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1.
Dev Dyn ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254141

RESUMEN

Twist1 is required for embryonic development and expresses after birth in mesenchymal stem cells derived from mesoderm, where it governs mesenchymal cell development. As a well-known regulator of epithelial-mesenchymal transition or embryonic organogenesis, Twist1 is important in a variety of developmental systems, including mesoderm formation, neurogenesis, myogenesis, cranial neural crest cell migration, and differentiation. In this review, we first highlight the physiological significance of Twist1 in cell differentiation, including osteogenic, chondrogenic, and myogenic differentiation, and then detail its probable molecular processes and signaling pathways. On this premise, we summarize the significance of Twist1 in distinct developmental disorders and diseases to provide a reference for studies on cell differentiation/development-related diseases.

2.
BMC Med Genomics ; 17(1): 216, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160503

RESUMEN

BACKGROUND: There is growing evidence for a relationship between gut microbiota and hepatic encephalopathy (HE). However, the causal nature of the relationship between gut microbiota and HE has not been thoroughly investigated. METHOD: This study utilized the large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and HE risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for HE. The inverse variance weighted (IVW) method was used as the primary MR analysis. Sensitive analyses were performed to validate the robustness of the results. RESULTS: The IVW method revealed that the genus Bifidobacterium (OR = 0.363, 95% CI: 0.139-0.943, P = 0.037), the family Bifidobacteriaceae (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039), and the order Bifidobacteriales (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039) were negatively associated with HE. However, no causal relationship was observed among them after the Bonferroni correction test. Neither heterogeneity nor horizontal pleiotropy was found in the sensitivity analysis. CONCLUSION: Our MR study demonstrated a potential causal association between Bifidobacterium, Bifidobacteriaceae, and Bifidobacteriales and HE. This finding may provide new therapeutic targets for patients at risk of HE in the future.


Asunto(s)
Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Encefalopatía Hepática , Análisis de la Aleatorización Mendeliana , Humanos , Encefalopatía Hepática/genética , Encefalopatía Hepática/microbiología , Bifidobacterium/genética
3.
J Colloid Interface Sci ; 677(Pt B): 417-428, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39153245

RESUMEN

Synthesis of catalysts with high catalytic degradation activity for formaldehyde (HCHO) at room temperature is highly desirable for indoor air quality control. Herein, a novel K-Mn3O4@CeO2 catalyst with excellent catalytic oxidation activity toward HCHO at near room temperature was reported. In particular, the K addition in K-Mn3O4@CeO2 considerably enhanced the oxidation activity, and importantly, 99.3 % conversion of 10 mL of a 40 mg/L HCHO solution at 30 °C for 14 h was achieved, with simultaneous strong cycling stability. Moreover, the addition of K species considerably influenced the chemical valence state of Mn from +4 (ε-MnO2) to +8/3 (Mn3O4) on the surface of CeO2, which obviously changed the tunnel structure and the number of oxygen vacancies. One part of K species is uniformly dispersed on K-Mn3O4@CeO2, and the other part exists in the tunnel structure of Mn3O4@CeO2, which is mainly used to balance the negative charge of the tunnel and prevent collapse of the structure, providing enough active sites for the catalytic oxidation of HCHO. We observed a phase transition from tunneled KMnO2 to Mn3O4 to tunneled MnO2 with the decreasing K+ content, in which K-Mn3O4@CeO2 exhibited higher HCHO oxidation activity. In addition, K-Mn3O4@CeO2 exhibited lower oxygen vacancy formation and HCHO adsorption energies in aqueous solution based on density functional theory calculations. This is because the K species provide more active oxygen species and richer oxygen vacancies on the surface of K-Mn3O4@CeO2, promote the mobility of lattice oxygen and the room-temperature reduction properties of oxygen species, and enhance the ability of the catalyst to replenish the consumed oxygen species. Finally, a possible HCHO catalytic oxidation pathway on the surface of K-Mn3O4@CeO2 catalyst is proposed.

4.
Nat Commun ; 15(1): 5697, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38972900

RESUMEN

Climate and environmental changes threaten human mental health, but the impacts of specific environmental conditions on neuropsychiatric disorders remain largely unclear. Here, we show the impact of a humid heat environment on the brain and the gut microbiota using a conditioned housing male mouse model. We demonstrate that a humid heat environment can cause anxiety-like behaviour in male mice. Microbial 16 S rRNA sequencing analysis reveals that a humid heat environment caused gut microbiota dysbiosis (e.g., decreased abundance of Lactobacillus murinus), and metabolomics reveals an increase in serum levels of secondary bile acids (e.g., lithocholic acid). Moreover, increased neuroinflammation is indicated by the elevated expression of proinflammatory cytokines in the serum and cortex, activated PI3K/AKT/NF-κB signalling and a microglial response in the cortex. Strikingly, transplantation of the microbiota from mice reared in a humid heat environment readily recapitulates these abnormalities in germ-free mice, and these abnormalities are markedly reversed by Lactobacillus murinus administration. Human samples collected during the humid heat season also show a decrease in Lactobacillus murinus abundance and an increase in the serum lithocholic acid concentration. In conclusion, gut microbiota dysbiosis induced by a humid heat environment drives the progression of anxiety disorders by impairing bile acid metabolism and enhancing neuroinflammation, and probiotic administration is a potential therapeutic strategy for these disorders.


Asunto(s)
Ansiedad , Ácidos y Sales Biliares , Disbiosis , Microbioma Gastrointestinal , Calor , Animales , Masculino , Ratones , Ácidos y Sales Biliares/metabolismo , Humanos , Disbiosis/microbiología , Ansiedad/microbiología , Ratones Endogámicos C57BL , Humedad , Ácido Litocólico/metabolismo , Lactobacillus , Encéfalo/metabolismo , FN-kappa B/metabolismo , ARN Ribosómico 16S/genética , Modelos Animales de Enfermedad , Trastornos de Ansiedad/metabolismo , Trastornos de Ansiedad/microbiología , Trastornos de Ansiedad/etiología , Transducción de Señal , Citocinas/metabolismo
5.
Genome Biol ; 25(1): 179, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38972974

RESUMEN

Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer's disease model, we demonstrate silencing of mutant APPswe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.


Asunto(s)
Enfermedad de Alzheimer , Silenciador del Gen , ARN Mensajero , ARN Mensajero/genética , ARN Mensajero/metabolismo , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Animales , Ratones , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , División del ARN , Vectores Genéticos , Dependovirus/genética
6.
Int J Mol Sci ; 25(14)2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39062949

RESUMEN

The communication mechanism of the gut-lung axis has received increasing attention in recent years, particularly in acute respiratory infectious diseases such as influenza. The peripheral immune system serves as a crucial bridge between the gut and the lungs, two organs that are not in close proximity to each other. However, the specific communication mechanism involving gut microbiota, immune cells, and their anti-influenza effects in the lung remains to be further elucidated. In this study, the effects of 731 species of peripheral immune cells and 211 different gut microbiota on influenza outcomes were analyzed using a two-sample Mendelian randomization analysis. After identifying specific species of gut microbiota and peripheral immune cells associated with influenza outcomes, mediation analyses were conducted to determine the mediating effects of specific immune cells in the protective or injurious effects of influenza mediated by gut microbiota. 19 species of gut microbiota and 75 types of peripheral immune cells were identified as being associated with influenza susceptibility. After rigorous screening, 12 combinations were analyzed for mediated effects. Notably, the down-regulation of CD64 on CD14- CD16- cells mediated 21.10% and 18.55% of the protective effect of Alcaligenaceae and Dorea against influenza, respectively. In conclusion, focusing on influenza, this study genetically inferred different types of gut microbiota and peripheral immune cells to determine their protective or risk factors. Furthermore, mediation analysis was used to determine the proportion of mediating effects of peripheral immune cells in gut microbiota-mediated susceptibility to influenza. This helps elucidate the gut-lung axis mechanism by which gut microbiota affects influenza susceptibility from the perspective of regulation of peripheral immune cells.


Asunto(s)
Microbioma Gastrointestinal , Gripe Humana , Microbioma Gastrointestinal/inmunología , Humanos , Gripe Humana/inmunología , Predisposición Genética a la Enfermedad , Susceptibilidad a Enfermedades , Análisis de la Aleatorización Mendeliana , Pulmón/inmunología , Pulmón/microbiología
7.
Int J Mol Sci ; 25(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39063036

RESUMEN

BACKGROUND: As a common soft tissue sarcoma, liposarcoma (LPS) is a heterogeneous malignant tumor derived from adipose tissue. Due to the high risk of metastasis and recurrence, the prognosis of LPS remains unfavorable. To improve clinical treatment, a robust risk prediction model is essential to evaluate the prognosis of LPS patients. METHODS: By comprehensive analysis of data derived from GEO datasets, differentially expressed genes (DEGs) were obtained. Univariate and Lasso Cox regressions were subsequently employed to reveal distant recurrence-free survival (DRFS)-associated DEGs and develop a prognostic gene signature, which was assessed by Kaplan-Meier survival and ROC curve. GSEA and immune infiltration analyses were conducted to illuminate molecular mechanisms and immune correlations of this model in LPS progression. Furthermore, a correlation analysis was involved to decipher the therapeutic significance of this model for LPS. RESULTS: A six-gene signature was developed to predict DRFS of LPS patients and showed higher precision performance in more aggressive LPS subtypes. Then, a nomogram was further established for clinical application based on this risk model. Via GSEA, the high-risk group was significantly enriched in cell cycle-related pathways. In the LPS microenvironment, neutrophils, memory B cells and resting mast cells exhibited significant differences in cell abundance between high-risk and low-risk patients. Moreover, this model was significantly correlated with therapeutic targets. CONCLUSION: A prognostic six-gene signature was developed and significantly associated with cell cycle pathways and therapeutic target genes, which could provide new insights into risk assessment of LPS progression and therapeutic strategies for LPS patients to improve their prognosis.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Liposarcoma , Microambiente Tumoral , Humanos , Liposarcoma/genética , Liposarcoma/inmunología , Liposarcoma/patología , Liposarcoma/mortalidad , Pronóstico , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Transcriptoma , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Nomogramas , Masculino , Femenino , Estimación de Kaplan-Meier , Curva ROC
8.
Eur Phys J C Part Fields ; 84(2): 202, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050377

RESUMEN

Scintillating fibre detectors combine sub-mm resolution particle tracking, precise measurements of the particle stopping power and sub-ns time resolution. Typically, fibres are read out with silicon photomultipliers (SiPM). Hence, if fibres with a few hundred µ m diameter are used, either they are grouped together and coupled with a single SiPM, losing spatial resolution, or a very large number of electronic channels is required. In this article we propose and provide a first demonstration of a novel configuration which allows each individual scintillating fibre to be read out regardless of the size of its diameter, by imaging them with Single-Photon Avalanche Diode (SPAD) array sensors. Differently from SiPMs, SPAD array sensors provide single-photon detection with single-pixel spatial resolution. In addition, O(us) or faster coincidence of detected photons allows to obtain noise-free images. Such a concept can be particularly advantageous if adopted as a neutrino active target, where scintillating fibres alternated along orthogonal directions can provide isotropic, high-resolution tracking in a dense material and reconstruct the kinematics of low-momentum protons (down to 150 MeV/c), crucial for an accurate characterisation of the neutrino-nucleus cross section. In this work the tracking capabilities of a bundle of scintillating fibres coupled to SwissSPAD2 is demonstrated. The impact of such detector configuration in GeV-neutrino experiments is studied with simulations and reported. Finally, future plans, including the development of a new SPAD array sensor optimised for neutrino detection, are discussed.

9.
J Antimicrob Chemother ; 79(9): 2263-2272, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38973619

RESUMEN

BACKGROUND: With the increasing prevalence of antibiotic resistance, real-world data on the optimal empirical second-line therapy for Helicobacter pylori are still limited. OBJECTIVES: To evaluate the real-world efficacy of various second-line therapies for H. pylori. PATIENTS AND METHODS: This was a retrospective population-based cohort study of all H. pylori-infected patients who had received the second-line treatment after the failure of primary clarithromycin triple therapy in Hong Kong between 2003 and 2018. The retreatment success rates of different second-line therapies were evaluated. RESULTS: A total of 7591 patients who received second-line treatment were included. Notably, the most commonly prescribed regimen was still clarithromycin triple therapy, but the frequency of use had decreased from 59.5% in 2003-06 to 28.7% in 2015-18. Concomitant non-bismuth quadruple therapy had emerged as the commonest regimen (from 3.3% to 43.9%). In a validation analysis, the sensitivity and specificity of retreatment-inferred second-line treatment failure were 88.3% and 97.1%, respectively. The overall success rate of second-line therapies was 73.6%. Bismuth quadruple therapy had the highest success rate of 85.6%, while clarithromycin triple therapy had the lowest success rate of 63.5%. Specifically, bismuth/metronidazole/tetracycline quadruple, metronidazole/tetracycline triple, levofloxacin/metronidazole/tetracycline quadruple, rifabutin/amoxicillin triple and amoxicillin/levofloxacin triple therapies had relatively higher success rates over 80%. Age, treatment duration, baseline conditions and first-line treatment used were associated with success rate. CONCLUSIONS: Bismuth quadruple therapy was the most effective second-line regimen for H. pylori in this real-world study. Despite a very low success rate, clarithromycin-containing triple therapies were still commonly used as second-line regimens.


Asunto(s)
Antibacterianos , Claritromicina , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Estudios Retrospectivos , Femenino , Masculino , Helicobacter pylori/efectos de los fármacos , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Claritromicina/uso terapéutico , Hong Kong , Adulto , Anciano , Resultado del Tratamiento , Metronidazol/uso terapéutico , Retratamiento , Amoxicilina/uso terapéutico , Insuficiencia del Tratamiento , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Levofloxacino/uso terapéutico
10.
J Pain Res ; 17: 2111-2120, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903397

RESUMEN

Objective: To separate the resting-state network of patients with dental pain using independent component analysis (ICA) and analyze abnormal changes in functional connectivity within as well as between the networks. Patients and Methods: Twenty-three patients with dental pain and 30 healthy controls participated in this study. We extracted the resting-state functional network components of both using ICA. Functional connectivity differences within 14 resting-state brain networks were analyzed at the voxel level. Directional interactions between networks were analyzed using Granger causality analysis. Subsequently, functional connectivity values and causal coefficients were assessed for correlations with clinical parameters. Results: Compared to healthy controls, we found enhanced functional connectivity in the left superior temporal gyrus of anterior protrusion network and the right Rolandic operculum of auditory network in patients with dental pain (p<0.01 and cluster-level p<0.05, Gaussian random field corrected). In contrast, functional connectivity of the right precuneus in the precuneus network was reduced, and were significantly as well as negatively correlated to those of the Visual Analogue Scale (r=-4.93, p=0.017), Hamilton Anxiety Scale (r=-0.46, p=0.027), and Hamilton Depression Scale (r=-0.563, p<0.01), using the Spearman correlation analysis. Regarding the causal relationship between resting-state brain networks, we found increased connectivity from the language network to the precuneus in patients with dental pain (p<0.05, false discovery rate corrected). However, the increase in causal coefficients from the verbal network to the precuneus network was independent of clinical parameters. Conclusion: Patients with toothache exhibited abnormal functional changes in cognitive-emotion-related brain networks, such as the salience, auditory, and precuneus networks, thereby offering a new imaging basis for understanding central neural mechanisms in dental pain patients.

11.
Nanomicro Lett ; 16(1): 218, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884868

RESUMEN

Microgels prepared from natural or synthetic hydrogel materials have aroused extensive attention as multifunctional cells or drug carriers, that are promising for tissue engineering and regenerative medicine. Microgels can also be aggregated into microporous scaffolds, promoting cell infiltration and proliferation for tissue repair. This review gives an overview of recent developments in the fabrication techniques and applications of microgels. A series of conventional and novel strategies including emulsification, microfluidic, lithography, electrospray, centrifugation, gas-shearing, three-dimensional bioprinting, etc. are discussed in depth. The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy. Additionally, we expound on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering. Through stimulating innovative ideas, the present review paves new avenues for expanding the application of microgels in cell delivery techniques.

12.
Int J Biol Macromol ; 270(Pt 2): 132409, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38768918

RESUMEN

Suture pull-through is a clinical problem in meniscus repair surgery due to the sharp leading edge of sutures. Several tissue adhesives have been developed as an alternative to traditional suturing; however, there is still no suitable tissue adhesive specific for meniscus repair treatment due to unsatisfactory biosafety, biodegradable, sterilizable, and tissue-bonding characteristics. In this study, we used a tissue adhesive composed of chitosan hydrochloride reacted with oxidative periodate-oxidized dextran (ChitHCl-DDA) combined with a chitosan-based hydrogel and oxidative dextran to attach to the meniscus. We conducted viscoelastic tests, viscosity tests, lap shear stress tests, Fourier transform infrared (FTIR) spectroscopy, swelling ratio tests, and degradation behavior tests to characterize these materials. An MTT assay, alcian blue staining, migration assay, cell behavior observations, and protein expression tests were used to understand cell viability and responses. Moreover, ex vivo and in vivo tests were used to analyze tissue regeneration and biocompatibility of the ChitHCl-DDA tissue adhesive. Our results revealed that the ChitHCl-DDA tissue adhesive provided excellent tissue adhesive strength, cell viability, and cell responses. This tissue adhesive has great potential for torn meniscus tissue repair and regeneration.


Asunto(s)
Materiales Biocompatibles , Quitosano , Regeneración , Adhesivos Tisulares , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Animales , Regeneración/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Quitosano/química , Quitosano/farmacología , Ensayo de Materiales , Menisco/efectos de los fármacos , Dextranos/química , Supervivencia Celular/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Conejos , Lesiones de Menisco Tibial/cirugía , Humanos , Inyecciones
13.
Hereditas ; 161(1): 17, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755697

RESUMEN

BACKGROUND: This study investigates the therapeutic mechanisms of dendrobine, a primary bioactive compound in Dendrobium nobile, for Metabolic Associated Fatty Liver Disease (MASLD) management. Utilizing network pharmacology combined with experimental validation, the clinical effectiveness of dendrobine in MASLD treatment was assessed and analyzed. RESULTS: The study demonstrates significant improvement in liver function among MASLD patients treated with Dendrobium nobile. Network pharmacology identified key targets such as Peroxisome Proliferator-Activated Receptor Gamma (PPARG), Interleukin 6 (IL6), Tumor Necrosis Factor (TNF), Interleukin 1 Beta (IL1B), and AKT Serine/Threonine Kinase 1 (AKT1), with molecular docking confirming their interactions. Additionally, dendrobine significantly reduced ALT and AST levels in palmitic acid-treated HepG2 cells, indicating hepatoprotective properties and amelioration of oxidative stress through decreased Malondialdehyde (MDA) levels and increased Superoxide Dismutase (SOD) levels. CONCLUSION: Dendrobine mitigates liver damage in MASLD through modulating inflammatory and immune responses and affecting lipid metabolism, potentially by downregulating inflammatory mediators like TNF, IL6, IL1B, and inhibiting AKT1 and Signal Transducer and Activator of Transcription 3 (STAT3). This study provides a theoretical basis for the application of dendrobine in MASLD treatment, highlighting its potential as a therapeutic agent.


Asunto(s)
Alcaloides , Farmacología en Red , Enfermedad del Hígado Graso no Alcohólico , Alcaloides/uso terapéutico , Humanos , Síndrome Metabólico/complicaciones , Hígado/efectos de los fármacos , Hígado/patología , Hígado/fisiología , Pioglitazona/uso terapéutico , Metformina/uso terapéutico , Células Hep G2 , Dendrobium/química , Farmacología en Red/métodos , Mapas de Interacción de Proteínas , Simulación del Acoplamiento Molecular , Reacción en Cadena en Tiempo Real de la Polimerasa , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Redes Reguladoras de Genes
14.
J Assist Reprod Genet ; 41(8): 2173-2183, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38819714

RESUMEN

PURPOSE: This study aimed to evaluate the effectiveness of a random forest (RF) model in predicting clinical pregnancy outcomes from intrauterine insemination (IUI) and identifying significant factors affecting IUI pregnancy in a large Chinese population. METHODS: RESULTS: A total of 11 variables, including eight from female (age, body mass index, duration of infertility, prior miscarriage, and spontaneous abortion), hormone levels (anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone), and three from male (smoking, semen volume, and sperm concentration), were identified as the significant variables associated with IUI clinical pregnancy in our Chinese dataset. The RF-based prediction model presents an area under the receiver operating characteristic curve (AUC) of 0.716 (95% confidence interval, 0.6914-0.7406), an accuracy rate of 0.6081, a sensitivity rate of 0.7113, and a specificity rate of 0.505. Importance analysis indicated that semen volume was the most vital variable in predicting IUI clinical pregnancy. CONCLUSIONS: The machine learning-based IUI clinical pregnancy prediction model showed a promising predictive efficacy that could provide a potent tool to guide selecting targeted infertile couples beneficial from IUI treatment, and also identify which parameters are most relevant in IUI clinical pregnancy.


Asunto(s)
Inseminación Artificial , Aprendizaje Automático , Humanos , Femenino , Embarazo , Masculino , Adulto , Inseminación Artificial/métodos , Índice de Embarazo , China/epidemiología , Resultado del Embarazo , Hormona Luteinizante/sangre , Hormona Folículo Estimulante/sangre , Infertilidad/terapia , Hormona Antimülleriana/sangre , Curva ROC , Pueblos del Este de Asia
16.
Foods ; 13(8)2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38672942

RESUMEN

BACKGROUND: Dietary intervention is the preferred approach for the prevention and clinical management of gout. Nevertheless, the existing evidence regarding the influence of specific foods on gout is insufficient. METHODS: We used two-sample Mendelian randomization for genetic prediction to analyze the relationship between the intake of more than a dozen daily food items, such as pork, beef, cheese, and poultry, and dietary macronutrient intake (fat, protein, carbohydrates, and sugar) and the risk of developing gout and elevating the serum uric acid level. Inverse-variance weighted MR analyses were used as the main evaluation method, and the reliability of the results was tested by a sensitivity analysis. RESULTS: Cheese intake was associated with lower serum uric acid levels, and tea intake (OR = 0.523, [95%CI: 0.348~0.784], p = 0.002), coffee intake (OR = 0.449, [95%CI: 0.229~0.882], p = 0.020), and dried fruit intake (OR = 0.533, [95%CI: 0.286~0.992], p = 0.047) showed a preventive effect on the risk of gouty attacks. In contrast, non-oily fish intake (ß = 1.08, [95%CI: 0.24~1.92], p = 0.012) and sugar intake (ß = 0.34, [95%CI: 0.03~0.64], p = 0.030) were risk factors for elevated serum uric acid levels, and alcohol intake frequency (OR = 1.422, [95%CI: 1.079~1.873], p = 0.012) was a risk factors for gout predisposition. CONCLUSIONS: These results will significantly contribute to the formulation and refinement of nutritional strategies tailored to patients afflicted with gout.

18.
Eur J Med Chem ; 268: 116282, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38430853

RESUMEN

The Son of Sevenless 1 (SOS1) guanine nucleotide exchange factor, prevalent across eukaryotic species, plays a pivotal role in facilitating the attachment of RAS protein to GTP, thereby regulating the activation of intracellular RAS proteins. This regulation is part of a feedback mechanism involving SOS1, which allows both activators and inhibitors of SOS1 to exert control over downstream signaling pathways, demonstrating potential anti-tumor effects. Predominantly, small molecule modulators that target SOS1 focus on a hydrophobic pocket within the CDC25 protein domain. The effectiveness of these modulators largely depends on their ability to interact with specific amino acids, notably Phe890 and Tyr884. This interaction is crucial for influencing the protein-protein interaction (PPI) between RAS and the catalytic domain of SOS1. Currently, most small molecule modulators targeting SOS1 are in the preclinical research phase, with a few advancing to clinical trials. This progression raises safety concerns, making the assurance of drug safety a primary consideration alongside the enhancement of efficacy in the development of SOS1 modulators. This review encapsulates recent advancements in the chemical categorization of SOS1 inhibitors and activators. It delves into the evolution of small molecule modulation targeting SOS1 and offers perspectives on the design of future generations of selective SOS1 small molecule modulators.


Asunto(s)
Núcleo Familiar , Transducción de Señal , Descubrimiento de Drogas , Dominio Catalítico
19.
BMC Womens Health ; 24(1): 153, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38431586

RESUMEN

BACKGROUND: Concurrent chemoradiation is the standard treatment for advanced cervical cancer. However some patients still have a poor prognosis, and currently, there is no effective treatment for recurrence. In recent years, 125I seed implantation therapy has emerged as a treatment for advanced malignant tumors including surgically unresectable tumors, residual tumors after surgical resection, and metastatic tumors. However, the use of 125I seeds implantation in primary advanced cervical cancer has not been reported. In this study, we present a case of stage IIIB cervical cancer in a patient who had poor response to radiotherapy and chemotherapy. Subsequently, a radical hysterectomy was performed, and 125I radioactive seeds were successfully implanted during the surgery. This effectively controlled the lesions that were resistant to radiotherapy and had the potential to improve the prognosis. CASE PRESENTATION: A 56-year-old woman was diagnosed with stage IIIB (FIGO 2009) IIIC1r (FIGO 2018) squamous carcinoma of the cervix. After receiving 4 cycles of platinum-based chemotherapy and 30 rounds of radiotherapy, she underwent a radical hysterectomy. The localized cervical lesions were reduced, but there was no reduction in the size of the enlarged pelvic lymph nodes. Therefore, 125I seed implantation was performed under direct surgical vision for the right paracervical lesion and the enlarged pelvic lymph nodes on the right side. During the 18-month follow-up period, the enlarged lymph nodes subsided without any signs of recurrence or metastasis. CONCLUSION: Intraoperative implantation of 125I seeds in lesions that are difficult to control with radiotherapy or in sites at high risk of recurrence is a feasible and effective treatment option for patients with advanced squamous cervical cancer, and it may contribute to improved survival.


Asunto(s)
Neoplasias del Cuello Uterino , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/cirugía , Radioisótopos de Yodo/uso terapéutico , Terapia Combinada , Estudios Retrospectivos , Pronóstico , Histerectomía , Estadificación de Neoplasias
20.
J Robot Surg ; 18(1): 107, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38436785

RESUMEN

The purpose was to investigate the safety and advantages of different surgical approaches applied to overweight or obese cervical cancer patients by comparing their surgical and oncological outcomes. This is a retrospective cohort study. 382 patients with a body mass index of at least 24.0 kg/m2 and stage IB-IIA (The International Federation of Gynecology and Obstetrics, FIGO 2009) cervical cancer were enrolled, and then were divided into three groups: open radical hysterectomy (ORH) group, laparoscopic radical hysterectomy (LRH) group, and robot-assisted radical hysterectomy (RRH) group according to the surgical approach. IBM SPSS version 25.0 was used to analyze data. There were 51 patients in ORH group, 225 patients in LRH group and 106 patients in RRH group. In the comparison of surgical outcomes, compared to LRH and ORH, RRH had the shortest operating time, the least estimated blood loss, the shortest postoperative hospital stay, and the shortest recovery time for bowel function (P < 0.05). In the comparison of postoperative complications, ORH has the highest rate of postoperative infection and wound complication compared to LRH and RRH (P < 0.05), and RRH has the highest proportion of urinary retention. After a median follow-up time of 61 months, there was no statistically significant difference between the three groups in terms of 5-year overall survival (OS) rate and 5-year recurrence-free survival (RFS) rate, (P = 0.262, P = 0.453). In patients with overweight or obese cervical cancer, the long-term outcomes of the three surgical approaches were comparable, with RRH showing significant advantages over ORH and LRH in terms of surgical outcomes.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Neoplasias del Cuello Uterino , Femenino , Embarazo , Humanos , Sobrepeso , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/cirugía , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/métodos , Obesidad/complicaciones , Complicaciones Posoperatorias/epidemiología
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