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One mechanism of ciprofloxacin resistance is attributed to chromosomal DNA-encoded efflux pumps such as the MepA and NorB proteins. The goal of this research is to find a way to bypass Staphylococcus aureus’ efflux pumps. Because of its high membrane permeability and low association with NorB and MepA efflux proteins, a liposome-encapsulating antibiotic is one of the promising, cost-effective drug carriers and coating mechanisms for overcoming active transport of methicillin-resistant S. aureus (MRSA) multidrug-resistant efflux protein . The calculated “Log Perm RRCK” membrane permeability values of 1,2-distearoyl-sn-glycerol-3-phosphocholine (DSPC) ciprofloxacin liposome-encapsulated (CFL) showed a lower negative value of − 4,652 cm/s and greater membrane permeability than ciprofloxacin free (CPF). The results of RT-qPCR showed that cationic liposomes containing ciprofloxacin in liposome-encapsulated form (CFL) improved CPF antibacterial activity and affinity for negatively charged bacterial cell surface membrane in comparison to free drug and liposome, as it overcame several resistance mechanisms and reduced the expression of efflux pumps. Ciprofloxacin liposome-encapsulated (CFL) is therefore more effective than ciprofloxacin alone. Liposomes can be combined with a variety of drugs that interact with bacterial cell efflux pumps to maintain high sustained levels of antibiotics in bacterial cells.

Restoration of the normoglycemic state is the basic tenet of diabetes research. Nowadays, using nanoemulsion drug delivery systems represent an alternative effective tool in Type 2 diabetes mellitus management. We aimed to investigate the anti-diabetic potential of metformin nanoemulsion and mesenchymal stem cells (MSCs) therapy on streptozotocin (STZ)-induced diabetic rat model. Nanoemulsion formulation was prepared with oil phase (5%v/v), 1gm metformin with a hydrophilic surfactant, then characterized for particle size and zeta potential.Adult male albino rats were induced for diabetes with 60 mg/kg STZ and were classified into 4 groups: STZ control group; STZ+MET group (orally administered daily dose of metformin 18 mg/200 g b.wt.); STZ+MSCs group (mono-therapeutic dose of BM-MSCs 1×106 cells/rat) and STZ+Nano-MET group (daily intraperitoneal dose of metformin nanoemulsion 18 mg/kg b.wt.). After 8 weeks, relative expression levels of hepatic IRS-1, AKT, Bcl-2, and Bax were assessed by qPCR. Also, histopathological investigations were performed. We reported cytoplasmic vacuolation, tissue necrosis, dilated blood sinusoid and congested hepatic vein in STZ group. Experimental animals either treated with metformin nanoemulsion or the mono-therapeutic dose of MSCs exhibited significant up-regulation in IRS-1/AKT pathway and Bcl-2 gene expression levels, as well as significant repression in Bax mRNA levels, besides a remarkable amelioration in a hepatic histological organization.Conclusion: Nano-MET holds an anti-diabetic potential that clearly surpasses metformin via affecting the insulin signaling pathway and apoptotic gene expression.

The use and manufacturing of silver nanoparticles (AgNPs) have recently received considerable attention in many fields. Methicillin resistant Staphylococcus aureus (MRSA) causes infectious diseases in humans. Therefore, the aim of this work was to bio-synthesize AgNPs using the cyanobacteria Phormidium sp. extract and to use this extract with AgNPs to kill MRSA. Extracellular bio-formation of AgNPs by Phormidium sp. was scrutinized at various pH points and temperatures. Then, characterization and assessment of the antimicrobial power of the produced particles were performed. Extract and extract + AgNPs were screened using Fourier Transform Infra-Red (FT-IR) spectroscopy and electron microscopy. The manufacturing and fastness of AgNPs were monitored visually (by color change) and spectroscopically. FT-IR analysis uncovered the biomolecules in the extract that caused the reduction of silver ions, protected them from aggregation and supplied them with high stability. Results indicated that AgNPs are spheres of 9 nm diameter. AgNPs combined with the extract proved to be a powerful antibacterial factor against MRSA. Consequently, biosynthesis of silver nano-spheres using Phormidium sp. with high antagonistic potency against MRSA is considered as an eco-friendly, time-saving strategy and with potential medicinal significance.

The broiler industry in the Middle East (ME) faces many challenges related to bacterial infections, including M. gallisepticum, M. synoviae, E. coli, and other gram-negative bacteria, exacerbated by various errors in the brooding process. Antibiotics use in the first three days of life, such as Linco-Spectin 100 SP, tilmicosin, enrofloxacin, tylosin, colistin, and doxycycline, is the trend in the market to control such challenges. This study aimed to evaluate the efficacy of the newly introduced aroA E. coli vaccine (Poulvac E. coli) and its ability to reduce over-reliance on the heavy use of antibiotics in the ME. The study was conducted on 160 broiler chicks, divided into eight even groups. Each group was treated differently in terms of antibiotic therapy and ages at the time of Poulvac E. coli administration and the challenge of virulent avian pathogenic E. coli (APEC), serotype O78. Spray application of Poulvac E. coli at seven days of age plus Linco-Spectin 100 SP during the first three days provided the best results for zero mortality after challenge with APEC, while Poulvac E. coli at seven days with enrofloxacin during the early three days resulted in 10% mortality. Poulvac E. coli hatchery vaccination protected birds against mortality but reduced body weight gain compared to the 7-day group vaccinated with Linco-Spectin 100 SP during the first three days. Poulvac E. coli given on day one or day seven did not affect the immune response to concurrent respiratory viral vaccines and, in some cases, improved response. This study shows that Poulvac E. coli at seven days of age, together with Linco-Spectin 100 during the first three days, has produced the best results in terms of protection and performance in the ME high presence of avian pathogenic E. coli field challenge.

Purpose Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. Methods Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. Results The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29-39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes' expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. Conclusion CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.

Objective: Evaluation antiviral effects of Withania somnifera (Ashwagandha) leaf extract against HCV. Methods: cell proliferation was assessed using MTT assay after isolation of lymphocyte cells and treated with Ashwagandha water extract (ASH-WX) (6.25 mg/ml - 100 mg/ml). Assessment of quantitative Real-time PCR, Colony forming assay, TNF-α and molecular docking studies after infection of normal lymphocyte cells with 1 ml (1.5 × 106 HCV) serum then incubated with ASH-WX at concentration 25 mg/ml & 50 mg/ml. Results: MTT assay revealed a significant increase (p α significantly decreased following ASH-WX treatment compared with control untreated infected cells (p 3 IU/mL. Colony formation assay test revealed colony formation reduction compared to positive untreated control. Molecular docking analysis revealed good prediction of binding between Ashwagandha and NS5B and PKN2 compared to Sovaldi. Conclusion: ASH-WX may be a powerful antiviral against HCV infection.

Antibiotic resistance represents the main challenge of Helicobacter pylori infection worldwide. This study investigates the potential bactericidal effects of fosfomycin combinations with clarithromycin, metronidazole, ciprofloxacin, amoxicillin, rifampicin, and doxycycline against thirty-six H. pylori strains using the checkerboard and time-kill assay methods. The results showed that ≥ 50% of the strains were resistant to the six antibiotics. Remarkably, only six strains exerted resistance to these antibiotics, with the minimum inhibitory concentrations (MICs) ranges of (3.2–12.8 mg/l), (32–256 mg/l), (3.2–51.2 mg/l), (3.2–25.6 mg/l), (1.6–3.2 mg/l), and (25.6 > 51.2 mg/l), respectively. The seven antibiotics were evaluated through in silico studies for their permeability and ability to bind UDP-N-acetylglucosamine1-carboxyvinyltransferase (MurA) of H. pylori. The results indicated that fosfomycin exhibited the highest predicted membrane permeability (membrane ∆G insert = − 37.54 kcal/mol) and binding affinity (docking score = − 5.310 kcal/mol) for H. pylori MurA, compared to other tested antibiotics. The combinations of fosfomycin with these antibiotics exerted synergistic interactions (Fractional inhibitory concentration, FIC index 10 cfu/ml) against the most resistant H. pylori strain. Notably, these effects increased with presence of metronidazole, which enhanced the activity of the fosfomycin combination with amoxicillin from a weak inhibition to bactericidal effect. This study provides evidence that the combination of fosfomycin with either clarithromycin, amoxicillin, doxycycline, or rifampicin (especially with the presence of metronidazole) could be a promising option for treating MDR H. pylori infection.

Loutfy SA, Elberry MH, Farroh KY, et al. Int J Nanomedicine. 2020;15:2699–2715. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of images in Figure 8. The authors responded to our queries and explained the western blot experiments were performed by a commercial laboratory; however, they were unable to provide all the original data. The data that was provided showed inconstancies between what was considered original western blot data and what was shown in Figure 8. This raised concerns over the reliability and validity of the findings and the Editor requested for the article to be retracted and the authors do not agree with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

The resistance of Candida albicans to azole drugs represents the great global challenge. This study investigates the potential fungicidal effects of atorvastatin (ATO) combinations with fluconazole (FLU), itraconazole (ITR), ketoconazole (KET) and voriconazole (VOR) against thirty-four multidrug-resistant (MDR) C. albicans using checkerboard and time-kill methods. Results showed that 94.12% of these isolates were MDR to ≥ two azole drugs, whereas 5.88% of them were susceptible to azole drugs. The tested isolates exhibited high resistance rates to FLU (58.82%), ITR (52.94%), VOR (47.06 %) and KET (35.29 %), whereas only three representative (8.82%) isolates were resistant to all tested azoles. Remarkably, the inhibition zones of these isolates were increased at least two-fold with the presence of ATO, which interacted in a synergistic (FIC index ≤ 0.5) manner with tested azoles. In silico docking study of ATO and the four azole drugs were performed against the Lanosterol 14-alpha demethylase enzyme (ERG11) of C. albicans. Results showed that the mechanism of action of ATO against C. albicans is similar to that of azole compounds, with docking score (-4.901) lower than azole drugs (> - 5.0) due to the formation a single H-bond with Asp 225 and a pi-pi interaction with Thr 229. Importantly, ATO combinations with ITR, VOR and KET achieved fungicidal effects (≥ 3 Log10 cfu/ml reduction) against the representative isolates, whereas a fungistatic effect (≤ 3 Log10 cfu/ml reduction) was observed with FLU combination. Thus, the combination of ATO with azole drugs could be promising options for treating C. albicans infection.

Objectives: The continuous reporting of bacterial resistance to antibiotics is an ongoing challenge that can be life-threatening. Actions to develop new chemicals to overcome the bacterial resistance has gained a significant importance. Methods: A series of ketene S,N-acetals 4a-k and their pyrazoles 6a-k were synthesized and their structures were established by spectral data. Membrane permeability predictions and in vitro antimicrobial activity against multi-drug resistant (MDR) Gram-positive bacteria and other microorganisms was determined. The binding affinity with DNA gyrase was assessed using in silico studies in comparison to ciprofloxacin then tthe gyrase inhibition assay was conducted to detect the mode of action. Results: All the synthesized compounds have a good affinity to pass through the phospholipid membrane of Staphylococcus aureus (S. aureus). Compound 6g exhibited the most potent antibacterial activity with MIC values ranged between 16 and 32 µg/mL. The compound also showed a higher binding affinity than ciprofloxacin with DNA gyrase in the in silico studies and this effect was clearly shown by a very good IC50 value of the gyrase inhibition assay. Conclusions: According to our data, compound 6g is a possible candidate to act against MDR bacteria and its main mode of action is through inhibition of the gyrase enzyme, further modifications are still required to enhance its activity.

One mechanism of ciprofloxacin resistance is attributed to chromosomal DNA-encoded efflux pumps such as the MepA and NorB proteins. The goal of this research is to find a way to bypass Staphylococcus aureus' efflux pumps. Because of its high membrane permeability and low association with NorB and MepA efflux proteins, a liposome-encapsulating antibiotic is one of the promising, cost-effective drug carriers and coating mechanisms for overcoming active transport of methicillin-resistant S. aureus (MRSA) multidrug-resistant efflux protein . The calculated "Log Perm RRCK" membrane permeability values of 1,2-distearoyl-sn-glycerol-3-phosphocholine (DSPC) ciprofloxacin liposome-encapsulated (CFL) showed a lower negative value of - 4,652 cm/s and greater membrane permeability than ciprofloxacin free (CPF). The results of RT-qPCR showed that cationic liposomes containing ciprofloxacin in liposome-encapsulated form (CFL) improved CPF antibacterial activity and affinity for negatively charged bacterial cell surface membrane in comparison to free drug and liposome, as it overcame several resistance mechanisms and reduced the expression of efflux pumps. Ciprofloxacin liposome-encapsulated (CFL) is therefore more effective than ciprofloxacin alone. Liposomes can be combined with a variety of drugs that interact with bacterial cell efflux pumps to maintain high sustained levels of antibiotics in bacterial cells.

COVID-19 is a pandemic disease caused by the SARS-CoV-2, which continues to cause global health and economic problems since emerging in China in late 2019. Until now, there are no standard antiviral treatments. Thus, several strategies were adopted to minimize virus transmission, such as social distancing, face covering protection and hand hygiene. Rhamnolipids are glycolipids produced formally by Pseudomonas aeruginosa and as biosurfactants, they were shown to have broad antimicrobial activity. In this study, we investigated the antimicrobial activity of rhamnolipids against selected multidrug resistant bacteria and SARS-CoV-2. Rhamnolipids were produced by growing Pseudomonas aeruginosa strain LeS3 in a new medium formulated from chicken carcass soup. The isolated rhamnolipids were characterized for their molecular composition, formulated into nano-micelles, and the antibacterial activity of the nano-micelles was demonstrated in vitro against both Gram-negative and Gram-positive drug resistant bacteria. In silico studies docking rhamnolipids to structural and non-structural proteins of SARS-CoV-2 was also performed. We demonstrated the efficient and specific interaction of rhamnolipids with the active sites of these proteins. Additionally, the computational studies suggested that rhamnolipids have membrane permeability activity. Thus, the obtained results indicate that SARS-CoV-2 could be another target of rhamnolipids and could find utility in the fight against COVID-19, a future perspective to be considered.

New antibiotics are desperately needed to overcome the societal challenges being encountered with methicillin-resistant Staphylococcus aureus (MRSA). In this study, a new tetracene derivative, named Mersaquinone (1), and the known Tetracenomycin D (2), Resistoflavin (3) and Resistomycin (4) have been isolated from the organic extract of the marine Streptomyces sp. EG1. The strain was isolated from a sediment sample collected from the North Coast of the Mediterranean Sea of Egypt. The chemical structure of Mersaquinone (1) was assigned based upon data from a diversity of spectroscopic techniques including HRESIMS, IR, 1D and 2D NMR measurements. Mersaquinone (1) showed antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 3.36 μg/mL.

In current study, we studied the phytochemicals of

In current study, we studied the phytochemicals of Cullen corylifolium (fruits) in which we identify twenty compounds, including two coumarins (1 and 2), three coumestans (3–5), fourchalcone (6–9), three dihydroflavones (10–12), four isoflavones (13–16), one flavonoid (17) and three meroterpenes (18–20). Among these, compounds 4, 5 and 12 were isolated from C. corylifolium for the first time. The ferroptosis inhibitory effects of the isolated phytochemicals were assessed using erastin-exposed HT22 mouse hippocampal cells. Compounds 3 and 18 showed the most potent inhibition with the IC50 values of 5.21 μM and 5.41 μM, respectively. Moreover, molecular docking study showed that compound 3 possessed tremendous inhibitory affinity for human 5-lipoxygenase (5-LOX) and Kelch-like ECH-related protein 1: nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) protein-protein interactions, two important ferroptosis-related targets. These findings indicate that compound 3 (psoralidin) may be a potential therapeutic agent for the treatment of ferroptosis-related diseases.

Loutfy SA, Elberry MH, Farroh KY, et al. Int JNanomedicine. 2020;15:2699–2715.The authors have advised Figure 8 on page 2712 is incorrect.The correct Figure 8 is shown below.The authors apologize for this error and advise it does notaffect the results of the paperRead the original article

Several actinomycetes strains were isolated from different marine sponges collected from the Red Sea shore in Egypt. The efficiency of their crude extracts to inhibit histone deacetylase (HDAC) enzyme was investigated in the nuclear extract of Hela cell line. The crude extract corresponding to Streptomyces sp. SP9 isolated from the marine sponge Pseudoceratina arabica showed a promising HDAC inhibitory activity with 64 and 81% at 50 and 100 µg/ml, respectively. The strain was identified as Streptomyces sp. by phylogenetic analyses based on its 16S rRNA gene sequence. The major compounds of Streptomyces sp. SP9 were isolated and purified by different chromatographic methods. The chemical structure of the isolated compounds was identified on the basis of their spectroscopic data including mass, 1H and 13C NMR, and by comparison with those of authenticated samples. Structures of compounds 1 and 2 were established as heliomycin and tetracenomycin D, respectively. These compounds exhibited HDAC inhibitory activities with IC50 values of 29.8 ± 0.04 µg/ml for heliomycin (1) and 10.9 ± 0.02 µg/ml for tetracenomycin D (2). A computational docking study for compounds 1 and 2 against HDAC1, HDAC2, and HDAC3 was performed to formulate a hypothetical mechanism by which the tested compounds inhibit HDAC. Tetracenomycin D (2) showed a good binding interactions with HDAC2 (- 5.230 kcal/mol) and HDAC3 (- 6.361 kcal/mol).

Several actinomycetes strains were isolated from different marine sponges collected from the Red Sea shore in Egypt. The efficiency of their crude extracts to inhibit histone deacetylase (HDAC) enzyme was investigated in the nuclear extract of Hela cell line. The crude extract corresponding to Streptomyces sp. SP9 isolated from the marine sponge Pseudoceratina arabica showed a promising HDAC inhibitory activity with 64 and 81% at 50 and 100 µg/ml, respectively. The strain was identified as Streptomyces sp. by phylogenetic analyses based on its 16S rRNA gene sequence. The major compounds of Streptomyces sp. SP9 were isolated and purified by different chromatographic methods. The chemical structure of the isolated compounds was identified on the basis of their spectroscopic data including mass, (1)H and (13)C NMR, and by comparison with those of authenticated samples. Structures of compounds 1 and 2 were established as heliomycin and tetracenomycin D, respectively. These compounds exhibited HDAC inhibitory activities with IC(50) values of 29.8 ± 0.04 µg/ml for heliomycin (1) and 10.9 ± 0.02 µg/ml for tetracenomycin D (2). A computational docking study for compounds 1 and 2 against HDAC1, HDAC2, and HDAC3 was performed to formulate a hypothetical mechanism by which the tested compounds inhibit HDAC. Tetracenomycin D (2) showed a good binding interactions with HDAC2 (− 5.230 kcal/mol) and HDAC3 (− 6.361 kcal/mol). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13205-018-1304-1) contains supplementary material, which is available to authorized users.