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Congenital adrenal hyperplasia (CAH) manifests as an autosomal recessive disorder characterized by defects in the enzymes responsible for steroid synthesis. This work aims to perform metabolic profiling of patients with CAH, screen key differential metabolites compared to the control group, and discover the associated metabolic pathways implicated in CAH. Serum samples obtained from 32 pediatric male patients with CAH and 31 healthy control group candidates were subjected to analysis using non-targeted metabolomics strategy using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A total of 278 differential metabolites were identified and annotated in KEGG. Operating characteristic curves (ROC) measurement exhibited 9 metabolites exhibiting high efficacy in differential diagnosis, as evidenced by an area under ROC curve (AUC) exceeding 0.85. Pathway analysis uncovered notable disruptions in steroid hormone biosynthesis (p <0.0001), purine metabolism and irregularities in lipid metabolism and amino acid metabolism, including tyrosine and alanine, in CAH patients. These findings demonstrate that metabolic pathways of purine, amino acid and lipid metabolism, apart from steroid hormone biosynthesis, may be disrupted and associated with CAH. This study helps provide insight into the metabolic profile of CAH patients and offers a new perspective for monitoring and administering follow-up care to CAH patients.
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BACKGROUND: Adverse intrauterine environment was believed to have deleterious effects on the gonadal function. However, the association between impaired intrauterine growth and fertility in adult males has not been established. OBJECTIVES: To compare the reproductive rates of males born small for gestational age (SGA), with low birth weight (LBW) or very low birth weight (VLBW) with control groups. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed to search PubMed, Web of Science, Cochrane Library, and Embase databases from inception to June 16, 2023. Cohort studies investigating the reproductive rates of males born SGA, with LBW or VLBW were included. A random or fixed effects model was used for different exposures. RESULTS: A total of 10 studies out of 3,801 records were included. Males born SGA showed a higher risk of infertility than the control group (odds ratio, OR = 0.91, 95% confidence interval, 95% CI 0.89-0.93, p = 0.000). The reproductive rates of individuals born with LBW or VLBW were lower than the control group (OR = 0.86, 95% CI 0.78-0.94, p = 0.001; OR = 0.57, 95% CI 0.40-0.81, p = 0.002, respectively). Participants were further divided into two age groups of 18-35 and 35-45 years. In both subgroups, the reproductive rates were lower in males born SGA, with LBW or VLBW compared with controls. Sensitivity analysis showed the robustness of the pooled estimates among LBW and VLBW. CONCLUSION: In summary, SGA, LBW, and VLBW were associated with a higher risk of male infertility in both early and middle adulthood. Achieving optimal intrauterine growth would be helpful to prevent male infertility.
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INTRODUCTION: Automated bone age assessment (BAA) is of growing interest because of its accuracy and time efficiency in daily practice. In this study, we validated the clinical applicability of a commercially available artificial intelligence (AI)-powered X-ray bone age analyzer equipped with a deep learning-based automated BAA system and compared its performance with that of the Tanner-Whitehouse 3 (TW-3) method. METHODS: Radiographs prospectively collected from 30 centers across various regions in China, including 900 Chinese children and adolescents, were assessed independently by six doctors (three experts and three residents) and an AI analyzer for TW3 radius, ulna, and short bones (RUS) and TW3 carpal bone age. The experts' mean estimates were accepted as the gold standard. The performance of the AI analyzer was compared with that of each resident. RESULTS: For the estimation of TW3-RUS, the AI analyzer had a mean absolute error (MAE) of 0.48 ± 0.42. The percentage of patients with an absolute error of < 1.0 years was 86.78%. The MAE was significantly lower than that of rater 1 (0.54 ± 0.49, P = 0.0068); however, it was not significant for rater 2 (0.48 ± 0.48) or rater 3 (0.49 ± 0.46). For TW3 carpal, the AI analyzer had an MAE of 0.48 ± 0.65. The percentage of patients with an absolute error of < 1.0 years was 88.78%. The MAE was significantly lower than that of rater 2 (0.58 ± 0.67, P = 0.0018) and numerically lower for rater 1 (0.54 ± 0.64) and rater 3 (0.50 ± 0.53). These results were consistent for the subgroups according to sex, and differences between the age groups were observed. CONCLUSION: In this comprehensive validation study conducted in China, an AI-powered X-ray bone age analyzer showed accuracies that matched or exceeded those of doctor raters. This method may improve the efficiency of clinical routines by reducing reading time without compromising accuracy.
Assessing bone age, or how developed a child's skeleton is, is important in medical care, but the standard method can be time-consuming. Using AI to automatically assess bone age from X-ray images may improve efficiency without reducing accuracy. In this study, we evaluated how well an AI-powered X-ray bone age analyzer performed compared to the established TannerWhitehouse 3 (TW-3) method. X-ray images from 900 Chinese children and adolescents were collected from 30 centers. Six doctors (three experts, three residents) and the AI system independently assessed the TW-3 radius, ulna, and short bones (RUS) and TW-3 carpal bone age. The experts' assessments were considered the gold standard. The AI analyzer had an average error of 0.48 years for TW3-RUS bone age, with 87% of assessments within 1 year of the experts. For TW3 carpal bone age, the AI had an average error of 0.48 years, with 89% within 1 year. These results were similar to or better than those of the resident raters. These findings show the AI-powered analyzer can assess bone age as accurately as human raters. This technology may improve clinical efficiency by reducing the time required for bone age assessments without compromising accuracy.
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PURPOSE OF REVIEW: The incidence of type 1 diabetes (T1D) in children and adolescents has been increased over decades worldwide. Recent studies showed that the trend of T1D incidences were different between developed and underdeveloped countries. This review aimed to summarize the changes of childhood T1D incidences in underdeveloped countries over the past decade. RECENT FINDINGS: Majority of the underdeveloped countries lacked of nationwide population-based studies on childhood T1D. We reviewed the trend of childhood T1D in important underdeveloped countries with available data in recent years. The incidences of childhood T1D in underdeveloped countries were low decades ago, but it increased significantly recently, particularly in the sub-Saharan African, Middle East and North African regions. SUMMARY: The incidences of childhood T1D increased significantly in underdeveloped countries, especially in the sub-Saharan African, Middle East and North African regions. T1D registry and population-based studies are helpful to understand the situation and characteristic of childhood T1D in underdeveloped countries.
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Países en Desarrollo , Diabetes Mellitus Tipo 1 , Humanos , Niño , Diabetes Mellitus Tipo 1/epidemiología , Incidencia , Adolescente , Medio Oriente/epidemiología , África del Sur del Sahara/epidemiologíaRESUMEN
A minority of children born small for gestational age (SGA) may experience catch-up growth failure and remain short in adulthood. However, the underlying causes and mechanisms of this phenomenon are not yet fully comprehended. We reviewed the present state of research concerning the growth hormone-insulin-like growth factor axis and growth plate in SGA children who fail to achieve catch-up growth. Additionally, we explored the factors influencing catch-up growth in SGA children and potential molecular mechanisms involved. Furthermore, we considered the potential benefits of supplementary nutrition, specific dietary patterns, probiotics and drug therapy in facilitating catch-up growth.
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Recién Nacido Pequeño para la Edad Gestacional , Humanos , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Recién Nacido , Niño , Trastornos del Crecimiento , Hormona de Crecimiento Humana , Desarrollo Infantil/fisiologíaRESUMEN
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 (0.95â¯%) 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.
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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 terapéuticoRESUMEN
Autism spectrum disorder (ASD) is a neurological disorder associated with brain inflammation. The underlying mechanisms could be attributed to the activation of PI3K signaling in the inflamed brain of ASD. Multiple studies highlight the role of GRPR in regulating ASD like abnormal behavior and enhancing the PI3K signaling. However, the molecular mechanism by which GRPR regulates PI3K signaling in neurons of individuals with ASD is still unclear. In this study, we utilized a maternal immune activation model to investigate the effects of GRPR on PI3K signaling in the inflamed brain of ASD mice. We used HT22 cells with and without GRPR to examine the impact of GRP-GRPR on the PI3K-AKT pathway with IL-6 treatment. We analyzed a dataset of hippocampus samples from ASD mice to identify hub genes. Our results demonstrated increased expression of IL-6, GRPR, and PI3K-AKT signaling in the hippocampus of ASD mice. Additionally, we observed increased GRPR expression and PI3K-AKT/mTOR activation in HT22 cells after IL-6 treatment, but decreased expression in HT22 cells with GRPR knockdown. NetworkAnalyst identified GSK-3ß as the most crucial gene in the PI3K-AKT/mTOR pathway in the hippocampus of ASD. Furthermore, we found that IL-6 upregulated the expression of GSK-3ß in HT22 cells by upregulating GRP-GRPR. Our findings suggest that IL-6 can enhance the activation of PI3K-AKT/mTOR-GSK-3ß in hippocampal neurons of ASD mice by upregulating GRPR.
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Trastorno del Espectro Autista , Trastorno Autístico , Hipocampo , Interleucina-6 , Animales , Ratones , Trastorno del Espectro Autista/metabolismo , Trastorno Autístico/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hipocampo/metabolismo , Interleucina-6/metabolismo , Neuronas , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Receptores de Bombesina/metabolismoRESUMEN
Objective: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with significant genetic heterogeneity. The ZIC gene family can regulate neurodevelopment, especially in the cerebellum, and has been implicated in ASD-like behaviors in mice. We performed bioinformatic analysis to identify the ZIC gene family in the ASD cerebellum. Methods: We explored the roles of ZIC family genes in ASD by investigating (i) the association of ZIC genes with ASD risk genes from the Simons Foundation Autism Research Initiative (SFARI) database and ZIC genes in the brain regions of the Human Protein Atlas (HPA) database; (ii) co-expressed gene networks of genes positively and negatively correlated with ZIC1, ZIC2, and ZIC3, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and receiver operating characteristic (ROC) curve analysis of genes in these networks; and (iii) the relationship between ZIC1, ZIC2, ZIC3, and their related genes with cerebellar immune cells and stromal cells in ASD patients. Results: (i) ZIC1, ZIC2, and ZIC3 were associated with neurodevelopmental disorders and risk genes related to ASD in the human cerebellum and (ii) ZIC1, ZIC2, and ZIC3 were highly expressed in the cerebellum, which may play a pathogenic role by affecting neuronal development and the cerebellar internal environment in patients with ASD, including immune cells, astrocytes, and endothelial cells. (iii) OLFM3, SLC27A4, GRB2, TMED1, NR2F1, and STRBP are closely related to ZIC1, ZIC2, and ZIC3 in ASD cerebellum and have good diagnostic accuracy. (iv) ASD mice in the maternal immune activation model demonstrated that Zic3 and Nr2f1 levels were decreased in the immune-activated cerebellum. Conclusion: Our study supports the role of ZIC1, ZIC2, and ZIC3 in ASD pathogenesis and provides potential targets for early and accurate prediction of ASD.
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Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype-phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism. Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: ⢠Aarskog-Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: ⢠We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype-phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.
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Anomalías Múltiples , Cara , Enfermedades Genéticas Ligadas al Cromosoma X , Genitales Masculinos , Factores de Intercambio de Guanina Nucleótido , Niño , Preescolar , Femenino , Humanos , Masculino , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico , Enanismo/genética , Enanismo/diagnóstico , Enanismo/tratamiento farmacológico , Cara/anomalías , Estudios de Asociación Genética , Genitales Masculinos/anomalías , Factores de Intercambio de Guanina Nucleótido/genética , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/diagnóstico , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/diagnóstico , Fenotipo , Dermatosis del Cuero Cabelludo/genética , Dermatosis del Cuero Cabelludo/diagnóstico , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/congénito , Anomalías Urogenitales/genética , Anomalías Urogenitales/diagnósticoRESUMEN
BACKGROUND: Recently, numerous studies have addressed the long-term effects of treatment with gonadotropin-releasing hormone analogue (GnRHa) in patients with central precocious puberty (CPP). However, the effects of GnRHa treatment on body mass index (BMI) in patients with CPP remain controversial. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the association between GnRHa treatment and BMI in patients with CPP. METHOD: A systematic search of databases, PubMed, EMBASE and Web of Science published before August 2021 identified relevant studies. The overall effect analysis was performed using STATA version statistical software 15.0. RESULTS: The study included a total of 28 studies. At the end of GnRHa treatment, the BMI-standard deviation score (BMI-SDS) was greater than baseline BMI-SDS (weighted mean difference (WMD) = 0.14, 95% CI, 0.04-0.23; P = .004), especially in girls with CPP (WMD = 0.15, 95% CI, 0.05-0.25; P = 0.005) and in patients with normal weight (WMD = 0.34, 95% CI, 0.19-0.48, P < 0.001). After reaching adult height, BMI-SDS returned to baseline, suggesting that the effect of GnRHa treatment on BMI would disappear as the child grew (WMD = -0.03, 95% CI, -0.39 to 0.32; P = 0.815). CONCLUSION: For patients with CPP, while treatment with GnRHa may increase the BMI in the short term after treatment, the BMI is likely to return to normal when the patients reach adult height.
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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.
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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/epidemiologíaRESUMEN
INTRODUCTION: Tricho-rhino-phalangeal syndrome (TRPS) is a rare genetic disorder characterized by craniofacial and skeletal abnormalities, which is caused by variants in the TRPS1 gene. METHODS: Clinical information and follow-up data were collected. Whole-exome sequencing (WES) was performed for variants and validated by Sanger sequencing. Bioinformatic analysis was performed to predict the pathogenicity of the identified variant. Moreover, wild-type and mutated TRPS1 vectors were constructed and transfected into human embryonic kidney (HEK) 293T cells. Immunofluorescence experiments were performed to assess the localization and expression of the mutated protein. Western blot analysis and RT-qPCR were used to detect the expression of downstream genes. RESULTS: The affected family members had typical craniofacial phenotype including sparse lateral eyebrows, pear-shaped nasal tip, and large prominent ears, plus skeletal abnormalities including short stature and brachydactyly. WES and Sanger sequencing identified the TRPS1 c.880_882delAAG variant in affected family members. In vitro functional studies showed that the TRPS1 variant did not affect the cellular localization and the expression of TRPS1, but the transcriptional repression effect of the TRPS1 on the RUNX2 and STAT3 was disturbed. The proband and his brother have been treated with growth hormone (GH) for 2 years until now, and we have observed the improvement of the linear growth in both. CONCLUSIONS: The variant of c.880_882delAAG in TRPS1 was responsible for the pathogenesis of the Chinese family with TRPS I. The treatment of GH could be beneficial for the height outcome in TRPS I patients, and earlier initiation and longer duration of the therapy in prepubertal or early pubertal stage could be associated with better height outcomes.
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Proteínas de Unión al ADN , Dedos/anomalías , Enfermedades del Cabello , Síndrome de Langer-Giedion , Nariz/anomalías , Masculino , Humanos , Proteínas de Unión al ADN/genética , Proteínas Represoras/genética , Síndrome de Langer-Giedion/tratamiento farmacológico , Síndrome de Langer-Giedion/genética , Síndrome de Langer-Giedion/patología , Síndrome , Hormona del Crecimiento , Biología Molecular , ChinaRESUMEN
The hydrodynamic behavior of phonons is of particular interest and importance owing to the strong demand for highly thermal conductive materials. Thermal transport in hydrodynamic regime becomes essentially nonlocal, which can give rise to a number of new and counterintuitive phenomena. In this work, we present a direct numerical study of nonlocal phonon thermal transport in graphene ribbon with vicinity geometry based on the phonon Boltzmann transport equation with first-principles inputs. We demonstrate the viscosity-dominated hydrodynamic transport behaviors with two abnormal thermal transport phenomena: heat current whirlpools and negative nonlocal effect, which originate from phonon viscosity. Phonon viscosity produces the vorticity of shear flows, leading to the backflow of the heat current and the generation of negative nonlocal vicinity response. The system average temperature and the ribbon width as well as the relative positions of the heat sources play a pivotal role in the occurrence of heat current whirlpools and negative nonlocal temperature response. The present work provides solid evidence for phonon hydrodynamic transport in graphene and a potential avenue for experimental detection in the future.
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Purpose: The present study aimed to explore the feasibility and safety of Transarterial embolization (TAE) in the treatment of obstetrics and gynecological hemorrhagic diseases transradial approach (TRA) compared to transfemoral approach (TFA). Methods: This cohort study was conducted on patients with obstetrics and gynecology bleeding diseases from June 2021 to November 2022. Clinical characteristics of the patients were comparable between the two groups. The success rate of puncture and embolization, radiation dose, operation time, fluoroscopy time (FT), as well as complications of each patient were recorded and then retrospectively analyzed the data. The European Five-dimensional Health Scale (ED-5Q) and visual analog scale (VAS) were used to assess the quality of life (QOL) on the day of discharge and 30 days after surgery between the two groups. Results: A total of 71 patients undergoing TAE were allocated to the TRA (n = 31) or TFA (n = 40) group in this study. Puncture and embolization were completed in all patients. Compared to the TFA group, the radiation dose of the TRA group (343.89 ± 108.81 mGy vs. 469.29 ± 198.66 mGy; p = 0.029) is significantly reduced. Minor complications occurred in only one patient (3.2%) in the TRA group. The surgery-related quality of life EQ-5D index score on the day of discharge in the TRA group (0.72 ± 0.12 vs. 0.65 ± 0.11; p = 0.017) was significantly higher than that in the TFA group, and the VAS score (2.55 ± 0.62 vs. 2.95 ± 0.85; p = 0.025) of catheter site discomfort was significantly lower in the TRA group were than in the TFA group, but no significant difference was observed in the QOL assessment at 30 days post-surgery. Conclusion: Transradial approach TAE has comparable efficacy and safety to TFA TAE in treating obstetrics and gynecological bleeding diseases. This access can improve patient QOL without affecting surgical safety.
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AIMS: To investigate the potential of imDCs with high expression of HO-1 in preventing or delaying the onset of Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice. MATERIALS AND METHODS: The phenotypic features of DCs in each group were assessed using flow cytometry. Western blot analysis was used to confirm the high expression of HO-1 in imDCs induced with CoPP. Additionally, flow cytometry was used to evaluate the suppressive capacity of CoPP-induced imDCs on splenic lymphocyte proliferation. Finally, the preventive effect of CoPP-induced imDCs was tested in NOD mice. KEY FINDINGS: Compared to imDCs, CoPP-induced imDCs exhibited a reduced mean fluorescence intensity (MFI) of the co-stimulatory molecule CD80 on their surface (P < 0.05) and significantly increased HO-1 protein expression (P < 0.05). Following LPS stimulation, the MFI of co-stimulatory molecules CD80 and CD86 on the surface of CoPP-induced imDCs remained at a lower level (P < 0.05). Furthermore, there was a reduced proliferation rate of lymphocytes stimulated with anti-CD3/28 antibodies. The adoptive transfer of CoPP-imDCs significantly reduced the incidence of T1DM (16.66 % vs. control group: 66.67 %, P = 0.004). Furthermore, at 15 weeks of age, the insulitis score was also decreased in the CoPP-induced imDC treatment group (P < 0.05). There were no significant differences in serum insulin levels among all groups. SIGNIFICANCE: ImDCs induced with CoPP and exhibiting high expression of HO-1 demonstrate a robust ability to inhibit immune responses and effectively reduce the onset of diabetes in NOD mice. This finding suggests that CoPP-induced imDCs could potentially serve as a promising treatment strategy for T1DM.
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Diabetes Mellitus Tipo 1 , Animales , Ratones , Traslado Adoptivo , Células Cultivadas , Células Dendríticas , Diabetes Mellitus Tipo 1/prevención & control , Diabetes Mellitus Tipo 1/metabolismo , Hemo-Oxigenasa 1/metabolismo , Ratones Endogámicos NODRESUMEN
Studying parasitic nematodes, which generate a massive hazard to animal health, is more difficult than studying free-living nematodes as appropriate animal models are essential, and the relationship between parasites and hosts is extremely complex. Strongyloides stercoralis is an intestinal nematode parasite that mainly infects dogs, humans and other primates. Currently, S. stercoralis worms needed for research mainly rely on their natural host, the dog. This study explored a method of using Meriones meridianus as a model for S. stercoralis. The immunosuppressed M. meridianus were infected with S. stercoralis subcutaneously, and post-parasitic, first-stage larvae (PP L1) were detected in the faeces, with more larvae in female gerbils. In addition, parasitic females (PFs), third-stage larvae (L3s) and rhabditiform larvae were found primarily in the small intestines and lungs of infected gerbils. The PFs and auto-infective third-stage larvae (aL3s) obtained from M. meridianus are morphologically identical to those obtained from beagles and Meriones unguiculatus. Moreover, the infection of S. stercoralis caused changes to biochemical indicators in the serum and in the physiology of M. meridianus. The results demonstrated that M. meridianus can be infected by S. stercoralis, and this model provides a great tool for exploring the biological processes of this parasite and its interaction with the host.
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BACKGROUND: Previous studies have demonstrated that natural killer (NK) cells migrated into the liver from peripheral organs and exerted cytotoxic effects on hepatocytes in virus-induced liver failure. AIM: This study aimed to investigate the potential therapeutic role of chemokine receptors in the migration of NK cells in a murine hepatitis virus strain 3 (MHV-3)-induced fulminant hepatic failure (MHV-3-FHF) model and its mechanism. RESULTS: By gene array analysis, chemokine (C-C motif) receptor 5 (CCR5) was found to have remarkably elevated expression levels in hepatic NK cells after MHV-3 infection. The number of hepatic CCR5+ conventional NK (cNK) cells increased and peaked at 48 h after MHV-3 infection, while the number of hepatic resident NK (rNK) cells steadily declined. Moreover, the expression of CCR5-related chemokines, including macrophage inflammatory protein (MIP)-1α, MIP-1ß and regulated on activation, normal T-cell expressed and secreted (RANTES) was significantly upregulated in MHV-3-infected hepatocytes. In an in vitro Transwell migration assay, CCR5-blocked splenic cNK cells showed decreased migration towards MHV-3-infected hepatocytes, and inhibition of MIP-1ß or RANTES but not MIP-1α decreased cNK cell migration. Moreover, CCR5 knockout (KO) mice displayed reduced infiltration of hepatic cNK cells after MHV-3 infection, accompanied by attenuated liver injury and improved mouse survival time. Adoptive transfer of cNK cells from wild-type mice into CCR5 KO mice resulted in the abundant accumulation of hepatic cNK cells and aggravated liver injury. Moreover, pharmacological inhibition of CCR5 by maraviroc reduced cNK cell infiltration in the liver and liver injury in the MHV-3-FHF model. CONCLUSION: The CCR5-MIP-1ß/RANTES axis played a critical role in the recruitment of cNK cells to the liver during MHV-3-induced liver injury. Targeted inhibition of CCR5 provides a therapeutic approach to ameliorate liver damage during virus-induced acute liver injury.
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Fallo Hepático Agudo , Virus de la Hepatitis Murina , Animales , Ratones , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CCL5 , Quimiocinas , Quimiocinas CC , Células Asesinas Naturales , Receptores CCR5 , Receptores de QuimiocinaRESUMEN
Titanium meshes are widely utilized in alveolar bone augmentation, and this study aims to enhance the properties of titanium meshes through heat treatment (HT) and the synergistic finishing technology of electric field and flow field (EFSF). Our findings illustrate that the titanium mesh exhibits improved mechanical properties following HT treatment. The innovative EFSF technique, in combination with HT, has a substantial impact on improving the surface properties of titanium meshes. HT initiates grain fusion and reduces surface pores, resulting in enhanced tensile and elongation properties. EFSF further enhances these improvements by significantly reducing surface roughness and eliminating adhered titanium powder, a byproduct of selective laser melting printing. Increased hydrophilicity and surface-free energy are achieved after EFSF treatment. Notably, the EFSF-treated titanium mesh exhibits reduced bacterial adhesion and is non-toxic to osteoblast proliferation. These advancements increase its suitability for clinical alveolar bone augmentation.
RESUMEN
PURPOSE: To evaluate the effect of surface treatment on bonding strength between pure titanium formed by selective laser melting and porcelain. METHODS: Pure titanium strips (64) and cobalt-chromium alloy strips (16) were laser machined to meet ISO 9693 standards. The pure titanium specimens were divided into 4 groups according to the sandblasting pressure and interlayer material. The sandblasting pressure of 0.25 MPa of bonder porcelain group was TB1, the sandblasting pressure of 0.25 MPa of gold coating group was TG1, the sandblasting pressure of 0.45 MPa of bonder porcelain group was TB2, and the sandblasting pressure of 0.45 MPa of the gold coating group was TG2(n=16). After porcelain fusing, half of the specimens in each group were tested for three-point bend bonding strength, and the other half were tested after 10 000 cycles of thermal cycling(n=8). The bonding strength of cobalt-chromium alloy after sandblasting at 0.25 MPa and 0.45 MPa was taken as the control group and recorded as group C1, C2(n=8). The bonding strength was tested using classical three-point bending experiment. The surface roughness of pure titanium was measured by laser scanning confocal microscope(LSCM). Field emission scanning electron microscopy(FE-SEM) was used to observe the interface morphology of titanium-ceramic. The surface morphology of titanium after porcelain stripping was observed with stereomicroscope and fracture modes were analyzed by it. Graphpad Prism 8.0 software package was used for statistical analysis of the data. RESULTS: The bonding strength of group TG2 was (40.16±3.97) MPa and (37.38±2.39) MPa of group TG1, which were significantly higher than that of group TB2 (36.32±1.44) MPa and group TB1 (33.75±2.31) MPa (Pï¼0.05). The bonding strength of group TB2 with 0.45 MPa sandblasting was significantly higher than that of group TB1 with 0.25 MPa sandblasting (Pï¼0.05). There was no significant decrease in titanium-ceramic bonding strength before and after thermal cycling. When the sandblasting pressure increased from 0.25 MPa to 0.45 MPa, the roughness increased significantly (Pï¼0.05). The fracture modes were mixed. CONCLUSIONS: Under the conditions of this study, gold coating can significantly improve the bonding strength of Ti22 porcelain and SLM pure titanium than bonder porcelain, and increase of sandblasting pressure can further improve the bonding strength of titanium-porcelain. After 10 000 cycles of thermal cycling, the titanium-porcelain bonding strength did not decrease significantly.