Acute phase clinical manifestations of patients with Vogt-Koyanagi-Harada disease in Southern China.

Backgrounds: To characterize the acute phase clinical manifestations and visual outcomes of the patients with Vogt-Koyanagi Harada (VKH) disease in southern China.

Methods: In total, 186 patients with acute-onset VKH disease were recruited. The demographic data, clinical signs, ophthalmic examinations, and visual outcomes were analyzed.

Dentin defects caused by a Dspp frameshift mutation are associated with the activation of autophagy.

Dentin sialophosphoprotein (DSPP) is primarily expressed by differentiated odontoblasts (dentin-forming cells), and transiently expressed by presecretory ameloblasts (enamel-forming cells). Disease-causing DSPP mutations predominantly fall into two categories: 5' mutations affecting targeting and trafficking, and 3' - 1 frameshift mutations converting the repetitive, hydrophilic, acidic C-terminal domain into a hydrophobic one. We characterized the dental phenotypes and investigated the pathological mechanisms of Dspp and Dspp mice that replicate the two categories of human DSPP mutations.

Enamel defects in Acp4 mice and human ACP4 mutations.

Human ACP4 (OMIM*606362) encodes a transmembrane protein that belongs to histidine acid phosphatase (ACP) family. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J, OMIM#617297). While ACP activity has long been detected in developing teeth, its functions during tooth development and the pathogenesis of ACP4-associated AI remain largely unknown.

Mouse Dspp frameshift model of human dentinogenesis imperfecta.

Non-syndromic inherited defects of tooth dentin are caused by two classes of dominant negative/gain-of-function mutations in dentin sialophosphoprotein (DSPP): 5' mutations affecting an N-terminal targeting sequence and 3' mutations that shift translation into the - 1 reading frame. DSPP defects cause an overlapping spectrum of phenotypes classified as dentin dysplasia type II and dentinogenesis imperfecta types II and III. Using CRISPR/Cas9, we generated a Dspp mouse model by introducing a FLAG-tag followed by a single nucleotide deletion that translated 493 extraneous amino acids before termination.

Odontogenesis-associated phosphoprotein truncation blocks ameloblast transition into maturation in Odaph mice.

Mutations of Odontogenesis-Associated Phosphoprotein (ODAPH, OMIM *614829) cause autosomal recessive amelogenesis imperfecta, however, the function of ODAPH during amelogenesis is unknown. Here we characterized normal Odaph expression by in situ hybridization, generated Odaph truncation mice using CRISPR/Cas9 to replace the TGC codon encoding Cys41 into a TGA translation termination codon, and characterized and compared molar and incisor tooth formation in Odaph, Odaph, and Odaph mice. We also searched genomes to determine when Odaph first appeared phylogenetically.

ENAM mutations and digenic inheritance.

Background: ENAM mutations cause autosomal dominant or recessive amelogenesis imperfecta (AI) and show a dose effect: enamel malformations are more severe or only penetrant when both ENAM alleles are defective.

Methods: Whole exome sequences of recruited AI probands were initially screened for mutations in known AI candidate genes. Sanger sequencing was used to confirm sequence variations and their segregation with the disease phenotype.

Experimental and numerical investigation on inspiration and expiration flows in a three-generation human lung airway model at two flow rates.

The respiration flow pattern plays a key role in fluid flow, heat and mass transfer in human lung airway. To reveal the complex flow pattern within human lung multiple-generation airway, both the steady inspiration and expiration flows are comprehensively studied using laser Doppler velocimetry technique and computational fluid dynamics method for an idealized human tracheobronchial three-generation airway model at two flow rates, corresponding to an adult male breathing under light activity and moderate exercise conditions, respectively. The comparison of mainstream velocity between the measurements and simulations are generally good.

Mutations in RELT cause autosomal recessive amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a collection of isolated (non-syndromic) inherited diseases affecting dental enamel formation or a clinical phenotype in syndromic conditions. We characterized three consanguineous AI families with generalized irregular hypoplastic enamel with rapid attrition that perfectly segregated with homozygous defects in a novel gene: RELT that is a member of the tumor necrosis factor receptor superfamily (TNFRSF). RNAscope in situ hybridization of wild-type mouse molars and incisors showed specific Relt mRNA expression by secretory stage ameloblasts and by odontoblasts.

Symptom-based network classification identifies distinct clinical subgroups of liver diseases with common molecular pathways.

Background And Objective: Liver disease is a multifactorial complex disease with high global prevalence and poor long-term clinical efficacy and liver disease patients with different comorbidities often incorporate multiple phenotypes in the clinic. Thus, there is a pressing need to improve understanding of the complexity of clinical liver population to help gain more accurate disease subtypes for personalized treatment.

Methods: Individualized treatment of the traditional Chinese medicine (TCM) provides a theoretical basis to the study of personalized classification of complex diseases.

DNA Methylation of the hTERT Gene in Breast Cancer Revisited: Diagnostic and Clinical Implications.

Background: It is documented that in tumor cell lines, the hTERT gene exhibits prominent methylation at a CpG island rich region about -600 bp upstream of the transcription start site, but mixed or allelically absent around ±150 bp region. Given the potential clinical implications of the findings in breast cancer diagnostics, we set out to investigate if such findings are reproducible on primary surgically resected invasive breast carcinomas.

Methods: The cohort consisted of 50 cases of freshly sampled and formalin-fixed paraffin embedded (FFPE) invasive breast cancers and normal tissue.

The potential of identification of a malignancy-associated biomarker in breast cancer diagnosis and research: hTERT gene DNA methylation.

Background: DNA hypermethylation has been documented to be prominent at a CpG island rich region about 600 bp upstream the transcription start site of the hTERT gene using qualitative methylation specific PCR on DNA isolated from tumor cell lines. In order to assess the potential significance of this biomarker in breast cancer research and diagnosis, we explored if such findings are reproducible on surgically resected fresh breast tumor cells.

Methods: Using quantitative pyrosequencing technology, we investigated and present methylation status of four CpG islands of this region in a cohort of 77 invasive breast carcinomas using normal breast tissue as controls.

Characterization of KRAS Mutation in Acinar and Langerhans Islet Cells of Patients With Pancreatic Ductal Adenocarcinoma.

Objectives: KRAS mutations are frequent in pancreatic ductal adenocarcinoma, chronic pancreatitis, and mucinous neoplasms. In animal studies, KRAS mutations in acinar and Langerhans islets are associated with pancreatic intraepithelial neoplasia. Clinically, KRAS mutation is sometimes requested on cytology/biopsy specimens and negative results are helpful to rule out pancreatic ductal adenocarcinoma.

Analysis of an ordered, comprehensive STM mutant library in infectious Borrelia burgdorferi: insights into the genes required for mouse infectivity.

The identification of genes important in the pathogenesis of Lyme disease Borrelia has been hampered by exceedingly low transformation rates in low-passage, infectious organisms. Using the infectious, moderately transformable B. burgdorferi derivative 5A18NP1 and signature-tagged versions of the Himar1 transposon vector pGKT, we have constructed a defined transposon library for the efficient genome-wide investigation of genes required for wild-type pathogenesis, in vitro growth, physiology, morphology, and plasmid replication.

[Numerical study on inspiratory flows in two and three generation bronchi of human lung airways].

The main physiological function of respiratory system is exchange of oxygen and carbon dioxide between atmosphere and blood. Its physiological process is closely related with air flow and transport in respiratory airway. This paper studies numerically the inspiratory flows in a two generation and a three generation bronchial airway.

Progressive loss of malignant behavior in telomerase-negative tumorigenic adrenocortical cells and restoration of tumorigenicity by human telomerase reverse transcriptase.

Replicative senescence/crisis is thought to act as a tumor suppressor mechanism. Although recent data indicate that normal human cells cannot be converted into cancer cells without telomerase, the original concept of senescence as a tumor suppressor mechanism is that senescence/crisis would act to limit the growth of telomerase-negative tumors. We show here that this concept is valid when oncogene-expressing human and bovine cells are introduced into immunodeficient mice using tissue reconstruction techniques, as opposed to conventional subcutaneous injection.

Porcine kallikrein-4 activation, glycosylation, activity, and expression in prokaryotic and eukaryotic hosts.

Kallikrein-4 (KLK4) is a serine proteinase believed to be important in the normal development of dental enamel. We isolated native KLK4 from developing pig enamel and expressed four recombinant forms. Pig KLK4 was expressed in bacteria with and without the propeptide, and in two eukaryotic systems.

Characterization of porcine dentin sialoprotein (DSP) and dentin sialophosphoprotein (DSPP) cDNA clones.

Dentin sialophosphoprotein (DSPP) is a chimeric glycoprotein with dentin sialoprotein (DSP) on its N-terminus and dentin phosphoprotein (DPP) on its C-terminus. We have constructed and screened a unidirectional cDNA library derived from the pulp organ of developing pig teeth, and isolated cDNA clones encoding DSP-only, as well as two DSPP clones with alternative sequences in their 3' coding regions. The DSP-only transcript has an open reading frame of 386 codons, and is generated through the use of a polyadenylation signal within intron 4, immediately following the DSP coding region.

Porcine N-acetylgalactosamine 6-sulfatase (GALNS) cDNA sequence and expression in developing teeth.

Mucopolysaccharidosis type IVA (Morquio A syndrome, MPS IVA) is a rare, autosomal recessive disorder with a prevalence of 1 in 170,000 live births. It is caused by a deficiency of N-acetylgalactosamine 6-sulfatase (GALNS), a lysosomal hydrolase encoded by a gene on human chromosome 16q24.3.

Enamelysin and kallikrein-4 mRNA expression in developing mouse molars.

Proteolytic processing and degradation of enamel matrix proteins appears to be an essential feature of dental enamel formation. The source and character of proteolytic activity in the enamel matrix of developing teeth changes as enamel formation progresses. Two proteinases have been isolated from the extracellular enamel matrix of developing teeth: enamelysin (MMP-20), a matrix metalloproteinase.