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Biomedical subjects

Xuemei Li

Publications and source records attributed to Xuemei Li.

9 recordsLinked to original sources

Transcription factor NtELF3 promotes the polyphenol accumulation by targeting NtFLS-1 and NtCHIL-2 genes in tobacco.

Tobacco (Nicotiana tabacum L.) is an important economic crop, from which polyphenols are crucial for regulating its growth and development as well as shaping its quality. However, few genes associated with polyphenol accumulation have been cloned from tobacco, and the molecular mechanisms underlying this process remain poorly understood. Here, we found that the tobacco transcription factor EARLY FLOWERING 3 (NtELF3), which is highly expressed in tobacco leaves, positively regulates the accumulation of chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, rutin, scopoletin, and total polyphenols in tobacco middle leaves. The metabolomic and transcriptomic analyses of middle leaves showed that a total of 177 differentially accumulated metabolites and 7409 differentially expressed genes (DEGs) were identified in ntelf3-1 mutant versus wild type, respectively. Further investigation identified that 17 DEGs were involved in phenylpropanoid metabolic and flavonoid metabolic processes. Combined analysis indicated that the phenylpropanoid and flavonoid biosynthesis pathways were also co-enriched in kyoto encyclopedia of genes and genomes enrichment analysis. Molecular biology experiment demonstrated that NtELF3 directly binds to the promoters of NtFLS-1 and NtCHIL-2 that are both associated with phenylpropanoid and flavonoid biosynthesis, and promotes their expression. Taken together, our results not only provide new theoretical support for in-depth understanding of the regulatory mechanisms underlying polyphenol accumulation in tobacco, but also offer excellent genes and germplasm resources for tobacco quality breeding.

NtCHIL↗

Efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis: a multicenter, randomized, open-label, active-controlled, phase III trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). METHODS: In this phase III, multicenter, randomized, open-label, non-inferiority trial, patients with hyperphosphatemia on maintenance hemodialysis were randomly assigned to receive either ferric citrate or sevelamer carbonate tablets for 12 weeks. The primary endpoint was the change in serum phosphorus levels from baseline to week 12, with a non-inferiority margin of 0.32 mmol/L. Secondary endpoints included changes in serum calcium, intact parathyroid hormone, and safety assessments. RESULTS: A total of 239 patients were randomized to the ferric citrate group (n = 119) or the sevelamer carbonate group (n = 120). The mean change in serum phosphorus levels was -0.70 ± 0.50 mmol/L in the ferric citrate group and -0.61 ± 0.59 mmol/L in the sevelamer carbonate group (least squares mean difference, -0.09 mmol/L; 95% CI, -0.24 to 0.05 mmol/L; non-inferiority margin, 0.32 mmol/L). No significant inter-group differences were found in the percentage of patients achieving target phosphorus levels (49.09% vs. 48.28%, p = 0.902). Ferric citrate significantly improved iron-related parameters and hemoglobin levels. Most treatment-emergent adverse events were mild, with gastrointestinal disorders being the most common. CONCLUSIONS: Ferric citrate tablets were non-inferior to sevelamer carbonate in reducing serum phosphorus levels in hyperphosphatemia patients on maintenance hemodialysis, with the added benefit of improving iron-related anemia and a favorable safety profile.

Adult↗

A healthy live birth after mosaic blastocyst transfer in preimplantation genetic testing for GATA1-related cytopenia combined with HLA matching.

BACKGROUND: GATA1-related cytopenia (GRC) is characterized by thrombocytopaenia and/or anaemia ranging from mild to severe. Haematopoietic stem cell transplantation (HSCT) is a healing therapeutic choice for GRC patients. We identified a novel pathogenic variant (GATA1: c.1019delG) in a boy with GATA1-related cytopenia. Then we performed preimplantation genetic testing (PGT) in this GRC family. After a mosaic embryo transfered, a healthy and HLA-compatible with the proband baby was delivered. CASE PRESENTATION: The proband is a 6-year-old boy who was diagnosed to have transfusion-dependent anaemia since 3 year old. Whole-exome sequencing (WES) showed that the proband has a hemizygous variant c.1019delG in GATA1, which is inherited from his mother. His parents decided to undergo PGT to have a health and HLA-compatible offspring. After whole genome amplification (WGA) of biopsied trophectoderm (TE) cells, next generation sequencing (NGS)-based PGT was preformed to analyse embryos on chromosomal aneuploidy, target mutation and HLA typing. There were 3 embryos HLA-matched to the proband. The genotypes of the 3 embryos were heterozygous variant, hemizygous variant, normal respectively. After a heterozygous, mosaic partial trisomy (chr)16, and HLA-matched embryo transfer, a healthy baby was delivered and whose HSCT is compatible with the proband. CONCLUSIONS: NGS-based PGT-HLA is a valuable procedure for the treatment of GATA1-related cytopenia caused by GATA1 variants, or other haematological disorders, oncological and immunological diseases. Furthermore, our study reconfirms that mosaic embryos transfer would bring healthy offspring.

Child↗

Kinetics of lactose hydrolysis by beta-galactosidase of Kluyveromyces lactis immobilized on cotton fabric.

A mathematic model for describing the Michaelis-Menten-type reaction kinetics with product competitive inhibition and side-reaction is proposed. A multiresponse nonlinear simulation program was employed to determine the coefficients of a four-parameter rate expression. The rate expression was compared with the conventional Michaelis-Menten reaction rate models with and without product inhibition. Experimental data were obtained using beta-galactosidase of Kluyveromyces lactis immobilized on cotton fabric in a batch system at a temperature of 37 degrees C and at various initial concentrations of dissolved lactose ranging from 3-12.5% (w/v). The reaction is followed by concentration changes with time in the tank. Samples were obtained after the outlet stream of the packed bed reactor is mixed in a well-stirred tank. High-performance liquid chromatography (HPLC) was applied to monitor the concentrations of all the sugars (reactants as well as products). The four-parameter rate model is featured with a term to describe the formation of trisaccharides, a side-reaction of the enzymatic hydrolysis. The proposed model simulates the process of lactose hydrolysis and the formation of glucose and galactose, giving better accuracy compared with the previous models.

Bioreactors↗

Therapeutic role of TGF-beta-neutralizing antibody in mouse cyclosporin A nephropathy: morphologic improvement associated with functional preservation.

TGF-beta is believed to play a central role in the development of Cyclosporin A (CsA)-induced nephropathy. This study investigated the effects of 1D11, a murine pan-specific TGF-beta-neutralizing monoclonal antibody, in an ICR mouse model of chronic CsA nephropathy. Mice were administered a low-salt diet (0.01% sodium) for 1 wk followed by CsA treatment (30 mg/kg, subcutaneously, daily) for 4 wk. 1D11 was administered (2.5 mg/kg, intraperitoneally, 3 times/wk) beginning immediately after the termination of CsA dosing and continued through 8 wk. CsA caused extensive renal histopathologic alterations, including tubular damage, interstitial infiltrates and fibrosis, deposition of collagen III, and apoptosis of tubular epithelial cells. 1D11 ameliorated the CsA-induced histopathologic alterations, with significant reduction in collagen III expression and deposition. Additionally, elevated levels of mRNA encoding TGF-beta1 and TGF-beta2 were significantly reduced. 1D11 also protected tubular epithelial cells from apoptosis by 48% (P < 0.05). In contrast, 13C4 (a control antibody) had no significant effect on any of the endpoints described above. Importantly, the effects of 1D11 on the CsA-induced morphologic alterations were followed by a reduction in serum creatinine level when compared with CsA mice treated with 13C4 (13C4, 0.45 +/- 0.09; 1D11, 0.30 +/- 0.08; P < 0.05) after 8 wk of treatment. Endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), nitrotyrosine, and tissue hypoxia were examined by immunostaining using specific antibodies. eNOS was significantly reduced in the endothelium of arterioles in the kidneys of mice treated with CsA, whereas iNOS was induced in the cortical tubules. Tissue hypoxia was found in both the arterioles and tubules, whereas nitrotyrosine was localized in the tubules. Administration of 1D11 improved tissue hypoxia and reduced nitrotyrosine formation. Moreover, the reciprocal changes in iNOS and eNOS expression were normalized by 1D11. This study demonstrates that 1D11 administration ameliorated morphologic alterations and preserved renal function in the context of existing chronic CsA nephropathy.

Animals↗

The MUR3 gene of Arabidopsis encodes a xyloglucan galactosyltransferase that is evolutionarily related to animal exostosins.

Xyloglucans are the principal glycans that interlace cellulose microfibrils in most flowering plants. The mur3 mutant of Arabidopsis contains a severely altered structure of this polysaccharide because of the absence of a conserved alpha-L-fucosyl-(1-->2)-beta-D-galactosyl side chain and excessive galactosylation at an alternative xylose residue. Despite this severe structural alteration, mur3 plants were phenotypically normal and exhibited tensile strength in their inflorescence stems comparable to that of wild-type plants. The MUR3 gene was cloned positionally and shown to encode a xyloglucan galactosyltransferase that acts specifically on the third xylose residue within the XXXG core structure of xyloglucan. MUR3 belongs to a large family of type-II membrane proteins that is evolutionarily conserved among higher plants. The enzyme shows sequence similarities to the glucuronosyltransferase domain of exostosins, a class of animal glycosyltransferases that catalyze the synthesis of heparan sulfate, a glycosaminoglycan with numerous roles in cell differentiation and development. This finding suggests that components of the plant cell wall and of the animal extracellular matrix are synthesized by evolutionarily related enzymes even though the structures of the corresponding polysaccharides are entirely different from each other.

Amino Acid Sequence↗

Hepatocyte nuclear factor 4 response to injury involves a rapid decrease in DNA binding and transactivation via a JAK2 signal transduction pathway.

The injury response is a complex set of events, which represents the reaction of a biological system to a perceived change in its environment in an attempt to maintain system integrity. Isolation of individual events or components of this response cannot describe the overall process, but may reflect general mechanisms that have evolved over time to solve the complex requirements of the injury response. The process, generally termed the acute phase response, is a series of organ-specific responses that begin shortly after a systemic injury. In the liver, this response involves both dramatic inductions and reductions in specific sets of genes, and an overall widespread global change in proteins produced. This can be thought of as a phenotypic change or 'reprogramming' of the liver. These changes in protein production are modulated and regulated at the level of transcription and involve significant manipulations of transcriptional regulatory mechanisms. Hepatocyte nuclear factor 4 (HNF-4) is a liver enriched transcription factor that regulates a large number of liver-specific genes, which play important roles in the critical pathways modulated by the response to injury. HNF-4 also performs an essential role in overall development and is critical for the normal expression of multiple genes in the developed liver, as well as being upstream of HNF-1 in a transcriptional hierarchy that drives hepatocyte differentiation. The role of HNF-4 in regulating liver-specific transcriptional changes directed by injury remains to be defined. In our cell-culture and whole-animal models, we demonstrate that the binding activity of HNF-4 decreases quickly after injury due to post-translational modification by phosphorylation. The mechanisms by which HNF-4 is modified after injury involve the activation of Janus kinase 2 (JAK2) signal transduction pathways, but the direct or indirect interaction of JAK2 with HNF-4 remains to be defined.

Animals↗

[Observation on the therapeutic effect of Lamivudin on chronic hepatitis B].

OBJECTIVE: To observe the therapeutic effect of Lamivudine on controlling hepatitis B virus DNA replication. METHODS: The liver disease patients were divided into two groups, the treated group (n=64) was given Lamivudine 100 mg once a day for one year and was additionally given liver protection drugs according to their liver function, while the control group (n=30) was given common liver protection drugs. The blood routine test, liver function and the viral markers were detected at defined times. RESULTS: The results showed that after one year treatment of chronic hepatitis B with Lamivudine, the recovery rate of ALT was 90.7%, the negative conversion rate of HBV DNA was 73.1% showing a significant difference as compared with the control group (P<0.05). The negative seroconversion rate of HBeAg was 50%, HBeAg/anti HBe changing rate was 38.2%, that had no significant different as compared with the control group (P<0.05). The percentage for disease relapse and second elevation of ALT was 3.1% in therapeutic group that was significantly different from that of the control group (P<0.05). Two cases with severe hepatitis in the treated group were all alive. CONCLUSIONS: Lamivudine could effectively control HBV DNA replication, making ALT normal, it also could decrease the relapse rate of chronic hepatitis B and raise the survival rate of the patients with liver disease.

Administration, Oral↗

Phosphoenolpyruvate carboxylase in mistletoe leaves: Regulation of gene expression, protein content, and covalent modification.

Seasonal changes in the activity of phosphoenolpyruvate carboxylase (PEPCase, EC 4.1.1.31), a key enzyme in the interaction of carbohydrate and nitrogen metabolism, were studied in leaves of the C3 semiparasitic mistletoe, Viscum album, growing on different host trees. Maximum extractable PEPCase activities were higher in leaves of mistletoes growing on Betula pendula and Alnus glutinosa hosts compared with those on the conifers, Abies alba and Larix decidua. Independent of host, maximum extractable PEPCase activities were high in spring and autumn while low in summer. Samples with higher PEPCase activities showed higher amounts of PEPCase protein and higher PEPCase mRNA levels. A curvilinear correlation between leaf total nitrogen content and the maximum extractable PEPCase activity as well as PEPCase mRNA level suggested that nitrogen might affect the activity of PEPCase of mistletoe by up-regulating gene expression. In addition to extractable activity, seasonal changes of the PEPCase activation state, the ratio of activities resulting from limited:non-limited assays, were found, which was correlated to the variation of malate content in leaves of mistletoe. ATP-dependent activation of PEPCase was characterized by an increase in I0.5(L-malate), indicating that PEPCase of leaves of mistletoes is probably regulated via phosphorylation.

Journal Article↗