Peptides with Dual Antimicrobial-Anticancer Activity Derived from the N-terminal Region of H. pylori Ribosomal Protein L1 (RpL1)

International Journal of Peptide Research and Therapeutics - Whereas the traditional approaches of cancer therapy including radiotherapy, chemotherapy, and immunotherapy have failed to properly...     

The survivin molecule as a double-edged sword in cellular physiologic and pathologic conditions and its role as a potential biomarker and therapeutic target in cancer

Survivin is a member of the family of apoptosis inhibitory proteins with increased expression level in most cancerous tissues. Evidence shows that survivin plays regulatory roles in proliferation or survival of normal adult cells, principally vascular endothelial cells, T lymphocytes, primitive hematopoietic cells, and polymorphonuclear neutrophils. Survivin antiapoptotic role is, directly and indirectly, related to caspase proteins and shows its role in cell division through the chromosomal passenger complex. Survivin contains many genetic polymorphisms that the role of some variations has been proven in several cancers. The −31G/C polymorphism is one of the most important survivin mutations which is located in the promoter region on a CDE/CHR motif. This polymorphism can upregulate the survivin messenger RNA. In addition, its allele C can increase the risk of cancers in 1.27-fold than allele G. Considering the fundamental role of survivin in different cancers, this protein could be considered as a new therapeutic target in cancer treatment. For this purpose, various strategies have been designed including the prevention of survivin expression through inhibition of mRNA translation using antagonistic molecules, inhibition of survivin gene function through small inhibitory molecules, gene therapy, and immunotherapy. In this study, we describe the structure, played roles in physiological and pathological states and genetic polymorphisms of survivin. Finally, the role of survivin as a potential target in cancer therapy given challenges ahead has been discussed.     

Usefulness of rpoB Gene Sequencing for Identification of Afipia and Bosea Species, Including a Strategy for Choosing Discriminative Partial Sequences

Bacteria belonging to the genera Afipia and Bosea are amoeba-resisting bacteria that have been recently reported to colonize hospital water supplies and are suspected of being responsible for intensive care unit-acquired pneumonia. Identification of these bacteria is now based on determination of the 16S ribosomal DNA sequence. However, the 16S rRNA gene is not polymorphic enough to ensure discrimination of species defined by DNA-DNA relatedness. The complete rpoB sequences of 20 strains were first determined by both PCR and genome walking methods. The percentage of homology between different species ranged from 83 to 97% and was in all cases lower than that observed with the 16S rRNA gene; this was true even for species that differed in only one position. The taxonomy of Bosea and Afipia is discussed in light of these results. For strain identification that does not require the complete rpoB sequence (4,113 to 4,137 bp), we propose a simple computerized method that allows determination of nucleotide positions of high variability in the sequence that are bordered by conserved sequences and that could be useful for design of universal primers. A fragment of 740 to 752 bp that contained the most highly variable area (positions 408 to 420) was amplified and sequenced with these universal primers for 47 strains. The variability of this sequence allowed identification of all strains and correlated well with results of DNA-DNA relatedness. In the future, this method could be also used for the determination of variability “hot spots” in sets of housekeeping genes, not only for identification purposes but also for increasing the discriminatory power of sequence typing techniques such as multilocus sequence typing.     

Multi-Pronged Interactions Underlie Inhibition of α-Synuclein Aggregation by β-Synuclein

The intrinsically disordered protein β-synuclein is known to inhibit the aggregation of its intrinsically disordered homolog, α-synuclein, which is implicated in Parkinson's disease. While β-synuclein itself does not form fibrils at the cytoplasmic pH?7.4, alteration of pH and other environmental perturbations are known to induce its fibrilization. However, the sequence and structural determinants of β-synuclein inhibition and self-aggregation are not well understood. We have utilized a series of domain-swapped chimeras of α-synuclein and β-synuclein to probe the relative contributions of the N-terminal, C-terminal, and the central non-amyloid-β component domains to the inhibition of α-synuclein aggregation. Changes in the rates of α-synuclein fibril formation in the presence of the chimeras indicate that the non-amyloid-β component domain is the primary determinant of self-association leading to fibril formation, while the N- and C-terminal domains play critical roles in the fibril inhibition process. Our data provide evidence that all three domains of β-synuclein together contribute to providing effective inhibition, and support a model of transient, multi-pronged interactions between IDP chains in both processes. Inclusion of such multi-site inhibitory interactions spread over the length of synuclein chains may be critical for the development of therapeutics that are designed to mimic the inhibitory effects of β-synuclein.     

The PI3K/Akt signaling axis in Alzheimer’s disease: a valuable target to stimulate or suppress?

Among the long list of age-related complications, Alzheimer’s disease (AD) has the most dreadful impact on the quality of life due to its devastating effects on memory and cognitive abilities. Although a plausible correlation between the phosphatidylinositol 3-kinase (PI3K) signaling and different processes involved in neurodegeneration has been evidenced, few articles reviewed the task. The current review aims to unravel the mechanisms by which the PI3K pathway plays pro-survival roles in normal conditions, and also to discuss the original data obtained from international research laboratories on this topic. Responses to questions on how alterations of the PI3K/Akt signaling pathway affect Tau phosphorylation and the amyloid cascade are given. In addition, we provide a general overview of the association between oxidative stress, neuroinflammation, alterations of insulin signaling, and altered autophagy with aberrant activation of this axis in the AD brain. The last section provides a special focus on the therapeutic possibility of the PI3K/Akt/mTOR modulators, either categorized as chemicals or herbals, in AD. In conclusion, determining the correct timing for the administration of the drugs seems to be one of the most important factors in the success of these agents. Also, the role of the PI3K/Akt signaling axis in the progression or repression of AD widely depends on the context of the cells; generally speaking, while PI3K/Akt activation in neurons and neural stem cells is favorable, its activation in microglia cells may be harmful.     

Twelve year experience of laparoscopic gastric plication in morbid obesity: development of the technique and patient outcomes

ABSTRACT: BACKGROUND: Laparoscopic Gastric Plication (LGP) is a new restrictive bariatric surgery, previously introduced by the author. The aim of this study is to explain the modifications and to present the 12-year experience, regarding early and long term results, complications and cost. METHODS: We used LGP for morbid obesity during the past 12 years. Anterior plication (10 cases), one-row bilateral plication while right gastroepiploic artery included (42 cases), and excluded from the plication (104 cases) and two-row plication (644 cases). The gastric greater curvature was plicated using 2/0 prolen from fundus at the level of diaphragm preserving the His angle to just proximal to the pylorus. The anatomic and functional volume of stomach was 50cc and 25cc respectively in two-row method. Ordered postop visits also included evaluation of weight loss, complications, change of diet and control of exercise. RESULTS: LGP was performed in 800 cases (mean age: 27.5, range: 12 to 65 years, nine under 18). Female to male ratio was 81% to 19% and average BMI was 42.1 (35-59). The mean excess weight loss (EWL) was 70% (40% to 100%) after 24 months and 55% (28% to 100%) after 5 years following surgery. 134 cases (16.7%) did not completed long term follow-up. The average time of follow up was 5 years (1 month to 12 years). 5.5% and 31% of cases complained from weight regain respectively during 4 and 12 years after LGP. The mean time of operation was 72 (49--152) minutes and average hospitalization time was 72 hours (24 hours to 45 days). The cost of operation was 2000 $ less than gastric banding or sleeve and 2500 $ less than gastric bypass. Eight patients out of 800 cases (1%) required reoperation due to complications like: micro perforation, obstruction and vomiting following adhesion of His angle. Other complications included hepatitis pneumonia, self-limiting intra-abdominal bleeding and hypocalcaemia. CONCLUSION: The percentage of EWL in this technique is comparable to other restrictive methods. The technique is safe with 1.6% complication (1% reoperated), and 31% regain during 12 years. The cost of operation is less than the other methods.     

Evaluation of Estrogenic Activity of Licorice Species in Comparison with Hops Used in Botanicals for Menopausal Symptoms

The increased cancer risk associated with hormone therapies has encouraged many women to seek non-hormonal alternatives including botanical supplements such as hops (Humulus lupulus) and licorice (Glycyrrhiza spec.) to manage menopausal symptoms. Previous studies have shown estrogenic properties for hops, likely due to the presence of 8-prenylnarigenin, and chemopreventive effects mainly attributed to xanthohumol. Similarly, a combination of estrogenic and chemopreventive properties has been reported for various Glycyrrhiza species. The major goal of the current study was to evaluate the potential estrogenic effects of three licorice species (Glycyrrhiza glabra, G. uralensis, and G. inflata) in comparison with hops. Extracts of Glycyrrhiza species and spent hops induced estrogen responsive alkaline phosphatase activity in endometrial cancer cells, estrogen responsive element (ERE)-luciferase in MCF-7 cells, and Tff1 mRNA in T47D cells. The estrogenic activity decreased in the order H. lupulus > G. uralensis > G. inflata > G. glabra. Liquiritigenin was found to be the principle phytoestrogen of the licorice extracts; however, it exhibited lower estrogenic effects compared to 8-prenylnaringenin in functional assays. Isoliquiritigenin, the precursor chalcone of liquiritigenin, demonstrated significant estrogenic activities while xanthohumol, a metabolic precursor of 8-prenylnaringenin, was not estrogenic. Liquiritigenin showed ERβ selectivity in competitive binding assay and isoliquiritigenin was equipotent for ER subtypes. The estrogenic activity of isoliquiritigenin could be the result of its cyclization to liquiritigenin under physiological conditions. 8-Prenylnaringenin had nanomolar estrogenic potency without ER selectivity while xanthohumol did not bind ERs. These data demonstrated that Glycyrrhiza species with different contents of liquiritigenin have various levels of estrogenic activities, suggesting the importance of precise labeling of botanical supplements. Although hops shows strong estrogenic properties via ERα, licorice might have different estrogenic activities due to its ERβ selectivity, partial estrogen agonist activity, and non-enzymatic conversion of isoliquiritigenin to liquiritigenin.     

miR-9: From function to therapeutic potential in cancer

Malignant neoplasms are regarded as the main cause of death around the world; hence, many research studies were conducted to further perceive molecular mechanisms, treatment, and cancer prognosis. Cancer is known as a major factor for health-related problems in the world. The main challenges associated with these diseases are prompt diagnosis, disease remission classification and treatment status forecast. Therefore, progressing in such areas by developing new and optimized methods with the help of minimally invasive biological markers such as circular microRNAs (miRNAs) can be considered important. miRNA interactions with target genes have specified their role in development, apoptosis, differentiation, and proliferation and also, confirm direct miRNA function in cancer. Different miRNAs expression levels in various types of malignant neoplasms have been observed to be associated with prognosis of various carcinomas. miR-9 seems to implement opposite practices in different tissues or under various cancer incidences by influencing different genes. Aberrant miR-9 levels have been observed in many cancer types. Therefore, we intended to investigate the precise role of miR-9 in patients with malignant neoplasms. To this end, in this study, we attempted to examine different studies to clarify the overall role of miR-9 as a prognostic marker in several human tumors. The presented data in this study can help us to find the novel therapeutic avenues for treatment of human cancers.     

Arabic version of the Geriatric Oral Health Assessment Index

Objectives: The purpose of this study was to translate the original English version of the Geriatric Oral Health Assessment Index (GOHAI) into an Arabic version, and to test the validity and reliability of the translated instrument (GOHAI‐Ar) for use among the elderly in Saudi Arabia. Methods: The 12‐item GOHAI was translated into Arabic using the back‐translation technique and performing a preliminary test to determine the comprehensibility and readability of the Arabic language version. A total of 156 elderly patients answered the questionnaire, and underwent a clinical examination by one calibrated dentist. Information on subjects’ socio‐demographic background and oral health conditions was collected. Convergent validity was evaluated by identifying the associations between perceived oral health status, general health status, perceived need for dental care and GOHAI‐Ar scores. Discriminant validity was examined by comparing the GOHAI‐Ar scores and six oral health parameters. Internal consistency was measured by Cronbach’s alpha. Test–retest reliability was assessed by intra‐class correlation coefficient (ICC) and weighted kappa. Factor structure of GOHAI‐Ar was evaluated using principal component factor analysis. Results: The mean GOHAI‐Ar was 32.1 (SD 12.2; range 11–59). Mean GOHAI‐Ar scores were higher for the elderly who rated their oral and general health as good. Subjects with perceived dental treatment needs had a lower mean GOHAI‐Ar score than those without any such needs. The caries experience, number of missing teeth, OHI‐S score, number of pathologically mobile teeth and number of oral lesions were negatively correlated with the GOHAI‐Ar score. The Cronbach’s alpha (0.93) indicated a high degree of internal consistency and homogeneity between items. The ICC for GOHAI‐Ar was 0.95, the weighted kappa coefficient for individual items varied between 0.42 and 0.71, and the correlation coefficients for the 12 items were above 0.70. Factor analysis didn’t support the expected dimensions of the index, and only one factor was found at eigenvalue greater than 1. Conclusions: The findings suggest an excellent reliability and validity of GOHAI‐Ar. Further research is needed to assess the value of this instrument in oral health‐related quality of life studies in Arabic elderly population.     

Partial rpoB gene sequencing for identification of Leptospira species

The usual target for sequence-based identification of Leptospira species is the 16S rRNA gene. However, because the 16S rRNA gene is not polymorphic enough, it is necessary to sequence a 1500 bp segment of this gene for accurate identification. Based on the alignment of previously determined rpoB of three Leptospira strains, we designed and tested a primer pair that enabled us to amplify and sequence a 600 bp segment of Leptospira rpoB. This segment was species-specific for the 16 species tested, but was unable to separate Leptospira interrogans serovars accurately. For the 11 L. interrogans serovars tested, only seven genotypes could be determined. We thus think that analysis of partial rpoB may be useful as an initial screening test for the identification of a new isolate of Leptospira and detection or identification of Leptospira in clinical or environmental samples, but not for serovar determination.