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Genetics of Anxiety
Published in Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen, Handbook of Depression and Anxiety, 2003
More recently, the inactivation of specific genes became feasible among mice using transgenic technology (knock-out lines) in order to study the impact of a specific gene on the behavior and underlying neurobiological circuits. By these means, new promising candidate genes can be identified beyond our current knowledge of the pathophysiology of the disease (what is particularly advantageous, given the limited knowledge on the pathophysiology of anxiety disorders). A large number of genes contributing to neuronal messengers, receptors, and intracellular regulations have been targeted in knock-out lines and tested for anxiety-like behavior (see overview, Ref. [100]. Apart from confirming the involvement of serotonin, gamma-aminobutyric acid, and corticotropin-releasing hormone as major mediators of anxiety and stress-related behaviors, two novel groups of anxietyrelevant molecules have been revealed. The first group consists of neurotrophic-type molecules, such as interferon-gamma, neural cell adhesion molecule, and midkine, which play important roles in neuronal development and cell-to-cell communication. The second group comprises regulators of intracellular signaling and gene expression, which emphasizes the importance of gene regulation in anxiety-related behaviors. Defects in these molecules are likely to contribute to the abnormal development and/or function of neuronal networks, which leads to the manifestation of anxiety disorders.
Efficient drug delivery by novel cell-penetrating peptide derived from Midkine, with two heparin binding sites braced by a length-specific helix
Published in Journal of Drug Targeting, 2022
Yihui Chen, Si Li, Jian Zhao, Xuewei Cao, Fujun Wang
It has reported that the internalisation of positively charged CPPs, such as TAT, depends on the interactions with membrane-associated heparan sulphate proteoglycans (HSPGs) [12]. Heparin-binding domain (HBD) is a special structure that exists in many proteins (such as proteases, growth factors and chemokines), which can interact with HSPGs on the cell surface and participate in various physiological activities and pathological processes [13,14]. In previous studies, HBDs has been developed into CPP or tumour targeting CPP, demonstrating that HBD is a suitable candidate for novel CPPs with high efficiency [15,16]. Midkine is a growth factor/cytokine and the binding sites in its C-terminal domain compose a typical HBD. The amino acid sequence (TKPCTPKTKAKAKAKKGKGKD, named HMD) with a heparin binding site at the C-terminus of Midkine was selected in this paper. Since containing an α-helix and a large number of positive charges (Figure S1), HMD has the potential to be developed into a novel CPP with high efficiency.
Involvement of midkine in autoimmune and autoinflammatory diseases
Published in Modern Rheumatology, 2019
Ahmet Şükrü Aynacıoğlu, Ayhan Bilir, Mehmet Yakup Tuna
UC is an IBD that causes long-lasting inflammation and ulcers in the digestive tract, an incurable disease of unknown pathology. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with UC, but as in CD, the most widely adopted biomarker used in the diagnosis of UC is CRP. However, additionally non-invasive biomarkers are needed to support the diagnosis of UC. In addition to CD, high expression of MK has been found in bowel inflammation in UC [13]. In UC, inflammation increased the bowel expression of midkine in a manner proportional to the disease clinical activity [12]. Furthermore, Krzystek-Korpacka et al. showed significant increase in serum MK levels in UC patients compared to healthy subjects. Combined assessment of MK and CRP improved sensitivity but substantially decreased specificity. The performance of MK as a marker of UC or active UC was comparable to that of CRP [13].
Advanced multimodal diagnostic approaches for detection of lung cancer
Published in Expert Review of Molecular Diagnostics, 2019
Pravin Shende, Steffi Augustine, Bala Prabhakar, R. S. Gaud
Urine analysis is another adjunct diagnostic technique that can help to detect changes in protein and metabolite levels in LC. It is a completely noninvasive and patient-friendly technique. The biomarkers are detected using specialized instruments like MALDI-TOF-MS or commercially available assays. A recent study involved the detection of biomarkers associated with adenocarcinoma of lung by examining changes in urine protein levels. The urine samples from 70 volunteers with LC were analyzed and compared with healthy volunteers’ urine samples using MALDI-TOF-MS with immunohistological staining. The results indicated that the IGKC, gelsolin, SH3BGRL3, osteopontin, and AAT levels were found to be higher in LC patients than in healthy volunteers. The sensitivity and specificity of this procedure was found to be 60–70% and 80–90%, respectively [31]. Furthermore, a recent study found that midkine, a heparin-building growth factor, emerges as a novel serum and urine biomarker for the detection of NSCLC. The study indicates that midkine levels are significantly upregulated in patients with LC and the sensitivity and specificity of this test were found to be 71% and 88%, respectively [32]. Another important study reported that urinary biomarkers can be employed for early detection of NSCLC using biomarker panel of IGFBP-1, sIL-1Ra, and CEACAM-1 with higher specificity (>70%). Hence, urine analysis emerges as a novel, noninvasive, and patient-friendly technique for detection of LC [33].