Escherichia coli is the most preferred microorganism to express heterologous proteins for therapeutic use, as around 30% of the approved therapeutic proteins are currently being produced using it as a host. Owing to its rapid growth, high yield of the product, cost-effectiveness, and easy scale-up process, E. coli is an expression host of choice in the biotechnology industry for large-scale production of proteins, particularly non-glycosylated proteins, for therapeutic use. The availability of various E. coli expression vectors and strains, relatively easy protein folding mechanisms, and bioprocess technologies, makes it very attractive for industrial applications. However, the codon usage in E. coli and the absence of post-translational modifications, such as glycosylation, phosphorylation, and proteolytic processing, limit its use for the production of slightly complex recombinant biopharmaceuticals. Several new technological advancements in the E. coli expression system to meet the biotechnology industry requirements have been made, such as novel engineered strains, genetically modifying E. coli to possess capability to glycosylate heterologous proteins and express complex proteins, including full-length glycosylated antibodies. This review summarizes the recent advancements that may further expand the use of the E. coli expression system to produce more complex and also glycosylated proteins for therapeutic use in the future.

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The gut microbiota is often affected by the dietary and lifestyle habits of the host, resulting in a better efficacy that favors energy harvesting from the consumed food. Our objective was to characterize the composition of gut microbiota in adult Saudis and investigate possible association with lifestyle and dietary practices. Feces from 104 Saudi volunteers (48% males) were tested for microbiota by sequencing the V3-V4 region of bacterial 16S ribosomal RNA (rRNA). For all participants, data were collected related to their lifestyle habits and dietary practices. The relative abundance (RA) of Fusobacteria was significantly higher in normal weight Saudis (P = 0.005, false discovery rate-FDR = 0.014). Individuals who consumed more coffee presented marginally significant more RA of Fusobacteria (P = 0.02, FDR = 0.20) in their gut microbiota compared to those reporting low or no coffee intake, but the RA of Fusobacteria was significantly higher in smokers compared to nonsmokers (P = 0.009, FDR = 0.027). The RA of Fusobacteria was also significantly higher in those reporting daily consumption of bread (P = 0.005, FDR = 0.015). At the species level, the gut microbiota of people who consumed coffee was dominated by Bacteroides thetaiotaomicron followed by Phascolarctobacterium faecium and Eubacterium rectale. Similarly, the gut microbiota of smokers was also enriched by B. thetaiotaomicron and Lactobacillus amylovorus. Smoking cessation, bread and coffee consumption induce changes in the intestinal microbial composition of Saudis.

Host Defense Peptides (HDPs) are small cationic peptides found in several organisms. They play a vital role in innate immunity response and immunomodulatory stimulation. This investigation was designed to study the antimicrobial activities of β-defensin peptide-4 (sAvBD-4) and 10 (sAvBD-4) derived from chickens against pathogenic organisms including bacteria and fungi. Ten bacterial strains and three fungal species were used in investigation. The results showed that the sAvBD-10 displayed a higher bactericidal potency against all the tested bacterial strains than that of sAvBD-4. The exhibited bactericidal activity was significant against almost the different bacterial strains at different peptide concentrations except for that of Pseudomonas aeruginosa (P. aeruginosa) and Streptococcus bovis (Str. bovis) strains where a moderate effect was noted. Both peptides were effective in the inactivation of fungal species tested yielding a killing rate of up to 95%. The results revealed that the synthetic peptides were resistant to salt at a concentration of 50 mM NaCl. However, they lost antimicrobial potency when applied in the presence of high salt concentrations. Based on blood hemolysis studies, a little hemolytic effect was showed in the case of both peptides even when applied at high concentrations. The data obtained from this study indicated that synthetic avian peptides exhibit strong antibacterial and antifungal activity. In conclusion, future work and research should be tailored to a better understanding of the mechanisms of action of those peptides and their potential use in the pharmaceutical industry to help reduce the incidence and impact of infectious agent and be marketed as a naturally occurring antibiotic.

Obesity is a chronic disorder that is associated with body mass index (BMI) of greater or equal to 30 kg/m2. The prevalence of obesity in the Kingdom of Saudi Arabia (KSA) is increasing at an alarming rate and is expected to reach 41% in men and up to 78% in women by 2022. Since chemokines are associated with involuntary weight loss, the objective of this study was to elucidate their association with BMI among Saudis. A questionnaire was used to collect information about diet, health conditions, and demographics from 15 men and 16 women who participated in the study. BMI was calculated based on clinical measurements and participants were classified according to their BMI category as: normal, underweight, overweight, or obese. Serum samples were collected for a multiplex assay using the Human Chemokine Magnetic 30-plex panel. The serum concentration of either the monokine induced by gamma interferon (MIG) or the CXC-motif chemokine ligand 9 (CXCL-9) was significantly increased in obese men (P = 0.0194) and women (P = 0.043) as compared to underweight men and women, respectively. However, the serum levels of other chemokines were not significantly different among the groups. We found that MIG levels are differentially regulated in serum, based on individuals’ BMI.

Tumor comprises of heterogeneous population of cells where not all the disseminated cancer cells have the prerogative and “in-build genetic cues” to form secondary tumors. Cells with stem like properties complemented by key signaling molecules clearly have shown to exhibit selective growth advantage to form tumors at distant metastatic sites. Thus, defining the role of cancer stem cells (CSC) in tumorigenesis and metastasis is emerging as a major thrust area for therapeutic intervention. Precise relationship and regulatory mechanisms operating in various signal transduction pathways during cancer dissemination, extravasation and angiogenesis still remain largely enigmatic. How the crosstalk amongst circulating tumor cells (CTC), epithelial mesenchymal transition (EMT) process and CSC is coordinated for initiating the metastasis at secondary tissues, and during cancer relapse could be of great therapeutic interest. The signal transduction mechanisms facilitating the dissemination, infiltration of CSC into blood stream, extravasations, progression of metastasis phenotype and angiogenesis, at distant organs, are the key pathologically important vulnerabilities being elucidated. Therefore, current new drug discovery focus has shifted towards finding “key driver genes” operating in parallel signaling pathways, during quiescence, survival and maintenance of stemness in CSC. Understanding these mechanisms could open new horizons for tackling the issue of cancer recurrence and metastasis-the cause of ~90% cancer associated mortality. To design futuristic & targeted therapies, we propose a multi-pronged strategy involving small molecules, RNA interference, vaccines, antibodies and other biotechnological modalities against CSC and the metastatic signal transduction cascade.

Effective diagnostic, prognostic and therapeutic biomarkers can help in tracking disease progress, predict patients’ survival, and considerably affect the drive for successful clinical management. The present review aims to determine how the metastatic-linked protein anterior gradient homologue 2 (AGR2) operates to affect cancer progression, and to identify associated potential diagnostic, prognostic and therapeutic biomarkers, particularly in central nervous system (CNS) tumors. Studies that show a high expression level of AGR2, and associate the protein expression with the resilience to chemotherapeutic treatments or with poor cancer survival, are reported. The primary protein structures of the seven variants of AGR2, including their functional domains, are summarized. Based on experiments in various biological models, this review shows an orchestra of multiple molecules that regulate AGR2 expression, including a feedback loop with p53. The AGR2-associated molecular functions and pathways including genomic integrity, proliferation, apoptosis, angiogenesis, adhesion, migration, stemness, and inflammation, are detailed. In addition, the mechanisms that can enable the rampant oncogenic effects of AGR2 are clarified. The different strategies used to therapeutically target AGR2-positive cancer cells are evaluated in light of the current evidence. Moreover, novel associated pathways and clinically relevant deregulated genes in AGR2 high CNS tumors are identified using a meta-analysis approach.

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