The role of IL-16 in the regulation of relapsing multiple sclerosis featured on Global Medical Discovery

Relapsing remitting MS, patients have distinct attacks of symptoms which then fade away either partially or completely. Around 85 per cent of patients with MS are diagnosed with this type. nterleukin 16 (IL-16), formerly known as lymphocyte chemoattractant factor or LCF, is a pro-inflammatory cytokine that is chemotactic for CD4+ T lymphocytes, monocytes, and eosinophils. IL-16 is the only exclusive chemotactic factor for CD4+ T cells and critical regulator of CD4+Tbet+ Th1 cell homing into the CNS in relapsing EAE and RRMS. IL-16 also induces migration of CD4+CD25+FOXP3+Treg cells and de novo FOXP3 transcription. Because of receptor cross-desensitization, IL-16 binding to CD4 has the potential to modulate chemokine-regulated migration of CCR5+CD4+Th1 cells. Similarly, it modulates CXCR3- and CXCR4-induced migrations, which are all implicated in the pathogenesis of MS. These studies demonstrate the potential use of Anti-IL16 therapy in multiple sclerosis treatment.

To read more about the featured article on the medical research news Global Medical Discovery

The citation for the original paper is below: 

Skundric DS, Cruikshank WW, Montgomery PC, Lisak RP, Tse HY. Cytokine. 2015 . pii: S1043-4666(15)00009-5.

Leptin promotes wound healing in the skin a new drug discovery featured on Global Medical Discovery

Leptin, a 16-kDa non-glycosylated polypeptide made by adipose cells, it is called anti-obesity hormone, is a product of the obese (ob) gene. Leptin was approved in the United States in 2014 for use in congenital leptin deficiency and generalised lipodystrophy. However, some past studies unveiled the effect of leptin on would healing by demonstrating that leptin acted as an autocrine/paracrine regulator in the wounded sites and that skin would healing delayed in leptin deficient ob/ob mice. These findings strongly suggest the possibility that leptin could be a potential medicine for promoting wound healing. In the present study, the authors investigated whether leptin exerted a promotive influence on the skin would healing even when administered with a low single dosage and one time by using MedGel, a bioabsorbable hydrogel used for a drug delivery system (DDS). First, the expression/localization of leptin receptor (Ob-R) in mouse and human skin was immunohistochemically confirmed. Some epithelial cells of hair follicles were also positive for Ob-R. This finding suggests that epidermal cells and hair follicle cells are target cells of leptin. The area of the wound created in mouse back skin decreased with time much faster in the leptin-treated group. Significantly more blood vessels were distributed in the connective tissue beneath the ulcer in the leptin-treated group. Moreover, leptin showed modest stimulatory effect on the proliferation of human epidermal keratinocytes. Quantitative RT-PCR analysis detected an elevated expression of mRNA encoding Cytokeratin 13, Cytokeratin 14, and Transglutaminase I of human epidermal keratinocytes in the presence of exogenous leptin. An in vitro wound healing assay also revealed that leptin promoted the migration of keratinocytes. The study by the authors demonstrated for the first time that topically administered leptin is capable of accelerating wound healing in the skin by promoting angiogenesis around the wounded area and by enhancing the proliferation, differentiation/function and migration of epidermal keratinocytes. Moreover, this study also clearly demonstrated that leptin is effective for wound healing acceleration even in a single dose when applied topically by using an adequate drug delivery system. These findings are considered to pave the way for the clinical utilization of leptin as a wound healing-promoting agent especially in the treatment and/or prevention of decubital ulcers of increasing elderly patients with poor ADL.

To read more about the featured research work and new potential medical applications of Leptin at Global Medical Discovery in wound healing




The reference for the original paper by the Japanese research team is: 
Tadokoro S, Ide S, Tokuyama R, Umeki H, Tatehara S, Kataoka S, Satomura K. PLoS One. 2015; 10(3):e0121242.

CXCL10/IP-10 is a biomarker and mediator for Kawasaki disease featured on Global Medical DiscoveryKawasaki disease (KD) is the most common cause of acquired heart disease in young children. To date, diagnosing Kawasaki disease is still difficult because of its varied clinical manifestations and lack of specific laboratory tests. Here we found that the IP-10 levels had extremely high area under the curve values through receiver operator characteristic (ROC) analysis from discovery and replication studies, which suggested that IP-10 can be used as a biomarker for differential diagnosis of Kawasaki disease, thus allowing Kawasaki disease patients to receive timely treatment. Moreover, IP-10 levels can be used for diagnosis of Kawasaki disease in the very early stage (getting fever less than 4 days) and monitoring the efficacy of intravenous immunoglobulin (IVIG) treatment. Based on the blinded validation study, this invention (IP-10 as a Kawasaki disease biomarker) has been proved to have a high potential to apply in clinic because of reproducible discrimination and extremely high sensitivity and specificity. Compared to the previously reported biomarkers in the blood, IP-10 appears to be the most significant biomarker that can be used as a predictor for Kawasaki disease diagnosis. In addition, this invention also provides an important clue to develop novel targets or therapeutic avenue for KD.

A new study to to identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of Kawasaki disease has been featured on Global Medical Discovery.  

Kawasaki disease (KD) is the most common cause of acquired heart disease in young children. To date, diagnosing Kawasaki disease is still difficult because of its varied clinical manifestations and lack of specific laboratory tests. Here we found that the IP-10 levels had extremely high area under the curve values through receiver operator characteristic (ROC) analysis from discovery and replication studies, which suggested that IP-10 can be used as a biomarker for differential diagnosis of Kawasaki disease, thus allowing Kawasaki disease patients to receive timely treatment. Moreover, IP-10 levels can be used for diagnosis of Kawasaki disease in the very early stage (getting fever less than 4 days) and monitoring the efficacy of intravenous immunoglobulin (IVIG) treatment. Based on the blinded validation study, this invention (IP-10 as a Kawasaki disease biomarker) has been proved to have a high potential to apply in clinic because of reproducible discrimination and extremely high sensitivity and specificity. Compared to the previously reported biomarkers in the blood, IP-10 appears to be the most significant biomarker that can be used as a predictor for Kawasaki disease diagnosis. In addition, this invention also provides an important clue to develop novel targets or therapeutic avenue for KD.

To read more about the featured paper in Global Medical Discovery

The original paper was published in Circulation Research: 

Ko TM, Kuo HC, Chang JS, Chen SP, Liu YM, Chen HW, Tsai FJ, Lee YC, ChenCH, Wu JY, Chen YT. Circ Res. 2015;116(5):876-83.

Coupling to a glioblastoma-directed antibody potentiates antitumor activity of curcumin- Global Medical Discovery

The paper entitled [Coupling to a glioblastoma-directed antibody potentiates antitumor activity of curcumin] is now featured on Global Medical Discovery as a Key Scientific Article. See the link: 

https://globalmedicaldiscovery.com/key-drug-discovery-articles/coupling-to-a-glioblastoma-directed-antibody-potentiates-antitumor-activity-of-curcumin/

Recognition of the anticancer properties of the food-derived agent curcumin has resulted in an explosion of literature on curcumin.  Although it is hydrophobic and can cross the blood-brain barrier, attempts to use it clinically have been thwarted by its poor solubility in the aqueous body fluids and also its rapid degradation in the body.  Alteration of its functional groups has been attempted, but such attempts either compromises curcumin’s anticancer activity or converts it into a toxic agent.  The referenced studies published in International Journal of Cancer in 2012 (131, E569-E578) and 2014 (135, 710-719) tackle this “poor bioavailability” of curcumin by coupling it in a releasable form to a glioblastoma-specific antibody.  This antibody-curcumin adduct gets rapidly concentrated in the cancer cells in vitro and in vivo. Once endocytosed by cancer cells, the curcumin molecule is released from the adduct by the action of intracellular esterases, thereby causing rapid elimination of the targeted cancer cells.  This versatile approach causes a hundred to two-hundred-fold increase in the anticancer activity of curcumin and can be used for any cancer cell that expresses a specific antigen molecule in excess over other cells.  Because curcumin targets multiple cancer cell-specific pathways and does not kill normal cells, any off-target delivery of curcumin does not eliminate normal cells. These two landmark publications in the International Journal of Cancer have initiated important follow-up studies, which have demonstrated that the relatively non-invasive intranasal route is effective in delivering the antibody-curcumin adduct into the brain. This has now improved the complete rescue rates to 50% in glioblastoma-implanted mice.