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Biomedical subjects

Na Chen

Publications and source records attributed to Na Chen.

12 recordsLinked to original sources
PubMed2026

CircRNA-based CD19-targeted CAR-NK therapy for B-cell acute lymphoblastic Leukemia using a Coccidioides immitis-derived group II intron platform.

Chimeric antigen receptor (CAR)-T cell therapy targeting CD19 has demonstrated notable clinical efficacy in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), but its wider clinical applicability is constrained by long manufacturing processes, substantial costs, and severe adverse events. A potentially safer and more accessible alternative is provided by CAR-Natural killer (CAR-NK) cell therapy. Currently, most CAR-NK cells are generated using viral transduction, which is labor-intensive and associated with risks of genomic integration. Electroporation of CAR-encoding mRNA provides a non-integrating alternative but results in only transient CAR expression. Circular RNA (circRNA), owing to its enhanced stability and prolonged protein expression capacity, has recently emerged as a promising alternative to linear mRNA. To overcome the limitations of transient mRNA expression, we generated circRNA using a Group II intron-mediated cyclization system incorporating a newly selected Coccidioides immitis-derived Group II intron. The newly established Coccidioides immitis-derived Group II intron circularization system efficiently generated circRNA and supported more durable EGFP expression than linear mRNA in both HEK293T and NK92 cells. Using this system, we successfully developed a circRNA-based CD19-targeted CAR-NK platform. CircRNA-engineered CD19-targeted CAR-NK92 cells maintained more durable CAR expression and showed stronger antitumor activity at later time points. In mouse models of B-ALL, circRNA-engineered CAR-NK92 cells demonstrated better tumor control and extended survival compared with their linear mRNA-engineered counterparts. These results support the potential of circRNA-based CAR-NK therapy as an effective approach for enhancing the safety and efficacy of cancer immunotherapy.

Humans↗
PubMed2025

A GDSL lipase confers resistance to piercing-sucking insects in tobacco by strengthening leaf cuticle.

Piercing-sucking insects, such as whiteflies and aphids, cause massive economic losses in major crops around the world. During feeding, the stylets of piercing-sucking insects navigate cuticles, cell walls, epidermal cells, and mesophyll cells; thus, these barriers are vital for the resistance of plants to insects. However, the relationship between insect stylet probing behavior and the composition and structure of these barriers remains unclear. Here, we identified a tobacco Cuticle Related Factor (NtCRF), which was induced significantly by whitefly infestation. Bioassays showed that NtCRF positively regulated plant resistance against whiteflies and green peach aphids. Silencing of NtCRF did not affect plant jasmonic acid (JA) and salicylic acid (SA) defenses but shortened the stylet probing time of phloem-feeders. Further studies confirmed that silencing of NtCRF resulted in significant structure destruction of the leaf cuticle and led to increased epidermal permeability. Overexpression of NtCRF in Arabidopsis also significantly enhanced the plant's resistance against whiteflies and green peach aphids. Our findings expand understanding of plant-insect interactions and provide a strategy for genetic improvement of crop resistance against piercing-sucking insects.

Animals↗
PubMed2006

Afterhyperpolarization improves spike programming through lowering threshold potentials and refractory periods mediated by voltage-gated sodium channels.

Neurons program various patterns of sequential spikes as neural codes to guide animal behavior. Studies show that spike programming (capacity and timing precision) is influenced by inhibitory synaptic inputs and membrane afterhyperpolarization (AHP). Less is clear about how these inhibitory components regulate spike programming, which we investigated at the cortical neurons. Whole-cell current-clamp recording for action potentials and single channel recording for voltage-gated sodium channels (VGSC) were conducted at regular-spiking and fast-spiking neurons in the cortical slices. With quantifying the threshold potentials and refractory periods of sequential spikes, we found that fast-spiking neurons expressing AHP possess lower threshold potentials and shorter refractory periods, and the hyperpolarization pulse immediately after each of spikes lowers threshold potentials and shortens refractory periods at regular-spiking neurons. Moreover, the hyperpolarization pulses shorten the refractory periods for VGSC reactivation and threshold potentials for its sequential activation. Our data indicate that inhibitory components immediately after spikes, such as AHP and recurrent inhibition, improve spike capacity and timing precision via lowering the refractory periods and threshold potentials mediated by voltage-gated sodium channels.

Action Potentials↗
PubMed2006

Sodium channel-mediated intrinsic mechanisms underlying the differences of spike programming among GABAergic neurons.

Neural codes to guide well-organized behavior are thought to be the programmed patterns of sequential spikes at central neurons, in which the coordinative activities of voltage-gated ion channels are involved. The attention has been paid to study the role of potassium channels in spike pattern; but it is not clear how the intrinsic mechanism mediated by voltage-gated sodium channels (VGSC) influences the programming of sequential spikes, which we investigated at GABAergic cerebellar Purkinje cells and hippocampal interneurons by patch-clamp recording in brain slices. Spike capacity is higher at Purkinje cells than interneurons in response to the given intensities of inputs, and is dependent on input intensity. Compared to interneurons, Purkinje cells express the lower threshold potentials and the shorter refractory periods of sequential spikes. The increases of input intensities shorten spike refractory periods significantly. The threshold potentials for VGSC activation and the refractory periods for its reactivation are lower at Purkinje cells, and are reduced by the strong depolarization. We suggest that the VGSC-mediated threshold potentials and refractory periods are regulated by synaptic inputs, and navigate the programming of sequential spikes at the neurons.

Action Potentials↗
PubMed2005

The refractory periods and threshold potentials of sequential spikes measured by whole-cell recording.

Neurons in the central nervous system are thought to program neural language via firing sequential spikes for guiding animal behaviors. The quantitative profiles of spike intrinsic properties are critically important to understand spike programming. We developed approaches with whole-cell recordings to measure the threshold potentials and refractory periods (RPs) of sequential spikes, and to analyze the relationships of these factors with spike timing precision and capacity at the regular-spiking and fast-spiking neurons in cortical slice. The RPs and threshold potentials of sequential spikes at these two groups of neurons are different and are linearly correlated with spike timing precision and capacity. These data suggest that RPs and threshold potentials essentially navigate the spike programming for the precise and loyal encoding of meaningful neural signals. Our study provides the avenues for decoding the spectrum of the neural signals quantitatively.

Action Potentials↗
PubMed2005

Quantification of endogenous retinoic acid in limited biological samples by LC/MS/MS.

We report a sensitive LC (liquid chromatography)/MS/MS assay using selected reaction monitoring to quantify RA (retinoic acid), which is applicable to biological samples of limited size (10-20 mg of tissue wet weight), requires no sample derivatization, provides mass identification and resolves atRA (all-trans-RA) from its geometric isomers. The assay quantifies over a linear range of 20 fmol to 10 pmol, and has a 10 fmol limit of detection at a signal/noise ratio of 3. Coefficients of variation are: instrumental, 0.5-2.9%; intra-assay, 5.4+/-0.4%; inter-assay 8.9+/-1.0%. An internal standard (all-trans-4,4-dimethyl-RA) improves accuracy by confirming extraction efficiency and revealing handling-induced isomerization. Tissues of 2-4-month-old C57BL/6 male mice had atRA concentrations of 7-9.6 pmol/g and serum atRA of 1.9+/-0.6 pmol/ml (+/-S.E.M.). Tissue 13-cis-RA ranged from 2.9 to 4.2 pmol/g, and serum 13-cis-RA was 1.2+/-0.3 pmol/ml. CRBP (cellular retinol-binding protein)-null mouse liver had atRA approximately 30% lower than wild-type (P<0.05), but kidney, testis, brain and serum atRA were similar to wild-type. atRA in brain areas of 12-month-old female C57BL/6 mice were (+/-S.E.M.): whole brain, 5.4+/-0.4 pmol/g; cerebellum, 10.7+/-0.3 pmol/g; cortex, 2.6+/-0.4 pmol/g; hippocampus, 8.4+/-1.2 pmol/g; striatum, 15.3+/-4.7 pmol/g. These data provide the first analytically robust quantification of atRA in animal brain and in CRBP-null mice. Direct measurements of endogenous RA should have a substantial impact on investigating target tissues of RA, mechanisms of RA action, and the relationship between RA and chronic disease.

Alitretinoin↗
PubMed2005

[cDNA cloning and expression of a cytosolic small heat shock protein gene (CaHSP18) from Capsicum annuum].

Full length 779 bp cytosolic clsss I sHSP cDNA was cloned from heat-shocked sweet pepper leaves using a PCR approach with degenerate primers designed from conserved motifs found in a number of plant cytosolic clsss I sHSP genes, named CaHSP18. Its accession number is AY284925. CaHSP18 was high identified with Nicotiana tabacum (Fig.1). A multi-gene family was found in sweet pepper genomic DNA by Southern-blot analysis (Fig.3). Northern blot revealed that the expression of CaHSP18 in sweet pepper was induced by heat treatment and was significantly different between different tissues (Fig.4). The transcription of CaHSP18 in leaves and stems were higher than those in roots. The expression of CaHSP18 could be detected after chilling treatment at 4 degrees C for 2 d. Recombinant CaHSP18 was overexpressed in Escherichia coli to study its possible function under heat and chilling stress. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of cell lysates suggested that CaHSP18 was expressed in Escherichia coli (Fig.6). The growth of wild type and transformed cells was similar at 37 degrees C (Fig. 5). Upon transfer from 37 degrees C to 50 degrees C, a temperature known to cause cell autolysis, those cells that accumulated CaHSP18 showed improved viability compared with the control lines (Fig.7). To test the hypothesis that sHSPs may be involved in protection against chilling stress, the viability of recombinant cells at 4 degrees C was studied. The sweet pepper CaHSP18 significantly enhanced cell survivability (Fig.8). These results indicate that plant cytosolic clsss I sHSP have protective functions not only against heat stress but also against chilling stress.

Amino Acid Sequence↗
PubMed2004

Ethanol increases retinoic acid production in cerebellar astrocytes and in cerebellum.

Several characteristics of fetal alcohol syndrome (FAS) are similar to the teratogenic effects of retinoic acid (RA) exposure. It has been suggested that FAS may result from ethanol-induced alteration in endogenous RA synthesis, leading to abnormal embryonic concentrations of this morphogen. We examined whether ethanol may interfere with RA synthesis in the postnatal cerebellum, as a region of the developing CNS particularly vulnerable to both ethanol and RA teratogenesis. It was found that astrocytes are the predominant source of postnatal RA synthesis in the cerebellum. They express both retinaldehyde dehydrogenase 1 and 2. In vitro cytosolic preparations of astrocytes, as well as live cell preparations, have an increased capacity to synthesize RA in the presence of ethanol. A mechanism by which ethanol could stimulate RA synthesis is via the ethanol-activated short-chain retinol dehydrogenases, which we show to be present in the postnatal cerebellum. To determine whether ethanol stimulated RA synthesis in vivo, a sensitive and highly specific HPLC/MSn technique was used to measure cerebellar RA after administration of ethanol to postnatal day 4 rat pups. Cerebellar RA levels climbed significantly after such treatment. These results suggest that the cerebellar pathology exerted by ethanol may occur, at least in part, through increased production of RA.

Alcohol Dehydrogenase↗
PubMed2002

Studies on adjuvanticity of sodium houttuyfonate and its mechanism.

The adjuvanticity of sodium houttuyfonate (SH) and its mechanism were studied in this research. Significant enhancement of antibody production was observed when co-injected with antigen. The levels of anti-BSA antibodies were measured by enzyme-linked immunosorbent assay (ELISA). The possible mechanism of this phenomenon was also investigated in this research, which included the effects of SH on the phagocytosis of macrophages, the production of lysozyme, acid phosphotase and IL-1beta generated by macrophages, the proliferation of the lymphocytes in spleen and the production of IL-2 generated by lymphocytes. IL-1beta is a co-stimulator in activating Th cells, which manifests its activity together with LFA-1, ICAM-1 and ICAM-2. These observations suggested that SH could be used as a new adjuvant.

Adjuvants, Immunologic↗
PubMed2002

[Analysis of randomized controlled trials on otorhinolaryngological diseases in China].

OBJECTIVE: To evaluate the quality of randomized controlled trials (RCT) in otorhinolaryngology in China and offer evidence for the improvement of RCT. METHODS: Five kinds of Chinese journals of clinical otorhinolaryngology were searched, and RCTs were identified and analyzed according to the standards of Evidence Based Medicine. RESULTS: Two hundred and eighty seven issues were referred to, and eighty-one RCTs were finally identified and analyzed. Of these RCTs, 34.57% (28/81) had definite diagnostic standards, 38.27% (31/81) had including standards and 33.33% (27/81) had excluding standards; only 1.23% (1/81) got the approval of the participants; 40.74% (33/81) had moderate sample size, 3.70% (3/81) had large sample size and non of them mentioned sample size estimation; 81.48% (66/81) didn't report the method of randomization and 38.27% (31/81) had baseline comparison; 18.52% (15/81) didn't define the control interventions and 8.64% (7/81) even didn't explicate the experimental intervention; 32.10% (26/81) used blank comparison; 86.42% (70/81) didn't use blindness; 37.04% (30/81) didn't mention the adverse effects; 23.46% (19/81) used accredited standards to evaluate the outcomes; 11.11% (9/81) mentioned the loss of following-up and only 1.23% (1/81) treated the loss with statistics methods. CONCLUSION: The quantity and quality of otorhinolaryngological RCTs couldn't meet the clinical need. More high quality RCTs are required to improve the level of prevention and cure of otorhinolaryngologic diseases.

China↗
PubMed2002

[Vasodilators for sudden sensorineural hearing loss: a systematic review of randomized controlled trials].

OBJECTIVE: To assess the effects and safety of vasodilators on sudden sensorineural hearing loss(SSHL). SEARCH STRATEGY: Electronic databases: MEDLINE from 1966, EMBASE from 1974, the Cochrane Controlled Trails Register, Chinese Bio-medicine Database from 1989. Hand search: Five kinds of Chinese otolaryngology journals were selected. Literature references were checked intensively. SELECTION CRITERIA: Randomized controlled trials comparing vasodilators with placebo or other drugs in patients with SSHL. DATA COLLECTION AND ANALYSIS: Three reviewers independently accessed the quality of trials and extracted the data. RESULTS: Thirteen trials with 1,155 patients were eligible and covered in the systematic review. Ten of the trials were conducted in developed countries, and three in China. None of the four trials showed the effects of vasodilators on SSHL were better than that of placebo. None of the seven trials comparing different drugs showed the effects of one kind of vasodilators were better than that of the other vasodilators. Two trials showed that some other drugs, such as batroxobin and hypaque were probably better than the vasodilators (dextran, papaverine, 654-2, danshen). Eight trials showed side effects of vasodilators, such as pruritus, allergy, etc. CONCLUSIONS: Based on the systematic review of current eligible randomized controlled clinical trials, there is no evidence to prove that vasodilator therapy is more effective than placebo or other therapies for SSHL, or the effects of one kind of vasodilators to be better than that of the other vasodilators. So far we can't draw a reliable conclusion about the effects of vasodilators for SSHL. In addition, we must pay attention to their potential adverse reactions.

Databases, Bibliographic↗