ABSTRACT
Membrane lipoproteins serve as primary pro-inflammatory virulence factors in Mycoplasma genitalium. Membrane lipoproteins primarily induce inflammatory responses by activating Toll-like Receptor 2 (TLR2); however, the role of the metabolic status of urethral epithelial cells in inflammatory response remains unclear. In this study, we found that treatment of uroepithelial cell lines with M. genitalium membrane lipoprotein induced metabolic reprogramming, characterized by increased aerobic glycolysis, decreased oxidative phosphorylation, and increased production of the metabolic intermediates acetyl-CoA and malonyl-CoA. The metabolic shift induced by membrane lipoproteins is reversible upon blocking MyD88 and TRAM. Malonyl-CoA induces malonylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and malonylated GAPDH could dissociate from the 3' untranslated region of TNF-α and IFN-γ mRNA. This dissociation greatly reduces the inhibitory effect on the translation of TNF-α and IFN-γ mRNA, thus achieving fine-tuning control over cytokine secretion. These findings suggest that GAPDH malonylation following M. genitalium infection is an important inflammatory signal that plays a crucial role in urogenital inflammatory diseases.
ABSTRACT
Early and differential diagnosis of sepsis is essential to avoid unnecessary antibiotic use and further reduce patient morbidity and mortality. Here, we aimed to identify predictors of sepsis and advance a machine-learning strategy to predict sepsis-induced respiratory tract infection (RTI). Patients with sepsis and RTI were selected via retrospective analysis, and essential population characteristics and laboratory parameters were recorded. To improve the performance of the primary model and avoid over-fitting, a recursive feature elimination with cross-validation (RFECV) strategy was used to screen the optimal subset of biomarkers and construct nine machine-learning models based on this subset; the average accuracy, precision, recall, and F1-score were used for evaluation of the models. We identified 430 patients with sepsis and 686 patients with RTI. A total of 39 features were collected, with 23 features identified for initial model construction. Using the RFECV algorithm, we found that the XGBoost classifier, which only needed to include seven biomarkers, demonstrated the best performance among all prediction models, with an average accuracy of 89.24 ± 2.28, while the Ridge classifier, which included 11 biomarkers, had an average accuracy of only 83.87 ± 4.69. The remaining models had prediction accuracies greater than 88%. We developed nine models for predicting sepsis using a strategy that combined RFECV with machine learning. Among these models, the XGBoost classifier, which included seven biomarkers, showed the best performance and highest accuracy for predicting sepsis and may be a promising tool for the timely identification of sepsis.
Subject(s)
Algorithms , Biomarkers , Machine Learning , Respiratory Tract Infections , Sepsis , Humans , Sepsis/diagnosis , Sepsis/blood , Biomarkers/blood , Respiratory Tract Infections/diagnosis , Male , Female , Aged , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Complex interconnections are evident among gut microbiota, circulating metabolites, inflammatory cytokines, and the pathogenesis of abdominal aortic aneurysms (AAA), with the causal dynamics yet to be comprehensively elucidated. The primary objective of this study was to elucidate the potential causal relationships involving gut microbiota-mediated plasma metabolites, inflammatory cytokines, and AAA. METHODS: We utilized data from genome-wide association studies predominantly comprising individuals of European ancestry, encompassing four major gut microbiota signatures, 233 plasma metabolite signatures (N = 136,016), 91 inflammatory cytokine signatures (N = 14,824), and AAA signatures (N = 1,458,875). Mendelian randomization (MR), employed in a two-sample format, was utilized as a tool to investigate the potential causal pathways from gut microbiota to the development of AAA. Additionally, a two-step MR approach was employed to dissect the impact of plasma metabolites and inflammatory cytokines on the relationship between gut microbiota and AAA and to ascertain the mediated fractions. RESULTS: Our findings indicate that five phylum or family-identical bacteria, 175 plasma metabolites, and seven inflammatory factors are causally associated with AAA. Among them, five bacterial species from the same phylum or family, identified from different GWAS data, were strongly associated with AAA. Of these, two exhibited negative causality and three exhibited positive causality. We found that the phylum Firmicutes and the families Oscillospiraceae might reduce the risk of AAA, whereas the families Prevotellaceae, Sutterellaceae, and Aminobacteriaceae might increase the risk of AAA. Further screening indicated that phylum Firmicutes id.1672 (GCST90017114) may confer a protective effect against AAA by reducing triglyceride levels in medium/small high-density lipoprotein (HDL). CONCLUSION: MR analysis has delineated a causal pathway from gut microbiota, through plasma circulating metabolites and inflammatory cytokines, to the pathogenesis of AAA. The role of intestinal flora and certain biomarkers may provide a reference for the diagnosis of AAA, and contribute to the prevention, diagnosis, and treatment of AAA disease.
Subject(s)
Aortic Aneurysm, Abdominal , Cytokines , Gastrointestinal Microbiome , Genome-Wide Association Study , Mendelian Randomization Analysis , Aortic Aneurysm, Abdominal/microbiology , Aortic Aneurysm, Abdominal/blood , Aortic Aneurysm, Abdominal/genetics , Humans , Gastrointestinal Microbiome/physiology , Gastrointestinal Microbiome/genetics , Cytokines/blood , Male , Female , Inflammation/blood , Inflammation/geneticsABSTRACT
Sepsis is a kind of systemic inflammatory response syndrome caused by infection, which has high morbidity and mortality. Studies have shown that reducing sepsis-related liver injury and restoring liver function can reduce the morbidity and mortality of it. Current clinical treatment methods for sepsis have many disadvantages. Our study aimed to investigate the mechanism of sepsis-induced liver injury and to find a proper therapeutic target for sepsis. In this paper, we have found that when miR-324-3p was overexpressed, the inflammatory infiltration and and ferroptosis in liver injury cells aggravated. Further studies showed that overexpression of miR-324-3p could bind to the 3'-UTR of SNHG11 directly so as to decrease the expression level of SNHG11. Our study indicated that LncRNA SNGH11 can mediate the ferroptosis of liver injury cells induced by sepsis through the miR-324-3p/GPX4 axis. Suggesting that it is a new drug target for clinical treatment of sepsis and sepsis-associated liver injury, then we can improve the survival rate for sepsis patients.
Subject(s)
Ferroptosis , MicroRNAs , RNA, Long Noncoding , Sepsis , 3' Untranslated Regions , Ferroptosis/genetics , Liver , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Sepsis/geneticsABSTRACT
OBJECTIVE: To explore the clinical manifestations and genetic characteristics of patients with congenital central hypothyroidism due to variants of IGSF1 gene. METHODS: Clinical data, results of genetic testing, and follow-up of four patients admitted to Children's Hospital of Soochow University during 2017 to 2021 were retrospectively analyzed. RESULTS: All of the four patients were males. Patient 1 had presented neonatal jaundice, patients 2 and 3 were admitted for growth retardation during childhood, and thyroid function test indicated slightly low free thyroxine (FT4), patient 4 was found to have reduced FT4 in the neonatal period. Genetic testing revealed that all of the four patients have harbored pathogenic variants of the IGSF1 gene, which were all inherited from their mothers. The thyroid functions in all patients were well controlled with oral levothyroxine and regular follow-up. CONCLUSION: Pathogenic variants of the IGSF1 gene probably underlay the congenital central hypothyroidism with a variety of clinical manifestations, and genetic testing can facilitate the diagnosis at an early stage.
Subject(s)
Hypothyroidism , Child , Male , Infant, Newborn , Female , Humans , Retrospective Studies , Hypothyroidism/genetics , Genetic Testing , Mothers , Immunoglobulins/genetics , Membrane Proteins/geneticsABSTRACT
BACKGROUND: This study aimed to investigate the effects of LINC00240/miR-155/Nrf2 axis on trophoblast function and macrophage polarization in the pathogenesis of preeclampsia. METHODS: Bindings between LINC00240, miR-155 and Nrf2 were validated by dual luciferase reporter assay or RNA-immunoprecipitation. Cell proliferation, migration, invasion, and pyroptosis were detected by CCK-8, clone formation, wound healing, Transwell system, and flow cytometry, respectively. Macrophage polarization was tested by flow cytometry. The expression levels of LINC00240, miR-155, Nrf2, and oxidative stress and pyroptosis-related markers in in vitro and in vivo preeclampsia models were analyzed by qPCR, western blot, or ELISA assays. Blood pressure, urine protein levels, liver and kidney damages, and trophoblast markers in placenta tissues were further studied in vivo. RESULTS: Placenta tissues from preeclampsia patients and animals showed decreased LINC00240 and Nrf2 and increased miR-155 expression levels, and the decreased M2 macrophage polarization. LINC00240 directly bound and inhibited expression of miR-155, which then inhibited oxidative stress-induced pyroptosis, promoting proliferation, migration and invasion abilities of trophoblasts, and M2 macrophage polarization. Inhibition of miR-155 led to increased Nrf2 expression and similar changes as LINC00240 overexpression in trophoblast function and macrophage polarization. Overexpression of LINC00240 in in vivo preeclampsia model decreased blood pressure, urine protein, liver and kidney damages, increased fetal weight and length, and induced trophoblast function and M2 macrophage polarization. CONCLUSION: LINC00240 inhibited symptoms of preeclampsia through regulation on miR-155/Nrf2 axis, which suppressed oxidative stress-induced pyroptosis to improve trophoblast function and M2 macrophage polarization. LINC00240 could be a potential therapeutic target for preeclampsia.
Subject(s)
MicroRNAs , Pre-Eclampsia , RNA, Long Noncoding , Animals , Apoptosis , Cell Movement , Cell Proliferation , Female , Humans , Macrophages/metabolism , MicroRNAs/genetics , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Pre-Eclampsia/genetics , Pregnancy , Pyroptosis , RNA, Long Noncoding/genetics , Sincalide/metabolism , Trophoblasts/metabolismABSTRACT
BACKGROUND: Soybean is a globally important legume crop that provides a primary source of high-quality vegetable protein and oil. Seed protein content (SPC) is a valuable quality trait controlled by multiple genes in soybean. RESULTS: In this study, we performed quantitative trait loci (QTL) mapping, QTL-seq, and RNA sequencing (RNA-seq) to reveal the genes controlling protein content in the soybean by using the high protein content variety Nanxiadou 25. A total of 50 QTL for SPC distributed on 14 chromosomes except chromosomes 4, 12, 14, 17, 18, and 19 were identified by QTL mapping using 178 recombinant inbred lines (RILs). Among these QTL, the major QTL qSPC_20-1 and qSPC_20-2 on chromosome 20 were repeatedly detected across six tested environments, corresponding to the location of the major QTL detected using whole-genome sequencing-based QTL-seq. 329 candidate DEGs were obtained within the QTL region of qSPC_20-1 and qSPC_20-2 via gene expression profile analysis. Nine of which were associated with SPC, potentially representing candidate genes. Clone sequencing results showed that different single nucleotide polymorphisms (SNPs) and indels between high and low protein genotypes in Glyma.20G088000 and Glyma.16G066600 may be the cause of changes in this trait. CONCLUSIONS: These results provide the basis for research on candidate genes and marker-assisted selection (MAS) in soybean breeding for seed protein content.
Subject(s)
Chromosome Mapping , Genetic Association Studies , Glycine max/chemistry , Glycine max/genetics , Plant Proteins/analysis , Plant Proteins/genetics , Seeds/chemistry , Crops, Agricultural/chemistry , Crops, Agricultural/genetics , Gene Expression Regulation, Plant , Genetic Markers , Genetic Variation , Genotype , Quantitative Trait Loci , Sequence Analysis, RNAABSTRACT
Plasma fibronectin 1 (FN1) levels are elevated in individuals with pre-eclampsia (PE), which may be applied as a possible b marker for vascular endothelial injury during PE. In the present study, the possible role of FN1 in the pathogenesis of PE and regulation of apoptosis and autophagy in vascular endothelial cells was explored. Plasma FN1 levels in 80 patients with PE and 40 healthy pregnant individuals were measured using ELISA to verify its relationship with the severity of PE. pcDNA3.1-FN1 or FN1-small interfering (si) RNA was used to manipulate the expression of FN1 in human umbilical vein endothelial cells (HUVECs) to assess the effects of FN1 on cell apoptosis, autophagy, and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. It was found that upregulation of FN1 promoted apoptosis and autophagy, in addition to significantly inhibiting the activation of AKT and mTOR in HUVECs. By contrast, downregulation of FN1 expression inhibited cell apoptosis and autophagy, but increased AKT and mTOR phosphorylation in HUVECs that were cultured in serum samples obtained from patients with PE. Rescue experiments found that the PI3K/AKT inhibitor LY294002 reversed the effects of FN1-siRNA on apoptosis and autophagy in HUVECs cultured in serum from patients with PE. Therefore, data from the present study suggest that FN1 participates in the pathogenesis of PE by promoting apoptosis and autophagy in vascular endothelial cells, which is associated with the PI3K/AKT/mTOR signaling pathway.
Subject(s)
Endothelial Cells/pathology , Fibronectins/physiology , Pre-Eclampsia/etiology , Adult , Apoptosis , Autophagy , Case-Control Studies , Chromones/pharmacology , Endothelial Cells/metabolism , Female , Fibronectins/biosynthesis , Fibronectins/blood , Fibronectins/genetics , Gene Expression Regulation , Gene Knockdown Techniques , Genes, Reporter , Human Umbilical Vein Endothelial Cells , Humans , Morpholines/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Pre-Eclampsia/blood , Pre-Eclampsia/pathology , Pregnancy , Proto-Oncogene Proteins c-akt/metabolism , Severity of Illness Index , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolismABSTRACT
INTRODUCTION: Although ultrasonography has been reported to have similar diagnostic accuracy to magnetic resonance imaging, it is not a standard imaging modality for cervical cancer. We aimed to summarize the ultrasonographic features of rare primary cervical cancer. METHODS: This was a retrospective study of patients with cervical cancer who were diagnosed between June 2014 and October 2019. They were divided into common-type cervical cancer (ie, cervical squamous cell carcinoma) and rare-type cervical cancer groups including adenocarcinoma, adenosquamous carcinoma, and small cell carcinoma. All patients were staged according to the tumor, nodes, and metastases criteria. RESULTS: Of the 64 patients, the diagnosis was suspected on ultrasonography in 61 (95.3%) patients and missed on ultrasonography in three patients. The tumor size was smaller in the rare-type cervical cancer group (p<0.05). Hypoechoic lesions in common-type cervical cancer and isoechoic lesions accounted for 74.4% (32/43) and 61.9% (13/21) of patients in the rare-type cervical cancer group, respectively (p<0.001). Meanwhile, 67.4% (29/43) of tumors in common-type cervical cancer were exophytic, while 66.7% (14/21) in rare-type cervical cancer were endophytic (p=0.01). Color Doppler blood signals, as compared with normal cervical tissue, were found in all patients. There was good consistency between ultrasonographic and pathologic diagnosis of rare-type cervical cancer (weighted kappa=0.87). CONCLUSIONS: Most patients with rare-type cervical cancer present with isoechoic lesions. The coincidence rate between ultrasonographic and pathologic diagnosis of rare-type cervical cancer is 87%.
Subject(s)
Adenocarcinoma/pathology , Carcinoma, Adenosquamous/pathology , Carcinoma, Squamous Cell/pathology , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , Adult , Carcinoma, Adenosquamous/diagnostic imaging , Carcinoma, Squamous Cell/diagnostic imaging , Female , Humans , Middle Aged , Ultrasonography, Doppler, Color/methods , Ultrasonography, Doppler, Color/standards , Uterine Cervical Neoplasms/diagnostic imagingABSTRACT
OBJECTIVE: To explore the predictive value of neutrophil-lymphocyte ratio (NLR) at presentation for delayed neurological sequelae (DNS) in carbon monoxide (CO) poisoning. METHODS: This single-center retrospective observational study included a total of 253 consecutive patients who visited the emergency department (ED) due to acute CO intoxication between 7 October 2015 and 31 December 2019. The included patients had a history of coma and their blood routine was measured within one hour of ED admission. They were divided into two groups according to the presence of DNS, including those who developed DNS (DNS group) and those who did not (non-DNS group). RESULTS: A total of 171 patients were included in this research, and 49 (28.7%) developed DNS. The median NLR at ED admission was obviously higher in the DNS group (10.60 [9.69-15.34]) than in the non-DNS group (7.53 [5.86-8.56]) (p < 0.001). Multivariate analysis indicated that a high NLR (adjusted odds ratio (AOR): 1.78, 95% confidence interval (CI): 1.46-2.18) and the occurrence of acute brain lesions (AOR: 7.50, 95%CI: 2.86-19.68) on diffusion-weighted imaging were independent predictors of DNS. The NLR was more than 8.97. The prediction of occurrence of DNS had a sensitivity of 93.88% and a specificity of 84.43%. Kappa value was 0.713. The predicted results showed good authenticity and consistency. CONCLUSION: The level of NLR at presentation had good predictive value for the development of DNS, showing the superior value for clinical application.
Subject(s)
Carbon Monoxide Poisoning/pathology , Central Nervous System Diseases/chemically induced , Lymphocyte Count , Lymphocytes , Neutrophils , Adult , Aged , Central Nervous System Diseases/pathology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective StudiesABSTRACT
Catalases are a large group of enzymes that decompose hydrogen peroxide to oxygen and hydrogen, and have been applied widely in numerous areas. Bacillus subtilis ATCC 6051a is a well-known host strain for high level secretion of heterologous peptides. However, the application of 6051a was seriously hampered by insufficient transformation efficiency. In this study, D-xylose inducible comK was integrated into the genome of B. subtilis ATCC 6051a, generating 164S, a mutant owns a transformation efficiency of 1 000-fold higher than its parent strain, thus allowing gene replacement by double crossover recombination using linear dsDNAs. The efficiency of the flanking arms for homologous recombination was then analyzed. We found that 400 bp was the minimal length of homologous fragments required to initiate efficient recombination in the 164S strain. In addition, DNA cassettes encoding two mesophilic catalases (Orf 2-62 and Orf 2-63) from B. licheniformis were integrated onto 164S. The catalytic properties of recombinant Orf 2-62 and Orf 2-63 were analyzed, and were found to be predominantly secreted into the fermentation broth, although they obviously lack any known secretory signal peptide. This work demonstrated that B. subtilis 164S is an excellent cell tool, not only for its superior secretion capacity, but also for its convenience in genetic modification.
Subject(s)
Bacillus subtilis/genetics , Bacillus subtilis/metabolism , Catalase/biosynthesis , Bacillus licheniformis/genetics , Bacterial Proteins/genetics , Fermentation , Genetic Engineering , Genome, Bacterial , Homologous Recombination , Industrial Microbiology , Recombinant Proteins/biosynthesis , Transcription Factors/genetics , Transformation, Bacterial , Xylose/metabolismABSTRACT
Background: Rare cases of concurrent primary aldosteronism (PA) and renal artery stenosis (RAS) have been reported. Methods: In this retrospective case-control study, we selected a cohort of 10 PA with RAS patients and a control group of 20 PA without RAS patients from January 1, 2006, to January 1, 2016. Results: All patients presented with refractory hypertension, and a nonstatistically significant trend toward lower mean serum potassium was seen in the PA with RAS group (p =.07). PA with RAS patients had lower mean orthostatic aldosterone-to-renin ratios (38.4 ± 41.4 ng dL-1/ng mL-1 h-1 vs. 87.4.4 ± 38.4 ng dL-1/ng mL-1 h-1, respectively; p < .01) and a higher false-negative rate (50% vs. 15%, respectively; p < .05) compared with controls. All misdiagnosed patients had the diagnosis of PA confirmed when we revaluated the repeated screening and confirmative tests because of residual hypertension or hypokalemia after successful revascularization of renal artery stenosis. Conclusions: PA is easily missed in patients with RAS because of the high false-negative rate for screening tests. RAS patients with residual hypertension after successful renal angioplasty should be monitored for coexisting PA. Reevaluation of screening and confirmatory tests is helpful in establishing the correct diagnoses.
Subject(s)
Hyperaldosteronism/physiopathology , Hypertension/physiopathology , Hypokalemia/blood , Renal Artery Obstruction/physiopathology , Adult , Aldosterone/blood , Case-Control Studies , Cohort Studies , Diagnostic Errors , Female , Humans , Hyperaldosteronism/blood , Hyperaldosteronism/complications , Hyperaldosteronism/diagnosis , Hypertension/etiology , Hypokalemia/etiology , Male , Mass Screening , Middle Aged , Renal Artery Obstruction/blood , Renal Artery Obstruction/complications , Renal Artery Obstruction/diagnosis , Renin/blood , Retrospective StudiesABSTRACT
AIM: Previous studies have indicated that early metastasis is a major cause of mortality in patients with choriocarcinoma. However, what determines whether early metastasis of choriocarcinoma has occurred is unknown. The emerging role of miRNA in regulating cancer development and progression has been recognized. miR-373 has been shown to play pivotal roles in tumorigenesis and metastasis. However, whether miR-373 functions to promote choriocarcinoma metastasis is not clear. The purpose of this study is to determine the function of miR-373-3p in the progression of this cancer. METHODS: In this study, we first compared epithelial-mesenchymal transition (EMT)-related markers, which were inversely correlated with miR-373-3p expression in trophoblast and choriocarcinoma cell lines. Using PCR and Western blot, upregulation of miR-373-3p was observed to inhibit EMT progression. Similarly, gain- and loss-of-function studies revealed that ectopic miR-373-3p overexpression inhibited the migration by transwell methods of choriocarcinoma cells. RESULTS: Our results revealed that miR-373-3p acted as an EMT inhibitor in JEG-3 and JAR cells; this was due to its mediation of the transforming growth factor-ß (TGFß) signaling pathway, which was responsible for EMT. miRNA microarray analysis demonstrated that miR-373-3p interacted with the 3' untranslated region of TGFßR2 mRNA, and then Western blot and dual-luciferase reporter gene assays verified this interaction. CONCLUSION: Our findings suggest that miR-373-3p upregulation partly accounts for TGFßR2 downregulation and leads to a restraint of EMT and migration. miR-373-3p may therefore serve as a valuable potential target in the treatment of choriocarcinoma.
Subject(s)
Choriocarcinoma , MicroRNAs , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Humans , Receptor, Transforming Growth Factor-beta Type IIABSTRACT
BACKGROUND: Penicillic acid (PA) is produced by Aspergillus spp. and Penicillium spp., which are common postharvest and storage fungi of fruits. PA can be of concern for human health because of its toxicity and high fruit consumption by the population. However, no data on PA occurrence in various fruits have yet been reported. A quick, easy, cheap, effective, rugged and safe (QuEChERS) approach for PA determination in various fruits was developed and applied to explore PA incidence in fruits. RESULTS: The modified QuEChERS procedure with extraction by ethyl acetate and purification by multi-walled carbon nanotubes (MWCNTs), primary secondary amine (PSA) and octadecyl silane (C18) was established to determine PA in various fruits by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The average recoveries were 72.9-102.2% and relative standard deviations (RSDs) were 1.3-7.9%. A total of 161 fruits samples, including kiwi, apple, peach, grape and mandarin/orange, were collected in southern China. The incidence of PA in fruits was 14.9% and the levels of PA contamination were 0.200-0.596 µg kg-1 . Our results suggested that orange/mandarin, grape and kiwi were favorable matrices for Aspergillus spp. and Penicillium spp. to produce PA, rather than peach and apple. CONCLUSION: To the best of our knowledge, this is the first report about PA contamination in various fruits in China. Our study emphasizes the necessity of the current established method, which could be used for continuous monitoring of PA and reducing the health risk to Chinese consumers. © 2020 Society of Chemical Industry.
Subject(s)
Chromatography, High Pressure Liquid/methods , Fruit/chemistry , Mycotoxins/chemistry , Penicillic Acid/chemistry , Tandem Mass Spectrometry/methods , Actinidia/chemistry , Aspergillus/metabolism , China , Citrus sinensis/chemistry , Food Contamination/analysis , Fruit/microbiology , Malus/chemistry , Mycotoxins/metabolism , Penicillic Acid/metabolism , Penicillium/metabolism , Vitis/chemistryABSTRACT
OBJECTIVE: To analyze the clinical and genetic characteristics of five Chinese pedigrees affected with short stature. METHODS: A retrospective analysis was carried out for the clinical data and results of genetic testing for the probands. A literature search was also conducted. RESULTS: The five probands have all featured short stature with a family history. Genetic testing has revealed that they have harbored variants of the ACAN gene, including p.Val2042Argfs*6, p.Val1597del, c.630-1G>A, c.23delT and c.2026+1G>A(previously reported). CONCLUSION: Except for short stature, children harboring heterozygous variants of the ACAN gene may have no involvement of other systems. Some of these children may response to short-term growth hormone treatment.
Subject(s)
Aggrecans , Body Height/genetics , Aggrecans/genetics , Child , China , Genetic Testing , Humans , Pedigree , Retrospective StudiesABSTRACT
Osteogenesis imperfecta (OI) is a rare heritable disease with systemic connective tissue disorder. Most of the patients represent autosomal dominant form of OI, and are usually resulting from the mutations in type I collagen genes. However, the gene mutations reported previously only account for â¼70% of the OI cases. Here, in a Chinese OI family, we examined seven patients and nine normal individuals using the whole genome sequencing and molecular genetic analysis. The mutation of rs66612022 (COL1A2:p.Gly328Ser) related to glycine substitution was found in the seven patients. Moreover, we identified a novel missense mutation (HMMR:p.Glu2Gln). Interestingly, the individuals of this family with both the mutations were suffering from OI, while the others carried one or none of them are normal. The mutations of COL1A2 and HMMR and their combined effect on OI would further expand the genetic spectrum of OI.
Subject(s)
Collagen Type I/genetics , Extracellular Matrix Proteins/genetics , Hyaluronan Receptors/genetics , Osteogenesis Imperfecta/genetics , Asian People/genetics , China , Female , Humans , Male , Mutation, Missense , Pedigree , Polymorphism, Single Nucleotide , Whole Genome SequencingABSTRACT
BACKGROUND: Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare. CASE PRESENTATION: Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography-mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up. CONCLUSIONS: Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases.
Subject(s)
Amino Acid Metabolism, Inborn Errors/complications , Hyperhomocysteinemia/complications , Proteinuria/diagnosis , Adolescent , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acids/blood , Base Sequence , Carnitine/analogs & derivatives , Carnitine/blood , Child, Preschool , DNA/blood , DNA/genetics , Gas Chromatography-Mass Spectrometry , Homocysteine/blood , Humans , Hyperhomocysteinemia/genetics , Male , Methylmalonic Acid/urine , Proteinuria/etiologyABSTRACT
Genetics might play various roles in susceptibility to recurrent miscarriage, and previous studies suggest that some gene polymorphisms might be associated with abortion and breast cancer onset. Colon cancer-associated transcript 2 (CCAT2) is a novel long noncoding RNA (lncRNA) transcript that might be correlated with susceptibility to multiple cancers, including breast cancer. However, whether lncRNA CCAT2 polymorphisms are related to susceptibility to recurrent miscarriage is unclear. We genotyped two lncRNA CCAT2 polymorphisms (rs6983267 and rs3843549) in 248 patients with recurrent miscarriage and 392 controls through a TaqMan real-time polymerase chain reaction assay, and the strength of each association was evaluated via 95% confidence intervals (CIs) and odds ratios (ORs). Our results showed that the rs6983267 G allele in lncRNA CCAT2 was associated with decreased susceptibility to recurrent miscarriage (TG vs. TT: adjusted OR = 0.603; 95% CI = 0.420-0.866; p = 0.0062; GG/TG vs. TT: adjusted OR = 0.620; 95% CI = 0.441-0.873; p = 0.0061). The combined analysis of the two protective polymorphisms (rs3843549 AA and rs6983267 TG/GG) revealed that individuals with two unfavorable alleles exhibited a lower risk of recurrent miscarriage than those with no or only one unfavorable allele (adjusted OR = 0.531; 95% CI = 0.382-0.739). Moreover, the decreased risk associated with the two protective alleles was most obvious in women aged less than 35 years (OR = 0.551; 95% CI = 0.378-0.8803; p = 0.0019) and in women with two to three miscarriages (adjusted OR = 0.466; 95% CI = 0.318-0.683; p < 0.0001). In conclusion, our study indicates that the rs6983267G allele might contribute to a decreased risk of recurrent miscarriage in the South Chinese population.
Subject(s)
Abortion, Habitual/genetics , Genetic Predisposition to Disease/genetics , RNA, Long Noncoding/genetics , Adult , Alleles , Case-Control Studies , Female , Genotype , Humans , Polymorphism, Genetic , PregnancyABSTRACT
The principle and experimental demonstration of a spectral resolution enhanced static Fourier transform spectrometer (SESFTS) is presented. The device, which is based on a birefringent retarder array and a Wollaston prism, offers significant advantages over previous static Fourier transform (FT) implementations. Specifically, its use of an ultra-compact common-path interference structure creates a simple and robust spectral resolution enhanced spectrometer while preserving their high throughput and wide free spectral range. The operation principle of the device is explained in detail with a design example with a spectral resolution of 7 cm-1, which is nearly two orders of magnitude higher than that of a conventional static FT spectrometer with a similar CCD detector. An experimental demonstration is performed by the measurement of a gas charge lamp and three diode laser sources with a SESFTS prototype working in 400-1000 nm with an approximate 25 cm-1 spectral resolution.
ABSTRACT
BACKGROUND/AIMS: Liddle syndrome (LS) is a rare autosomal dominant disease caused by mutations in genes coding for epithelial sodium channel (ENaC) subunits. The aim of this study was to identify the mutation responsible for the LS in an extended Chinese family. METHODS: DNA samples from the proband with early-onset, treatment-resistant hypertension, and hypokalemia and 19 additional relatives were all sequenced for mutations in exon 13 of the ß-ENaC and γ-ENaC genes, using amplification by polymerase chain reaction and direct DNA sequencing. RESULTS: Genetic testing of exon 13 of SCNN1B revealed duplication of guanine into a string of 3 guanines located at codon 602. This frameshift mutation is predicted to generate a premature stop codon at position 607, resulting in truncated ß-ENaC lacking the remaining 34 amino acids, including the crucial PY motif. Among a total of 9 participants with the identical mutation, different phenotypes were identified. Tailored treatment with amiloride was safe and effective in alleviating disease symptoms in LS. No mutation of SCNN1G was identified in any of the examined participants. CONCLUSIONS: We report here a family affected by LS harboring a frameshift mutation (c.1806dupG) with a premature stop codon deleting the PY motif of ß-ENaC. Our study demonstrates that the earlier LS patients are diagnosed by genetic testing and treated with tailored medication, the greater the likelihood of preventing or minimizing complications in the vasculature and target organs.