Biomedical subjects

Jin Chen

Publications and source records attributed to Jin Chen.

At least 19 recordsLinked to original sources

PubMed2025

Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions.

Understanding how genes influence drug responses is critical for advancing personalized cancer treatments. However, identifying these gene-drug interactions in a physiologically relevant human system remains a challenge, as it requires a model that reflects the complexity and heterogeneity among individuals. Here we show that large-scale CRISPR-based genetic screens, including knockout, interference (CRISPRi), activation (CRISPRa), and single-cell approaches, can be applied in primary human 3D gastric organoids to systematically identify genes that affect sensitivity to cisplatin. Our screens uncover genes that modulate cisplatin response. By combining CRISPR perturbations with single-cell transcriptomics, we resolve how genetic alterations interact with cisplatin at the level of individual cells and uncover an unexpected link between fucosylation and cisplatin sensitivity. We identify TAF6L as a regulator of cell recovery from cisplatin-induced cytotoxicity. These results highlight the utility of human organoid models for dissecting gene-drug interactions and offer insights into therapeutic vulnerabilities in gastric cancer.

Humans↗

PubMed2004

Elastic behavior of adsorbed polymer chains.

Elastic behaviors of single polymer chains adsorbed on the attractive surface are first investigated using Monte Carlo simulation method based on the bond fluctuation model. We investigate the chain size and shape of adsorbed chains, such as mean-square radius of gyration S2, mean-square bond length b2, shape factors sf(i) and delta*, and the orientation of chain segments P2 , to illuminate how the shape of polymer chains changes during the process of tensile elongation. There are some special behaviors of the chain size and shape at the beginning of elongation, especially for strong attraction interaction. For example, mean fraction of adsorbed segments decreases abruptly in the region of small elongation ratio and then decreases slowly with increasing elongation ratio. In fact, the chain size and shape also changes abruptly for small elongation ratio with strong attraction interaction. Some thermodynamics properties are also investigated here. Average Helmholtz free energy increases fast for elongation ratio lambda<1.15, especially with strong attraction, and increases slowly for lambda>1.15. Similar behaviors are obtained for average energy per bond. Elastic force (f ) and energy contribution to force (f(U)) are also studied, and we find that elastic force decreases abruptly for lambda<1.15, and there is a minimum of elastic force for strong attraction interaction, then increases very slowly with increasing elongation ratio. However, there are different behaviors for weak attraction interaction. For energy contribution to force (f(U)), there is a maximum value for strong attraction interaction in the region of lambda<1.15. Some comparisons with the atomic force microscopy experiments are also made. These investigations may provide some insights into the elastic behaviors of adsorbed polymer chains.

Journal Article↗

PubMed2004

Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling.

Trends in increased tuberculosis infection and a fatality rate of approximately 23% have necessitated the search for alternative biomarkers using newly developed postgenomic approaches. Here we provide a systematic analysis of Mycobacterium tuberculosis (Mtb) by directly profiling its gene products. This analysis combines high-throughput proteomics and computational approaches to elucidate the globally expressed complements of the three subcellular compartments (the cell wall, membrane, and cytosol) of Mtb. We report the identifications of 1044 proteins and their corresponding localizations in these compartments. Genome-based computational and metabolic pathways analyses were performed and integrated with proteomics data to reconstruct response networks. From the reconstructed response networks for fatty acid degradation and lipid biosynthesis pathways in Mtb, we identified proteins whose involvements in these pathways were not previously suspected. Furthermore, the subcellular localizations of these expressed proteins provide interesting insights into the compartmentalization of these pathways, which appear to traverse from cell wall to cytoplasm. Results of this large-scale subcellular proteome profile of Mtb have confirmed and validated the computational network hypothesis that functionally related proteins work together in larger organizational structures.

Automation↗

PubMed2004

Reverse endocytosis of transmembrane ephrin-B ligands via a clathrin-mediated pathway.

Eph/ephrin receptors and ligands mediate cell-cell interaction through reciprocal signaling upon juxtacrine contact, and play a critical role in embryonic patterning, neuronal targeting, and vascular assembly. To study transmembrane ephrin-B ligand trafficking, we determined the cellular localization of ephrin-B1-GFP upon engagement by EphB1. Under normal culture conditions ephrin-B1-GFP is localized to the plasma membrane, mostly at the lateral cell borders. Addition of soluble EphB1-Fc receptor induces ephrin-B1-GFP clustering on the cell surface and subsequent internalization, as judged by biochemical studies, electron microscopy, and co-localization with endosomal markers. A dominant-negative mutant of dynamin or potassium depletion blocks ephrin-B1 endocytosis. These results suggest that ephrin-B1 internalization is an active receptor-mediated process that utilizes the clathrin-mediated endocytic pathway.

Animals↗

PubMed2004

Observation of a threshold enhancement in the plambda invariant-mass spectrum.

An enhancement near the m(p)+M(Lambda) mass threshold is observed in the combined pLambda and pLambda invariant-mass spectrum from J/psi-->pK(-)Lambda;+c.c. decays. It can be fit with an S-wave Breit-Wigner resonance with a mass m=2075+/-12(stat)+/-5(syst) MeV and a width of Gamma=90+/-35(stat)+/-9(syst) MeV; it can also be fit with a P-wave Breit-Wigner resonance. Evidence for a similar enhancement is also observed in psi(')-->pK(-)Lambda;+c.c. decays. The analysis is based on samples of 5.8x10(7)J/psi and 1.4x10(7)psi(') decays accumulated in the BES II detector at the Beijing Electron-Positron Collider.

Journal Article↗

PubMed2004

Interspecific variation of plant traits associated with resistance to herbivory among four species of Ficus (moraceae).

BACKGROUND AND AIMS: To understand the defensive characteristics of interspecies varieties and their responses to herbivory damage, four species of Ficus plants (Ficus altissima, F. auriculata, F. racemosa and F. hispida) were studied. They were similar in life form, but differed in successional stages. Of these, Ficus altissima is a late successional species, F. hispida is a typical pioneer and F. auriculata and F. racemosa are intermediate successional species. We addressed the following questions: (1) What is the difference in plant traits among the four species and are these traits associated with differences in herbivory damage levels? (2) What is the difference in the damage-induced changes among the four species? METHODS: Herbivory damage was measured in the field on randomly planted seedlings of the four species of the same age. Defences to herbivory were also tested by feeding leaves of the four species to larvae of Asota caricae in the laboratory. A total of 14 characters such as water content, thickness, toughness, pubescence density on both sides, leaf expansion time, lifetime and the contents of total carbon (C), nitrogen (N), phosphorous (P), potassium (K), magnesium (Mg) and calcium (Ca) were measured. Leaf calcium oxalate crystal (COC) density, total Ca and N content, leaf toughness and height were measured to investigate induced responses to artificial herbivory among the four species. KEY RESULTS: and conclusions Herbivory damage in the four studied species varied greatly. The pioneer species, F. hispida, suffered the most severe herbivory damage, while the late successional species, F. altissima, showed the least damage. A combination of several characteristics such as high in content of N, Ca and P and low in leaf toughness, lifetime and C : N ratio were associated with increased herbivore damage. The late successional species, F. altissima, might also incorporate induced defence strategies by means of an increase in leaf COC and toughness.

Adaptation, Physiological↗

PubMed2004

Gene distribution of cagII in Helicobacter pylori-infected patients of Zhejiang Province.

AIM: To determine the prevalence of genotypes of cagII in Helicobacter pylori (H pylori)-infected patients in Zhejiang Province and investigate the relationship between these genotypes and the types of gastroduodenal diseases. METHODS: One hundred and seventy one clinical isolates were collected from 70 chronic superficial gastritis, 31 chronic atrophic gastritis, 41 gastric ulcer, 21 duodenal ulcer, 3 gastric and duodenal ulcer, and 5 gastric adenocarcinoma patients. Polymerase chain reaction assays were performed for analysis of cagT, ORF13 and ORF10 genes in the cagII region. RESULTS: Of 171 H pylori isolates from Zhejiang patients, 159(93.0%) were positive for all the three loci. One isolate (0.6%) was negative for all the three loci, and 11(6.4%) were partially deleted in cagII. The positive rates of cagT, ORF13 and ORF10 genes were 97.1%, 94.7% and 99.4%, respectively. In the strains isolated from the patients with diseases including chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer and duodenal ulcer, the sitive rates of cagT were 95.7%, 100.0%, 95.1% and 100.0%, respectively. The positive rates of ORF13 were 94.3%, 93.5%, 95.1% and 100.0%, respectively. The sitive rates of ORF10 were 98.6%, 100.0%, 100.0% and 100.0%, respectively. The three genes were all positive in the three H pylori strains isolated from the patients with both gastric and duodenal ulcer. In the five strains isolated from the patients with gastric adenocarcinoma, only one isolate was negative for ORF13. There were no significant differences of the cagT, ORF13 and ORF10 genes among the different gastroduodenal diseases including chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer, duodenal ulcer, both gastric and duodenal ulcer and gastric adenocarcinoma (chi(2)=3.098, P>0.05 for cagT; chi(2)=3.935, P>0.05 for ORF13 and chi(2)=6.328, P>0.05 for ORF10). CONCLUSION: The cagII is not a uniform and conserved entity. Although the genes in cagII are highly associated with the gastroduodenal diseases, the clinical outcome of H pylori infection is not reliably predicted by the three genes in cagII in patients from Zhejiang Province.

Adolescent↗

PubMed2004

EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation.

Angiogenesis is critical for vascular remodeling during development and contributes to the pathogenesis of diseases such as cancer. Targeted disruption of several EphB class receptor tyrosine kinases results in vascular remodeling defects during embryogenesis. The role of EphA class receptors in vascular remodeling, however, is not well-characterized. We recently demonstrated that global inhibition of EphA receptors disrupts endothelial migration induced by ephrin, VEGF or tumor-derived signals, though the specific target remained undefined. Here, we report that EphA2 regulates endothelial cell assembly and migration through phosphoinositide (PI) 3-kinase-mediated activation of Rac1 GTPase in two model systems: primary bovine and murine pulmonary microvascular endothelial cells. EphA2-deficient endothelial cells fail to undergo vascular assembly and migration in response to ephrin-A1 in vitro. Ephrin-A1 stimulation induces PI3-kinase-dependent activation of Rac1 in wild-type endothelial cells, whereas EphA2-deficient cells fail to activate Rac1 upon stimulation. Expression of dominant negative PI3-kinase or Rac1 inhibits ephrin-A1-induced endothelial cell migration. Consistent with in vitro data, EphA2-deficient mice show a diminished angiogenic response to ephrin-A1 in vivo. Moreover, EphA2-deficient endothelial cells fail to assemble in vivo when transplanted into recipient mice. These data suggest that EphA2 is an essential regulator of post-natal angiogenesis.

Adenoviridae↗

PubMed2004

Elastic behavior of short compact polymers.

In this paper, we investigate the elastic behaviors of short compact polymers using the enumeration calculation method and the HP model on a two-dimensional square lattice. Both the mean-square end-to-end distance R(2) and the ratio of R(2)/S(2) increase with lambda. However, when the elongation ratio becomes larger, the curves of R(2)/S(2) become smooth and they are close to the limit of 10.50 for different compact polymers. We also investigate the changes of interior conformations in the process of tensile elongation through calculating the probabilities of three bond angles (i.e., 90 degrees, 180 degrees, and 270 degrees). The average energy and Helmholtz free energy per bond are both negative and increase with elongation ratio lambda. In the meantime, the elastic force per bond (f ) also increases with elongation ratio lambda, and the energy contribution to the elastic force (f(U)) increases first and then drops, and there exists the maximum of f(U) in the region of lambda=1.40-1.80 for different sequences. The entropy contribution to force (f(S)) is close to zero at a small elongation ratio lambda and then increases with lambda. Some comparisons with different sequences (including nonfolding and folding sequences) are also made.

Journal Article↗

PubMed2004

Subpopulation of store-operated Ca2+ channels regulate Ca2+-induced Ca2+ release in non-excitable cells.

Ca2+-induced Ca2+ release (CICR) is a well characterized activity in skeletal and cardiac muscles mediated by the ryanodine receptors. The present study demonstrates CICR in the non-excitable parotid acinar cells, which resembles the mechanism described in cardiac myocytes. Partial depletion of internal Ca2+ stores leads to a minimal activation of Ca2+ influx. Ca2+ influx through this pathway results in an explosive mobilization of Ca2+ from the majority of the stores by CICR. Thus, stimulation of parotid acinar cells in Ca2+ -free medium with 0.5 microm carbachol releases approximately 5% of the Ca2+ mobilizable by 1 mm carbachol. Addition of external Ca2+ induced the same Ca2+ release observed in maximally stimulated cells. Similar results were obtained by a short treatment with 2.5-10 microm cyclopiazonic acid, an inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase pump. The Ca2+ release induced by the addition of external Ca2+ was largely independent of IP(3)Rs because it was reduced by only approximately 30% by the inhibition of the inositol 1,4,5-trisphosphate receptors with caffeine or heparin. Measurements of Ca2+ -activated outward current and [Ca2+](i) suggested that most CICR triggered by Ca2+ influx occurred away from the plasma membrane. Measurement of the response to several concentrations of cyclopiazonic acid revealed that Ca2+ influx that regulates CICR is associated with a selective portion of the internal Ca2+ pool. The minimal activation of Ca2+ influx by partial store depletion was confirmed by the measurement of Mn2+ influx. Inhibition of Ca2+ influx with SKF96365 or 2-aminoethoxydiphenyl borate prevented activation of CICR observed on addition of external Ca2+. These findings provide evidence for activation of CICR by Ca2+ influx in non-excitable cells, demonstrate a previously unrecognized role for Ca2+ influx in triggering CICR, and indicate that CICR in non-excitable cells resembles CICR in cardiac myocytes with the exception that in cardiac cells Ca2+ influx is mediated by voltage-regulated Ca2+ channels whereas in non-excitable cells Ca2+ influx is mediated by store-operated channels.

Animals↗

PubMed2004

Modulation of intracellular Na+ concentration by BmK AS, a scorpion toxin, in B104 cell line.

ABSL Effects of BmK AS, a toxin from scorpion Buthus mortensi Karsch and an activator of skeletal muscle RyRs, on the intracellular Na+ concentration have been investigated in the B104 neuroblastoma cell line by fluorescence digital imaging techniques. The intracellular Na+ concentration was elevated by 500 nM BmK AS significantly over a 30 min period, and the effect could be enhanced by addition of ouabain. In addition, BmK AS induced a biphasic modulation of [Na+]i in the dose-dependent range from 20 to 500 nM in the presence of ouabain. The results suggest that BmK AS may modulate intracellular signals by altering the intracellular Na+ concentration in the B104 cells.

Animals↗

PubMed2004

[Allogeneic chimerism induced by B7 antisense peptide pre-treated splenocytes prolongs the survival of allograft in mice].

OBJECTIVE: To investigate the roles of B7 antisense peptide (B7AP) in blocking the CD28-B7 pathway and inducing the allogeneic chimerism. METHODS: B7 antisense peptide was synthesized by solid phase synthetic methods and purified with HPLC. The C57BL/6 splenocytes of mice were pre-treated by B7AP, and subsequently injected in travenously to BALB/c mice. Three days later the mice were injected with fresh-made bone marrow cells derived from C57BL/6 mice. The B7 expression and allogeneic chimerism were analyzed with FACS. The lymphocyte proliferation reaction and the mice pinna cardiac transplantation model were exerted to study the relation between chimerism and prolongation of allograft in vitro and in vivo. RESULTS: Lymphoproliferation of the splenocytes derived from BALB/c mice immunized with the B7AP pretreated C57BL/6 splenocytes versus splenocytes from C57BL/6 mice was inhibited dramatically with a inhibition rates up to 43%. Under this condition, the allogeneic chimerism was successfully induced after BMT. Both the chimerism and the survival of allogeneic cardiac grafts were prolonged over 100 days (n = 6). CONCLUSION: Synthetic B7 antisense peptide can induce allogeneic chimerism in mice and consequently prolong the survival of allogeneic cardiac grafts.

Animals↗

PubMed2004

The CD28 peptidemimic can induce mixed chimerism and prolong the survival of cardiac allografts.

Costimulatory blockade with CD28 peptidemimic (CD28PM, CD28 PM was synthesized by solid phase synthetic methods) prolongs cardiac allograft survival in mice, but has not reliably induced tolerance when used alone. In the current studies, we evaluated the effect of adding B7 blockade to a chimerism inducing nonmyeloablative regimen in mice and observed a significant improvement of donor bone marrow cells (BMC) engraftment, which had been associated with mixed chimerism and long-term survival of cardiac allografts. The mixed lymphocyte reaction (MLR) and the ear pinna cardiac transplantation model were performed to evaluate the effects of CD28PM in induction of specific immune hypo-response and extension of allograft survival. The expressed rates of B7.1 and B7.2 on the C57BL/6 splenocytes were 56.25% and 20.52%, respectively. The specific hypo-response status was established after immunization with CD28PM pre-treated donor splenocytes and the average inhibition rate was only 43% compared with normal control. Subsequently, a total number of 2 x 10(7) bone marrow cells per mouse were implanted to the recipients. The allogenic chimerism was obviously observed with the rate as high as 8.84% (mean) at the time point of day 14. During the first 50 days post bone marrow transfusion (BMT) the chimerism rate declined stepwise. But from 50 to 100 days, the chimerism rate sustained in a range of 3.35% to 4.6%. The results of transplantation experiments showed the survival of allgenic cardiac grafts were maintained over 100 days in recipients. Thus, donor BMC engraftment with mixed chimerism appears essential for induction of allograft tolerance using this conditioning regimen. Mixed chimerism approach, by the addition of CD28-B7 costimulatory blockade with CD28PM, has been shown to establish mixed chimerism and induce cardiac allograft tolerance in mice.

Animals↗

PubMed2004

Eph receptor tyrosine kinases in angiogenesis: from development to disease.

Angiogenesis, the process by which new blood vessels sprout and branch from existing vasculature, is crucial for vascular remodeling during embryogenesis and in normal tissue homeostasis, such as in the female reproductive tract. Angiogenesis can also contribute to the pathogenesis of diseases such as cancer and retinopathy. The Eph family of receptor tyrosine kinases and their ligands, called ephrins, has emerged as critical regulators of vascular remodeling in the embryo. More recently, these molecules have been associated with post-natal angiogenic remodeling and tumor neovascularization. This review provides an overview of recent advances in our understanding of Eph/ephrins in angiogenesis, with an emphasis on development and disease, and the potential for targeting these molecules in anti-angiogenic therapy.

Animals↗

PubMed2004

Eph receptor tyrosine kinases in tumor and tumor microenvironment.

Eph receptors are a unique family of receptor tyrosine kinases (RTK) that play critical roles in embryonic patterning, neuronal targeting, and vascular development during embryogenesis. In adults, Eph RTKs and their ligands, the ephrins, are frequently overexpressed in a variety of cancers and tumor cell lines, including breast, prostate, non-small cell lung and colon cancers, melanomas, and neuroblastomas. Unlike traditional oncogenes that often function only in tumor cells, recent data show that Eph receptors mediate cell-cell interaction both in tumor cells and in tumor microenvironment, namely the tumor stroma and tumor vasculature. As such, Eph RTKs represent attractive potential targets for drug design, as targeting these molecules could attack several aspects of tumor progression simultaneously. This review will focus on recent advances in dissecting the role of Eph RTKs in tumor cells, tumor angiogenesis, and possible contribution to trafficking of inflammatory cells in cancer.

Animals↗

PubMed2004

[Expression of chemokine receptor CXCR4 in nasopharyngeal carcinoma cells].

BACKGROUND & OBJECTIVE: It was reported that chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1(SDF-1) were involved in the proliferation, differentiation, and metastasis of tumor. This study was designed to observe the expression of CXCR4 in NPC cells with different differentiation grade and proliferative ability to primitively clarify the relationship between CXCR4 and the malignity of NPC cells. METHODS: After treated with all-trans-retinoic acid(RA) and telomerase antisense oligodeoxynucleotide (ASODN) respectively, the expression of CXCR4 mRNA and CXCR4 protein in NPC CNE1 and CNE2Z cells were determined by in situ hybridization and immunohistochemistry, respectively; the distribution of cell cycle was examined with flow cytometry and the proliferation of cells was identified by MTT method. RESULTS: CXCR4 mRNA and CXCR4 protein were strongly expressed in both CNE1 and CNE2Z cells, and their expression in CNE2Z cells was stronger than that in CNE1 cells. After treated with 1x10(-5) mol/L and 1x10(-4) mol/L RA, CNE1 cells were arrested in G1 phase and CNE2Z cells in S phase, while the CXCR4 mRNA expression was significantly decreased in both CNE1 and CNE2Z cells compared with control group cells (P< 0.01). The effect of 1x10(-4) mol/L RA was more powerful than that of 1x10(-5) mol/L RA. After treated with ASODN, the proliferation of CNE1 and CNE2Z cells was inhibited, and the expression of CXCR4 protein was decreased compared with the control (P< 0.01). CONCLUSION: CXCR4 is highly expressed in NPC cells,and its expression was associated with differentiation grade and proliferation ability of NPC cells.

Cell Cycle↗

PubMed2004

[Study on bone marrow megakaryocytes in children patients with myelodysplastic syndrome].

The study was aimed to observe morphological characteristics and hematopoiesis function of bone marrow megakaryocyte in children patients with myelodysplastic syndrome (MDS), and analyse the cause and mechanism of thrombocytopenia. CD41 McAb immunohistochemical technique was used to detect micromegakaryocytes of bone marrow smear. Plasma clot culture and CD41 McAb immunohistochemical technique were used for the MK-colony forming assay. The colony formations of CFU-MK and BFU-MK were measured. The results showed that there was no significant difference of CFU-MK colony formation rate between groups of MDS and control. But, in 62.5% of children patients the colony formation rate of CFU-MK decreased, in 25% increased, and in 12.5% was normal while BFU-MK formation rate decreased in MDS group significantly. The number of micromegakaryocyte and the positive rate of type I lymphoid micromegakaryocyte were significantly higher than those of the control group. In conclusion, there may be two kinds of megakaryocyte clones in bone marrow of children patients with MDS. One is supposed to be pathologic and potentially malignant micromegakaryocytes, the another may be the normal megakaryocytic precursors. The thrombocytopenia in MDS patients induced by increase of pathologic MK leads to abnormal development and maturation of MK in bone marrow.

Adolescent↗

PubMed2004

[Effect of S-2-(3-aminopropylamino) ethyl phosphorothioic acid on apoptosis and proliferation inhibition of HL-60 cell line].

To study the effects of S-2-(3-aminopropylamino) ethyl phosphorothioic acid (WR-2721, amifostine) on proliferation inhibition and apoptosis of HL-60 human leukemia cell line, the cell apoptosis rate of HL-60 was determined by annexin V/PI double staining method. Cell proliferation and chemotherapy sensitivity were analyzed with XTT assay, and the changes of cell cycle were observed through flow cytometry. The results showed that WR-2721 could significantly inhibit HL-60 cell proliferation. After treatment (30 min, 37 degrees C) with WR-2721, the sensitivity of HL-60 cells to VP16 was enhanced, and the IC(50) descended from 52.5 micro g/ml to 40.5 microg/ml. After 72 hours treatment of HL-60 cells with WR-2721, the early apoptotic cells (annexin V-FITC positive/PI negative) were increased from (5.5 +/- 1.9)% to (48.5 +/- 8.4)% (P < 0.001), late apoptotic cells (annexin V-FITC positive/PI positive) were increased from (1.2 +/- 0.5)% to (39.0 +/- 4.0)% (P < 0.001), and HL-60 cells were arrested in G(2)-M phase. In conclusion, WR-2721 treatment can enhance HL-60 cell chemotherapy sensitivity to VP16, inhibit proliferation, induce apoptosis and accumulation of cells in G(2)-M phase.

Amifostine↗