Modulation of the immune response by Middle East respiratory syndrome coronavirus

Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells.     

Optimization of parameters affecting on CHO cell culture producing recombinant erythropoietin

Abstract

Several factors may affect erythropoietin (EPO) sugar structures including designing cell culture procedure, pH, concentration of additives, dissolved oxygen, and other physicochemical parameters. In this study, we investigated the influence of changes in effective parameters and compounds on the growth rate of Chinese hamster ovary cell (CHO) cells producing recombinant EPO. Cell culture was performed at different temperature, buffering conditions, and varied concentrations of additives such as pyruvic acid, insulin, GlutaMAX, and sodium butyrate. Results indicated that the optimal temperature and pH were 37?°C and 7.2, respectively. Also, optimal concentrations for pyruvic acid, butyrate, glutamate, and insulin were obtained to be 20?mM, 1?mM, 2?mM, and 40?μg/mL, respectively. Then, cell culture was performed in microcarrier-coated spinner flasks under the optimized condition. The results showed recombinant human EPO (rhEPO) production with adequate purity. Optimization of physicochemical conditions and culture media are important factors to improve the quantity and quality of protein products. This study showed that cell growth and recombinant EPO protein production significantly increased under the optimized conditions. The results of this research can also be used in scale-up to increase the efficiency of EPO production.

Abbreviations: EPO: erythropoietin; CHO cell: Chinese hamster ovary cell; rhEPO: recombinant human EPO; DMEM: modified eagle’s medium; FBS: fetal bovine serum; SDS-PAGE: sodium dodecyl sulfate–polyacrylamide gel electrophoresis; IGF-1: insulin-like growth factor 1     

The enhanced expression of heat stress-related genes in scleractinian coral ‘Porites harrisoni’ during warm episodes as an intrinsic mechanism for adaptation in ‘the Persian Gulf’

Coral Reefs - Shallow water tropical reefs are widely threatened by anthropogenic ocean warming which sometimes exceeds their thermal tolerance limit. The majority of reefs have been currently...     

Incorporation of the Tat cell‐penetrating peptide into nanofibers improves the respective antitumor immune response

A major challenge for the development of anticancer vaccines is the induction of a safe and effective immune response, particularly mediated by CD8+ T lymphocytes, in an adjuvant‐free manner. In this respect, we present a simple strategy to improve the specific CD8+ T cell responses using KFE8 nanofibers bearing a Class I (Kb)‐restricted peptide epitope (called E. nanofibers) without the use of adjuvant. We demonstrate that incorporation of Tat, a cell‐penetrating peptide (CPP) of the HIV transactivator protein, into E. nanofibers remarkably enhanced tumor‐specific CD8+ T cell responses. E. nanofibers containing 12.5% Tat peptide (E.Tat_12.5 nanofiber) increased antigen cross‐presentation by bone marrow‐derived dendritic cells as compared with E. nanofibers, or E. nanofibers containing 25 or 50% the Tat peptide. Uptake of KFE8.Tat_12.5 nanofibers by dendritic cells (DCs) was significantly increased compared with KFE8 nanofiber lacking Tat. Peritoneal and lymph node DCs of mice immunized with E.Tat_12.5 nanofibers exhibited increased presentation of the H2kb‐epitope (reminiscent for cross‐presentation) compared with DCs obtained from E. nanofiber vaccinated mice. Tetrameric and intracellular cytokine staining revealed that vaccination with E.Tat_12.5 triggered a robust and specific CD8+ T lymphocyte response, which was more pronounced than in mice vaccinated with E. nanofibers alone. Furthermore, E.Tat_12.5 nanofibers were more potent than E. nanofiber to induce antitumor immune response and tumor‐infiltrating IFN‐γ CD8 T lymphocyte. In terms of cancer vaccine development, we propose that harnessing the nanofiber‐based vaccine platform with incorporated Tat peptide could present a simple and promising strategy to induce highly effective antitumor immune response.     

Resource allocation mechanisms for maximizing provider’s revenue in infrastructure as a service (IaaS) cloud

Infrastructure as a Service (IaaS) is a cloud computing service provided over the internet to facilitate the provisioning of various services such as storage, processes, etc. The provider in the IaaS market may offer some purchasing plans including: reservation, on-demand, and spot plans for its resources. As in real scenarios, demand volume for each plan is assumed to be a random variable with a given probability distribution. The provider maximizes its average revenue in the long run by optimal allocation of its resources among the plans. We formulate an Integer Linear Programming (ILP) model with a stochastic constraint, to determine the number of resources to be allocated for each plan in every time slot in the planning horizon. First, fixed prices are considered for each plan, then two mechanisms of Continuous Double Auction and Second Price Sealed Bid Auction are considered for reservations and spot plans, respectively, to obtain market-driven prices of the services. The Seasonal Weighted Moving Average method is used to predict the amount of demand in every slot. Finally, the proposed mechanisms are evaluated through simulations and the results confirm the effectiveness of the methods in maximizing the revenue and overall utilization of the available IaaS capacity.

     

Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in colorectal cancer

Colorectal cancer (CRC) is known as the most common form of malignancies in the world and its occurrence is annually increasing. Due to the relatively high death rates in patients, finding better diagnostic and prognostic factors are required. Substance P (SP) belongs to the tachykinin family that acts as an immunomodulator by binding to the neurokinin-1 receptor (NK1R). The interaction of SP with NK1R might be involved in tumor cell proliferation, angiogenesis, and migration. Hence, this study was aimed to evaluate the serum SP level and tissue distribution of NK1Rs in CRC. Also, we assessed the relationship between tissue distribution of NK1R and some different tumor characteristics, including tumor size, and lymph node status. Recruiting 38 patients primarily diagnosed with CRC, the tissue distribution of NK1R was immunohistochemically evaluated in tumor tissues and their adjacent normal tissue. The serum level of SP was measured using an ELISA method in both cases and healthy control group. The SP value was significantly increased in the serum of patients in comparison with the healthy group (p?=?0.001). Tumor tissues expressed a higher number of NK1R than adjacent normal tissues (p?=?0.01) considering both the percentage of stained cells and intensity of staining. However, there was not any statistically significant relevance between NK1R distribution and tumor characteristics. The SP/NK1R system is involved in tumorigenesis of CRC, and might be suggested as a potent prognostic or diagnostic factor, or a new target in the treatment of CRC.