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1.
Plant Biotechnol J ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39166471

RESUMEN

RNA silencing plays a crucial role in defending against viral infections in diverse eukaryotic hosts. Despite extensive studies on core components of the antiviral RNAi pathway such as DCLs, AGOs and RDRs proteins, host factors involved in antiviral RNAi remain incompletely understood. In this study, we employed the proximity labelling approach to identify the host factors required for antiviral RNAi in Nicotiana benthamiana. Using the barley stripe mosaic virus (BSMV)-encoded γb, a viral suppressor of RNA silencing (VSR), as the bait protein, we identified the DEAD-box RNA helicase RH20, a broadly conserved protein in plants and animals with a homologous human protein known as DDX5. We demonstrated the interaction between RH20 and BSMV γb. Knockdown or knockout of RH20 attenuates the accumulation of viral small interfering RNAs, leading to increased susceptibility to BSMV, while overexpression of RH20 enhances resistance to BSMV, a process requiring the cytoplasmic localization and RNA-binding activity of RH20. In addition to BSMV, RH20 also negatively regulates the infection of several other positive-sense RNA viruses, suggesting the broad-spectrum antiviral activity of RH20. Mechanistic analysis revealed the colocalization and interaction of RH20 with SGS3/RDR6, and disruption of either SGS3 or RDR6 undermines the antiviral function of RH20, suggesting RH20 as a new component of the SGS3/RDR6 bodies. As a counter-defence, BSMV γb VSR subverts the RH20-mediated antiviral defence by interfering with the RH20-SGS3 interaction. Our results uncover RH20 as a new positive regulator of antiviral RNAi and provide new potential targets for controlling plant viral diseases.

2.
Discov Med ; 36(187): 1672-1677, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39190382

RESUMEN

BACKGROUND: Severe neonatal hyperbilirubinemia can cause hearing impairment. Bilirubin can be deposited in nerve cells, and the brainstem and the 8th nerve are especially sensitive to bilirubin toxicity. Abnormal changes in brainstem auditory evoked potential (BAEP) can be observed, and the BAEP test measures a nerve potential induced by short, high-frequency sound stimulation; thus, it is able to detect damage to the auditory conduction pathway in children. We aimed to identify relationships between clinical features and BAEP abnormalities in children with hyperbilirubinemia and to assess the predictive power of these risk factors for bilirubin-induced neurological damage. METHODS: Children with hyperbilirubinemia were evaluated with BAEP and retrospectively enrolled in the study between January 2012 and December 2018. Multivariate logistic regression was performed to identify independent predictors of BAEP abnormalities. RESULTS: Of the 561 children with hyperbilirubinemia enrolled, the BAEP anomaly group accounted for 198 (35.3%) cases. Except for body weight, there were no significant differences in the general data between the two groups with hyperbilirubinemia (p > 0.05). Univariate analysis showed that prematurity, abnormal umbilical cord, and gestational diabetes during pregnancy were significantly correlated with abnormal BAEP. Multivariate logistic regression analysis identified prematurity (p = 0.001), gestational diabetes (p = 0.03), Premature rupture of membranes (p = 0.013), total serum bilirubin (TSB), bilirubin/albumin (B/A) as independent risk factors for BAEP abnormalities. The prediction accuracy of TSB (Area Under Curve (AUC) = 0.557) and B/A (AUC = 0.566) was low, indicating that abnormal BAEP should be detected by multiple factors. CONCLUSIONS: Multivariate detection is beneficial for predicting the occurrence of auditory nerve injury in patients with hyperbilirubinemia.


Asunto(s)
Potenciales Evocados Auditivos del Tronco Encefálico , Hiperbilirrubinemia Neonatal , Humanos , Femenino , Recién Nacido , Masculino , Estudios Retrospectivos , Hiperbilirrubinemia Neonatal/sangre , Hiperbilirrubinemia Neonatal/fisiopatología , Hiperbilirrubinemia Neonatal/complicaciones , Hiperbilirrubinemia Neonatal/diagnóstico , Factores de Riesgo , Bilirrubina/sangre , Embarazo , Diabetes Gestacional/fisiopatología , Diabetes Gestacional/sangre
3.
Mol Plant ; 17(9): 1369-1391, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39066482

RESUMEN

Suppressor of G2 allele of skp1 (SGT1) is a highly conserved eukaryotic protein that plays a vital role in growth, development, and immunity in both animals and plants. Although some SGT1 interactors have been identified, the molecular regulatory network of SGT1 remains unclear. SGT1 serves as a co-chaperone to stabilize protein complexes such as the nucleotide-binding leucine-rich repeat (NLR) class of immune receptors, thereby positively regulating plant immunity. SGT1 has also been found to be associated with the SKP1-Cullin-F-box (SCF) E3 ubiquitin ligase complex. However, whether SGT1 targets immune repressors to coordinate plant immune activation remains elusive. In this study, we constructed a toolbox for TurboID- and split-TurboID-based proximity labeling (PL) assays in Nicotiana benthamiana and used the PL toolbox to explore the SGT1 interactome during pre- and post-immune activation. The comprehensive SGT1 interactome network we identified highlights a dynamic shift from proteins associated with plant development to those linked with plant immune responses. We found that SGT1 interacts with Necrotic Spotted Lesion 1 (NSL1), which negatively regulates salicylic acid-mediated defense by interfering with the nucleocytoplasmic trafficking of non-expressor of pathogenesis-related genes 1 (NPR1) during N NLR-mediated response to tobacco mosaic virus. SGT1 promotes the SCF-dependent degradation of NSL1 to facilitate immune activation, while salicylate-induced protein kinase-mediated phosphorylation of SGT1 further potentiates this process. Besides N NLR, NSL1 also functions in several other NLR-mediated immunity. Collectively, our study unveils the regulatory landscape of SGT1 and reveals a novel SGT1-NSL1 signaling module that orchestrates plant innate immunity.


Asunto(s)
Nicotiana , Inmunidad de la Planta , Transducción de Señal , Inmunidad de la Planta/genética , Nicotiana/genética , Nicotiana/inmunología , Nicotiana/metabolismo , Proteínas NLR/metabolismo , Proteínas NLR/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Arabidopsis/genética , Arabidopsis/inmunología , Arabidopsis/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Glucosiltransferasas
4.
Nat Sci Sleep ; 16: 787-800, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38894977

RESUMEN

Purpose: Clinical studies have demonstrated the intricate association between the onset and progression of obstructive sleep apnea (OSA) and the activation of the inflammatory cascade reaction. This study delves into investigating the causal links between 91 circulating inflammatory proteins (CIPs) and OSA through the application of Mendelian randomization (MR) techniques. Methods: Utilizing genetic data on OSA sourced from the Finnish Biobank (FinnGen) Genome-wide Association Studies (GWAS) of the European population, alongside summary-level GWAS data of CIPs from 14,824 European participants, we conducted a bidirectional MR study. Results: This study suggests that several factors may be associated with the risk of OSA. IL-17C (odds ratio (OR) = 1.090, p = 0.0311), CCL25 (OR = 1.079, p = 0.0493), FGF-5 (OR = 1.090, p = 0.0003), CD5 (OR = 1.055, p = 0.0477), and TNFSF14 (OR = 1.092, p = 0.0008) may positively correlate with OSA risk. Conversely, IL-20RA (OR = 0.877, p = 0.0107), CCL19 (OR = 0.933, p = 0.0237), MIP-1 alpha (OR = 0.906, p = 0.0042), Flt3L (OR = 0.941, p = 0.0019), CST5 (OR = 0.957, p = 0.0320), OPG (OR = 0.850, p = 0.0001), and TRAIL (OR = 0.956, p = 0.0063) may reduce the risk of OSA. Additionally, elevated levels of IL-10RA (OR = 1.153, p = 0.0478) were observed as a consequence of OSA. Conversely, OSA may potentially lead to decreased levels of CCL28 (OR = 0.875, p = 0.0317), DNER (OR = 0.874, p = 0.0324), FGF-21 (OR = 0.846, p = 0.0344), and CSF-1 (OR = 0.842, p = 0.0396). Conclusion: Through this bidirectional MR study, we have identified 12 upstream regulatory proteins and 5 downstream effect proteins that are linked to OSA. These findings hold promise in providing potential therapeutic targets for the inflammatory mechanisms underlying OSA.

5.
Front Immunol ; 15: 1396246, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846949

RESUMEN

Background: Allergic rhinitis (AR), a prevalent chronic inflammatory condition triggered by immunoglobulin E (IgE), involves pivotal roles of immune and metabolic factors in its onset and progression. However, the intricacies and uncertainties in clinical research render current investigations into their interplay somewhat inadequate. Objective: To elucidate the causal relationships between immune cells, metabolites, and AR, we conducted a mediation Mendelian randomization (MR) analysis. Methods: Leveraging comprehensive publicly accessible summary-level data from genome-wide association studies (GWAS), this study employed the two-sample MR research method to investigate causal relationships among 731 immune cell phenotypes, 1400 metabolite levels, and AR. Additionally, employing the mediation MR approach, the study analyzed potential mediated effect of metabolites in the relationships between immune cells and AR. Various sensitivity analysis methods were systematically employed to ensure the robustness of the results. Results: Following false discovery rate (FDR) correction, we identified three immune cell phenotypes as protective factors for AR: Naive CD8br %CD8br (odds ratio (OR): 0.978, 95% CI = 0.966-0.990, P = 4.5×10-4), CD3 on CD39+ activated Treg (OR: 0.947, 95% CI = 0.923-0.972, P = 3×10-5), HVEM on CD45RA- CD4+ (OR: 0.967, 95% CI = 0.948-0.986, P = 4×10-5). Additionally, three metabolite levels were identified as risk factors for AR: N-methylhydroxyproline levels (OR: 1.219, 95% CI = 1.104-1.346, P = 9×10-5), N-acetylneuraminate levels (OR: 1.133, 95% CI = 1.061-1.211, P = 1.7×10-4), 1-stearoyl-2-arachidonoyl-gpc (18:0/20:4) levels (OR: 1.058, 95% CI = 1.029-1.087, P = 5×10-5). Mediation MR analysis indicated a causal relationship between Naive CD8br %CD8br and N-methylhydroxyproline levels, acting as a protective factor (OR: 0.971, 95% CI = 0.950-0.992, P = 8.31×10-3). The mediated effect was -0.00574, accounting for 26.1% of the total effect, with a direct effect of -0.01626. Naive CD8+ T cells exert a protective effect on AR by reducing N-methylhydroxyproline levels. Conclusion: Our study, delving into genetic information, has substantiated the intricate connection between immune cell phenotypes and metabolite levels with AR. This reveals a potential pathway to prevent the onset of AR, providing guiding directions for future clinical investigations.


Asunto(s)
Linfocitos T CD8-positivos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Rinitis Alérgica , Humanos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Rinitis Alérgica/inmunología , Rinitis Alérgica/genética , Fenotipo , Predisposición Genética a la Enfermedad
6.
Asian J Pharm Sci ; 19(2): 100891, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38584690

RESUMEN

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvß3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

7.
J Stroke Cerebrovasc Dis ; 33(4): 107609, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38331009

RESUMEN

OBJECTIVES: Ultrasound guidance endoscopic surgery (ES) has been widely used in the treatment of cerebral hemorrhage in recent years, but relevant research articles are still scarce. Our study aims to investigate the effect of ES compared with conventional craniotomy (CC) on the postoperative complications, and prognosis of patients with intracerebral hemorrhage. MATERIALS AND METHODS: The clinical data of 1201 patients with ICH treated in our hospital from January 2017 to January 2020 were collected. The t-test, Chi-squared test and Fisher's exact test were used to analyze the clinical baseline data. Among 1021 spontaneous ICH patients, 193 patients who underwent hematoma evacuation were included in the present analysis. RESULTS: The Glasgow Outcome Scale (GOS) score at 6 months had a favorable prognosis in ES group (p = 0.003). ES group had fewer postoperative complications compared with CC group. Operating time and intraoperative blood loss were significantly lower in ES group than CC group (p = 0.001 and p = 0.002). CONCLUSIONS: Our study revealed that receiving ES improved the prognosis of ICH patients. Additionally, endoscopic surgery diminishes operative time, and intraoperative blood loss and reduces the incidence of postoperative complications.


Asunto(s)
Pérdida de Sangre Quirúrgica , Hemorragia Cerebral , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/cirugía , Craneotomía/efectos adversos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Hematoma/diagnóstico por imagen , Hematoma/cirugía
8.
J Phys Chem A ; 128(7): 1274-1279, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38334079

RESUMEN

Iodomethane and bromomethane (CH3I/CH3Br) are common chemicals, but their chemistry on nanometals is not fully understood. Here, we analyze the reactivity of Rhn+ (n = 3-30) clusters with halomethanes and unveil the spin effect and concentration dependence in the C-H and C-X bond activation. It is found that the reactions under halomethane-rich conditions differ from those under metal-rich conditions. Both CH3I and CH3Br undergo similar dehydrogenation on the Rhn+ clusters in the presence of small quantity reactants; however, different reactions are observed in the presence of sufficient CH3I/CH3Br, showing dominant Rh(CH3Br)x+ (x = 1-4) products but a series of RhnCxHyIz+ species (x = 1-4, y = 1-12, and z = 1-5) pertaining to H2, HI, or CH4 removal. Density functional theory calculations reveal that the dehydrogenation and demethanation of CH3Br are relatively less exothermic and will be deactivated by sufficient gas collisions if helium cooling takes away energy immediately; instead, the successive adsorption of CH3Br gives rise to a series of Rh(CH3Br)x+ species with accidental C-Br bond dissociation.

9.
Pharmaceutics ; 16(2)2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38399358

RESUMEN

The Pharmaceutics Editorial Office retracts the article, "A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy" [...].

10.
Meat Sci ; 210: 109433, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38278006

RESUMEN

This paper investigated the effect of yeast protein (YP)-fat replacement on the nutritional composition, spatial structure, gel performance, and sensory quality of emulsified sausages. YP is enriched with essential amino acids (36.49 g/100 g), which improved the nutritional quality of sausages whereas reducing its fat content. Moreover, YP could absorb water and fat, thus the YP-added sausages exhibiting an amount-dependent increase in emulsion stability and water migration. The microstructure illustrated that YP acted as a filler to improve structural homogeneity and compactness of the pork gel network. And YP-fat replacement could significantly enhance the hardness, gel strength and elasticity of sausages whereas decreasing the viscosity. Additionally, at partial or full YP-fat replacement (25-100%), the YP-added sausages scored higher in odor and texture, as well as better antioxidant stability than controls. Overall, YP can be employed as a new fat substitute for the preparation of healthy and nutritional sausages, while maintaining the sensory quality.


Asunto(s)
Sustitutos de Grasa , Productos de la Carne , Animales , Saccharomyces cerevisiae , Gusto , Sustitutos de Grasa/química , Dureza , Agua , Productos de la Carne/análisis
11.
Eur Arch Otorhinolaryngol ; 281(4): 1865-1875, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38180605

RESUMEN

OBJECTIVES: To characterize treatment response of recurrent respiratory papillomatosis (RRP) including adult-onset RRP (AORRP) and juvenile-onset RRP (JORRP) to systemic bevacizumab (bev), and share our treatment regimen experience. METHODS: Patients were enrolled in bev treatment based on a pathologically confirmed diagnosis of squamous papilloma. According to lesion characteristics and medical history, systemic bev was used as preoperative adjuvant therapy, postoperative adjuvant therapy, or primary therapy. The assessment of treatment response relied on the morphological changes of lesions. Vocalization and voice-related quality of life were evaluated using the voice handicap index-30 (VHI-30) for adults and the pediatric VHI (pVHI) for children. Adverse effect was monitored through patient self-reported symptoms and regular follow-ups. RESULTS: This study included 24 patients, comprising nine AORRP and 15 JORRP cases. In AORRP, all patients (100%) exhibited various degrees of response to systemic bev, with 5 (55.56%) achieving complete response (CR). Among JORRP patients, 14 (93.33%) showed a response to systemic bev, with 8 (53.33%) achieving CR and currently being followed up. No instances of aggravation were observed during systemic bev treatment. A total of 21 patients (21/24, 87.50%) reported voice improvement, accompanied by reduced VHI-30 or pVHI scores across all aspects, including total, functional, physical, and emotional dimensions. No grade 3 or higher adverse events occurred. The most common adverse events were grade 1 gum bleeding (n = 4, 16.67%) and grade 1 proteinuria (n = 4, 16.67%). CONCLUSIONS: Systemic bev can be used as a powerful therapy for both AORRP and JORRP. The findings provide a reference to the systemic bev treatment for RRP.


Asunto(s)
Infecciones por Papillomavirus , Infecciones del Sistema Respiratorio , Adulto , Niño , Humanos , Bevacizumab/uso terapéutico , Calidad de Vida , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones por Papillomavirus/diagnóstico , Respuesta Patológica Completa
12.
Opt Express ; 32(1): 355-365, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38175066

RESUMEN

Rydberg-state excitation of stretched model molecules subjected to near-infrared intense laser fields has been investigated based on a fully quantum model (QM) proposed recently and the numerical solutions of time-dependent Schrödinger equation (TDSE). Given the good agreement between QM and TDSE, it is found that, as the molecules are stretched, the electron tends to be trapped into low-lying Rydberg-states after its ionization from the core, which can be attributed to the shift of the ionization moments corresponding to maximum excitation populations. Moreover, the n-distribution is broadened for molecules with increasing internuclear distance, which results from the change of momentum distribution of emitted electrons. Analysis indicates that both of the above phenomena are closely related to the interference effect of electronic wave packets emitted from different nuclei. Our study provides a more comprehensive understanding of the molecular excitation in intense laser fields, as well as a means of possible applications to related experimental observations.

13.
Int J Biol Macromol ; 260(Pt 2): 129572, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38253141

RESUMEN

This study investigated the effects of radio frequency air cold plasma (RFACP) pretreatment on the multi-scale structures, physicochemical properties, enzymatic hydrolysis, and hydroxypropylation of tapioca starch. The results showed that cold plasma (CP) made starch granules rough on the surface and disrupted long- and short-range ordered structures, reducing relative crystallinity from 43.8 % to 37.4 % and R1047/1022 value from 0.992 to 0.934. Meanwhile, the starch molecules were depolymerized and oxidized by CP, reducing weight-average molecular weight from 9.64 × 107 to 2.17 × 107 g/mol, while increasing carbonyl and carboxyl groups by up to 118 % and 53 %. Additionally, CP-treated starches exhibited higher solubility and swelling power, along with lower gelatinization enthalpy. Short-time CP pretreatment (10 min) promoted the hydroxypropylation of starch and increased the molar substitution (0.081-0.112). Also, CP pretreatment accelerated enzymatic hydrolysis of starch, as indicated by the increase in hydrolysis rate (1.846 × 10-3-2.033 × 10-3 min-1) and degree of hydrolysis (51.45 % - 59.92 %). Overall, the multi-scale structural disruption induced by CP treatment facilitated the accessibility of enzymes/chemical reagents into starch granules and glucan chains. This study suggested that RFACP could be used for starch pretreatment to increase production efficiency in modified starch production, as well as in brewing and fermentation industries.


Asunto(s)
Manihot , Gases em Plasma , Hidrólisis , Almidón/química , Solubilidad , Amilosa
14.
Chinese Journal of School Health ; (12): 244-247, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1012513

RESUMEN

Objective@#To explore the latent categories and general demographic characteristics of short form video addiction among college students, so as to provide empirical reference for prevention and intervention of short form video addiction among college students.@*Methods@#Convenience sampling method was used to select 1 386 college students from a certain university in Anhui Province in June 2023. A questionnaire survey was conducted among college students by using the Short Video Addiction Scale. The latent profile analysis method of "individual center" was used to explore the categories of college students short form video addiction, and multiple Logistic regression was used to explore the influence of demographic variables on the latent classification of short form video addiction.@*Results@#College students with short form video addiction were divided into three latent categories:non addiction group (22.15%, n =307), low addiction group (63.28%, n =877) and high addiction group (14.57%, n =202). The results of multiple Logistic regression analysis showed that gender, major type and family location were related with short form video addiction among college students:male students (low addiction group: OR =0.47; high addiction group: OR =0.41), cultural and historical majors (low addiction group: OR =0.66), and students from cities (high addiction group: OR =0.51) were less likely to be involved in short form video addiction ( P <0.05).@*Conclusions@#There is significant group heterogeneity in short form video addiction among college students. Families, schools and society should attach importance and pay attention to the phenomenon of short form video addiction among college students, actively take targeted intervention measures to prevent and reduce the occurrence of short form video addiction symptoms among college students.

15.
Diabetologia ; 66(11): 2139-2153, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37581618

RESUMEN

AIMS/HYPOTHESIS: An increasing body of evidence has shown that the catabolism of branched-chain amino acids (BCAAs; leucine, isoleucine and valine) is impaired in obese animals and humans, contributing to the development of insulin resistance and type 2 diabetes. Promoting BCAA catabolism benefits glycaemic control. It remains unclear whether BCAA catabolism plays a role in the therapeutic efficacy of currently used glucose-lowering drugs such as metformin. METHODS: Mice were treated with vehicle or metformin (250 mg/kg per day) for more than 4 weeks to investigate the effects of metformin in vivo. In vitro, primary mouse hepatocytes and HepG2 cells were treated with 2 mmol/l metformin. The therapeutic efficacy of metformin in the treatment of type 2 diabetes was assessed in genetically obese (ob/ob) mice and high-fat-diet-induced obese (DIO) mice. Enhancing BCAA catabolism was achieved with a pharmacological agent, 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2). The ob/ob mice were treated with a low-BCAA diet or intermittent protein restriction (IPR) to reduce BCAA nutritional intake. RESULTS: Metformin unexpectedly inhibited the catabolism of BCAAs in obese mice, resulting in an elevation of BCAA abundance. AMP-activated protein kinase (AMPK) mediated the impact of metformin on BCAA catabolism in hepatocytes. Importantly, enhancing BCAA catabolism via a pharmacological agent BT2 significantly potentiated the glucose-lowering effect of metformin while decreasing circulating BCAA levels in ob/ob and DIO mice. Similar outcomes were achieved by a nutritional approach of reducing BCAA intake. IPR also effectively reduced the circulating BCAA abundance and enhanced metformin's glucose-lowering effect in ob/ob mice. BT2 and IPR treatments reduced the expression of fructose-1,6-bisphosphatase 1, a rate-limiting enzyme in gluconeogenesis, in the kidney but not liver, indicating the involvement of renal gluconeogenesis. CONCLUSIONS/INTERPRETATION: Metformin self-limits its therapeutic efficacy in the treatment of type 2 diabetes by triggering the suppression of BCAA catabolism. Enhancing BCAA catabolism pharmacologically or reducing BCAA intake nutritionally potentiates the glucose-lowering effect of metformin. These data highlight the nutritional impact of protein on metformin's therapeutic efficacy and provide new strategies targeting BCAA metabolism to improve metformin's effects on the clinical outcome in diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Humanos , Ratones , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Aminoácidos de Cadena Ramificada/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Dieta Alta en Grasa , Glucosa
16.
Ear Nose Throat J ; : 1455613231185041, 2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37464765

RESUMEN

Objective:Many problems of parapharyngeal abscess (PPA), such as etiology, predisposing factors, and therapeutic methods, are still controversial. We aim to investigate the characteristics of PPA to better understand the therapeutic effects of the disease. Methods: We retrospectively collated the medical record reviews of 49 PPA patients who were treated as PPA inpatients when a patient was hospitalized and diagnosed with PPA, and empiric antibiotics were used. Only if the drug treatment was ineffective, the abscess was large, or the disease continued to progress, and surgical treatment was adopted. Results: In total, 49 patients who met the research criteria were identified. Streptococcus was the most common organism in PPA patients. The morbidity of diabetes in PPA patients was higher than the prevalence of diabetes in the overall population. Interestingly, the length of hospital stay was shorter in the antibiotic-only group than in the surgery group (P < 0.05). Furthermore, the duration from onset to treatment in the antibiotic-only group was shorter than in the surgery group. Conclusion: Our treatment protocol is effective. Antibiotic-only method is also recommended for the PPA which was effective for the empiric antibiotics and localized. Early diagnosis and treatment of PPA could ultimately reduce the severity of PPA.

17.
Sci China Life Sci ; 66(11): 2527-2542, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37428305

RESUMEN

Alveolar macrophages (AMs) are self-maintained immune cells that play vital roles in lung homeostasis and immunity. Although reporter mice and culture systems have been established for studying macrophages, an accurate and specific reporter line for alveolar macrophage study is still not available. Here we reported a novel Rspo1-tdTomato gene reporter mouse line that could specifically label mouse AMs in a cell-intrinsic manner. Using this reporter system, we visualized the dynamics of alveolar macrophages intravitally under steady state and characterized the alveolar macrophage differentiation under in vitro condition. By performing ATAC-seq, we found that insertion of the tdTomato cassette in the Rspo1 locus increased the accessibility of a PPARE motif within the Rspo1 locus and revealed a potential regulation by key transcription factor PPAR-γ for alveolar macrophage differentiation in vitro and in vivo. Consistently, perturbation of PPAR-γ by its agonist rosiglitazone or inhibitor GW9662 resulted in corresponding alteration of tdTomato expression in alveolar macrophages together with the transcription of PPAR-γ downstream target genes. Furthermore, global transcriptomic analyses of AMs from the wild type mice and the Rspo1-tdTomato mice showed comparable gene expression profiles, especially those AM-specific genes, confirming that the insertion of the tdTomato cassette in the Rspo1 locus does not impact the cell identity and biological function of AMs under normal condition. Taken together, our study provides an alternative tool for in vivo and in vitro labeling of alveolar macrophages with high specificity which could also be utilized as an indicator of PPAR-γ activity for future development of PPAR-γ specific targeting drugs.


Asunto(s)
Pulmón , Macrófagos Alveolares , Ratones , Animales , Macrófagos Alveolares/metabolismo , Pulmón/metabolismo , Macrófagos/metabolismo , Regulación de la Expresión Génica , PPAR gamma/genética , PPAR gamma/metabolismo
18.
J Voice ; 2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37422361

RESUMEN

OBJECTIVES: To study the effect of virtual reality (VR) on satisfaction, discomfort, stress, and cooperation in patients undergoing in-office potassium titanyl phosphate (KTP) laser procedure. STUDY DESIGN: Prospective study. METHODS: Thirty-seven patients were enrolled in this prospective study. The State Anxiety Scale of Spielberg's State-Trait Anxiety Inventory was used to measure the level of state anxiety. Satisfaction, discomfort, pain, stress, acceptance of VR, relaxation with VR, and willingness to wear VR were evaluated using a 100-mm visual analog scale (VAS). A 5-point Likert-like scale was used to rate the patient cooperation. RESULTS: All procedures were completed successfully with cooperation of patients. Satisfaction score in VR group was 88.3 ± 9.0, and in control group was 81.6 ± 9.7 (P = 0.040). There were significant differences in both nasal cavity and laryngopharynx discomfort between two groups (P = 0.030 and P = 0.016, respectively). The pain score of control group was higher than that of VR group but it was not statistically significant (P = 0.140). The stress of control group during procedure was more obvious than that of VR group (30.5 ± 24.0 versus 17.0 ± 9.2, P = 0.021). The mean VAS scores of acceptance of VR were all more than 75. The results of regression analysis showed that VR had significant effects on satisfaction with the procedure (P = 0.004), discomfort of nasal cavity (P = 0.030) and laryngopharynx (P = 0.016), and feeling of stress (P = 0.021) during the procedure. CONCLUSION: Distraction of VR can enhance satisfaction in both procedure and stress management for patients undergoing in-office KTP laser procedure. Acceptance of VR in VR group was relatively good.

19.
BMC Pediatr ; 23(1): 358, 2023 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-37442965

RESUMEN

BACKGROUND: We aimed to analyze the characteristics of the body composition of children and adolescents aged 3-17 in Suzhou, China. METHODS: A cross-sectional study between January 2020 and June 2022 using bioelectrical impedance was conducted to determine the fat mass (FM), fat-free mass (FFM), skeletal muscle mass, and protein and mineral contents of 24,845 children aged 3-17 who attended the Department of Child and Adolescent Healthcare, Children's Hospital of Soochow University, China. Measurement data was presented in tables as mean ± SD, and groups were compared using the independent samples t-test. RESULTS: FM and fat-free mass increased with age in both boys and girls. The fat-free mass of girls aged 14-15 decreased after reaching a peak, and that of boys in the same age group was higher than that of the girls (p < 0.05). There were no significant differences in FM between boys and girls younger than 9- and 10-years old. The percentage body fat (PBF) and FM index of girls increased rapidly between 11 and 15 years of age (p < 0.05), and those of boys aged 11-14 were significantly lower (p < 0.05), suggesting that the increase in body mass index (BMI) was mainly contributed by muscle mass (MM) in boys. CONCLUSIONS: The body composition of children and adolescents varies according to their age and sex. A misdiagnosis of obesity made on the basis of BMI alone can be avoided if BMI is used in combination with FM index, percentage body fat, and other indexes.


Asunto(s)
Composición Corporal , Obesidad , Masculino , Femenino , Humanos , Niño , Adolescente , Estudios Transversales , Índice de Masa Corporal , China , Tejido Adiposo
20.
Cell Commun Signal ; 21(1): 95, 2023 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-37143096

RESUMEN

The higher prevalence of metabolic syndrome (MetS) in women after menopause is associated with a decrease in circulating 17ß-oestradiol. To explore novel treatments for MetS in women with oestrogen deficiency, we studied the effect of exogenous butyrate on diet-induced obesity and metabolic dysfunctions using ovariectomized (OVX) mice as a menopause model. Oral administration of sodium butyrate (NaB) reduced the body fat content and blood lipids, increased whole-body energy expenditure, and improved insulin sensitivity. Additionally, NaB induced oestrogen receptor alpha (ERα) expression, activated the phosphorylation of AMPK and PGC1α, and improved mitochondrial aerobic respiration in cultured skeletal muscle cells. In conclusion, oral NaB improves metabolic parameters in OVX mice with diet-induced obesity. Oral supplementation with NaB might provide a novel therapeutic approach to treating MetS in women with menopause. Video Abstract.


Asunto(s)
Receptor alfa de Estrógeno , Síndrome Metabólico , Ratones , Femenino , Animales , Receptor alfa de Estrógeno/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Músculo Esquelético/metabolismo , Dieta Alta en Grasa , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Síndrome Metabólico/tratamiento farmacológico , Ácido Butírico/metabolismo , Ácido Butírico/farmacología , Ácido Butírico/uso terapéutico , Receptores de Estrógenos/metabolismo , Ratones Endogámicos C57BL
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