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Brain site-specific proteome changes in aging-related dementia
Arulmani Manavalan,Manisha Mishra,Lin Feng,Siu Kwan Sze,Hiroyasu Akatsu,Klaus Heese 생화학분자생물학회 2013 Experimental and molecular medicine Vol.45 No.9
This study is aimed at gaining insights into the brain site-specific proteomic senescence signature while comparing physiologically aged brains with aging-related dementia brains (for example, Alzheimer’s disease (AD)). Our study of proteomic differences within the hippocampus (Hp), parietal cortex (pCx) and cerebellum (Cb) could provide conceptual insights into the molecular mechanisms involved in aging-related neurodegeneration. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) brain sitespecific proteomic strategy, we identified 950 proteins in the Hp, pCx and Cb of AD brains. Of these proteins, 31 were significantly altered. Most of the differentially regulated proteins are involved in molecular transport, nervous system development, synaptic plasticity and apoptosis. Particularly, proteins such as Gelsolin (GSN), Tenascin-R (TNR) and AHNAK could potentially act as novel biomarkers of aging-related neurodegeneration. Importantly, our Ingenuity Pathway Analysis (IPA)-based network analysis further revealed ubiquitin C (UBC) as a pivotal protein to interact with diverse AD-associated pathophysiological molecular factors and suggests the reduced ubiquitin proteasome degradation system (UPS) as one of the causative factors of AD.
Toll-like receptor modulators: a patent review (2006 -?? 2010)
Basith, Shaherin,Manavalan, Balachandran,Lee, Gwang,Kim, Sang Geon,Choi, Sangdun Informa UK, Ltd. 2011 Expert opinion on therapeutic patents Vol.21 No.6
<P><B><I>Introduction:</I></B> The immune response is mediated via two parallel immune components, innate and adaptive, whose effector functions are highly integrated and coordinated for the protection of the human body against invading pathogens and transformed cells. The discovery of pathogen recognition receptors (PRRs), most notably toll-like receptors (TLRs), in innate immunity has evoked increased interest in the therapeutic handling of the innate immune system. TLRs are germ line-encoded receptors that play a potent role in the recognition of a diverse variety of ligands ranging from hydrophilic nucleic acids to lipopolysaccharide (LPS) or peptidoglycan (PGN) structures in pathogens.</P><P><B><I>Areas covered:</I></B> This review discusses recent updates (2006 -?? 2010) in completed, ongoing and planned clinical trials of TLR immunomodulator-based therapies for the treatment of infectious diseases, inflammatory disorders and cancer.</P><P><B><I>Expert opinion:</I></B> Since the discovery of human TLRs, modulating immune responses using TLR agonists or antagonists for therapeutic purposes has provoked intense activity in the pharmaceutical industry. The ability of TLRs to initiate and propagate inflammation makes them attractive therapeutic targets. We are now at the stage of evaluating such molecules in human diseases. Additionally, there is also extensive literature available on TLRs in diseased states. These data provide a basis for the identification of novel immunomodulators (agonists and antagonists) for the therapeutic targeting of TLRs.</P>
Roles of Toll-like Receptors in Cancer: A Double-edged Sword for Defense and Offense
BASITHSHAHERIN,최상돈,Balachandran Manavalan,유태현,김상건 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.8
Toll-like receptors (TLRs) belong to a class of pattern-recognition receptors that play an important role in host defense against pathogens by recognizing a wide variety of pathogen-associated molecular patterns (PAMPs). Besides driving inflammatory responses, TLRs also regulate cell proliferation and survival by expanding useful immune cells and integrating inflammatory responses and tissue repair processes. TLR signaling, which is centrally involved in the initiation of both innate and adaptive immune responses, has been thought to be restricted to immune cells. However, recent studies have shown that functional TLRs are expressed not only on immune cells, but also on cancer cells, thus implicating a role of TLRs in tumor biology. Increasing bodies of evidence have suggested that TLRs act as a double-edged sword in cancer cells because uncontrolled TLR signaling provides a microenvironment that is necessary for tumor cells to proliferate and evade the immune response. Alternatively, TLRs can induce an antitumor immune response in order to inhibit tumor progression. In this review, we summarize the dual roles of TLRs in tumor cells and, more importantly, delve into the therapeutic potential of TLRs in the context of tumorigenesis.
Devi K. Gayathri,Mooventhan A.,Mangaiarkarasi N.,Manavalan N. 사단법인약침학회 2023 Journal of Acupuncture & Meridian Studies Vol.16 No.6
Iron deficiency anemia (IDA) is an important public health issue in India. This study was performed to determine the impact of acupuncture at the GB39, BL17, and LR13 points on hemoglobin levels, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red cell distribution width (RDW) in people with IDA. One hundred women with IDA were randomly allocated to the acupuncture group (AG) or placebo control group (PCG). For 30 minutes per day, daily for 2 weeks, the AG received acupuncture at GB39, BL17, and LR13, while the PCG received needling at non-acupuncture points. Outcomes were assessed before and after the intervention. We found a significant increase (p < 0.001) in hemoglobin level (AG 10.39-11.38 g/dl, effect size 0.785; PCG 10.58-10.40 g/dl, effect size 0.191), MCH (AG 25.69-27.50 fl, effect size 0.418; PCG 27.43-27.23 fl, effect size 0.058), and RDW (AG 15.12-16.41 fl, effect size 0.626; PCG 14.91-14.94 fl, effect size 0.017) in the AG compared to the PCG. Results suggest that needling at the GB39, BL17, and LR13 acupuncture points is more effective in treating people with IDA than needling at non-acupuncture points.