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Biomedical subjects

Min Zheng

Publications and source records attributed to Min Zheng.

At least 19 recordsLinked to original sources
PubMed2026

Cell type-selective targeting by heterobifunctional protein binders via in-cell enrichment.

Non-catalytic heterobifunctional protein binders promise to expand the range of therapeutic options by establishing complexes between key target proteins and accessory presenter proteins equipped with additional properties. Here, we systematically investigate the rational design of such molecules, explore the biochemical basis of complex formation and determine how they achieve cellular efficacy using the endogenously expressed immunophilin FKBP12 as presenter protein and the transcriptional regulator BRD4 as target protein. We present classes of bifunctional molecules that enable selective, FKBP12-dependent killing of specific cell types at subnanomolar concentrations and allow to differentiate between closely related bromodomains of the BET family. We propose that the strongly potentiated efficacy of these bifunctional compounds is based on cellular enrichment through binding to the highly abundant presenter protein FKBP12, a mechanism we term "CellTrap". Our findings substantiate the concept that highly expressed, non-essential proteins can be repurposed as selective recruiters to expand therapeutic windows of existing small-molecule inhibitors, opening new avenues for designing targeted drugs with improved cell-type specificity.

Tacrolimus Binding Protein 1A↗
PubMed2026

Comprehensive evaluation of new sequencer T20 and well-established T7 with 507 human samples.

The DNBSEQ-T20×2 (T20) sequencer, developed by MGI Tech, enables cost-effective human whole-genome sequencing (WGS) at 30× coverage for less than $100 per genome. Here, we evaluate the sequencing performance and data quality of the T20 platform by benchmarking it against the established DNBSEQ-T7 (T7) sequencer using 507 samples derived from blood (N = 75), stool (N = 242), and saliva (N = 190). The T20 exhibited lower sequencing quality metrics compared with the T7, with Q20 scores of 95.76%-95.83% and Q30 scores of 87.25%-87.40%, compared with 97.81%-97.93% and 93.26%-93.60%, respectively, for T7 data. Quality differences were more evident toward the end of reads, and PCR-free libraries sequenced on the T20 showed similar reductions in quality scores. The median empirical base error rate estimated from 102 ZymoBIOMICS samples was 0.33%. The T20 demonstrated comparable coverage uniformity to the T7 and showed high concordance in microbiome composition analysis, with a median Bray-Curtis dissimilarity of 0.02. Variant calling performance was highly consistent between the two platforms. Among variants with non-missing genotype calls on both platforms, 94.92% of SNPs and 87.20% of InDels showed concordant genotypes between T20 and T7. Overall, the T20 delivers reliable sequencing accuracy and reproducibility for large-scale genomic and microbiome studies, providing a cost-effective alternative for high-throughput sequencing applications.

Metagenomics↗
PubMed2007

Negative differential resistance and memory effect in diodes based on 1,4-dibenzyl C60 and zinc phthalocyanine doped polystyrene hybrid material.

Negative differential resistance (NDR) and memory effect were observed in diodes based on 1,4-dibenzyl C60 (DBC) and zinc phthalocyanine doped polystyrene hybrid material. Certain negative starting sweeping voltages led to a reproducible NDR, making the hybrid material a promising candidate in memory devices. It was found that the introduction of DBC enhanced the ON/OFF current ratio and significantly improved the memory stability. The ON/OFF current ratio was up to 2 orders of magnitude. The write-read-erase-reread cycles were more than 106, and the retention time reached 10,000 s without current degradation.

Journal Article↗
PubMed2006

Expression of VEGFR-2 on HaCaT cells is regulated by VEGF and plays an active role in mediating VEGF induced effects.

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 play important roles in mitogenesis and chemotaxis of endothelial cells. In normal human skin, VEGF is expressed and secreted by epidermal keratinocytes. Emerging data suggest that keratinocyte-derived VEGF targets other cell types besides the dermal endothelial cells. We have recently showed that keratinocytes from human normal skin expressed all five known VEGF receptors and co-receptors (neuropilin 1 and 2). To define the functional significance of VEGFR-2 in epidermis, we examined its role in a keratinocyte cell line, HaCaT cells, in response to VEGF treatment. Expression of VEGFR-2 on HaCaT cells was confirmed at both RNA and protein levels and was regulated by VEGF165 treatment. Treatment of HaCaT cells with VEGF165 induced tyrosine-autophosphorylation of VEGFR-2 and phosphorylation of PLC-gamma and p44/42 MAPK in a time-dependent manner. Preincubation with a neutralizing antibody for VEGFR-2 (MAB3571) completely abrogated these phosphorylation effects. Furthermore, VEGF165 stimulated proliferation and migration of HaCaT cells, and this effect was significantly blocked by a pretreatment with MAB3571. Neutralizing VEGFR-2 in HaCaT cells increased cell adhesion during culture. Our results suggest that VEGFR-2 expressed on HaCaT cells plays a crucial role in VEGF-mediated regulation of cell activity.

Cell Adhesion↗
PubMed2006

HAIRY-like transcription factors and the evolution of the nematode vulva equivalence group.

BACKGROUND: Nematode vulva formation provides a paradigm to study the evolution of pattern formation and cell-fate specification. The Caenorhabditis elegans vulva is generated from three of six equipotent cells that form the so-called vulva equivalence group. During evolution, the size of the vulva equivalence group has changed: Panagrellus redivivus has eight, C. elegans six, and Pristionchus pacificus only three cells that are competent to form vulval tissue. In P. pacificus, programmed cell death of individual vulval precursor cells alters the size of the vulva equivalence group. RESULTS: We have identified the genes controlling this cell-death event and the molecular mechanism of the reduction of the vulva equivalence group. Mutations in Ppa-hairy, a gene that is unknown from C. elegans, result in the survival of two precursor cells, which expands the vulva equivalence group. Mutations in Ppa-groucho cause a similar phenotype. Ppa-HAIRY and Ppa-GROUCHO form a molecular module that represses the Hox gene Ppa-lin-39 and thereby reduces the size of the vulva equivalence group. The C. elegans genome does not encode a similar hairy-like gene, and no typical HAIRY/GROUCHO module exists. CONCLUSIONS: We conclude that the vulva equivalence group in Pristionchus is patterned by a HAIRY/GROUCHO module, which is absent in Caenorhabditis. Thus, changes in the number, structure, and function of nematode hairy-like transcription factors are involved in the evolutionary alteration of this equivalence group.

Amino Acid Sequence↗
PubMed2006

Construction and immunogenicity of a recombinant fowlpox virus containing the capsid and 3C protease coding regions of foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV) is an important pathogen with worldwide economic consequences. Consequently, an important goal is the development of a vaccine that can provide rapid protection while overcoming the potential risk associated with the production of conventional inactivated vaccines. An important secondary feature of the vaccine would be the ability to distinguish vaccinated from infected animals. A recombinant fowlpox virus (vUTAL3CP1) containing FMDV capsid polypeptide and 3C coding regions of O/NY00 was constructed and evaluated for its ability to induce humoral and cellular responses in mice and guinea pigs. In addition, the ability to protect guinea pigs against homologous virus challenge was examined. Mice and guinea pigs were given booster vaccinations twice and once, respectively, and guinea pigs were challenged 20 days after the booster vaccination. Control groups included animals inoculated with commercial vaccine, fowlpox virus or phosphate-buffered saline (PBS). All animals vaccinated with vUTAL3CP1 developed specific anti-FMDV antibody and neutralizing antibody, as well as T lymphocyte proliferation response and CTL cytotoxic activity. Three of four guinea pigs vaccinated with vUTAL3CP1 were completely protected from viral challenge. The results demonstrated the potential of a fowlpox virus-based recombinant FMD vaccine.

3C Viral Proteases↗
PubMed2006

Biological characterization of cultured dermal papilla cells and hair follicle regeneration in vitro and in vivo.

BACKGROUND: Dermal papilla cells (DPC) are a group of mesenchyme-derived cells at the base of the hair follicle, where they regulate and control hair follicle growth through the expression and secretion of cytokines. Nevertheless, the role of DPC derived chemokines and other cytokines in the hair follicle biology remain speculative. In this study, we investigated the expression of basic fibroblast growth factor (bFGF), endothelin-1 (ET-1) and stem cell factor (SCF) in different passages of cultured DPC and their effects on the biological behaviour of DPC. METHODS: The expression of bFGF, ET-1 and SCF in different passages of cultured DPC and their possible effects on the biological behavior of DPC are investigated using in situ hybridization and immunochemistry. In addition, we performed transplantation of hair follicle cells into nude mice. The cultured DPC, dermal sheath cells and fibroblast of human scalp, respectively, were mixed with cells of the hair follicle epithelium in different ratios, and then were cultured in hair follicle organotypic cultures or implanted into the subcutis of nude mice. RESULTS: The expression of ET-1 and SCF in early passages of cultured DPC became stronger, but turned weaker and even negative in late passages (> 6 passages). Hair follicle-like structures were formed after DPC combined with the cells of hair follicle epithelium cells in hair follicle organotypic cultures. When hair follicle organotypic cultures were implanted into the subcutis of nude mice, the relative intact hair follicles were formed. After the transplantation of hair follicle cells into the nude mice, the hair follicle-like structure was formed in the group that contained DPC mixed with hair follicle epithelium cells. However, no hair follicles were formed in the other two groups. It was found that the higher the expression of ET-1 and SCF in DPC, the stronger the ability of DPC to induce hair follicle regeneration. CONCLUSIONS: The cultured DPC can induce hair follicle regeneration and sustain hair growth in vivo and in vitro. Moreover, the expression of ET-1 and SCF is correlated with the ability of DPC inducing hair follicle regeneration.

Animals↗
PubMed2006

Differential glycosylation of rhLf expressed in the mammary gland of transgenic mice.

Differential glycosylation of natural hLf and rhLf from hLf-transgenic mice, which harbored a 146 Kb BAC insert that includes the intact hLf gene sequence, was studied in the present report. There were significant differences between the immunoblotting results of rhLf and natural hLf, which were denatured with nonreducing SDS sample buffer. The differences disappeared after rhLf and natural hLf samples were digested with N-glycosidase F, respectively. The results showed that there were significant differences (P<0.01) between the glycosylation of natural hLf and rhLf that were purified, respectively, from milk samples of seven hLf-transgenic mouse lines.

Animals↗
PubMed2006

Maternally derived recombinant human anti-hantavirus monoclonal antibodies are transferred to mouse offspring during lactation and neutralize virus in vitro.

Transgenic mice expressing a recombinant human monoclonal antibody (rHMAb) against hantavirus were generated. These mice could be used as models to explore the possibilities of producing rHMAbs for therapeutic purposes. The highest concentration of the rHMAb in the milk of the transgenic females was 6.6 mg/ml. The rHMAb was also detected in the sera of pups fed by the transgenic females. Both the rHMAbs in the milk of transgenic mice and those in the sera of suckling pups were found to be active against hantaviruses, although the light chain of the antibody absorbed by the pups was modified by N-linked glycosylation.

Animals↗
PubMed2006

Determinants that control the specific interactions between TAB1 and p38alpha.

Previous studies have revealed that transforming growth factor-beta-activated protein kinase 1 (TAB1) interacts with p38alpha and induces p38alpha autophosphorylation. Here, we examine the sequence requirements in TAB1 and p38alpha that drive their interaction. Deletion and point mutations in TAB1 reveal that a proline residue in the C terminus of TAB1 (Pro412) is necessary for its interaction with p38alpha. Furthermore, a cryptic D-domain-like docking site was identified adjacent to the N terminus of Pro412, putting Pro412 in the phi(B)+3 position of the docking site. Through mutational analysis, we found that the previously identified hydrophobic docking groove in p38alpha is involved in this interaction, whereas the CD domain and ED domain are not. Furthermore, chimeric analysis with p38beta (which does not bind to TAB1) revealed a previously unidentified locus of p38alpha comprising Thr218 and Ile275 that is essential for specific binding of p38alpha to TAB1. Converting either of these residues to the corresponding amino acid of p38beta abolishes p38alpha interaction with TAB1. These p38alpha mutants still can be fully activated by p38alpha upstream activating kinase mitogen-activated protein kinase kinase 6, but their basal activity and activation in response to some extracellular stimuli are reduced. Adjacent to Thr218 and Ile275 is a site where large conformational changes occur in the presence of docking-site peptides derived from p38alpha substrates and activators. This suggests that TAB1-induced autophosphorylation of p38alpha results from conformational changes that are similar but unique to those seen in p38alpha interactions with its substrates and activating kinases.

Adaptor Proteins, Signal Transducing↗
PubMed2006

[Acitretin induces apoptosis and changes of relative signaling pathway in epidermoid carcinoma cell line A431].

OBJECTIVE: To study the effects of Acitretin on growth inhibition and apoptosis of epidermoid carcinoma cell line A431 and its molecular mechanisms. METHODS: A431 cells were treated with Acitretin at the concentration of 10(-5)mol/L in different time intervals. The inhibition of cell growth was determined by MTT method, morphological changes were observed by electron microscopy, apoptosis was assessed by flow cytometry and Annexin-V staining. The mRNA expression levels of STAT3, cyclinD1 and p42/44MAPK were detected by reverse transcriptase polymerase chain reaction (RT-PCR). The protein expression levels of P-STAT3 and CyclinD1 were observed by Western blot in A431 cells. RESULT: (1)Acitretin inhibited the growth of A431 cells in vitro in a dose-and time-dependent manner. Morphological changes revealed characteristics of cell apoptosis. Flow cytometry showed more sub-G(1) phase in A431 cells and more cells positively stained with Annexin-V. (2)Acitretin significantly inhibited the expression of STAT3 and CyclinD1 mRNA in A431 cells in vitro in a time-dependent manner(P<0.05). The p-STAT3 and CyclinD1 protein levels were down regulated. The Acitretin could also down regulate the p42/4MAPK mRNA in A431 cells. (3) After incubation with Acitretin, the mRNA level of CyclinD1 in A431 cells was positively correlated with that of STAT3(p<0.05). The protein level of CyclinD1 was also positively correlated with that of p-STAT3(p<0.05). However, there was no correlation between Mrna levels of CyclinD1 and p42/44MAPK. CONCLUSION: (1)Acitretin plays an inhibitory role in the tumor cell growth and induces the cell apoptosis in A431 cells. (2)The regulation of the Jak/STAT3 signaling pathway may play an important role in inducing growth inhibition and apoptosis by Acitretin in A431 cells.

Acitretin↗
PubMed2006

[Effects of traditional Chinese herbs on growth of mouse hair follicles and hair bulb cells in vitro].

OBJECTIVE: To investigate the effect of water soluble extracts of traditional Chinese herbs on growth of mouse hair follicles and hair bulb cells in vitro. METHODS: Mouse hair follicles and hair bulb cells were cultured in Williams E medium with (experimental groups) or without (control group) water soluble extracts of Chinese herbs; the experimental group was further divided into mixture and single herb groups. Hair growth was observed by microscopy and growth activity of hair bulb cells was detected by MTT colorimetric assay. RESULT: On day 7 of culture, the hair growth in the mixture groups was faster than that in the control group (P<0.05). On day 3 and 5 of culture, the cell growth activity in the mixture groups was greater than that in the control group (P<0.05). While the hair growth and the cell growth activity between the single herb groups and the control group were not significantly different. CONCLUSION: The water soluble extracts of mixed traditional Chinese medicines can promote the growth of mouse hair in vitro and stimulate the proliferation of hair bulb cells; while those of the single traditional Chinese herb have no effect.

Angelica sinensis↗
PubMed2006

[Advances in research on relationship between DNA hypomethylation and systemic lupus erythematosus].

T-cell DNA hypomethylation can increase expression of genes that have potential relation to autoimmunity. CD70 overexpression may be associated with B-cell activation and immunoglobulin secretion, while perforin plays an important role in T-cell-mediated macrophage apoptosis. DNA hypomethylation can activate human endogenous retroviruses (HERV) sequences. Expression of HERV components may elicit autoantibodies production. Polyamines change structure of chromosome and interfere with DNA methylation process, which is involved in the pathogenesis of autoimmune diseases.

DNA Methylation↗
PubMed2006

[Advances in pathogenesis of psoriasis].

OBJECTIVE: The pathogenesis of psoriasis recently made great advancement due to the introduction of transgenic mouse model. K14-VEGF transgenic mouse showed many of the cellular and molecular features of psoriasis, including angiogenesis in dermis, altered epidermal proliferation and differentiation. Psoriasis of early onset and severe disease showed significantly increased frequency of the +405CC genotype and the C allele. Transgenic mice with keratinocytes expressing active Stat3 (K5. Stat3C mice) developed a skin phenotype closely resembling psoriasis. Stat 3 may link activated keratinocytes and immunocytes required for development of psoriasis. More recently, a novel mouse model with epidermal specific double-knockout of the c-Jun and JunB genes showed developments of psoriasis-like skin phenotype and arthritic lesions. All these data provided more profound understanding in pathogenesis and therapy of psoriasis.

Animals↗
PubMed2006

[Observation on therapeutic effect of electroacupuncture at points Baliao and Huiyang (BL 35) on retention of urine induced by spinal cord injury].

OBJECTIVE: To explore a more effective therapy for retention of urine induced by spinal cord injury. METHODS: Eighty-four cases were randomly divided into a treatment group of 46 cases and a control group of 38 cases. The treatment group were treated with electroacupuncture at Baliao and Huiyang (BL 35), and the control group with electroacupuncture at acupoints routinely selected. RESULTS: The total effective rate and the cured rate were 82.6% and 43.5% in the treatment group and 63.2% and 23.7% in the control group respectively, with a very significant difference between the two groups (P < 0. 01). CONCLUSION: Electroacupuncture at Baliao and Huiyang (BL 35) has obvious therapeutic effect on retention of urine induced by spinal cord injury.

Acupuncture Points↗
PubMed2006

Expression of c-fos in rat brain as a prelude marker of central nervous system injury in response to methylmercury-stimulation.

OBJECTIVE: To probe into the prelude marker of central nervous system injury in response to methyl mercury chloride (MMC) stimulation and the signal transduction molecular mechanism of injury in rat brain induced by MMC. METHODS: The expression of c-fos mRNA in brain and the expression of c-FOS protein in cortex, hippocampus and ependyma were observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. The control group was injected with physiological saline of 0.9%, while the concentrations for the exposure groups were 0.05 and 0.5, 5 mg/kg MMC respectively, and the sampling times points were 20, 60, 240, 1440 min. RESULTS: The expression of c-FOS protein in cortex and hippocampus increased significantly, the accumulation of mercury in the brain induced by 0.05 mg/Kg MMC for 20 min had no significant difference compared with the control group. The mean value was 0.0044 mg/Kg, while the protein c-FOS expression had significant difference compared with the control group (P < 0.01). More sensitive expression occurred in hippocampus and cortex, but not in ependyma. Conclusion The expression of c-FOS protein in cortex and hippocampus can predict the neurotoxicity of MMC in the early time, and immediately early gene (IEG) c-fos participates in the process of brain injury induced by MMC.

Animals↗
PubMed2006

[Effects of acitretin on the expression of signaling pathway-related genes in epidermal squamous-cell carcinoma cells].

OBJECTIVE: To study the effects of acitretin on the expression of signaling pathway-related genes in an epidermal squamous-cell carcinoma cell line. METHODS: The mRNA expression levels of STAT3, cyclin D1 and p42/44MAPK were detected in a human epidermal carcinoma cell line A431 by RT-PCR. Their expressions at protein level were studied by Western blot. The expression levels were studied in cells treated with or without 10(-5) mol/L acitretin at different time intervals. RESULTS: (1) Acitretin could significantly inhibit the expression of STAT3 and cyclin D1 mRNA in a time-dependent manner (P < 0.05). The STAT3 and cyclin D1 protein expression levels were down-regulated. Acitretin could also down-regulate the p42/4MAPK mRNA expression. (2) After incubation with acitretin, the mRNA level of cyclin D1 cells was positively correlated with that of STAT3 (P < 0.05). The cyclin D1 protein level was also positively correlated with that of STAT3 (P < 0.05). However there was no correlation of mRNA levels between cyclin D1 and p42/44MAPK. CONCLUSION: Regulation of the Jak/STAT3 signaling pathway may play an important role in the effect of acitretin on epidermal squamous-cell carcinoma cells. The abnormal expression of STAT3 can be regarded as a prerequisite for acitretin treatment effect.

Acitretin↗