Biomedical subjects

Bin Zhang

Publications and source records attributed to Bin Zhang.

At least 37 records · Page 2Linked to original sources

PubMed2025

Unsupervised multiscale clustering of single-cell transcriptomes to identify hierarchical structures of cell subtypes.

BACKGROUND: Cell clustering is an essential step in uncovering cellular architectures in single-cell RNA sequencing (scRNA-seq) data. However, the existing cell clustering approaches are not well designed to dissect complex structures of cellular landscapes at a finer resolution. RESULTS: Here, we develop a multiscale clustering (MSC) approach to construct a sparse cell-cell correlation network for unsupervised identification of de novo cell types and subtypes across multiple resolutions. Based upon simulated silver- and gold-standard data as well as real scRNA-seq data in diseases, MSC demonstrates significantly improved performance compared to established benchmark methods and reveals a biologically meaningful cell hierarchy to facilitate the discovery of novel disease-associated cell subtypes and mechanisms. CONCLUSIONS: We present MSC as a new single-cell multiscale clustering framework as a powerful tool for advancing discoveries in disease-associated cell populations using single-cell sequencing data.

Single-Cell Analysis↗

PubMed2024

An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing.

Colorectal cancer (CRC) ranks as the second leading cause of cancer deaths globally. In recent years, short-read single-cell RNA sequencing (scRNA-seq) has been instrumental in deciphering tumor heterogeneities. However, these studies only enable gene-level quantification but neglect alterations in transcript structures arising from alternative end processing or splicing. In this study, we integrated short- and long-read scRNA-seq of CRC samples to build an isoform-resolution CRC transcriptomic atlas. We identified 394 dysregulated transcript structures in tumor epithelial cells, including 299 resulting from various combinations of splicing events. Second, we characterized genes and isoforms associated with epithelial lineages and subpopulations exhibiting distinct prognoses. Among 31,935 isoforms with novel junctions, 330 were supported by The Cancer Genome Atlas RNA-seq and mass spectrometry data. Finally, we built an algorithm that integrated novel peptides derived from open reading frames of recurrent tumor-specific transcripts with mass spectrometry data and identified recurring neoepitopes that may aid the development of cancer vaccines.

Colorectal Neoplasms↗

PubMed2007

Structure-dependent response of a chemiluminescence nitrogen detector for organic compounds with adjacent nitrogen atoms connected by a single bond.

High-throughput screening (HTS) of chemical libraries is indispensable for drug discovery research. However, the HTS data quality for lead discovery, lead optimization, and quantitative structure activity relationship studies has been severely compromised due to the uncertain compound concentrations in screening plates. In order to address this issue, we compared various high-throughput technologies for quantification of compounds in microtiter plate format without the need for authentic compounds as standards and identified the chemiluminescence nitrogen detector (CLND) as the method of choice at the present time. However, the structure dependence of this detector has not been well studied. A proposed rule suggested that the only exception to equimolar response is for compounds that contain adjacent nitrogen atoms. The response should be zero when the adjacent nitrogen atoms are connected by a double bond and 0.5 when they are connected by a single bond. In this investigation, we studied a broad range of compounds with isolated and adjacent nitrogen atoms. We confirmed that compounds with isolated nitrogen atoms produce an equimolar response with a 15-20% variation depending on structures and compounds with adjacent nitrogen atoms connected by a double bond giving nearly zero response. We discovered that the CLND response for compounds containing adjacent nitrogen atoms that are connected with a single bond is highly structure dependent. Substitutions on the nitrogen atoms or nearby in the molecule can increase the CLND response to approach a value higher than the predicted value 0.5 (maximal value 0.82/nitrogen atom). Without substitution, much lower values than predicted (minimal value 0.0-0.08/nitrogen atom) are obtained. Therefore, the prediction of response of 0.5/nitrogen atom for compounds with adjacent nitrogen atoms connected by a single bond should be abandoned. Compounds with similar structures should be used to generate calibration curves for quantification of this class of compounds.

Luminescence↗

PubMed2007

Induced sensitization of tumor stroma leads to eradication of established cancer by T cells.

Targeting cancer cells, as well as the nonmalignant stromal cells cross-presenting the tumor antigen (Ag), can lead to the complete destruction of well-established solid tumors by adoptively transferred Ag-specific cytotoxic T lymphocytes (CTLs). If, however, cancer cells express only low levels of the Ag, then stromal cells are not destroyed, and the tumor escapes as Ag loss variants. We show that treating well-established tumors expressing low levels of Ag with local irradiation or a chemotherapeutic drug causes sufficient release of Ag to sensitize stromal cells for destruction by CTLs. This was shown directly using high affinity T cell receptor tetramers for visualizing the transient appearance of tumor-specific peptide-MHC complexes on stromal cells. Maximum loading of tumor stroma with cancer Ag occurred 2 d after treatment and coincided with the optimal time for T cell transfer. Under these conditions, tumor rejection was complete. These findings may set the stage for developing rational clinical protocols for combining irradiation or chemotherapy with CTL therapy.

Adoptive Transfer↗

PubMed2007

[Efficacy and safety of coupled plasma filtration adsorption combined with continuous veno-venous hemofiltration for multiple organ dysfunction syndrome patients with acute liver failure].

OBJECTIVE: To evaluate efficacy and safety of coupled plasma filtration adsorption (CPFA) combined with continuous veno-venous hemofiltration (CVVH) for the treatment of multiple organ dysfunction syndrome (MODS) patients with acute liver failure (ALF), and to evaluate the effect of CPFA plus CVVF on inflammatory mediators in these patients. METHODS: A total of 38 cases of 11 MODS patients with ALF (male 6, female 5) were treated with CPFA plus CVVH, and the following clinical indicators including changes in mean arterial pressure (MAP), oxygen index (PaO(2)/FiO(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, IL-8, biochemical parameters of liver and kidney function, parameters of systemic inflammatory response syndrome (SIRS) score, and acute physiology and chronic health evaluation II (APACHE II) score were determined before and after the treatment. The degree of improvement in clinical symptoms, feasibility, tolerance toward CPFA plus CVVH, therapy-related adverse reactions and security were simultaneously evaluated. RESULTS: MAP increased by 12 mmHg (1 mmHg=0.133 kPa), and PaO(2)/FiO(2) increased by 40 mmHg after the application of CPFA plus CVVH (both P<0.05), along with significant decrease in TNF-alpha, IL-1 beta, IL-6, IL-8 and markedly lowered levels of serum total bilirubin (IBIL), direct bilirubin (DBIL), blood urea nitrogen (BUN), serum creatinine (SCr) and blood ammonia (all P<0.05). Besides, clinical symptoms, including urinary volume, mental disturbance, jaundice, debility, nausea, vomiting, fever, abdominal distention, anepithymia, and SIRS, APACHE II scores were improved significantly after the CPFA plus CVVH (all P<0.05). No therapy-related adverse reactions, including severe haemorrhage, shock, hypersensitivity, were noted, and patients tolerated well toward CPFA plus CVVH. The total survival rate of patients was 45.5% (5/11 cases) at the end of the treatment. CONCLUSION: Our data indicate that CPFA combined with CVVH is an effective and safe method to improve the prognosis of MODS patients with ALF, the mechanism of which may be related to its effective removal of inflammatory cytokines.

Adult↗

PubMed2006

Steamed American ginseng berry: ginsenoside analyses and anticancer activities.

This study was designed to determine the changes in saponin content in American ginseng berries after treatment by heating and to assess the anticancer effects of the extracts. After steaming treatment (100-120 degrees C for 1 h, and 120 degrees C for 0.5-4 h), the content of seven ginsenosides, Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd, decreased; the content of five ginsenosides, Rh1, Rg2, 20R-Rg2, Rg3, and Rh2, increased. Rg3, a previously identified anticancer ginsenoside, increased significantly. Two hours of steaming at 120 degrees C increased the content of ginsenoside Rg3 to a greater degree than other tested ginsenosides. When human colorectal cancer cells were treated with 0.5 mg/mL steamed berry extract (120 degrees C 2 h), the antiproliferation effects were 97.8% for HCT-116 and 99.6% for SW-480 cells. At the same treatment concentration, the effects of unsteamed berry extract were 34.1% for HCT-116 and 4.9% for SW-480 cells. After staining with Hoechst 33258, apoptotic cells increased significantly by treatment with steamed berry extract compared with unheated extracts. Induction of apoptosis activity was confirmed by flow cytometry after staining with annexin V/PI. The steaming of American ginseng berries augments ginsenoside Rg3 content and increases the antiproliferative effects on two human colorectal cancer cell lines.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Characterization of a novel effect of hPinX1 on hTERT nucleolar localization.

The factor PinX1 has been shown as a telomerase inhibitor evolutionarily conserved in both the yeast and the human being. yPinX1 inhibits telomerase activity by sequestering yTERT (telomerase reverse transcriptase) from uniting with yTR (telomerase template RNA) in the nucleolus of yeast cells. However, the mechanism underlying the action of hPinX1 on telomerase regulation in human cells is not known. We here demonstrated that hPinX1 actually has an effect on mediating hTERT nucleolar localization and this effect is mediated by a novel domain enclosed within the central section of the polypeptide. Interestingly, we showed that a reported cancerous mutant form of hPinX1, in which residues of Ser254 and Cys265 are, respectively, mutated to Cys and Tyr, lost the activity on mediating hTERT nucleolar localization. Finally, we provided evidence that mediation of hTERT nucleolar localization and telomerase enzymatic inhibition are two separated function of hPinX1 on telomerase regulation in human cells.

Binding Sites↗

PubMed2006

Involvement of the purinergic P2X7 receptor in the formation of multinucleated giant cells.

Multinucleated giant cells (MGC), a hallmark of chronic inflammatory reactions, remain an enigma of cell biology. There is evidence implicating the purinergic P2X7 receptor in the fusion process leading to MGC. To investigate this, we used HEK 293 cells stably transfected with either 1) the full-length rat P2X7 receptor (P2X7 cells), 2) a rat P2X7 receptor lacking the C-terminal domain (P2X7TC), or 3) a mock vector, and rat alveolar macrophages (MA) expressing the native receptor. P2X7 cells cultured in serum-free medium formed increased numbers of MGC and displayed a higher fusion index compared with mock transfectants. Stimulation of P2X7 pore-forming activity in P2X7 cells by polymyxin B (PMB) further increased significantly the formation of MGC. Conversely, blockers of P2X-receptors including oxidized ATP, brilliant blue G, and pyridoxal phosphate-6-azophenyl-2'-4'-disulfonic acid inhibited significantly MGC formation in both unstimulated and PMB-stimulated P2X7-transfected cells. In contrast, cells transfected with the truncated P2X7TC were devoid of pore-forming activity, did not respond to PMB stimulation, and failed to form enhanced numbers of MGC, thus behaving as mock transfectants. As found for P2X7-transfected cells, PMB also potentiated dose-dependently the formation of multinucleated MA by rat alveolar MA. Pretreatment with oxidized ATP abrogated the PMB stimulatory effects. Together, these data demonstrate unequivocally the participation of P2X7 receptor in the process of MGC formation. Our study also provides evidence suggesting that stimulation of the P2X7 receptor pathway in MA may mediate increased formation of MGC during chronic inflammatory reactions.

Adenosine Triphosphate↗

PubMed2006

Algebraic iterative algorithm for deflection tomography and its application to density flow fields in a hypersonic wind tunnel.

A novel algebraic iterative algorithm based on deflection tomography is presented. This algorithm is derived from the essentials of deflection tomography with a linear expansion of the local basis functions. By use of this algorithm the tomographic problem is finally reduced to the solution of a set of linear equations. The algorithm is demonstrated by mapping a three-peak Gaussian simulative temperature field. Compared with reconstruction results obtained by other traditional deflection algorithms, its reconstruction results provide a significant improvement in reconstruction accuracy, especially in cases with noisy data added. In the density diagnosis of a hypersonic wind tunnel, this algorithm is adopted to reconstruct density distributions of an axial symmetry flow field. One cross section of the reconstruction results is selected to be compared with the inverse Abel transform algorithm. Results show that the novel algorithm can achieve an accuracy equivalent to the inverse Abel transform algorithm. However, the novel algorithm is more versatile because it is applicable to arbitrary kinds of distribution.

Journal Article↗

PubMed2006

Signatures for Majorana neutrinos at hadron colliders.

The Majorana nature of neutrinos may only be experimentally verified via lepton-number violating processes involving charged leptons. We explore the Delta L = 2 like-sign dilepton production at hadron colliders to search for signals of Majorana neutrinos. We find significant sensitivity for resonant production of a Majorana neutrino in the mass range of 10-80 GeV at the current run of the Tevatron with 2 fb(-1) integrated luminosity and in the range of 10-400 GeV at the CERN LHC with 100 fb(-1).

Journal Article↗

PubMed2006

An immediate after-backprojection filtering method with blob-shaped window functions for voxel-based iterative reconstruction.

Spherically symmetric volume elements (blobs) have better resolution-noise performance than voxels because of the overlapping of their rotational symmetric basis functions; however, using blobs is more computationally expensive than using voxels due to blob overlap. In this paper, we propose an immediate after-backprojection filtering method (ABF) with blob-shaped window functions for a voxel-based reconstruction. We compared this method with the general voxel-based method (without filtering), the blob-based method, the voxel-based method with between-iteration filtering (BIF) and with post-filtering (POF), using computer simulations. Both the quality of the reconstruction and the computational cost were evaluated. The reconstruction quality was measured by the contrast recovery coefficient (CRC) versus the background noise. It is shown that images reconstructed using this method are characterized by less image noise and preserved image contrast in comparison with both the general voxel-based method and the voxel-based method with BIF. The improvement in image quality achieved by this method varies with the parameters chosen for the Kaiser-Bessel (KB) windows. As with blobs, wider KB windows achieve better contrast-noise trade-offs in the reconstructed images, but are more computationally expensive. When using a KB window of a = 2.0, alpha = 10.4 and m = 2, known as the basis function of a 'standard' blob, this new method achieves identical CRC-noise features to the blob-based method with 'standard' blobs. In addition, the ABF method can be combined with the post-filtering method to achieve better noise-resolution performance than the general voxel-based post-filtering method. The computational cost of the ABF method is slightly greater than that of the general voxel-based method, but much less than that of the blob-based method.

Algorithms↗

PubMed2006

Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection.

BACKGROUND/AIMS: Exposure to HBV leads to a distinct clinical course which is partially pertained to host genetic variability. We aimed to study polymorphisms of type I interferon receptor 1 (IFNAR1) promoter and their potential effects on chronic HBV infection. METHODS: Polymorphisms of IFNAR1 promoter were identified in 320 chronic hepatitis B patients, 148 spontaneously recovered individuals, 148 healthy Chinese donors and 114 Caucasians. Their functional capability in driving reporter gene expression was analyzed. RESULTS: Four polymorphic alleles were identified at loci -568, -408, -77 and -3. Association analysis revealed that carriers of alleles -568G, -408C and their related haplotype I were less susceptible to chronic HBV infection whereas those of alleles -568C, -408T and related haplotype III were significantly associated with higher risk to chronic hepatitis B (P<0.01). In a reporter-driven system, the promoter variants with alleles -408C and -3C could drive higher expression of the reporter gene than those with alleles -408T and -3T (P<0.01). Interestingly, an allele with 9 GT repeats at -77 that was rarely found in Chinese but prevalent in Caucasian exhibited the highest transcriptional ability. CONCLUSIONS: Our results showed that polymorphisms of IFNAR1 promoter may affect, at least in part, the outcomes of HBV infection.

Asian People↗

PubMed2006

[Improved method of acute myocardial ischemic rat model].

OBJECTIVE: To improve the successful rate of operation and the livability in establishing acute myocardial ischemic rat model. METHODS: The successful rate of animal experiment is compared between traditional method and improved method. RESULTS: The successful rate of improved method was 90%, which was much higher than 30% in successful rate of traditional method. CONCLUSION: The improved method may reduce the difficulty of operation remarkably and cut down the experiment expenditure, which is superior to traditional method.

Acute Disease↗

PubMed2006

Direct aperture optimization of breast IMRT and the dosimetric impact of respiration motion.

We have studied the application of direct aperture optimization (DAO) as an inverse planning tool for breast IMRT. Additionally, we have analysed the impact of respiratory motion on the quality of the delivered dose distribution. From this analysis, we have developed guidelines for balancing the desire for a high-quality optimized plan with the need to create a plan that will not degrade significantly in the presence of respiratory motion. For a DAO optimized breast IMRT plan, the tangential fields incorporate a flash field to cover the range of respiratory motion. The inverse planning algorithm then optimizes the shapes and weights of additional segments that are delivered in combination with the open fields. IMRT plans were generated using DAO with the relative weights of the open segments varied from 0% to 95%. To assess the impact of breathing motion, the dose distribution for the optimized IMRT plan was recalculated with the isocentre sampled from a predefined distribution in a Monte Carlo convolution/superposition dose engine with the breast simulated as a rigid object. The motion amplitudes applied in this study ranged from 0.5 to 2.0 cm. For a range of weighting levels assigned to the open field, comparisons were made between the static plans and the plans recalculated with motion. For the static plans, we found that uniform dose distributions could be generated with relative weights for the open segments equal to and below 80% and unacceptable levels of underdosage were observed with the weights larger than 80%. When simulated breathing motion was incorporated into the dose calculation, we observed a loss in dose uniformity as the weight of the open field was decreased to below 65%. More quantitatively, for each 1% decrease in the weight, the per cent volume of the target covered by at least 95% of the prescribed dose decreased by approximately 0.10% and 0.16% for motion amplitudes equal to 1.5 cm and 2.0 cm, respectively. When taking into account the motion effects, the most uniform and conformal dose distributions were achieved when the open segment weights were in the range of 65-80%. Within this range, high-quality IMRT plans were produced for each case. The study demonstrates that DAO with tangential fields provides a robust and efficient technique for breast IMRT planning and delivery when the open segment weight is selected between 65% and 80%.

Breast Neoplasms↗

PubMed2006

Cargo selectivity of the ERGIC-53/MCFD2 transport receptor complex.

Exit of soluble secretory proteins from the endoplasmic reticulum (ER) can occur by receptor-mediated export as exemplified by blood coagulation factors V and VIII. Their efficient secretion requires the membrane lectin ER Golgi intermediate compartment protein-53 (ERGIC-53) and its soluble luminal interaction partner multiple coagulation factor deficiency protein 2 (MCFD2), which form a cargo receptor complex in the early secretory pathway. ERGIC-53 also interacts with the two lysosomal glycoproteins cathepsin Z and cathepsin C. Here, we tested the subunit interdependence and cargo selectivity of ERGIC-53 and MCFD2 by short interference RNA-based knockdown. In the absence of ERGIC-53, MCFD2 was secreted, whereas knocking down MCFD2 had no effect on the localization of ERGIC-53. Cargo binding properties of the ERGIC-53/MCFD2 complex were analyzed in vivo using yellow fluorescent protein fragment complementation. We found that MCFD2 is dispensable for the binding of cathepsin Z and cathepsin C to ERGIC-53. The results indicate that ERGIC-53 can bind cargo glycoproteins in an MCFD2-independent fashion and suggest that MCFD2 is a recruitment factor for blood coagulation factors V and VIII.

Bacterial Proteins↗

PubMed2006

Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells.

PURPOSE: Panax notoginseng is a commonly used Chinese herb. Although a few studies have found that notoginseng shows anti-tumor effects, the effect of this herb on colorectal cancer cells has not been investigated. 5-Fluorouracil (5-FU) is a chemotherapeutic agent for the treatment of colorectal cancer that interferes with the growth of cancer cells. However, this compound has serious side effects at high doses. In this study, using HCT-116 human colorectal cancer cell line, we investigated the possible synergistic anti-cancer effects between notoginseng flower extract (NGF) and 5-FU on colon cancer cells. METHODS: The anti-proliferation activity of these modes of treatment was evaluated by MTS cell proliferation assay. Apoptotic effects were analyzed by using Hoechst 33258 staining and Annexin-V/PI staining assays. The anti-proliferation effects of four major single compounds from NGF, ginsenosides Rb1, Rb3, Rc and Rg3 were also analyzed. RESULTS: Both 5-FU and NGF inhibited proliferation of HCT-116 cells. With increasing doses of 5-FU, the anti-proliferation effect was slowly increased. The combined usage of 5-FU 5 microM and NGF 0.25 mg/ml, significantly increased the anti-proliferation effect (59.4 +/- 3.3%) compared with using the two medicines separately (5-FU 5 microM, 31.1 +/- 0.4%; NGF 0.25 mg/ml, 25.3 +/- 3.6%). Apoptotic analysis showed that at this concentration, 5-FU did not exert an apoptotic effect, while apoptotic cells induced by NGF were observed, suggesting that the anti-proliferation target(s) of NGF may be different from that of 5-FU, which is known to inhibit thymidilate synthase. CONCLUSIONS: This study demonstrates that NGF can enhance the anti-proliferation effect of 5-FU on HCT-116 human colorectal cancer cells and may decrease the dosage of 5-FU needed for colorectal cancer treatment.

Animals↗

PubMed2006

Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis.

Conventional nonsteroidal antiinflammatory drugs (NSAIDs) are associated with acute renal failure, but cyclooxygenase-2 inhibitors have not been comparatively evaluated. The authors conducted a nested case-control study to assess the association between exposure to NSAIDs, including cyclooxygenase-2 inhibitors, and hospitalization for acute renal failure. They identified 121,722 new NSAID users older than age 65 years from the administrative health care databases of Quebec, Canada, in 1999-2002. Data for 4,228 cases and 84,540 controls matched on age and follow-up time were analyzed by using conditional logistic regression, adjusted for sex, age, health status, health care utilization measures, exposure to contrast agents, and nephrotoxic medications. The risk of acute renal failure for all NSAIDs combined was highest within 30 days of treatment initiation (adjusted rate ratio (RR) = 2.05, 95% confidence interval (CI): 1.61, 2.60) and receded thereafter. The association with acute renal failure within 30 days of therapy initiation was comparable for rofecoxib (RR = 2.31, 95% CI: 1.73, 3.08), naproxen (RR = 2.42, 95% CI: 1.52, 3.85), and nonselective, non-naproxen NSAIDs (RR = 2.30, 95% CI: 1.60, 3.32) but was borderline lower for celecoxib (RR =1.54, 95% CI: 1.14, 2.09; test for interaction comparing celecoxib with rofecoxib, p = 0.057). There was a significant association for both selective and nonselective NSAIDs with acute renal failure, but confirmatory studies are required.

Acute Kidney Injury↗

PubMed2006

Selective induction of necrotic cell death in cancer cells by beta-lapachone through activation of DNA damage response pathway.

Most efforts thus far have been devoted to develop apoptosis inducers for cancer treatment. However, apoptotic pathway deficiencies are a hallmark of cancer cells. We propose that one way to bypass defective apoptotic pathways in cancer cells is to induce necrotic cell death. Here we show that selective induction of necrotic cell death can be achieved by activation of the DNA damage response pathways. While beta-lapachone induces apoptosis through E2F1 checkpoint pathways, necrotic cell death can be selectively induced by beta-lapachone in a variety of cancer cells. We found that beta-lapachone, unlike DNA damaging chemotherapeutic agents, transiently activates PARP1, a main regulator of the DNA damage response pathway, both in vitro and in vivo. This occurs within minutes of exposure to beta-lapachone, resulting in selective necrotic cell death. Inhibition of PAR blocked beta-lapachone-induced necrosis. Furthermore, necrotic cell death induced by beta-lapachone was significantly reduced in PARP1 knockout cell lines. Our data suggest that selective necrotic cell death can be induced through activation of DNA damage response pathways, supporting the idea of selective necrotic cell death as a therapeutic strategy to eliminate cancer cells.

Animals↗