Superantigen as a Promising Immunotherapy Treatment against Cancer: A Review Article

Superantigens are toxins produced in hosts by some pathogenic microbes as a mechanism to sustain their pathogenicity. Superantigens are highly resistant to degradation by proteases enzyme, heat denaturation, and cause many dangerous diseases that in severe cases lead to death. Superantigens are atypical antigens that stimulate a profound proliferation of polyclonal T cells at low concentrations. All superantigens have a standard architecture even though they differ in amino acid sequences and are divided into two groups: endogenous superantigens and exogenous superantigens. The major histocompatibility complex molecules on antigen-presenting cells and T cell receptors on T cells are the major players in identifying foreign antigens. Superantigens can bind nonspecifically to both the major histocompatibility complex class II molecules and T cell receptors and form a trimolecular complex. Superantigens do not follow conventional antigens processing and presentation; they bind as intact macromolecules outside the antigen-binding groove of the major histocompatibility complex class II and to Vβ of T cells receptors. Thus, triggering an excessive release of proinflammatory cytokines, radiotherapy and chemotherapy often develop radio/drug resistance. Hence, cancer immunotherapy has been mainly considered as it instigates the patient’s immune system to fight cancer. Superantigens are one of the most potent T cell mitogens as 0.1 pg/ml is adequate to excite T lymphocytes. Accordingly, extensive in-vivo/in-vitro investigations have been conducted on the potential role of superantigens in eradicating tumors. The safety and effectiveness of superantigens as a cancer treatment have been verified in many clinical trials. Nevertheless, the vast inflammation after the potent T cell activation is known to promote diseases, including cancer. This paper reviews the potentiality of superantigen as an immunotherapy treatment against cancer

Superantigen as a Promising Immunotherapy Treatment against Cancer: A Review Article

Superantigens are toxins produced in hosts by some pathogenic microbes as a mechanism to sustain their pathogenicity. Superantigens are highly resistant to degradation by proteases enzyme, heat denaturation, and cause many dangerous diseases that in severe cases lead to death. Superantigens are atypical antigens that stimulate a profound proliferation of polyclonal T cells at low concentrations. All superantigens have a standard architecture even though they differ in amino acid sequences and are divided into two groups: endogenous superantigens and exogenous superantigens. The major histocompatibility complex molecules on antigen-presenting cells and T cell receptors on T cells are the major players in identifying foreign antigens. Superantigens can bind nonspecifically to both the major histocompatibility complex class II molecules and T cell receptors and form a trimolecular complex. Superantigens do not follow conventional antigens processing and presentation; they bind as intact macromolecules outside the antigen-binding groove of the major histocompatibility complex class II and to Vβ of T cells receptors. Thus, triggering an excessive release of proinflammatory cytokines, radiotherapy and chemotherapy often develop radio/drug resistance. Hence, cancer immunotherapy has been mainly considered as it instigates the patient’s immune system to fight cancer. Superantigens are one of the most potent T cell mitogens as 0.1 pg/ml is adequate to excite T lymphocytes. Accordingly, extensive in-vivo/in-vitro investigations have been conducted on the potential role of superantigens in eradicating tumors. The safety and effectiveness of superantigens as a cancer treatment have been verified in many clinical trials. Nevertheless, the vast inflammation after the potent T cell activation is known to promote diseases, including cancer. This paper reviews the potentiality of superantigen as an immunotherapy treatment against cancer

The Anti-Colon Cancer Effects of Probiotic and Postbiotic: A Review Article

Cancer, the leading cause of death worldwide, is a name for more than 100 types of diseases that evolved from normal cells and tissues in the body. Cancer cells fail to control cell proliferation and homeostasis due to mutations. These mutations arise from intensive environmental factors or alterations in genes that aid genetic instability. The immune system is the first defense line against cancer cells as it inhibits tumor development, growth, invasion, and metastasis. However, cancer cells develop many mechanisms to escape and avoid destruction by the immune system. Probiotics is a term used to describe the entire population of microorganisms that inhabit the human body. Probiotics and their metabolites stimulate the immune system and maintain gastrointestinal integrity. Postbiotics are bioactive products produced by probiotics. They facilitate cell-cell interaction and regulate signaling pathways. Postbiotics also promote health through different mechanisms. In this review, the anti-colon-cancer effects of probiotics and postbiotics have been investigated

Sequence analysis of sub-genotype D hepatitis B surface antigens isolated from Jeddah, Saudi Arabia

Little is known about the prevalence of HBV genotypes/sub-genotypes in Jeddah province, although the hepatitis B virus (HBV) was identified as the most predominant type of hepatitis in Saudi Arabia. To characterize HBV genotypes/sub-genotypes, serum samples from 15 patients with chronic HBV were collected and subjected to HBsAg gene amplification and sequence analysis. Phylogenetic analysis of the HBsAg gene sequences revealed that 11 (48%) isolates belonged to HBV/D while 4 (18%) were associated with HBV/C. Notably, a HBV/D sub-genotype phylogenetic tree identified that eight current isolates (72%) belonged to HBV/D1, whereas three isolates (28%) appeared to be more closely related to HBV/D5, although they formed a novel cluster supported by a branch with 99% bootstrap value. Isolates belonging to D1 were grouped in one branch and seemed to be more closely related to various strains isolated from different countries. For further determination of whether the three current isolates belonged to HBV/D5 or represented a novel sub-genotype, HBV/DA, whole HBV genome sequences would be required. In the present study, we verified that HBV/D1 is the most prevalent HBV sub-genotype in Jeddah, and identified novel variant mutations suggesting that an additional sub-genotype designated HBV/DA should be proposed. Overall, the results of the present HBsAg sequence analyses provide us with insights regarding the nucleotide differences between the present HBsAg/D isolates identified in the populace of Jeddah, Saudi Arabia and those previously isolated worldwide. Additional studies with large numbers of subjects in other areas might lead to the discovery of the specific HBV strain genotypes or even additional new sub-genotypes that are circulating in Saudi Arabia. Keywords: Hepatitis B virus, HBV sub-genotypes, HBV/D, HBsAg, Viral isolates, Population studie

Partial sequencing analysis of the <i>NS5B</i> region confirmed the predominance of hepatitis C virus genotype 1 infection in Jeddah, Saudi Arabia

<div><p>Chronic hepatitis C virus (HCV) infection and its progression are major health problems that many countries including Saudi Arabia are facing. Determination of HCV genotypes and subgenotypes is critical for epidemiological and clinical analysis and aids in the determination of the ideal treatment strategy that needs to be followed and the expected therapy response. Although HCV infection has been identified as the second most predominant type of hepatitis in Saudi Arabia, little is known about the molecular epidemiology and genetic variability of HCV circulating in the Jeddah province of Saudi Arabia. The aim of this study was to determine the dominance of various HCV genotypes and subgenotypes circulating in Jeddah using partial sequencing of the <i>NS5B</i> region. To the best of our knowledge, this is the first study of its kind in Saudi Arabia. To characterize HCV genotypes and subgenotypes, serum samples from 56 patients with chronic HCV infection were collected and subjected to partial <i>NS5B</i> gene amplification and sequence analysis. Phylogenetic analysis of the <i>NS5B</i> partial sequences revealed that HCV/1 was the predominant genotype (73%), followed by HCV/4 (24.49%) and HCV/3 (2.04%). Moreover, pairwise analysis also confirmed these results based on the average specific nucleotide distance identity: ±0.112, ±0.112, and ±0.179 for HCV/1, HCV/4, and HCV/3, respectively, without any interference between genotypes. Notably, the phylogenetic tree of the HCV/1 subgenotypes revealed that all the isolates (100%) from the present study belonged to the HCV/1a subgenotype. Our findings also revealed similarities in the nucleotide sequences between HCV circulating in Saudi Arabia and those circulating in countries such as Morocco, Egypt, Canada, India, Pakistan, and France. These results indicated that determination of HCV genotypes and subgenotypes based on partial sequence analysis of the <i>NS5B</i> region is accurate and reliable for HCV subtype determination.</p></div

Phylogenetic tree of HCV/3 NS5B gene sequences constructed using the neighbor-joining method (MEGA 6 Software).

<p>Tree shows the phylogenetic relationship of 14 HCV-NS5B reference sequences and 1 HCV-NS5B sequence from the present study. Reference HCV/3 subgenotype isolates are indicated by different colored branches along with their accession numbers and countries of origin. A closed red triangle represents the isolate from the present study. Bootstrap values indicate the major nodes as a percentage of the data obtained from 1000 replications.</p

HCV genome organization.

<p>The HCV genome consists of an open reading frame (ORF) of approximately 9400 bp, which is translated as a single polypeptide of approximately 3000 amino acids. The polypeptide is cleaved to produce 10 mature protein products, and the positions of the hypervariable regions 1 and 2 are shown [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178225#pone.0178225.ref008" target="_blank">8</a>].</p

Phylogenetic tree of HCV/4 NS5B gene sequences constructed using the neighbor-joining method (MEGA 6 Software).

<p>Tree shows the phylogenetic relationship of 18 HCV-NS5B reference sequences and 12 HCV-NS5B sequences from the present study. Reference HCV/4 subgenotype isolates are indicated by different colored branches along with their accession numbers and countries of origin. The 12 isolates from the present study are indicated by closed red triangles. Bootstrap values indicate the major nodes as a percentage of the data obtained from 1000 replications.</p

Phylogenetic tree for HCV/1 NS5B gene sequences constructed using the neighbor-joining method (MEGA 6 Software).

<p>Tree shows the phylogenetic relationship of 25 HCV-NS5B reference sequences and 36 HCV-NS5B sequences from this study. The reference HCV/1 subgenotype isolates are indicated by different colored branches along with their accession numbers and countries of origin. The 36 isolates from the present study are indicated by closed red triangles. Bootstrap values indicate the major nodes as a percentage of the data obtained from 1000 replications.</p

Amplification of the <i>NS5B</i> gene using nested PCR.

<p>“L” represents the 100-bp DNA ladder ranging from 100–1000 bp. Lanes 1, 2, 3, 4, and 5 contain DNA fragments of the <i>HCV-NS5B</i> gene, whereas lane 6 shows negative results.</p