Successful antibiotic treatment of infections relies on accurate and rapid identification of the infectious agents. Pseudomonas aeruginosa is implicated in a wide range of human infections that ...mostly become complicated and life threating, especially in immunocompromised and critically ill patients. Conventional microbiological methods take more than three days to obtain accurate results. Pyocyanin is a distinctive electroactive biomarker for Pseudomonas aeruginosa. Here, we have prepared polyaniline/gold nanoparticles decorated ITO electrode and tested it to establish a rapid, diagnostic and highly sensitive pyocyanin sensor in a culture of Pseudomonas aeruginosa clinical isolates with high selectivity for traces of pyocyanin when measured in the existence of different interferences like vitamin C, uric acid, and glucose. The scanning electron microscopy and cyclic voltammetry techniques were used to characterize the morphology and electrical conductivity of the constructed electrode. The determined linear range for pyocyanin detection was from 238 μM to 1.9 μM with a detection limit of 500 nM. Compared to the screen-printed electrode used before, the constructed electrode showed a 4-fold enhanced performance. Furthermore, PANI/Au NPs/ITO modified electrodes have demonstrated the ability to detect pyocyanin directly in Pseudomonas aeruginosa culture without any potential interference with other species.
Water splitting using photoelectrochemical (PEC) techniques is thought to be a potential method for creating green hydrogen as a sustainable energy source. How to create extremely effective electrode ...materials is a pressing concern in this area. In this work, a series of Nix/TiO2 anodized nanotubes (NTs) and Auy/Nix/TiO2NTs photoanodes were prepared by electrodeposition via cyclic voltammetry and UV-photoreduction, respectively. The photoanodes were characterized by several structural, morphological, and optical techniques and their performance in PEC water-splitting for oxygen evolution reaction (OER) under simulated solar light was investigated. The obtained results revealed the nanotubular structure of TiO2NTs was preserved after deposition of NiO and Au nanoparticles while the band gap energy was reduced allowing for effective utilization of solar light with lower charge recombination rate. The PEC performance was monitored and it was found that the photocurrent densities of Ni20/TiO2NTs and Au30/Ni20/TiO2NTs were 1.75-fold and 3.25-fold that of pristine TiO2NTs, respectively. It was confirmed that the performance of the photoanodes depends on the number of electrodeposition cycles and duration of photoreduction of gold salt solution. The observed enhanced OER activity of Au30/Ni20/TiO2NTs could be attributed to the synergism between the local surface plasmon resonance (LSPR) effect of nanometric gold which increased solar light harvesting and the p–n heterojunction formed at the NiO/TiO2 interface which led to better charge separation and transportation suggesting its potential application as an efficient and stable photoanode in PEC water splitting for H2 production.
A series of rosmarinic acid-β-amino-α-ketoamide hybrids were synthesized and rationally repurposed towards the identification of new antileishmanial hit compounds. Two hybrids, 2g and 2h, showed ...promising activity (IC50 values of 9.5 and 8.8 μM against Leishmania donovani promastigotes, respectively). Their activities were comparable to erufosine. In addition, cytotoxicity evaluation employing human THP-1 cells revealed that the two hybrids 2g and 2h possess no cytotoxic effects up to 100 µM, while erufosine possessed cytotoxicity with CC50 value of 19.4 µM. In silico docking provided insights into structure–activity relationship emphasizing the importance of the aliphatic chain at the α-carbon of the cinnamoyl carbonyl group establishing favorable binding interactions with LdCALP and LARG in both hybrids 2g and 2h. In light of these findings, hybrids 2g and 2h are suggested as potential safe antileishmanial hit compounds for further development of anti-leishmanial agents.
A chromone-peptidyl hybrids series was synthesised and rationally repurposed towards identification of potential antileishmanial hits against visceral leishmaniasis. Three hybrids 7c, 7n, and 7h ...showed potential IC
50
values (9.8, 10, and 12 µM, respectively) which were comparable to erufosine IC
50
(9.8 µM) but lower potency than miltefosine IC
50
(3.5 µM). Preliminary assessment of cytotoxicity using human THP-1 cells presented chromone-peptidyl hybrids 7c and 7n as non-cytotoxic up to 100 µM while erufosine and miltefosine had CC
50
of 19.4 µM and >40 µM, respectively. In silico studies pinpointed the N-p-methoxyphenethyl substituent at the peptidyl moiety together with the oxygen-based substituted functions of the phenyl ring of the chromone moiety as crucial players in binding to LdCALP. Together, these findings present chromone-peptidyl hybrids 7c and 7n as potential and anticipated non-cytotoxic antileishmanial hit compounds for possible development of potential antileishmanial agents against visceral leishmaniasis.
Amongst different forms of leishmaniasis, visceral leishmaniasis caused by L. donovani is highly mortal. Identification of new hit compounds might afford new starting points to develop novel ...therapeutics. In this lieu, a rationally designed small library of bestatin analogs-4-quinolone hybrids were prepared and evaluated. Analysis of SAR unveiled distinct profiles for hybrids type 1 and type 2, which might arise from their different molecular targets. Amongst type 1 bestatin analog-4-quinolone hybrids, hybrid 1e was identified as potential hit inhibiting growth of L. donovani promastigotes by 91 and 53% at 50 and 25 μM concentrations, respectively. Meanwhile, hybrid 2j was identified amongst type 2 bestatin analog-4-quinolone hybrids as potential hit compound inhibiting growth of L. donovani promastigotes by 50 and 38% at 50 and 25 μM concentrations, respectively. Preliminary safety evaluation of the promising hit compounds showed that they are 50–100 folds safer against human derived monocytic THP-1 cells relative to the drug erufosine. In silico study was conducted to predict the possible binding of hybrid 1e with methionine aminopeptidases 1 and 2 of L. donovani. Molecular dynamic simulations verified the predicted binding modes and provide more in depth understanding of the impact of hybrid 1e on LdMetAP-1 and LdMetAP-2.
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•Design and synthesis and evaluation of bestatin analogs-4-quinolinone hybrids as antileishmanial agents.•Hybrid 1e was identified as a potential hit against of L. donovani.•Hybrid 1e was safe against used human cells.•In silico studies of hybrid 1e to get molecular insights.
The study aimed to evaluate the association of demographic, clinical, and histopathologic characteristics with renal and disease outcomes. Persistent lack of partial or complete remission despite ...sequential induction therapy, chronic kidney disease (CKD) or endstage renal disease (ESRD), and/or mortality were determined as poor renal outcomes. Disease damage was investigated through the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI). Of 201 biopsy-proven lupus nephritis patients, a poor outcome was present in 56 (27.9%) patients, with nine (4.5%), 22 (10.9%), and 29 (14.4%) patients demonstrating lack of response, CKD, and ESRD, respectively, and the prevalence of mortality was 5.5% (11/201). The outcome was poor among males 29/201 (14.4%) P = 0.008; odds ratio (OR): 2.8; 95% confidence interval (CI): 1.2-6.4, yet comparable between adult- and juvenile-onset patients 80/201 (39.8%) (≤16 years) (P = 0.6; OR: 0.8; 95% CI: 0.4-1.6). Hypertension (P <0.001; OR: 6.3; 95% CI: 2.6-14.9), elevated creatinine (P <0.001; OR: 5.2; 95% CI: 2.6-10.3), and hematuria (P <0.001; OR: 3.7; 95% CI: 1.9-7.5) at presentation, and fibrinoid necrosis P <0.001; odds ratio (OR): 4.1; 95% confidence interval (CI): 2.1-8.1, wire loops (P = 0.006; OR: 2.4; 95% CI: 1.2-4.6), crescents (P <0.001; OR: 5.4 95% CI: 2.8-10.5), interstitial fibrosis (P = 0.001; OR: 2.7; 95% CI: 1.4-5.1), and acute vascular lesions (P = 0.004; OR: 3.6; 95% CI: 1.4-9.4) on biopsy were associated with a poor outcome. Chronic glomerular (P = 0.003) and acute vascular lesions (P <0.001), and a higher chronicity index (r = 0.1; P = 0.006) on biopsy, and frequent renal (r = 0.3; P <0.001) and extra-renal flares (r = 0.2; P <0.001) were associated with higher SDI scores. Among the studied renal and extra-renal parameters, independent predictors of higher disease damage solely included frequent renal flares (ᵝ= 1; P <0.001). To conclude, a poor renal outcome (27.9%) was associated with distinct features. Disease damage was associated with frequent renal flares.
In this paper, new metal ions complexes of chromium (III), iron (III), cobalt(II), nickel(II), copper(II) and cadmium(II) were prepared from mixed Schiff base ligands 1-(2-aminoethyl) ...pyrrolidine-2,5-dione ligand which was prepared form the reaction of the succinic anhydride with ethylenediamine then reacted with salicyaldehyde to form a new Schiff base ligand1-2-(2-hydroxybenzylideneamino)ethylpyrrolidine-2,5-dione(HL1). The amino acid (glycine) was reacted with salicyaldehyde to form another new Schiff base ligand (2-hydroxybenzaldine)glycine(HL2). The two types of Schiff bases ligands (HL1), (HL2) were mixed with some metal ions (Cr+3, Fe+3, Co+2, Ni+2, Cu+2 and Cd+2) to obtain a new metal complexes. The Schiff base ligands were characterized by physic-chemical spectroscopic techniques such as: FT-IR Spectra, UV-Vis. Spectra, mass spectroscopy, 1HNMR and microanalysis techniques (C.H.N). Which is indicated the purity of Schiff base ligands. The fragments of the prepared free Schiff base ligand (HL1) were identified by mass spectrometer technique. The metal complexes were characterized by spectroscopic techniques such as: FT-IR Spectra, UV-Vis. Spectra, molar conductivity, magnetic moment and microanalysis techniques (C.H.N) and chloride ion percentage. All the analysis of ligands and their metal complexes were in good agreement with the theoretical values which indicated the purity of Schiff base ligands and their metal complexes. From the above data, the molecular structures for all the metal complexes were proposed to be octahedral. The values of magnetic moments showed that all metal complexes are paramagnetic except cadmium (II) complex which is diamagnetic. The values of molar conductivity also appeared that all metal complexes are non-electrolytic nature except iron (III) complex which is electrolytic.
The study aim was to compare the alterations in the expression levels of proinflammatory and chemotactic cytokines as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17A and IL-8, the down ...regulatory cytokine IL-10, in addition to the vascular cell adhesion molecule-1 (VCAM-1) gene in different groups of patients with cirrhosis due to various etiologies. This case-control study included 84 patients suffering from cirrhosis of viral and non-viral etiologies and 20 sex and age-matched healthy controls. All patients were subjected to detailed history taking, clinical examination, and liver function assessment. The expression levels of TNF-α, IL-17A, IL-8, IL-10, and VCAM-1 were assessed in peripheral blood mononuclear cells by real-time PCR. Patients with cirrhosis showed marked changes in the tested gene expression levels relative to the control group. Higher expression levels of all genes except IL-10 were seen in patients of the viral than in the non-viral groups. Most of the significant correlations of liver function parameters were observed with TNF-α in both the viral and non-viral groups, followed by IL-17A. Increased TNF-α and IL-17A presented potential risk factors for disease progression to cirrhosis of Child class C.
Pseudomonas aeruginosa is the most common pathogenic gram-negative bacteria causing corneal ulcers globally. In severe cases, often after trauma and eye injury, corneal destruction progresses rapidly ...and may be completed within 24-48 h causing blindness. In our preliminary work, we have established an ultrasensitive polyaniline (PANI)/gold nanoparticles (Au NPs)/indium tin oxide (ITO) modified sensor for rapid detection of pyocyanin (PYO) in P. aeruginosa infections with a linear range from 238 μM to 1.9 μM and a detection limit of 500 nM. In the present study, we evaluated the efficiency of the established modified electrochemical sensor in the diagnosis of P. aeruginosa in 50 samples collected from patients suffering from corneal ulcers. The obtained results were compared with the results gained by the screen-printed electrode, conventional techniques, automated identification method, and the amplification of the 16 s rRNA gene by PCR as a gold standard test for P. aeruginosa identification. We have found that the electrochemical detection of PYO by square wave voltammetry technique using PANI/Au NPs modified ITO electrode was the only technique showing 100% agreement with the molecular method in sensitivity, specificity, positive and negative predictive values when compared with the SPE, conventional and automated methods.
Exposure to ultraviolet (UV) radiation is one of the major factors that causes skin aging, erythema, sunburns, and skin cancer. This study aimed to select probiotic bacterial isolates able to produce ...high yield of hyaluronic acid (HA) to be employed for skin photoprotection and other possible biological applications. The selected isolates K11 and St3 were able to produce the highest yields of HA 4.8 and 4.4 mg/ml, respectively. Both isolates were identified as
Enterococcus durans
strain K11 and
Lactiplantibacillus plantarum
strain St3 using 16S rRNA gene sequencing. The antioxidant activity of HA produced by
E. durans
strain K11 and
L. plantarum
strain St3 was (65.4 0.2%) and (66.6 0.1%), respectively. The viability of UVB-irradiated keratinocytes pre-treated with HA produced by
E. durans
strain K11 and
L. plantarum
strain St3 was 91.3 and 91.4%, respectively, compared with the control. While the viability of UVB-irradiated keratinocytes post-treated with HA produced by
E. durans
strain K11 and
L. plantarum
strain St3 was 86 and 88.5%, respectively. To the best of our knowledge, this is the first recordation of HA production by
Enterococcus durans
and
Lactiplantibacillus plantarum
which revealed a significant radioprotection of the human keratinocytes against UVB radiation
.
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