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Biomedical subjects

Shuai Chen

Publications and source records attributed to Shuai Chen.

16 recordsLinked to original sources
PubMed2026

[Pathogenicity analysis and prenatal genetic counseling for five Chinese pedigrees harboring a hemizygous c.-32C>G variant of FGF13 gene].

OBJECTIVE: To explore the pathogenicity and prenatal counseling strategies for five Chinese pedigrees harboring a hemizygous c.-32C>G (NM_001139500.2) variant of fibroblast growth factor 13 (FGF13) gene. METHODS: Five Chinese pedigrees found to carry a hemizygous c.-32C>G variant of the FGF13 gene at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2024 and January 2025 were selected as study subjects. The pedigrees had undergone prenatal diagnosis for a family history of genetic disorders, abnormal fetal ultrasound findings, or advanced maternal age. A retrospective analysis was carried out, wherein clinical data for all members of the pedigrees were obtained through the medical records system and outpatient visit system. Peripheral blood samples were collected from all pedigree members, and amniotic fluid samples were obtained from the probands. Following extraction of genomic DNA, prenatal diagnosis was performed using chromosomal microarray analysis (CMA) and trio whole-exome sequencing (trio-WES). Sanger sequencing was used to determine the carrier status for the candidate variant, and Mini-Mental State Examination (MMSE) was used to assess the cognitive function of hemizygous individuals carrying the FGF13 gene c.-32C>G variant. Pathogenicity of candidate variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-171). RESULTS: CMA and trio-WES revealed no pathogenic variants in all probands, whilst trio-WES and Sanger sequencing had identified 11 male individuals carrying a hemizygous c.-32C>G variant of the FGF13 gene from the five pedigrees, which included six adult males, a young boy, and four fetuses. One fetus had undergone termination of pregnancy due to hydrocephalus, one was born pre-term at 34+1 weeks of gestation owing to maternal hypertension, and other two were delivered at full term. Follow-up of the survived males revealed no phenotypic manifestations related to language or intellectual impairment. Among these, three adult males underwent the MMSE assessment, all of whom showed normal cognitive function. Search of the gnomAD database suggested the carrier frequency of FGF13 c.-32C>G variant in the East Asian population to be 0.125%, with 11 hemizygous males documented. Three male patients harboring the variant showed severe intellectual disability. Both in vitro and in vivo studies suggested that it could reduce the translation levels of FGF13 protein. Based on the ACMG guidelines, it was classified as variant of uncertain significance (BS4+PS3_Supporting). CONCLUSION: There is insufficient evidence to classify the FGF13 c.-32C>G as a pathogenic variant in clinical practice, and its presence should not be considered an indication for pregnancy termination due to major birth defects.

Adult↗
PubMed2026

Uncovering metabolite-immune interactions in the pathogenesis of psoriatic arthritis: A 2-sample Mendelian randomization study.

PsA is a chronic inflammatory joint condition associated with psoriasis, and its underlying mechanisms are not fully elucidated. Serum metabolites, as direct reflections of metabolic status, may influence disease progression by regulating immune cell function; however, the causal relationships and specific pathways require further investigation. The present investigation utilized a 2-sample bidirectional MR methodology, leveraging extensive pooled GWAS data to thoroughly evaluate the causal relationships between 1440 serum metabolites and PsA. Additionally, mediation MR analysis was performed to explore the possible mediating effects of 731 immune cell characteristics. In the primary analysis, inverse-variance weighted was employed, and this was further supported by various sensitivity analyses to confirm the reliability of the findings. The genetic method to infer causality analysis revealed significant positive causal associations between 10 serum metabolites and PsA risk, with quinolinate levels demonstrating the most significant correlation (OR = 1.56, 95% CI: 1.26-1.93); while 4 metabolites (e.g., citrate levels, OR = 0.74, 95% CI: 0.61-0.89) exhibited protective effects. Regarding immune cells, 6 cellular features (e.g., CD20 on B cells) were positively correlated with disease risk, whereas 5 features (primarily HLA-DR expression on monocyte subsets) showed negative correlations. Mediation analysis identified 3 significant pathways,the percentage of the effect explained by the mediator: N6,N6,N6-trimethyllysine levels mediated via B cells (CD20 on IgD+ CD38br), with a proportion of 33.2%; 1-stearoyl-2-docosahexaenoyl-GPE (18:0/22:6) levels mediated through monocytes (HLA-DR on CD14- CD16-) with a 32.0% proportion; the unknown metabolite X-24736 also mediated 42.1% of the protective effect via the same monocyte phenotype. This study revealed that elevated amino acid-related metabolites and glycerophospholipids significantly increase PsA risk through immune cell effects. These are closely associated with PsA pathogenesis and may serve as potential biomarkers. The novel findings underscore metabolic-immune interactions as targets for biomarkers and therapies in PsA, advancing personalized medicine.

Humans↗
PubMed2026

Integrin α3 (ITGA3) expression across breast cancer subtypes: Prognosis and therapeutic relevance.

BACKGROUND: Integrin &#x3b1;3 (ITGA3), which heterodimerizes with integrin &#x3b2;1, has emerged as a potential biomarker and therapeutic target in several epithelial malignancies; however, its clinical relevance in breast cancer remains incompletely characterized. This study evaluated ITGA3 expression across breast cancer molecular subtypes and assessed its prognostic and predictive significance. METHODS: Immunohistochemistry (IHC) was performed on archival breast cancer specimens using tissue microarrays (n = 148) and whole-tissue sections (n = 21). Complete clinicopathologic and outcome data were available for 108 patients, including hormone receptor-positive/human epidermal growth factor receptor 2-negative, HER2-positive, and triple-negative breast cancer (TNBC) subtypes. ITGA3 expression was quantified using H-scores and correlated with clinicopathologic features and survival outcomes. Independent transcriptomic analyses were conducted using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) cohorts to evaluate ITGA3 mRNA expression, co-expressed signaling pathways, and associations with therapeutic response. RESULTS: ITGA3 protein expression was detected in 85.2% of breast cancer specimens and was significantly higher in HR-positive/HER2-negative and HER2-positive tumors compared with TNBC (p < 0.0050). High ITGA3 expression was associated with shorter recurrence-free survival (p < 0.0001). In the METABRIC cohort, tumors with ITGA3 alterations demonstrated significantly worse relapse-free survival (p < 0.0001) and overall survival (p < 0.0500). Transcriptomic analyses revealed that ITGA3 co-expressed with estrogen receptor 1(ESR1), erb-b2 receptor tyrosine kinase 2 (ERBB2), and luminal markers, along with enrichment of estrogen receptor and phosphoinositide 3-kinase-protein kinase B-mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathways. ITGA3 expression was not predictive of response to tamoxifen or trastuzumab. CONCLUSION: Elevated ITGA3 expression is associated with breast cancer recurrence and poor clinical outcomes, supporting its potential role as a prognostic biomarker and candidate therapeutic target.

Biomarkers↗
PubMed2025

A consensus guide to preclinical indirect calorimetry experiments.

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data repository built on shared standards. This overdue initiative stands to markedly improve the accuracy and depth of efforts to interrogate mammalian metabolism. Data sharing according to established best practices will also accelerate the translation of basic findings into clinical applications for metabolic diseases afflicting global populations.

Calorimetry, Indirect↗
PubMed2006

Discovering severe acute respiratory syndrome coronavirus 3CL protease inhibitors: virtual screening, surface plasmon resonance, and fluorescence resonance energy transfer assays.

An integrated system has been developed for discovering potent inhibitors of severe acute respiratory syndrome coronavirus 3C-like protease (SARS-CoV 3CL(pro)) by virtual screening correlating with surface plasmon resonance (SPR) and fluorescence resonance energy transfer (FRET) technologies-based assays. The authors screened 81,287 small molecular compounds against SPECS database by virtual screening; 256 compounds were subsequently selected for biological evaluation. Through SPR technology-based assay, 52 from these 256 compounds were discovered to show binding to SARS-CoV 3CL(pro). The enzymatic inhibition activities of these 52 SARS-CoV 3CL(pro) binders were further applied to FRET-based assay, and IC(50) values were determined. Based on this integrated assay platform, 8 new SARS-CoV 3CL(pro) inhibitors were discovered. The fact that the obtained IC(50) values for the inhibitors are in good accordance with the discovered dissociation equilibrium constants (K(D)s) assayed by SPR implied the reliability of this platform. Our current work is hoped to supply a powerful approach in the discovery of potent SARS-CoV 3CL(pro) inhibitors, and the determined inhibitors could be used as possible lead compounds for further research.

Binding Sites↗
PubMed2006

Deterministic and storable single-photon source based on a quantum memory.

A single-photon source is realized with a cold atomic ensemble (87Rb atoms). A single excitation, written in an atomic quantum memory by Raman scattering of a laser pulse, is retrieved deterministically as a single photon at a predetermined time. It is shown that the production rate of single photons can be enhanced considerably by a feedback circuit while the single-photon quality is conserved. Such a single-photon source is well suited for future large-scale realization of quantum communication and linear optical quantum computation.

Journal Article↗
PubMed2006

An overall picture of SARS coronavirus (SARS-CoV) genome-encoded major proteins: structures, functions and drug development.

A severe atypical pneumonia designated as severe acute respiratory syndrome (SARS) by The World Health Organization broke out in China and menaced to more than other 30 countries between the end of the year 2002 and June of the year 2003. A novel coronavirus called severe acute respiratory syndrome coronavirus (SARS-CoV) has been recently identified as the etiological agent responsible for the infectious SARS disease. Based on extensively scientific cooperation and almost two-year's studies, remarkable achievements have been made in the understanding of the phylogenetic property and the genome organization of SARS-CoV, as well as the detailed characters of the major proteins involved in SARS-CoV life cycle. In this review, we would like to summarize the substantial scientific progress that has been made towards the structural and functional aspects of SARS-CoV associated key proteins. The progress focused on the corresponding key proteins' structure-based drug and vaccine developments has been also highlighted. The concerted and cooperative response for the treatment of the SARS disease has been proved to be a triumph of global public health and provides a new paradigm for the detection and control of future emerging infectious disease threats.

Antiviral Agents↗
PubMed2005

Differential expression of sucrose-phosphate synthase isoenzymes in tobacco reflects their functional specialization during dark-governed starch mobilization in source leaves.

Sucrose (Suc)-phosphate synthase (SPS) plays a crucial role in the synthesis of Suc in photosynthetic and nonphotosynthetic tissues. Several isoforms of SPS exist in dicotyledonous plants that can be grouped into the different families A, B, and C. To explore whether functional differences between the SPS gene families might exist, we characterized a representative for each family from tobacco (Nicotiana tabacum). RNA-blot analysis revealed a distinct expression pattern for each of the three SPS genes. While the A-family member (NtSPSA) was found to be expressed in all tissues examined, expression of the B isoform (NtSPSB) was mainly confined to the reproductive organs and NtSPSC mRNA was exclusively detected in mature source leaves. We used RNA interference to assess the in planta function of NtSPSA and C. While silencing of NtSPSA had no detectable influence on leaf carbohydrate metabolism, reduction of NtSPSC led to an increase in leaf starch content by a factor of 3 to 8. Further analysis revealed that starch accumulation in NtSPSC-silenced plants was not due to an increased partitioning of carbon into starch, but rather showed that starch mobilization was impaired. The transgenic plants were unable to efficiently mobilize their transitory leaf starch during a prolonged period of darkness and accumulated maltose as a major intermediate of starch breakdown. NtSPSC mRNA level increased appreciably during the dark period while transcript levels of the other isoforms showed no diurnal changes. Together, these results suggest that NtSPSC is specifically involved in the synthesis of Suc during starch mobilization in the dark. The roles of the other SPS isoforms are discussed.

Amino Acid Sequence↗
PubMed2005

Decreased sucrose-6-phosphate phosphatase level in transgenic tobacco inhibits photosynthesis, alters carbohydrate partitioning, and reduces growth.

The aim of this work was to examine the role of sucrose-6-phosphate phosphatase (SPP; EC 3.1.3.24) in photosynthetic carbon partitioning. SPP catalyzes the final step in the pathway of sucrose synthesis; however, until now the importance of this enzyme in plants has not been studied by reversed-genetics approaches. With the intention of conducting such a study, transgenic tobacco plants with reduced SPP levels were produced using an RNA interference (RNAi) strategy. Transformants with less than 10% of wild-type SPP activity displayed a range of phenotypes, including those that showed inhibition of photosynthesis, chlorosis, and reduced growth rates. These plants had strongly reduced levels of sucrose and hexoses but contained 3-5 times more starch than the control specimens. The leaves were unable to export transient starch during extended periods of darkness and as consequence showed a starch- and maltose-excess phenotype. This indicates that no alternative mechanism for carbon export was activated. Inhibition of SPP resulted in an approximately 1,000-fold higher accumulation of sucrose-6-phosphate (Suc6P) compared to wild-type leaves, whereas the content of hexose-phosphates was reduced. Although the massive accumulation of Suc6P in the cytosol of transgenic leaves was assumed to impair phosphate-recycling into the chloroplast, no obvious signs of phosphate-limitation of photosynthesis became apparent. 3-Phosphoglycerate (3-PGA) levels dropped slightly and the ATP/ADP ratio was not reduced in the transgenic lines under investigation. It is proposed that in SPP-deficient plants, long-term compensatory responses give rise to the observed acceleration of starch synthesis, increase in total cellular Pi content, decrease in protein content, and related reduction in photosynthetic activity.

Carbohydrate Metabolism↗
PubMed2005

Enzymatic activity characterization of SARS coronavirus 3C-like protease by fluorescence resonance energy transfer technique.

AIM: To characterize enzymatic activity of severe acute respiratory syndrome (SARS) coronavirus (CoV) 3C-like protease (3CL(pro)) and its four site-directed mutants. METHODS: Based on the fluorescence resonance energy transfer (FRET) principle using 5-[(2'-aminoethyl)-amino] naphthelenesulfonic acid (EDANS) and 4-[[4-(dimethylamino) phenyl] azo] benzoic acid (Dabcyl) as the energy transfer pair, one fluorogenic substrate was designed for the evaluation of SARS-CoV 3CL(pro) proteolytic activity. RESULTS: The kinetic parameters of the fluorogenic substrate have been determined as Km=404 micromol.L(-1), kcat=1.08 min(-1), and kcat/Km=2.7 mmol(-1).L.min(-1). SARS-CoV 3CL(pro) showed substantial pH and temperature-triggered activity switches, and site-directed mutagenesis analysis of SARS-CoV 3CL(pro) revealed that substitutions of His41, Cys145, and His163 resulted in complete loss of enzymatic activity, while replacement of Met162 with Ala caused strongly increased activity. CONCLUSION: This present work has provided valuable information for understanding the catalytic mechanism of SARS-CoV 3CL(pro). This FRET-based assay might supply an ideal approach for the exploration SARS-CoV 3CL(pro) putative inhibitors.

Alanine↗
PubMed2005

Co-evolution analysis on endocrine research: a methodological approach.

The rapid growth of different kinds of biological information allows a good opportunity to analyze the co-evolutionary characteristics in endocrine regulatory pathways. Data ranging from kinds of species' genome, gene sequence, protein structure, and expression profile of different organisms can reveal the inner co-evolutionary relationship of ligands, receptors, and other related molecules. In return, these co-evolutionary characteristics can help us determine uncharacterized ligands and receptors, annotate gene functions, highlight amino acid residues with biochemical significance, and identify regulated genes in the endocrine process. Encouraging examples in this field, although at their starting stage, have emerged. Here we focus on recent progress in endocrine-related co-evolution research from a methodological approach.

Endocrine System↗
PubMed2004

Severe acute respiratory syndrome coronavirus 3C-like proteinase N terminus is indispensable for proteolytic activity but not for enzyme dimerization. Biochemical and thermodynamic investigation in conjunction with molecular dynamics simulations.

Severe acute respiratory syndrome (SARS) coronavirus is a novel human coronavirus and is responsible for SARS infection. SARS coronavirus 3C-like proteinase (SARS 3CL(pro)) plays key roles in viral replication and transcription and is an attractive target for anti-SARS drug discovery. In this report, we quantitatively characterized the dimerization features of the full-length and N-terminal residues 1-7 deleted SARS 3CL(pro)s by using glutaraldehyde cross-linking SDS-PAGE, size-exclusion chromatography, and isothermal titration calorimeter techniques. Glutaraldehyde cross-linking SDS-PAGE and size-exclusion chromatography results show that, similar to the full-length SARS 3CL(pro), the N-terminal deleted SARS 3CL(pro) still remains a dimer/monomer mixture within a wide range of protein concentrations. Isothermal titration calorimeter determinations indicate that the equilibrium dissociation constant (K(d)) of the N-terminal deleted proteinase dimer (262 microm) is very similar to that of the full-length proteinase dimer (227 microm). Enzymatic activity assay using the fluorescence resonance energy transfer method reveals that N-terminal deletion results in almost complete loss of enzymatic activity for SARS 3CL(pro). Molecular dynamics and docking simulations demonstrate the N-terminal deleted proteinase dimer adopts a state different from that of the full-length proteinase dimer, which increases the angle between the two protomers and reduces the binding pocket that is not beneficial to the substrate binding. This conclusion is verified by the surface plasmon resonance biosensor determination, indicating that the model substrate cannot bind to the N-terminal deleted proteinase. These results suggest the N terminus is not indispensable for the proteinase dimerization but may fix the dimer at the active state and is therefore vital to enzymatic activity.

Binding Sites↗
PubMed2003

Temporal and spatial control of gene silencing in transgenic plants by inducible expression of double-stranded RNA.

Downregulation of endogenous genes via post-transcriptional gene silencing (PTGS) is a key to the characterization of gene function in plants. The recent discovery that double-stranded RNA (dsRNA) is an extremely effective trigger of gene silencing greatly enhanced the predictability of this approach. However, strong constitutive silencing often leads to pleiotropic effects, which make it difficult to directly relate phenotype to gene function, or even interferes with the recovery of viable transgenic plants. Here, we show that strong genetic interference can be achieved in a chemically inducible fashion, allowing for temporal and spatial control of gene silencing in transgenic plants. To this end, transgenic tobacco plants were established expressing dsRNA in the form of intron-spliced hairpin structures under the control of the ethanol-inducible alc gene expression system. Targeting magnesium (Mg)-chelatase subunit I (Chl I) and glutamate 1-semialdehyde aminotransferase (GSA), both involved in chlorophyll (chl) biosynthesis, resulted in rapid and specific mRNA degradation upon induction with ethanol. Ethanol-inducible silencing of the target genes caused strong but transient phenotypical alterations featured by a progressive loss of chl in young leaves, which persisted for about 7-9 days before newly growing leaves completely recovered. About 10-30% of the primary transformants showed phenotype development upon induction. Local silencing of Chl I could be achieved by confined ethanol treatment of a single leaf without affecting any other part of the plant. Inducible gene silencing using the alc system promises to obviate the problems associated with constitutive RNA silencing and enables to dissect primary and secondary effects of PTGS at temporal and spatial resolution.

Enzymes↗
PubMed2003

Isolation, expression pattern of a novel human RAB gene RAB41 and characterization of its intronless homolog RAB41P.

Small GTPases form a big family including Ras, Rho, Rac, Rab, Sar1/Arf subfamilies and Ran homologs, playing important roles in diverse cellular processes. Through data mining, a novel human RAB41 gene was predicted and subsequently isolated from human testis. The open reading frame of RAB41 is 636bp in length. RAB41 was composed of three exons, and it was mapped to chromosome 3q21.3 by comparing with the human genomic data. RAB41 protein contains a RAB domain. Similarity analysis indicated that RAB41 is closely similar to RAB19. The results of PCR amplification indicated that human RAB41 is widely expressed in brain, testis, lung, heart, ovary, colon, kidney, uterus and spleen but not in liver. By genomic searching, an intronless pseudogene homologous to RAB41 at chromosome 16--RAB41P was identified at human chromosome 16q11.2. Flanking the pseudogene RAB41P in human genome, there exist some transposable elements LINEs--L1, whose contribution in the generation of this intronless homolog is discussed.

Amino Acid Sequence↗
PubMedDate not supplied

Cloning and characterization of human CAGLP gene encoding a novel EF-hand protein.

The EF-hand proteins, containing conserved Ca2+ binding motifs, play important roles in many biological processes. Through data mining, a novel human gene, CAGLP (calglandulin-like protein) was predicted and subsequently isolated from human skeleton muscle. The open reading frame of CAGLP is 543 bp in length, coding a putative Ca2+ binding protein with four EF-hand motifs. The deduced amino acid sequence of CAGLP displays high similarity with Bothrops insularis snake protein calglandulin (80%). The results of PCR amplification using cDNA from 17 human tissues indicated that human CAGLP is expressed in prostate, thymus, heart, skeleton muscle, bone marrow and ovary. Functional CAGLP::EGFP (enhanced green fluorescent protein) fusion protein revealed that CAGLP accumulated through-out Hela cells. Western blot using anti-EGFP antibodies indicated that the CAGLP protein has a molecular weight of about 19 kD. A phylogenetic tree showed that CAGLP and calglandulin may be orthologous proteins representing a distinct group in the EF-hand proteins.

Base Sequence↗