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     

miR-200c-3p upregulation and ACE2 downregulation via bacterial LPS and LTA as interesting aspects for COVID-19 treatment and immunity

Molecular Biology Reports -     

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...     

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.

     

Incorporation of SPION-casein core-shells into silk-fibroin nanofibers for cardiac tissue engineering

Mimicking the structure of extracellular matrix (ECM) of myocardium is necessary for fabrication of functional cardiac tissue. The superparamagnetic iron oxide nanoparticles (SPIONs, Fe₃O₄), as new generation of magnetic nanoparticles (NPs), are highly intended in biomedical studies. Here, SPION NPs (1 wt%) were synthesized and incorporated into silk-fibroin (SF) electrospun nanofibers to enhance mechanical properties and topography of the scaffolds. Then, the mouse embryonic cardiac cells (ECCs) were seeded on the scaffolds for in vitro studies. The SPION NPs were studied by scanning electron microscope (SEM), X-ray diffraction (XRD), and transmission electron microscope (TEM). SF nanofibers were characterized after incorporation of SPIONs by SEM, TEM, water contact angle measurement, and tensile test. Furthermore, cytocompatibility of scaffolds was confirmed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. SEM images showed that ECCs attached to the scaffolds with elongated morphologies. Also, the real-time PCR and immunostaining studies approved upregulation of cardiac functional genes in ECCs seeded on the SF/SPION-casein scaffolds including GATA-4, cardiac troponin T, Nkx 2.5, and alpha-myosin heavy chain, compared with the ones in SF. In conclusion, incorporation of core-shells in SF supports cardiac differentiation, while has no negative impact on ECCs' proliferation and self-renewal capacity.     

Modulatory effects of statins on the autophagy: A therapeutic perspective

Autophagy is considered as an important mechanism for maintaining homeostasis and responsible for the degradation of superfluous or potentially toxic components and organelles. Autophagy impairment is associated with a number of pathological conditions, such as aging, neurological disorders, cancer, and infection. Autophagy also plays a significant role in cancer chemotherapy. The multiple cancer drugs have been notably developed with the strategy of autophagy modulation. Statins, 3-hydroxy-3-methyl-glutaryl-CoA inhibitors, are known due to their efficacy in decreasing low-density lipoprotein and extensively used for the management of cardiovascular diseases. Statins have other therapeutic and biological activities, such as antioxidant, anti-inflammatory, antitumor, and neuroprotective known as pleiotropic effects. It seems that statins are capable of targeting various signaling pathways in the induction of their great pharmacological effects. At the present study, we demonstrate the therapeutic effects of statins mediated via autophagy regulation.     

Alveolar mimics with periodic strain and its effect on the cell layer formation

We report on the development of a new model of alveolar air–tissue interface on a chip. The model consists of an array of suspended hexagonal monolayers of gelatin nanofibers supported by microframes and a microfluidic device for the patch integration. The suspended monolayers are deformed to a central displacement of 40–80 µm at the air–liquid interface by application of air pressure in the range of 200–1,000 Pa. With respect to the diameter of the monolayers, that is, 500 µm, this displacement corresponds to a linear strain of 2–10% in agreement with the physiological strain range in the lung alveoli. The culture of A549 cells on the monolayers for an incubation time of 1–3 days showed viability in the model. We exerted a periodic strain of 5% at a frequency of 0.2 Hz for 1 hr to the cells. We found that the cells were strongly coupled to the nanofibers, but the strain reduced the coupling and induced remodeling of the actin cytoskeleton, which led to a better tissue formation. Our model can serve as a versatile tool in lung investigations such as in inhalation toxicology and therapy.     

Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers

Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.     

Molecular mapping of QTLs for wheat flag leaf senescence under water-stress

A segregating population from the cross between drought sensitive (Variant-2) and drought tolerant (Cham-6) genotypes was made to identify molecular markers linked to wheat (Triticum aestivum L.) flag leaf senescence under water-stress. From 38 random amplified polymorphic DNA (RAPD) primers, 25 inter-simple sequence repeat (ISSR) primers and 46 simple sequence repeat (SRR) primers, tested for polymorphism among parental genotypes and F2 population. Quantitative trait locus (QTL) for flag leaf senescence was associated with 1 RAPD marker (Pr9), 4 ISSR markers (Pr8, AD5, AD2 and AD3), and 1 SSR marker (Xgwm382) and explained 44, 50, 35, 31, 22 and 73 % phenotypic variation, respectively. The genetic distance between flag leaf senescence gene and Pr9 was 10.0 cM (LOD score 22.9). The markers Pr8, AD5, AD2 and AD3 had genetic distances of 10.5, 14.6, 15.6 and 18.1 cM, respectively (LOD scores 22.6, 17.8, 17.5 and 14.6). The genetic distance between Xgwm382 was 3.9 cM (LOD score 33.8). Therefore, the RAPD, ISSR and SSR markers linked to the QTL for the drought-induced flag leaf senescence can be further used in breeding for drought tolerance in wheat.