Single-stranded guanine-rich DNA sequences can fold into four-stranded DNA structures called G-quadruplexes (G4s) that arise from the self-stacking of two or more guanine quartets. There has been considerable recent progress in the detection and mapping of G4 structures in the human genome and in biologically relevant contexts. These advancements, many of which align with predictions made previously in computational studies, provide important new insights into the functions of G4 structures in, for example, the regulation of transcription and genome stability, and uncover their potential relevance for cancer therapy.

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DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential.

Quadruplex-forming sequences are widely prevalent in human and other genomes, including bacterial ones. These sequences are over-represented in eukaryotic telomeres, promoters, and 5′ untranslated regions. They can form quadruplex structures, which may be transient in many situations in normal cells since they can be effectively resolved by helicase action. Mutated helicases in cancer cells are unable to unwind quadruplexes, which are impediments to transcription, translation, or replication, depending on their location within a particular gene. Small molecules that can stabilize quadruplex structures augment these effects and produce cell and proliferation growth inhibition. This article surveys the chemical biology of quadruplexes. It critically examines the major classes of quadruplex-binding small molecules that have been developed to date and the various approaches to discovering selective agents. The challenges of requiring (and achieving) small-molecule targeted selectivity for a particular quadrup...

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Quadruplex Nucleic Acids as Novel Therapeutic Targets.

The increasing incidence of drug-resistant pathogens has drawn the attention of the pharmaceutical and scientific communities towards studies on the potential antimicrobial activity of plant-derived substances, an untapped source of antimicrobial chemotypes, which are used in traditional medicine in different countries. The aim of this review is to provide recent insights regarding the possibilities of the most important natural antimicrobial compounds derived from plant sources containing a wide variety of secondary metabolites, which are useful as alternative strategies to control infectious diseases. This review will focus on natural plant products as a useful source of antimicrobial molecules, active in particular, on bacteria and fungi. When considering that many of these compounds, which have been used for centuries, are a source of new drugs and that there are ever-increasing technical breakthroughs, it can be envisaged that in the next years some different molecules discovered by ingenious screeni...

Plant-derived antimicrobial compounds: alternatives to antibiotics.

In some diseases, a very important role is played by the ability of bacteria to form multi-dimensional complex structure known as biofilm. The most common disease of the oral cavity, known as dental caries, is a top leader. Streptococcus mutans, one of the many etiological factors of dental caries, is a microorganism which is able to acquire new properties allowing for the expression of pathogenicity determinants determining its virulence in specific environmental conditions. Through the mechanism of adhesion to a solid surface, S. mutans is capable of colonizing the oral cavity and also of forming bacterial biofilm. Additional properties enabling S. mutans to colonize the oral cavity include the ability to survive in an acidic environment and specific interaction with other microorganisms colonizing this ecosystem. This review is an attempt to establish which characteristics associated with biofilm formation—virulence determinants of S. mutans—are responsible for the development of dental caries. In order to extend the knowledge of the nature of Streptococcus infections, an attempt to face the following problems will be made: Biofilm formation as a complex process of protein–bacterium interaction. To what extent do microorganisms of the cariogenic flora exemplified by S. mutans differ in virulence determinants “expression” from microorganisms of physiological flora? How does the environment of the oral cavity and its microorganisms affect the biofilm formation of dominant species? How do selected inhibitors affect the biofilm formation of cariogenic microorganisms?

https://link.springer.com/content/pdf/10.1007%2Fs10096-013-1993-7.pdf

The virulence of Streptococcus mutans and the ability to form biofilms.

Antimicrobial activities of the crude ethanolic extracts of five plants were screened against multidrug resistant (MDR) strains of Escherichia coli, Klebsiella pneumoniae and Candida albicans. ATCC strains of Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus bovis, Pseudimonas aeruginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae and Candida albicans were also tested. The strains that showed resistance against the maximum number of antibiotics tested were selected for an antibacterial assay. The MDR strains were sensitive to the antimicrobial activity of Acacia nilotica, Syzygium aromaticum and Cinnamum zeylanicum, whereas they exhibited strong resistance to the extracts of Terminalia arjuna and Eucalyptus globulus. Community-acquired infections showed higher sensitivity than the nosocomial infections against these extracts. The most potent antimicrobial plant was A. nilotica (MIC range 9.75-313µg/ml), whereas other

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Antimicrobial activity of five herbal extracts against multi drug resistant (MDR) strains of bacteria and fungus of clinical origin.

Interaction of mitoxantrone with human serum albumin: spectroscopic and molecular modeling studies.

Dental caries is one of the most prevalent diseases in humans, second only to the common cold. It causes irreversible damage to the grinding machinery involved in the intake of food and hence causes great distress. The changes in the homeostasis of the oral cavity with an overgrowth of Streptococcus mutans is recognized as the primary cause of the disease. Most treatments are now aimed at either elimination of this bacterium or suppression of its virulence. S. mutans strongly adheres and releases acids by the fermentation of carbohydrates, leading to the demineralization of the tooth. This attachment is mediated mostly by the interaction of surface proteins and bacterial polysaccharides. Ambiguities in the basic treatment of dental caries, such as the use of fluoride and antibiotics, vitalize the deployment of probiotic therapies for its cure. The growing research in herbal treatments has led to the discovery of various phytochemicals to limit the virulence of S. mutans. This review focuses on the properties of S. mutans in cariogenicity and outlines ways to combat dental caries.

Dental caries: from infection to prevention.

Objectives: The present study focused on isolation, characterization and evaluation of purified compounds from Morus alba against Streptococcus mutans biofilm formation. Methods: The effect of crude extract from M. alba leaves was evaluated against oral pathogens, chiefly S. mutans. MICs were determined by the microdilution method. The compound was purified by employing silica gel chromatography and critically analysed with GC‐MS, NMR and IR spectroscopy. The S. mutans traits of adherence and biofilm formation were assessed at sub-MIC concentrations of the crude extract and purified compound. Both water-soluble and alkali-soluble polysaccharide were estimated to determine the effect of the purified compound on the extracellular polysaccharide secretion of S. mutans. Its effect on biofilm architecture was also investigated with the help of confocal microscopy. Results: The purified compound of M. alba showed an 8-fold greater reduction of MIC against S. mutans than the crude extract (MICs, 15.6 and 125 mg/L, respectively). The extract strongly inhibited biofilm formation of S. mutans at its active accumulation and plateau phases. The purified compound led to a 22% greater reduction in alkali-soluble polysaccharide than in water-soluble polysaccharide. The purified compound was found to be 1-deoxynojirimycin (DNJ). Confocal microscopy revealed that DNJ distorts the biofilm architecture of S. mutans. Conclusions: The whole study reflects a prospective role of DNJ as a therapeutic agent by controlling the overgrowth and biofilm formation of S. mutans.

Novel anti-adherence activity of mulberry leaves: inhibition of Streptococcus mutans biofilm by 1-deoxynojirimycin isolated from Morus alba

Mutations in the cytochrome p450 (CYP)21A2 gene, which encodes the enzyme steroid 21-hydroxylase, cause the majority of cases in congenital adrenal hyperplasia, an autosomal recessive disorder. To date, more than 100 CYP21A2 mutations have been reported. These mutations can be associated either with severe salt-wasting or simple virilizing phenotypes or with milder nonclassical phenotypes. Not all CYP21A2 mutations have, however, been characterized biochemically, and the clinical consequences of these mutations remain unknown. Using the crystal structure of its bovine homolog as a template, we have constructed a humanized model of CYP21A2 to provide comprehensive structural explanations for the clinical manifestations caused by each of the known disease-causing missense mutations in CYP21A2. Mutations that affect membrane anchoring, disrupt heme and/or substrate binding, or impair stability of CYP21A2 cause complete loss of function and salt-wasting disease. In contrast, mutations altering the transmembrane region or conserved hydrophobic patches cause up to a 98% reduction in enzyme activity and simple virilizing disease. Mild nonclassical disease can result from interference in oxidoreductase interactions, salt-bridge and hydrogen-bonding networks, and nonconserved hydrophobic clusters. A simple in silico evaluation of previously uncharacterized gene mutations could, thus, potentially help predict the often diverse phenotypes of a monogenic disorder.

https://www.pnas.org/content/pnas/110/7/2605.full.pdf

Barira Islam

Papers

Antimicrobial activity of five herbal extracts against multi drug resistant (MDR) strains of bacteria and fungus of clinical origin.

Interaction of mitoxantrone with human serum albumin: spectroscopic and molecular modeling studies.

Dental caries: from infection to prevention.

Novel anti-adherence activity of mulberry leaves: inhibition of Streptococcus mutans biofilm by 1-deoxynojirimycin isolated from Morus alba

Structure-phenotype correlations of human CYP21A2 mutations in congenital adrenal hyperplasia.