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Abstract Background Claudin-5 is a vital constituent of tight junctions, which are critical elements of the blood-brain barrier. In people with neuropsychiatric disorders, peripheral inflammation is often found, although it is less common in healthy populations. The objective of this study was to examine the relationship between Claudin-5, peripheral immune cells, and the severity of symptoms in children with attention deficit hyperactivity disorder (ADHD). Methods The study included a cohort of 33 children diagnosed with ADHD and 29 control subjects, all aged between 5 and 12 years. The intensity of ADHD symptoms was evaluated using Conner’s questionnaire, which the parents completed. Each kid had serum level measurements of Claudin-5 and a complete blood count in order to establish a correlation with symptoms of ADHD. Results Serum Claudin-5 levels are lower in the ADHD group compared to the control group; median (IQR) = 30.94 (4-137) and 44.12 (4–223.3) respectively (p = 0.69). The levels of neutrophils and neutrophil/lymphocyte ratio are significantly higher in ADHD than in controls (p = 0.011 and 0.015, respectively). Lymphocytes have a significant positive correlation with ADHD symptoms severity, namely, total Conner’s scale and inattention (p = 0.021 and 0.004 respectively), while NLR has a significant negative correlation with total Conner’s score and impulsivity (p = 0.046, p = 0.038), also a negative correlation yet not significant between serum Claudin-5 level and total Conner’s score, hyperactivity, impulsivity, and inattention. Neutrophils were found to have a significant positive linear regression with Claudin-5 (p = 0.023). Conclusion These results revealed that BBB integrity is affected in ADHD children, as claudin-5 levels were found to be lower in children with ADHD, lymphocytes were found to be associated with increased ADHD symptoms severity, and NLR was associated with decreased symptoms severity, which may be via the positive effects of increased neutrophils on Claudin-5 levels.

Abstract Background Resistance to carbapenem, the last line of treatment for gram-negative bacterial infections has been increasing globally and becoming a public health threat. Since integrons may aid in the transmission of resistance genes, the purpose of this study was to detect the frequency of class 1, 2, and 3 integrons as well as carbapenem-resistant genes in clinical isolates of P. aeruginosa that are resistant to carbapenem. Methods This study was carried out on 97 clinical isolates of P. aeruginosa isolated from wound and urine samples. The antimicrobial susceptibility for all isolates was tested by the disc diffusion method. The presence of integrons and carbapenem-resistant genes among carbapenem-resistant P. aeruginosa isolates was evaluated by conventional PCR. Results The antimicrobial resistance rate among P. aeruginosa clinical isolates was high, with imipenem resistance in 58.8% of the studied isolates. In this study, 86% of the carbapenem-resistant P. aeruginosa isolates carry carbapenemase genes, with bla VIM being the most common gene followed by the bla OXA−48 gene. Class 1 and class 2 integrons were reported in 37 (64.9%) and 10 (17.5%) of the tested carbapenem-resistant P. aeruginosa isolates, respectively. Conclusion Our data reported a high prevalence of class 1 integrons in carbapenem-resistant P. aeruginosa clinical isolates, suggesting the important role of integrons in carbapenem-resistant gene transfer among such isolates.

Abstract Staphylococcus aureus produces a plethora of virulence factors to invade and establish infections in the host system, and biofilms are more resistant to antibiotics than planktonic cells. In this study, we aimed to investigate the anti-virulence and anti-biofilm potentials of zinc sulfate against S. aureus isolates. The synergistic effect of zinc sulfate in combination with antibiotics on S. aureus was characterized using the checkerboard method. The influence of zinc sulfate on biofilm formation and virulence factors production by S. aureus was experimentally assessed. RT-qPCR was used to investigate the effect of zinc sulfate on the expression of biofilm-related genes. Zinc sulfate exhibited good antibacterial activity against S. aureus with a MIC of 128 µg/ml against all tested isolates. Also, the findings indicate a synergistic effect of a combination of zinc sulfate and antibiotics against the tested isolates. Zinc sulfate at 256 µg/ml concentration inhibited biofilm formation for all isolates. The expression of biofilm-related genes was significantly repressed in zinc sulfate-treated bacteria compared to untreated cells. Zinc sulfate could inhibit the hemolytic ability of S. aureus. Moreover, zinc sulfate-treated bacteria exhibited a significant decrease in coagulase and catalase activity relative to control untreated S. aureus. Our results support that zinc sulfate is a potential antimicrobial and anti-virulence agent against S. aureus infections.

Abstract Background There are few epidemiological or molecular data on Escherichia coli (E. coli) strains resistant to fosfomycin. In this study, we described the occurrence and characterization of fosfomycin-resistant uropathogenic E. coli (UPEC) isolated from children. Materials and methods This study was carried out on 96 E. coli isolates obtained from children with urinary tract infections. Two methods were performed to detect fosfomycin resistance: The agar dilution method and the rapid fosfomycin test. The disc diffusion method was done to detect the antimicrobial susceptibility pattern of all isolates. The phylogenetic grouping of all isolates was done according to the modified Clermont method. Conventional PCR was performed to detect plasmid-mediated fosfomycin-resistant genes (fos genes) and the bla CTX−M gene. Results Analyses of data were performed by SPSS software. A high percentage of fosfomycin resistance (37/96; 38.5%) was reported among UPEC isolates. The fosfomycin-resistant strains showed a higher resistance rate than fosfomycin-susceptible isolates to different antibiotics. E group (62.2%) was the most predominant phylogenetic group among the fosfomycin-resistant UPEC isolates, followed by Group B2 (21.6%) and group D (13.5%). The fos genes were detected in 21 isolates with the fosA3 gene as the most frequent, which was detected in 11 isolates followed by fosA (8), fosC2 (4), fosA4(1), and fosA5(1) genes. Conclusion This is the first report of a high prevalence of plasmid-mediated fosfomycin-resistant UPEC in Egypt. All of these isolates were multidrug-resistant to the tested antibiotics. Close monitoring of such strains is mandatory to prevent widespread dissemination of the genes code for antibiotic resistance.

Abstract Background Resistance to antibiotics has increased steadily over time, thus there is a pressing need for safer alternatives to antibiotics. Current study aims to evaluate the influence of vitamin C as an antibacterial and anti-biofilm agent against uropathogenic E. coli (UPEC) strains. The expression of beta-lactamases and biofilm encoding genes among E. coli isolates before and after treating the isolates with sub MIC of vitamin C was analyzed by Real-time PCR. The in vivo assessment of the antibacterial and anti-biofilm effects of vitamin C against uropathogenic E. coli strains was done using a urinary tract infection (UTI) rat model. Results The effective concentration of vitamin C that could inhibit the growth of most study isolates (70%) was 1.25 mg/ml. Vitamin C showed a synergistic effect with most of the studied antibiotics; no antagonistic effect was detected at all. Vitamin C showed an excellent anti-biofilm effect against studied isolates, where 43 biofilm-producing isolates were converted to non-biofilm at a concentration of 0.312 mg/ml. The expression levels of most studied genes were down-regulated after treatment of E. coli isolates with vitamin C. In vivo assessment of vitamin C in treating UTIs showed that vitamin C has a rapid curative effect as the comparable antibiotic. Administration of both vitamin C and nitrofurantoin at a lower dose for treatment of UTI in rats had a better effect. Conclusion Vitamin C as an antibacterial and anti-biofilm agent either alone or in combination with antibiotics could markedly improve UTI in experimental rats.

Abstract Background Multidrug resistant (MDR) and biofilm producing Staphylococcus aureus strains are usually associated with serious infections. This study aimed to evaluate the antibacterial and antibiofilm-formation effects of zinc oxide nanoparticles (ZnO-NPs) against staphylococcus aureus (S. aureus) isolates. Methods A total of 116 S. aureus isolates were recovered from 250 burn wound samples. The antimicrobial/antibiofilm effects of ZnO-NPs against methicillin, vancomycin and linezolid resistant S. aureus (MRSA, VRSA and LRSA) isolates were examined using phenotypic and genotypic methods. The minimum inhibitory concentration (MIC) of ZnO-NPs was determined by microdilution method. The effects of sub-MIC concentrations of ZnO-NPs on biofilm formation and drug resistance in S. aureus were determined by the microtiter plate method. The change in the expression levels of the biofilm encoding genes and resistance genes in S. aureus isolates after treatment with ZnO-NPs was assessed by real time reverse transcriptase PCR (rt-PCR). Results MICs of ZnO-NPs in S. aureus isolates were (128–2048 µg/ml). The sub-MIC of ZnO-NPs significantly reduced biofilm formation rate (the highest inhibition rate was 76.47% at 1024 µg/ml) and the expression levels of biofilm genes (ica A, ica D and fnb A) with P

There is a persistent need to look for alternative therapeutic modalities to help control the pandemic of antimicrobial resistance. Assessment of antibacterial and anti-biofilm effects of vitamin C (ascorbic acid) was the aim of the current study. The micro-dilution method determined the minimal inhibitory concentration (MIC) of ascorbic acid or antibiotics alone and in combinations against Pseudomonas aeruginosa (P. aeruginosa) clinical isolates. The micro-titer plate method monitored the effect of ascorbic acid on the biofilm-producing isolates of P. aeruginosa. The effect of ascorbic acid on the differential expression of different antibiotic-resistant genes and biofilm encoding genes of P. aeruginosa isolates were also tested using real-time polymerase chain reaction (PCR). For in vivo assessment of the antibacterial effects of ascorbic acid alone or combined with an antibiotic, rats were infected with P. aeruginosa clinical isolate followed by different treatment regimens. MICs of ascorbic acid among P. aeruginosa isolates were in the range of 156.2–1,250 μg/ml, while MIC50 and MIC90 were 312.5 and 625 μg/ml, respectively. At sub-inhibitory concentrations (19.5–312.5 μg/ml), ascorbic acid had 100% biofilm inhibitory effect. Furthermore, ascorbic acid-treated bacteria showed downregulation of genes underpinning biofilm formation and antibiotic resistance. In vivo assessment of vitamin C and ceftazidime in rats showed that administration of both at a lower dose for treatment of pseudomonas infection in rats had a synergistic and more powerful effect. Vitamin C shows excellent in vitro results as an antibacterial and anti-biofilm agent. Vitamin C should be routinely prescribed with antibiotics to treat bacterial infections in the clinical setting.

Endometrial hyperplasia (EH) is a common gynecological problem and may progress to carcinoma. Early detection and management of EH are mandatory for the prevention of endometrial cancer. Activation of the renin–angiotensin system and angiotensin II signaling are involved in the progression of precancerous and cancerous lesions. However, no studies have evaluated the role of this system in estradiol benzoate (EB)-induced EH and atypia. Irbesartan (IRB), an angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma (PPARγ) agonistic activity was administered (30 mg/kg/d) in EB-treated (60 µg/100 g bodyweight, intramuscularly, three times per week) or untreated rats for 4 weeks. Uterine weight changes, malondialdehyde, superoxide dismutase (SOD), tumor necrosis factor-alpha (TNFα), survivin, cleaved caspase 3, interleukin-10 (IL10), and PPARγ were measured in addition to undergoing histopathological examination. Results showed that EB-induced EH and atypia significantly increased the uterine body weight, malondialdehyde, TNFα, and survivin, accompanied with significantly decreased SOD, cleaved caspase 3, IL10, and PPARγ, with typical histopathological changes of EH and atypia. Coadministration of IRB significantly prevented EB-induced biochemical and histopathological changes. The protective effects of IRB may be attributed to its anti-inflammatory and antioxidant properties, reduction of survivin, and increased levels of cleaved caspase 3.