(1): 151, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773578

RESUMO

OBJECTIVE: This study aims to assess the relationship between NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) and Type 2 diabetes mellitus (T2DM) in US adults, using National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2018. METHODS: This study explored the connection between NHHR and T2DM by analyzing a sample reflecting the adult population of the United States (n = 10,420; NHANES 2007-2018). NHHR was characterized as the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol. T2DM was defined based on clinical guidelines. This research used multivariable logistic models to examine the connection between NHHR and T2DM. Additionally, it included subgroup and interaction analyses to assess variations among different groups. Generalized additive models, smooth curve fitting, and threshold effect analysis were also employed to analyze the data further. RESULTS: The study included 10,420 subjects, with 2160 diagnosed with T2DM and 8260 without. The weighted multivariate logistic regression model indicated an 8% higher probability of T2DM for each unit increase in NHHR (OR: 1.08, 95% CI: 1.01-1.15) after accounting for all covariates. Subgroup analysis outcomes were uniform across various categories, demonstrating a significant positive relationship between NHHR and T2DM. Interaction tests showed that the positive link between NHHR and T2DM remained consistent regardless of age, body mass index, smoking status, moderate recreational activities, hypertension, or stroke history, with all interaction P-values exceeding 0.05. However, participants' sex appeared to affect the magnitude of the connection between NHHR and T2DM (interaction P-value < 0.05). Also, a nonlinear association between NHHR and T2DM was discovered, featuring an inflection point at 1.50. CONCLUSIONS: Our study suggests that an increase in NHHR may be correlated with a heightened likelihood of developing T2DM. Consequently, NHHR could potentially serve as a marker for estimating the probability of T2DM development.


Assuntos
HDL-Colesterol , Diabetes Mellitus Tipo 2 , Inquéritos Nutricionais , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , HDL-Colesterol/sangue , Adulto , Fatores de Risco , Modelos Logísticos , Idoso , Estados Unidos/epidemiologia , LDL-Colesterol/sangue
17.
iScience ; 27(6): 109850, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38779481

RESUMO

Milk fat is an important indicator for evaluating the quality of cow's milk. In this study, we used bovine mammary epithelial cells (BMECs) to investigate the role and molecular mechanism of KLF4 in the regulation of milk fat synthesis. The results showed that KLF4 was more highly expressed in mammary tissues of high-fat cows compared with low-fat cows. KLF4 positively regulated the expression of genes related to milk fat synthesis in BMECs, increasing intracellular triglycerides content, and KLF4 promoted milk fat synthesis by activating the PI3K-AKT-mTOR signaling pathway. Furthermore, the results of animal experiments also confirmed that knockdown of KLF4 inhibited milk fat synthesis. In addition, yeast one-hybrid assays and dual-luciferase reporter gene assays confirmed that KLF4 directly targets and binds to the fatty acid synthase (FASN) promoter region to promote FASN transcription. These results demonstrate that KLF4 is a key transcription factor for milk fat synthesis in BMECs.

18.
Food Funct ; 15(10): 5466-5484, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38690672

RESUMO

Inflammatory bowel disease (IBD) is difficult to cure, and formulating a dietary plan is an effective means to prevent and treat this disease. Wheat peptide contains a variety of bioactive peptides with anti-inflammatory and antioxidant functions. The results of this study showed that preventive supplementation with wheat peptide (WP) can significantly alleviate the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. WP can increase body weight, alleviate colon shortening, and reduce disease activity index (DAI) scores. In addition, WP improved intestinal microbial disorders in mice with colitis. Based on LC-MS, a total of 313 peptides were identified in WP, 4 of which were predicted to be bioactive peptides. The regulatory effects of WP and four bioactive peptides on the Keap1-Nrf2 signaling pathway were verified in Caco-2 cells. In conclusion, this study demonstrated that WP alleviates DSS-induced colitis by helping maintain gut barrier integrity and targeting the Keap1-Nrf2 axis; these results provided a rationale for adding WP to dietary strategies to prevent IBD.


Assuntos
Colite , Sulfato de Dextrana , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , Peptídeos , Transdução de Sinais , Triticum , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Sulfato de Dextrana/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Humanos , Triticum/química , Células CACO-2 , Peptídeos/farmacologia , Masculino , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos
19.
World J Surg ; 48(1): 86-96, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38686746

RESUMO

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Estudos Retrospectivos , Masculino , Feminino , Neoplasias do Apêndice/terapia , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Pessoa de Meia-Idade , Adulto , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Idoso , Terapia Combinada , Resultado do Tratamento , Taxa de Sobrevida , Gradação de Tumores , Perfuração Intestinal/etiologia , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/mortalidade
20.
J Vasc Surg ; 80(2): 574-585.e4, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38580159

RESUMO

OBJECTIVE: Although carotid body tumors (CBTs) are rare, they attract particular attention because of their propensity for malignant transformation and the high surgical risk. Because data are scarce and as it is difficult to achieve a large sample size, no study has yet comprehensively analyzed the characteristics, management, or operative complications of CBTs. Therefore, we collected and analyzed all currently available information on CBTs and used the pooled data to derive quantitative information on disease characteristics and management. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and the Web of Science up to December 1, 2022, for studies that investigated the characteristics and management of CBTs. The primary objective was to identify the prevalence of the various characteristics and the incidence of complications. The secondary objective was to compare patients who underwent preoperative embolization (PE) and those who did not (non-PE), as well as to compare patients with different Shamblin grades and those with and without succinate dehydrogenase (SDH) mutations in terms of CBT characteristics and complications. Two reviewers selected studies for inclusion and independently extracted data. All statistical analyses were performed using the standard statistical procedures of Review Manager 5.2 and Stata 12.0. RESULTS: A total of 155 studies with 9291 patients and 9862 tumors were identified. The pooled results indicated that the median age of patients with CBT was 45.72 years, and 65% were female. The proportion of patients with bilateral lesions was 13%. In addition, 16% of patients had relevant family histories, and the proportion of those with SDH gene mutations was 36%. Sixteen percent of patients experienced multiple paragangliomas, and 12% of CBTs had catecholamine function. The incidence of cranial nerve injury (CNI) was 27%, and 14% of patients suffered from permanent CNI. The incidence rates of operative mortality and stroke were both 1%, and 4% of patients developed transient ischemic attacks. Of all CBTs, 6% were malignant or associated with metastases or recurrences. The most common metastatic locations were the lymph nodes (3%) and bone (3%), followed by the lungs (2%). Compared with non-PE, PE reduced the estimated blood loss (standardized mean difference, -0.95; 95% confidence interval [CI], -1.70 to -0.20) and the operation time (standardized mean difference, -0.56; 95% CI, -1.03 to -0.09), but it increased the incidence of stroke (odds ratio, 2.44; 95% CI, 1.04-5.73). Higher Shamblin grade tumors were associated with more operative complications. Patients who were SDH gene mutation-positive were more likely to have a relevant family history and had more symptoms. CONCLUSIONS: CBT was most common in middle-aged females, and early surgical resection was feasible; there was a low incidence of serious operative complications. Routine PE is not recommended because this may increase the incidence of stroke, although PE somewhat reduced the estimated blood loss and operation time. Higher Shamblin grade tumors increased the incidence of operative complications. Patients who were SDH gene mutation-positive had the most relevant family histories and symptoms.


Assuntos
Tumor do Corpo Carotídeo , Embolização Terapêutica , Humanos , Tumor do Corpo Carotídeo/cirurgia , Tumor do Corpo Carotídeo/epidemiologia , Tumor do Corpo Carotídeo/terapia , Tumor do Corpo Carotídeo/genética , Prevalência , Fatores de Risco , Feminino , Masculino , Embolização Terapêutica/efeitos adversos , Resultado do Tratamento , Pessoa de Meia-Idade , Adulto , Medição de Risco , Idoso , Adulto Jovem , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adolescente , Mutação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...