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Zi-Chun Hua

Bio: Zi-Chun Hua is an academic researcher from China Pharmaceutical University. The author has contributed to research in topics: FADD & Apoptosis. The author has an hindex of 42, co-authored 294 publications receiving 6101 citations. Previous affiliations of Zi-Chun Hua include University of California, Berkeley & Industrial Technology Research Institute.


Papers
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Journal ArticleDOI
TL;DR: It is shown that haem, rather than free ferrous iron, is predominantly responsible for artemisinin activation, which derives primarily from the parasite's haem biosynthesis pathway at the early ring stage and from haemoglobin digestion at the latter stages.
Abstract: The mechanism of action of artemisinin and its derivatives, the most potent of the anti-malarial drugs, is not completely understood. Here we present an unbiased chemical proteomics analysis to directly explore this mechanism in Plasmodium falciparum. We use an alkyne-tagged artemisinin analogue coupled with biotin to identify 124 artemisinin covalent binding protein targets, many of which are involved in the essential biological processes of the parasite. Such a broad targeting spectrum disrupts the biochemical landscape of the parasite and causes its death. Furthermore, using alkyne-tagged artemisinin coupled with a fluorescent dye to monitor protein binding, we show that haem, rather than free ferrous iron, is predominantly responsible for artemisinin activation. The haem derives primarily from the parasite's haem biosynthesis pathway at the early ring stage and from haemoglobin digestion at the latter stages. Our results support a unifying model to explain the action and specificity of artemisinin in parasite killing.

449 citations

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TL;DR: Current understandings and knowledge of apoptosis were summarized and discussed with a focus on apoptosis-related therapeutic applications and ApoBDs.
Abstract: Apoptosis is widely known as programmed cell death eliciting no inflammatory responses. The intricacy of apoptosis has been a focus of an array of researches, accumulating a wealth of knowledge which led to not only a better understanding of the fundamental process, but also potent therapies of diseases. The classic intrinsic and extrinsic signaling pathways of apoptosis, along with regulatory factors have been well delineated. Drugs and therapeutic measures designed based on current understanding of apoptosis have long been employed. Small-molecule apoptosis inducers have been clinically used for eliminating morbid cells and therefore treating diseases, such as cancer. Biologics with improved apoptotic efficacy and selectivity, such as recombinant proteins and antibodies, are being extensively researched and some have been approved by the FDA. Apoptosis also produces membrane-bound vesicles derived from disassembly of apoptotic cells, now known as apoptotic bodies (ApoBDs). These little sealed sacs containing information as well as substances from dying cells were previously regarded as garbage bags until they were discovered to be capable of delivering useful materials to healthy recipient cells (e.g., autoantigens). In this review, current understandings and knowledge of apoptosis were summarized and discussed with a focus on apoptosis-related therapeutic applications and ApoBDs.

375 citations

Journal ArticleDOI
TL;DR: Evidence is given that the modified chitosan vector has the potential to be used as a safe gene-delivery system and has relatively low cytotoxicity.

158 citations

Journal ArticleDOI
TL;DR: A novel regulatory role of B10 cells is suggested in arthritic progression via the suppression of Th17 cell generation during the acute stage of collagen-induced arthritis in mice.
Abstract: IL-10–producing CD1d hi CD5 + B cells, also known as B10 cells, have been shown to possess a regulatory function in the inhibition of immune responses, but whether and how B10 cells suppress the development of autoimmune arthritis remain largely unclear. In this study, we detected significantly decreased numbers of IL-10–producing B cells, but increased IL-17–producing CD4 + T (Th17) cells in both spleen and draining lymph nodes of mice during the acute stage of collagen-induced arthritis (CIA) when compared with adjuvant-treated control mice. On adoptive transfer of in vitro expanded B10 cells, collagen-immunized mice showed a marked delay of arthritis onset with reduced severity of both clinical symptoms and joint damage, accompanied by a substantial reduction in the number of Th17 cells. To determine whether B10 cells directly inhibit the generation of Th17 cells in culture, naive CD4 + T cells labeled with carboxyfluorescein succinimidyl ester (CFSE) were co-cultured with B10 cells. These B10 cells suppressed Th17 cell differentiation via the reduction of STAT3 phosphorylation and retinoid-related orphan receptor γt (RORγt) expression. Moreover, Th17 cells showed significantly decreased proliferation when co-cultured with B10 cells. Although adoptive transfer of Th17 cells triggered the development of collagen-induced arthritis in IL-17 −/− DBA/1J mice, co-transfer of B10 cells with Th17 cells profoundly delayed the onset of arthritis. Thus, our findings suggest a novel regulatory role of B10 cells in arthritic progression via the suppression of Th17 cell generation.

153 citations

Journal ArticleDOI
TL;DR: Study of the mechanism of plasmid DNA cleavage by added radical scavengers, using rigorously anaerobic experiments, analyses for malondialdehyde-like products, religation assays, and HPLC analyses, indicate thatDNA cleavage mediated by Cu(L-His) occurs via a hydrolytic path.
Abstract: Copper(II)−l-histidine complexes effectively promote the cleavage of plasmid DNA and dideoxynucleotide dApdA at physiological pH and temperature. Studies of the mechanism of plasmid DNA cleavage by added radical scavengers, using rigorously anaerobic experiments, analyses for malondialdehyde-like products, religation assays, and HPLC analyses, indicate that DNA cleavage mediated by Cu(l-His) occurs via a hydrolytic path. The hydrolytic cleavage rate constants at 37 °C are estimated to be 0.76 h-1 for the decrease of form I and 0.25 h-1 for the increase of form III. The phosphoimager picture reveals that Cu(l-His) cleaves DNA with a certain sequence specificity (preferentially at 5‘-GT-3‘). The dinucleotide hydrolysis shows, with [Cu(l-His)] = 0.8 mM, rate enhancement factors of >108. Interestingly, histidine−metal ion interactions (with Cu(II), Ni(II), Zn(II), etc.) have been used for various applications, e.g., protein purification, cross-linking, and targeting proteins to lipid bilayers. Our findings ma...

146 citations


Cited by
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TL;DR: This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012, and the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide.
Abstract: This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012. In the case of all approved therapeutic agents, the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide. As mentioned in the 2012 review, we have continued to utilize our secondary subdivision of a “natural product mimic”, or “NM”, to join the original primary divisions and the designation “natural product botanical”, or “NB”, to cover those botanical “defined mixtures” now recognized as drug entities by the U.S. FDA (and similar organizations). From the data presented in this review, the utilization of natural products and/or their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over t...

4,337 citations

Journal ArticleDOI
TL;DR: Clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.
Abstract: The integrin family of cell adhesion receptors regulates a diverse array of cellular functions crucial to the initiation, progression and metastasis of solid tumours. The importance of integrins in several cell types that affect tumour progression has made them an appealing target for cancer therapy. Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. These exciting clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.

2,894 citations

Journal ArticleDOI
TL;DR: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. S. Nagar, Punjab-160 062, India, Institute of Biochemistry, Faculty of Medicine, Polytechnic University, Via Ranieri 67, IT-60100 Ancona, Italy, and Department of Medicinal Chemistry & Natural Products,The Hebrew University of Jerusalem, School of Pharmacy-Faculty of medicine, Jerusalem 91120, Israel.
Abstract: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar,Mohali, Punjab-160 062, India, Institute of Biochemistry, Faculty of Medicine, Polytechnic University, Via Ranieri 67, IT-60100 Ancona, Italy,Green Biotechnology Research Group, The Special Division for Human Life Technology, National Institute of Advanced Industrial Science andTechnology, 1-8-31 Midorigaoka, Ikeda, Osaka-563-8577, Japan, and Department of Medicinal Chemistry & Natural Products,The Hebrew University of Jerusalem, School of Pharmacy-Faculty of Medicine, Jerusalem 91120, IsraelReceived March 2, 2004

2,570 citations

Journal ArticleDOI
TL;DR: Two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells.
Abstract: The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (~200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less

2,189 citations

01 Jan 2007
TL;DR: The terms "antioxidant", "oxidative stress" and "oxoidative damage" are widely used but rarely defined as discussed by the authors, and a brief review attempts to define them and to examine the ways in which oxidative stress and oxidative damage can affect cell behaviour both in vivo and in cell culture, using cancer as an example.
Abstract: The terms 'antioxidant', 'oxidative stress' and 'oxidative damage' are widely used but rarely defined. This brief review attempts to define them and to examine the ways in which oxidative stress and oxidative damage can affect cell behaviour both in vivo and in cell culture, using cancer as an example.

1,309 citations