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1.
Ital J Pediatr ; 50(1): 162, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227971

RESUMEN

BACKGROUND: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. METHODS: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. RESULTS: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL. CONCLUSIONS: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity.


Asunto(s)
Hidrolasas de Éster Carboxílico , Síndrome Metabólico , Obesidad Infantil , Humanos , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Masculino , Femenino , Niño , Adolescente , Obesidad Infantil/complicaciones , Obesidad Infantil/sangre , Hidrolasas de Éster Carboxílico/sangre , China/epidemiología , Biomarcadores/sangre , Hígado Graso/sangre
2.
Int J Gen Med ; 17: 3443-3452, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39139709

RESUMEN

Objective: This study aims to investigate their correlation and predictive utility for in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI). Methods: We collected medical records of 668 patients who underwent PCI treatment from January 2022 to December 2022. Based on follow-up results (ISR defined as luminal narrowing ≥ 50% on angiography), all participants were divided into ISR and non-ISR groups. The XGBoost machine learning (ML) model was employed to identify the optimal predictive variables from a set of 31 variables. Discriminatory ability was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), while calibration and performance of the prediction models were assessed using the Hosmer-Lemeshow (HL) test and calibration plots. Clinical utility of each model was evaluated using decision curve analysis (DCA). Results: In the XGBoost importance ranking of predictive factors, LMR and RC ranked first and fourth, respectively. The AUC of the entire XGBoost ML model was 0.8098, whereas the model using traditional stepwise backward regression, comprising five predictive factors, had an AUC of 0.706. The XGBoost model showed superior predictive performance with a higher AUC, indicating better discrimination and predictive accuracy for ISR compared to traditional methods. Conclusion: LMR and RC are identified as cost-effective and reliable biomarkers for predicting ISR risk in ACS patients following drug-eluting stent (DES) implantation. LMR and RC represent cost-effective and reliable biomarkers for predicting ISR risk in ACS patients following drug-eluting stent implantation. Enhances the accuracy and clinical utility of ISR prediction models, offering clinicians a robust tool for risk stratification and personalized patient management.

3.
Clin Exp Nephrol ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39168882

RESUMEN

BACKGROUND: CKD currently affects 8.2% to 9.1% of the global population and the CKD mortality rate has increased during recent decades, making it necessary to identify new therapeutic targets. This study investigated the role of nicotinamide N-methyltransferase (NNMT) in renal fibrosis following ischemia-reperfusion injury (IRI), a key factor in chronic kidney disease (CKD) progression. METHODS: We established a mouse model with a knockdown of NNMT to investigate the impact of this enzyme on renal fibrosis after unilateral IRI. We then utilized histology, immunohistochemistry, and metabolomic analyses to investigate fibrosis markers and sphingolipid metabolism in NNMT-deficient mice. We also utilized an Nnmt lentivirus interference vector or an Nnmt overexpression plasmid to transfect mouse kidney proximal tubule cells, stimulated these cells with TGF-ß1, and then measured the pro-fibrotic response and the expression of the methylated and unmethylated forms of Sphk1. RESULTS: The results demonstrated that reducing NNMT expression mitigated fibrosis, inflammation, and lipid deposition, potentially through the modulation of sphingolipid metabolism. Histology, immunohistochemistry, and metabolomic analyses provided evidence of decreased fibrosis and enhanced sphingolipid metabolism in NNMT-deficient mice. NNMT mediated the TGF-ß1-induced pro-fibrotic response, knockdown of Nnmt decreased the level of unmethylated Sphk1 and increased the level of methylated Sphk1 in renal tubular epithelial cells. CONCLUSIONS: Our findings suggest that NNMT functions in sphingolipid metabolism and has potential as a therapeutic target for CKD. Further research is needed to elucidate the mechanisms linking NNMT to sphingolipid metabolism and renal fibrosis.

4.
J Inflamm Res ; 17: 5285-5291, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39157589

RESUMEN

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis classified as an autoimmune small-vessel vasculitis. Clinically, approximately 80% of affected organs in GPA involve the upper/lower respiratory tract and kidneys, with cardiovascular system involvement being rare. Here, we report a case of a 50-year-old female patient who presented with sudden-onset chest pain lasting for 1 hour. The patient had normal body temperature, and markers of infection such as C-reactive protein and erythrocyte sedimentation rate were within normal limits. Electrocardiography revealed ST-segment elevation in inferior, precordial, and posterior leads. Emergency coronary angiography showed no significant obstructive disease, prompting consideration of vasospastic angina given the patient's recurrent chest pain symptoms and findings on laboratory and imaging studies. The patient underwent treatment including coronary vasospasm antagonists and immunomodulation, resulting in clinical improvement and subsequent discharge. During a 7-month follow-up period, the patient did not experience any further adverse cardiovascular events.

5.
PLoS One ; 19(8): e0308532, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39116068

RESUMEN

Chlamydia psittaci-a zoonotic pathogen in birds-may be transmitted to humans, causing severe respiratory disease. Individuals working in or living near poultry farms are highly susceptible to C. psittaci infection. In this study, we assessed the prevalence and genotypes of C. psittaci in poultries and humans in three cities of China by collecting fecal samples from different poultry species and throat swab samples and serum samples from workers in poultry farms and zoos. These samples were screened by real-time fluorescence quantitative PCR (qPCR) targeting C. psittaci ompA. The positive samples were subjected to PCR amplification and sequencing of ompA. The strains detected in the samples were genotyped on the basis of the phylogenetic analysis of ompA sequences. In total, 3.13% (40/1278) poultry fecal samples were positive in the qPCR assay, whereas 3.82% (6/157) of throat swab samples and 42.59% (46/108) of serum samples from the workers were positive in the qPCR and indirect fluorescent antibody assays, respectively. The strains detected in the 32 poultry samples and 6 human samples were genotyped as type A, indicating that the workers were infected with C. psittaci that originated in poultry birds in farms. Additionally, eight peacocks showed strains with the genotype CPX0308, which was identified in China for the first time. Elucidating the distribution of C. psittaci in animals and poultry-related workers may provide valuable insights for reducing the risk of C. psittaci infection within a population.


Asunto(s)
Chlamydophila psittaci , Genotipo , Filogenia , Psitacosis , Animales , Chlamydophila psittaci/genética , Chlamydophila psittaci/aislamiento & purificación , China/epidemiología , Humanos , Psitacosis/epidemiología , Psitacosis/veterinaria , Psitacosis/microbiología , Prevalencia , Aves de Corral/microbiología , Ciudades/epidemiología , Heces/microbiología , Proteínas de la Membrana Bacteriana Externa/genética , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/epidemiología
6.
Int J Infect Dis ; 147: 107180, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39059574

RESUMEN

From January 2022 to November 2022, sporadic psittacosis occurred in Lishui city, China. The patients were presented with fever, cough, and pulmonary infiltration. Their clinical symptoms were not relieved after receiving cephalosporin, penicillin, beta-lactamase inhibitors, and quinolones. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid samples from the patients revealed Chlamydia psittaci infection. Then, three C. psittaci strains were isolated from the patients. Their whole genome sequences (WGSs) were obtained, and a core genome multilocus sequence typing (cgMLST) method was developed to study the population structure of C. psittaci. Using the constructed cgMLST method, 72 WGSs were divided into four related groups and ten sub-clusters. The Lishui strains formed a unique population of C. psittaci, which might represent a new variant of C. psittaci. In vitro antimicrobial susceptibility testing suggested that the Lishui strains were sensitive to tetracycline, macrolides, quinolones, and no drug-resistance was observed.

7.
Risk Manag Healthc Policy ; 17: 1779-1786, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38989249

RESUMEN

Introduction: Coronary artery disease (CAD) remains a significant global health challenge, with percutaneous coronary intervention (PCI) being a primary revascularization method. In-stent restenosis (ISR) post-PCI, although reduced, continues to impact patient outcomes. Inflammation and platelet activation play key roles in ISR development, emphasizing the need for accurate risk assessment tools. The systemic inflammation aggregation index (AISI) has shown promise in predicting adverse outcomes in various conditions but has not been studied in relation to ISR. Methods: A retrospective observational study included 1712 patients post-drug-eluting stent (DES) implantation. Data collected encompassed demographics, medical history, medication use, laboratory parameters, and angiographic details. AISI, calculated from specific blood cell counts, was evaluated alongside other variables using machine learning models, including random forest, Xgboost, elastic networks, logistic regression, and multilayer perceptron. The optimal model was selected based on performance metrics and further interpreted using variable importance analysis and the SHAP method. Results: Our study revealed that ISR occurred in 25.8% of patients, with a range of demographic and clinical factors influencing the risk of its development. The random forest model emerged as the most adept in predicting ISR, and AISI featured prominently among the top variables affecting ISR prediction. Notably, higher AISI values were positively correlated with an elevated probability of ISR occurrence. Comparative evaluation and visual analysis of model performance, the random forest model demonstrates high reliability in predicting ISR, with specific metrics including an AUC of 0.9569, accuracy of 0.911, sensitivity of 0.855, PPV of 0.81, and NPV of 0.948. Conclusion: AISI demonstrated itself as a significant independent risk factor for ISR following DES implantation, with an escalation in AISI levels indicating a heightened risk of ISR occurrence.

8.
Mol Cell Biochem ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980592

RESUMEN

Melanoma is a primary malignant tumor with high lethality, which occurs in the skin and eye tissues, while the molecular mechanisms of melanomagenesis remain largely unknown. Here, we show that death-associated protein-like 1 (DAPL1) expression is lower in melanoma tissues than in paracancerous tissues or nevus tissues, and Uveal melanoma patients with lower DAPL1 expression have a poorer survival rate than those with higher expression of DAPL1. Overexpression of DAPL1 inhibits proliferation of cultured melanoma cells, whereas knockdown of DAPL1 increases cell proliferation. Tumor transplantation experiment results also demonstrate that DAPL1 inhibits tumorigenesis of melanoma cells both in subretinal and subcutaneous tissues of nude mice in vivo. Finally, DAPL1 inhibits proliferation of melanoma cells by increasing the protein level of P21 via decreasing the ubiquitin mediated degradation of P21 and promoting its stability. Conversely, knockdown of P21 neutralizes the effects of inhibition of DAPL1 on melanoma cell proliferation and enhances the severity of melanoma tumorigenesis. These results suggest that DAPL1 is a novel melanoma tumor suppressor gene and thus a potential therapeutic target for melanoma.

9.
BMC Genomics ; 25(1): 631, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914930

RESUMEN

BACKGROUND: Current RNA-seq analysis software for RNA-seq data tends to use similar parameters across different species without considering species-specific differences. However, the suitability and accuracy of these tools may vary when analyzing data from different species, such as humans, animals, plants, fungi, and bacteria. For most laboratory researchers lacking a background in information science, determining how to construct an analysis workflow that meets their specific needs from the array of complex analytical tools available poses a significant challenge. RESULTS: By utilizing RNA-seq data from plants, animals, and fungi, it was observed that different analytical tools demonstrate some variations in performance when applied to different species. A comprehensive experiment was conducted specifically for analyzing plant pathogenic fungal data, focusing on differential gene analysis as the ultimate goal. In this study, 288 pipelines using different tools were applied to analyze five fungal RNA-seq datasets, and the performance of their results was evaluated based on simulation. This led to the establishment of a relatively universal and superior fungal RNA-seq analysis pipeline that can serve as a reference, and certain standards for selecting analysis tools were derived for reference. Additionally, we compared various tools for alternative splicing analysis. The results based on simulated data indicated that rMATS remained the optimal choice, although consideration could be given to supplementing with tools such as SpliceWiz. CONCLUSION: The experimental results demonstrate that, in comparison to the default software parameter configurations, the analysis combination results after tuning can provide more accurate biological insights. It is beneficial to carefully select suitable analysis software based on the data, rather than indiscriminately choosing tools, in order to achieve high-quality analysis results more efficiently.


Asunto(s)
RNA-Seq , Programas Informáticos , Flujo de Trabajo , RNA-Seq/métodos , Hongos/genética , Biología Computacional/métodos , Análisis de Secuencia de ARN/métodos , Empalme Alternativo
10.
Biomol Biomed ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38907736

RESUMEN

This study aims to analyze the correlation between Systemic Inflammatory Response Index (SIRI) and the severity of coronary artery stenosis in patients with coronary heart disease (CHD). It also aims to assess the predictive value of SIRI for the severity of coronary artery stenosis. A total of 2990 patients who underwent coronary angiography were included in this study. The Gensini score was used to estimate the severity of coronary vascular lesions. The predictive ability of SIRI for CHD was evaluated using receiver operating characteristic (ROC) curves. Binary multivariate logistic regression analysis was used to predict the likelihood of CHD based on the SIRI index. The results showed that people with higher SIRI index were more likely to have CHD (P < 0.001). After controlling for other risk factors, the highest quartile had a significantly higher incidence of coronary artery disease compared to the lowest quartile (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.73-3.92, P < 0.001). Furthermore, the Gensini score was significantly higher in the fourth quartile group (T4) compared to the first (T1) and second (T2) quartile groups (P < 0.001). Additionally, the SIRI index was significantly higher in the group with severe coronary artery lesions compared to the mild and moderate groups (P < 0.001). The SIRI index also showed a higher predictive ability for the extent of coronary lesions under the ROC curve compared to other commonly used markers, including platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) (P < 0.001). Therefore, SIRI index positively correlates with coronary artery stenosis in CHD patients, serving as an effective early screening marker for assessing stenosis severity.

11.
Plant Physiol Biochem ; 213: 108870, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38914038

RESUMEN

Populus, a significant fast-growing tree species with global afforestation and energy potential, holds considerable economic value. The abundant production of secondary xylem by trees, which serves as a vital resource for industrial purposes and human sustenance, necessitates the orchestration of various regulatory mechanisms, encompassing transcriptional regulators and microRNAs (miRNAs). Nevertheless, the investigation of microRNA-mediated regulation of poplar secondary growth remains limited. In this study, we successfully isolated a novel microRNA (Pag-miR257) from 84 K poplar and subsequently integrated it into the 35 S overexpression vector. The overexpression of Pag-miR257 resulted in notable increases in plant height, stem diameter, and fresh weight. Additionally, the overexpression of Pag-miR257 demonstrated a significant enhancement in net photosynthetic rate. The findings from the examination of cell wall autofluorescence indicated a substantial increase in both xylem area and the number of vessels in poplar plants overexpressing Pag-miR257. Furthermore, the cell wall of the Pag-miR257 overexpressing plants exhibited thickening as observed through transmission electron microscopy. Moreover, the Fourier Transforms Infrared (FTIR) analysis and phloroglucinol-HCl staining revealed an elevation in lignin content in Pag-miR257 overexpressing poplar plants. The findings of this study suggest that microRNA257 may play a role in the control of secondary growth in poplar stems, thereby potentially enhancing the development of wood engineering techniques for improved material and energy production.


Asunto(s)
MicroARNs , Populus , Populus/genética , Populus/crecimiento & desarrollo , Populus/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Xilema/metabolismo , Xilema/genética , Regulación de la Expresión Génica de las Plantas , Lignina/metabolismo , Lignina/biosíntesis , Plantas Modificadas Genéticamente , ARN de Planta/genética , Tallos de la Planta/genética , Tallos de la Planta/metabolismo , Tallos de la Planta/crecimiento & desarrollo , Fotosíntesis/genética , Pared Celular/metabolismo , Pared Celular/genética
12.
J Pediatr Endocrinol Metab ; 37(7): 652-656, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-38814569

RESUMEN

OBJECTIVES: To analyze and summarize the clinical characteristics and treatment of juvenile patients with type 1 diabetes mellitus (T1DM) complicated by early cataract. CASE PRESENTATION: This retrospective study collected clinical data from 210 children and adolescents newly diagnosed with T1DM who were admitted to the Department of Pediatrics, Tongji Hospital (Wuhan) between 2015 and 2022. Among 210 patients with T1DM, early cataract developed within 3 months before diabetes onset and 12 months thereafter in 2 (0.95 %) patients. The two patients were both females, aged 13 and 9 years, respectively. In both cases, cataracts in both eyes appeared in the early stages of T1DM, showing a short course and rapid development. After intensive insulin treatment for stringent and stable blood glucose control, one patient underwent cataract extraction with significant improvement, and her visual acuity returned to normal. The other patient received intensive insulin therapy and insulin pump therapy for 8 years. Subsequently, she underwent cataract surgery after achieving stable blood glucose levels, without complete recovery of vision. CONCLUSIONS: Cataract is a rare complication in the early stages of T1DM in children and adolescents. Ophthalmic surgery is the preferred treatment for patients with diabetic cataract after achieving stable glycemic control, which may help prevent visual impairment.


Asunto(s)
Catarata , Diabetes Mellitus Tipo 1 , Humanos , Catarata/diagnóstico , Femenino , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Adolescente , Niño , Estudios Retrospectivos , Pronóstico , Insulina/uso terapéutico , Insulina/administración & dosificación , Extracción de Catarata , Glucemia/análisis , Hipoglucemiantes/uso terapéutico
13.
Heliyon ; 10(8): e29653, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38660289

RESUMEN

Vitamin degradation may be affected differently by various food matrices. In this study, the kinetics of vitamin A, B1, and C degradation were directly compared in two types of enteral feeding formulas (EFFs) with different energy densities over a nine-month storage period at 4, 25, and 30 °C. The content of vitamins A, B1, and C was measured in the initial and stored formulas. The results justified the finding that the content of these vitamins was gradually decreased with storage time or temperature increases during the period. At each temperature during storage, the degradation of vitamins A, B1, and C followed first-order kinetics, and the rate constants calculated indicated the degradation of vitamins was temperature-dependent. The EFF-B exhibited a higher activation energy for vitamin degradation than that in the EFF-A, and the activation energy indicated an inverse relationship with the fat content of EFFs. The outcomes might provide a reference for the development and application of EEFs.

14.
J Mol Biol ; 436(17): 168530, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38462130

RESUMEN

Through an extensive literature survey, we have upgraded the Leaf Senescence Database (LSD v5.0; https://ngdc.cncb.ac.cn/lsd/), a curated repository of comprehensive senescence-associated genes (SAGs) and their corresponding mutants. Since its inception in 2010, LSD undergoes frequent updates to encompass the latest advances in leaf senescence research and its current version comprises a high-quality collection of 31,740 SAGs and 1,209 mutants from 148 species, which were manually searched based on robust experimental evidence and further categorized according to their functions in leaf senescence. Furthermore, LSD was greatly enriched with comprehensive annotations for the SAGs through meticulous curation using both manual and computational methods. In addition, it was equipped with user-friendly web interfaces that facilitate text queries, BLAST searches, and convenient download of SAG sequences for localized analysis. Users can effortlessly navigate the database to access a plethora of information, including literature references, mutants, phenotypes, multi-omics data, miRNA interactions, homologs in other plants, and cross-links to various databases. Taken together, the upgraded version of LSD stands as the most comprehensive and informative plant senescence-related database to date, incorporating the largest collection of SAGs and thus bearing great utility for a wide range of studies related to plant senescence.


Asunto(s)
Bases de Datos Genéticas , Hojas de la Planta , Senescencia de la Planta , Hojas de la Planta/genética , Senescencia de la Planta/genética , Mutación , Biología Computacional/métodos , Genes de Plantas
15.
Plant Biotechnol J ; 22(8): 2113-2128, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38470397

RESUMEN

Plants face a relentless onslaught from a diverse array of pathogens in their natural environment, to which they have evolved a myriad of strategies that unfold across various temporal scales. Cell surface pattern recognition receptors (PRRs) detect conserved elicitors from pathogens or endogenous molecules released during pathogen invasion, initiating the first line of defence in plants, known as pattern-triggered immunity (PTI), which imparts a baseline level of disease resistance. Inside host cells, pathogen effectors are sensed by the nucleotide-binding/leucine-rich repeat (NLR) receptors, which then activate the second line of defence: effector-triggered immunity (ETI), offering a more potent and enduring defence mechanism. Moreover, PTI and ETI collaborate synergistically to bolster disease resistance and collectively trigger a cascade of downstream defence responses. This article provides a comprehensive review of plant defence responses, offering an overview of the stepwise activation of plant immunity and the interactions between PTI-ETI synergistic signal transduction.


Asunto(s)
Inmunidad de la Planta , Transducción de Señal , Receptores de Reconocimiento de Patrones/metabolismo , Receptores de Reconocimiento de Patrones/inmunología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Plantas/inmunología , Plantas/metabolismo , Resistencia a la Enfermedad/inmunología
16.
Cell Rep ; 43(4): 114010, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38536817

RESUMEN

Although the small GTPase RAB37 acts as an organizer of autophagosome biogenesis, the upstream regulatory mechanism of autophagy via guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange in maintaining retinal function has not been determined. We found that retinitis pigmentosa GTPase regulator (RPGR) is a guanine nucleotide exchange factor that activates RAB37 by accelerating GDP-to-GTP exchange. RPGR directly interacts with RAB37 via the RPGR-RCC1-like domain to promote autophagy through stimulating exchange. Rpgr knockout (KO) in mice leads to photoreceptor degeneration owing to autophagy impairment in the retina. Notably, the retinopathy phenotypes of Rpgr KO retinas are rescued by the adeno-associated virus-mediated transfer of pre-trans-splicing molecules, which produce normal Rpgr mRNAs via trans-splicing in the Rpgr KO retinas. This rescue upregulates autophagy through the re-expression of RPGR in KO retinas to accelerate GDP-to-GTP exchange; thus, retinal homeostasis reverts to normal. Taken together, these findings provide an important missing link for coordinating RAB37 GDP-GTP exchange via the RPGR and retinal homeostasis by autophagy regulation.


Asunto(s)
Autofagia , Proteínas Portadoras , Proteínas del Ojo , Factores de Intercambio de Guanina Nucleótido , Ratones Noqueados , Retina , Proteínas de Unión al GTP rab , Animales , Retina/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab/genética , Ratones , Humanos , Factores de Intercambio de Guanina Nucleótido/metabolismo , Factores de Intercambio de Guanina Nucleótido/genética , Proteínas del Ojo/metabolismo , Proteínas del Ojo/genética , Células HEK293 , Ratones Endogámicos C57BL , Guanosina Trifosfato/metabolismo , Guanosina Difosfato/metabolismo , Unión Proteica
17.
New Phytol ; 242(5): 2043-2058, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38515251

RESUMEN

MicroRNAs are essential in plant development and stress resistance, but their specific roles in drought stress require further investigation. Here, we have uncovered that a Populus-specific microRNAs (miRNA), miR6445, targeting NAC (NAM, ATAF, and CUC) family genes, is involved in regulating drought tolerance of poplar. The expression level of miR6445 was significantly upregulated under drought stress; concomitantly, seven targeted NAC genes showed significant downregulation. Silencing the expression of miR6445 by short tandem target mimic technology significantly decreased the drought tolerance in poplar. Furthermore, 5' RACE experiments confirmed that miR6445 directly targeted NAC029. The overexpression lines of PtrNAC029 (OE-NAC029) showed increased sensitivity to drought compared with knockout lines (Crispr-NAC029), consistent with the drought-sensitive phenotype observed in miR6445-silenced strains. PtrNAC029 was further verified to directly bind to the promoters of glutathione S-transferase U23 (GSTU23) and inhibit its expression. Both Crispr-NAC029 and PtrGSTU23 overexpressing plants showed higher levels of PtrGSTU23 transcript and GST activity while accumulating less reactive oxygen species (ROS). Moreover, poplars overexpressing GSTU23 demonstrated enhanced drought tolerance. Taken together, our research reveals the crucial role of the miR6445-NAC029-GSTU23 module in enhancing poplar drought tolerance by regulating ROS homeostasis. This finding provides new molecular targets for improving the drought resistance of trees.


Asunto(s)
Resistencia a la Sequía , Glutatión Transferasa , MicroARNs , Proteínas de Plantas , Populus , Especies Reactivas de Oxígeno , Adaptación Fisiológica , Secuencia de Bases , Depuradores de Radicales Libres/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Populus/genética , Populus/fisiología , Populus/enzimología , Regiones Promotoras Genéticas/genética , Especies Reactivas de Oxígeno/metabolismo , Estrés Fisiológico/genética
19.
Artículo en Inglés | MEDLINE | ID: mdl-38379402

RESUMEN

BACKGROUND: This study reported a case of micropenis caused by a novel hemizygous mutation in the ADGRG2 gene, which aimed to expand the understanding of sexual dysplasia caused by ADGRG2 gene mutation. CASE PRESENTATION: We present the clinical data and genetic test results of a patient with micropenis admitted in September, 2022, to the Tongji Hospital. The patient was a 9-year-10- month-old male whose chief complaint was the presence of a short penis over a period of three years. In April 2016, the patient underwent corrective surgery for a clubbed penis. Upon admission to the study hospital, his height and weight were 145.0 cm (75-90th percentile) and 37.8 kg (50-75th percentile), respectively, and his BA was 12 years old. His physical characteristics included a normal face, bilateral testicle size of 2 ml, and penile length of about 3 cm. A gonadotrophin-releasing hormone-stimulating test revealed normal hypothalamic-pituitary-gonadal axis function. An HCG stimulation test indicated normal sperm production in the testis. Key abnormalities from auxiliary examinations included low testosterone and high ACTH, dehydroepiandrosterone sulfate, androstenedione, and 17-OH-P levels. Genetic testing revealed a new hemizygous mutation, a splicing mutation in intron 4 of the ADGRG2 gene (ChrX: 19040187 (NM_001079858.3): c.154 + 2T > A, inherited from the mother. CONCLUSION: This study reported a case of micropenis caused by a new hemizygous mutation in the ADGRG2 gene. This indicates the importance of genetic testing and gene-guided treatments to improve prognosis.

20.
BMC Pediatr ; 24(1): 13, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178064

RESUMEN

OBJECTIVE: This study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017-2022 in China. RESEARCH DESIGN AND METHODS: Single-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L. RESULTS: The median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8-10.0 years; 51.83% male). The mean annual incidence of T1DM was 2.98 per 1,000,000 child years. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020-2022 group and 2017-2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The frequency of DKA among the entire cohort was 57.93% (n = 95), and peaked in 2020 at 78.9% (15/19 patients). The frequency of DKA was not significantly higher in the 2020-2022 group compared with the 2017-2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020-2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2-0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2-0.6 ng/ml) in patients without DKA (p = 0.044). CONCLUSIONS: This study showed the annual incidence of T1DM was 2.98 per 1,000,000 child years, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020-2022 in China compared with the previous 3 years. Furthermore, the frequency of DKA was peaked in 2020, and were not significantly different between patients who were negative vs. positive for auto-antibodies.


Asunto(s)
Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Niño , Humanos , Masculino , Adolescente , Preescolar , Femenino , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Péptido C , Pandemias , Estudios Retrospectivos , Cetoacidosis Diabética/diagnóstico , Cetoacidosis Diabética/epidemiología
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