Biomedical subjects

Huiping Li

Publications and source records attributed to Huiping Li.

13 recordsLinked to original sources

PubMed2025

Identification of pathogenic variants in six Chinese families with keratoconus of autosomal dominant inheritance: pathogenicity analysis and variable phenotype.

PURPOSE: Keratoconus (KC) is a bilateral, asymmetric disease causing corneal thinning, irregular astigmatism, and vision decline, with unclear etiology. This study aims to investigate pathogenic variants of candidate genes in Chinese KC families via whole exome sequencing (WES). METHODS: The Pentacam 3D anterior segment analysis system was applied for keratectasia detection, and the Corvis ST was used for corneal biomechanics measurement. Probands from KC families were screened via WES and further verified in other family members through Sanger sequencing. Additionally, qPCR was used to validate copy number variants and identify pathogenic gene loci. The identified variants were then classified according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the American College of Medical Genetics and Genomics (ACMG). Finally, STRING protein-protein interaction (PPI) networks analysis was performed to investigate interactions among candidate gene-related proteins. RESULTS: Using WES, four heterozygous missense variants were detected in the ZNF469, KRT12, COL8A2, and COL18A1 genes: c.4384G > A: p.Asp1462Asn, c.1229T > G:p.Val410Gly, c.505A > G:p.Ile169Val, and c.1159G > A:p.Gly387Arg. Additionally, a heterozygous frameshift variant was detected in the PMS2 gene: c.1551_1572del:p.Ser517Argfs*71. The affected parents carried the same variants as the probands verified by Sanger sequencing. A copy number variant was detected in the DPP6 gene: seq[GRCh38] dup(7)(q36.2q36.2) chr7:g.153782360_ 153982491dup. According to ACMG guidelines, ZNF469, KRT12, COL8A2, and COL18A1 gene variants are Likely Pathogenic; PMS2 and DPP6 gene variants are Pathogenic. STRING analysis highlights a tightly interconnected network centered on COL8A2, involving COL18A1, FN1, ZNF469, and KRT12. DPP6 was involved in KC via affecting FN1. In four of six autosomal dominant KC (adKC) families, affected parents had the same variants as probands but milder phenotypes. CONCLUSION: In this study, six novel variants in ZNF469, KRT12, COL8A2, COL18A1, PMS2, and DPP6 were linked to adKC. Family phenotypes showed variable expressivity with irregular dominance inheritance. Abnormal KC-related gene protein expression may contribute to corneal structural instability. This study broadened KC genetic screening candidates and suggested genetic testing could aid early KC diagnosis and intervention.

Adult↗

PubMed2006

Molecular characterization of water-selective AQP (EbAQP4) in hagfish: insight into ancestral origin of AQP4.

Hagfish (Eptatretus burgeri) are agnathous and are the earliest vertebrates still in existence. Pavement cells adjacent to the mitochondria-rich cells show orthogonal arrays of particles (OAPs) in the gill of hagfish, a known ultrastructural morphology of aquaporin (AQP) in mammalian freeze-replica studies, suggesting that an AQP homolog exists in pavement cells. We therefore cloned water channels from hagfish gill and examined their molecular characteristics. The cloned AQP [E. burgeri AQP4 (EbAQP4)] encodes 288 amino acids, including two NPA motifs and six transmembrane regions. The deduced amino acid sequence of EbAQP4 showed high homology to mammalian and avian AQP4 (rat, 44%; quail, 43%) and clustered with AQP4 subsets by the molecular phylogenetic tree. The osmotic water permeability of Xenopus oocytes injected with EbAQP4 cRNA increased eightfold compared with water-injected controls and was not reversibly inhibited by 0.3 mM HgCl(2). EbAQP4 mRNA expression in the gill was demonstrated by the RNase protection assay; antibody raised against the COOH terminus of EbAQP4 also detected (by Western blot analysis) a major approximately 31-kDa band in the gill. Immunohistochemistry and immunoelectron microscopy showed EbAQP4 localized along the basolateral membranes of gill pavement cells. In freeze-replica studies, OAPs were detected on the protoplasmic face of the split membrane comprising particles 5-6 nm long on the basolateral side of the pavement cells. These observations suggest that EbAQP4 is an ancestral water channel of mammalian AQP4 and plays a role in basolateral water transport in the gill pavement cells.

Amino Acid Sequence↗

PubMed2006

Upregulation of nestin, vimentin, and desmin in rat podocytes in response to injury.

Podocytes in the renal glomerulus express unusual intermediate filament (IF) proteins for epithelial cells. To gain insight into the role of IF proteins in podocytes, we investigated the expression of nestin, vimentin, and desmin in puromycin aminonucleoside (PAN) nephrosis. A Western blot analysis for nestin, vimentin, and desmin demonstrated their exclusive expression in glomeruli and showed their increase in expression in nephrotic glomeruli. Immunolocalization studies showed nestin and vimentin to be located predominantly in the podocytes in both normal and nephrotic glomeruli and that enhancement of desmin staining only occurred in podocytes. A ribonuclease protection assay showed high levels of vimentin and nestin expression in normal glomeruli and an upregulation of all three IF transcripts in nephrotic glomeruli. One day after the PAN injection, however, the vimentin transcripts were found to already have significantly increased, whereas those of nestin or desmin showed no such increase. These findings indicate that podocytes express three IF proteins, namely, vimentin, desmin, and nestin, which are differentially regulated in response to injury. An upregulation of IF proteins may increase the mechanical stability of cells, thus enabling podocytes to undergo morphological changes on the tensile glomerular capillary wall.

Animals↗

PubMed2005

Expression and localization of two isoforms of AQP10 in human small intestine.

BACKGROUND INFORMATION: AQP10 (aquaporin 10) is a new member of water channels and two different transcripts have been reported. The difference between these transcripts is in the presence or the absence of an insertion of 475 nt, which leads to a translation frame shift resulting in a different termination of amino acid translation and synthesis of a shorter form of AQP10. Thus an AQP10 molecule deduced from the transcript with an insertion has a distinct C-terminus, different from that translated from the transcript without the insertion. In the present study, we investigated the expression and localization of these AQP10 isoforms. RESULTS: Two transcripts were expressed in human duodenum and jejunum. Western-blot analysis using antibodies for these AQP10 isoforms immunoblotted two bands of approx. 35 and 30 kDa respectively. Immunohistochemistry and immunoelectron microscopy demonstrated localization of the AQP10 with an insertion in the capillary endothelium in villi of the small intestine and the isoform without the insertion in the gastro-entero-pancrestic endocrine cells. CONCLUSION: The different forms of localization of the AQP10 isoforms indicate that they may play different roles in the proximal portion of human small intestine.

Amino Acid Sequence↗

PubMed2005

A parallel-line detection algorithm based on HMM decoding.

The detection of groups of parallel lines is important in applications such as form processing and text (handwriting) extraction from rule lined paper. These tasks can be very challenging in degraded documents where the lines are severely broken. In this paper, we propose a novel model-based method which incorporates high-level context to detect these lines. After preprocessing (such as skew correction and text filtering), we use trained Hidden Markov Models (HMM) to locate the optimal positions of all lines simultaneously on the horizontal or vertical projection profiles, based on the Viterbi decoding. The algorithm is trainable so it can be easily adapted to different application scenarios. The experiments conducted on known form processing and rule line detection show our method is robust, and achieves better results than other widely used line detection methods.

Algorithms↗

PubMed2004

Fc receptor-mediated accumulation of macrophages in crescentic glomerulonephritis induced by anti-glomerular basement membrane antibody administration in WKY rats.

Anti-glomerular basement membrane (GBM) glomerulonephritis induced in WKY rats is characterized by glomerular accumulation of CD8(+) T cells and monocytes/macrophages, followed by crescent formation. The mechanism of leukocyte accumulation after antibody binding to GBM is still unclear. To unveil an involvement of Fcgamma receptors (FcgammaR) in leukocytes recruitment we examined the expression of FcgammaR in glomeruli and the effects of the administration of F(ab')(2) fragment of anti-GBM antibody or FcgammaR blocking on the initiation and progression of this model. A gradual increase of FcgammaR mRNA expression in glomeruli during the time course of disease suggested their significance in the development of glomerulonephritis. Glomerular lesions and proteinuria were induced only in rats injected with intact IgG of anti-GBM antibody, but not with the F(ab')(2) fragment. In vivo blocking of FcgammaR by administering heat-aggregated IgG led to the decrease of mRNA expression for all types of FcgammaR (types 1, 2 and 3) and a significant amelioration of glomerulonephritis manifestations. By flow cytometry and immunohistochemistry FcgammaR2-expressing cells in glomeruli were identified as macrophages, but not CD8(+) T cells. The expression of FcgammaR1 and 3 was significantly decreased, and that of FcgammaR2 became undetectable in CD8(+) T cell-depleted rats. Thus, CD8(+) T cells may stimulate FcgammaR expression on macrophages, contributing to their glomerular accumulation and injury. These studies provide direct evidence for a crucial involvement of IgG Fc-FcgammaR interaction in glomerular recruitment of macrophages and following induction of anti-GBM glomerulonephritis in WKY rats.

Animals↗

PubMed2004

Machine printed text and handwriting identification in noisy document images.

In this paper, we address the problem of the identification of text in noisy document images. We are especially focused on segmenting and identifying between handwriting and machine printed text because: 1) Handwriting in a document often indicates corrections, additions, or other supplemental information that should be treated differently from the main content and 2) the segmentation and recognition techniques requested for machine printed and handwritten text are significantly different. A novel aspect of our approach is that we treat noise as a separate class and model noise based on selected features. Trained Fisher classifiers are used to identify machine printed text and handwriting from noise and we further exploit context to refine the classification. A Markov Random Field-based (MRF) approach is used to model the geometrical structure of the printed text, handwriting, and noise to rectify misclassifications. Experimental results show that our approach is robust and can significantly improve page segmentation in noisy document collections.

Algorithms↗

PubMed2004

MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met.

A cDNA encoding a novel mucin protein, MUC20, was isolated as a gene that is up-regulated in the renal tissues of patients with immunoglobulin A nephropathy. We demonstrate here that the C terminus of MUC20 associates with the multifunctional docking site of Met without ligand activation, preventing Grb2 recruitment to Met and thus attenuating hepatocyte growth factor (HGF)-induced transient extracellular signal-regulated kinase-1 and -2 activation. Production of MUC20 reduced HGF-induced matrix metalloproteinase expression and proliferation, which require the Grb2-Ras pathway, whereas cell scattering, branching morphogenesis, and survival via the Gab1/phosphatidylinositol 3-kinase (PI3K) pathways was not affected. Thus, MUC20 reduces HGF-induced activation of the Grb2-Ras pathway but not the Gab1/PI3K pathways. We further demonstrate that the cytoplasmic domain of MUC20 has the ability to oligomerize and that the oligomerization augments its affinity for Met. Taken together, these results suggest that MUC20 is a novel regulator of the Met signaling cascade which has a role in suppression of the Grb2-Ras pathway.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Molecular cloning, genomic structure, and expression analysis of MUC20, a novel mucin protein, up-regulated in injured kidney.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Here, we identify a cDNA encoding a novel mucin protein, shown previously to be up-regulated in IgAN patients, from a human kidney cDNA library. This protein contains a mucin tandem repeat of 19 amino acids consisting of many threonine, serine, and proline residues and likely to be extensively O-glycosylated; thus, this gene was classified in the mucin family and named MUC20. The human MUC20 gene contains at least four exons and is localized close to MUC4 on chromosome 3q29. We found variations in repeat numbers in the mucin tandem domain, suggesting polymorphism of this region. Northern blot and reverse transcription-PCR analyses revealed that human MUC20 mRNA was expressed most highly in kidney and moderately in placenta, colon, lung, prostate, and liver. Immunohistochemical analysis of human kidney revealed that MUC20 protein was localized in the proximal tubules. Immunoblotting analysis of MUC20 proteins produced in Madin-Darby canine kidney and HEK293 cells indicated the localization of MUC20 protein in a membrane fraction and extensive posttranslational modification. Immunoelectron microscopy of MUC20-producing Madin-Darby canine kidney cells demonstrated that MUC20 protein was localized on the plasma membrane. Expression of MUC20 mRNA in a human kidney cell line was up-regulated by tumor necrosis factor-alpha, phorbol 12-myristate 13-acetate, or lipopolysaccharide. Two species of MUC20 mRNA (hMUC20-L and hMUC20-S), resulting from alternative transcription, were identified in human tissue, whereas only one variant was observed in mouse tissues. Mouse MUC20 mRNA was expressed in the epithelial cells of proximal tubules, and the expression increased dramatically with the progression of lupus nephritis in the kidney of MRL/MpJ-lpr/lpr mice. Moreover, the expression of mouse MUC20 was augmented in renal tissues acutely injured by cisplatin or unilateral ureteral obstruction. These characteristics suggest that the production of MUC20 is correlated with development and progression of IgAN and other renal injuries.

Amino Acid Sequence↗

PubMed2003

Different expression patterns of Bcl-2, Bcl-xl, and Bax proteins after sublethal forebrain ischemia in C57Black/Crj6 mouse striatum.

BACKGROUND AND PURPOSE: Ischemic injury in neurons can be strongly reduced by a preceding sublethal ischemic episode, of which the mechanism is poorly understood. Although changes in the expression of apoptosis-related proteins (Bcl-2, Bcl-xl, and Bax) have been considered to be crucially important in ischemic injury, the roles these proteins play in ischemic preconditioning induced by sublethal forebrain ischemia have not been elucidated. Therefore, we investigated the transcription and expression of Bcl-2, Bcl-xl, and Bax in striatum of mice subjected to sublethal forebrain ischemia and lethal ischemia, with or without ischemic preconditioning. METHODS: Sublethal forebrain ischemia was induced in C57Black/Crj6 (C57BL/6) mice by 6 minutes of bilateral common carotid artery occlusion. The transcription and expression of Bcl-2 family genes were detected by reverse transcription-polymerase chain reaction, Western blot, and immunofluorescent staining. RESULTS: No detectable neuronal loss was induced in striatum by 6 minutes of bilateral common carotid artery occlusion. Transcription and expression of Bcl-2 and Bcl-xl were increased after sublethal forebrain ischemia, which attenuated the DNA fragmentation induced by lethal ischemia. The transcription and expression of Bax remained unchanged. CONCLUSIONS: Upregulation of Bcl-2 and Bcl-xl but not Bax may have a role in protective ischemic preconditioning. This result indicates a potential strategy for further ischemic neuronal injury therapies.

Animals↗

PubMed2003

A step-wise application of methylprednisolone versus dexamethasone in the treatment of acute exacerbations of COPD.

OBJECTIVE: The aim of the study was to explore the clinical value of a step-wise application of methylprednisolone (MP) compared to dexamethasone (DXM) in acute exacerbations of COPD. METHODOLOGY: One hundred and forty-two patients with an acute exacerbation of COPD were divided randomly into two groups: 71 patients were treated with MP and the other 71 patients were treated with DXM. Otherwise each group was given the same basic treatments: antibiotics, bronchodilators, oxygen therapy as well as standard hospital care. The patients in the MP group were given a tapering dose of MP for 7-14 days, and the patients in the DXM group were given a corresponding tapering dose of DXM for 7-14 days. Then both groups were given a gradually reducing dose of oral prednisone for 2-3 weeks. Two weeks before the prednisone was tapered off, inhaled corticosteroid was introduced. The patients' symptom scores, physical signs, per cent predicted FEV1%, and arterial blood gases were monitored before treatment and after the seventh day of treatment. RESULTS: There was an obvious improvement in symptoms after 1-3 days in all 71 patients in the MP group, with their wheezing being distinctly reduced or disappearing entirely. The maximum benefit that occurred in the MP group (90.14%) was considerably higher than that of the DXM group (25.35%), P < 0.05. The predicted FEV1% in the MP group increased from 46.7 +/- 10.6 to 67.5 +/- 12.4, compared with an increase in the DXM group from 50.1 +/- 7.6 to 58.9 +/- 10.8. The difference between the two groups was significant (P < 0.05). CONCLUSIONS: An adequate and tapering dose of MP used in acute exacerbations of COPD can relieve the inflammatory reaction in airways and reduce airway spasm more promptly than DXM.

Acute Disease↗

PubMed2003

Nucleocytoplasmic shuttling of p53 is essential for MDM2-mediated cytoplasmic degradation but not ubiquitination.

As a shuttling protein, p53 is constantly transported through the nuclear pore complex. p53 nucleocytoplasmic transport is carried out by a bipartite nuclear localization signal (NLS) located at its C-terminal domain and two nuclear export signals (NES) located in its N- and C-terminal regions, respectively. The role of nucleocytoplasmic shuttling in p53 ubiquitination and degradation has been a subject of debate. Here we show that the two basic amino acid groups in the p53 bipartite NLS function collaboratively to import p53. Mutations disrupting individual amino acids in the NLS, although causing accumulation of p53 in the cytoplasm to various degrees, reduce but do not eliminate the NLS activity, and these mutants remain sensitive to MDM2 degradation. However, disrupting both parts of the bipartite NLS completely blocks p53 from entering the nucleus and causes p53 to become resistant to MDM2-mediated degradation. Similarly, mutations disrupting four conserved hydrophobic amino acids in the p53 C-terminal NES block p53 export and prohibit it from MDM2 degradation. We also show that colocalization of a nonshuttling p53 with MDM2 either in the nucleus or in the cytoplasm is sufficient for MDM2-induced p53 polyubiquitination but not degradation. Our data provide new insight into the mechanism and regulation of p53 nucleocytoplasmic shuttling and degradation.

Active Transport, Cell Nucleus↗

PubMed2002

[A clinicopathologic study of nonspecific interstitial pneumonia].

OBJECTIVE: To investigate the clinicopathologic features of nonspecific interstitial pneumonia (NSIP). METHODS: The clinical and pathological data of 8 cases with NSIP confirmed by open or video-assisted thoracoscopic lung biopsy were reviewed retrospectively. RESULTS: NSIP occurred more in female (male:female 1:3, 2/6), and the patients' average age was 48 years. The clinical manifestation was progressive dyspnea, cough and sputum, crackles over both lungs and restrictive ventilating abnormalities. Reticular changes and patchy ground-glass attenuation in lower lung fields were the main findings on high resolution computed tomography. The pathological characteristic was uniform interstitial inflammation and fibrosis. Three cases showed fibroblast foci, was BOOP like changes in 4 and honeycombing in 1 case. of the 8 patients, 6 had cellular and fibrosing patterns; 2 had fibrosing patterns only; the former showed better response to glucocorticoid therapy than the latter. CONCLUSIONS: The histologic patterns of NSIP correlated closely with the therapeutic effect of glucocorticoids. It is difficult to differentiate pathologically the fibrosing pattern of NSIP from usual interstitial pneumonia, therefore clinical data are indispensable in the diagnosis.

Adult↗