Abstract Nowadays, foodborne diseases are one of the main problems of the world that infect humans due to consumption of contaminated water or food. Typhoid fever is one of the major causes of illness and death in the world caused by  Salmonella typhi . Vaccination is one of the most effective approaches in order to reduction of the disease risk. The main goal of this study is designing and characterization of antigenic determinants of a fusion protein originated from S.typhi   usable as an effective vaccine. In this study, the outer membrane proteins of salmonella have been considered as candidates conferring protection against typhoid. Considering the evidence, OmpA, OmpF and OmpC proteins of salmonella applied in a multivalent vaccine design. Conserved motives of these proteins were selected using the CLC software and then their extracellular regions of these peptides were identified with PRED-TMBB server. Appropriate motives were combined for design of final fusion protein. Finally epitops of designed protein with high antigenic properties were identified using BCPREDS, Ellipro, ABCpred, EpiJen, NetCTL-1.2, CTLpred, TAPpred, ProPred and VaxiJen servers. Predicted designed protein in this study reached a very high scores for antigenic indexes. Encoding Genetic construction of this fusion protein could be applied for production of the recombinant OmpA.OmpF.OmpC derived fusion protein with effective antigenic properties as a new vaccine against S.typhi . Laboratory experiments and animal challenging analyses is ongoing. 

Abstract Peroxisome proliferator-activated receptors (PPARs) are fatty acid activated transcription factors that belong to the nuclear hormone receptor family. They are initially known as transcriptional regulators of lipid and glucose metabolism, although further evidence has also been accumulated for other functions. Due to the nature of all PPAR isotypes which are expressed and exert effects by regulating the functions of cell types residing and infiltrating in the skin, PPARs represent a major research target for the understanding and treatment of many skin diseases. Atopic dermatitis (AD) is a chronic and relapsing disease c haracterized by skin barrier dysfunction and immune dysregulation.  Skin barrier disturbance is one of the exacerbation factors of AD, due to facile penetration of molecules such as antigens. From the aspect of immune dysregulation, innate and acquired immunity including cell proliferation, cell differentiation, and cytokine network are involved in the pathogenesis. In this review, the role of PPAR in AD and the possibility of its agonist for the treatment of AD are discussed.

Abstract Perturbation of cutaneous homeostasis including immune dysregulation and skin barrier dysfunction evokes skin disorders. In this study, we examined the effect of Eucalyptus citriodora (Euc-c) extract on cytokine production, cell proliferation and cell differentiation in HaCaT cells to elucidate its influence on cutaneous homeostasis. Euc-c suppressed significantly LPS-induced IL-6 and TNF-a-induced IL-8 production from HaCaT cells. Conversely IL-1ra production was significantly enhanced by Euc-c. The expressions of IVL, CERS3 and CERS4, keratinocyte differentiation markers, were upregulated to 3.1, 2.8 and 2.7-fold respectively by Euc-c treatment, compared to the control, while the proliferation was downregulated. The lipid contents in Euc-c-treated cells tended to increase, compared with non-treated cells. To explore the underlying mechanism of these effect, we next performed siRNA experiments against PPAR-b/d. Euc-c enhanced PPAR-b/d mRNA expression to 3.25-fold, while PPAR-b/d mRNA expression in transfected cells was suppressed. The expressions of IVL, CERS3 and CERS4 in transfected cells were suppressed to 1.48, 0.82 and 0.72-fold respectively, concomitant with suppression of PPAR-b/d mRNA expression. These results indicated that Euc-c exerts anti-inflammatory effects and regulates keratinocyte differentiation via the modulation of PPAR-b/d pathway. Therefore, the application of Euc-c is expected to exert beneficial effect on skin disorders evoked by perturbation of skin homeostasis.

Abstract Although epidermal growth factor receptor (EGFR) inhibitors are one of the most effective treatment options for lung cancer, they frequently cause cutaneous toxicity that can lead to treatment discontinuation. Dryness, which is a common form of cutaneous toxicity, is usually treated using medical moisturizing agents. We aimed to investigate the treatment of cutaneous toxicity caused by EGFR inhibitors by comparing patients who used a cosmetic moisturizer with those who used conventional medical moisturizers. This study included 12 patients with lung cancer, who were receiving EGFR inhibitors and using topical medical moisturizers. The participants were assigned to a group that continued using medical moisturizers or a group that began using NOV ®  skin cream D. The study’s findings showed that like conventional medical moisturizers, NOV ® skin cream D improved the cutaneous dryness caused by EGFR inhibitors and that it might additionally improve patients’ quality of life. Also, we obtained novel findings that NOV ® skin cream D normalized keratinization, which is a component of normal skin cell differentiation impeded by EGFR inhibitors. Hence, the cosmetic moisturizer may help to prevent the discontinuation of EGFR inhibitors, thereby ensuring their continuous therapeutic effects.

Abstract The recent approval of two CAR-T therapies by US Food and Drug Administration (FDA) marks a very significant development in cell-based cancer immunotherapy. This milestone was demonstrated by the effectiveness of eradicating hematologic cancers using CD19-specific CARs. The success spurred development of immune cell therapies for other cancers, especially solid tumors. The generation of novel CAR constructs for these cancer types represents a major challenge in bringing the technology ‘from-bench-to-bedside‘.In this review, we outline some new technologies we have developed to equip CAR-T cells to enhance efficiency while decreasing toxicity of CAR-T therapies in solid tumors.

Abstract Systemic sclerosis (SSc) or scleroderma is an autoimmune disorder characterized by tissue fibrosis of the skin and internal organs. The etiology of the skin fibrosis is thought to be thickened dermis due to uncontrolled excessive deposition of various extracellular matrix, mainly type I collagen.Systemic treatments with anti-inflammatory and cytotoxic immunosuppressive properties, such as corticosteroids and immunosuppressants, are usually considered for skin sclerosis of patients with SSc. However, their approach must be initiated at the early stage, before the fibrosis is completed, and the effects of the corticosteroids and immunosuppressants are known to be reduced in the late stages of the sclerosis. Furthermore, various significant adverse effects of these treatments must be considered.This paper discusses the present day understanding of therapeutic options using disease-modifying drugs against skin sclerosis of SSc patients and the possible mechanisms.