Targeted Delivery Platforms for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative condition of the central nervous system (CNS) that presents with varying levels of disability in patients, displaying the significance of timely and effective management of this complication. Though several treatments have been developed to protect nerves, comprehensive improvement of MS is still considered an essential bottleneck. Therefore, the development of innovative treatment methods for MS is one of the core research areas. In this regard, nanoscale platforms can offer practical and ideal approaches to the diagnosis and treatment of various diseases, especially immunological disorders such as MS, to improve the effectiveness of conventional therapies. It should be noted that there is significant progress in the development of neuroprotective strategies through the implementation of various nanoparticles, monoclonal antibodies, peptides, and aptamers. In this study, we summarize different particle systems as well as targeted therapies, such as antibodies, peptides, nucleic acids, and engineered cells for the treatment of MS, and discuss their potential in the treatment of MS in the preclinical and clinical stages. Future advances in targeted delivery of medical supplies may offer new strategies for complete recovery as well as practical treatment of progressive forms of MS.

Bioactivity of a Novel Glycolipid Produced by a Halophilic Buttiauxella sp. and Improving Submerged Fermentation Using a Response Surface Method.

An antimicrobial glycolipid biosurfactant (GBS), extracted and identified from a marine bacterium, was studied to inhibit pathogenic microorganisms. Production of the GBS was optimized using a statistical method, a response surface method (RSM) with a central composite design (CCD) for obtaining maximum yields on a cost-effective substrate, molasses. The GBS-producing bacterium was identified as Buttiauxella Species in terms of biochemical and molecular characteristics. This compound showed a desirable antimicrobial activity against some pathogens such as E. coli, Bacillus subtilis, Bacillus cereus, Candida albicans, Aspergilus niger, Salmonella enterica. The rheological studies described the stability of the GBS at high values in a range of pH (7-8), temperature (20-60) and salinity (0%-3%). The statistical optimization of GBS fermentation was found to be pH 7, temperature 33 °C, Peptone 1%, NaCl 1% and molasses 1%. The potency of the GBS as an effective antimicrobial agent provides evidence for its use against food and human pathogens. Moreover, favorable production of the GBS in the presence of molasses as a cheap substrate and the feasibility of pilot scale fermentation using an RSM method could expand its uses in food, pharmaceutical products and oil industries.

Bio-synthesis, purification and structural analysis of Cyclosporine-A produced by Tolypocladium inflatum with valorization of agro-industrial wastes.

Cyclosporine A (CyA) holds significant importance as a strategic immunosuppressive drug for organ transplant patients. In this study, we aimed to produce pure and cost-effective Cyclosporine A (CyA) by fermenting a culture medium containing dairy sludge, using Tolypocladium inflatum PTCC 5253. Following the fermentation stage, ethyl acetate extraction and fast protein liquid chromatography were employed for sample purification. The initial evaluation of the effectiveness of CyA obtained from these processes was performed through bioassay, wherein the antimicrobial clear zone diameter was found to be larger compared to the sample obtained from the fermentation culture. The concentration of CyA was determined using high-performance liquid chromatography, yielding values of 334 mg/L, 456 mg/L, and 578 mg/L for the fermented, extracted, and purified samples, respectively. Further analysis utilizing liquid chromatography tandem mass spectrometry (LC/MS/MS) confirmed a purity of 91.9% and proper agreement with the standard sample based on the ion intensity of Z/m 1205. To validate the structure of CyA, nuclear magnetic resonance spectroscopy, Fourier-transform infrared (FT-IR), and Raman spectroscopy were employed. X-ray diffraction and differential scanning calorimetry analyses demonstrated that the purified CyA exhibited a crystal structure similar to the standard sample, characterized by two broad peaks at 2θ = 9° and 20°, and comparable glass transition temperatures (57-68 °C for the purified sample; 53-64 °C for the standard sample). Dynamic light scattering analysis confirmed a uniform particle size distribution in both the purified and standard samples. The zeta potentials of the purified and standard samples were determined to be - 25.8 ± 0.16 and - 23.63 ± 0.12 mV, respectively. Our results demonstrate that dairy sludge can serve as a suitable culture medium for the production of (CyA).

Production of haloduracin by Bacillus halodurans using solid-state fermentation.

Bacillus halodurans was cultivated on wheat bran as a solid-state substrate and produced haloduracin, a bacteriocin, at about 245 AU per wheat bran. Supplementation of the bran with Lauria-Bertani broth decreased haloduracin production. However, production was stimulated by addition of Mg(2)SO(4) and K(2)HPO(4). The highest production was achieved at a wheat bran/moisture ratio of 1:1.8 and in the presence of 10% (w/w) Na(2)CO(3). Under optimum conditions, the organism produced about 3,000 AU per gram dry bran.

Anti-MRSA activity of a bioactive compound produced by a marine Streptomyces and its optimization using statistical experimental design.

OBJECTIVES: To address the alarming problem of methicillin-resistant Staphylococcus aureus (MRSA), herein, a marine Streptomyces capable of producing an anti-MRSA compound has been studied. MATERIALS AND METHODS: Strain MN41 was morphologically and physiologically characterized and then, molecularly identified using 16SrRNA analysis. To produce the bioactive compound in large scale, a kind of submerged liquid fermentation was adopted. The antibacterial agent was purified using a silica gel column followed by a semi-preparative HPLC and the isolated metabolite was identified using mass spectrometry, Nuclear magnetic resonance (NMR) and Fourier-transform infrared (FTIR). Finally, the production process was subjected to a two steps optimization using Plackett-Burman design (PBD) and Response Surface Method (RSM), respectively. In addition, the antitumor activity of the active agent was studied. RESULTS: The purified compound with a molecular weight of 421.2 was identified as a natural pyrrole-derivative. The optimization revealed a significant effect for starch, pH, calcium carbonate and peptone on the production of this anti-MRSA compound and resulted in a 218% increase in the production yield. CONCLUSION: The isolated pyrrole-derivative showed a remarkable activity against MRSA and also showed some promising anti-tumor activity.

Marine Actinomycetes with Probiotic Potential and Bioactivity against Multidrug-resistant Bacteria.

Considering antimicrobial resistance problem, marine microorganisms with the bioactivity against multi-drug resistant (MDR) pathogens have attracted many scientific interests. To address this issue, a total of 21 marine actinomycetes isolated from the Caspian Sea have been screened out. Primary screening via cross-streak method revealed that 3 strains: MN2, MN39, and MN40 produce antimicrobial agents with wide spectrum activity. In the second step, the potent strains were characterized morphologically, and then identified genetically using 16S rRNA analysis. After that, the bioactivity of the ethyl acetate extracts of liquid culture against some MDR bacteria has been studied using disc diffusion method. Finally, the exoenzymatic activity of the strains, and the anti-vibrio activity of the extracts have been evaluated. The nucleotide sequence of the 16S rRNA gene (1.5 kb) showed that the potent strains belong to the genus Streptomyces. The results of disk diffusion method indicated that among the 3 potent isolates, MN39 and MN2 produce biomolecules with antibacterial activity against MDR bacteria specially methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). In addition, potent strains showed remarkable anti-vibrio activity as well as extracellular enzyme production including amylase and protease. The results of this study revealed that the marine actinomycetes isolated from the sediments of Caspian Sea produce biomolecules effective against MDR bacteria, and suggested that these strains deserve to be studied as potential probiotics due to their anti-vibrio activity besides exoenzyme production.

Synergistic effect of haloduracin and chloramphenicol against clinically important Gram-positive bacteria.

The emergence of drug-resistant pathogens has triggered the search for more efficient antimicrobial agents and formulations for treatment of infections. In recent years, combination therapy has become one of the effective clinical practices in treating infections. The present study deals with the effect of haloduracin, a lantibiotic bateriocin and chloramphenicol against clinically important bacteria. The combined use of haloduracin and chloramphenicol resulted in remarkable synergy against a spectrum of microorganisms including strains of Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis and different groups of Streptococcus. The synergy allowed using these antimicrobial agents at substantially reduced concentrations without compromising their efficiency. Use of lower doses of chloramphenicol can avoid the severity of its side effects. In addition to minimizing undesirable side effects of some drugs, this approach brings the possibility of using antibiotics that are no longer effective due to drug resistance. Furthermore, the observed synergy between haloduracin and chloramphenicol opens a new window of using bacteriocins and antibiotics in combination therapy of infections.