Resorufin Enters the Photodynamic Therapy Arena: A Monoamine Oxidase Activatable Agent for Selective Cytotoxicity

A red-absorbing, water-soluble, and iodinated resorufin derivative (R1) that can be selectively activated with a monoamine oxidase (MAO) enzyme was synthesized, and its potential as a photodynamic therapy (PDT) agent was evaluated. R1 showed high ¹O₂ generation yields in aqueous solutions upon addition of MAO isoforms, and it was further tested in cell culture studies. R1 induced photocytotoxicity after being triggered by endogenous MAO enzyme in cancer cells with a much higher efficiency in SH-SY5Y neuroblastoma cells with high MAO-A expression. Additionally, R1 displayed differential cytotoxicity between cancer and normal cells, without any considerable dark toxicity. To the best of our knowledge, R1 marks the first example of a resorufin-based photosensitizer (PS) as well as the first anticancer drug that is activated by a MAO enzyme. Remarkably, the target PDT agent was obtained only in three steps as a result of versatile resorufin chemistry.     

SiO2 Nanoparticule-induced size-dependent genotoxicity – an in vitro study using sister chromatid exchange,micronucleus and comet assay

Fine particles with a characteristic size smaller than 100?nm (i.e. nanoparticlesspread out in nowadays life. Silicon or Si, is one of the most abundant chemical elements found on the Earth. Its oxide forms, such as silicate (SiO₄) and silicon dioxide, also known as silica (SiO₂), are the main constituents of sand and quartz contributing to 90% of the Earth's crust. In this work, three genotoxicity systems “sister chromatid exchange, cytokinesis block micronucleus test and single cell gel electrophoresis (comet) assay” were employed to provide further insight into the cytotoxic and mutagenic/genotoxic potential of SiO₂ nanoparticules (particle size 6?nm, 20?nm, 50?nm) in cultured peripheral blood lymphocytes as in vitro. It was observed that there is a significant decrease in Mitotic index (MI), Cytokinesis block proliferation index (CBPI), proliferation index (PRI) values expressed as Cell Kinetic parameters compared with negative control (p?2 (6?nm, 20?nm, 50?nm) (p?p?p?2 nanoparticles at different size (6, 20, 50?nm) progressively increased the SCE frequency and DNA damage on the basis the AU values compared with negative control (p?2 nanoparticules is dependent to particule size.     

The Influence of Different Nonsteroidal Anti-Inflammatory Drugs on Alveolar Bone in Rats: An Experimental Study

The aim

The aim of this study was to investigate the effect of dexketoprofen trometamol, meloxicam, diclofenac sodium on any untreated alveolar bone when they are used as drugs for another indication.

Materials and Methods

Twenty eight male Spraque-Dawley rats were randomized into four groups as dexketoprofen trometamol (Group I), meloxicam (Group II), diclofenac sodium (Group III) and control group. Nonsteroidal anti-inflammatory drugs (NSAID) were administered after a fibula fracture for 10 days. Untreated alveolar bone was histopathologically examined for spongious bone density, osteoclastic density and osteoblastic density.

Results

Spongious bone density was lower in study groups (Group I, group II and group III) than the control group (p<0.05). In contrast, the increase in osteoclastic density was observed in other groups apart from the control group (p<0.05). Osteoblastic density was evaluated and it was determined that group II and group III had lower results than the control group (p<0.05) but group I was equal to the control group.

Conclusion

This study showed that systemically administrated NSAIDs have the potential to affect untreated alveolar bone. This should also be considered in long term use of NSAIDs.Key Words: Non-steroidal anti-inflammatory agents, bone remodeling, osteoblast, osteoclast, maxillary bone     

Whole-body vibration-induced muscular reflex: Is it a stretch-induced reflex?

[Purpose] Whole-body vibration (WBV) can induce reflex responses in muscles. A number of studies have reported that the physiological mechanisms underlying this type of reflex activity can be explained by reference to a stretch-induced reflex. Thus, the primary objective of this study was to test whether the WBV-induced muscular reflex (WBV-IMR) can be explained as a stretch-induced reflex. [Subjects and Methods] The present study assessed 20 healthy males using surface electrodes placed on their right soleus muscle. The latency of the tendon reflex (T-reflex) as a stretch-induced reflex was compared with the reflex latency of the WBV-IMR. In addition, simulations were performed at 25, 30, 35, 40, 45, and 50 Hz to determine the stretch frequency of the muscle during WBV. [Results] WBV-IMR latency (40.5 ± 0.8 ms; 95% confidence interval [CI]: 39.0–41.9 ms) was significantly longer than T-reflex latency (34.6 ± 0.5 ms; 95% CI: 33.6–35.5 ms) and the mean difference was 6.2 ms (95% CI of the difference: 4.7–7.7 ms). The simulations performed in the present study demonstrated that the frequency of the stretch signal would be twice the frequency of the vibration. [Conclusion] These findings do not support the notion that WBV-IMR can be explained by reference to a stretch-induced reflex.Key words: Skeletal muscle function, Gravitational physiology, Tonic vibration reflex     

Recombinant activin A enhances the growth and survival of isolated preantral follicles cultured three-dimensionally in extracellular basement matrix protein (matrigel) under serum-free conditions

Development of in vitro technologies that will allow the culture of early stage follicles before antral stage is an essential part of research in reproductive biology in order to understand the ovarian folliculogenesis better. Current evidence suggests that oocyte and somatic cells-derived growth factors interacting with each other and extracellular matrix proteins at paracrine level are involved in this early, gonadotrophin-independent phase of follicle growth. Basement membrane matrix protein (Matrigel?) is a soluble gel rich in extracellular matrix proteins and growth factors. Activin A promotes preantral follicle growth in vivo by inducing the proliferation of granulosa cells and by upregulating the expression of FSH receptor and aromatase enzyme. We hypothesized that activin A and matrigel may provide a better in vitro environment for early stage preantral follicles. Preantral follicles isolated from 14–21 day old BALB/c mice were cultured in matrigel?±?activin A for four days. The growth (119.4% versus 45.4%, p?p?in vitro milieu for the growth of isolated ovarian follicles.     

COVID-19-related oral mucosa lesions among confirmed SARS-CoV-2 patients: a systematic review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019 (COVID-19), which manifests as a flu-like respiratory infection affecting multiple organ systems, including the gastrointestinal system, central nervous system, cardiovascular system, skin, and mucosa. In this review, we investigated the literature on specific manifestations of COVID-19 in the oral mucosa. An online literature search in PubMed, Scopus, Google Scholar, and Medline was conducted to retrieve relevant studies on confirmed COVID-19 patients with oral mucosa findings published between December 31, 2019, and April 07, 2021. After an independent review by two authors, 39 articles considering 59 laboratory-confirmed cases of SARS-CoV-2 infection were included in the final analysis. The most common finding, reported in 29 patients (43.9%), was Kawasaki-like syndrome. In addition, oral ulcers including aphthous, hemorrhagic, and necrotic ulcers were reported in 24 patients (36.3%). Other lesions reported included pustules, macules, bullae, maculopapular enanthema, and erythema multiforme-like lesions. Concomitant skin lesions were present in 60.6% of patients. Fever was reported in 86.2% of patients. Forty-eight patients (76.1%) were hospitalized. Loss of taste and smell was present in 30.8% of the patients. A comprehensive understanding of the dermatologic manifestations of COVID-19 can improve and facilitate patient management and referrals.     

Design,synthesis, molecular docking study,and antibacterial evaluation of some new fluoroquinolone analogues bearing a quinazolinone moiety

BackgroundIncreasing bacterial resistance to quinolones is concerning. Hence, the development of novel quinolones by chemical modifications to overcome quinolone resistance is an attractive perspective in this context.ObjectiveIn this study, it is aimed to design and synthesize a novel series of functionalized fluoroquinolones using ciprofloxacin and sarafloxacin cores by hybridization of quinazolinone derivatives. This objective was tested by a comprehensive set of in vitro antibacterial assays in addition to SAR (structure–activity relationship) characterisation studies.MethodsA nucleophilic reaction of ciprofloxacin and sarafloxacin with 2-(chloromethyl)quinazolin-4(3H)-one in the presence of NaHCO₃ in dimethylformamide (DMF) was performed to obtain the desired compounds 5a-j. Novel compounds were characterised by ¹H, ¹³C- NMR and IR spectroscopy, MS and elemental analysis. In silico pharmacokinetics prediction assays and molecular docking studies were performed to explore the binding characteristics and interactions. Antibacterial activities of the novel compounds were evaluated by Broth microdilution, well diffusion and disc diffusion assays against three gram-positive (Methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus and Enterococcus faecalis) and three gram-negative bacteria (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli).ResultsThe compounds exhibited moderate to good activities against gram-positive bacteria and weak to moderate activities against gram-negative bacteria. Amongst all ciprofloxacin-derivatives, compound 5d was the most potent agent with high antibacterial activity against gram-positive bacteria, including MRSA and S. aureus ((minimum inhibitory concentration (MIC) = 16 nM for both), that is 60 times more potent than ciprofloxacin as parent drug. Compound 5i from sarafloxacin-derivatives was the most potent compound against MRSA and S. aureus (MIC = 0.125 μM). Well diffusion and disk diffusion assay results demonstrated confirmatory outcomes for the quantitative broth microdilution assay. Molecular docking study results were in accordance with the results of antibacterial activity assays.ConclusionThe results of the current study demonstrated that the novel ciprofloxacin and sarafloxacin derivatives synthesized here have promising antibacterial activities. Particularly, compounds 5d and 5i have potential for wider antibacterial applications following further analysis.Graphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00373-6) contains supplementary material, which is available to authorized users.