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1.
Front Pediatr ; 12: 1338404, 2024.
Article En | MEDLINE | ID: mdl-38903768

Introduction: Hyponatremia is one of the most prevalent water-electrolyte disturbances encountered in clinical practice in pediatrics and can arise from various conditions. However, there are limited reports on hyponatremia in hospitalized infants. The objective of this study was to provide an overview of the incidence, etiologies, and clinical characteristics of hyponatremia in hospitalized babies (from birth to 3 years old) at a tertiary hospital. Method: Computer records of all hospitalized babies (from birth to 3 years old) with hyponatremia were extracted from the First Affiliated Hospital of Guangxi Medical University's clinical databases. Results: 801 patients from 39,019 hospital admissions were found to have hyponatremia and the overall prevalence of this condition was 2.05% in babies. Patients with hyponatremia due to aldosterone signaling abnormalities, neurological disorders, and liver diseases exhibited more severe outcomes than those with other etiologies. Conclusions: Various conditions can result in hyponatremia in hospitalized babies. Aldosterone signaling abnormalities were not that uncommon and it could lead to severe hyponatremia in babies.

2.
Endokrynol Pol ; 75(2): 216-221, 2024.
Article En | MEDLINE | ID: mdl-38646987

INTRODUCTION: Central precocious puberty (CPP) is a prevalent endocrine disorder. Research has indicated that pubertal development is linked to nutritional metabolism. Irisin, a novel myokine/adipokine, has been identified as a potential predictor of CPP in girls. This study aims to examine the relationship between serum irisin levels and CPP in boys. MATERIAL AND METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to measure serum irisin levels in 32 boys diagnosed with CPP and 33 prepubertal age-matched boys as normal controls (NC). To assess the impact of body mass index (BMI) on irisin levels, both the CPP and NC groups were divided into overweight/obese and normal-weight subgroups. Spearman correlation analysis was employed to assess the connection between irisin and clinical and biochemical parameters. Additionally, a receiver operating characteristic curve was utilised to determine the optimal threshold value for irisin. RESULTS: In the normal-weight subgroups, boys with CPP exhibited elevated irisin levels compared to controls, but not in the overweight/obese subgroups. The optimal cut-off value for irisin levels to predict CPP in the normal-weight groups was 93.09 ng/mL, yielding a sensitivity of 47.6% and a specificity of 100%. Furthermore, a positive correlation was noted between irisin levels and bone age (BA), bone age advancement (BA-CA), and BMI. CONCLUSIONS: Serum irisin levels correlate with BMI and pubertal development. Given its limited sensitivity, irisin level can only be utilised as a supplementary rather than a standalone diagnostic indicator for CPP.


Body Mass Index , Fibronectins , Puberty, Precocious , Child , Humans , Male , Case-Control Studies , Fibronectins/blood , Puberty, Precocious/blood , Puberty, Precocious/diagnosis
3.
Theranostics ; 13(13): 4449-4468, 2023.
Article En | MEDLINE | ID: mdl-37649599

Background: Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. Adoptive cell therapy using engineered T-cell receptors (TCRs) targeting cancer-testis antigens, such as Melanoma-associated antigen 3 (MAGE-A3), is a potential approach for the treatment of NSCLC. However, systematic analysis of T cell immune responses to MAGE-A3 antigen and corresponding antigen-specific TCR is still lacking. Methods: In this study, we comprehensively screened HLA-A2 restricted MAGE-A3 tumor epitopes and characterized the corresponding TCRs using in vitro artificial antigen presentation cells (APC) system, single-cell transcriptome and TCR V(D)J sequencing, and machine-learning. Furthermore, the tumor-reactive TCRs with killing potency was screened and verified. Results: We identified the HLA-A2 restricted T cell epitopes from MAGE-A3 that could effectively induce the activation and cytotoxicity of CD8+ T cells using artificial APC in vitro. A cohort of HLA-A2+ NSCLC donors demonstrated that the number of epitope specific CD8+ T cells increased in NSCLC than healthy controls when measured with tetramer derived from the candidate MAGE-A3 epitopes, especially epitope Mp4 (MAGE-A3: 160-169, LVFGIELMEV). Statistical and machine-learning based analyses demonstrated that the MAGE-A3-Mp4 epitope-specific CD8+ T cell clones were mostly in effector and proliferating state. Importantly, T cells artificially expressing the MAGE-A3-Mp4 specific TCRs exhibited strong MAGE-A3+ tumor cell recognition and killing effect. Cross-reactivity risk analysis of the candidates TCRs showed high binding stability to MAGE-A3-Mp4 epitope and low risk of cross-reaction. Conclusions: This work identified candidate TCRs potentially suitable for TCR-T design targeting HLA-A2 restricted MAGE-A3 tumor antigen.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Male , Humans , HLA-A2 Antigen , Epitopes , Receptors, Antigen, T-Cell , Antigens, Neoplasm
5.
Mol Genet Genomic Med ; 11(6): e2161, 2023 06.
Article En | MEDLINE | ID: mdl-36897110

BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD2) is a rare form of muscular dystrophy that is inherited as an autosomal dominant trait. In some patients, it is inherited from parental mosaicism, and this increases the recurrence risk significantly. The presence of mosaicism is underestimated due to the limitations of genetic testing and the difficulty in obtaining samples. METHODS: A peripheral blood sample from a 9-year-old girl with EDMD2 was analyzed by enhanced whole exome sequencing (WES). Sanger sequencing in her unaffected parents and younger sister was performed for validation. In the mother, ultra-deep sequencing and droplet digital PCR (ddPCR) in multiple samples (blood, urine, saliva, oral epithelium, and nail clippings) were performed in order to identify the suspected mosaicism of the variant. RESULTS: WES revealed a heterozygous mutation (LMNA, c.1622G>A) in the proband. Sanger sequencing of the mother suggested the presence of mosaicism. The ratio of mosaic mutation was confirmed in different samples by ultra-deep sequencing and ddPCR (19.98%-28.61% and 17.94%-28.33%, respectively). This inferred that the mosaic mutation may have occurred early during embryonic development and that the mother had gonosomal mosaicism. CONCLUSION: We described a case of EDMD2 caused by maternal gonosomal mosaicism which was confirmed by using ultra-deep sequencing and ddPCR. This study illustrates the importance of a systematic and comprehensive screening of parental mosaicism with more sensitive approaches and the use of multiple tissue samples.


Mosaicism , Muscular Dystrophy, Emery-Dreifuss , Humans , Female , Child , Muscular Dystrophy, Emery-Dreifuss/genetics , Mutation , Polymerase Chain Reaction , High-Throughput Nucleotide Sequencing
6.
Front Pediatr ; 11: 1092388, 2023.
Article En | MEDLINE | ID: mdl-36726778

Introduction: Hyperkalemia is a rare but severe condition in young children and usually discovered as a result of hemolysis of the blood samples taken. However, patients with defects in either aldosterone biosynthesis or function can also present with hyperkalemia- as well hyponatremia-associated, and metabolic acidosis. It is a challenge to make an accurate diagnosis of these clinical conditions. We conducted this study to investigate the clinical and genetic features of aldosterone signaling defects associated hyperkalemia in young children. Method: A retrospective review was conducted at the pediatric department of the First Affiliated Hospital of Guangxi Medical University from 2012 to 2022. Results: 47 patients with hyperkalemia were enrolled, of which 80.9% (n = 38) were diagnosed with primary hypoaldosteronism, including congenital adrenal hyperplasia due to 21-hydroxylase deficiency (n = 32), isolated hypoaldosteronism (n = 1) due to CYP11B2 gene mutation and Xp21 contiguous gene deletion syndrome (n = 1). Additionally, 4 patients were clinically-diagnosed with primary adrenal insufficiency. Nine patients were confirmed with aldosterone resistance, of which one child was diagnosed with pseudohypoaldosteronism (PHA) type 1 with a mutation in the NR3C2 gene and 3 children were identified with PHA type 2 due to novel mutations in either the CUL3 or KLHL3 genes. Five patients had PHA type 3 because of pathologies of either the urinary or intestinal tracts. Conclusions: The etiologies of infants with hyperkalemia associated with aldosterone defects were mostly due to primary hypoaldosteronism. An elevated plasma aldosterone level may be a useful biomarker for the diagnosis an aldosterone functional defect in patients presented with hyperkalemia. However, a normal plasma aldosterone level does rule out an aldosterone defect in either its biosynthesis or function, especially in young infants. Molecular genetic analyses can greatly help to clarify the complexity of disorders and can be used to confirm the diagnosis.

7.
J Clin Endocrinol Metab ; 108(8): 2078-2086, 2023 Jul 14.
Article En | MEDLINE | ID: mdl-36669772

CONTEXT: The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited. OBJECTIVE: This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes. DESIGN: A prospective, observational, posttrial study (NCT03290235). SETTING, PARTICIPANTS AND INTERVENTION: Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to <0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months. MAIN OUTCOMES MEASURES: Height SD score (Ht SDS) at 12, 24, and 36 months. RESULTS: A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred. CONCLUSIONS: PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.


Dwarfism, Pituitary , Human Growth Hormone , Humans , Child , Prospective Studies , Human Growth Hormone/therapeutic use , Growth Disorders/drug therapy , Dwarfism, Pituitary/drug therapy , Insulin-Like Growth Factor I , Polyethylene Glycols/adverse effects , Recombinant Proteins/adverse effects
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(11): 1231-1237, 2022 Nov 15.
Article Zh | MEDLINE | ID: mdl-36398549

OBJECTIVES: To summarize the skeletal muscle magnetic resonance imaging (MRI) features of the lower limbs in common subtypes of muscular dystrophy (MD) and the experience in the application of MRI in the diagnosis of MD. METHODS: A total of 48 children with MD who were diagnosed by genetic testing were enrolled as subjects. The muscle MRI features of the lower limbs were analyzed. Cumulative fatty infiltration score was calculated for each subtype, and the correlation of cumulative fatty infiltration score with clinical indices was analyzed for Duchenne muscular dystrophy (DMD). RESULTS: DMD was characterized by the involvement of the gluteus maximus and the adductor magnus. Becker muscular dystrophy was characterized by the involvement of the vastus lateralis muscle. Limb-girdle muscular dystrophy was characterized by the involvement of the adductor magnus, the vastus intermedius, the vastus medialis, and the vastus lateralis muscle. For DMD, the cumulative fatty infiltration score of the lower limb muscles was significantly correlated with age, course of the disease, muscle strength, and motor function (P<0.05), while it was not significantly correlated with the serum creatine kinase level (P>0.05). CONCLUSIONS: Different subtypes of MD have different MRI manifestations, and MRI may help with the diagnosis and assessment of MD.


Muscular Dystrophies, Limb-Girdle , Muscular Dystrophy, Duchenne , Child , Humans , Muscular Dystrophy, Duchenne/diagnostic imaging , Muscular Dystrophies, Limb-Girdle/diagnostic imaging , Muscular Dystrophies, Limb-Girdle/pathology , Muscle, Skeletal/diagnostic imaging , Magnetic Resonance Imaging/methods , Thigh/pathology
9.
Front Endocrinol (Lausanne) ; 13: 951552, 2022.
Article En | MEDLINE | ID: mdl-35966072

Background: Central precocious puberty (CPP) is a multifactorial and complex condition. Traditional studies focusing on a single indicator cannot always elucidate this panoramic condition but these may be revealed by using omics techniques. Objective: Proteomics and metabolomics analysis of girls with CPP were compared to normal controls and the potential biomarkers and pathways involved were explored. Methods: Serum proteins and metabolites from normal girls and those with CPP were compared by LC-MS/MS. Multivariate and univariate statistical analysis were used to identify the differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs). Functional annotation and pathway enrichment analysis were performed by using GO and KEGG databases, and candidate markers were screened. Finally, bioinformatic analysis was used to integrate the results of proteomics and metabolomics to find the key differential proteins, metabolites and potential biomarkers of CPP. Results: 134 DEPs were identified in girls with CPP with 71 up- and 63 down-regulated, respectively. Up-regulated proteins were enriched mainly in the extracellular matrix, cell adhesion and cellular protein metabolic processes, platelet degranulation and skeletal system development. The down-regulated proteins were mainly enriched in the immune response. Candidate proteins including MMP9, TIMP1, SPP1, CDC42, POSTN, COL1A1, COL6A1, COL2A1 and BMP1, were found that may be related to pubertal development. 103 DEMs were identified, including 42 up-regulated and 61 down-regulated metabolites which were mainly enriched in lipid and taurine metabolic pathways. KGML network analysis showed that phosphocholine (16:1(9Z)/16:1(9Z)) was involved in arachidonic acid, glycerophospholipid, linoleic acid and α-linolenic acid metabolism and it may be used as a biomarker of CPP. Conclusions: Our study is the first to integrate proteomics and metabolomics to analyze the serum of girls with CPP and we found some key differential proteins and metabolites as well as a potential biomarker for this condition. Lipid metabolism pathways are involved and these may provide a key direction to further explore the molecular mechanisms and pathogenesis of CPP.


Puberty, Precocious , Biomarkers , Chromatography, Liquid , Female , Humans , Proteomics , Tandem Mass Spectrometry
10.
Front Pharmacol ; 13: 955809, 2022.
Article En | MEDLINE | ID: mdl-36034802

Objective: Polyethylene glycol recombinant human growth hormone (PEG-rhGH, Jintrolong®) is the first long-acting rhGH preparation that is approved to treat children with growth hormone deficiency (GHD) in China. Clinical experience with dose selections of PEG-rhGH is scarce. The present study compared the efficacy and safety of a lower dose to increase dosing regimens of PEG-rhGH treatment. Methods: A multicenter, randomized, open-label, dose-comparison clinical study was conducted to compare the improvements in the height standard deviation score (Ht SDS), height velocity (HV), insulin-like growth factor-1 (IGF-1) SDS, and safety profiles of children with GHD who are treated with 0.2 mg/kg/week of PEG-rhGH dose or 0.14 mg/kg/week for 26 weeks. Results: Ht SDS, HV, and IGF-1 SDS increased significantly after PEG-rhGH treatment in the two dose groups (p < 0.05). The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). Ht SDS improvement in low-dose group was not non-inferiority to that in the high-dose group (p = 0.2987). The incidences of adverse events were comparable between the two groups. Conclusion: The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). PEG-rhGH at the dose of 0.14 mg/kg/week was effective and safe for children with GHD. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02908958.

11.
Front Neurol ; 13: 921785, 2022.
Article En | MEDLINE | ID: mdl-35873767

Creatine kinase (CK) as a biomarker has long been expected to be replaced by other fluid biomarkers for Duchenne muscular dystrophy (DMD) because it is independent of disease severity. Growing evidence has demonstrated that muscle-specific microRNAs, known as myomiRs, can act as biomarkers for monitoring muscle pathology and disease severity of DMD patients. To gain insights into the relationship between serum myomiRs and clinical assessment, we measured serum levels of miR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, and miR-499 in 48 DMD patients by using real-time quantitative reverse transcription polymerase chain reaction. These were then compared with age, muscle strength, muscle functions, CK levels, cardiac manifestations, and mutation types (deletions, duplications, and small mutations). When compared to 53 controls, the expression levels of myomiRs were all significantly elevated (p < 0.05). The receiver operating characteristic curves of all seven myomiRs reflected marked differences between DMD patients and healthy controls (p < 0.05). We also showed that serum levels of myomiRs were positively correlated with lower limb distal muscle strength in patients of all age groups. The levels of miR-499, miR-208b, miR-133a, and miR-133b had significant negative correlations with the time to be upright from the supine position (Gowers' time) and the time taken to climb four stairs in DMD patients older than 7 years. Serum levels of miR-1, miR-133a, miR-133b, and miR-499 in patients with cardiac involvement were remarkably higher than those in non-cardiac-involved patients. There was no significant difference in levels of myomiRs between the different mutation groups. Our results indicated that serum myomiRs could be considered as novel biomarkers for monitoring pathology/pathophysiology of DMD patients. In particular, miR-499, miR-208b, miR-133a, and miR-133b might have the ability to reflect the extent of muscle impairment.

12.
Small ; 18(27): e2106718, 2022 Jul.
Article En | MEDLINE | ID: mdl-35678595

Stable lithiophilic sites in 3D current collectors are the key to guiding the uniform Li deposition and thus suppressing the Li dendrite growth, but such sites created by the conventional surface decoration method are easy to be consumed along with cycling. In this work, carbon fiber (CF)-based 3D porous networks with built-in lithiophilic sites that are stable upon cycling are demonstrated. Such heterostructured architecture is constructed by the introduction of zeolitic imidazolate framework-8-based nanoparticles during the formation of the 3D fibrous carbonaceous network and the following annealing. The introduced Zn species are found to be re-distributed along the entire individual CF in the 3D network, and function as lithiophilic sites that favor the homogenous lithium nucleation and growth. The 3D network also presents a multi-scale porous structure that improves the space utilization of the host. The corresponding symmetric cells adopting such 3D anode demonstrate excellent cycling performance, especially at a high rate (300 cycles at 10 mA cm-2 with a capacity of 5 mA h cm-2 ). A full cell with LiFePO4 cathode shows a capacity retention of 98% after cycling at 1C for 300 cycles. This method provides an effective design strategy for 3D hosting electrodes in dendrite-free alkali metal anode applications.

13.
Endocr Connect ; 11(4)2022 Apr 22.
Article En | MEDLINE | ID: mdl-35258485

Objective: The objective of this study is to investigate the role of serum irisin level in diagnosis of central precocious puberty (CPP) in girls and its major determinants. Methods: This study was conducted in 67 girls with CPP, 19 girls with premature thelarche (PT) and 59 normal controls. The major determinants of irisin were assessed by multivariate linear regression (MLR) analysis. Propensity score matching (PSM) analysis was performed to minimize the bias that can result from BMI. A receiver operating characteristic curve was used to obtain the optimal threshold value of irisin. Results: The girls with CPP and PT had higher irisin levels than controls (P < 0.05). The optimal cutoff value of irisin levels for predicting CPP was 91.88 ng/mL, with a sensitivity of 70.1% and a specificity of 72.9%. MLR analysis showed that BMI was a predictor of irisin (P < 0.05). Serum irisin levels remained higher in the CPP girls than the controls with adjustment for BMI (P < 0.05). Conclusions: Increased serum irisin levels with CPP suggest that irisin is involved in puberty. However, due to low sensitivity and specificity, irisin level can only be used as an auxiliary indicator rather than a single diagnostic indicator of CPP.

14.
Front Physiol ; 12: 768122, 2021.
Article En | MEDLINE | ID: mdl-34858213

The local gill production of corticotropin releasing hormone (crh) and crh-receptor (crhr) is hypothesized to play important roles during seawater (SW) and freshwater (FW) acclimation in euryhaline black porgy (Acanthopagrus schlegelii). The mRNA expression of crh, crhr, and Na +/K + -ATPase (a-nka) was examined in SW and FW diencephalon (Dien) and in the gills at different exposure time by Q-PCR analysis. The in situ hybridization results indicate that crh mRNA hybridization signals were more abundant in FW fish in the gigantocellular (PMgc) and parvocellular (PMpc) part of the magnocellular preoptic nucleus versus SW fish. The crh and crhr-expressing cells were located in basal cells of gill filament. Furthermore, in vitro dexamethasone (DEX) treatment could increase the crh-system in the gill. Increased transcripts of the crh-system in the gill via in vitro and in vivo CRH treatments suggest that CRH may regulate the system in a local manner. The a-Nka cells were localized in the filament and secondary lamellae mitochondria rich cells (MRCs) of FW fish at 8 h and 1 day. a-Nka cells were seen in both filament and lamellae in the FW but much less in SW fish indicating that gills play key roles in black porgy osmoregulation. Gill crh and crhr play important roles in the response to salinity stress.

15.
Endocr Connect ; 10(9): 1147-1154, 2021 Sep 20.
Article En | MEDLINE | ID: mdl-34414898

OBJECTIVE: To evaluate the characteristics and significance of serum kisspeptin and makorin ring finger protein 3 (MKRN3) levels for the diagnosis of central precocious puberty (CPP) in girls. METHOD: Thirty four individuals with CPP, 17 individuals with premature thelarche (PT), and 28 age-matched prepubertal girls as normal control (NC) were recruited in this case-control study. Physical measurements included BMI and tests for breast, bone, and sexual characteristics. Biochemical measurements included serum LH, FSH, estradiol, insulin-like growth factor-1, MKRN3, and kisspeptin. Blood samples were taken from individuals with CPP and PT before the gonadotrophin-releasing hormone stimulation test and at 30, 60, 90, and 120 min after injection with triptorelin. RESULTS: Serum kisspeptin levels were higher in the CPP group when compared to the NC group (P = 0.020), while serum MKRN3 levels were lower in the two groups (P = 0.028). There were no significant differences between the CPP and PT groups as well as the PT and NC groups (all, P > 0.05). The cut-off value of serum kisspeptin differentiating patients with CPP from those without CPP was 0.40 nmol/L, with 82.4% sensitivity and 57.1% specificity, while the cut-off value of serum MKRN3 was 0.33 pmol/L, with 79.4% sensitivity and 53.6% specificity. The area under the curves (AUCs) of both kisspeptin and MKRN3 for differentiating those girls with CPP from PT were less than 0.5. CONCLUSIONS: Serum levels of kisspeptin and MKRN3 may play an auxiliary role in predicting CPP. However, the two measurements were not able to differentiate girls with CPP from PT and prepubertal control. This study emphasizes the need to search for markers to simplify the accurate diagnosis of CPP in girls.

16.
Int J Mol Med ; 47(3)2021 03.
Article En | MEDLINE | ID: mdl-33537799

Bethlem myopathy (BM) is an autosomal dominant or autosomal recessive disorder and is usually associated with mutations in the collagen VI genes. In the present study, the pathogenicity of a novel splice­site mutation was explored using RNA­sequencing in a family with suspected BM, and a myopathy panel was performed in the proband. The genetic status of all family members was confirmed using Sanger sequencing. Clinical data and magnetic resonance imaging (MRI) features were also documented. In silico analysis was performed to predict the effects of the splice mutation. RNA­sequencing and reverse transcription (RT)­PCR were used to assess aberrant splicing. Immunocytochemistry was conducted to measure collagen VI protein levels within the gastrocnemius and in cultured skin fibroblasts. The results revealed that three patients in the family shared a similar classic BM presentation. MRI revealed distinct patterns of fatty infiltration in the lower extremities. A novel splicing mutation c.736­1G>C in the collagen α­2 (VI) chain (COL6A2) gene was found in all three patients. In silico analysis predicted that the mutation would destroy the normal splice acceptor site. RNA­sequencing detected two abnormal splicing variants adjacent to the mutation site, and RT­PCR confirmed the RNA­sequencing findings. Furthermore, a defect in the collagen protein within cultured fibroblasts was detected using immunocytochemistry. The mutation c.736­1G>C in the COL6A2 gene caused aberrant splicing and led to premature termination of protein translation. In conclusion, these findings may improve our knowledge of mutations of the COL6A2 gene associated with BM and demonstrated that RNA­sequencing can be a powerful tool for finding the underlying mechanism of a disease­causing mutations at a splice site.


Collagen Type VI , Contracture , Muscular Dystrophies/congenital , Point Mutation , RNA Splice Sites , RNA-Seq , Transcription, Genetic , Adolescent , Adult , Collagen Type VI/biosynthesis , Collagen Type VI/genetics , Contracture/genetics , Contracture/metabolism , Humans , Male , Muscular Dystrophies/genetics , Muscular Dystrophies/metabolism
18.
J Pediatr Endocrinol Metab ; 33(12): 1605-1608, 2020 Dec 16.
Article En | MEDLINE | ID: mdl-33035187

OBJECTIVES: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes that is usually diagnosed in the first six months of life. CASE PRESENTATION: We report on a male infant with neonatal diabetes who presented with diabetic ketoacidosis at two months and 16 days. A novel homozygous missense mutation (c.259T>G) was identified in the ABCC8 gene. In this case, insulin was replaced with glimepiride at a dosage of 0.49 mg/kg/day at five months, and this achieved metabolic control and satisfactory growth as observed at follow-up. CONCLUSIONS: This report improves our understanding of the mutational spectrum of ABCC8, which is normally associated with NDM, and shows that the treatment regimen for this condition can be successfully switched from insulin therapy to the use of sulfonylurea.


Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Mutation , Sulfonylurea Compounds/therapeutic use , Sulfonylurea Receptors/genetics , Diabetes Mellitus/etiology , Diabetes Mellitus/pathology , Humans , Infant , Infant, Newborn , Male , Prognosis
19.
Front Neurol ; 11: 563609, 2020.
Article En | MEDLINE | ID: mdl-33071947

Background: Duchenne/Becker muscular dystrophy (DMD/BMD) is an X-linked recessive lethal neuromuscular disease. MicroRNAs expressed in striated muscle, myomiRs, have been proposed as its potential biomarkers. Serum creatine kinase (CK) is commonly used as a biomarker in clinical practice, but it is not reliable. The aim of this study was to assess whether serum levels of myomiRs has diagnostic value for detection of female DMD/BMD carriers with normal or elevated CK. Methods: Thirty four female carriers and 33 age-matched healthy female controls were enrolled. Peripheral blood samples were collected and serum miRNAs were extracted for measurement of miR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, and miR-499 by quantitative real-time polymerase chain reaction. Results: MiR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, and miR-499 were upregulated in all female carriers in comparison to healthy controls. MiR-1 (Spearman's rho = +0.406, p = 0.017) was correlated with CK in the female carrier group. Receiver operating characteristic curve analysis of all seven myomiRs showed that the area under the curve (AUC) for miR-499, miR-133b, miR-1, miR-208b, and miR-133a exceeded 70.0%, and for miR-206 and miR-208a exceeded 60.0%. MiR-133b and miR-499 were significantly increased in all female carriers, even those with normal CK. AUC for the combination of all seven miRNAs was 87.2%. CK (OR 0.406, 95% CI 0.000-0.001, p < 0.0001) and miR-499 (OR 0.323, 95% CI 0.023-0.106, p = 0.003) were considered to be independent predictors for female carriers presence in the multivariable regression analysis model. Conclusions: MiR-133b and miR-499 are potentially useful biomarkers for female carriers with DMD/BMD (including those with normal CK). The combination of all seven serum miRNAs and their respective combinations with CK have better diagnostic value for female carriers than either CK or any separate miRNA.

20.
Biomed Res Int ; 2020: 6416451, 2020.
Article En | MEDLINE | ID: mdl-33102586

Salmonella enteritidis can cause significant morbidity and mortality in humans and economic loss in the animal industry. Improving the innate immunity is an effective method to prevent S. enteritidis infection. Pediococcus pentosaceus is a Gram-positive coccus which had probiotics properties. Numerous previously published studies reported that probiotics were beneficial to gut microbiota by changing the intestinal flora structure and inhibiting the harmful microbial growth to enhance the innate immunity. We investigated the immunological effects of P. pentosaceus on Salmonella-infected chickens by the following experiment. A total of 120 broilers from AA line were fed and divided into 2 groups (treated and control groups) for the experiment from day 1. The control group was fed with the basic diet, while the treated group was fed with the basic diet adding P. pentosaceus microcapsule with the bacterial concentration of 1 g/kg in the feed and bacterial counts 2.5 × 109 CFU/g. All the birds were given with 0.5 ml of S. enteritidis bacterial suspension (109 CFU/ml) through oral cavity at day 9. The number of dead birds was recorded and used in the analysis. The bacterial culture method and quantitative real-time PCR analysis were used to evaluate the effects of P. pentosaceus on chickens infected with S. enteritidis and to ascertain the mechanism of the effect. The results showed that the P. pentosaceus could restrain the pathogenicity of S. enteritidis and reduce the death rate from 44.4% to 23.3%. The flora in the caecum exhibited "rising-declining" trends, and the gene (TLR4, MyD88, TRAF6 NF-κB, IFN-ß, TNF-a, IL6, and IL8) expression pattern was different between the experimental and control group. P. pentosaceus as a probiotic may competitively inhibit the growth of S. enteritidis and control the inflammatory response through regulating the gene expression which involved in the toll-like receptor pathway and inflammation pathway.


Chickens/microbiology , Pediococcus pentosaceus/immunology , Poultry Diseases/microbiology , Poultry Diseases/therapy , Probiotics/therapeutic use , Salmonella Infections, Animal/microbiology , Salmonella Infections, Animal/therapy , Salmonella enteritidis/pathogenicity , Animals , Avian Proteins/genetics , Avian Proteins/immunology , Cecum/immunology , Cecum/microbiology , Gastrointestinal Microbiome/genetics , Gastrointestinal Microbiome/immunology , Gene Expression , Immunity, Innate , Poultry Diseases/immunology , Salmonella Infections, Animal/immunology , Signal Transduction/genetics , Signal Transduction/immunology , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology
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