Computational Biology Analysis of COVID-19 Receptor-Binding Domains: A Target Site for Indocyanine Green Through Antimicrobial Photodynamic Therapy

Introduction: The receptor-binding domain (RBD) in SARS-CoV-2 binds strongly to angiotensin-converting enzyme 2 (ACE2) receptors and causes coronavirus disease 2019 (COVID-19). Antimicrobial photodynamic therapy (aPDT) is a well-established treatment option for the treatment of several viral infections. This in silico study was conducted to target the RBD of SARS-CoV-2 as a target site for aPDT.Methods: SARS-CoV-2-RBD was selected as a novel target for indocyanine green (ICG) as a photosensitizer during aPDT to exploit its molecular modeling, hierarchical nature of protein structure, and physico-chemical properties using several bioinformatic tools. The binding mode of the RBD to ICG was assessed via protein-ligand docking.Results: The results of a computational biology analysis revealed that SARS-CoV-2-RBD has 223 amino acids with a molecular weight of 25098.40 Da. RBD is most similar to 6W41 with an E-value of 4e-167, an identity of 100%, and a query cover of 100%. The aliphatic index of the RBD protein sequences was 71.61, suggesting that the protein is stable in a broad spectrum of temperatures. The predicted structure of RBD showed that it is a protein with a positive charge and a random coil structure (69.51%). Four ligands were modeled in this entry, including one N-acetyl-D-glucosamine (NAG), one glycerol (GOL), and two sulfate ions (SO4), to which ICG desires to bind in the molecular docking analysis.Conclusion: Molecular modeling and simulation analysis showed that SARS-CoV-2-RBD could be a substrate for binding to ICG during aPDT to control the spread of COVID-19

The Photomodulation Activity of Metformin Against Oral Microbiome

Periodontitis is one of the most common inflammatory diseases of the periodontium, which results in the inflammatory destruction of supporting structures around teeth and is closely associated with the development of systemic disease. Due to a wide variety of antibiotic resistance periodontopathic bacteria, photodynamic therapy (PDT) is a non-invasive adjunctive therapeutic modality that is capable of destroying the whole range of microbes. Metformin (Metf) is an antidiabetic drug, and recent studies suggest that cancer patients who receive Metf and are exposed to radiotherapy and chemotherapy show better outcomes. Our surveys in this review introduce Metf as a potent stimulus in increasing the efficacy of PDT in the induction of destruction in microbial cells

Clinical Approach of High Technology Techniques for Control and Elimination of Endodontic Microbiota

The main goal in endodontic treatment is to eradicate or at least reduce intraradicular microbial population to levels that are more compatible with periapical lesions healing process. Since endodontic infections are polymicrobial in nature, intraradicular survival of endodontic microbiota and their pathogenic properties are influenced by a combination of their virulence factors. The purpose of this article is to review the endodontic microbiota and their respective virulence attributes, as well as perform a literature review of the effects of disinfection procedures in the treatment of endodontic infections to gain best practices. Conventional technique for root canal preparation includes mechanical debridement and application of antimicrobial irrigants. Recently, laser irradiation has been used to enhance the results of root canal treatment through its thermal effect. To reduce thermal side effects, laser activated irrigation (LAI) and photon induced photoacoustic streaming (PIPS) were introduced. Antimicrobial photodynamic therapy (aPDT) by photochemical reaction uses light at a specific wavelength to activate a nontoxic photosensitizer (PS) in the presence of oxygen to produce cytotoxic products. Different PSs are used in dentistry including methylene blue (MB), toluidine blue O (TBO), indocyanine green (ICG) and curcumin. Among different options, ICG could be the best choice due to its peak absorption at wavelength of 808 nm, which coincides with the commercial diode laser devices. Also, this wavelength has more penetration depth compared to other wavelengths used in aPDT

Antimicrobial Photodynamic Therapy: An Effective Alternative Approach to Control Bacterial Infections

Introduction: The purpose of this review was to evaluate the available literature for in vitro and in vivo effectiveness of antimicrobial Photodynamic therapy (aPDT) in the field of bacteriology.Methods: A review of the relevant articles carried out in PubMed and Scopus to determine the efficiency of aPDT used in the reduction of microbial infection. Thirty-one relevant documents retrieved from PubMed, Scopus by inserting “antimicrobial photodynamic therapy” and “bacterial infection” and “photodynamic therapy” keywords.Results: According to different results, aPDT can be used as an adjuvant for the treatment of infectious diseases. The use of photosensitizer methylene blue, toluidine blue O (TBO), indocyanine green with light diode laser centered at (630±10 nm) and (650±10 nm) wavelengths have been shown to have significant results for the treatment of infectious diseases and bactericidal propertiesConclusion: These findings suggest that, aPDT can be an efficient method in the treatment of localized and superficial infections

Oropharyngeal candidiasis and resistance to antifungal drugs in patients receiving radiation for head and neck cancer

BACKGROUND: Oropharyngeal candidiasis is a common infection in patient receiving radiotherapy for head and neck cancer. Accurate and rapid identification of candida species is very important in clinical laboratory, because the incidence of candidiasis continues to rise after radiotherapy. The genus Candida has about 154 species that show different level of resistance to antifungal drugs and have high degree of phenotypic similarity. The aim of this study was to investigate oral yeast colonization and infection and resistance to antifungal drugs in these patients. METHODS: Thirty patients receiving a 6-week course of radiation therapy for treatment of head and neck cancer at the Oncology Unit in Shafa Hospital, in 2008, were enrolled in the study. Specimens from patients were cultured weekly for Candida. All isolates were plated on CHROM agar and RPMI-based medium. They were subcultured and submitted for antifungal susceptibility testing (nystatin, fluconazole, clotrimazole and ketoconazole) and molecular typing. RESULTS: Infection (clinical and microbiological evidence) occurred in 50% of the patients and Candida colonization (only microbiological evidence) occurred in 70% of subjects in the first week. Candida albicans alone was isolated in 94.9% of patient visits with positive cultures. Candida tropicalis was isolated from 5.1% of patient visits with positive cultures. All isolates were susceptible to nystatin, but did not respond to the other antifungal drugs CONCLUSIONS: The irradiation-induced changes of the intraoral environment such as xerostomia lead to increased intraoral colonization by Candida species. All yeast isolates were susceptible to nystatin. Thus prophylactic therapy with nystatin should be considered for these patients. KEY WORDS: Oropharyngeal candidiasis, radiation, colonization, antifungal drugs, cance

Can Antimicrobial Photodynamic Therapy (aPDT) Enhance the Endodontic Treatment?

  In order to achieve a long-lasting effect, one of the main goals in root canal treatment is to eliminate the endodontic bacteria. Conventional chemomechanical debridement is considered as the basic treatment in root canal therapy, but adjunctive techniques such as antimicrobial photodynamic therapy (aPDT) can also be helpful. The aim of this study was to evaluate reports in the scientific literature that used different photosensitizers (PSs) for bacterial reduction. The literature search was conducted using databases including PubMed, Scopus, and Google Scholar with the keywords “photodynamic therapy,” “antimicrobial photodynamic therapy,” or “photoactivated disinfection” and “endodontic,” “Enterococcus faecalis,” or “root canal treatment,” from 2000 to 2015. By evaluating different studies, it was concluded that aPDT should be applied in combination with conventional mechanical debridement and irrigants. However, it is also important to note that the success rate is critically dependent on the type of the PS, output power of the laser used, irradiation time, pre-irradiation time, and type of tips used.  

Photoelimination Potential of Chitosan Nanoparticles-Indocyanine Green Complex Against the Biological Activities of Acinetobacter baumannii Strains: A Preliminary In Vitro Study in Burn Wound Infections

Introduction: Acinetobacter baumannii strains are important agents causing serious nosocomial infections including soft-tissue and skin infections in patients with burn wounds which have become resistant to several classes of antibiotics. Antimicrobial photodynamic therapy (aPDT) as an alternative antimicrobial procedure is suggested for the treatment of these kinds of infections. The aim of the current study is to evaluate the antibacterial and anti-biofilm efficiency of aPDT by the utilization of an improved form of indocyanine green (ICG) which is encapsulated in chitosan nanoparticles (NCs@ICG).Methods: NCs@ICG were synthesized and confirmed by the scanning electron microscope (SEM). aPDT was performed using NCs@ICG with an 810 nm wavelength of the diode laser at the fluency of 31.2 J/cm2 on 50 A. baumannii strains isolated from burn wounds. The antibacterial and anti-biofilm potential of NCs@ICG-aPDT was determined via the colony forming unit (CFU)/mL and crystal violet assays, respectively. In addition, microbial biofilm degradation was evaluated by the SEM.Results: According to the results, NCs@ICG-aPDT showed a significant reduction of 93.2% on the CFU/mL of planktonic A. baumannii strains compared to the control group (untreated group; P < 0.05). In addition, the biofilm formation of A. baumannii strains was significantly reduced by 55.3% when the bacteria were exposed to NCs@ICG-aPDT (P < 0.05). In contrast, NCs@ICG, ICG, and the diode laser alone were not able to inhibit the CFU/mL and biofilm of A. baumannii strains (P > 0.05). Based on the results of SEM images, NCs@ICG-aPDT disrupted the biofilm structure of A. baumannii strains more than other groups.Conclusion: NCs@ICG-aPDT demonstrates a promising treatment candidate for exploitation in wound infections against both planktonic and biofilm forms of A. baumannii strains

The Effect of Quorum-Sensing and Efflux Pumps Interactions in Pseudomonas aeruginosa Against Photooxidative Stress

Resistant infections essentially cause mortality in a burn unit. Several bacteria contribute to burn infections; among these, Pseudomonas aeruginosa majorly contributes to these infections revealing significant drug resistance. Similar to other bacteria, P. aeruginosa reveals various mechanisms to attain highest pathogenicity and resistance; among these, efflux pumps and quorum sensing are crucial. Quorum sensing enables effective communication between bacteria and synchronizes their gene expression resulting in optimum effect of the secreted proteins; alternatively, efflux pumps increase the bacterial resistance by pumping out the antimicrobial factors as well as the QS signals and precursors. Of recent, increasing episodes of drug resistance led to new findings and approaches for killing pathogenic bacteria without inducing the drug-resistant species. Photodynamic therapy (PDT), considered as an adjuvant and innovative method for conventional antibiotic therapy, is a photochemical reaction that includes visible light, oxygen, and a photosensitizer (PS). In this therapy, after exposure to visible light, the PS generates reactive oxygen species (ROS) that are bacteriostatic or bactericidal. Furthermore, this oxidative stress can disrupt the coordination of gene expression and alter the bacterial behavior. Considering the fact that the adaption and several gene expression patterns of microorganisms within the biofilm make them notably resistant to the recent antimicrobial treatments, this study aimed to emphasize the relationship between the efflux pump and QS under oxidative stress and their role in P. aeruginosa’s reaction to PDT

Modulation of Toxin-Antitoxin System Rnl AB Type II in Phage-Resistant Gammaproteobacteria Surviving Photodynamic Treatment

Type II toxin-antitoxin (TA) systems are the particular type of TA modules which take part in different kinds of cellular actions, such as biofilm formation, persistence, stress endurance, defense of the bacterial cell against multiple phage attacks, plasmid maintenance, and programmed cell death in favor of bacterial population. Although several bioinformatics and Pet lab studies have already been conducted to understand the functionality of already discovered TA systems, still, more work in this area is required. Rnl AB type II TA module, which is composed of RnlA toxin and RnlB antitoxin, is a newly discovered type II TA module which takes part in the defense mechanism against T4 bacteriophage attack in Escherichia coli K-12 strain MH1 that has not been widely studied in other bacteria. Because of the significant role of class Gammaproteobacteriacea in a diverse range of health problems, we chose here to focus on this class to survey the presence of the Rnl AB TA module. For better categorization and description of the distribution of this module in this class of bacteria, the corresponding phylogenetic trees are illustrated here. Neighbor-joining and the maximum parsimony methods were used in this study to take a look at the distribution of domains present in RnlA and RnlB proteins, among members of Gammaproteobacteria. Also, the possible roles of photodynamic therapy (PDT) in providing a substrate for better phage therapy are herein discussed

Gender, Scaffolding Mechanism and Output Complexity in Task-based Language Learning

The purpose of this study was to investigate the role of gender in Iranian EFL learners’ output complexity and scaffolding mechanism as they were performing the tasks. The participants were 18 intermediate learners from both genders who were selected based on a proficiency test and an interview. They were placed into three groups based on their gender. They were also assigned into nine different collaborative pairs and were required to perform four tasks while being tape-recorded for 36 sessions. The audio-recorded dialogues were then transcribed and divided into AS-units. Ohta’s (2001) seven types of scaffolding methods were used as a framework to analyze the data. The findings indicated that the interlocutors in female-female pairs scaffolded their struggling partners more than the other pairs and produced a more complex output; however, the interlocutors in male-male pairs underperformed the other groups. It can be concluded that gender plays an important role in EFL learners’ output complexity and scaffolding mechanisms they employ