David Stejskal, MD has completed his Ph.D at the age of 38 years from Palacký University Olomouc, Czech Republic and postdoctoral studies from Palacký University Olomouc, CZ, too. He is the medical director of Agel Laboratories and head of Department of Laboratory Medicine Central Moravian Hospital Group. He has published more than 175 papers in reputed journals and serving as an editorial board member of two repute journals. He is specialisated in laboratory problems in cardiology, neurology and oncology.

Background: Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exhibits anti-obesity and anti-diabetes effects. Recently was presented that metformin in patients with type 2 diabetes modulates FGF21 expression and glood concentration. Results indicate that metformin and other oral antidiabetic drugs induced expression of FGF21 through an ATF4-dependent mechanism by inhibiting mitochondrial respiration independently of AMPK and it´s concentration in blood. Aim: Studying the effect of metformin, derivates of sulphonylurea, glinidines, gliptines, glitazones on the concentration of FGF21 in serum in type 2 diabetes patients. Methods: The study was approved by the Ethics Commission of the Hospital Šternberk, Czech Republic. Study was monocentric, prospective and randomized. A total of 196 individuals were recruited for our study (18 healthy controls (HC), 18 T2D individuals without diabetes therapy (W), 18 T2D individuals, diabetes monotherapy with derivates of sullfonylurea (SU),18 T2D individuals diabetes monotherapy with 500 mg metformin per day (M5), 18 T2D individuals diabetes therapy with 1000 mg metformin per day (M10), 18 T2D individuals, diabetes monotherapy therapy 1500 mg metformin per day (M15), 18 T2D individuals, diabetes monotherapy with 2000 mg metformin per day (M2), 18 T2D individuals diabetes monotherapy with SU derivates (SU), 18 T2D individuals diabetes monotherapy with gliptines (GP), 18 T2D individuals diabetes monotherapy with glitazones (GL), 18 T2D individuals diabetes monotherapy with glinidines (GN). Anthropometric (height, weight, BMI, waist circumference (WC)), clinical (systolic and diastolic pressures) and laboratory fasting analyses were performed. Blood samples were drawn under aseptic precautions from vena cubiti, after a several-minute rest in the half-sitting position. Serum samples were separated in a cooled centrifuge at 3000 g for 20 minutes and immediatelly analyzed for total cholesterol, HDLcholesterol, LDL-cholesterol, triglycerides, glucose, high sensitivity CRP, creatinine, uric acid, AST, ALT (all Siemens, Advia 1800). FGF21 serum level was determined by a commercially available ELISA kit (Biovendor, Czech Republic) in serum samples stored at -80ºC. Results: The study analyzed 196 subjects, of which 18 were in good health while 180 probands suffered from type 2 diabetes. In-defined subgroups, no significant differences were found by gender in FGF21 concentration. Healthy individuals had the lowest values of FGF21, other subjects increased by the value of the diagnosis, the type of metformin therapy and dose (HC 84.2 ng/l vs. W 111.6; P<0.01) (M5 269.7 vs. M10 404.1 vs. M15 558.7, M2 711.4 ng/l; P<0.01). High values of FGF21 were found in patients with the highest dose of metformin 2000/mg per day. Changes remained significant after adjustment for age, sex and BMI. The values of FGF21 in patients treated with SU, GL, GP and GN did not differ significantly from diabetic patients without therapy (SU 115 ng/l, GL 121 ng/l, GN 105 ng/l, GP 127 ng/l). Conclusion: In randomized prospective study we or the first time confirmed the recently presented hypothesis that metformin leads to the rise of FGF21 (unlike other antifdiabetic drugs). GF21 induction by metformin might explain a portion of the beneficial metabolic effects of metformin.

Hyung-Min Kim has completed as a Pharmacist from Wonkwang University and Postdoctoral studies with a major in Pathologyfrom Osaka University. He has published more than 400 papers in reputed journals and serving as an Editor-in-Chief of international journal, TANG (Humanitas Medicine).

Crataeguspinnatifida Bunge regulates allergic inflammatory diseases. The compoundhyperoside (HYP) is the principle active component of Crataeguspinnatifida Bunge. Thymic stromal lymphopoietin(TSLP) plays a vital role in the pathogenesis of allergic inflammation. Here, we investigated how HYP regulates thelevels of TSLP in a human mast cell line, HMC-1 cells. We analyzed the levels of TSLP by treatment with HYPinphorbolmyristate acetate plus calciumionophoreA23187-activatedHMC-1 cells with ELISAand a polymerasechain reaction analysis.We also analyzed the pathway that HYP regulates TSLP by measuring the level of fluorescentintracellular calciumand using aWestern blot analysis.It also significantly diminished the production and mRNA expression of TSLP in activatedHMC-1 cells.HYP diminished the level of intracellular calciumin activatedHMC-1 cells.It significantly diminished the levels of receptor-interacting protein 2 and active caspase-1 in activatedHMC-1 cells. HYP significantly diminished the translocation of NF-κB into the nucleus and degradation of IκBα inthe cytoplasm in activatedHMC-1 cells. Furthermore, it significantly diminished the production and mRNA expressionof interleukin-1β and interleukin-6 in activatedHMC-1 cells. Taken together, our findings establish HYP as apotential agent for the treatment of allergic inflammation.

Hyun-JaJeong has completed Postdoctoral studies with a major in Molecular Biology from Chonbuk National University. She has published more than 200 papers in reputed journals and serving as a Deputy Editor of international journal, TANG (Humanitas Medicine).

β-sitosterol (BS) is one of the most common forms of phytosterols and has anti-cancer, anti-oxidant, anti-bacterial,and anti-inflammatory effects. However, the effect of BS on atopic dermatitis (AD) has not been elucidated. In the present study, weinvestigated whether BS would be an effective treatment against AD. We treated BS on 2,4-dinitrofluorobenzene (DNFB)-inducedAD-like skin lesions in NC/Nga mice and anti-CD3/anti-CD28-stimulated splenocytes. BS decreased the clinical symptoms in DNFB-treated NC/Nga mice. Infiltration of eosinophils, mast cells, CD4+ T cells, and macrophages and number of scratching were clearly decreased in the BS-treated group compared with the DNFB-treated group. BS significantlydecreased the protein and mRNA levels of inflammation-related genes in the AD skin lesions. BS significantly decreased the levels ofinterleukin-4,IgE, and histamine in the serum of DNFB-treated NC/Nga mice. The activation of mast cell-derived caspase-1was reduced by treatment with BS in the AD skin lesions. BS also significantly decreased the production of inflammatory cytokine from the stimulated splenocytes. These results provide additional evidence thatBS may be considered an effective therapeutic drug for the treatment of AD.

Ling Chen has completed his M D and Ph D at the age of 28 years from Xiang-Yale Hospital of Hunan Medical University and postdoctoral studies from Xuanwu Hospital of Capital Medical University. He studied as a visiting scholar in INI-Hannover Germany and learnt from professor Madjid Samii who has been the president and now honorary president of the WFNS（The World Federation of Neurosurgical Societies. He has published more than 70 papers in reputed journals and serving as an editorial board member of the Journal of Current Signal Transduction Therapy.

Stroke is a devastating neurological disorder and one of the leading causes of death and serious disability. After cerebral ischemia, revascularization in the ischemic boundary zone provides nutritive blood flow as well as various growth factors to promote the survival and activity of neurons and neural progenitor cells. Enhancement of angiogenesis and the resulting improvement of cerebral microcirculation are key restorative mechanisms and represent an important therapeutic strategy for ischemic stroke. In the present study, the hypothesis that post-stroke angiogenesis would be enhanced by omega-3 polyunsaturated fatty acids (n−3 PUFAs), a major component of dietary fish oil was tested. To this end, found that transgenic fat-1 mice that overproduce n−3 PUFAs exhibited long-term behavioral and histological protection against transient focal cerebral ischemia (tFCI). Importantly, fat-1 transgenic mice also exhibited robust improvements in revascularization and angiogenesis compared to wild type littermates, suggesting a potential role for n−3 fatty acids in post-stroke cerebrovascular remodeling. Mechanistically, n−3 PUFAs induced upregulation of angiopoietin 2 (Ang 2) in astrocytes after tFCI and stimulated extracellular Ang 2 release from cultured astrocytes after oxygen and glucose deprivation. Ang 2 facilitated endothelial proliferation and barrier formation in vitro by potentiating the effects of VEGF on phospholipase Cγ1 and Src signaling. Consistent with these findings, blockade of Src activity in post-stroke fat-1 mice impaired n−3 PUFA-induced angiogenesis and exacerbated long-term neurological outcomes. Taken together, findings strongly suggest that n−3 PUFA supplementation is a potential angiogenic treatment capable of augmenting brain repair and improving long-term functional recovery after cerebral ischemia.

Shailesh Adhikary qualified as a Surgeon from Post Graduate Institute in Chandigarh, India in 1994 and currently working as a clinical teacher and a Surgeon at the Community Based Medical College in Eastern Nepal for 12 years and has published 34 papers at national and international journals and is serving as an Editorial Board Member for Asian Journal of Surgery. He is also the Governor of Endoscopic Laparoscopic Surgeons of Asia working to promote the Minimal Access Surgery development across Nepal and in Asia.

Background:Thefoot affections in diabetes are usually severe, costly, disabling and have a prolonged hospitalization or morbidity. An understanding of the pathogenesis, disease spectrum, reporting to a health care provider early on, and the treatment efficiency in the main is poor. The disease prototype has been observed in this study: Reasons for good and bad outcomes have been identified and the specific management strategy useful for our setup has been proposed. Methods: All patients presenting to the surgical clinics with diabetes and foot problems over a one year period were included in the present study. The details regarding the feet status, the demographics, their medical surgical treatment and their outcomes were documented on a prospective basis. Logistic regression analysis was undertaken to determine the association between factors of interest and outcomes of healing in the form of major or minor amputation has been done. Results: 43 Patients were recorded and the male to female ratio was 5:1 where 20% had neuropathic ulcers and 59% had severe disease at presentation. Two types of diabetes foot pathology were recognized that are not usually classified: Acute injury without neuropathy and deep soft tissue infections; 41% required major and 34% required minor amputations respectively and 25% did improve with dressings and debridement. The total number of hospital bed days was 764 days. Major amputation was associated with ischaemia, severe disease at presentation and aging. Conclusion: Patternsof diabetic foot which were not commonly recognized are described. The magnitude of disease and factors which lead to poor outcome are identified. Attention should be waged through a multidisciplinary team approach to timely referral from a primary care centre facility are: Patient education, early diagnosis and appropriate definitive management.

Do Joon Park has completed his MD at the age of 25 years from Seoul National University College of Medicine. After completing internship and residency training at the Seoul National University, he went to the U.S. and studied at NIH and Harvard Medical School for 6 years. After coming back to Korea, he has worked at the Seoul National University Hospital. He is the director of the thyroid center, head of the division of endocirinology and metabolism, and the professor of the department of the translational medicine, Seoul National University College of Medicine.

Purification of protein is laborious and time-consuming task. Furthermore, purification of very small amount of proteins such as phosphorylated proteins isextremely difficult. A 120-kDa phophoprotein, which is phosphorylated by TSH stimulation, was a target protein which our group tried to purify. Although this phosphoprotein band was reported years ago, this protein is not purified yet thus its role in FRTL-5 cell is yet to be elucidated.Treatment of TSH induces increases of tyrosine phosphorylated protein bands in FRTL-5 cells, although TSH receptor is not a tyrosine kinase itself. Because this TSH effect requires hours of treatment, it seems that TSH receptor does not directly activate tyrosine kinases, but may induce tyrosine kinases or their target proteins. Among these tyrosine phosphorylated proteins, 120-kDa phophoprotein is the most prominent one, whose phosphorylation increases by the treatment of TSH. Analysis of this 120-kDa phosphoprotein by 2D protein gel and anti-phosphotyrosine blot showed that this protein seems to be multiply phosphorylated by TSH, which implies that activity of this protein is tightly regulated by phosphorylation. To purify this 120-kDa phosphoprotein, we combined a series of conventional HPLCs, protein 2D electrophoresis and MALDI-TOF. FRTL-5 cells were harvested after stimulation, and sequential HPLC of DEAE- 5PW, phenyl-5PW and gel filtration chromatography followed by 2D protein electrophoresis could isolate tyrosine phosphorylated spots which were compatible with 120 kDa-phosphoprotein. Results of MALDI-TOF analysis revealed that the peptide sequence of this protein matched perfectly with already known protein, which is important in cell division. This finding suggests that this protein might play some important role in TSH-induced growth of thyrocytes.Combination of proteomic techniques including 2D protein electrophoresis, mass spectrometry as well as Western blot analysis was very effective method to purify very small amount of phosphorylated proteins, which can be used widely to purify very small amount of proteins.

Magdalena Hagner-Derengowska is academic clinician physiotherapist. She works as Associate Proffessor at The Universiy of Nicolaus Copernicus in Toruń – Collegium Medicum in Bydgoszcz, Chair and Department of Clinical Neuropsychology, sheisalsoclinician physiotherapist in Rehabilitation Clinic in University Hospital nr 1 in Bydgoszcz. Magdalena Hagner-Derengowska graduated as masters of physiotherapy in 2006 at Nicolaus Copernicus University in Toruń. Masters and doctoral graduated with honors. In 2010 she graduated PhD degree in medical science in the field of biology and medicine at the Medical University in Łódź. From 2011 is a Vice Chancellor and Dean of the Faculty of Physiotherapy in Private Univesity in Bydgoszcz. She is also a Vice President of Kujawsko-Pomorski Polish Rehabilitation Society and Member of the Polish Society of Physiotherapy. She cooperates on academic, research and clinician field with many units in Poland and overseas including The University of Michigan and Sports Medicine Clinic MedSports in Ann Arbor, USA, University of South Australia in Adelaide, South Australia, Hampstead Rehabilitation Centre in Adelaide, South Australia, HanYan Korean University in Seoul, Korea. She is the author and co-author of many publications in the field of medical rehabilitation and physiotherapy. Her current research is focused on exercise physiology, aging and neuropsychology in rehabilitation.

Gait is a complex motor activity associated with a precise synergy of the musculoskeletal system and the nervous system. It also involves the use of cognitive functions.The aim of the paper is to evaluate the influence of cognitive tests performed at various levels of difficulty on gait biomechanics. The said evaluation was carried out with the use of a three-dimensional BTS SMART system. The study comprised of 53 women, the average age was 64.5±6.7 years (age range: 47-79). The study was carried out with the use of a BTS SMART system – a system for comprehensive gait analysis. An analysis of gait parameters was performed during free gait and during gait combined with the performance of simple and complex cognitive tests.Performance of cognitive tests during gait resulted in a statistically significant extension of the left and right foot gait cycle, shortening of the length of steps made with the right extremity, reduction of speed of swings made with the left and right extremity and reduction of gait speed. Some of the above changes were recorded only with regard to more difficult tests.Performance of cognitive tests during gait hinders, to a statistically significant degree, gait biomechanics. An increase in the level of difficulty of cognitive tasks only amplifies these disorders.

Tomihara received his Ph.D. degree in 2006 from Sapporo Medical University, working on immune gene therapy by adenovirus vector. He then moved to Cancer Therapy and Research Center (CTRC) at The University of Texas Health Science Center at San Antonio (UTHSCSA) to work with Dr. Shin as a post-doctoral fellow. He obtained an assistant professor position in 2013 in the Department of Oral and Maxillofacial Surgery Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, where he started independent research on cancer immunology.

Gemcitabine (GEM) is a pyrimidine nucleoside analogue that is a new chemotherapeutic agent used for treating various cancers. Because accumulating evidence indicates that GEM may activate host immune responses, its potential as an immune modulator in cancer chemotherapy has generated considerable interest. In the present study, we sought to identify the antitumor immune effects of GEM in a mouse oral cancer model using immunological analyses. GEM induced significant oral cancer-cell apoptosis in vitro, and in vivo GEM administration markedly attenuated established mouse tumor growth. In vivo GEM administration decreased the numbers of both myeloid-derived suppressor cells (MDSCs) and B cells in tumor-bearing mice and enhanced dendritic cell maturation. Moreover, GEM treatment upregulated tumor-cell surface expressions of several immune accessory molecules and adhesion molecules, including CD80, CD86, CD40, ICAM-1, VCAM-1, and P-selectin. Remarkably, these tumor cells augmented T-cell responses. These results suggest that GEM can induce host antitumor immune responses, which would facilitate antitumor effects in the treatment of oral cancer.