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Topical Photodynamic Therapy for Skin Diseases: Current Status of Preclinical and Clinical Research, Nanocarriers and Physical Methods for Photosensitizer Delivery
Published in Andreia Ascenso, Sandra Simões, Helena Ribeiro, Carrier-Mediated Dermal Delivery, 2017
Fabíola Silva Garcia Praça, Patricia Mazureki Campos, Josimar O. Eloy, Raquel Petrilli, Maria Vitória Lopes Badra Bentley, Wanessa Silva Garcia Medina
Moreover, there is number of clinical trials that successfully treated acne with both ALA and MAL-PDT using different light sources and protocols [21,119–122] and most of them considered that neutral or anionic photosensitizers are able to bind and inactivate the Gram positive bacteria but only bind to the outer membrane of Gram-negative bacteria because the latter has physical and functional barrier provided of two cell envelope membranes, which influence the response of PDT [123]. Wardlaw and colleagues showed a greater PDT susceptibility for Gram-positive bacteria than Gram-negative using topical ALA treatment of skin wound caused by Staphylococcus intermedius, Streptococcus canis, Pseudomonas aeruginosa, and Escherichia coli. Staphylococcus intermedius and S. canis had 60-70% cell death and Pseudomonas aeruginosa also responded significantly, but to a lesser extent with about 30% cell death, while E. coli did not have any significant bacterial death with PDT treatment [123].
Culture-negative periprosthetic joint infection: is there a diagnostic role for next-generation sequencing?
Published in Expert Review of Molecular Diagnostics, 2020
Next-generation sequencing (NGS) has already shown promise in the context of PJI for organism detection. Tarabichi et al. first demonstrated the utility of 16S-amplicon targeted NGS with the detection of Streptococcus canis in a culture-negative PJI patient [42]. In a prospective study of 78 patients, NGS was a useful adjunct for organism detection in 81.8% of culture-negative PJI where intra-operative tissue samples were analyzed [16]. Furthermore, in a series of 86 synovial fluid samples, high concordance with microbiological culture was seen with NGS of synovial fluid alone [43]. However, these studies were partly limited by sample size and future work is needed to determine the clinical significance of aseptic revisions that tested positive for microbial DNA (25%; n = 9/36 aseptic revision TJA) on NGS [16,43].
Genome-wide CRISPR screens for the identification of therapeutic targets for cancer treatment
Published in Expert Opinion on Therapeutic Targets, 2020
Vivian Weiwen Xue, Sze Chuen Cesar Wong, William Chi Shing Cho
Besides, some engineered Cas9 proteins with high fidelity and broad PAM range such as eSpCas9(1.1), SpCas9-HF1, and ScCas9, have been produced and applied to genome editing for finding new cancer therapeutic targets. For example, eSpCas9(1.1) is a mutated Cas9 with three alanine mutations K848A, K1003A, and R1060A in the nt-groove structure of Cas9. This Cas9 variant produced less off-target indels because of the positive charge in its nt-groove was neutralized [27]. Maggio et al. further improved this Cas9 variant to a novel editing system eCas9.4NLS with additional nuclear localization signals. This system provided a 2.3-fold higher nuclear enrichment compared to eSpCas9(1.1) [28]. SpCas9-HF1 is a quadruple substitution (N497A, R661A, Q695A, and Q926A) variant with high-fidelity in human genome editing. In a previous study, the on-target editing rate of this system was over 70%, and there are no detectable off-target genetic variations introduced by SpCas9-HF1 based on the detection using GUIDE-seq [29]. Liu et al. reported a new Cas9 variant xCas9 with broad PAM compatibility. xCas9 recognizes not only NGG sequence, but also PAMs such as NG, GAA, and GAT, which highly increased in editing efficiency and specificity [30]. A powerful variant engineered from Streptococcus canis Cas9 (ScCas9) with Thr1227Lys mutation and the additional loop structure from Streptococcus anginosus was introduced in a recent study as ScCas9++. Similarly, this system also demonstrated broad PAM compatibility [31]. Besides, HypaCas9 is a high-fidelity Cas9 variant that discriminates single-nucleotide mismatch during editing. Therefore, it can be used to distinguish single-nucleotide polymorphisms (SNPs) and perform allele-specific genome editing [32].