Immune Suppression Mediated by Myeloid and Lymphoid Derived Immune Cells

Thyroid cancer is the most common endocrine malignancy and is predicted to be the 4th most commonly diagnosed cancer by 2030. Approximately one-half of follicular thyroid carcinomas (FTC) contain genetic alterations in RAS family members.

Furthermore, Cowden’s disease, which is characterized by loss of PTEN, predisposes for the development of FTC in humans. We have shown that thyroid specific expression of HrasG12V at endogenous levels and Pten inactivation (HrasG12V/Pten-/-/TPO-cre mice) leads to the development of FTCs that closely recapitulate human disease, with complete penetrance at one year.

In patients, FTCs metastasize via the bloodstream to distant sites, frequently the lungs, bones and brain. The first objective of the study was to determine if these mice developed de novo metastasis to relevant sites. Indeed, spontaneous metastasis to the lungs was observed in 56% of HrasG12V/ Pten-/-/TPO-cre mice. We next sought to identify the cellular components within the tumor microenvironment (TME) of FTC that contribute to tumor progression and metastasis via FACS analysis.

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Biomarkers of Bone Turnover | Potential, Challenges and Pitfalls from the Laboratory Point of view

Bone turnover markers (BTM) may give information on bone formation and resorption, risk of fracture and response to treatments. BTMs have been extensively studied as markers in the diagnosis and monitoring of osteoporosis (OP), and resulted potentially useful as tools to evaluate the estimation of fracture future risk, although their significance was essentially demonstrated helpful to monitor efficacy of anti-OP treatments. Other possible application includes the prediction rate of bone loss, the identification of secondary OP, the improvement of targeted treatments and patient compliance, although other data are needed in such areas.

However, they are influenced by a number of pathophysiological factors, and by analytical aspects, still need to be overcome to extend their application and significance in the clinical practice.

Thus, BTMs practical use requires careful awareness of their advantages as well as their limitations to interpret results produced by the laboratory.The present review aim to describe the most commonly used serum bone formation and resorption biochemical markers, discuss their advantages and disadvantages and give practical information on their use and result interpretation in the laboratory and clinical settings.

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Constructivism A Paradigm for Teaching and Learning

Constructivism A Paradigm for Teaching and Learning

The Role of Sulforaphane on Duchenne Muscular Dystrophy by Activation of Nrf2

Duchenne muscular dystrophy (DMD) is the most common type of muscular dystrophy, which is also regarded as a severe muscle disease with an incidence of 1 in 3,500 live male newborns in the world. The leading cause is dyctrophin gene mutations, which lose regulation of the muscle protein.

Cell death, progressive damage of muscle fibers, oxidative stress, and inflammation are the remarkable characteristics of DMD in humans and mdx mice. Glucocorticoid play a role on boosting muscle function and strength in a short time in DMD therapy, but it is not effective and with plentiful side effects, like hypertension, diabetes, mood/behavioral affection for a long time using.

Therefore, there is not noticeably effective method for treatment of DMD yet.Nrf2 (NF-E2 related factor 2) is one of the momentous transcription factors, which exists in biological body and affect genes expression of numerous oxidative stress proteins, detoxifying enzymes and antioxidant enzymes.

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Alexithymia in Systemic Lupus Erythematosus: A Tight Relation with Mood States

Alexithymia describes the difficulty of people in identifying, differentiating, and articulating emotions of others and themselves and in discriminating those from bodily sensations, with a limited fantasy and a concrete, externally oriented cognitive style.

Sifneos described alexithymia construct in 1973 in relation to classic psychosomatic diseases and failure to respond to dynamic psychotherapy. Actually alexithymia is defined by cognitive and affective characteristics comprising difficulty identifying feelings and distinguishing between feelings and the bodily sensations of emotional arousal; difficulty describing feelings to others; a restricted imagination, as evidenced by a paucity of fantasies.

A cognitive style that is literal, utilitarian, and externally oriented. Numerous studies revealed positive associations between alexithymia and pain intensity and sensitivity.

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Eph/Ephrin-mediated Mesenchymal Stem Cell Regulation of T-cell Activation and Function

Mesenchymal stem cells (MSC) represent a promising cellular therapy for the treatment of immune-related conditions due to their immunomodulatory properties, which include the capacity to inhibit the proliferation and function of T-cells.

Despite the fact that MSC have been the subject of intense investigation as therapeutic agents for diseases in which cellular immune response is exacerbated, the underlying mechanisms of how MSC exert their T cell suppressive properties remain to be fully understood.

Eph surface tyrosine kinase receptors and their ephrin ligands are involved in T-cell development, maturation, activation and proliferation. Recent findings have demonstrated Eph/ephrin interactions as potential mechanisms mediating human MSC inhibition of activated T-cells.

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Lipid Mediator Regulation of Group 2 Innate Lymphoid Cells

ILC2s were originally found to be activated by epithelial cell derived cytokines to induce the secretion of Th2 cytokines, IL-5 and IL-13. Recent research has shown that lipid mediators play a large role in the activation and inhibition of ILC2 function.

Unlike the traditional epithelial cell derived cytokines IL-33 and IL-25, lipid mediators have been shown to promote ILC2 secretion of not only IL-5 and IL-13, but the secretion of IL-4 as well. Prostaglandin D2 has been shown to be a potent chemoattractant of ILC2s as well as a potent activator of ILC2s to release Th2 cytokines.

In addition to prostaglandin D2, cysteinyl leukotrienes also activate ILC2s to secrete Th2 cytokines during inflammation. Notably, lipid mediators have been shown to work in concert with epithelial cell derived cytokines to increase IL-5 and IL-13 secretion from ILC2s.

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Physiology and Medicine: The Gifted Saga of the Last Decade

Over the last century, Science and Technology moved forward and witnessed exceptional inventions and discoveries due to individual and collaborative research efforts. This momentum opened doors for the deep understanding of biological systems by which it permitted the advancement in technologies and designing of new tools in biomedical field.

Since 1901, discoveries and inventions in various fields of science (Chemistry, Physics, Physiology and Medicine, Economics) including literature which can influence the betterment of human race were being awarded with Nobel Prize.

Over the past decade, numerous groundbreaking discoveries in physiology and medicine have been reported. This short note is intended to summarize the significance of these findings and few remarkable controversies associated with them.

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Alpha-Defensin 5 Expression is Regulated by microRNAs in the Caco-2 Intestinal Epithelial Cell Line

In inflammatory bowel disease (IBD), an inappropriate immune response leads to chronic mucosal inflammation. This response may be partly due to dysregulation of defensins, which are endogenously produced antimicrobial peptides.

This study determined whether microRNAs (miRNAs) regulate α-defensin 5 (DEFA5), which could further implicate both in IBD pathogenesis. Methods: Induction of DEFA5 mRNA and protein expression was determined in Caco-2 cells.

An in silico analysis identified putative miRNA binding sites of DEFA5. Expression of these miRNAs was assessed in Caco-2 cells. Regulation of DEFA5 expression by these miRNAs was measured by luciferase assays. Caco-2 cells were transfected with miR-124 and miR-924 mimics, and DEFA5 mRNA and protein expression was measured.

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International Consensus: Paraneoplastic Neurological Antibodies - are we there yet?

Laboratory contribution to clinical diagnosis is an essential part of patient care. In order to accurately diagnose, treat and advise patients, physicians rely on timely laboratory data that remains consistent regardless of its origin and most will take the quality (accuracy, reproducibility, clinical relevance) of the result for granted. Most physicians rightly assume that quality is assured as a routine part of the work of the laboratory and would not expect that different versions of tests would produce different results on the same sample, or that exactly the same test on the same sample might produce different results in different places.

Laboratories and their suppliers strive to achieve this by monitoring and standardizing test methodologies with the aid of robust internal and external quality control. Where standardization (same result in same units on the same sample, everywhere) is not possible, we aim for harmonization of reporting outcomes(all positive and negative results match, irrespective of units). Despite such an ethos, laboratory results on the same patient sample can vary due to rapid development in the diagnostic service or methodology, or the pressures of increasing workload. 

Influence of Culture Medium on Production of Nitric Oxide and Expression of Inducible Nitric Oxide Synthase by Activated Macrophages In Vitro

Macrophages play important roles in biology and pathology including those in innate immune responses to pathogens, tumor cells, and apoptotic cells of the host.

Macrophages also have a unique phenotype, known as “macrophage activation,” which refers to changes their properties in response to pathogen-associated molecular patterns (PAMPs), various cytokines, hormones, and other factors acting as both endogenous and exogenous stimuli, which changes occur through activation processes.

Among activated-macrophage phenotypes, the production of reactive oxygen species (O2- and H2O2), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) [8-11] is the major, as well as an important, function of macrophages to exert pivotal roles in the body and to maintain homeostasis.

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Anticancer Molecules in Brain: Implication for Novel Strategy for Cancer Immunotherapy

Clinical and epidemiological studies have demonstrated that macroenvironmental factors are risk factors for the development and progression of tumor.

Macroenvironmental factors include a patient's physical, social environment and specific psychosocial factors such as chronic stress, depression, and lack of social support. These observations raise intriguing questions on the brain-cancer connection.

What are the molecules in brain linking environmental factors to cancer? Through which pathways do these brain molecules modulate the peripheral cancer? How do these molecules impact tumour growth and progression? The effects and mechanisms of the macroenvironment on systemic cancer are much less well defined, because most basic cancer research focuses on microenvironmental factors of tumor.

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Antarctic Fish IgT, a Weird Option of Immunoglobulin Genes

Antarctic fish, most of which belonging to the Perciform Suborder Notothenioidei, have acquired, during their evolution, specific features that allow them to thrive, at present, at cold and stable temperature (-1.86°C).

The morphological evolution and diversification of AntarCtic Notothenioid teleosts into over 120 species is one of the best examples of adaptive radiation in the marine environment triggered by new ecological chances, for instance the extinction of antagonists, the colonization of vacant niches, or the emergence of key innovative features such as the gain of antifreeze glycoproteins that allow them to live in cold habitats where other species would die.

The evolution of the antifreeze glycoprotein genes from a trypsinogen-like gene is a striking innovation, in terms of genetic fitness, that guarantees the survival.

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M1 and M2 Myeloid Cells in Inflammation

Inflammation is triggered in the innate immune response by tissue myeloid cells, macrophages in peripheral tissue and microglia in the nervous system, in response to microbial or endogenous danger signals.

The plasticity of these cells developing into pro-inflammatory M1 and anti-inflammatory M2 phenotypes is remarkable. Polarization of macrophages depends on local environmental factors, especially cytokines and growth factors. Interferon-γ (IFN-γ) and bacterial lipopolysaccharide (LPS) together polarize macrophage into the M1 phenotype which produces reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines such as tumor necrosis factor-α (TNF-α).

However, NO appears to play a negative role in M1 macrophage differentiation. M2 polarized phenotypes can be polarized by interleukins 4, 10 or 13 (IL-4 or IL-10 or IL-13) and produce anti-inflammatory molecules such as the autocrine IL-10, and are responsible for tissue remodeling and angiogenesis.

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HERE IS THE BIO MARKER FOR HEPATITIS C DIAGNOSIS

Hepatitis C Virus (HCV) strongly contributes to the development of chronic hepatitis, liver cirrhosis and liver cancer. As HCV replicates in the cytoplasm of hepatocytes, fibrosis or cirrhosis can result from immune-mediated mechanisms.

In spite of the detection of many antivirals to help combat the virus, little is known about suitable biomarkers for HCV virulence, patient adherence to therapy, or the development of therapy resistance. Immunoregulatory cytokines in HCV have previously been studied, but reports on elevated levels of cytokines are inconclusive with one study even showing decreased cytokine levels in HCV patients.

The standard treatment for patients with HCV is pegylated interferon plus ribavirin administration, which results in the reduction of serum cytokine levels. Indeed, interactions between HCV and the immune system are important for efficient treatment and elimination of the virus.

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Basal Serum Cortisol and Adrenocorticotropic Hormone Levels in Patients with Atopic Dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease with an onset in infancy or early childhood. It is characterized by severe pruritus, chronic and relapsing course, and typical clinical morphology including xerosis and eczematous lesions.

The incidence of AD has been increasing during past 30 years, whereas its current prevalence is estimated 12%. Atopic dermatitis is often associated with remarkable morbidity which results in patient hospitalization, absence from work or school, and loss of several work days.

In children, one of the most hazardous effects of AD is sleep disorders which may lead to behavioral disturbances. Furthermore, children are at risk of growth retardation as a complication of the disease.

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Physical Activity after High Tibial Osteotomy for Treatment of Medial Compartment Knee Osteoarthritis

High tibial osteotomy (HTO) is a surgical option in the treatment of medial femorotibial osteoarthritis. Although the lateral closingwedge proximal tibial osteotomy is well documented in the literature, several shortcomings have been reported, such as the lack of precision of the correction and difficulties in conversion to a total knee arthroplasty (TKA).

To avoid these problems, medial opening-wedge proximal tibial osteotomies have been advocated. The clinical outcome after HTO is satisfying, even though long-term results have been shown to deteriorate.

When successful, HTO can improve pain and function; postpone disease progression and early TKA. In young active individuals, it can facilitate a return to sports and allow them to continue to participate in sporting activity into later life.

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Influenza Virus Evolution, Host Factors and the Assessment of Influenza Vaccine Effectiveness

Influenza virus vaccines are the main prophylactic strategy for reducing the burden of influenza morbidity and mortality. Nevertheless the currently available influenza vaccines induce a narrow and strain specific immunity and their protective effect is limited by the continuous evolution of influenza viruses associated with rapidly evolving mutations in key antigenic sites of the hemagglutinin surface protein.

Besides viral factors, also host and environmental factors considerably influence the protective effect of influenza vaccines considerably. Assessment of vaccine effectiveness (VE) using the test-negative case-control design has revolutionized VE monitoring and has contributed to a better understanding of suboptimal VE of seasonal influenza vaccines.

This methodology first described for the 2004/05 influenza season in Canada is now the preferred observational study design to reliably calculate the effectiveness of seasonal influenza vaccines against medically attended influenza virus infections.

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A Contagious Fatal Cancer that Threatens the Tasmanian Devils

The fact that Tasmanian devils are prone to a bizarre type of contagious facial cancer disease was first noted in 1996 in the far north east of Tasmania, and since then, the disease has spread south and west and now affects devils in over 85% of their distribution territory.

The disease, termed devil facial tumor disease (DFTD), is spread by biting, causing the appearance of tumors on the face, jaws and in the oral cavity. The tumors often become very large and in ~60% of the cases, metastasize to internal organs, including regional lymph nodes, lungs, spleen, heart and kidneys.

The tumors kill the host within 6 months of the emergence of first lesions, due to starvation, secondary infection and metastases formation.In contrast to other transmissible cancer diseases, such as the human Burkitt’s lymphoma and adult T-cell leukemia, which are spread by viruses (Epstein-Barr virus (EBV) and adult T-cell leukemia/ lymphoma (HTLV-I), respectively), the DFTD which is spread by biting, appears to be transduced by the cancer cells themselves being passed from one animal to another.

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T Cell Immunoglobulin Mucin-3 (TIM-3) Expression on Peripheral Blood Lymphocytes in Chronic Hepatitis Virus C Infection

Hepatitis C virus (HCV) is a major causative agent of chronic hepatitis, affecting approximately 200 million people throughout the world. There is a broad array of functional impairments of virusspecific T cells including decreased antiviral cytokine production and cytotoxicity; with impaired proliferative capacity and arrested stages of differentiation.

In liver infections, CD81 T cells may show features of cells that did not receive sufficient help. Thus, in chronic lymphocytic choriomeningitis virus in mice, failure to eliminate the virus is associated with “exhausted” T cells that persist, but do not function.

These cells express a characteristic surface phenotype, including the markers programmed cell death 1 (PD- 1), T-cell 3 immunoglobulin and mucin domain containing protein 3 (TIM-3), and lymphocyte activation gene 3 which are also expressed on human exhausted T cells.

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Genetic and Demographic Correlates of Quality of Life after Ileal Pouch Anal Anastomosis for Ulcerative Colitis

Total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is the operation of choice for ulcerative colitis (UC) patients with medically refractory symptoms, steroid dependence and/or dysplasia or cancer. The IPAA constructs a functional reservoir using a length of small bowel folded over to create a neorectum and attaches it to the preserved sphincters to maintain continence.

Overall, this operation has a high rate of patient satisfaction. However, a subgroup of patients experience poor quality of life (QOL) after pouch creation with continued physical symptoms and/or a decrease in emotional or social QOL.

Although it has been suggested that females and those with pouchitis or inflammation of the pouch are generally unhappier after IPAA, results are conflicting and confounded by the inclusion of patients with indeterminate colitis and Crohn’s disease. Presently, there are few studies identifying clear clinical or histological variables that can predict poor pouch outcome to aid in surgical decision making preoperatively.

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A 66 year old female with a past medical history of end stage renal disease presumed secondary to diabetic nephropathy (no kidney biopsy performed), who underwent hemodialysis for 3 years, presented for cadaveric renal transplant. Her major medical co-morbidities included essential hypertension, mild coronary artery disease, prior bleeding gastric ulcer, hypothyroidism, and obesity.

Her past surgical history was remarkable for failed arteriovenous fistula, appendectomy, and tonsillectomy. Her prior known sensitizing events included a prior pregnancy, one miscarriage, remote blood transfusion, but no previous transplants.

Her relevant family history included diabetes, hypertension, with no known family history of HUS or thrombotic thrombocytopenic purpura (TTP). Her relevant laboratory values pretransplant were serum hemoglobin of 12.9, CMV antibody negative, blood type B+, and calculated panel reactive antibody (PRA) of 55%.

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Neutrophil Biology: JAGN1 Deficiency is Responsible for Neutropenia

Granulocyte-Macrophage colony stimulating factor can salvage JAGN1 defect in bone marrow precursors causing congenital neutropenia. Neutrophils are the sentinel of host immune systems that are dispatched to surveil, engage and combat microbial pathogens.

Neutropenic patients with low neutrophil counts are unable to mount neutrophil based immune responses and as a result become vulnerable to infections. JAGN1 encoding Jagunal homolog 1 expressed in hematopoietic progenitors and it’s deficiency makes neutrophil incompetent effector cells.

In JAGN1 mutant mice, Penniger et al. demonstrated that the defect in JAGN1 function is rescued by granulocyte/ macrophage colony stimulating factor (GM-CSF) when afflicted by Candida albicans.

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Sophisticate Mechanisms and Unsolved Problems in the Resolution of Acute Gouty Arthritis

Different from allantoin in avian species, the end-product of purine metabolism in human being is uric acid due to 2 non-sense mutations at codons 33 and 187 of urate oxidase during hominoid evolution.

The solubility of uric acid in the fluid milieu reaches a maximum of 6.8 mg/dl and becomes hyper-saturation status in plasma when over its solubility capacity. Many factors including [Na+], pH, temperature, oncostatic pressure, and in presence of nucleating factors/growth promoting factors may accelerate crystal formation in the joints, periarticular soft tissues, renal tubules or subcutaneous locations.

Thus, acute inflammation elicited by monosodium urate monohydrate (MSU) crystal deposition occurs usually in the low-temperature joints especially in the lower limbs. Usually, the acute inflammation in the joint of patients with acute attack may last a few days from 7-10 days.

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Basal Serum Cortisol and Adrenocorticotropic Hormone Levels in Patients with Atopic Dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease with an onset in infancy or early childhood. It is characterized by severe pruritus, chronic and relapsing course, and typical clinical morphology including xerosis and eczematous lesions.

The incidence of AD has been increasing during past 30 years, whereas its current prevalence is estimated 12%. Atopic dermatitis is often associated with remarkable morbidity which results in patient hospitalization, absence from work or school, and loss of several work days.

In children, one of the most hazardous effects of AD is sleep disorders which may lead to behavioral disturbances. Furthermore, children are at risk of growth retardation as a complication of the disease. Unpredictable course, chronic and relapsing nature of the disease and disturbing pruritus can impose extensive psychological and emotional burden to patients with AD and their families.

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Improved Immunohistochemical Detection of Type 1 Insulin-Like Growth Factor Receptor in Human Tumors

The contribution of insulin-like growth factors (IGFs) to cancer biology has been extensively studied in cell lines, revealing that IGFs activate type 1 IGF receptors (IGF-1Rs) to promote cell cycle progression, cell survival, motility and invasion. These findings provoked interest in studying IGF-1R expression in clinical cancers, and in development of drugs that block IGF signaling.

However, there has been striking variation in reported IGF-1R expression in tumors and normal tissues when detected by immunohistochemistry. For example IGF-1R was reported to be unchanged or down -regulated in prostate cancer compared with benign prostate, although since our report of IGF-1R up-regulation at the mRNA and protein level most publications support up-regulation.

This lack of consensus also confounds attempts to interpret results of clinical trials of novel IGF inhibitory drugs. Early trials reported striking clinical responses to IGF-1R inhibition but later trials showed very limited activity in unselected patients. This raises the question as to whether tumor IGF-1R expression correlates with sensitivity to IGF-1R inhibition. Preclinical reports supporting such a link include studies in non-small cell lung cancer.

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Dermatological Aspects of a Humanitarian Mission

Patients with dermatological patholgies represent an important population, especially in developing countries. The cosmetological aspects are important. Objective: To determine the incidence and epidemiology of skin diseases during a humanitarian mission. Methods: 679 patients who presented to our general medical consultations were examined.

Patient data was registered to be analyzed retrospectively. The rare and difficult cases were systematically discussed during the consultation. The patient charts were correlated by the corresponding photos.The ethnic origin of the patients was different. The majority of our patients were younger than 50 years old.

The dermatological problems represented a major motivation to consult, namely itching and skin lesions. The incidence was higher when secondary findings and complaints were also considered. Besides scabies, mycosis and tropical pathologies, the problems of scarring represented a major cosmetological demand.

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Rationales for a Multi-Epitope Approach in an Autologous Renal Cell Cancer Tumor Vaccine

Renal cell carcinoma is an orphan disease with an incidence of less than 1.6:10.000. The median age of patients at primary diagnosis is 60 years and the male to female ratio is 3:2. Until now only a 1997 initiated prospective randomized phase-III trial showed a significant effect in overall survival after radical nephrectomy accompanied by treatment with an autologous renal tumor cell vaccine.

Furthermore, by comparing data from a compassionate use program with a historical group of patients observed for more than 10 years and treated by radical nephrectomy, May et al. demonstrated the same significant effect on the overall survival (42.3 months) for T3 tumors.

Discussions on common tumor markers or tumor associated antigens (TAA) as potential targets for immunotherapy are ongoing especially since authorities like the EMA and the FDA request additional information about the potency and potential risks of these autologous applied antigens.

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Eph/Ephrin-mediated Mesenchymal Stem Cell Regulation of T-cell Activation and Function

Mesenchymal stem cells (MSC) are self-renewing stem cells identified in rodent and human bone marrow aspirates based on their ability to form adherent clonogenic clusters (CFU-F; colony forming units-fibroblastic) in vitro, and by their capacity to differentiate into multiple specialized mesodermal cell lineages.

Similar MSC-like populations have been described in various tissues with different growth and differentiation potentials. These MSC-like populations share a common immunophenotype based on the cell surface expression of various markers, but not limited, to STRO-1, CD73, CD105, CD106, CD90, CD146 and CD166, while lacking expression of CD34, CD3, CD14, CD19, CD31, CD34, CD45, Glycophorin-A and HLA-DR.

In the last few decades, MSC have generated considerable interest due to their production of cytokines and growth factors, which act as potent mediators of angiogenesis, regeneration of damaged tissues, hematopoiesis and immune cell responses. In particular, the paracrine properties of MSC, makes them highly desirable as potential cellular therapies to treat a variety of immune/inflammatory based diseases and conditions.

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Jatropha Curcas Linn can Reduce the Expression of Hsp70 that will Result in Reduced Errors in Protein Folding and Promotion of Normal Protein Function in Proliferation and Apoptosis

Jatropha curcas Linn as a local plant have phytochemical contents, like anti-inflammatory and cytotoxicity properties of phenolic extract. Leaf of J.curcas contents higher phenolic compound, flavonoid and saponin. Application of different varieties of J.curcas in traditional medicine had been reported.

However, information regarding the bioactive compounds and the therapeutic activities is still lacking. These studies suggest that components from J.curcas may have anticancer function and potentially be useful for prevention and treatment strategies.All organisms respond to heat (heat shock response) by upregulating specific heat shock or stress proteins.

Research over the last decade has shown that increased expression of heat shock protein 70 (Hsp70) plays a role in protein folding errors from denaturised proteins and new protein translation, causing proteins to function abnormally. Multiple hits – multiple steps – multiple stage stressors may experience distress and express Hsp70, among other cellular factors, to inhibit cell proliferation and enhance apoptosis.

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Anti-inflammatory Effects of Kelussia odoratissima in Rats Model of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and other body organs, which 1 % of the human population is affected. RA induced in the fourth and fifth decades of life and in women is more common. Kelussiao doratissima contains compounds such as flavonoids, mainly aggregated in the inflorescence and stems of Kelussia, has anti-inflammatory effects. Present study aimed to investigate the anti-inflammatory effect of Kelussia odoratissima on rheumatoid arthritis induced in Wistar rats.

A total of 30 female Wistar rats using subcutaneous injection of complete Freund's adjuvant has been induced and were randomly divided into five groups containing negative control (no treatment), positive control (receiving indomethacin (3mg/ Kg) and three rheumatoid arthritis group receiving three different doses (100,200and 300mg/kg) of hydroalcoholic Kelussia odoratissima extract. material injection were tested in the animals for 10 days.

The symptoms of Rheumatoid arthritis were evaluated according to standardized scoring method at paw and double-blind for the different categories daily. CRP levels were measured and Data were analyzed using the SPSS statistical program (version 17 for Windows). In all the cases for comparison between different groups, Mann-Whitney U-test was used.

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Solute Carrier Family 6 Member 12 Gene Polymorphisms in Japanese Patients with Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD), so-called aspirinintolerant asthma, is a clinical syndrome characterized by severe asthmatic attacks after ingestion of aspirin and/or nonsteroidal antiinflammatory drugs (NSAIDs). AERD is known to be associated with less atopic tendency, persistent eosinophilic infiltration in the airway mucosa, and a more severe clinical course.

The inhibitory action of aspirin and NSAID on cyclooxygenase activity may cause diversion to the 5-lipoxygenase pathway, leading to the overproduction of cysteinyl leukotrienes (LTs). A general consensus exists that increased levels of cysteinyl LTs are key inflammatory mediators in AERD.

However, a study of Japanese asthmatic patients demonstrated that prostaglandin D2 was overproduced during aspirin-intolerant bronchoconstriction, and the urinary concentrations of LTE4 and metabolites of prostaglandin D2 correlatively increased during the reaction.

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