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1.
J Environ Sci (China) ; 149: 21-34, 2025 Mar.
Article in English | MEDLINE | ID: mdl-39181636

ABSTRACT

During the water treatment process, chlorination and ultraviolet (UV) sterilization can modify microplastics (MPs) and alter their physicochemical properties, causing various changes between MPs and other pollutants. In this study, the impact of chlorination and UV modification on the physicochemical properties of polystyrene (PS) and polyvinyl chloride (PVC) were investigated, and the adsorption behavior of pefloxacin (PEF) before and after modification was examined. The effect of pH, ionic strength, dissolved organic matter, heavy metal ions and other water environmental conditions on adsorption behavior was revealed. The results showed that PS had a higher adsorption capacity of PEF than PVC, and the modification increased the presence of O-containing functional groups in the MPs, thereby enhancing the adsorption capacity of both materials. Chlorination had a more significant impact on the physicochemical properties of MPs compared to UV irradiation within the same time period, leading to better adsorption performance of chlorination. The optimal pH for adsorption was found to be 6, and NaCl, sodium alginate and Cu2+ would inhibit adsorption to varying degrees, among which the inhibition caused by pH was the strongest. Chlorination and UV modification would weaken the inhibitory effect of environmental factors on the adsorption of PEF by MPs. The main mechanisms of adsorption involved electrostatic interaction and hydrogen bonding. The study clarified the effects of modification on the physicochemical properties of MPs, providing reference for subsequent biotoxicity analysis and environmental protection studies.


Subject(s)
Halogenation , Pefloxacin , Polystyrenes , Polyvinyl Chloride , Ultraviolet Rays , Water Pollutants, Chemical , Water Purification , Adsorption , Polyvinyl Chloride/chemistry , Water Pollutants, Chemical/chemistry , Polystyrenes/chemistry , Water Purification/methods , Pefloxacin/chemistry , Hydrogen-Ion Concentration
2.
Front Public Health ; 12: 1405358, 2024.
Article in English | MEDLINE | ID: mdl-39086797

ABSTRACT

Objectives: This study aimed to investigate the epidemiological and drug resistance (DR) characteristics of extrapulmonary tuberculosis (EPTB) in South-Central China. Methods: EPTB inpatients who were culture-positive for Mycobacterium tuberculosis were retrospectively included in a study at a provincial TB hospital in Hunan, a province in South-Central China, from January 2013 to December 2021. Demographic, clinical, and drug susceptibility data were retrieved from TB treatment records. Descriptive statistical methods and a Chi-squared test were used to analyze the epidemiological and DR characteristics of EPTB patients. A logistic regression model was used to explore the risk factors of rifampicin-resistant/multidrug-resistant (RR/MDR)-EPTB. Results: A total of 1,324 cases were included. The majority of EPTB patients were in the age range of 20-29 years, were predominantly men (male-to-female ratio: 2.03), and were farmers (65.63%). Most EPTB cases were found in 2013 and 2017 from 2013 to 2021. The most prevalent subtypes of EPTB were lymphatic TB (29.83%, 395/1,324), multiple EPTB (20.85%, 276/1,324), and musculoskeletal TB (14.65%, 194/1,324). Musculoskeletal TB and genitourinary TB predominantly presented as exclusive EPTB forms, while lymphatic TB and pharyngeal/laryngeal TB often co-occurred with pulmonary TB (PTB). Drug susceptibility testing results showed that total DR rates (resistance to any of RFP, isoniazid [INH], streptomycin [STR], and/or ethambutol [EMB]) and RR/MDR rates in EPTB were 25.23% and 12.39%, respectively. Musculoskeletal TB exhibited the highest rates of total DR (31.40%), INH resistance (28.90%), STR resistance (20.10%), EMB resistance (6.20%), MDR (13.90%), and poly-DR (6.70%). The multivariable logistic regression model showed that patients aged from 20 to 59 years (compared to those aged 10 years), workers (compared to retirees), and EPTB patients from the south and west of Hunan (compared to those from the east of Hunan) were at an increased risk of developing RR/MDR EPTB (all OR values > 1). Conclusion: Our study provided a detailed account of the epidemiological and DR characteristics of EPTB in Hunan province, China. The significant DR rates, particularly in musculoskeletal TB cases, highlight the need for timely diagnosis, effective drug susceptibility testing, and the development of more effective treatment regimens for EPTB, especially targeting musculoskeletal TB treatments.


Subject(s)
Antitubercular Agents , Mycobacterium tuberculosis , Tuberculosis, Extrapulmonary , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , Antitubercular Agents/therapeutic use , Antitubercular Agents/pharmacology , China/epidemiology , Microbial Sensitivity Tests , Mycobacterium tuberculosis/isolation & purification , Mycobacterium tuberculosis/drug effects , Retrospective Studies , Rifampin/therapeutic use , Rifampin/pharmacology , Risk Factors , Tuberculosis, Extrapulmonary/drug therapy , Tuberculosis, Extrapulmonary/epidemiology , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy
3.
J Clin Immunol ; 44(7): 166, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060684

ABSTRACT

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder featuring chronic lymphadenopathy, splenomegaly, cytopenias, and increased lymphoma risk. Differentiating ALPS from immunodeficiencies with overlapping symptoms is challenging. This study evaluated the performance and the diagnostic yield of a 15-gene NGS panel for ALPS at Cincinnati Children's Hospital Medical Center. Samples from 802 patients submitted for ALPS NGS panel were studied between May 2014 and January 2023. A total of 62 patients (7.7%) had a definite diagnosis: 52/62 cases (84%) showed 37 unique pathogenic/likely pathogenic germline FAS variants supporting ALPS diagnosis (6.5%, 52/802). The ALPS diagnostic yield increased to 30% in patients who additionally fulfilled abnormal ALPS immunology findings criteria. 17/37 (46%) diagnostic FAS variants were novel variants reported for the first time in ALPS. 10/802 cases (1.2%) showed diagnostic findings in five genes (ADA2, CTLA4, KRAS, MAGT1, NRAS) which are related to autoimmune lymphoproliferative immunodeficiency (ALPID). Family studies enabled the reclassification of variants of unknown significance (VUS) and also the identification of at-risk family members of FAS-positive patients, which helped in the follow-up diagnosis and treatment. Alongside family studies, complete clinical phenotypes and abnormal ALPS immunology and Fas-mediated apoptosis results helped clarify uncertain genetic findings. This study describes the largest cohort of genetic testing for suspected ALPS in North America and highlights the effectiveness of the ALPS NGS panel in distinguishing ALPS from non-ALPS immunodeficiencies. More comprehensive assessment from exome or genome sequencing could be considered for undefined ALPS-U patients or non-ALPS immunodeficiencies after weighing cost, completeness, and timeliness of different genetic testing options.


Subject(s)
Autoimmune Lymphoproliferative Syndrome , Genetic Testing , Humans , Autoimmune Lymphoproliferative Syndrome/diagnosis , Autoimmune Lymphoproliferative Syndrome/genetics , Genetic Testing/methods , Female , Male , Child , Child, Preschool , Infant , Adolescent , fas Receptor/genetics , High-Throughput Nucleotide Sequencing , Genetic Predisposition to Disease , Hospitals, Pediatric , Mutation/genetics
4.
Front Public Health ; 12: 1432065, 2024.
Article in English | MEDLINE | ID: mdl-39035178

ABSTRACT

Objectives: To investigate the clinical epidemiological and drug resistance (DR) characteristics of lymph node tuberculosis (LNTB) in Hunan Province which locates in South-central China, and to provide scientific clues for effective prevention and treatment of LNTB. Methods: We retrospectively collected LNTB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital, the biggest TB reference hospital in South-central China, from January 2013 to December 2021. The multiple demographic, clinical and drug susceptibility data of patients were collected from the hospital's electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods. Results: Of the 577 LNTB cases, 373 (64.64%) were males, 352 (61.01%) were farmers; majority (161, 33.10%) aged at 20-29 years old; 147 (25.48%) had simple LNTB, 350 (60.66%) had LNTB combined with pulmonary TB (PTB) (defined as LNTB-PTB), and 80 (13.86%) had LNTB combined with other extrapulmonary TB (EPTB) (defined as LNTB-EPTB). A total of 345 (59.79%, 345/577) LNTB patients had cervical node infection, and the simple LNTB patients (81.63%, 120/147) had higher proportion of this infection than LNTB-PTB (51.71%, 181/350) and LNTB-EPTB (55.00%, 44/80) (both p values <0.017), respectively. LNTB-EPTB was more inclined to have abdominal tuberculous LNs (20%, 16/80) and at least four tuberculous lesions (22.50%, 18/80) than simple LNTB and LNTB-PTB. Seventy-seven (13.34%) and 119 (20.62%) were resistant to rifampicin (RIF) and isoniazid (INH), respectively; 72 (12.48%) were multi-drug resistant (MDR), and a total of 150 (26.00%) were DR (resistant to at least one of RIF, INH, ethambutol and streptomycin). LNTB patients aged 30-34 and 50-54 years old (compared to those aged <30 years) were independent predictors of RIF resistance (RR) (ORs were 3.47 and 2.83, respectively; 95% CIs were 1.64-7.35 and 1.08-7.46, respectively). Conclusion: Our study disclosed the epidemiological and DR characteristics of LNTB in Hunan Province, China. High LNTB prevalence was found in younger people while high RR LNTB prevalence was found in older ones, suggesting that we should conduct further studies to clarify the occurrence of RR in LNTB, meanwhile, strengthen the diagnoses and treatments of LNTB to prevent the emergence of RR.


Subject(s)
Antitubercular Agents , Mycobacterium tuberculosis , Tuberculosis, Lymph Node , Tuberculosis, Multidrug-Resistant , Humans , China/epidemiology , Male , Female , Adult , Middle Aged , Retrospective Studies , Antitubercular Agents/therapeutic use , Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Tuberculosis, Lymph Node/epidemiology , Tuberculosis, Lymph Node/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy , Young Adult , Adolescent , Aged , Microbial Sensitivity Tests , Drug Resistance, Bacterial
5.
Molecules ; 29(7)2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38611942

ABSTRACT

OBJECTIVE: To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content determination, and to provide a basis for the processing, handling, and clinical application of this herb. METHODS: Ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to conduct a preliminary analysis of the chemical constituents in GTHP before and after fermentation. High-performance liquid chromatography (HPLC) was used to determine some major differential components of GTHP and establish fingerprints. Cluster analysis (CA), and principal component analysis (PCA) were employed for comprehensive evaluation. RESULTS: Seventy-nine compounds were identified, including flavonoids, organic acids, nucleosides, terpenoids, and others. The CA and PCA results showed that ten samples were divided into three groups. Through standard control and HPLC analysis, 10 compounds were identified from 22 peaks, namely uracil, guanosine, adenosine, 5-hydroxymethylfurfural (5-HMF), daidzin, genistin, glycitein, daidzein, genistein, and ergosterol. After fermentation, GTHP exhibited significantly higher contents of uracil, guanosine, adenosine, 5-hydroxymethylfurfural, and ergosterol and significantly lower genistein and daidzein contents. CONCLUSIONS: The UHPLC-Q-Orbitrap HRMS and HPLC methods can effectively identify a variety of chemical components before and after the fermentation of GTHP. This study provides a valuable reference for further research on the rational clinical application and quality control improvement of GTHP.


Subject(s)
Furaldehyde/analogs & derivatives , Gastrodia , Genistein , Chromatography, High Pressure Liquid , Fermentation , Powders , Adenosine , Ergosterol , Guanosine , Uracil
6.
BMC Neurol ; 24(1): 136, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664634

ABSTRACT

BACKGROUD: This study aims to compare the clinical manifestations, imaging findings, routine tests, biochemistry indicators and cerebrospinal fluid cytology between neurobrucellosis and tuberculous meningitis. The objective is to evaluate the similarities and differences of these two diseases and improve early diagnosis. METHODS: A comprehensive evaluation was conducted by comparing clinical data, imaging results, routine tests findings, biochemistry indicators and cerebrospinal fluid cytology of patients admitted to the Department of Neurology, the Second Hospital of Hebei Medical University from 2019 to 2021. Statistical analysis was applied to identify significant differences and similarities between the two diseases. RESULTS: Preliminary analysis demonstrated both diseases commonly present with symptoms such as fever, headache. However, there were no statistical differences between neurobrucellosis and tuberculous meningitis in early clinical data, imaging results, routine tests findings, biochemistry indicators. Further analysis indicates there is a statistically significantly difference in the lymphocyte ratio and neutrophil ratio in the cerebrospinal fluid between the two groups. CONCLUSIONS: Neurobrucellosis and tuberculous meningitis share similarities in early clinical manifestations, imaging findings and initial cerebrospinal fluid parametes, making early-stage differentiation challenging. The ratio of lymphocytes and neutrophil in the cerebrospinal fluid and a detailed medical history investigation can provide clues for early clinical diagnosis. So the examination of CSF cytology might be a potential to distinguish these two diseases and become a powerful tool in the future.


Subject(s)
Brucellosis , Tuberculosis, Meningeal , Humans , Tuberculosis, Meningeal/diagnosis , Tuberculosis, Meningeal/cerebrospinal fluid , Male , Female , Adult , Middle Aged , Brucellosis/diagnosis , Diagnosis, Differential , Aged , Young Adult
7.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6347-6360, 2023 Dec.
Article in Chinese | MEDLINE | ID: mdl-38211991

ABSTRACT

Xanthoceras sorbifolium seeds have a wide range of applications in the food and pharmaceutical industries. To compare and analyze the chemical compositions of different parts of X. sorbifolium seeds and explore the potential value and research prospects of non-medicinal parts, this study used ultra-high-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) to detect the chemical composition of various parts of the seeds. A total of 82 components were preliminary identified from X. sorbifolium seeds, including 5 amino acids, 4 polyphenols, 3 phenylpropionic acids, 7 organic acids, 15 flavonoids, 6 glycosides, and 23 saponins. Mass spectrometry molecular networking(MN) analysis was conducted on the results from different parts of the seeds, revealing significant differences in the components of the seed kernel, seed coat, and seed shell. The saponins and flavonoids in the seed kernel were superior in terms of variety and content to those in the seed coat and shell. Based on the chromatographic peaks of different parts from multiple batches of samples, multivariate statistical analysis was carried out. Four differential components were determined using HPLC, and the average content of these components in the seed kernel, seed coat, and seed shell were as follows: 0.183 6, 0.887 4, and 1.440 1 mg·g~(-1) for fraxin; 0.035 8, 0.124 1, and 0.044 5 mg·g~(-1) for catechin; 0.032 9, 0.072 0, and 0.221 5 mg·g~(-1) for fraxetin; 0.435 9, 2.114 7, and 0.259 7 mg·g~(-1) for epicatechin. The results showed that catechin and fraxetin had relatively low content in all parts, while fraxin had higher content in the seed coat and seed shell, and epicatechin had higher content in the seed kernel and seed coat. Therefore, the seed coat and seed shell possess certain development value. This study provides rapid analysis and comparison of the chemical compositions of different parts of X. sorbifolium seeds, which offers an experimental basis for the research and clinical application of medicinal substances in X. sorbifolium seeds.


Subject(s)
Catechin , Saponins , Chromatography, High Pressure Liquid/methods , Catechin/analysis , Flavonoids/analysis , Seeds/chemistry , Saponins/analysis
8.
Article in English | MEDLINE | ID: mdl-36225193

ABSTRACT

Postinfectious irritable bowel syndrome (PI-IBS) is a highly prevalent gastrointestinal disorder associated with immune dysregulation and depression- and anxiety-like behaviors. Through traditional medicine, the active ingredient of Paeoniae Radix called paeoniflorin (PF) was previously found to prevent the symptoms of PI-IBS. However, there is limited information on the effects of PF on intestinal function and depression- and anxiety-like symptoms in PI-IBS animal models. Here, we aimed to determine the effects of PF treatment on the symptoms of PI-IBS in a rat model. The PI-IBS rat model was established via early postnatal sibling deprivation (EPSD), trinitrobenzenesulfonic acid (TNBS), and chronic unpredictable mild stress (CUMS) stimulation and then treated with different dosages of PF (10, 20, and 40 mg/kg) and leptin (1 and 10 mg/kg). The fecal water content and body weight were measured to evaluate the intestinal function, while the two-bottle test for sucrose intake, open field test (OFT), and elevated plus maze test (EMT) were performed to assess behavioral changes. The serum leptin levels were also measured using an enzyme-linked immunosorbent assay. Furthermore, the expressions of leptin and its receptor, LepRb, were detected in colonic mucosal tissues through an immunohistochemical assay. The activation of the PI3K/AKT signaling pathway and the expression of brain-derived neurotrophic factor (BDNF) were also detected via western blotting. After the experimental period, the PI-IBS rats presented decreased body weight and increased fecal water content, which coincided with elevated leptin levels and heightened depression- and anxiety-like behaviors (e.g., low sucrose intake, less frequency in the center areas during OFT, and fewer activities in the open arms during EMT). However, the PF treatment ameliorated these observed symptoms. Furthermore, PF not only inhibited leptin/LepRb expression but also reduced the PI3K/AKT phosphorylation and BDNF expression in PI-IBS rats. Notably, cotreatment with leptin (10 mg/kg) reduced the effects of PF (20 mg/kg) on colonic fibrosis, leptin/LepRb expression, and PI3K/AKT activation. Therefore, our findings suggest that leptin is targeted by PF via the leptin/LepRb pathway, consequently ameliorating the symptoms of PI-IBS. Our study also contributes novel insights for elucidating the pharmacological action of PF on gastrointestinal disorders and may be used for the clinical treatment of PI-IBS in the future.

9.
Front Genet ; 13: 887698, 2022.
Article in English | MEDLINE | ID: mdl-35937981

ABSTRACT

Exome sequencing (ES) became clinically available in 2011 and promised an agnostic, unbiased next-generation sequencing (NGS) platform for patients with symptoms believed to have a genetic etiology. The diagnostic yield of ES has been estimated to be between 25-40% and may be higher in specific clinical scenarios. Those who remain undiagnosed may have no molecular findings of interest on ES, variants of uncertain significance in genes that are linked to human disease, or variants of uncertain significance in candidate genes that are not definitively tied to human disease. Recent evidence suggests that a post-exome evaluation consisting of clinical re-phenotyping, functional studies of candidate variants in known genes, and variant reevaluation can lead to a diagnosis in 5-15% of additional cases. In this brief research study, we present our experience on post-exome evaluations in a cohort of patients who are believed to have a genetic etiology for their symptoms. We have reached a full or partial diagnosis in approximately 18% (6/33) of cases that have completed evaluations to date. We accomplished this by utilizing NGS-based methods that are available on a clinical basis. A sample of these cases highlights the utility of ES reanalysis with updated phenotyping allowing for the discovery of new genes, re-adjudication of known variants, incorporating updated phenotypic information, utilizing functional testing such as targeted RNA sequencing, and deploying other NGS-based testing methods such as gene panels and genome sequencing to reach a diagnosis.

10.
J Autism Dev Disord ; 52(11): 4828-4842, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34773222

ABSTRACT

Our institution developed and continuously improved a Neurodevelopmental Reflex (NDR) algorithm to help physicians with genetic test ordering for neurodevelopmental disorders (NDDs). To assess its performance, we performed a retrospective study of 511 patients tested through NDR from 2018 to 2019. SNP Microarray identified pathogenic/likely pathogenic copy number variations in 27/511 cases (5.28%). Among the 484 patients tested for Fragile X FMR1 CGG repeats, a diagnosis (0.20%) was established for one male mosaic for a full mutation, a premutation, and a one-CGG allele. Within the 101 normocephalic female patients tested for MECP2, two patients were found to carry pathogenic variants (1.98%). This retrospective study suggested the NDR algorithm effectively established diagnoses for patients with NDDs with a yield of 5.87%.


Subject(s)
Autism Spectrum Disorder , Fragile X Syndrome , Neurodevelopmental Disorders , Autism Spectrum Disorder/diagnosis , Child , DNA Copy Number Variations , Female , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/diagnosis , Fragile X Syndrome/genetics , Genetic Testing , Hospitals , Humans , Male , Mutation , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/genetics , Retrospective Studies , Trinucleotide Repeat Expansion
11.
Sensors (Basel) ; 21(18)2021 Sep 17.
Article in English | MEDLINE | ID: mdl-34577441

ABSTRACT

Neural decoding is useful to explore the timing and source location in which the brain encodes information. Higher classification accuracy means that an analysis is more likely to succeed in extracting useful information from noises. In this paper, we present the application of a nonlinear, nonstationary signal decomposition technique-the empirical mode decomposition (EMD), on MEG data. We discuss the fundamental concepts and importance of nonlinear methods when it comes to analyzing brainwave signals and demonstrate the procedure on a set of open-source MEG facial recognition task dataset. The improved clarity of data allowed further decoding analysis to capture distinguishing features between conditions that were formerly over-looked in the existing literature, while raising interesting questions concerning hemispheric dominance to the encoding process of facial and identity information.


Subject(s)
Facial Recognition , Magnetoencephalography , Algorithms , Electroencephalography , Signal Processing, Computer-Assisted
12.
Front Psychol ; 12: 603878, 2021.
Article in English | MEDLINE | ID: mdl-34305695

ABSTRACT

Studies have suggested that visually presented words are obligatorily decomposed into constituents that could be mapped to language representations. The present study aims to elucidate how orthographic processing of one constituent affects the other and vice versa during a word recognition task. Chinese orthographic system has characters representing syllables and meanings instead of suffixation roles, and the majority of Chinese characters are phonograms that can be further decomposed into phonetic radical and semantic radical. We propose that semantic radical combinability indexed by semantic radicals and the effect of phonological consistency indexed by phonetic radicals would interact with each other during the reading of Chinese phonograms. Twenty-six right-handed native Chinese speakers were recruited to the study. Participants were presented with phonograms divided into four conditions following their semantic radical combinability (large vs. small) and phonological consistency (high vs. low). EEG signals were recorded throughout the covert naming task. Our results show that there is an interaction effect between phonological consistency and semantic radical combinability on the right hemisphere N170 activity while reading phonograms. Semantic radical combinability influenced the right hemisphere N170 during the process of low-consistency character reading but not high-consistency character reading. On the other hand, the left hemisphere N170 revealed a more significant activity during reading high-consistency characters and was not affected by radical combinability. In addition, while low-consistency characters revealed a larger P200 than high-consistency characters, the semantic radical combinability effect on P200 was only significant when participants were reading high-consistency characters but not low-consistency characters. These results provide new information about how ERPs are involved in word recognition within the context of interaction among orthographic and phonological dimensions.

13.
Front Pharmacol ; 11: 581230, 2020.
Article in English | MEDLINE | ID: mdl-33597871

ABSTRACT

Background: Triptolide (TP), a naturally derived compound from Tripterygium wilfordii, has been proven effective in protecting against cardiovascular system, but the molecular mechanisms underlying its protective effects are poorly understood. In the current study, we sought to test the potential protective role of TP in the regulation of vascular calcification in a rat model and explore whether TP attenuates medial vascular calcification by upregulating miRNA-204. Methods: Vitamin D3 plus nicotine (VDN) was used to induce a vascular calcification (VC) model of rat aorta. Von Kossa and Hematoxylin-Eosin staining were applied to assess the degree of calcification of rat aortas. Calcium content and alkaline phosphatase activity were measured. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was applied to quantify miRNA-204 expression. The localization of runt-related transcription factor-2 (RUNX2) and bone morphogenetic protein-2 (BMP2) expressions were detected by immunohistochemistry and western blotting. Results: Administration of TP greatly reduced vascular calcification in a dose-dependent manner compared with VC controls. The increase in ALP activity and calcium content was ameliorated by TP. Moreover, protein expression levels of BMP2 and RUNX2 were significantly reduced in calcified aortas. MiRNA-204 expression was increased in the TP-treated groups compared with VC controls and the effects of TP were reversed by the intravenous injection of miRNA-204-interfering lentivirus. However, the miRNA-204-overexpressing lentivirus had no additional effects on ALP activity, calcium content, BMP2 and RUNX2 expressions compared with those from TP group. Conclusion: TP inhibited BMP2 and RUNX2 expression and attenuated vascular calcification via upregulating the level of miRNA-204. TP appears to be a potential new therapeutic option for treating vascular calcification.

14.
Cell Death Dis ; 8(9): e3034, 2017 09 07.
Article in English | MEDLINE | ID: mdl-28880267

ABSTRACT

The generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming holds great potential for modeling human diseases. However, the reprogramming process remains very inefficient and a better understanding of its basic biology is required. The mesenchymal-to-epithelial transition (MET) has been recognized as a crucial step for the successful reprogramming of fibroblasts into iPSCs. It has been reported that the p53 tumor suppressor gene acts as a barrier of this process, while its homolog p63 acts as an enabling factor. In this regard, the information concerning the role of the third homolog, p73, during cell reprogramming is limited. Here, we derive total Trp73 knockout mouse embryonic fibroblasts, with or without Trp53, and examine their reprogramming capacity. We show that p73 is required for effective reprogramming by the Yamanaka factors, even in the absence of p53. Lack of p73 affects the early stages of reprogramming, impairing the MET and resulting in altered maturation and stabilization phases. Accordingly, the obtained p73-deficient iPSCs have a defective epithelial phenotype and alterations in the expression of pluripotency markers. We demonstrate that p73 deficiency impairs the MET, at least in part, by hindering BMP pathway activation. We report that p73 is a positive modulator of the BMP circuit, enhancing its activation by DNp73 repression of the Smad6 promoter. Collectively, these findings provide mechanistic insight into the MET process, proposing p73 as an enhancer of MET during cellular reprogramming.


Subject(s)
Bone Morphogenetic Protein 4/pharmacology , Fibroblasts/metabolism , Induced Pluripotent Stem Cells/metabolism , Phosphoproteins/genetics , Trans-Activators/genetics , Tumor Protein p73/genetics , Tumor Suppressor Protein p53/genetics , Animals , Cell Line , Cellular Reprogramming , Fibroblasts/cytology , Fibroblasts/drug effects , Gene Expression Regulation , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Kruppel-Like Factor 4 , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Mice , Octamer Transcription Factor-3/genetics , Octamer Transcription Factor-3/metabolism , Phosphoproteins/deficiency , Promoter Regions, Genetic , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , SOXB1 Transcription Factors/genetics , SOXB1 Transcription Factors/metabolism , Signal Transduction , Smad6 Protein/genetics , Smad6 Protein/metabolism , Trans-Activators/deficiency , Tumor Protein p73/deficiency , Tumor Suppressor Protein p53/deficiency
16.
Am J Med Genet C Semin Med Genet ; 172(2): 102-8, 2016 06.
Article in English | MEDLINE | ID: mdl-27075776

ABSTRACT

We report on a 4-year-old female who presented with unilateral sensorineural hearing loss and a concern for developmental delay. A genome-wide SNP array analysis was performed and revealed a de novo 3.2 Mb interstitial deletion of chromosome 7q31.2q31.31. This region contains thirteen protein-encoding genes. It is unknown whether haploinsufficiency of any of these genes is responsible for the clinical features of our patient. We reviewed, the clinical phenotype of a previously published 7q31.3 deletion patient and 18 additional patients with overlapping 7q31 deletions listed in the DECIPHER database. The most consistent feature in these patients and our proband is delayed speech and language development. Hearing loss is presented both in our proband and the published 7q31.3 patient. Our study suggests that a small region on chromosome 7q31.3 encompassing four genes, CFTR, CTTNBP2, NAA38, and ANKRD7, may represent a new locus for congenital hearing loss and/or speech development. © 2016 Wiley Periodicals, Inc.


Subject(s)
Chromosome Deletion , Developmental Disabilities/genetics , Hearing Loss, Sensorineural/genetics , Carrier Proteins/genetics , Child, Preschool , Chromosomes, Human, Pair 7/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Female , Genome, Human , Humans , Membrane Transport Proteins , N-Terminal Acetyltransferase C/genetics , Nerve Tissue Proteins/genetics , Nuclear Proteins , Polymorphism, Single Nucleotide , Proteins/genetics , Ribonucleoprotein, U4-U6 Small Nuclear/genetics
17.
Am J Med Genet C Semin Med Genet ; 172(2): 109-16, 2016 06.
Article in English | MEDLINE | ID: mdl-27125467

ABSTRACT

Distal deletion of the long arm of chromosome 10 with breakpoints mapped at 10q26 is a well-recognized contiguous genomic disorder. A wide spectrum of clinical findings is seen in affected individuals and the common clinical features include craniofacial dysmorphia, developmental delay, intellectual disability, hypotonia, cardiovascular defects, and urogenital malformations. We report herein on a male patient with a 5.5 Mb interstitial deletion of 10q26.11q2613 and compare his clinical presentation to previously reported cases. Apart from characteristic phenotypes seen in 10q26 deletion syndrome, he presents with colobomas and left ventricle enlargement. These are cardiovascular and ophthalmological findings that have not been described in prior cases. © 2016 Wiley Periodicals, Inc.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 10/genetics , Coloboma/genetics , Hearing Loss/genetics , Hypertrophy, Left Ventricular/genetics , Abnormalities, Multiple , Humans , Male , Phenotype
18.
PLoS Genet ; 11(11): e1005655, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26544867

ABSTRACT

Individuals with Cornelia de Lange Syndrome (CdLS) display diverse developmental deficits, including slow growth, multiple limb and organ abnormalities, and intellectual disabilities. Severely-affected individuals most often have dominant loss-of-function mutations in the Nipped-B-Like (NIPBL) gene, and milder cases often have missense or in-frame deletion mutations in genes encoding subunits of the cohesin complex. Cohesin mediates sister chromatid cohesion to facilitate accurate chromosome segregation, and NIPBL is required for cohesin to bind to chromosomes. Individuals with CdLS, however, do not display overt cohesion or segregation defects. Rather, studies in human cells and model organisms indicate that modest decreases in NIPBL and cohesin activity alter the transcription of many genes that regulate growth and development. Sister chromatid cohesion factors, including the Nipped-B ortholog of NIPBL, are also critical for gene expression and development in Drosophila melanogaster. Here we describe how a modest reduction in Nipped-B activity alters growth and neurological function in Drosophila. These studies reveal that Nipped-B heterozygous mutant Drosophila show reduced growth, learning, and memory, and altered circadian rhythms. Importantly, the growth deficits are not caused by changes in systemic growth controls, but reductions in cell number and size attributable in part to reduced expression of myc (diminutive) and other growth control genes. The learning, memory and circadian deficits are accompanied by morphological abnormalities in brain structure. These studies confirm that Drosophila Nipped-B mutants provide a useful model for understanding CdLS, and provide new insights into the origins of birth defects.


Subject(s)
DNA-Binding Proteins/genetics , De Lange Syndrome/genetics , Drosophila Proteins/genetics , Drosophila/growth & development , Drosophila/physiology , Models, Biological , Mutation , Animals , Drosophila/genetics , Heterozygote
19.
J Ind Microbiol Biotechnol ; 42(9): 1233-41, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26173497

ABSTRACT

The xylanase regulator 1 protein in Myceliophthora thermophila ATCC42464 (MtXyr1) is 60 % homologous with that of Trichoderma reesei. However, MtXyr1's regulatory role on cellulolytic and xylanolytic genes in M. thermophila is unknown. Herein, MtXyr1 was overexpressed under the control of the MtPpdc (pyruvate decarboxylase) promoter. Compared with the wild type, the extracellular xylanase activities of the transformant cultured in non-inducing and inducing media for 120 h were 25.19- and 9.04-fold higher, respectively. The Mtxyr1 mRNA level was 300-fold higher than in the wild type in corncob-containing medium. However, the filter paper activity and endoglucanase activities were unchanged in corncob-containing medium and glucose-containing medium. The different zymograms between the transformant and the wild type were analyzed and identified by mass spectrometry as three xylanases of the glycoside hydrolase (GH) family 11. Thus, overexpression of xyr1 resulted in enhanced xylanase activity in M. thermophila. Xylanase production could be improved by overexpressing Mtxyr1 in M. thermophila.


Subject(s)
Fungal Proteins/biosynthesis , Sordariales/enzymology , Trans-Activators/biosynthesis , Xylosidases/biosynthesis , Enzyme Induction , Fungal Proteins/genetics , Gene Expression Regulation, Fungal , Promoter Regions, Genetic , Sordariales/genetics , Trans-Activators/genetics , Xylosidases/genetics
20.
Am J Med Genet A ; 167(6): 1179-92, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25899772

ABSTRACT

Cornelia de Lange Syndrome (CdLS) is the most common example of disorders of the cohesin complex, or cohesinopathies. There are a myriad of clinical issues facing individuals with CdLS, particularly in the neurodevelopmental system, which also have implications for the parents and caretakers, involved professionals, therapists, and schools. Basic research in developmental and cell biology on cohesin is showing significant progress, with improved understanding of the mechanisms and the possibility of potential therapeutics. The following abstracts are presentations from the 6th Cornelia de Lange Syndrome Scientific and Educational Symposium, which took place on June 25-26, 2014, in conjunction with the Cornelia de Lange Syndrome Foundation National Meeting in Costa Mesa, CA. The Research Committee of the CdLS Foundation organizes the meeting, reviews and accepts abstracts, and subsequently disseminates the information to the families through members of the Clinical Advisory Board. In addition to the scientific and clinical discussions, there were educationally focused talks related to practical aspects of behavior and development. AMA CME credits were provided by Greater Baltimore Medical Center, Baltimore, MD.


Subject(s)
Cell Cycle Proteins/genetics , Chromosomal Proteins, Non-Histone/genetics , De Lange Syndrome/genetics , Gene Expression Regulation, Developmental , Mutation , Adult , Animals , California , Cell Cycle Proteins/metabolism , Child , Chromosomal Proteins, Non-Histone/metabolism , De Lange Syndrome/metabolism , De Lange Syndrome/pathology , Disease Models, Animal , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Humans , Mice , Phenotype , Signal Transduction , Zebrafish/genetics , Zebrafish/metabolism , Cohesins
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