Jinhua Chen

Bio: Jinhua Chen is an academic researcher from Shandong University. The author has contributed to research in topics: Cell cycle checkpoint & Apoptosis. The author has an hindex of 6, co-authored 6 publications receiving 95 citations.

The role of nerve growth factor and its receptors in tumorigenesis and cancer pain.

Abstract: The nerve growth factor (NGF) is a growth factor that belongs to the neurotrophin family. NGF has two structurally different receptors, the p75 neurotrophin receptor (p75NTR) and the tropomyosin-related kinase A (TrkA). Interaction of NGF with its receptors regulates a variety of physiological processes of neuronal system. Recent studies have shown that NGF and its receptors were involved in the regulation of tumourigenesis by either supporting or suppressing tumor growth depending on the tumor types. This review summarizes the current views of NGF and its receptors in tumorigenesis and cancer pain.

Combination treatment of ligustrazine piperazine derivate DLJ14 and adriamycin inhibits progression of resistant breast cancer through inhibition of the EGFR/PI3K/Akt survival pathway and induction of apoptosis

Abstract: A ligustrazine (TMP) derivative, (E)-2-(2, 4-dimethoxystyryl)-3,5,6-trimethylpyrazine (DLJ14) was synthesized for the improvement of low bioavailability and short half-life of ligustrazine. We have observed potential reversal effects of DLJ14 on adriamycin (Adr)-resistant human myelogenous leukemia cells (K562/A02) and Adr-resistant human breast cancer cells (MCF-7/A) in vitro or in vivo in previous studies. The aim of the present study was to investigate the underlying molecular mechanism of DLJ14 and Adr combination treatment on Adr-resistant human breast cancer. Inhibition of cancer cell growth was estimated by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell cycle distribution was analyzed by flow cytometry and apoptosis determined using Annexin V-FITC/propidium iodide (PI) double staining and Hoechst 33258 nuclear staining. The expression of proteins in the epidermal growth factor receptor (EGFR)/phosphatidylinositol-3 kinase (PI3K)/Akt survival pathway and mitochondrial-mediated apoptosis pathway were measured by Western blotting analysis. Results showed that DLJ14 and Adr combination treatment exhibited stronger inhibition of the survival of MCF-7/A cells than Adr treatment alone. This effect might be associated with its role in cell cycle arrest and apoptosis induction. DLJ14 combined with Adr induced cell cycle arrest in the G2/M-phase by activating p21(wafl /cip1) and p53 in mitochondria and increased cleavage of caspase-9 and caspase-3, and Bax/Bcl-2 ratio. Mitochondrial membrane potential (MMP) disruption and cytochrome c (Cytc) release from mitochondria to cytosol suggested that apoptosis induction might be mediated by the mitochondrial pathway. Moreover, the combination of DLJ14 and Adr could down-regulate the expression of EGFR, p-EGFR, PI3K, and p-Akt in MCF-7/A cells. Overall, DLJ14 and Adr combination treatment may inhibit proliferation of Adr-resistant human breast cancer cells through inhibition of the EGFR/PI3K/Akt survival pathway and induction of apoptosis via the mitochondrial-mediated apoptosis pathway.

The beneficial and deleterious role of dietary polyphenols on chronic degenerative diseases by regulating gene expression.

Abstract: Dietary polyphenols, a natural component in many kinds of foods such as fruits and vegetables, play essential roles in a wide range of plant functions. Importantly, the discovery of the functions of polyphenols including anti-oxidant, anti-carcinogenic and anti-inflammatory has been appealing to researchers' attentions. Dietary polyphenols have shown protective effects on chronic degenerative diseases (CDD) such as cardiovascular diseases, cancers, and neurodegenerative diseases by regulating gene expression. Dietary polyphenols also affect the composition and activity of gut microbiota, in reverse, gut microbiota influences the bioavailability and physiological activity of dietary polyphenols. However, not all kinds of dietary polyphenols are beneficial for human health. The potential deleterious effects of several dietary polyphenols have been reported by inducing DNA damage and gene mutants. This review summarizes the potential therapeutic effects of dietary polyphenols on chronic degeneration diseases, the polyphenols-gut microbiota interactions, and the potential dangers of individual dietary polyphenols on human health.

Flavonoids as Anticancer Agents

Abstract: Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.

Pathological unfoldomics of uncontrolled chaos: intrinsically disordered proteins and human diseases

Abstract: Many biologically important proteins lack stable tertiary and/or secondary structure under physiological conditions in vitro as a whole or in part.1–5 These intrinsically disordered proteins (IDPs), or intrinsically disordered protein regions (IDPRs) of hybrid proteins possessing both structured and disordered domains, do not have unique well-defined 3D structures, existing instead as collapsed or extended dynamically mobile conformational ensembles. Therefore, natural proteins can be found in one of three major protein forms: functional and folded, nonfunctional and misfolded, or functional and intrinsically disordered. Although IDPs and IDPRs are highly dynamic, their structures can be described reasonably well by a rather limited number of lower-energy conformations.6,7 The structural plasticity and conformational adaptability of IDPs/IDPRs and their intrinsic lack of rigid structure leads to a number of exceptional functional advantages, providing them with unique capabilities to act in functional modes not achievable by ordered proteins.5 As a result, intrinsic disorder is a common feature of proteins involved in signaling, regulation, and recognition, and IDPs/IDPRs play diverse roles in modulation and control of their binding partners’ functions and in promoting the assembly of supramolecular complexes. The biological actions of IDPs/IDPRs, which frequently serve as major regulators of their binding partners, are controlled by extensive posttranslational modifications (PTMs), such as phosphorylation, acetylation, ubiquitination, and sumoylation,5 and by alternative splicing.8 In fact, many IDPs/IDPRs are known to contain multiple functional elements that contribute to their ability to be involved in interaction with, regulation of, and control by multiple structurally unrelated partners.9 Given the existence of multiple functions in a single disordered protein, and given that each functional element is typically relatively short, alternative splicing could readily generate sets of protein isoforms with highly diverse regulatory elements.8 The complexity of the disorder-based interactomes is further increased by the capacity of a single IDPR to bind to multiple partners, gaining very different structures in the bound state.10 IDPs can form highly stable complexes or be involved in signaling interactions where they undergo constant “bound–unbound” transitions, thus acting as dynamic and sensitive “on–off” switches. The ability of these proteins to return to highly flexible conformations after the completion of a particular function, and their predisposition to adopt different conformations depending on their environment, are unique physiological properties of IDPs that allow them to exert different functions in different cellular contexts according to a specific conformational state.5 Although the field of protein disorder has started from careful analysis of a very limited number of biologically active proteins without unique structures (which, for a long time, were taken as rare exceptions from the general “one sequence–one unique structure–one unique function” paradigm),1–4 applications of various disorder predictors to different proteomes revealed that IDPs are highly abundant in nature,11–16 and the overall amount of disorder in proteins increases from bacteria to archaea to eukaryota, with over half of all eukaryotic proteins predicted to contain extended IDPRs.11,12,15–17 One explanation for this trend is a change in the cellular requirements for certain protein functions, particularly cellular signaling. In support of this hypothesis, an analysis of a eukaryotic signal protein database indicated that the majority of known signal transduction proteins were predicted to contain significant regions of disorder.18 A detailed study focused on the intricate mechanisms of IDP regulation inside the cell was recently conducted by Gsponer et al.19 These authors grouped all the Saccharomyces cerevisiae proteins into three classes according to their predicted disorder propensities and evaluated the correlations between intrinsic disorder and the various regulation steps of protein synthesis and degradation.19 Although the transcriptional rates of mRNAs encoding IDPs and ordered proteins were comparable, IDP-encoding transcripts were generally less abundant than transcripts encoding ordered proteins because of increased decay rates of IDP mRNAs.19 Also, IDPs were found to be less abundant than ordered proteins because of lower rates of protein synthesis and shorter protein half-lives.19 Curiously, IDPs were shown to be substrates of twice as many kinases as ordered proteins. Furthermore, the vast majority of kinases whose substrates were IDPs were either regulated in a cell-cycle-dependent manner or activated upon exposure to specific stimuli or stress.19 Similar regulation trends were also found in proteomes of Schizosaccharomyces pombe and Homo sapiens,19 suggesting that both unicellular and multicellular organisms use evolutionarily conserved mechanisms to regulate the availability of their IDPs. This tight regulation is directly related to the major roles of IDPs/IDPRs in signaling, where it is crucial for a given protein to be available in appropriate amounts and not to be present longer than needed.19 It was also pointed out5 that although the abundance of many IDPs may be closely regulated, some disordered proteins could be present in cells in large amounts or/and for long periods of time, either due to specific PTMs or via interactions with other factors. These events could promote changes in cellular localization of IDPs or protect them from degradation.3,20–23 Taken together, these data highlight that the chaos seemingly associated with highly flexible and promiscuous IDPs/IDPRs is under tight control.24

Role of JNK activation in apoptosis： A double-edged sword

Abstract: JNK is a key regulator of many cellular events, including programmed cell death (apoptosis). In the absence of NF-κB activation, prolonged JNK activation contributes to TNF-α induced apoptosis. JNK is also essential for UV induced apoptosis. However, recent studies reveal that JNK can suppress apoptosis in IL-3-dependent hematopoietic cells via phosphorylation of the proapoptotic Bcl-2 family protein BAD. Thus, JNK has pro- or antiapoptotic functions, depending on cell type, nature of the death stimulus, duration of its activation and the activity of other signaling pathways.