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Biomedical subjects

Fei Yan

Publications and source records attributed to Fei Yan.

16 recordsLinked to original sources

Ergothioneine Alleviated the Apoptosis of HK Cells by Regulating Ferroptosis.

INTRODUCTION/OBJECTIVE: Ergothioneine (EGT) is a naturally occurring antioxidant with protective effects on various human cell types. The impact of this substance on HK-2 cells, a human renal proximal tubular epithelial cell line, and the associated molecular mechanisms remain incompletely elucidated. METHODS: The present study aims to elucidate the effects of EGT on apoptosis induced by RAS-selective Lethal Molecule 3 (RSL3) and Erastin in HK-2 cells, as well as the potential mechanisms involved. The renal cortical proximal tubular epithelial HK-2 cells were cultured and exposed to RSL3 and Erastin, with or without EGT treatment. Cell viability and apoptosis were assessed using the Cell Counting Kit-8 (CCK-8) assay, while the detection of ferrous ion content and mitochondrial membrane potential changes was accomplished through the utilisation of flow cytometry and the JC-1 staining method, respectively. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, proteomic analysis, and western blotting were employed to explore the molecular pathways involved. RESULTS: The data demonstrated that RSL3 and Erastin exhibited a substantial inhibitory effect on HK-2 cell proliferation, concomitant with the accumulation of intracellular ferrous ions and a shift in mitochondrial membrane potential. The EGT treatment effectively mitigated RSL3- and Erastin-induced apoptosis in HK-2 cells. GO and KEGG enrichment analysis demonstrated that EGT suppressed pathways and functions associated with oxidative stress during ferroptosis. Proteomics analysis further demonstrated that EGT modulated various biological processes, molecular functions, and cellular components in HK-2 cells. The protective mechanism of EGT against RSL3- and Erastin-induced HK-2 cells was potentially mediated through regulation of ferroptosis. The results of the western blot analysis demonstrated that EGT modulated the expression levels of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 member 11 (SLC7A11) in HK-2 cells. CONCLUSION: These data demonstrated that EGT exerts an alleviating effect on the apoptosis of HK-2 cells induced by RSL3 and Erastin by modulating ferroptosis. These findings suggest that EGT has the potential to serve as a therapeutic candidate for the treatment of kidney diseases in the future.

Ergothioneine↗

Inflammatory Serum Olink Proteomics in Cancer-Related Pain Treated with Opioids: A Pilot Cross-Sectional and Longitudinal Study.

Opioid analgesia shows substantial interindividual variability in cancer patients, yet the underlying serum inflammatory alterations remain poorly characterized. This study collected plasma samples from 44 cancer pain patients before and after opioid initiation, quantifying 92 immunoinflammation proteins by Olink proteomics. Cross-sectional analysis identified nine differentially expressed proteins between responders and nonresponders. A five-protein nomogram involving TGF-α, EN-RAGE, CASP-8, ST1A1, and IL-10RA demonstrated superior predictive performance for opioid efficacy (AUC 0.902) compared to traditional CRP (AUC 0.625). Longitudinal analysis of this population revealed upregulation of β-NGF, MCP-4, IL-1alpha, and IL-13, and downregulation of CD6, IL-12beta, and SCF after treatment. STRING analysis clustered these proteins into three functional groups: efficacy-related (NGF), bowel-inflammation-related (IL-12/IL-13), and CD6-related. Notably, expression of IL-12β showed a significant efficacy-constipation interaction: constipation completely reversed the efficacy-IL-12 association, and higher IL-12 levels predicted favorable response only in nonconstipated patients. These findings established a pretreatment protein signature for predicting opioid efficacy and revealed systemic immune reprogramming following opioid therapy.

Humans↗

Novel Genetic Loci in Early-Onset Gout Derived From Whole-Genome Sequencing of an Adolescent Gout Cohort.

OBJECTIVE: Mechanisms underlying the adolescent-onset and early-onset gout are unclear. This study aimed to discover variants associated with early-onset gout. METHODS: We conducted whole-genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12 to 19 years) to discover common and low-frequency single-nucleotide variants (SNVs) associated with gout. Candidate common SNVs were genotyped in an early-onset gout cohort of 2,834 individuals (gout onset &#x2264;30 years old), and meta-analysis was performed with the discovery and replication cohorts to identify loci associated with early-onset gout. Transcriptome and epigenomic analyses, quantitative real-time polymerase chain reaction and RNA sequencing in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated the regulation and function of candidate gene RCOR1. RESULTS: In addition to ABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified two novel loci (Pmeta < 5.0 &#xd7; 10-8): rs12887440 (RCOR1) and rs35213808 (FSTL5-MIR4454). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low-frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte messenger RNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. CONCLUSION: This is the first comprehensive genetic characterization of adolescent-onset gout. The identified risk loci of early-onset gout mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent-onset gout.

Humans↗

Multiple perspectives on diagnosis delay for tuberculosis from key stakeholders in poor rural China: case study in four provinces.

This study aims to understand the contextual barriers to accessing timely TB diagnosis after first seeking care, especially among the poor and vulnerable in rural China. Both quantitative and qualitative methods were used to elicit the experiences and perspectives of TB patients and suspected TB patients, community residents, health providers and policy makers in poor, rural areas of four provinces. Between 30 and 60% of patients across the four provinces experienced a delay in receiving a diagnosis after first seeking care. Most patients had to visit health facilities more than once before diagnosis, with 17-30% patients making more than 6 visits. These delays and multiple visits mainly occurred because of the limited capacity of health providers to recognize TB, and financial disincentives to refer patients to TB dispensaries, due to the pressures of the cost recovery system. Poverty and socio-economic disadvantage amongst patients also influenced their capability to seek further care to obtain a reliable diagnosis. Qualitative data showed that women and the elderly patients were likely to experience more 'system' delay, and these findings were to some extent supported by the survey. The study concludes that 'system' delay is a serious problem, which is influenced by the financing mechanisms for both TB control and general health services as well as poverty and disadvantage amongst patients. This requires a comprehensive strategy to shorten 'system' delay in order to enable successful DOTS expansion, including developing appropriate financing mechanisms to improve general provider capacity and encourage referral, as well as measures to improve financial and social access to services for potential TB patients.

Adolescent↗

Transdifferentiation of pulmonary arteriolar endothelial cells into smooth muscle-like cells regulated by myocardin involved in hypoxia-induced pulmonary vascular remodelling.

Myocardin gene has been identified as a master regulator of smooth muscle cell differentiation. Smooth muscle cells play a critical role in the pathogenesis of hypoxia-induced pulmonary hypertension (PH) and pulmonary vascular remodelling (PVR). The purpose of this study was to investigate the change of myocardin gene expression in the pulmonary vessels of hypoxia-induced PH affected by Sildenafil treatment and the involvement of endothelial cells transdifferentiation into smooth muscle cells in the process of hypoxia-induced PH and PVR. Myocardin and relative markers were investigated in animal models and cultured endothelial cells. Mean pulmonary artery pressure (mPAP) was measured. Immunohistochemistry and immunofluorescence were used to show the expression of smooth muscle alpha-actin (SMA), in situ hybridization (ISH) and reverse transcription polymerase chain reaction (RT-PCR) were performed respectively to detect the myocardin and SMA expression at mRNA levels. Small interfering RNA (siRNA) induced suppression of myocardin in cultured cells. We confirmed that hypoxia induced the PH and PVR in rats. Sildenafil could attenuate the hypoxia-induced PH. We found that myocardin mRNA expression is upregulated significantly in the hypoxic pulmonary vessels and cultured cells but downregulated in PH with Sildenafil treatment. The porcine pulmonary artery endothelial cells (PAECs) transdifferentiate into smooth muscle-like cells in hypoxic culture while the transdifferentiation did not occur when SiRNA of myocardin was applied. Our results suggest that myocardin gene, as a marker of smooth muscle cell differentiation, was expressed in the pulmonary vessels in hypoxia-induced PH rats, which could be downregulated by Sildenafil treatment, as well as in hypoxic cultured endothelial cells. Hypoxia induced the transdifferentiation of endothelial cells of vessels into smooth muscle-like cells which was regulated by myocardin.

Actins↗

[The establishment and identification of the stable transfectant of HeLa cell expressing human new gene (PCIA1)].

OBJECTIVE: To construct a stable transfectant of human cervical cancer cell line HeLa that can highly express human novel gene (PCIA1). METHODS: RT-PCR technique was applied to amplify the cDNA of PCIA1 gene from total RNA isolated from HUVEC. After sequenced, the open reading frame (ORF) of PCIA1 cDNA was cloned into eukaryotic expression vector pcDNA3.1 (+) to form the recombinant plasmid named as pcDNA3.1-PCIA1. Then lipofectamine 2000 was used to transfected the pcDNA3.1-PCIA1 into HeLa cells. The PCIA1-transfected HeLa cells were selected with G418, for 4 weeks. Finally, RT-PCR and Western blot were used to detect the expression of human PCIA1 in HeLa cells. RESULTS: By RT-PCR and Western blot, we found that the human novel gene PCIA1 stably expressed in HeLa cells. CONCLUSION: This study indicated that human PCIA1 could be stably expressed in HeLa cells and its functions on tumor cells could be further analyzed by this stable transfectant of PCIA1.

Animals↗

[Components and assembly of RNA-induced silencing complex].

Degradation of homologous RNA in RNA interference is carried out by functional RNA-induced silencing complex (RISC). RISC contains Dicer, Argonaute proein, siRNA and other components. Researching structures and functions of these components is primary important for understanding assembly and functional mechanism of RISC, as well as the whole RNAi pathway. Recent research works showed that Dicer, containing RNaseIII domain, is responsible for production of siRNA at the beginning of RNAi, and guarantees the stability of RISC intermediate in assembly process. As the core component of RISC, Argonaute protein functions as slicer to cleave target RNA and offers the binding site of siRNA in RISC assembly, which are depended on PIWI domain and PAZ domain separately. Although there is only one strand of siRNA that is the guider of RISC, the double stranded structural character of siRNA is determinant of RNAi. Except those, there are still other components with unknown functions in RISC. The knowledge about RISC components and assembly now, is basis of a presumed RISC assembly model.

Animals↗

Near-real-time determination of hydrogen peroxide generated from cigarette smoke.

The ability to monitor hydrogen peroxide (H2O2) in aqueous smoke extracts will advance our understanding of the relationship between cigarette smoke-induced oxidative stress, inflammation, and disease and help elucidate the pathways by which the various smoke constituents exert their pathogenic effects. We have demonstrated, for the first time, the measurement of H2O2 production from cigarette smoke without prior separation of the sample. Cigarettes were tested on a commercial smoking machine, such that the whole smoke or gas vapor phase was bubbled through phosphate buffered saline solution at pH 7.4. Aliquots of these solutions were analyzed using an Amplex Red/horseradish peroxidase fluorimetric assay that required only a 2 minute incubation time, facilitating the rapid, facile collection of data. Catalase was used to demonstrate the selectivity and specificity of the assay for H2O2 in the complex smoke matrix. We measured approximately 7-8 microM H2O2 from two reference cigarettes (i.e., 1R4F and 2R4F). We also observed 9x more H2O2 from whole smoke bubbled samples compared to the gas vapor phase, indicating that the major constituent(s) responsible for H2O2 formation reside in the particulate phase of cigarette smoke. Aqueous solutions of hydroquinone and catechol, both of which are particulate phase constituents of cigarette smoke, generated no H2O2 even though they are free radical precursors involved in the production of reactive oxygen species in the smoke matrix.

Air Pollutants↗

Plasmonics-based nanostructures for surface-enhanced Raman scattering bioanalysis.

Surface-enhanced Raman scattering (SERS) spectroscopy is a plasmonics-based spectroscopic technique that combines modern laser spectroscopy with unique optical properties of metallic nanostructures, resulting in strongly increased Raman signals when molecules are adsorbed on or near nanometer-size structures of special metals such as gold, silver, and transition metals. This chapter provides a synopsis of the development and application of SERS-active metallic nanostructures, especially for the analysis of biologically relevant compounds. Some highlights of this chapter include reports of SERS as an immunoassay readout method, SERS gene nanoprobes, near-field scanning optical microscopy SERS probes, SERS as a tool for single-molecule detection, and SERS nanoprobes for cellular studies.

DNA↗

[Progress of RNA interference mechanism].

RNA interference (RNAi) is a phenomenon that the double-stranded RNA (dsRNA) intermediates the degradation of complementary mRNA found in many organisms. This is a specifically mechanism involved in kinds of proteins to complete the interference function. Structure of siRNA affects which strand will be assembled into RISC. Another role of siRNA is directing RITS complex to bind with homologue chromosome, and then induces heterochromatinization. Although systemic silence induced by dsRNA is observed in Caenorhabditis elegans and plants, this progress is probably transmembrane protein-dependent, and mostly, the systemic silencing is controlled by multi-factors.

Animals↗

Novel fluorescent biosensor for pathogenic toxins using cyclic polypeptide conjugates.

This work describes a two-step conjugate synthesis of a new fluorescent analog of microcystin-LR and its subsequent utilization for the development of an optical biosensor for cyanobacteria toxins. The biosensor concept is based on the competitive binding between the native microcystin and its fluorescent analog at immobilized alkaline phosphatase enzymes.

Bacterial Toxins↗

Room-temperature preparation and characterization of poly (ethylene glycol)-coated silica nanoparticles for biomedical applications.

Monodisperse, spherical, polyethylene glycol (PEG)-coated silica nanoparticles have been prepared at room temperature and characterized for the purpose of biomedical applications. The particles were synthesized by the hydrolysis of tetramethyl orthosilicate (TMOS) in alcohol media under catalysis by ammonia, and their size can range from about 50-350 nm in diameter. We studied the particle size and size distribution using a scanning electron microscope (SEM) and an asymmetric field-flow fractionation (AFFF) multiangle static light-scattering instrument. The chemical and/or physical binding of PEG to the silica nanoparticles was studied by infrared spectroscopy, and the weight percentage of PEG attached to the particles was quantified. The PEG-coated silica nanoparticles showed enhanced colloidal stability when redispersed into aqueous solutions from the dried state as a result of the steric stabilization function of the PEG polymer grafted on the surface of particles. A nonspecific protein-binding test was also carried out to show that the PEG coating can help reduce the protein adsorption onto the surface of the particles, relating to the biocompatibility of these PEG-coated particles. Also, the inclusion of magnetic nanoparticles into the silica particles was shown as an example of the possible applications of PEG-coated silica particles. These silica nanoparticles, as a matrix for encapsulation of certain reagents, have potential for applications to in vivo diagnosis, analysis, and measurements inside intact biologic systems.

Biocompatible Materials↗

The embedding of meta-tetra(hydroxyphenyl)-chlorin into silica nanoparticle platforms for photodynamic therapy and their singlet oxygen production and pH-dependent optical properties.

This study relates to nanoparticle (NP) platforms that attach to tumor cells externally and only deliver singlet oxygen for photodynamic therapy (PDT) while conserving the embedded photosensitizers (PS). As a model, we demonstrate the successful embedding of the PS meta-tetra(hydroxyphenyl)-chlorin (m-THPC) in NP that are based on a sol-gel silica matrix and also show its positive effect on the singlet oxygen production. The embedding of m-THPC inside silica NP is accomplished by a modified Stöber sol-gel process, in which (3-aminopropyl)-triethoxysilane is introduced during the reaction. Singlet oxygen delivery by the targetable photodynamic NP exceeds that from free PS molecules. In the physiological pH range, there is no significant pH-induced decrease in the fluorescence of m-THPC embedded in silica NP, which might otherwise affect the efficiency of PDT.

Antineoplastic Agents↗

[Allelopathic effect of p- and m-hydroxy-phenylacetic acid on soybean (Glycine max L.) germination].

In present work the p-hydroxy-phenylacetic acid (PHPA) and m-hydroxy-phenylacetic acid(MHPA) in rhizospheric soil solutions and decomposed root residues were detected by High Performance Liquid Chromatography (HPLC), and their effects on soybean germination at the level of 0, 30, 60, 150, 300 and 600 mg.kg-1, on melting temperature of DNA at the level of 600 mg.kg-1 and on cytoplasm protein patterns at the level of 0, 30, 150, 300 mg.kg-1 were also studied. PHPA and MHPA were detected in decomposed products of root residue and soil solutions collected from rhizosphere in which soil sickness was occurred, but not detected in soil on which soybean rotated with wheat. The standard samples of PHPA and MHPA were used for bioassay in Petri dish. The main root length and lateral root number of soybean were seriously reduced, even at the level of 30 mg.L-1. Soybean germination and root growth were retarded seriously by MHPA, in contrast with PHPA. At the level of 600 mg.kg-1, the melting temperature (Tm) of soybean DNA was increased sharply from 77 degrees C to 84.5 degrees C with PHPA, and from 77 degrees C to 88.5 degrees C with MHPA. Tm was affected markedly by MHPA, compared to PHPA, and the result was consistent with that of bioassay. The cytoplasm protein patterns of soybean leaves were obtained from SDS-PAGE, showing several low weight molecular proteins were affected, especially on 16. 1 kD and 20.2 kD. The results implied that PHPA and MHPA had allelopathic effect on soybean, and might have a role in soil-sickness of soybean.

DNA, Plant↗

Synthesis and characterization of silica-embedded iron oxide nanoparticles for magnetic resonance imaging.

In this communication, a conceptually new approach to the delivery of magnetic resonance imaging (MRI) contrast agents is presented. Our experiments demonstrate the feasibility of using silica-embedded iron oxide nanoparticles as contrast agents in magnetic resonance imaging, where a reduction in signal intensity (increased contrast) in the T2-weighted images is observed. The surface of these particles can be chemically modified by attachment of polyethylene glycol molecules, which are found to reduce nonspecific protein binding. The design of the nanoparticle is universal and flexible and allows for facile addition or interchange of its active components (i.e., MRI contrast agents and targeting moiety) with photodynamic dyes.

Coated Materials, Biocompatible↗