In vitro activity of juglone (5-hydroxy-1,4-naphthoquinone) against both fluconazole-resistant and susceptible Candida isolates.

BACKGROUND: The rise in antifungal resistance and drug class limitations are causing higher morbidity and mortality rates all over the world. This issue highlights the urgent need for new and improved antifungal drugs with a novel target. AIMS: In order to evaluate whether juglone can be served as an alternative antifungal to cure drug-resistant Candida infections, we studied the in vitro susceptibility of juglone against fluconazole-susceptible and -resistance Candida isolates, alone and in combination. METHODS: Antifungal susceptibility testing was performed according to the CLSI (Clinical and Laboratory Standards Institute) guidelines. RESULTS: Juglone exhibited the highest minimal inhibitory concentration (MIC) values, followed by fluconazole and nystatin. Voriconazole showed significantly better antifungal activity than juglone, fluconazole, and nystatin, with MIC50 and MIC90 of 0.031 and 0.5µg/mL. There were significant differences in MICs of fluconazole (p<0.001) and juglone (p<0.0003) between Candidaalbicans and the rest of the species. Combination of juglone with fluconazole revealed insignificant effects against fluconazole-susceptible and -resistant Candida isolates. Juglone increased the antifungal activity of fluconazole; however, no synergism effects were observed for any combination, and only an insignificant effect was found against all tested Candida species. CONCLUSIONS: Although obtaining new antifungal drugs is a critical point, a completely novel approach should be implemented.

In vitro activity of juglone (5-hydroxy-1, 4-naphthoquinone) against both fluconazole-resistant and susceptible Candida isolates

Background:The rise in antifungal resistance and drug class limitations are causing higher morbidity and mortality rates all over the world. This issue highlights the urgent need for new and improved antifungal drugs with a novel target.Aims:In order to evaluate whether juglone can be served as an alternative antifungal to cure drug-resistant Candida infections, we studied the in vitro susceptibility of juglone against fluconazole-susceptible and -resistance Candida isolates, alone and in combination.Methods:Antifungal susceptibility testing was performed according to the CLSI (Clinical and Laboratory Standards Institute) guidelines.Results:Juglone exhibited the highest minimal inhibitory concentration (MIC) values, followed by fluconazole and nystatin. Voriconazole showed significantly better antifungal activity than juglone, fluconazole, and nystatin, with MIC50 and MIC90 of 0.031 and 0.5μg/mL. There were significant differences in MICs of fluconazole (p<0.001) and juglone (p<0.0003) between Candidaalbicans and the rest of the species. Combination of juglone with fluconazole revealed insignificant effects against fluconazole-susceptible and -resistant Candida isolates. Juglone increased the antifungal activity of fluconazole; however, no synergism effects were observed for any combination, and only an insignificant effect was found against all tested Candida species.Conclusions:Although obtaining new antifungal drugs is a critical point, a completely novel approach should be implemented. (AU)

Antecedentes:El aumento de la resistencia a los antifúngicos y las limitaciones propias de los fármacos son responsables de mayores tasas de morbimortalidad en todo el mundo. Este trabajo destaca la urgente necesidad de nuevos y mejorados fármacos antimicóticos contra una nueva diana.Objetivos:Con el fin de evaluar si la juglona puede servir como un antifúngico alternativo para curar las infecciones por Candida resistentes a los fármacos antifúngicos, hemos estudiado la sensibilidad in vitro a la juglona de aislamientos de Candida sensibles y resistentes al fluconazol, solo y en combinación.Métodos:La prueba de sensibilidad a los antifúngicos se realizó de acuerdo con las guías del Clinical and Laboratory Standards Institute (CLSI).Resultados:La juglona mostró los valores de concentración mínima inhibitoria (CMI) más altos, seguida por el fluconazol y la nistatina. El voriconazol mostró una actividad antifúngica significativamente mejor que la juglona, el fluconazol y la nistatina, con valores de CMI50 y CMI90 de 0,031 y 0,5μg/mL. Hubo diferencias significativas en las CMI del fluconazol (p<0,001) y la juglona (p<0,0003) entre los aislamientos de Candida albicans y aquellos de otras especies. La combinación de juglona con fluconazol reveló efectos insignificantes contra cepas de Candida sensibles y resistentes al fluconazol. La juglona aumentó la actividad antifúngica del fluconazol; sin embargo, no se observaron efectos de sinergia para ninguna combinación y solo se encontró un efecto insignificante contra todas las especies de Candida ensayadas.Conclusiones:Aunque el diseño o el descubrimiento de nuevos fármacos antimicóticos es una tarea crítica, es necesario planificar un abordaje completamente novedoso. (AU)

Bismuth nanoparticles against microbial infections.

The destructive effect of infectious diseases on human life and the emergence of antibiotic-resistant strains highlight the importance of developing new and appropriate treatment strategies, one of which is the use of metals as therapeutic agents. Bismuth nanoparticles are an example of prominent metal-containing drugs. The therapeutic effects of bismuth-based drugs in the treatment of wounds have been proven. Various laboratory studies have confirmed the antimicrobial effects of bismuth nanoparticles, including the clinical treatment of ulcers caused by Helicobacter pylori. Therefore, considering the performance of this nanoparticle and its potent effect on infectious agents and its therapeutic dimensions, the present study fully investigated the properties and performance of this metal-based nanoparticle.

Scolicidal and Apoptotic Activities of 5-hydroxy-1, 4-naphthoquinone as a Potent Agent against Echinococcus granulosus Protoscoleces.

Cystic hydatid disease (CHD) is a zoonotic disease with different clinical stages caused by the larval stage of the cestode Echinococcus granulosus. It is important to highlight as a public health problem in various regions of the world. In the current study, the efficacy and apoptotic activity of the liposomal system containing juglone (5-hydroxy-1,4-naphthoquinone) were assessed against protoscoleces (PSCs) in vitro. To this aim, firstly, liposomal vesicles were prepared by the thin-film method. Their physico-chemical features were assessed using Zeta-Sizer and Scanning Electron Microscope (SEM). Subsequently, various concentrations (50, 100, 200, 400, and 800 µg/mL) of juglone nanoliposomes at different exposure times (15, 30, 60, and 120 min) were used against PSCs. Results showed that juglone nanoliposomes at all tested concentrations induced scolicidal effect, however, 800 µg/mL and 400 µg/mL of juglone nanoliposomes could reach 100% mortality in 60 and 120 min, respectively. Additionally, we found that caspase-3 mRNA expression was higher in PSCs treated with juglone nanoliposomes compared to control groups (p < 0.001). Therefore, juglone nanoliposomes are suggested to have a more potent apoptotic effect on PSCs. Generally, optimized doses of juglone nanoliposomes could display significant scolicidal effects. Moreover, further in vivo studies are required to evaluate the efficacy of this nanoliposome.

Effects of high-intensity interval training on the expression of microRNA-499 and pro- and anti-apoptotic genes in doxorubicin-cardiotoxicity in rats.

BACKGROUND: Because clinical use of doxorubicin (DOX) in chemotherapy is limited due to cardiotoxicity, finding new strategies to alleviate DOX burden and improving patients' health are necessary. Due to positive cardiovascular impacts of high-intensity interval training (HIIT), here we have investigated the effect of HIIT on DOX-induced cardiotoxicity by evaluating the myocardial apoptosis mechanism as well as microRNA-499a-5p expression. METHODS: Male Wistar rats (250-270 g) were randomly allocated into four groups: control, HIIT, DOX, and HIIT+DOX. HIIT was performed as 7 sets of alternative intervals of high and low trainings for 1 h a day, 5 days a week for 6 weeks using a rodent treadmill. After the last session of HIIT, the trained and time-matched control rats received intraperitoneal injection of DOX (20 mg/kg). Three days later, the left ventricular samples were obtained to determine the expression of microRNA and genes and proteins regulating apoptosis via real-time PCR. Myocardial apoptosis was also evaluated using TUNEL staining method. RESULTS: DOX administration significantly increased the expression levels of Bax and caspase-6 mRNAs, Bax protein and Bax/Bcl2 ratio, while reduced the expression levels of Bcl2 mRNA and protein in comparison to control group (P < 0.01). Pre-treatment of DOX-received rats with HIIT significantly up-regulated the Bcl2 and reduced the Bax, Bax/Bcl2, and caspase-6 expression profiles toward control values (P < 0.05), not affecting GSK-3ß expression. In addition, DOX toxicity significantly overexpressed microRNA-499, comparing to control rats (P < 0.01). HIIT significantly reversed this overexpression and also reduced TUNEL-positive apoptotic cells in DOX-received rats (P < 0.05). CONCLUSIONS: The data suggested that prior training of rats with HIIT had protective effect on DOX cardiotoxicity through reversing the expression profiles of pro- and anti-apoptotic factors and microRNA-499 and reducing myocardial apoptosis.

The comparison of MAMA PCR and SSCP PCR to study chromosomal resistance against Ciprofloxacin and Nalidixic acid in Escherichia coli and Klebsiella pneumoniae.

The mutation in gyrA and parC genes alters amino acids. Also, it causes resistance against Fluoroquinolones in E. coli and K. pneumoniae. The purpose of this study was to diagnose the significant mutation of gyrA (ser83-asp87) and parC (ser80-glu84) genes through using MAMA PCR and SSCP PCR methods. In so doing, the isolated samples were collected. Then, utilizing agar disc diffusion method, the researchers performed antibiotic sensitivity test. Moreover, Fluoroquinolones resistance was confirmed by E-test method (MIC experiment). Furthermore, the obtained data from MAMA PCR method were sequenced accidentally. According to the findings, among 103 isolated samples, 65 samples (63/2%) were belonged to E. coli and 38 samples (36/8%) to K. pneumoniae. In all E. coli that resisted to Ciprofloxacin, at least one mutation were observed. Also, at least one mutation was observed in all K. pneumoniae samples that resisted to Ciprofloxacin. However, four mutation points were detected for each of seven samples and, interestingly, there was no mutation in five sensitive samples to Ciprofloxacin. In addition, the results revealed that the mutation in gyrA and parC genes was closely related to Quinolones resistance. Based on the findings, preparing an infection control program in Iran is highly required.

Recombinant M2e-HA2 fusion protein induced immunity responses against intranasally administered H9N2 influenza virus.

Influenza is a highly contagious respiratory tract disease and is considered a serious community health problem. Influenza viruses possess multiple conserved epitopes which are used for designing universal vaccines. To this aim, the gene coding for N-terminal part of M2e (SLLTEVET) and HA2 (GLFGAIAGF), was synthesized, linked by a (Gly4Ser)4 peptide linker, and cloned into pGS-21a vector. Afterwards, the construct was transferred into E. coli BL21 (DE3) cells to produce the designed antigenic protein called M2e-HA2. Immunization of mice with these peptides significantly induced humoral immune responses against the influenza virus. Three weeks after the last booster, mice were inoculated intranasally with 1 × 106 EID50 of H9N2 virus. The results indicated that the recombinant M2e-HA2 fusion protein could protect mice against H9N2 virus.