Insight into novel anti-mucormycosis therapies: investigation of new anti-mucormycosis laser-induced photodynamic therapy based on a sulphone bis-compound loaded silica nanoemulsion.

For drug delivery applications, silica nanoemulsion encapsulated with organic compounds are becoming increasingly more desirable. Therefore, the emphasis of this research was on the synthesis of a new potent antifungal drug-like candidate (1,1'-((sulfonylbis(4,1-phenylene)bis(5-methyl-1H-1,2,3-triazole-1,4-diyl))bis(3-(dimethylamino)prop-2-en-1-one), SBDMP), the chemical structure of which was confirmed on the basis of its spectral and microanalytical data. Then, silica nanoemulsion loaded with SBDMP was prepared using Pluronic F-68 as a potent surfactant. The particle shape, hydrodynamic size, and zeta potential of the produced silica nanoemulsion (with and without drug loading) were assessed. The antitumoral activity of the synthesized molecules showed the superiority of SBDMP and silica nanoemulsion with and without SBDMP loading against Rhizopus microsporous and Syncephalastrum racemosum. Subsequently, the laser-induced photodynamic inactivation (LIPDI) of Mucorales strains was determined using the tested samples. The optical properties of the samples were investigated using UV-vis optical absorption and the photoluminescence. The photosensitivity of the selected samples appeared to enhance the eradication of the tested pathogenic strains when exposed to a red (640 nm) laser light. The optical property results verified that the SBDMP-loaded silica nanoemulsion has a high depth of penetration into biological tissues due to a two-absorption photon (TAP) mechanism. Interestingly, the photosensitizing of the nanoemulsion loaded with a newly synthesized drug-like candidate, SBDMP, opens up a new route to apply new organic compounds as photosensitizers under laser-induced photodynamic therapy (LIPDT).

Production and optimization of novel Sphorolipids from Candida parapsilosis grown on potato peel and frying oil wastes and their adverse effect on Mucorales fungal strains.

BRIEF INTRODUCTION: Mucormycosis disease, which has recently expanded with the Covid 19 pandemic in many countries, endangers patients' lives, and treatment with common drugs is fraught with unfavorable side effects. AIM AND OBJECTIVES: This study deals with the economic production of sophorolipids (SLs) from different eight fungal isolates strains utilizing potato peels waste (PPW) and frying oil waste (FOW). Then investigate their effect against mucormycetes fungi. RESULTS: The screening of the isolates for SLs production revealed the highest yield (39 g/100 g substrate) with most efficiency was related to a yeast that have been identified genetically as Candida parapsilosis. Moreover, the characterizations studies of the produced SLs by FTIR, 1H NMR and LC-MS/MS proved the existence of both acidic and lactonic forms, while their surface activity was confirmed by the surface tension (ST) assessment. The SLs production was optimized utilizing Box-Behnken design resulting in the amelioration of yield by 30% (55.3 g/100 g substrate) and ST by 20.8% (38mN/m) with constant level of the critical micelle concentration (CMC) at 125 mg/L. The studies also revealed the high affinity toward soybean oil (E24 = 50%), in addition to maintaining the emulsions stability against broad range of pH (4-10) and temperature (10-100℃). Furthermore, the antifungal activity against Mucor racemosus, Rhizopus microsporus, and Syncephalastrum racemosum proved a high inhibition efficiency of the produced SLs. CONCLUSION: The findings demonstrated the potential application of the SLs produced economically from agricultural waste as an effective and safer alternative for the treatment of infection caused by black fungus.

Purification, Characterization and anticancer activity of L-methionine γ-lyase from thermo-tolerant Aspergillus fumigatus.

Purification of L-methionine γ-lyase (MGL) from A. fumigatus was sequentially conducted using heat treatment and gel filtration, resulting in 3.04 of purification fold and 73.9% of enzymatic recovery. The molecular mass of the purified MGL was approximately apparent at 46 KDa based on SDS-PAGE analysis. The enzymatic biochemical properties showed a maximum activity at pH 7 and exhibited plausible stability within pH range 5.0-7.5; meanwhile the highest catalytic activity of MGL was observed at 30-40 °C and the enzymatic stability was noted up to 40 °C. The enzyme molecule was significantly inhibited in the presence of Cu2+, Cd2+, Li2+, Mn2+, Hg2+, sodium azide, iodoacetate, and mercaptoethanol. Moreover, MGL displayed a maximum activity toward the following substrates, L-methionine < DL-methionine < Ethionine < Cysteine. Kinetic studies of MGL for L-methioninase showed catalytic activity at 20.608 mM and 12.34568 µM.min-1. Furthermore, MGL exhibited anticancer activity against cancerous cell lines, where IC50 were 243 ± 4.87 µg/ml (0.486 U/ml), and 726 ± 29.31 µg/ml (1.452 U/ml) against Hep-G2, and HCT116 respectively. In conclusion, A. fumigatus MGL had good catalytic properties along with significantly anticancer activity at low concentration which makes it a probably candidate to apply in the enzymotherapy field.

L-arginase from Streptomyces diastaticus MAM5 as a potential therapeutic agent in breast cancer: Purification, characterization, G1 phase arrest and autophagy induction.

Targeting cancer metabolic processes has increased interest over the last century. Cancer cells have an enhanced proliferation rate that requires high quantities of amino acids, including arginine. Therefore, arginine deprivation by L-arginase impairs tumor growth resulting in cell death. In the present study, L-arginine amidinohydrolase (L-arginase) from Streptomyces diastaticus was purified successfully by heat treatment, ethanol precipitation, and Sephadex G75-120 column. The molecular mass of the purified enzyme was 39 kDa. It showed maximum activity at pH 9.0 and a temperature of 50 °C. Moreover, the enzyme stability was observed at temperatures up to 50 °C and a pH range of 7.5 to 9.0. Then, the potential cytotoxicity of L-arginase was examined. L-arginase has an IC50 value of 595 µg/ml for MCF-7 (breast adenocarcinoma cells), 915 µg/ml for HepG2 (hepatocellular carcinoma cells), and 1200 µg/ml for SW620 cells (colorectal carcinoma cells) at 72 h post-treatment. Noteworthy, MCF-7 showed the lowest IC50 value of arginase treatment, therefore was further investigated for the underlying cytotoxic mechanisms using flow cytometric analysis of cell-cycle distribution, apoptosis, and autophagy. Moreover, SI values indicating a high selective cytotoxicity of arginase toward MCF-7 cells. L-arginase induced significant cell cycle arrest at the G1 phase, and no apparent apoptosis was detected. Interestingly, arginine deprivation by arginase leads to a prominent activation of autophagy in the apoptosis defected MCF-7 cells. Moreover, treatment with arginase significantly attenuated MCF-7 cell migration compared with control medium-treated cells. Collectively, L-arginase might potentially be involved in treating breast cancer.

A novel pressed coal from citrus and cooking oil wastes using fungi.

Nowadays renewable energy with low prices is a global target that has taken the attention to compare alternatives energy sources with fossil fuels. Therefore, this study was established to find suitable and sustainable alternative low-cost fuels source. Cooking oil waste (COW) was mixed with non-pretreated citrus tree fibers (CTF) (0.5 mL to 1 g ratio) and pressed to formulate coal (CTF/COW). Otherwise, this mixture was subjected to in situ fungal pretreated using Aspergillus flavus isolate to simplify the mixture composition and pressed to offer in a usable form with enhancing their heating value for the first time. CTF/COW was characterized using attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), scanning electron microscope (SEM) and thermal analysis (TGA) before and after treatment. The fungal isolate was observed with enzyme productivity and activity of CMCase, avicelase, xylanase, mannanase, α-glucosidase, ß-glucosidase, lignin peroxidase and lipase according to enzyme assays and the chemical compositions of CTF before and after fungal treatment, where the best PH for enzymes extraction was between 5 and 7. The fungal enzymes increased the heating value by about two and half folds in comparison with non-pretreated coal. Moreover, the calorific value of tCTF/COW was 43,422 kJ/kg, which was higher than CTF recorded 18,214 kJ/kg and COW recorded 39,823 kJ/kg. Our result suggests that fungal treatment of the mixture of citrus trees and cooking oil waste presents as a promising low-cost and eco-friendly coal.

Development of Antimicrobial Laser-Induced Photodynamic Therapy Based on Ethylcellulose/Chitosan Nanocomposite with 5,10,15,20-Tetrakis(m-Hydroxyphenyl)porphyrin.

The development of new antimicrobial strategies that act more efficiently than traditional antibiotics is becoming a necessity to combat multidrug-resistant pathogens. Here we report the efficacy of laser-light-irradiated 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin (mTHPP) loaded onto an ethylcellulose (EC)/chitosan (Chs) nanocomposite in eradicating multi-drug resistant Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. Surface loading of the ethylcelllose/chitosan composite with mTHPP was carried out and the resulting nanocomposite was fully characterized. The results indicate that the prepared nanocomposite incorporates mTHPP inside, and that the composite acquired an overall positive charge. The incorporation of mTHPP into the nanocomposite enhanced the photo- and thermal stability. Different laser wavelengths (458; 476; 488; 515; 635 nm), powers (5-70 mW), and exposure times (15-45 min) were investigated in the antimicrobial photodynamic therapy (aPDT) experiments, with the best inhibition observed using 635 nm with the mTHPP EC/Chs nanocomposite for C. albicans (59 ± 0.21%), P. aeruginosa (71.7 ± 1.72%), and S. aureus (74.2 ± 1.26%) with illumination of only 15 min. Utilization of higher doses (70 mW) for longer periods achieved more eradication of microbial growth.