An in-depth and systematic literature review on the blockchain-based approaches for cloud computing

Cluster Computing - Cloud computing enables businesses to decrease the total costs by outsourcing their required services. Therefore, it provides a new challenge of data protection regarding...     

Altered levels of Salmonella DNA adenine methylase are associated with defects in gene expression, motility, flagellar synthesis, and bile resistance in the pathogenic strain 14028 but not in the laboratory strain LT2

Comparative genomic analysis has revealed limited strain diversity between Salmonella pathogenic and nonpathogenic isolates. Thus, some of the relative virulence and host-immune response disparities may be credited to differential gene regulation rather than gross differences in genomic content. Here we show that altered levels of Salmonella DNA adenine methylase (Dam) resulted in acute defects in virulence-associated gene expression, motility, flagellin synthesis, and bile resistance in the Salmonella pathogenic strain 14028 but not in avirulent laboratory strain LT2. The defects in motility exhibited by 14028 in response to altered Dam levels was not dependent on the presence of the regulatory protein, RpoS. The transitioning between flagellar types (phase variation) was also differentially regulated in 14028 versus LT2 in response to dam levels, resulting in distinct differences in flagellin expression states. These data suggest that differential gene regulation may contribute to the relative virulence disparities observed between Salmonella serovars that are closely related at the DNA level.     

The Effects of Soy Milk Enriched with Lactobacillus casei and Omega-3 on the Tibia and L5 Vertebra in Diabetic Rats: a Stereological Study

Bone fragility, despite relatively high BMD values, is an important complication related to insulin resistance and oxidative stress in diabetes mellitus type 1. The present study aimed to compare the effects of soy milk (SM), soy milk containing Lactobacillus casei (PSM), and soy milk enriched with Lactobacillus casei and omega-3 (OPSM) on the stereology of the tibia and vertebra, and antioxidant activity in type 1 diabetic rats. Sixty-five male Sprague Dawley rats were randomly assigned into 5 groups of 13 animals each. Diabetes was induced by a single injection of STZ (60 mg/kg); two control groups (non-diabetic: CN and diabetic: CD) were selected and then fed with 1 mL of distilled water. Three treatment groups were fed 1 ml of SM, PSM, and OPSM via intragastric gavage for 60 days. Treatment with SM, PSM, and OPSM significantly decreased (P < 0.05) the number of the osteoclasts in both tibia and L5 vertebra, and plasma alkaline phosphatase level. Also, the osteoblast number, calcium level, catalase activity, and total antioxidant capacity were increased in the SM, PSM, and OPSM groups compared to the STZ group. OPSM had the greatest effects on the stereological and biochemical parameters compared to the SM and PSM groups. Soy milk combination with Lactobacillus casei and omega-3 can ameliorate the stereological changes in the tibia and vertebra. In addition, this combination increased the antioxidant activity and improved the redox homeostasis in diabetic rats. These results suggest the potential role of soy milk containing Lactobacillus casei enriched with omega-3 in preventing and delaying osteoporosis in diabetic patients.

     

Supportive Role of Probiotic Strains in Protecting Rats from Ovariectomy-Induced Cortical Bone Loss

Osteoporosis is a major health problem that occurs as a result of an imbalance between bone formation and bone resorption. Different approaches have been established for treating osteoporosis. Recently, because of their health benefits and also low adverse reaction, probiotics have been receiving considerable attention. In this study, we compared the effectiveness of five probiotic strains, Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans, in protecting rats from ovariectomized (OVX)-induced bone loss. Forty-nine adult female Sprague-Dawley rats were allocated into seven groups as follows: group 1, control; group 2, OVX; group 3, OVX + Lactobacillus acidophilus; group 4, OVX + Lactobacillus casei; group 5, OVX + Bacillus coagulans; group 6, OVX + Bifidobacterium longum; and group 7, OVX + Lactobacillus reuteri. Probiotics were fed to OVX groups at the concentration of (1 × 10⁹ CFU/ml/day) for 4 weeks. Then, biochemical parameters, including vitamin D, calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP), were assessed. Dual-energy X-ray absorptiometry (DEXA) scans were used that assess bone mineral density (BMD), bone marrow concentration (BMC), and area of global, femur, spine, and tibia. Lactobacillus acidophilus and Lactobacillus casei significantly increased Ca and ALP and decreased P in treated groups. Lactobacillus casei, Lactobacillus reuteri, and Bifidobacterium longum increased vitamin D significantly. Lactobacillus acidophilus and Lactobacillus casei indicated the most effects on BMD. In terms of BMC, and bone area, Lactobacillus acidophilus, Lactobacillus reuteri, and Lactobacillus casei demonstrated the significant enhancement in OVX groups treated with. Among the probiotics used in this study, Lactobacillus acidophilus and Lactobacillus casei showed the most effects in terms of BMD, BMC, bone area, and biochemical parameters. It seems that probiotics effects on bone health are strain dependent, but further studies should be done to prove these findings.

     

The viral approach to breast cancer immunotherapy

Despite years of intensive research, breast cancer remains the leading cause of death in women worldwide. New technologies including oncolytic virus therapies, virus, and phage display are among the most powerful and advanced methods that have emerged in recent years with potential applications in cancer prevention and treatment. Oncolytic virus therapy is an interesting strategy for cancer treatment. Presently, a number of viruses from different virus families are under laboratory and clinical investigation as oncolytic therapeutics. Oncolytic viruses (OVs) have been shown to be able to induce and initiate a systemic antitumor immune response. The possibility of application of a multimodal therapy using a combination of the OV therapy with immune checkpoint inhibitors and cancer antigen vaccination holds a great promise in the future of cancer immunotherapy. Display of immunologic peptides on bacterial viruses (bacteriophages) is also increasingly being considered as a new and strong cancer vaccine delivery strategy. In phage display immunotherapy, a peptide or protein antigen is presented by genetic fusions to the phage coat proteins, and the phage construct formulation acts as a protective or preventive vaccine against cancer. In our laboratory, we have recently tested a few peptides (E75, AE37, and GP2) derived from HER2/neu proto-oncogene as vaccine delivery modalities for the treatment of TUBO breast cancer xenograft tumors of BALB/c mice. Here, in this paper, we discuss the latest advancements in the applications of OVs and bacterial viruses display systems as new and advanced modalities in cancer immune therapeutics.     

The Role of the Possible Receptors and Intracellular Pathways in Protective Effect of Exogenous Anandamide in Kindling Model of Epilepsy

In this research, the involvement of CB1 and TRPV1 receptors in the possible protective effects of anandamide were investigated in the kindling model of epilepsy. The basolateral amygdala of the rat brain was chosen to put stimulating electrodes. Semi-rapid kindling was induced by a repetitive sub-threshold stimulation for 5–9 consecutive days. There were seven groups, six of which were kindled and used for drug testing by intracerebroventricular (i.c.v.) microinjection. (i) Sham, (ii) control group received vehicles, (iii) anandamide (AEA; 100 ng/rat), (iv) capsazepine (TRPV1 antagonist; 100 ng/rat), (v) AM251 (CB1 antagonist; 100 ng/rat), (vi) AM251?+?anandamide, and (vii) capsazepine?+?anandamide. The after-discharge duration, seizure duration, and stage five duration were measured in rats. Moreover, the expressions of the extracellular signal-regulated kinase (ERK) and the cAMP responsive element binding (CREB) proteins in the hippocampus were also studied. The anandamide-treated group showed a significant decrease in seizure scores, while no change was shown in seizure scores in the capsazepine- and AM251-treated groups compared with the control group. Co-administrations of either capsazepine?+?AEA or AM251?+?AEA attenuated the protective effect of AEA against seizure. Furthermore, the group received AEA showed a decrease in the expressions of CREB and p-CREB possibly through the activation of the CB1 and TRPV1 receptors. Activation of CB1 and TRPV1 receptors might be involved in AEA anticonvulsant effect in kindling model of epilepsy. This effect could be due to suppression of CREB phosphorylation in hippocampal neurons.

     

HIV-1 Vpr Protein Enhances Proteasomal Degradation of MCM10 DNA Replication Factor through the Cul4-DDB1[VprBP] E3 Ubiquitin Ligase to Induce G2/M Cell Cycle Arrest

Human immunodeficiency virus type 1 Vpr is an accessory protein that induces G₂/M cell cycle arrest. It is well documented that interaction of Vpr with the Cul4-DDB1[VprBP] E3 ubiquitin ligase is essential for the induction of G₂/M arrest. In this study, we show that HIV-1 Vpr indirectly binds MCM10, a eukaryotic DNA replication factor, in a Vpr-binding protein (VprBP) (VprBP)-dependent manner. Binding of Vpr to MCM10 enhanced ubiquitination and proteasomal degradation of MCM10. G₂/M-defective mutants of Vpr were not able to deplete MCM10, and we show that Vpr-induced depletion of MCM10 is related to the ability of Vpr to induce G₂/M arrest. Our study demonstrates that MCM10 is the natural substrate of the Cul4-DDB1[VprBP] E3 ubiquitin ligase whose degradation is regulated by VprBP, but Vpr enhances the proteasomal degradation of MCM10 by interacting with VprBP.     

The Lck inhibitor,AMG-47a,blocks necroptosis and implicates RIPK1 in signalling downstream of MLKL

Necroptosis is a form of caspase-independent programmed cell death that arises from disruption of cell membranes by the mixed lineage kinase domain-like (MLKL) pseudokinase after its activation by the upstream kinases, receptor interacting protein kinase (RIPK)-1 and RIPK3, within a complex known as the necrosome. Dysregulated necroptosis has been implicated in numerous inflammatory pathologies. As such, new small molecule necroptosis inhibitors are of great interest, particularly ones that operate downstream of MLKL activation, where the pathway is less well defined. To better understand the mechanisms involved in necroptosis downstream of MLKL activation, and potentially uncover new targets for inhibition, we screened known kinase inhibitors against an activated mouse MLKL mutant, leading us to identify the lymphocyte-specific protein tyrosine kinase (Lck) inhibitor AMG-47a as an inhibitor of necroptosis. We show that AMG-47a interacts with both RIPK1 and RIPK3, that its ability to protect from cell death is dependent on the strength of the necroptotic stimulus, and that it blocks necroptosis most effectively in human cells. Moreover, in human cell lines, we demonstrate that AMG-47a can protect against cell death caused by forced dimerisation of MLKL truncation mutants in the absence of any upstream signalling, validating that it targets a process downstream of MLKL activation. Surprisingly, however, we also found that the cell death driven by activated MLKL in this model was completely dependent on the presence of RIPK1, and to a lesser extent RIPK3, although it was not affected by known inhibitors of these kinases. Together, these results suggest an additional role for RIPK1, or the necrosome, in mediating human necroptosis after MLKL is phosphorylated by RIPK3 and provide further insight into reported differences in the progression of necroptosis between mouse and human cells.Subject terms: Kinases, Necroptosis     

LncRNA‐miRNA network analysis across the Th17 cell line reveals biomarker potency of lncRNA NEAT1 and KCNQ1OT1 in multiple sclerosis

Differentiation of CD⁴⁺ T cells into Th17 cells is an important factor in the onset and progression of multiple sclerosis (MS) and Th17/Treg imbalance. Little is known about the role of lncRNAs in the differentiation of CD⁴⁺ cells from Th17 cells. This study aimed to analyse the lncRNA‐miRNAs network involved in MS disease and its role in the differentiation of Th17 cells. The lncRNAs in Th17 differentiation were obtained from {"type":"entrez-geo","attrs":{"text":"GSE66261","term_id":"66261"}}GSE66261 using the GEO datasets. Differential expression of lncRNAs in Th17 primary cells compared to Th17 effector cells was investigated by RNA‐seq analysis. Next, the most highlighted lncRNAs in autoimmune diseases were downloaded from the lncRNAs disease database, and the most critical miRNA was extracted by literature search. Then, the lncRNA‐miRNA interaction was achieved by the Starbase database, and the ceRNA network was designed by Cytoscape. Finally, using the CytoHubba application, two hub lncRNAs with the most interactions with miRNAs were identified by the MCODE plug‐in. The expression level of genes was measured by qPCR, and the plasma level of cytokines was analysed by ELISA kits. The results showed an increase in the expression of NEAT1, KCNQ1OT1 and RORC and a decrease in the expression of FOXP3. In plasma, an upregulation of IL17 and a downregulation of TGFB inflammatory cytokines were detected. The dysregulated expression of these genes could be attributed to relapsing‐remitting MS (RR‐MS) patients and help us understand MS pathogenesis better.