Methylene blue in anticancer photodynamic therapy: systematic review of preclinical studies.

Background: Methylene blue has a long history of clinical application. Thanks to phenothiazine chromophore, it has potential in photodynamic anticancer therapy. In spite of the growing body of literature that has evaluated the action of this dye on different types of cancer, the systematic understanding of this problem is still lacking. Therefore, this systematic review was performed to study the efficacy of methylene blue in photodynamic anticancer therapy. Methods: This systematic review was carried out in accordance with the PRISMA guidelines, and the study protocol was registered in PROSPERO (CRD42022368738). Articles for the systematic review were identified through the PubMed database. SYRCLE's risk of bias tool was used to assess the studies. The results of systematic analysis are presented as narrative synthesis. Results: Ten studies met the inclusion criteria and these full texts were reviewed. In the selected articles, the dosage of dye infusion ranged from 0.04 to 24.12 mg/kg. The effectiveness of photodynamic therapy with methylene blue against different types of cancer was confirmed by a decrease in tumor sizes in seven articles. Conclusion: The results of the systematic review support the suggestions that photodynamic therapy with methylene blue helps against different types of cancer, including colorectal tumor, carcinoma, and melanoma. In cases of nanopharmaceutics use, a considerable increase of anticancer therapy effectiveness was observed. The further research into methylene blue in photodynamic anticancer therapy is needed. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=368738), identifier (CRD42022368738).

Insights into the Pharmacological Effects of Flavonoids: The Systematic Review of Computer Modeling.

Computer modeling is a method that is widely used in scientific investigations to predict the biological activity, toxicity, pharmacokinetics, and synthesis strategy of compounds based on the structure of the molecule. This work is a systematic review of articles performed in accordance with the recommendations of PRISMA and contains information on computer modeling of the interaction of classical flavonoids with different biological targets. The review of used computational approaches is presented. Furthermore, the affinities of flavonoids to different targets that are associated with the infection, cardiovascular, and oncological diseases are discussed. Additionally, the methodology of bias risks in molecular docking research based on principles of evidentiary medicine was suggested and discussed. Based on this data, the most active groups of flavonoids and lead compounds for different targets were determined. It was concluded that flavonoids are a promising object for drug development and further research of pharmacology by in vitro, ex vivo, and in vivo models is required.

cDNA cloning, structural, and functional analyses of venom phospholipases A2 and a Kunitz-type protease inhibitor from steppe viper Vipera ursinii renardi.

Snake venom phospholipases A2 (PLA2s) display a wide array of biological activities and are each characteristic to the venom. Here, we report on the cDNA cloning and characterization of PLA2s from the steppe viper Vipera ursinii renardi venom glands. Among the five distinct PLA2 cDNAs cloned and sequenced, the most common were the clones encoding a basic Ser-49 containing PLA2 (Vur-S49). Other clones encoded either ammodytin analogs I1, I2d and I2a (designated as Vur-PL1, Vur-PL2 and Vur-PL3, respectively) or an ammodytoxin-like PLA2 (Vurtoxin). Additionally, a novel Kunitz-type trypsin inhibitor for this venom species was cloned and sequenced. Comparison of these PLA2 and Kunitz inhibitor sequences with those in the sequence data banks suggests that the viper V. u. renardi is closely related to Vipera ammodytes and Vipera aspis. Separation of V. u. renardi venom components by gel-filtration and ion-exchange chromatography showed the presence of many PLA2 isoforms. Remarkably, the most abundant PLA2 isolated was Vur-PL2 while Vur-S49 analog was in very low yield. There are great differences between the proportion of cDNA clones and that of the proteins isolated. Two Vur-PL2 isoforms (designated as Vur-PL2A and Vur-PL2B) indistinguishable by masses, peptide mass fingerprinting, N-terminal sequences and CD spectroscopy were purified from the pooled venom. However, when rechromatographed on cation-exchanger, Vur-PL2A showed only one peak corresponding to Vur-PL2B, suggesting the existence of conformers for Vur-PL2. Vur-PL2B was weakly cytotoxic to rat pheochromocytoma PC12 cells and showed both strong anticoagulant and anti-platelet activities. This is the first case of a strong anticoagulating ammodytin I analog in Vipera venom.